In the past nearly 20 years, organ-sparing when no apparent viable tumour is present after neoadjuvant therapy has taken an increasingly relevant role in the therapeutic management of locally-advanced rectal cancer patients. The decision to include a patient or not in a “Watch-and-Wait” program relies mainly on endoscopic assessment by skilled surgeons, and MR imaging by experienced radiologists. Strict surveillance using the same modalities is required, given the chance of a local regrowth is of approximately 25–30%, almost always surgically salvageable if caught early. Local regrowths occur at the endoluminal aspect of the primary tumour bed in almost 90% of patients, but the rest are deep within it or outside the rectal wall, in which case detection relies solely on MR Imaging. In this educational review, we provide a practical guide for radiologists who are, or intend to be, involved in the re-staging and follow-up of rectal cancer patients in institutions with an established “Watch-and-Wait” program. First, we discuss patient preparation and MR imaging acquisition technique. Second, we focus on the re-staging MR imaging examination and review the imaging findings that allow us to assess response. Third, we focus on follow-up assessments of patients who defer surgery and confer about the early signs that may indicate a sustained/non-sustained complete response, a rectal/extra-rectal regrowth, and the particular prognosis of the “near-complete” responders. Finally, we discuss our proposed report template. MR Imaging is one of the pillars for the selection and follow-up of patients when “Watch-and-Wait” is an option.Radiologists participating in “Watch-and-Wait” programs should be familiar with the imaging findings that indicate a poor/incomplete response, a complete response and a “near-complete” response.Given deep rectal and extra-rectal regrowth detection relies on MR imaging only, radiologists should combine a high index of suspicion with a high precision, to propel salvage surgery only when needed.The concept of “locally-advanced rectal cancer” is intrinsically linked with a clinical indication for neoadjuvant therapy (NAT). It traditionally applies to all clinically staged T3/T4 and/or N+ tumours, although in the UK and other centres across Europe criteria may be more strict , 2. NAT Before MR imaging acquisition, there are two preparatory steps which may significantly contribute to improve image quality. The first step is to ask patients to perform a small enema for rectal emptying before entering the MR equipment . The secThe use of endoluminal gel is not advocated routinely because distension of the rectum may result in misinterpretation of the distance between the tumour bed and circumferential resection margin (CRM), an essential re-staging information when surgery is a possibility . If consRegarding technique, examinations should be performed on a 1.5T or 3T equipment using an external coil , 12. 2D ectively , 12. In ectively , 12. A Dectively , 12. Intectively , 12 but The issue of when to first assess tumour response is controversial. While the rate of pCR may increase after 12 weeks post-RT  some surAlthough clinical and laboratory evaluation is relevant, re-staging relies heavily on rectal endoscopy and MR imaging. If the two are to be performed on the same day and given endoscopy requires the insufflation of air into the rectum, to perform MR imaging first may be preferable in order to minimise air-induced susceptibility artefacts.Endoscopic assessment  may be sApproximately 20% of locally advanced rectal cancer patients show a poor response to neoadjuvant therapy, which may imply a shift in the neoadjuvant treatment scheme or early surgery , 18. PooLittle reduction in tumour size2.MR Tumour regression grades (mrTRG) 3–5A tumour volume reduction below 70%, as based on slice-by-slice segmentation on T2-WI, is associated with a poor response –22. GiveMrTRG is an ordinal scale developed by Patel et al.to assess response on MR T2-WI in a parallel manner to the Mandard pathological TRG score , 25 and 3.Significant restriction to diffusion on Diffusion-weighted Imaging (DWI)There are multiple ordinal scales in the literature that represent variations or adaptations to it but in general, when T2-WI intermediate “tumour” signal predominates over hypointense fibrosis or clear hyperintense “acellular mucin” , a poor response is assumed, and the 3-year disease free survival is 21% inferior compared to favourable mrTRG1-3s . mrTRG3 DWI is highly sensitive to susceptibility artefacts and dependent on good acquisition technique. Good patient preparation is essential as well as adequate training in image reading. T2-shine through effects from luminal content, which will present with high signal intensity on high b value images and high signal intensity in the ADC map, should not to be mistaken for true restriction, which will present with high signal intensity on high b value images and low signal intensity in the ADC map; or with dense fibrosis, which will present with low signal intensity in both high b value images and ADC map. While on T2-WI mrTRG the proportion of intermediate “tumour” signal at tumour bed is taken into consideration, in most studies focusing on response assessment using DWI, assessment is binary—restriction indicates viable tumour whereas its absence suggests a complete response –31. AlsoMucinous tumours have an intrinsically higher ADC compared to non-mucinous tumours, making response assessment based on DWI more difficult and less reliable .An example of a poor tumour response is given in Fig. Short axis ≥ 5 mm, which may be associated with a likelihood of residual disease up to 63% [p to 63% , 34.Residual intermediate “tumour” signal intensity or heterogeneous signal intensity on T2-WI, which usually represents residual macroscopic tumour [c tumour .With respect to mesorectal lymph nodes, lymph nodes with incomplete/poor response usually present with Fig. a–c:Fig. 3.Residual high “mucin” signal on high b-value T2-WI — Mucinous tumours with lymph node involvement present with a higher frequency of residual viable tumour after neoadjuvant therapy and as such, lymph nodes with visible “mucin” high signal intensity on T2-WI at re-staging MR imaging are frequently positive [positive .Residual high signal intensity on high b value DWI with low ADC does not aid in the identification of viable tumour in lymph nodes given it may be observed in both lymphoid and tumour tissue.An example of a poor lymph node response is given in Fig. Size reduction < 33% between pre and post-neoadjuvant treatment [reatment .Short axis > 5 mm on post-neoadjuvant therapy MR [erapy MR .Residual “tumour” signal intensity or heterogeneous signal intensity on T2-W,I just the same as applied to mesorectal lymph nodes.Involvement of lateral pelvic sidewall lymph nodes is more likely to occur in tumours located at the level or below the peritoneal reflection, particularly if ≥ T3 . The lowRegarding response of extramural venous invasion (EMVI) to neoadjuvant therapy, Chand et al.have established a specific TRG score for EMVI (mr-vTRG) on T2-WI and concluded grades 4 (< 25% fibrosis) and 5  were associated with higher local recurrence rates (44%) and lower disease-free survival (46%) compared to grades 1–3 (50% fibrosis or more)—9% local recurrence and 88% 3-year disease-free survival . In our Given incomplete/poor responders may undergo early surgery, it is particularly important that their identification is followed by detailed information on residual tumour location and relations. The most important of all items is the re-evaluation of the circumferential resection margin (CRM) given a clearance of the margin on re-staging high-resolution T2-WI has a positive predictive value of up to 90% for a clear margin at pathology, which may justify a shift towards less mutilating surgery –42. On tApproximately 10–25% of patients with locally-advanced rectal cancer undergoing NAT prior to surgery achieve a pCR , escalatVery large reduction in tumour sizeThere are some factors at staging MR that may be associated with a higher likelihood of a pCR, namely tumour length < 4 cm, tumour circumference < 180º, distance to anal verge < 45 mm and mrT stage ≤ 3 , 44. Als2.mrTRG 1Volume reduction > 70–89% at T2-WI (T2-hypointense “fibrosis” included in the measurements) and > 95–98% at DWI  associate with a complete response to treatment –47.2.mrT3.Positive split scar signConversion to a linear/crescentic, 1–2 mm scar in the mucosa or submucosa or normalisation of the rectal all have very high specificity for complete response, in the range of 92–98% .3.Positimuscularis propria; and an outer, irregular, hypointense layer of mesorectal fibrosis, which may be absent and usually is in staged ≦ T2 tumours [4.Absence of high signal intensity on high b value DWIThe split scar sign has a very high specificity (97%) and positive predictive value (93/94%) for a sustained complete response , but it  tumours . The splComplete response on DWI is supported by the absence of high signal intensity at high b-value DWI images  –31 and iAn example of a complete tumour response is given in Fig. Significant size reduction or disappearance on T2-WI. A ≥ 70% short axis reduction or disappearance of the LN on T2-WI may indicate ypN0 status in 100% of cases [of cases  and accoof cases .Disappearance on DWI—Absence of visible lymph nodes in high b value DWI may be a reliable predictor of ypN0 status [0 status  but if hWith respect to mesorectal lymph nodes, a complete response may present with Fig. d–f:SigniAn example of a complete lymph node response is provided in Fig. Lateral pelvic sidewall lymph nodes that shrink to 4 mm or less in short axis on re-staging MR imaging present no risk of local recurrence at 3 years according to Ogura et al. . DisappeRegarding response of extramural venous invasion, as stated above, mrV-TRG grades 1–3 (50% fibrosis or more) are associated with a good response, with only 9% LR rate and 88% 3-year DFS . Even wiComplete responders may be offered the possibility of entering a specialised surveillance program for organ preservation.The criteria presented above are very specific but not very sensitive for a complete response. The concept of “near-complete response” was introduced more recently, driven by the observation that a significant proportion of patients presenting with a very good but incomplete response at first assessment may convert into a cCR if given a longer interval and re-assessment . This coPatients with dense fibrosis or with dense fibrosis and minimal residual intermediate signal may be considered near-complete responders , 53.A small focal area of high signal intensity on high b value DWI is admissible for a near-complete response .There is no evidence regarding expected tumour size reduction for these patients.An example of a near-complete tumour response is provided in Fig. same criteria as for complete responders should be applied  and the following (median 23 weeks post-RT) signaled a non-sustained complete response with a very high specificity 91/94%) . To meas1/94% . TFor patients who enroll W&W, a scar thickness > 10 mm in the first follow-up examination (median 23 weeks post-RT) was > 90% specific for a non-sustained complete response, irrespective of other findings, according to the results of the same study as above . Tumour Scar thickening Scar thickening may be the first hint to a local regrowth and may present before any other MR imaging or endoscopic signs of macroscopic tumour [c tumour .Depth angle increase Depth angle increase may also be present before any obvious signs of a local regrowth on MR imaging or endoscopy and in fact 1. and 2. may be observed together [together .In upfront clinical complete responders, we may expect a bit of scar “contraction” and/or scar “thinning” over time  but over3.Intermediate “tumour” signal intensity/heterogeneity “de novo” at tumour scar on T2-WI An mrTRG of 5 should be given when intermediate “tumour” signal appears de novo at tumour bed on W&W follow-up.4.High signal intensity at high b value DWI “de novo” A bright spot or area de novo at tumour bed may indicate tumour regrowth with high specificity at it is particularly important when observed in depth, because it will be out of the scope of endoscopy.More obvious changes indicating a local regrowth are:Conformation change, such as apparently “sterilised” lymph nodes/tumour deposits that become rounder or more irregular.Increase in size, which may be subtle and require zoomed-in measurement in multiple planes.Intermediate “tumour” signal intensity/heterogeneity on T2-WI de novo.Focus/foci of high signal intensity on high b-value DWI de novo.Extra-rectal local regrowth is uncommon (3%) . Its earIt is important to state that not all extra-rectal pelvic recurrences are clear regrowths. Uncommonly, disease may emerge in lymph nodes classified as innocent upon staging or as extranodal tumour deposits in a location in which only fat/vessels were present before, so carefull evaluation of the whole pelvis is imperative Fig. .Fig. 10EIt is important to state that the management for this group of patients is controversial. In the study by Simpson et al. , 63% of Our proposed re-staging and follow-up reporting template is shown in Fig. Compared to the re-staging report template provided by ESGAR , ours is“Watch-and-Wait” rectal cancer programs are growing around the world and revolve around endoscopy and pelvic MR imaging, both for re-staging and patient follow-up. Radiologists involved in such programs should be familiar with the imaging findings that suggest a poor/incomplete response, a complete response or a “near-complete” response and their prognostic implications. They should also be equipped for the early detection of local regrowths, in depth at tumour bed or extra-rectal in particular, given their invisibility at rectoscopy.


DOI: 10.1039/D1RA07500D.Correction for ‘Thermal, mechanical investigation and neutron shielding analysis for Gd-MOF/polyimide materials’ by Chen Hu  The authors regret that the grant number quoted in the original acknowledgements section was incorrect. The correct acknowledgments section is given here:This work was supported by the National Key Research and Development Program of China [Grant numbers 2020YFB1901900]; and the “115” Industrial Innovation Team of Anhui Province.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.


VOLUME 19 (2020) PAGES 540-553There was an error in the grant information in which a grant acknowledgment was omitted. The Partnership for Clean Competition  should be added to this section.


We evaluated malignancy according to the characteristics of pericardial fluid in symptomatic Japanese patients undergoing pericardiocentesis and computed tomography (CT).This was a retrospective, single-center, observational study of 125 symptomatic patients undergoing pericardiocentesis. The patients were classified into two groups: a malignancy group and a non-malignancy group, according to the primary disease and cytology of the pericardial effusion (PE). We compared the pericardial fluid sample and CT measurements between both groups.p = 0.017). Lower serum brain natriuretic peptide (BNP) concentration was also associated with malignancy . A significant difference was observed in pericardial fluid glucose level between the malignancy and non-malignancy groups . Moreover, CT attenuation values (Hounsfield units (HU)) tended to be higher in the malignancy group vs the non-malignancy group (22.7  vs 17.4 , respectively; p = 0.08). The sensitivity and specificity of pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were 40.9% and 89.6%, respectively, in the malignancy group. The positive- and negative predictive values of pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were 85.7% and 50.0%, respectively, in the malignancy group. Pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were cutoff values associated with malignancy (p = 0.012).All patients were diagnosed as having exudative PE by Light’s criteria. PE with malignant cells was demonstrated in 76.8% of the malignancy group patients. Pericardial to serum lactate dehydrogenase (LDH) ratio > 0.6, as one of Light’s criteria, was associated with malignancy (Lower pericardial fluid glucose level with higher CT attenuation values may suggest malignancy-related PE.The online version contains supplementary material available at 10.1186/s12872-021-02091-6. The normal pericardial sac contains up to 50 ml of pericardial fluid as a plasma ultrafiltrate. Pericardial effusion (PE), which is classified according to composition, distribution, and volume, results from many diseases . In patiWe enrolled 125 consecutive symptomatic patients undergoing pericardiocentesis between April 2010 and April 2020 as a retrospective observational study in a single institution.Twenty-eight patients without pericardial fluid sampling and CT data were excluded because of out-of-hospital cardiopulmonary arrest, Stanford type A aortic dissection, and blow-out rupture in acute myocardial infarction as an intra-procedural complication. All patients who did not undergo thoracic CT scans because of cardiac shock were diagnosed on echocardiography in the emergency room. Therefore, 97 patients were finally enrolled in this study. The patients were classified into two groups: a malignancy group and a non-malignancy group. The malignancy group constituted patients with known existing malignancy or documented malignant cells in drained PE.According to the patients’ medical records, blood samples were collected for routine care approximately 24 h after the first drainage. The following were evaluated in the drained pericardial fluid: pH, total protein, lactate dehydrogenase (LDH), albumin, glucose, adenosine deaminase (ADA), hyaluronic acid, hemoglobin (Hb), and hematocrit. Collected pericardial fluid was cytologically diagnosed with malignant cells or non-malignant cells by two pathologists. Pericardial fluid testing was performed in 88 patients, and cytological analysis was performed in 94 patients. Patients were diagnosed with exudative PE according to Light’s criteria, which constitute a pericardial fluid-to-serum total protein ratio > 0.5 and a pericardial fluid-to-serum LDH ratio > 0.6 or two-thirds of the upper limit of the normal (UNL) serum LDH value . The interobserver agreement for determining CT attenuation values also indicated good agreement .p = 0.006)  tended to be higher in the malignancy group compared with the non-malignancy group (22.7  vs 17.4 IQR, 13.7–26.4], respectively). However, the p-value was 0.08; therefore, no significant difference in CT attenuation values was observed between the malignancy and non-malignancy groups. In contrast, CT attenuation values > 20 HU were associated with malignancy . CT attenuation values were also correlated with pericardial fluid glucose level (r =  − 0.425), protein level (r = 0.541), glucose ratio (r =  − 0.461), and protein ratio (r = 0.583). The sensitivity and specificity of pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were 40.9% and 89.6%, respectively, in the malignancy group. The positive- and negative predictive values of pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were 85.7% and 50.0%, respectively, in the malignancy group. Pericardial fluid glucose ≤ 70 mg/dl and CT attenuation values > 20 HU were cutoff values associated with malignancy (Fig. The relationship between pericardial fluid measurements and CT attenuation values is shown in Fig.  r = 0.54, glucoseTo the best of our knowledge, the current study is the first to investigate malignancy-related PE by adding the characteristics of CT images to the pericardial fluid examination. We found that lower pericardial fluid glucose level and higher CT attenuation values were related to PE owing to malignancy. In particular, pericardial fluid analysis in patients undergoing pericardiocentesis is performed routinely, but the results of this analysis are not effectively used in clinical practice.Malignant PE is a serious manifestation associated with a poor prognosis , 5. HoweStrobbe et al. evaluated the etiologies of PE and distinguished radiation therapy for malignancy as a cause of PE . MoreoveIn the current study, the number of patients in the malignancy group was higher than the number in the non-malignancy group, and approximately 60% of the patients in the malignancy group had lung cancer. While the percentage of patients with an idiopathic etiology in our study was 7.2%, one study in Western Asia and another in Africa reported PE attributed to unknown causes at rates of approximately 10%–15% . In contAlthough pericardial fluid analysis is performed routinely, the results of this analysis are not effectively used owing to a lack of specificity. Meyers et al. reported that pericardial fluid glucose level was lower in patients with exudates than in those with transudates, and there was a significant overlap in the etiology of PE between patients with transudates vs exudates . All casIn our study, PE for differentiating the malignancy group from the non-malignancy group was evaluated by the combination of pericardial fluid glucose level and CT attenuation values. Pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU had 40.9% sensitivity and 89.6% specificity for discriminating the malignancy group from the non-malignancy group. Additionally, our study demonstrated that CT attenuation values had a good correlation with pericardial fluid glucose level. According to our results, the combination of pericardial fluid glucose ≤ 70 mg/dl and CT attenuation values > 20 HU might be associated with malignancy in PE. In addition, this study showed that this combination was associated with positive-cytology patients.Recent studies showed that pericarditis related to malignancy, except for pericardial infiltration of malignant cells and radiation therapy, was associated with antineoplastic agents, such as tyrosine kinase inhibitors and immune checkpoint inhibitors , 24. AltThe strength of this study is that we evaluated diagnostic procedures that are readily available in clinical practice. Pericardial fluid analysis and CT imaging are simple and routine tools to diagnose malignancy-related PE. Pericardial fluid glucose level and CT attenuation values can be obtained quickly; therefore, this effective method should be used in clinical practice.There are several limitations to our study. First, the size of the non-malignancy group was small because this was a single-institution study. Second, the malignancy group had higher proportions of patients with lung cancer. The retrospective nature of this study is another limitation.Lower pericardial fluid glucose level in addition to higher CT attenuation values may suggest malignancy-related PE. In patients with pericardial fluid glucose ≤ 70 mg/dl and CT attenuation values > 20 HU, malignant disease as the cause of PE must be excluded by other examinations and imaging modalities, even if there are no malignant cells in pericardial fluid cytology.Additional file 1: Fig. S1. Relationship between pericardial fluid glucose or CT attenuation values and positive cytologyvs negative cytology. Pericardial fluid glucose ≤ 70 mg/dl and CT attenuation values > 20 HU were cutoffvalues associated with positive cytology. Pfpericardial fluid, CT computed tomography.


S. aureus has been well established. We evaluated the in vitro activity of lefamulin against S. aureus from patients with cystic fibrosis (CF). Lefamulin is a first-in-class, oral and IV pleuromutilin antibiotic approved in the US, EU, and Canada for the treatment of community-acquired bacterial pneumonia (CABP) in adults. Lefamulin inhibits bacterial protein synthesis via a unique mechanism of action and its potency against n=224) were collected from the lower respiratory tract (LRT) of children (≤17 years old) with CF and LRT infection. Organisms were from qualified respiratory specimens and determined to be the probable cause of infection by the participant center. The isolates were collected in 2018-2020 from 22 medical centers in 11 countries and tested by broth microdilution methods at JMI Laboratories. Most isolates were from the US (43.3%), Spain (24.1%), France (20.5%), and Costa Rica (7.1%). Unique isolates , with 99.6% of isolates inhibited at ≤0.25 mg/L, consistent with the susceptible [S] breakpoint published by the US FDA, CLSI, and EUCAST. Only 1 lefamulin-non-S  isolate was observed, a methicillin-susceptible (MSSA) collected in Costa Rica in 2018 and carrying a vga(A) gene. Lefamulin retained potent activity against methicillin-resistant (R) S. aureus , azithromycin-R , levofloxacin-R , clindamycin-R , and gentamicin-R  isolates as well as those isolates with multiple resistance phenotypes. Against MRSA, susceptibility to azithromycin was 23.5% and to levofloxacin 64.7%. All isolates were susceptible to vancomycin, linezolid and ceftaroline (Table). Among isolates from the US (n=97), the MRSA rate was 30.9% and all isolates were Lefamulin-S .Lefamulin was highly active against the CF in vitro antibacterial activity against S. aureus from children with CF, regardless of resistance phenotype. Lefamulin may represent a valuable treatment option for CF patients with S. aureus LRT infections. Lefamulin demonstrated potent Helio S. Sader, MD, PhD, FIDSA, AbbVie (formerly Allergan) (Research Grant or Support)Basilea Pharmaceutica International, Ltd. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)Department of Health and Human Services Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Susanne Paukner, PhD, Nabriva Therapeutics GmbH (Employee) Steven P. Gelone, PharmD, Nabriva Therapeutics US, Inc. (Employee) S J Ryan Arends, PhD, AbbVie (formerly Allergan) (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Rodrigo E. Mendes, PhD, AbbVie (Research Grant or Support)AbbVie (formerly Allergan) (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)ContraFect Corporation (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support)


Social networks are now essential tools for promoting research and researchers. However, there is no study investigating the link between presence or not on professional social networks and scientific publication or citation for a given researcher.The objective of this study was to study the link between professional presence on social networks and scientific publications/citations among anesthesia researchers.We included all the French full professors and associate professors of anesthesia. We analyzed their presence on the social networks Twitter  and ResearchGate. We extracted their bibliometric parameters for the 2016-2020 period via the Web of Science Core Collection  database in the Science Citation Index-Expanded index.P=.31) or ResearchGate . Researchers with an active Twitter account (median [IQR]) had more scientific publications , a higher h-index , a higher number of citations per publication , and a higher number of citations . Researchers with a ResearchGate account (median [IQR]) had more scientific publications  and a higher h-index . There was no difference between researchers with a ResearchGate account and those without it concerning the number of citations per publication and overall number of citations. In multivariate analysis including sex, academic status, and presence on social networks, the presence on Twitter was associated with the number of publications , the number of citations , and the h-index .A total of 162 researchers were analyzed; 42 (25.9%) had an active Twitter account and 110 (67.9%) a ResearchGate account. There was no difference between associate professors and full professors regarding active presence on Twitter (8/23 [35%] vs. 34/139 [24.5%], respectively; Among French anesthesia researchers, an active presence on Twitter is associated with higher scientific publication and citations. In a globalized world, social networks have now taken a major place in the scientific field and are essential tools for promoting research and researchers (including the recruitment or the promotion of a researcher) -3. TwittMedical journals use Twitter to increase their visibility within the scientific community. It is by far the most used social network to share publications because more than 20% of published articles receive at least one announcement on Twitter  . MoreoveThe objective of this study was to study the link between presence on social networks and scientific publication and citation among anesthesia researchers.We used publicly available data; as a retrospective analysis that did not involve human participants (and in accordance with French laws), this study was exempt from institutional ethics board review .We included all French physicians with an academic function of teaching and research in anesthesia .The main objective of this work was to compare the scientific publication and citation of French anesthesia researchers according to the presence or absence of an active Twitter account. The secondary objectives were:to compare, in the same population, the scientific publication and citation according to the presence or absence on ResearchGate;to assess if the presence or absence from Twitter and ResearchGate was associated with scientific publication and citation of researchers.To limit the impact of profile variations on social networks and publication citations in the bibliometric database, the entire data collection was carried out manually over 10 consecutive days in March 2021.We analyzed the presence of included researchers on the social networks Twitter  and ResearchGate. The screening for finding social network accounts followed a step-by-step procedure:The first and last name were entered into the social network search engine. On Twitter, the author was searched on the account search tool and also on the “TOP” (most relevant Tweets for a given search) and “LATEST” (the most recently posted Tweets matching a given search) tabs;If no author was found after this first search, only the last name was used in association with the following keywords: “Dr”, “Pr”, “Anesthésie”, “Réanimation” (French keywords), “Anesthesia”, and “Intensive care”;If no author was still found, the first and last name were entered into the Google search engine with the keyword “Twitter” or “ResearchGate”;If several accounts were found for a given name, all accounts were manually analyzed in search of information on the account, to identify whether or not it was the researcher’s account .When an account was found, the following data were collected:For Twitter: existence of a professional Twitter profile . For each active Twitter account, the recorded data were presence or not of a photograph, information concerning profession (academic or anesthetist), number of tweets, number of followers, and date of creation of the account (to determine the number of tweets and followers by month spent on Twitter);For ResearchGate, existence of an active ResearchGate profile (with a least one research work documented); if there is an existing profile, the following data were collected: presence or not of a photograph, number of followers, RG score (which is a measure of scientific reputation on ResearchGate), and Total Research Interest score .Bibliometric parameters were extracted from the Web of Science Core Collection  database in the Science Citation Index-Expanded index. To limit the risk of errors due to homonyms in other research disciplines, we used a search algorithm focused on medical specialties that correspond to the fields of activity of anesthetists in France. Thus, the analysis focused on the publication of reviews, original articles, and editorials in medical journals over the period 2016-2020 on the advanced search tool of Web of Science with the following search formula: AND (PY=2016 OR PY=2017 OR PY=2018 OR PY=2019 OR PY=2020) AND (DT=ARTICLE OR DT=REVIEW OR DT=EDITORIAL MATERIAL) AND AU=“NAME OF THE AUTHOR, surname of the author”For each researcher, the following parameters were recorded: number of publications, h-index, number of citations per publication, and overall number of citations.U test. The qualitative variables were analyzed using a Fisher test. The Pearson correlation test was used to assess the strength of association between 2 quantitative variables. A multivariate analysis using a linear regression model was realized to identify whether the presence or absence from Twitter and ResearchGate was related to the number of citations, the h-index, and the number of publications. The multivariate analysis included the following variables: presence on Twitter, presence on ResearchGate, sex, and academic status (full professor or associate professor). All statistical tests were 2-sided and the .05 probability level was used to establish statistical significance. All statistics and graphs were produced using GraphPad PRISM software .The values are presented as n (%) for qualitative variables, and as median (IQR) for quantitative variables. The quantitative variables were compared using a Mann-Whitney The raw data supporting the conclusions of this manuscript can be made available on request by the authors to any qualified researcher.Of the 162 researchers analyzed (147 men and 15 women), 68 (42.0%) had a Twitter account, of which 42 (25.9%) were considered active, and 110 (67.9%) had a ResearchGate account. A total of 36 (22.2%) researchers had both an active Twitter account and a ResearchGate account. The characteristics of the Twitter and ResearchGate accounts identified are presented in P=.31) or on ResearchGate (15/23 (65%) vs. 95/139 (68.3%), respectively; P=.81).There was no difference between associate professor and full professor regarding active presence on Twitter (8/23 (35%) vs. 34/139 (24.5%), respectively; P<.001; P<.001; P=.01; P<.001; Over the period 2016-2020, researchers with an active Twitter account had more (median [IQR]) scientific publications , the number of publications , and the h-index . There was also a correlation between the number of followers/month and the number of publications  and the h-index . There was no correlation between the number of tweets/month or the number of followers/month and the number of citations per publication or the overall number of citations.Among researchers with an active Twitter account, there was a correlation between the number of tweets/month and the number of followers/month  scientific publications , the h-index , the number of citations per publication , and the overall number of citations .Among researchers with a ResearchGate account, there was a correlation between the number of followers and the number of scientific publications  was associated with the number of publications, the number of citations, and the h-index .To our knowledge, we describe for the first time the participation rates and professional use patterns of social networks among all academics from a medical specialty of a given country. We also explore for the first time the link between researchers’ medical publication activity and their presence on social networks.The 2 social networks analyzed in this work have different use in professional life. Twitter, which is not a network designed solely for professional use, allows subscribers to give their opinion, to follow some influencers, and also to exchange personal information. ResearchGate is reserved for researchers, and is used to promote their work and to connect with people working in the same field of research. Twitter is a network that requires active and frequent participation to disseminate information, whereas ResearchGate automatically imports publications from authors  and gives visibility to researchers with a high RG score, even if they are not very active on the network, allowing a more passive management of the account once it has been created. This may partially explain why the rate of researchers with a ResearchGate account is higher than that of researchers with an active Twitter account. Another likely explanation is that as ResearchGate is a social network specifically dedicated to research, it makes more sense for a researcher to be present there than to have a professional account on a mainstream network such as Twitter. The rates of use of professional social networks (Twitter: 42% 68/162) and ResearchGate: 67.9% (110/162)) are higher than those recently described among ENT surgeons, neurosurgeons, or pediatric orthopedists (Twitter: 2%-13% and ResearchGate: 23%-36%) 2 and Res. The preAmong anesthesia researchers, an active presence on Twitter is associated with better bibliometric parameters, in terms of both number of publications and citations. The same trend is observed on ResearchGate. However, our study methodology does not allow to establish a causal link between scientific activity and presence on social networks. There are several possible explanations for the link we have identified. It is possible that very prolific researchers have the desire to disseminate their numerous publications and are therefore more inclined to use social networks. It is also possible that being on a professional social network allows to widely disseminate publications to the connected scientific community and thus have a greater chance of being read and cited. By analogy with the studies conducted on medical journals and showing the effectiveness of Twitter in increasing citations, it may seem logical that a researcher who posts his/her new publications on Twitter would also have more citations at an individual level ,13,14. IDespite interesting results, our study has several limitations. First, this work was limited to French anesthesia researchers on a 5-year period. Given the academic organization of the medical professions in France , it is easy to have exhaustive access to the list of all academics in a given specialty. In other countries with a more decentralized academic organization , it is more complex to compile an exhaustive list of all academics in a country. In addition, social networks evolve very quickly , so it was essential to use data collected over a short period. However, because of the manual standardized procedure needed to detect all the accounts (which is time-consuming), the number of researchers that could be included was limited. Nevertheless, it seems necessary to confirm our observations in the academics of other countries. We chose the 2016-2020 period to analyze bibliometrics parameters because it corresponds to the period where social networks were started to be used in a massive way to promote research in France. It did not seem relevant for us to go further back in time, as the use of social networks was less common and the population studied would have been too disparate (old researchers who had retired or young researchers who had not yet started their academic activity). Second, even a standardized manual account search procedure has its flaws; some authors may use a pseudonym, a diminutive, or misspell their name when they register, etc. Third, some bibliometric parameters of ResearchGate such as RG score and total Research Interest score were not analyzed in our work. However, these scores are based on the number of publications and citations of researchers and have already been shown to be correlated with the h-index, the number of citations, the number of publication, and the academic level of registered researchers ,18,22,23Among French anesthesia researchers, an active presence on Twitter is associated with higher scientific publication and citations. Future studies could explore a possible causal link between these parameters.


Rectal cancer constitutes approximately one-third of all colorectal cancers and contributes to considerable mortality globally. In contrast to colon cancer, the standard treatment for localized rectal cancer often involves neoadjuvant chemoradiotherapy. Tumour response rates to treatment show substantial inter-patient heterogeneity, indicating a need for treatment stratification. Consequently researchers have attempted to establish new means for predicting tumour response in order to assist in treatment decisions. In this review we have summarized published findings regarding potential biomarkers to predict neoadjuvant treatment response for rectal cancer tumours. In addition, we describe cell-based models that can be utilized both for treatment prediction and for studying the complex mechanisms involved. Rectal cancers make up approximately one-third of colorectal cancers (CRCs) and contribute to a high cancer-related mortality in both men and women globally. Tumours in the rectum share molecular aspects with tumours in the colon , though Little is known about the underlying mechanisms governing tumour response to neoadjuvant chemoradiotherapy . Clinical and radiological factors that may play a role have been identified, such as size of the tumour, TNM stage, radiation dose and fractioning, as well as the time period between neoadjuvant chemoradiotherapy and surgery . HoweverIn recent years, novel methods to improve the prediction of sensitivity to therapies have been developed, such as proposed novel biomarkers . While mThe outstanding complexity of molecular cell signalling is disrupted in cancer. The dysregulations that result in cancer growth originate in changes to the DNA. While the exact mutational progression and tumour development differ from patient to patient, many cancer types share common features. Rectal tumours can be sub-grouped based on genetic traits such as gene mutations, RNA expression and epigenetic modifications . These gDNA mismatch repair deficiency is a well-established biomarker in colorectal cancer. Tumours are typically classified as either MMR proficient (pMMR) or MMR deficient (dMMR), where the latter can lead to microsatellite instability (MSI). MSI accounts for about 15% of all CRC . Due to For rectal cancers, mismatch repair does not seem to fulfil the criteria for a useful predictive marker due to its applicability to the majority of patients.BRAF, KRAS, NRAS, ERBB2, and ERBB3) and the PI3K/AKT/mTOR pathway  are frequent in rectal cancer , > 0.2 [n = 45]) ) . A high n = 45]) . However+ T cells both prior to neoadjuvant treatment and post-treatment have been shown in most [+ as well as CD4+ TILs in pre-treatment biopsies were correlated to a good tumour response after chemoradiotherapy in terms of reduced tumour size and histological grade [+ TILs both in pre-treatment samples and in post-treatment samples were associated with a poor treatment outcome [+ T cells is significantly increased in post-treatment samples compared to pre-treatment [+ and CD8+ TILs in pre-neoadjuvant chemoradiotherapy samples were shown to be associated with good response to the treatment [+ and CD8+ TILs in post-neoadjuvant chemoradiotherapy samples were found to be higher compared to their corresponding pre-treatment samples [+ T cells and T cells expressing granzyme B (GrzB+)  in tumour stroma is increased in rectal cancer after neoadjuvant chemoradiotherapy [+ and CD8+ T cells in tumour epithelium as well as in tumour stroma were found to be significantly lower after treatment. The increase in number of CD8+/GrzB+ cytotoxic T cells in post-treatment tumour samples was also associated with a lower likelihood of local recurrence and higher regression grade, suggesting that CD8+/GrzB+ T cells may promote a better outcome and contribute to local tumour control. Indeed, a high density of CD8+ TILs has been suggested as a useful biomarker for a better prognosis of rectal cancers [Having high amounts of CD8 in most –99 but n in most , 101 to al grade . Another outcome . Yet othreatment , 94. Denreatment , 96. In  samples , 96, andotherapy . Interes cancers . A recen+ and CD8+ T cells in the invasive margin and in the tumour itself. From this, tumours are stratified into categories where for example the category of tumours with high densities of T cells at both locations have the most favorable prognosis. The prognostic applicability of immunoscore for rectal cancer patients not receiving chemoradiotherapy has been confirmed [N = 17) showed no relapse during the study.A forthcoming histochemical assessment of T cell infiltration termed ‘immunoscore’ has been extensively validated and is a powerful prognostic tool for patients with colon cancer. Its capacity has indeed been demonstrated to surpass that of classical TNM scoring , 103. Imonfirmed . In a reonfirmed . ISB was+ TILs, constitute an important variable for predicting the response to neoadjuvant chemoradiotherapy  have, in this regard, received extra attention. These T cells are targets for immune checkpoint blockade treatment with anti-CTLA4, and a low density of FoxP3+ TILs is associated with favorable prognosis in most solid tumours [+ TILs remained stable while stromal CD8+ T cells increased [+ TILs numbers were found strongly correlated with better prognosis, and a high pre-treatment intraepithelial CD8/FoxP3 ratio was found to be a predictor of tumour regression. Neoadjuvant chemoradiotherapy has also been reported to increase the density of CD4+ TILs but with maintained expression of CTLA-4 and densities of FoxP3+ [+ cell density after radiotherapy was associated with a favorable regression grade [+ nor CD8+ T cells correlated with treatment outcome [+ TIL density correlated with better progression-free survival [+ TILs and survival was detected, while a decrease in CD8/FoxP3 ratio after treatment predicted better overall and progression-free survival. A more recent study comparing pre-treatment and biopsy material obtained from rectal tumours 7 days after irradiation showed that a high density of CD4+ and FoxP3+ cells pre-treatment was significantly associated with tumour shrinkage, and that this link was most pronounced in the 7 day biopsies [+ and FoxP3+ T cells in relation to each other as well as the distance from the tumour cells  could reflect functionality. This might help to explain some of the differences obtained in the correlations of patient survival and histochemical analyses of TILs in rectal cancers, as the latter have not been enumerated in the stromal and intra-tumoural areas separately in all studies. Indeed, a study investigating the distance between FoxP3+ and CD8+ T cells pre- and post- chemoradiotherapy in the stroma and the tumour has also indicated that a short distance between the two cell types in the tumour epithelium is associated with a favorable prognosis, and that the opposite was observed in the stromal compartment [+ and to FoxP3+ cells were assessed and suggested to be a more precise prognostic tool than mere cell counting of the two cell types [CD4 tumours , 107. So tumours , 109. A ncreased . High pof FoxP3+ . An immuon grade . However outcome . Also, asurvival . In the biopsies . The locpartment . In a rell types .These studies showed that the density of CD4+ T cells might play an important role in the tumour microenvironment as another subset of tumour-infiltrating lymphocytes. However, as there are some controversial results, further investigation on this specific T cell subtype is required to evaluate the clinical relevance in neoadjuvant chemoradiotherapy in rectal cancer.+ T cell density in the tumour before the treatment and a higher CD8+ T cell density in the stromal compartment after treatment. It has also been reported that the density of CD8+ TILs and PD-L1 expression in the tumour was significantly increased after neoadjuvant chemoradiotherapy treatment [+ TILs both pre- and post-treatment had improved disease-free survival. In a patient cohort of colorectal tumours not receiving neoadjuvant therapy, PD-L1 expression was reported to be associated with a poorer prognosis for patients with rectal tumours, but not for patients with colon tumours [PD-L1  is a cell-surface protein that is frequently upregulated in cancer cells. It binds to the PD1 receptor on activated T cells to transmit inhibitory signals and as such prevents cell killing. This ligand/receptor interaction can be blocked by immune checkpoint inhibitor drugs. Consequently PD-L1 expression in rectal cancers after treatment has also been assessed together with T cell stainings. An increase in stromal immune PD-L1 expression after chemoradiotherapy has been reported . This inreatment . In addi tumours .. Also,  tumours . Finally tumours .In summary, PD-L1 appears to be induced by chemoradiotherapy, but how to interpret the levels of PD-L1 staining before and after treatment for prediction and prognostication is still unclear. Since PD-1 functions as an immune checkpoint, PD-1 and its ligand PD-L1 are promising targets for immunotherapy. Evaluation of PD-L1 in the tumour microenvironment could be valuable for predicting the response to neoadjuvant chemoradiotherapy.Circulating tumour cells (CTCs) are potentially promising biomarkers to predict response to treatment, prognosticate and predict recurrence in various types of cancers, including colorectal cancer . Most reKRAS mutations and/or O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation has been determined in LARC patients [KRAS mutations was lower in both poor and good responders. Moreover, the status of MGMT methylation in baseline cfDNA was significantly higher in responders compared to non-responders. Thus CTCs and cfDNA hold a certain promise as useful tools to evaluate the effect of chemoradiotherapy in patients with rectal cancer.Cell-free DNA (cfDNA) is another potential biomarker in rectal cancer. The concentration of cell-free DNA in plasma and whether it include patients . The conTP53 and APC genes in pre-treatment samples were detected and these mutations were negatively correlated with the response to neoadjuvant chemoradiotherapy [Moreover, circulating tumour DNA (ctDNA) provides important information for the diagnosis of several malignant tumours . ctDNA motherapy . In a reotherapy . All theAlterations in carcinoembryonic antigen (CEA) levels following neoadjuvant chemoradiotherapy has been extensively studied . HFusobacteria correlated with a worse pathological response [Dorea, Anaerostipes and Clostridium XVIII were biomarkers of neoadjuvant chemoradiotherapy responders, and Eisenbergiella, Granulicatella and Ralstonia were biomarkers of neoadjuvant chemoradiotherapy non-responders. In a similar study, albeit with fewer samples, Bacteroidales were found enriched in patients who did not reach complete response post-treatment, and Duodenibacillus massiliensis was associated with a tumour response [The gut microbiota has been identified as a potentially important factor in how cancer respond to therapies , and theresponse . Anotherresponse . From prresponse .In summary, we have described potential biomarkers including molecular genetic markers, immunological markers and other biomarkers that have been analyzed from patients samples to predict the survival of rectal cancer patients and patients outcomes from chemoradiotherapy. In the next section, we will discuss cell-based models including commercial cancer cell lines and patient-derived xenografts/organoids originally from tumour cells of patients to predict tumour response to neoadjuvant chemoradiotherapy.Immunohistochemical analyses of tumour biopsies have been used to enumerate cells in the tumour microenvironment with the aim of predicting effectiveness of therapies. Formalin-fixed paraffin-embedded (FFPE) tissues can be stored long-term and utilized for both immunohistochemical studies and for genetic analysis. However, although FFPE tissues can be useful in identifying new potential biomarkers, these tissues are not biologically active. Analysis of FFPE material is as such not applicable for gaining mechanistic insight into cellular interactions, unlike cell-based models Fig. . Cell-baCancer cell lines kept in culture have been used for decades for in vitro modeling of cancer. The maintenance of cell lines grown in 2D cultures is fairly simple and genetic modifications can be performed using genome-editing techniques to knock genes of interest in or out . In broaKRAS wild-type. This, and reported overall response rates in the study well resembles what is seen in the clinical setting [KRAS mutations showed resistance to anti-EGFR therapy, while PDXs without KRAS mutations responded to anti-EGFR therapy [With the aim of better recapitulating patient tumours and striving for personalized medicine, 3D culture platforms including patient-derived xenografts (PDX) and organoids have been developed. In the PDX approach, dissected tumour tissue from the patient is engrafted to severely immunocompromised mice . Compare setting . In addi setting . A few s setting . Moreove therapy , 161. In therapy . However therapy , and the therapy . AnotherPatient-derived organoids are 3D cell culture systems where tumour cells from the patient tumour are expanded within a matrix. Organoids have been shown to largely recapitulate histopathological and cellular structures of the original tumour –167. ThoRAS mutations, tumour organoids and colon organoids with wild-type RAS as well as tumour organoids and colon organoids with CRISPR-introduced oncogenic KRAS mutations [RAS showed a correlation with resistance to RAS inhibitors. In another study, a colorectal cancer biobank comprising 35 patient-derived organoids and 59 patient-derived xenografts were used to identify novel biomarkers for prediction of sensitivity to the EGFR inhibitors [BRAF mutated, poorly differentiated and/or of mucinous type [Several studies have demonstrated that patient-derived organoids can be used to study how various factors can affect therapy sensitivity. One study assembled a panel of patient-derived colorectal organoids including tumour organoids harbouring utations . The prehibitors . Drug-schibitors . In thishibitors . Establious type , which mAlthough there are several advantages of using patient-derived organoids there is still a need to improve the technique. Generated patient-derived organoids in published studies mostly lack fundamental extracellular elements and are grown in a highly artificial media, factors that could challenge clinical transition of findings .KRAS were more sensitive to cetuximab compared to those with mutated KRAS [The established organoids maintained the mutation status of actionable gene targets in corresponding tumour samples and recapitulated patient-specific clinical responses to radiation and chemotherapy. Tumouroids have been successfully transplanted orthotopically in vivo and both cancer-specific ex vivo and in vivo sensitivity to treatments could be assayed within 6–12 weeks after establishment . A livinted KRAS . Anotherted KRAS . This stTaken together it is probable that patient-derived organoids of rectal cancers could be a valuable translational research tool to discover novel biomarkers and personalized treatment strategies.A potential consequence of mutations in cancer cells is the creation of neoantigens, which following display by MHC molecules on the surface of the tumour cell, can become visible to the immune system . The recIdentifying biomarkers to predict the response of rectal tumours to neoadjuvant therapy is of great interest. As treatment responses vary drastically, such tools would aid patient care in the clinical setting. An abundance of various types of biomarkers have been evaluated, including many molecular genetic markers and immunological markers, several of which have been found correlating with clinical outcome. In addition, several types of cell-based models of rectal cancer have been developed and successfully used to predict sensitivity of tumour cells to treatment. Rectal cancer tumours are infiltrated by immune cells and have an active interplay with their microenvironment. This seems to play an important role both for the response to therapy and for long term survival of rectal cancers patients. Cell-based models can facilitate integration of both patient-specific tumour characteristics and the immune microenvironment, which has been utilized to predict treatment sensitivity and could potentially be used to further elucidate the mechanisms at play. Although a number of biomarkers and cell-based models have been shown to predict tumour response to treatment to various degrees, none are yet recommended for clinical use. The search for robust, novel methods to predict tumour sensitivity is on-going, and additional validation of identified markers is needed in order to facilitate clinical implementation.


Pharmaceutical compounding ensures access of individuals with specific requirements to individualized therapy. However, there is an inconsistency of compounded medication quality. Therefore, advancing the rational use of compounded medication is essential for patient safety and medication effectiveness.The presented study was aimed to investigate the healthcare practitioners’ knowledge, perception, and practice of extemporaneous compounding and its contribution to the prevalence of antimicrobial resistance.A descriptive cross-sectional survey using a structured questionnaire was conducted. The study participants were 300 healthcare practitioners working in Jimma University Medical Center, hospital pharmacies, and community pharmacies in Jimma and Mettu Town, Southwest Ethiopia.Most respondents were pharmacists (62.7%) and first-degree holders (48.3%). The majority of them had experience in administering (57.7%), preparing (38%), prescribing (21%), and repackaging and labeling (14%) compounded medications. Commonly they request compounded medications when prepackaged products (77.7%) and needed dosage regimens (72.3%) were not available in the market. However, most of them believed that compounded medications might lack quality (49%) and had poor patient compliance (40.7%). Moreover, they fear that inappropriate preparation processes (75%) and under-dose administration (59%) of compounded medication might contribute to the development and prevalence of antimicrobial resistance.Most healthcare practitioners practice rational use of compounded medications and strongly agree that inappropriate compounding of antimicrobials contributes to antimicrobial resistance development. Ensuring medication availability in healthcare facilities (HCFs) is crucial to providing good quality healthcare and reducing avoidable patient readmissions. In addition to manufacturing in the licensed pharmaceutical industries, extemporaneous compounding is the essential source of medication availability, especially for personalized healthcare –4.Since the mid-1980s, the number of patients seeking personalized healthcare has been increasing. It is due to one size medicine (strength and dosage form) does not fit all. Therefore prescribing, dispensing, and administering extemporaneously compounded medication is a good solution. Extemporaneous compounding is the art and science of combining, mixing, repackaging, and labeling a drug product. Historically, it has been a crucial part of the pharmaceutical process. It has long been a service provided by licensed pharmacists since the origin of pharmacy. Today, with the technological advancements in the pharmaceutical field and increased need, the compounding pharmacy industry is experiencing a resurgence and becoming more relevant than ever , 5–11.The medicine compounders compound according to a licensed practitioner’s prescription, medication order, or initiative based on the practitioner-patient-pharmacist relationship in the course of professional practice , 12. It The compounded medications should be developed to meet unique medical needs and ensure patient safety. Therefore, compounding prescriptions should be prescribed by a licensed practitioner, compounded and dispensed by the licensed pharmacist, administered and used correctly. Compounding pharmacies must also comply with good compounding practice regulations for compounding within hospitals, community pharmacies, home infusion pharmacies, and, more recently, outsourced compounding facilities , 8, 9.The regulatory scrutiny of pharmaceutical compounding practices is significantly less rigorous than that required for FDA-approved medications . It is exempted from regular inspections, quality control testing, and rejection of material not meeting specifications. Furthermore, they are not clinically assessed for safety or efficacy before marketing. Moreover, there is no standard labeling or prescribing information with instructions for the safe use of compounded products. They are the potential causes for poor quality medication preparation . Finally, they may pose potentially fatal health risks for the users , 15–19. Poor quality of compounded medication causes administration of a low dose of active ingredients. Administration of lower-dose antimicrobials can cause microbes, including bacteria, fungi, parasites, and viruses, to adapt and become less susceptible to medical treatment. Therefore, it can play a role in the emergence and spread of antimicrobial resistance (AMR), which causes a profound threat to human health. Moreover, irrational prescribing, packaging and labeling, administering, and using compounded medicine can contribute to AMR prevalence , 22–24. A descriptive cross-sectional study was conducted from March 15 to May 25, 2021, among the HCPs working in selected HCFs. The HCFs were Jimma University Medical Center, hospital pharmacies, and community pharmacies located in Jimma Town and Mettu Town. These towns are located at 346 km (Jimma Town) and 600 km (Mettu Town) from Addis Ababa, the Capital City of Ethiopia in the Southwest. The study settings have been giving healthcare services to a large population. They were selected through convenience sampling.Jimma University Medical Center is the only teaching and referral hospital in the southwestern part of Ethiopia. With 800-bed capacity and hospital pharmacies, it provides healthcare services for inpatient and outpatient attendants coming to the hospital from the catchment population. Moreover, community pharmacies in study settings are giving pharmaceutical care. It includes compounding pharmaceutical products and dispensing.The study participants were HCPs such as physicians, pharmacists, nurses, medical laboratory technologists, and midwives. They were chosen since the study focused on one of the most important elements of healthcare. So, they should be aware of the need for compounded medications and their safety. Additionally, they should be encouraged to report potential risks linked to poor quality compounded drugs and effectively protect the patients.The voluntary study participants were selected and sampled using the convenience sampling technique. Accordingly, 243 HCPs from Jimma Town and 57 19%) pharmacists from Mettu Town were involved in the study. Due to pharmacy professionals being formally licensed and experienced professionals for compounding both sterile and non-sterile medications 9% pharma, most ofData was collected using a self-administered structured questionnaire. It was constructed using the English language after an intensive review of published relevant literature , 26, 27.A pilot study was conducted using the first draft of the survey instrument. Randomly selected four respondents from each HCF have filled the questionnaire and commented on the clarity of each question. Their comments and responses were evaluated and used to guide revisions. Finally, minor editions were performed to avoid the ambiguity of the questionnaire. Data obtained from the pilot study was not included in the final analysis.The principal and co-investigators provided training for data collectors (pharmacists and nurses). Before data collection, potential study participants were verbally provided all pertinent information about the study. After allowing them ample opportunity to ask for uncertainty, data collectors provided the data collection sheet. Following sufficient time for reading, the study participants were asked for their voluntarism and requested to agree to verbal informed consent before filling the questionnaire. The data collector supplies the questionnaire for the voluntary participant and collects it after fill. The collected data were checked for completeness and de-identified to ensure confidentiality.After collecting the filled questionnaire, data were entered and descriptively analyzed using Statistical Package for the Social Sciences (SPSS), version 21.0. Descriptive analysis, such as frequency distribution and percentage, was used to analyze categorical data.Inclusion criteria: Voluntary HCPs on duty during the study period were contacted and included in the study.Exclusion criteria: Involuntary HCPs were excluded from the study.Rational use of compounded medication: Compounded medication accomplishing key elements of rational drug use such as effective, acceptable quality, acceptable safety, accurate prescribing , appropriate and timely administration, affordable and dispensed correctly for the right patient .Extemporaneous compounding: Small scale preparation, altering, mixing, repackaging, and labeling of medication with prescriber’s instructions .RationalThe present study was conducted using 300 study participants who were voluntarily consented to participate in the study. They were working at different units at Jimma University Medical Center, such as hospital pharmacies and wards 148), Jimma Town community pharmacies (95), and Mettu Town community pharmacies (57). The respondents had worked as healthcare professionals for a mean of 5.78 ± 4.6 years (range 1–32 years)  (p = 0.53). Most first-degree and specialty (master degree) holders had practiced more on prescribing (47), preparation (75), and repackaging and labeling (27) of compounded medications. However, most diploma holders (91) had practiced administration of compounded medications.Multiple response analysis indicated that 262 (87.33%) of the study participants had participated in at least one process of rational use of extemporaneously compounded medications Fig. . They inThe study respondents practiced rational use of extemporaneously compounded antimicrobials at different frequencies. Most of them practiced like monthly  108 36%), almost every day 93 (31%), not at all 77 (25.7%) and always 22 (7.3%), respectively. Most of the time, the respondents didn’t prescribe, dispense or prepare antimicrobial medicine extemporaneously due to different challenges . The main findings of the present investigation showed that most of the HCPs participated in the preparation and administration of the compounded medications Fig. . PharmacAn earlier study has linked the prevalence of compounding services to requests for individualized therapy , 30. SimVarious studies indicated the high demand for pharmaceutical compounding services at different levels of HCFs. However, the service is not prevalent due to several challenges , 31. AccPrevious studies reported a lack of prescriptions for requesting compounding services as one of the key reasons for not providing compounding services . However, the present study did not. It might be due to the prescribers' lack of confidence in the quality and effectiveness of the compounded medication.Extemporaneously compounded medications are not undergoing regular inspections, quality control testing, and rejection of material not meeting specifications. However, their quality should be regulated to ensure safety . The preThe present study indicated that most healthcare practitioners provide healthcare services using compounded medications. They apply rational use principles mainly for administering and preparing compounded medications. Unavailability of prepackaged products in the market and unavailability of needed dosage regimens were the most common reasons mentioned for practicing rational use of compounded medication. However, lack of trust in the quality of the compounded medication and poor patient compliance was the most listed challenges. The majority of them revealed that compounding caused inappropriate preparation processes, and under-dose medication administration can lead to the development and prevalence of antimicrobial resistance.Due to individualized therapy is being in high demand, compounding services are becoming critical. Thus, healthcare practitioners should take training on extemporaneous compounding. Moreover, compounding services should be incorporated into professional development and continuing education programs, and the quality of compounded medication should be regulated.The present study did not statistically analyze the degree of correlation between challenges and reasons of compounding to compounding practices. It can be a basic study point for future researchers.


This study examines the influence of an indigenous concept – face on online purchases in China. Specifically, we test the mediating role of materialism and the moderating role of price consciousness. We conduct a survey of 315 Chinese consumers. The results demonstrate that consumers tend to make online purchases to satisfy some facets of their materialistic needs and then gain face, especially for those highly conscious of price. The current research can help both scholars and practitioners better understand Chinese consumers and their decision-making processes. Implications, limitations, and directions for future research are also provided. Over the last two decades, the Internet has developed considerably in China. As of December 2020, the number of netizens in China reached 989 million, accounting for approximately one-fifth of the world’s netizens, among which the number of online shopping users reached 782 million, accounting for 79.1% of the total number of netizens . The devDue to its profound influence on human behavior, culture has been widely considered in consumer research . Howevermianzi), which is defined as the sense of favorable social self-worth that a person wants others to have of him or her in social interactions  was performed with AMOS for all the latent variables to develop a good measurement model. The results of CFA indicated a sound model fit : Chi-squr = 0.515, p < 0.001) but does not significantly correlate with the acquisition centrality facet of materialism. The results shown in R2 value resulting from adding materialism-S&H to the equation is relatively large, demonstrating that the influence of face on online purchases is completely mediated by materialism-S&H. However, when we include materialism-AC in the regression model (Model 4), both face and acquisition centrality have impacts on online purchases.To examine the mediating effect, the steps proposed by We further examined the mediation effect of materialism-S&H between face and online purchase with the bootstrap method proposed by r = 0.190, p < 0.001). The model achieves substantial incremental variance (ΔR2 = 0.036), and the change in F is significant at the p < 0.001 level. This result indicates that a higher level of price consciousness can lead to a stronger relationship between materialism-S&H and online purchases. The graphical depiction given in Last, a hierarchical regression analysis is performed to test the moderating effect of price consciousness. Control variables, independent and moderating variables and the interaction term were added to the model in sequence. The results in The results of the current research explore the roles of face, materialism, and price consciousness in stimulating Chinese online shopping behavior. First, it is noteworthy that the three-factor structure of materialism originally derived from Acquisition centrality is a self-directed enduring value and thus not related to others. The first dimension of materialism correlates with face and fully mediates the relationship between face and online purchases, whereas the second does not, further showing that this dimension of materialism is socially directed. Moreover, both of the dimensions influence online consumption, while the impact of the first dimension is much stronger than that of the second, as social influence greatly drives consumption in China. This result verifies In addition, there is no direct correlation between price consciousness and online consumption. This may be the case because price consciousness has converse effects on online purchases. First, price-conscious consumers are likely to be frugal , and theThere is no study without limitations. First, we only use a general item to measure consumers’ online purchase frequency in this study. Future research should develop multidimensional scales that measure consumers’ buying behavior across different categories of online products. Such work would help brand managers develop appropriate strategies for this large market.In addition, this study focuses on the younger generation between 20 and 30 years of age because this cohort makes the majority of online purchases. Considering that e-commerce is so prevalent across China, it will be necessary to extend the present research to other generation cohorts. Moreover, the current study was conducted online. We did not consider the regions/cities where the respondents lived even though within-country diversity in consumer preferences and behavior has been found in China . Future Finally, in our contemporary consumption-oriented society where materialism is a sign of prosperity , the matThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.GS developed the theoretical framework and worked on literature review and manuscript writing. FS was in charge of data collection and analysis. XM took part in literature review and data analysis. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


N-cyanomethyl-4-trifluoromethylnicotinamide, FLO) is a new type of pyridinamide insecticide that regulates insect growth. Because of its wide application in agricultural production and high solubility in water, it poses potential risks to aquatic environments and food chain.Flonicamid (Ensifer adhaerens CGMCC 6315 was shown to efficiently transform FLO into N-(4-trifluoromethylnicotinoyl) glycinamide (TFNG-AM) via a hydration pathway mediated by two nitrile hydratases, PnhA and CnhA. In pure culture, resting cells of E. adhaerens CGMCC 6315 degraded 92% of 0.87 mmol/L FLO within 24 h at 30 °C . Both free and immobilized  E. adhaerens CGMCC 6315 cells effectively degraded FLO in surface water. PnhA has, to our knowledge, the highest reported degradation activity toward FLO, Vmax = 88.7 U/mg (Km = 2.96 mmol/L). Addition of copper ions could increase the enzyme activity of CnhA toward FLO by 4.2-fold. Structural homology modeling indicated that residue β-Glu56 may be important for the observed significant difference in enzyme activity between PnhA and CnhA.In the present study, E. adhaerens may be a good strategy for bioremediation of FLO in surface water. This work furthers our understanding of the enzymatic mechanisms of biodegradation of nitrile-containing insecticides and provides effective transformation strategies for microbial remediation of FLO contamination.Application of The online version contains supplementary material available at 10.1186/s12934-021-01620-4. E. adhaerens efficiently degrades the insecticide FLO via a hydration pathway.Both free and immobilized cells effectively degrade FLO in surface water.E. adhaerens nitrile hydratases CnhA and PnhA both hydrolyze FLO to TFNG-AM.PnhA has, to our knowledge, the highest reported degradation activity toward FLO.β-Glu56) may cause a significant difference in two NHase activities.The key residue (The online version contains supplementary material available at 10.1186/s12934-021-01620-4. N-cyanomethyl-4-trifluoromethylnicotinamide, FLO) is a novel systemic insecticide with selective activity that exhibits very good efficacy in pest control . The half-life (t1/2) was calculated as t1/2 = (ln2)/k, where k is the apparent elimination constant. The first-order equation provided a satisfactory fit for the data (r > 0.9) [Half-life values for the degradation of FLO were determined by plotting ln(r > 0.9) .E. adhaerens CGMCC 6315 were constructed using Phyre2 (http://www.sbg.bio.ic.ac.uk/phyre2/html/) and the SWISS-MODEL website (https://swissmodel.expasy.org/interactive). The crystal structures of NHase subunits from Pseudonocardia thermophila and Pseudomonas putida  [α-subunit of PnhA, the β-subunit of PnhA, the α-subunit of CnhA, and the β-subunit of CnhA, respectively. Global model quality estimation (GMQE) and quantitative model energy analysis (QMEAN) were used to assess the quality of the constructed NHase structures [Structural homology models of the NHases from qz9.1.B) , 36 wereructures .E. adhaerens CGMCC 6315 metabolized FLO to one apparent polar metabolite with retention time 3.25 min by HPLC analysis  in Fig. E. adhaerens CGMCC 6315 was only 7.4 h, significantly shorter than that in FLO degradation by A. faecalis CGMCC 17553 (15 h), E. meliloti CGMCC 7333 (60 h), and Aminobacter sp. CGMCC 1.17253 (178.8 h) [E. adhaerens CGMCC 6315 may be more advantageous for microbial restoration of FLO-contaminated environments. Metabolic pathways of FLO degradation in various microbes and the FLO metabolites in common fruit and vegetable crops are shown in Fig. Resting cells of 178.8 h) . TherefoE. adhaerens CGMCC 6315 was inoculated into surface water to examine its ability to degrade FLO. After incubation for 4 d, the FLO content was reduced from the initial value of 0.21 mmol/L to 0.01 mmol/L (95.2% degradation) in Fig. FLO is highly soluble in water and can remain as residue in the edible parts of crops that enter the food chain . E. adha E. adhaerens CGMCC 6315 cells immobilized by gel beads using calcium alginate as a carrier were also prepared for evaluation of FLO degradation ability in surface water. The control beads adsorbed some FLO over the first 2 d; 11.1% of the initial FLO was adsorbed  [M. flocculans is usually limited to microbe–plant combined remediation. E. adhaerens, as a nitrogen-fixing and plant growth-promoting rhizobacterium, is a common inhabitant of soil and water environments, and shows great potential to decompose complex organic pollutants [E. adhaerens breaks down the pesticide thiamethoxam and produces secondary metabolites that are beneficial to plant growth and germination. In the present study, E. adhaerens CGMCC 6315 is shown to be capable of removing FLO from surface water.We previously isolated an effective thiacloprid-degrading strain, llutants . Zhou etllutants  reportedEs. coli Rosetta (DE3) overexpressing E. adhaerens CGMCC 6315 NHase genes were constructed in our previous study [E. adhaerens CGMCC 6315 contains genes encoding two nitrile hydratases, one (CnhA) encoded on the chromosome and the other (PnhA) on a plasmid. Their NHase gene clusters composition in E. adhaerens CGMCC 6315 is ⟨α-subunit⟩, ⟨β-subunit⟩, and ⟨activator protein⟩. cnhA has gene structure α-subunit (648 bp), β-subunit (660 bp), and activator protein (375 bp). There is a four-base (ATGA) overlapping sequence between the α-subunit and β-subunit genes, and there is an overlapping sequence of 14 bases (TTGAACACGTGTAA) between the β-subunit gene and the activator gene, which is similar to our previous report for E. meliloti CGMCC 7333 nitrile hydratase , β-subunit (657 bp), and activator protein (360 bp). The overlapping sequence between the α-subunit and β-subunit genes is simply the base “A”, which differs from the four bases in cnhA, E. meliloti CGMCC 7333 NHase, Variovorax boronicumulans CGMCC 4969 NHase [us study . E. adhasubunit 68 bp, β-s69 NHase , 33, andα-subunits indicated that CnhA clustered in a branch with the NHase of other FLO degrading bacteria, E. meliloti CGMCC 7333 and Aminobacter sp. CGMCC 1.17253 [E. adhaerens CGMCC 6315 PnhA and CnhA with the enzymes from E. meliloti CGMCC 7333, the protein similarities were 51.63% and 82.33%, respectively. E. adhaerens CGMCC 6315 PnhA and CnhA clustered in different branches, indicating evolutionary divergence  had no activity toward FLO. The results indicated that PnhA and CnhA each degrade FLO to TFNG-AM via hydration.SDS-PAGE analysis suggested that the solubility of CnhA was good Fig. B, lane 4 1.16731 . RestingAminobacter sp. CGMCC 1.17253 NHase activity also decreased dramatically, like that of CnhA [M. flocculans CGMCC 1.6731 was preincubated for 2 h at 20–60 °C and the residual activity remained at about 60% [The optimal pH for FLO hydration by CnhA was 8.0 Fig. A, and thbout 60% .Fig. 5En2+ ions increased the activity by 4.2-fold compared with the control treatment   [2+ ions may promote enzyme folding, thereby forming a larger amount of NHase with the correct conformation and hence increasing the enzyme activity [Addition of many types of metal ion slightly promoted CnhA activity in hydration of FLO. However, strikingly, addition of Cuns) Fig. E. This pCC 4969) , 28. We activity . Among tVmax was 9.55 U/mg. The Michaelis constant and Vmax of PnhF from M. flocculans CGMCC 1.16731 involved in the formation of TFNG-AM from FLO were 32.9 mmol/L and 5.9 U/mg   Fig. G. FurtheVmax was 88.7 U/mg. The Vmax values of NitA, NitD, PnhF and Aminobacter sp. CGMCC 1.17253 NHase involved in the formation of TFNG-AM from FLO were 0.58 U/mg, 0.18 mU/mg, 5.9 U/mg, and 14.98 mU/mg, respectively  play important roles in the catalytic activity of P. putida NHase [β-subunit of E. adhaerens CGMCC 6315 PnhA (Fig. The second-shell residues da NHase , 46. TheE. adhaerens CGMCC 6315 efficiently degrades the insecticide FLO, and showed that two NHases from this bacterium, PnhA and CnhA, mediate the hydrolysis of FLO to metabolite TFNG-AM. Both free and immobilized E. adhaerens CGMCC 6315 cells were found to effectively degrade FLO in surface water. PnhA has the highest degradation activity toward FLO of any NHase yet reported. CnhA is more tolerant to a wide range of pH, heavy metal ions, and organic solvents. These findings could help to generate effective strategies for microbial remediation of FLO contamination.In this study, we found that Additional file 1: Figure S1. Phylogenetic analysis of NHases; Figure S2. Kinetic parameters of FLO degradation reactions catalyzed by E. adhaerens CGMCC 6315 PnhA and CnhA; Figure S3. Alignment of sequences of E. adhaerens CGMCC 6315 NHases PnhA and CnhA with sequences of NHases from Pseudonocardia thermophila and Pseudomonas putida that were used as templates for homology modelling.


Opioids are administered to cancer patients in the period surrounding tumour excision, and in the management of cancer-associated pain. The effects of opioids on tumour growth and metastasis, and their consequences on disease outcome, continue to be the object of polarised, discrepant literature. It is becoming clear that opioids contribute a range of direct and indirect effects to the biology of solid tumours, to the anticancer immune response, inflammation, angiogenesis and importantly, to the tumour-promoting effects of pain. A common misconception in the literature is that the effect of opioid agonists equates the effect of the mu-opioid receptor, the major target of the analgesic effect of this class of drugs. We review the evidence on opioid receptor expression in cancer, opioid receptor polymorphisms and cancer outcome, the effect of opioid antagonists, especially the peripheral antagonist methylnaltrexone, and lastly, the evidence available of a role for opioids through non-opioid receptor mediated actions. Opioids are administered to cancer patients to manage the pain associated with the disease, its treatment and in palliative care. The possibility that opioids may alter the course of cancer is therefore of high clinical relevance. Opioids given to cancer surgery patients in the perioperative period are of particular interest because despite the short time frame when they are administered, they have been hypothesised to contribute, together with a number of other optimisable variables, to long-term cancer outcome , 2.In vitro and animal studies evaluating the influence of opioids on tumour growth and metastasis are abundant and highly discrepant, as reviewed elsewhere . Finally, we suggest that the effects of opioids on non-opioid receptors, including but not limited to TLR4, may offer novel insights into the role of opioids on cancer in the future.th, 2021, further adding relevant studies that were cited by these articles. The results are compiled in We searched the literature for studies comparing the expression of opioid receptors in cancer cells or tissues to that of relevant, healthy control cell or tissues. We used the following search protocol in PubMed: (“opioid receptor expression”) AND (((cancer) OR (tumour)) OR (tumor)) and screened all the hits produced by the search up to September 10Altered opioid receptor expression in cancer has been observed as early as 1996 . ChangesWhile μOR has long been the focus of attention in the tumour microenvironment, δOR also showed an increase in expression compared to normal tissue –30, and in vitro and in small, medium, or large tumours  were reduced from 5 µM to 7 nM and from 25 ng/mL to 6 ng/mL, respectively, the potential clinical implications being increased effectiveness of 5-Fluorouracil and Bevacizumab. However, the mechanism for the effect of MNTX involved a membrane-bound phosphatase acting on Src downstream of VEGFR. Together with the fact that naloxone and naltrexone did not replicate the effect of MNTX, these results show that the synergistic effect of MNTX on endothelial cells is non-µopioid receptor mediated  in both the pre-inoculation and post-inoculation groups. Furthermore, the time to tumour appearance was prolonged by 6-21 days past the median 28 days observed in the control groups. Tumour size was also reduced, however, at the time of death there was no difference in tumour sizes between any of the groups, implying the delay in tumour development as the cause of the size disparity . The secin vivo effects of naltrexone in a study using different dosing regimens: in mice inoculated intradermally with syngeneic neuroblastoma cells, subcutaneous administration of 0.1 mg/kg naltrexone daily led to a reduction in tumour incidence, delay in the time before the tumour appeared and increase in the mean (42%) and median (36%) survival times. However, increasing the dose of naltrexone to 1 mg/kg was less efficacious than 0.1 mg/kg, with the 1 mg/kg group showing no statistically significant reduction in tumour appearance after 29 days, and a survival time comparable to that of the controls. Strikingly, the group receiving 10 mg/kg had statistically significant shorter mean (19%) and median (22%) survival times as well as a reduced time to tumour appearance. Furthermore, this was the only group with a statistically significant difference in the size of tumour at time of death, with an increased mean from 26.2 mm to 32.4 mm anthracene (DMBA). After 25 days of receiving a 75 mg/kg naltrexone-supplemented diet, the volume of the mammary tumours was decreased by 23% compared to the control group. Furthermore, tumour regression was observed in 70% of the treatment group. Interestingly, the naltrexone-responsive tumours showed observable amounts of oestrogen and progesterone receptors, contrasting with the unresponsive tumours which were progesterone and oestrogen receptor-negative . Moreove control . Naltrex control .post-hoc analysis was conducted on a cohort of patients with advanced cancer being treated with MNTX for opioid-induced constipation. The difference in the median overall survival was statistically significant favouring those being treated with MNTX. Comparison with seriously ill, non-cancer patients in the same study that had no increase in the median overall survival, hints at potential anti-cancer effects of MNTX  and radiotherapy plus Naltrexone. In the combination group a 40% increase in the overall survival at one year was reported . Extensi of MNTX .In this last section, we highlight the growing awareness that some of the effects of opioids on cancer may not be mediated by the classical μ, δ or κOR. The role of Toll-like receptor 4 (TLR4) in this context has been reviewed elsewhere . In brievia an opioid receptor-independent mechanism of suppression of Ras and STAT5 pathways  and the European Association of Cardiothoracic Anaesthesiology (EACTA); and has received compensation from Eurocept Pharmaceuticals BV and IDD for service as a consultant.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Electroencephalogram (EEG) is a record obtained by amplifying and recording the electrical activity, produced by electrical flows in the brain, from the human scalp   has become the most commonly used tool for EEG signal analysis. Wavelet transform is a modern development of Fourier analysis. WT can not only extract high-dimensional features from EEG, but also has high computational efficiency , Project of Youth Talent Lift Program of Shaanxi University Association for Science and Technology (Grant No. 20200408), Fundamental Research Funds for the Central Universities (Grant No. JB211303), and Fundamental Research Funds for the Central Universities under Grant (No. 20720190009).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


While fluid–structure interaction (FSI) problems are ubiquitous in various applications from cell biology to aerodynamics, they involve huge computational overhead. In this paper, we adopt a machine learning (ML)-based strategy to bypass the detailed FSI analysis that requires cumbersome simulations in solving the Navier–Stokes equations. To mimic the effect of fluid on an immersed beam, we have introduced dissipation into the beam model with time-varying forces acting on it. The forces in a discretized set-up have been decoupled via an appropriate linear algebraic operation, which generates the ground truth force/moment data for the ML analysis. The adopted ML technique, symbolic regression, generates computationally tractable functional forms to represent the force/moment with respect to space and time. These estimates are fed into the dissipative beam model to generate the immersed beam’s deflections over time, which are in conformity with the detailed FSI solutions. Numerical results demonstrate that the ML-estimated continuous force and moment functions are able to accurately predict the beam deflections under different discretizations. FSI pheet al. T represents the position vector and u = T is the velocity vector evolving with time t; 2/∂x2) + (∂2/∂y2)). ρ, p, μ are the fluid density, pressure and kinematic viscosity, respectively. f = T is the external force applied to the fluid domain at position x and time t. Equation (μ = 0.798 × 10−3 (Ns m−2)(30°C) and density ρ = 997 (kg m −3). The domain has a constant inlet velocity v = 0.01 (m s−1) with an associated Reynolds number Re = (ρv d/μ) = 187 406. Note that the Reynolds number changes  around the beam owing to the fluid velocity variations.Consider an incompressible fluid in a two-dimensional domain that is governed by the N-S equations, as shown below:. 2.1.2n. Fluid is flowing along the length of a channel and a constant flow is maintained at its inlet. The fluid velocity is kept constant for the initial 1.5 m of the channel. However, the same varies for all the remaining grids of this channel. A simply supported beam of 10 m length is immersed in this fluid domain.Various discretization techniques, such as, FEM, finite difference approximation (FDA) and Lattice Boltzmann , have be. 2.2. 2.2.1η ∈ , L is the length of the beam and q is the force per unit length distributed over the beam. Equation (w(η) of a beam and the force q applied onto it, as shown in EI) with E being the modulus of elasticity and I being the second moment of area. It is worth mentioning that different orders of spatial derivatives of w convey distinct attributes of an E-B beam, such as: —w(η)/dη gives the slope θ at any point along the length of the beam;d —E(η)I(η)(d2w(η)/dη2)) gives the moment in the beam; and(− —η(−E(η)I(η)(d2w(η)/dη2)) gives the shear at beam cross sections.d/dE-B beam theory, also known as the classical beam theory ,33, is cL = 10 m with the properties: modulus of elasticity E = 2 × 1011 N m−2, area moment of inertia I = 2.133 × 10−10 m4 and linear mass density ρL = 8050 × 0.008 × 0.005 kg m−1. The immersed beam shown in w = w = 0 and /∂x2) = /∂x2) = 0, the end nodes of the beam are stationary though the intermediate nodes get displaced owing to the fluid flow, which in turn deforms the beam without pushing (moving) it along the flow direction.In the present work, we consider a simply supported beam of length . 2.2.2N − 1) number of two-nodded elements, where N is the number of nodes. The beam is immersed into a fluid of constant velocity at the inlet of the channel. The direction of fluid flow is orthogonal to the beam’s longitudinal axis. While the above E-B equation is discretized using FEM, we integrate the structure with the fluid in the following way. The bending behaviour can be captured using minimum three adjacent nodes as given below T denote the deformed cartesian coordinate of the beam at r ∈ , and F = T is the corresponding force vector, which is the elastic deformation force per unit area exerted by the beam on the surrounding fluid. According to Peskin’s IB method, the backbone of the FSI dynamics lies in the local force and velocity transfers, governed byIB2d method is elaborated in  = η/L denoting the node locations per unit length of the beam and b ∈  = t representing time in seconds. The output variables are the nodal forces at all the saved time-stamps, gplearn’ solver , although their periodicities do not differ; —sin(a) versus a)sin ∈  is same as that of sin(a); however, the frequency of the former function increases exponentially though the latter has a constant frequency; —ae versus a)sin(e & esin(a): the function ea ∈  is non-periodic and unbounded, whereas a)sin(e & esin(a) are periodic and bounded functions.Thus, equations  functions. Still, the accuracy of the achieved moment fit is slightly worse than that of the force fit; however, the reported result is the best among various solutions obtained with different parameter settings in SR.. 4.2ψ. In order to validate the interpolation ability of the achieved functional forms, we calculate beam deflections for varying number of nodes and present a performance evaluation study in N = 65, The continuous expressions in equations  and 4.24.2 enablequation  to compu. 5In this study, we have devised an ML-based strategy to solve an FSI problem by extracting the underlying functional forms that capture the effect of the fluid on an immersed beam. The ML estimate of the forces, applied to the EB equation with dissipation, performs well in predicting the deflections of the immersed beam as found from the detailed FSI simulations. The functional forms (expressions) generated by the employed SR technique, accurately fits the ground truth force landscape. Moreover, the achieved expressions provide interpretability in understanding the spatio-temporal behaviour of the fluid forces/moments on the immersed beam. Although the input to SR is discrete, the results demonstrate that the output force/moment functions, continuous in space and time, can capture the beam deflections following different FE discretizations. To this end, the proposed approach helps us reduce the computational overhead involved in the traditional FSI analysis and produces continuum functional relations.In the future, we plan to extend the study for higher dimensional FSI problems involving a two-dimensional plate or a three-dimensional object immersed in the fluid. We believe this work has potential to generate computationally tractable and interpretable solutions to real-life aerodynamic and marine engineering applications.Click here for additional data file.