Non-inflammatory features are also observed, like the sarcoplasmic accumulation of proteins including TDP-43 and p62. This study aimed to investigate the effect of IFNγ and interleukin 1-β (IL-1β) on TDP-43 and p62 aggregation in vitro. Primary human myotubes were treated with IL-1β (20 ng/mL) and IFNγ (750 ng/mL) separately or combined for 48 hr. Sarcoplasmic TDP-43 aggregates and p62 puncta were assessed using image analysis for size, frequency, and colocalization with each other. Total protein expression of TDP-43, p62 and LC3 was assessed using western blotting. The subcellular localization of TDP-43 was also analyzed using image analysis. Combined IL-1β and IFNγ treatment increased puncta size of p62 compared to control (0.49 ± 0.13 µm2 versus 0.28 ± 0.06 µm2), without affecting puncta frequency or p62 expression but with an increased LC3II/LC3I ratio, suggesting autophagic alterations. IL-1β or IFNγ did not alter p62 puncta size or frequency, suggesting a combined insult of multiple inflammatory mediators is necessary to cause p62 alterations. IL-1β increased p62 protein expression in an autophagy-independent manner. None of the cytokine treatments affected TDP-43 protein expression, size, or frequency of TDP-43 aggregates or localization, suggesting IL-1β and IFNγ may influence TDP-43 processing in human skeletal muscle cells. TDP-43 was localized to the sarcoplasm under control conditions, suggesting this may not be a pathological feature. Overall, sIBM-like TDP-43/p62 features were not triggered by IL-1β and/or IFNγ.Skeletal muscle of patients with sporadic inclusion body myositis (sIBM) presents with inflammation, including upregulation of inflammatory cytokines such as interferon  Sporadic inclusion body myositis (sIBM) is the most common form of myositis in people over the age of 50 , 2. Sympγ (IFNγ), tumor necrosis factor α (TNFα), interleukin (IL)-7, and IL-32 [At present, the cause of sIBM symptoms is unknown, and there are many mechanisms that appear dysregulated in this disease. Pathological features of sIBM can broadly be split into inflammatory or non-inflammatory. Infiltrates of mononucleated immune cells, mostly consisting of CD8+ cytotoxic T cells, can be seen in the endomysium and the muscle fibers themselves , 5. A raNoninflammatory features of sIBM include rimmed vacuoles  and inclTDP-43 has a plethora of roles surrounding DNA and RNA processing, such as mRNA transport, stability, and splicing regulation. TDP-43 also has roles in stress sensing and cell survival by forming stress granules with halted mRNA transcripts . Proteinp62 is involved in the degradation of ubiquitinated proteins through both the ubiquitin proteasome system (UPS) and autophagic pathways . In sIBMγ transcripts are elevated in sIBM compared to control and other inflammatory myopathies [γ receptor 2 (IFNGR2) was observed compared to healthy or non-attacked myofibres. The amount of IFNGR2 upregulation in skeletal muscle was partially correlated with the number of attacking CD8+ cells [γ signaling [Inflammatory cytokines are upregulated in sIBM. Notably, IFNopathies , 22. In 8+ cells . Transcrignaling , was sevignaling .β and IFNγ to examine pathological features related to sIBM, such as TDP-43 aggregation and mislocalization in rat myotubes [β amyloid aggregation [β and IFNγ on TDP-43 and p62 in human myotubes has not previously been investigated. The aim of this study was to further investigate the roles of IL-1β and IFNγ on the sIBM-like pathological features of TDP-43 and p62 aggregation as well as TDP-43 mislocalization in human myotubes, with the hypothesis that IL-1β and/or IFNγ treatment triggers these non-inflammatory features.Previous work has used in vitro treatment of myotubes with inflammatory cytokines IL-1myotubes , β amyloregation , and othregation –29. HoweAll materials were purchased from ThermoFisher Scientific, UK, unless otherwise stated.µM dexamethasone , 10 ng/mL human basic fibroblast growth factor , and 1% penicillin-streptomycin. After 48 hr in growth media, 4 × 104 cells in 24 well plates were differentiated in N2 differentiation medium  for 7 days. Cells were maintained at 37°C with 5% CO2. Most experiments were conducted at passage 7. For cytokine treatment, 20 ng/mL IL-1β or 750 ng/mL IFNγ  separately or combined was added to differentiation media and incubated for 48 hr. Control samples consisted of the addition of no cytokine. Different myogenic donors were used for different experiments.Skeletal muscle-derived cells from Lonza Clonetics (UK CC-2580) and Cook MyoSite  were grown in either Skeletal Muscle Growth Media  with 1% penicillin-streptomycin and 10% fetal bovine serum (FBS) or Ham's F10 nutrient mix supplemented with 20% FBS, 1 The cytotoxic effect of cytokine treatment was measured using the CytoTox 96® non-radioactive cytotoxicity assay . Myotubes were differentiated for 7 days before 48 hr incubation with the cytokines. Results were normalized to a positive lysis control where cells were incubated with lysis solution for 45 min before commencing the assay.4 skeletal muscle cells were seeded onto Gibco Geltrex-coated 13 mm round coverslips  in 24 well plates. After differentiation, cells were fixed with 4% formaldehyde solution for 10 min and permeabilized in 0.1% triton X 100 for 15 min, then blocked with 5% goat serum for up to 1 hr. Primary antibodies were incubated by inverting the coverslip onto a 30 µL drop of antibody solution on Parafilm overnight at 4°C  counterstaining. Coverslips were mounted onto glass slides with DAKO fluorescence mounting medium  and imaged using either an Olympus IX81-ZDC inverted widefield microscope or a Zeiss LSM 980 Airyscan 2 confocal microscope.4 × 10z-stacks composed of 6 images each with a voxel depth of 0.3 µm were obtained using confocal microscopy for each treatment condition. p62 particle frequency was determined using NIH Image J using the “analyse particles” function with a pixel size of over 2 for each slice of the z-stack. p62 particle frequencies were normalized to percentage area coverage per image using HCS CellMask staining to account for differences in myotube size.Four z-stacks slices as punctate areas of staining with higher intensity than surrounding sarcoplasmic staining. Using NIH Image J, freehand regions were drawn around aggregates to measure their area in µm2. TDP-43 aggregate frequencies were normalized to the percentage area coverage of the cell mask area. TDP-43 co-localization with p62 was assessed for each identified TDP-43 aggregate. Any area of overlap between TDP-43 and p62 objects over 2 pixels was considered co-localized.The same samples for p62 analysis were used for TDP-43 sarcoplasmic aggregate analysis. Sarcoplasmic aggregates were identified manually in 3 Fluorescent images were obtained using an Olympus IX81-ZDC inverted widefield microscope. TDP-43 was classified as being within the nucleus, sarcoplasm, nucleus and sarcoplasm, or neither (not expressed) by manual identification. TDP-43 localization was classified for all visible cells, both multinucleated and single-nucleated cells. A multinucleated cell was classed as having nuclear (or nuclear and sarcoplasmic) staining if one or more nuclei showed clear TDP-43 expression. The median number of cells per image in all conditions was 44. All image analysis for TDP-43 and p62 was conducted blind.5 skeletal muscle-derived cells were lysed in RIPA buffer  with Pierce™ protease and phosphatase inhibitors. The protein concentration of lysates was determined using a Micro Lowry kit with Peterson's modification . Approximately 10 µg of protein was denatured at 95°C for 5 min in Bolt SDS (sodium dodecyl sulfate) sample buffer and Bolt reducing agent. PAGE (polyacrylamide gel electrophoresis) separation was performed with Bolt 4%–12% Bis-Tris mini protein gels at 200 V, followed by Western blotting onto PVDF membranes at 30 V. Blots were blocked in 5% milk-TBS-T, incubated with primary antibodies overnight at 4°C, and secondary antibodies for 1 hr at room temperature  for normally distributed data or median ± interquartile range for non-normally distributed data.β and IFNγ treatments were not causing excessive cell death in cultured myotubes, the cytotoxicity of cytokine treatments was measured via lactate dehydrogenase release after 48 hr of treatment. Firstly, a range of concentrations of each cytokine were tested in a preliminary experiment on one myogenic donor with 5 days of differentiation and 48 hr of cytokine treatment . TDP-43 aggregate frequency . The subcellular localization that showed the highest percentage of TDP-43 was nuclei and sarcoplasm.Widefield microscopy was used to investigate whether IL-1lization . There wartments . The disβ or IFNγ treatment on TDP-43 sarcoplasmic aggregation was also assessed to determine single cytokine effects (χ2p=0.392). The frequency of TDP-43 sarcoplasmic aggregates relative to cell area was not affected by any cytokine treatment  [αB-crystallin expression [β and IFNγ can influence many processes that have a basis in sIBM pathology; therefore, it was expected these cytokines would dysregulate TDP-43 and p62. The concentration of IFNγ used here was higher than that used previously, which may have caused differential effects than lower concentrations. Therefore, a range of concentrations of both cytokines should have been tested. As well as IL-1β and IFNγ, IFNγ and TNFα combined treatment has been used to investigate sIBM features in vitro [Previously, IL-1in (APP) , increaspression , increaspression , as wellpression , increaspression , and uprpression . This shin vitro , 27, 29,β + IFNy treatment increased p62 puncta size, showing promotion of p62 aggregation. However, these puncta were small and not reflective of the large aggregates observed in the sIBM sarcoplasm. p62 aggregation suggests a potential change in autophagy, which was corroborated by an increase in LC3II/LC3I protein. However, this was not accompanied by increased total LC3II, which is observed with increased autophagy [β + IFNγ treatment. Increased p62 puncta size was not seen with IL-1β or IFNγ individually, suggesting activation of multiple inflammatory insults may be necessary to induce p62 puncta alterations.IL-1utophagy , 32, 33.utophagy . Therefoβ + IFNγ despite the p62 puncta size increase, showing muscle damage was not the reason for p62 alterations here. IL-1β increased p62 protein expression without alteration in LC3II, suggesting increased p62 was not due to autophagic alterations. Instead, this may reflect alterations in pathways other than autophagy. For example, NF-κB, which is downstream of the IL-1 receptor, activates p62 expression [κB signaling; therefore, it would be interesting to examine NF-κB activity in myotubes with IL-1β treatment.Despite p62 aggregation being suggested as a marker for sIBM, p62 aggregates are also found in other inflammatory myopathies, most notably autoimmune necrotizing myopathy, as well as polymyositis and dermatomyositis , 34. p62pression , and p62pression . The curβ, contradictory to previous experiments with primary rat myotubes using IL-1β at the same concentration [β + IFNγ or IFNγ on TDP-43 localization in primary human muscle cells has not previously been reported. The analysis here was not restricted to multinucleated myotubes, but as TDP-43 localization was not affected by myotube differentiation (Figure Mislocalization of TDP-43 has been described in sIBM skeletal muscle as well as other conditions such as amyotrophic lateral sclerosis , 37–39. n Figure , this shSome cells without cytokine treatment showed TDP-43 localization to the sarcoplasm without clear nuclear expression, suggesting this “mislocalization” can be displayed in healthy myotubes. A study culturing healthy myotubes found approximately 60% of myogenic nuclei contained TDP-43 , corroboβ and/or IFNγ did not consistently affect TDP-43 aggregates or expression. The size of the TDP-43 aggregates was small and observable in the control conditions, so they may be performing homeostatic functions such as myogenic RNA processing [IL-1ocessing . As p62 β, IL-6, and TNFα [β secretion [α and IL-1β expression [β APP [β APP in myotubes triggered TDP-43 aggregates and mislocalization [As an alternative to the hypothesis tested here, it is possible that noninflammatory features of sIBM, including TDP-43 and p62-containing inclusion bodies, can trigger inflammation. In fact, TDP-43 overexpression in astrocytes caused increased secretion of proinflammatory cytokines, including IL-1and TNFα . Exposurpression . Investin [β APP . Furtherlization , showingβ and/or IFNγ at the concentrations tested failed to recapitulate the sIBM-like phenotype of sarcoplasmic TDP-43 and p62 aggregation. Although the size of p62 puncta increased with IL-1β + IFNγ treatment, this was not accompanied by increased protein expression and was likely due to autophagic changes. This suggests treating myotubes with IL-1β + IFNγ may not trigger some non-inflammatory sIBM-like features. IL-1β increased expression of the p62 protein without influencing p62 puncta, most likely through an autophagy-independent mechanism. The lack of effect on TDP-43, along with some effects observed with p62, along with the lack of colocalization suggests differential regulation of these two proteins under exposure to inflammatory cytokines. There were limitations to this study due to the short time period of IL-1β and IFNγ exposure considering the progressive, chronic nature of myositis conditions, as well as a lack of investigation of different IL-1β and IFNγ concentrations.Overall, the addition of IL-1


The search for biological markers, which allow a relatively accurate assessment of the individual course of pulmonary sarcoidosis at the time of diagnosis, remains one of the research priorities in this field of pulmonary medicine. The aim of our study was to investigate possible prognostic factors for pulmonary sarcoidosis with a special focus on cellular immune inflammation markers. A 2-year follow-up of the study population after the initial prospective and simultaneous analysis of lymphocyte activation markers expression in the blood, as well as bronchoalveolar lavage fluid (BALF) and lung biopsy tissue of patients with newly diagnosed pulmonary sarcoidosis, was performed. We found that some blood and BAL fluid immunological markers and lung computed tomography (CT) patterns have been associated with a different course of sarcoidosis. We revealed five markers that had a significant negative association with the course of sarcoidosis (worsening pulmonary function tests and/or the chest CT changes)—blood CD4+CD31+ and CD4+CD44+ T lymphocytes, BALF CD8+CD31+ and CD8+CD103+ T lymphocytes and a number of lung nodules on chest CT at the time of the diagnosis. Cut-off values, sensitivity, specificity and odds ratio for predictors of sarcoidosis progression were calculated. These markers may be reasonable predictors of sarcoidosis progression. Sarcoidosis is an inflammatory disease that can affect various tissues, the most common being the lungs . The manMany clinical, biological, radiological and PFT markers as possible predictors of the course of the disease have been studied. These include serum angiotensin-converting enzyme, C-reactive protein, immunoglobulins, soluble form of interleukin-2 receptor (sIL-2R), Krebs von den Lungen-6, blood and bronchoalveolar lavage fluid (BALF) T and B lymphocytes subtypes/activation markers expression, high-resolution computed tomography (CT) and fluorine-18 fluorodeoxyglucose-positron emission tomography/CT ,10,11. HOriginally, sarcoidosis was described as a disease driven by CD4+ T cells. During the later years of research, it was shown that cells that trigger granuloma formation are strongly Th1-polarized ,18. DecaThe aim of our study was to investigate the possible prognostic factors for pulmonary sarcoidosis. In the search for a potentially suitable marker for daily clinical practice, we hypothesized that these factors could include radiological lung signs and PFT indices. Moreover, special focus was paid to cellular immune inflammation markers. As sarcoidosis is a disease of the immune response, we searched for potential cellular immune markers that could reflect persistent inflammation and the onset of pulmonary fibrosis. Bearing in mind that the most abundant immune cell type both in peripheral blood and in BALF is T lymphocytes, and sarcoidosis is mostly driven by T cell mechanisms, we investigated adhesion molecules’ expression on T cell subpopulations CD4+ and CD8+. Adhesion molecules are essential for cell accumulation in inflamed tissues, allowing for T cell attachment and transmigration through the endothelium. In this paper, we extended our previous study ,21 throuA total of 71 consecutive patients  with newly diagnosed pulmonary sarcoidosis were prospectively enrolled in the study at the Center of Pulmonology and Allergology of Vilnius University Hospital Santaros Klinikos . The diaAll study patients were Caucasian. None of the patients had any relevant medical history or comorbidity. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).After the initial comprehensive examination of the patients, all subjects were followed up. In this study, the final assessment for patients was accomplished 2 years after the initial investigation, 52 patients came for re-examination. The dynamics of PFT indices  and chest CT changes  were evaluated as described earlier ,21. NoneThe dynamics of PFT indices were assessed as follows: (1) negative (progressive disease) when the value of the indices worsened by ≥10%, (2) positive when the value of the PFT indices has improved by ≥10%, (3) in other cases, the status was assessed as stable.For chest CT findings, a profusion score for consolidation and ground glass was assigned to each lung area based on the percentage of the lung area involved: 0 points (no involvement), 1 point (1–25%), 2 points (26–50%), 3 points (51–75%) and 4 points (>75% of lung area). A nodule profusion score was based on the number of nodules per area : 0 = no The dynamics of chest CT changes were assessed as follows: (1) negative, when the score worsened by ≥1 point, (2) positive  when the score improved by ≥1 point, (3) in other cases, the condition was assessed as stable.Modeling the dependence of disease progression on other variables, a univariate and multivariate logistic regression model was constructed.t-test was used to analyze two independent samples satisfying normality, while the Mann–Whitney test was used for those that did not satisfy normality. The cut-off values of quantitative indicators were determined based on ROC (receiver operating characteristic) curves. Corresponding cut-off values, sensitivity and specificity, and AUC (area under the ROC curve) and its 95% confidence interval (CI) were presented. Indicators were divided into groups using a cut-off value, and odds ratios (ORs) and their 95% CIs were calculated. Differences were considered statistically significant when the p < 0.05.Statistical analysis was performed using SPSS software, Version 20.0  to present mean and standard deviation. Shapiro–Wilk test was used to check the normality of quantitative variables. The Student’s For the majority of the subjects, the PFT indices did not change or improve over 2 years. Overall, 10% or more FVC (%) increased in 25.0%, decreased in 9.6% and remained unchanged in 65.4% of the patients; FEV1 (%) increased in 25.0%, decreased in 5.8% and remained unchanged in 69.2% of the patients; TLC (%) increased in 32.7%, decreased in 15.4% and remained unchanged in 51.9% of patients; RV (%) increased in 51.9%, decreased in 23.1% and remained unchanged in 25.0% of the patients; DLCO (%) increased in 40.4%, decreased in 17.3% and remained unchanged in 42.3% of the patients. However, when comparing the entire study group values of the PFT indices determined at the time of inclusion and after two years of observation, no statistically reliable differences were found.Radiologic changes on CT images improved or remained unchanged at 2 years in most of the patients. The enlargement of the mediastinal lymph nodes shown by CT at the time of diagnosis resolved in 50.0%, decreased in 25.0% and remained unchanged in 25.0% of the patients. Nodules that were seen in the lungs at the time of disease manifestation and resolved in 41.4%, decreased score in 9.8%, increased score in 4.9% and remained unchanged in 43.9% of the patients. Ground-glass opacity that was seen on CT disappeared in 75.0% and remained in 25.0% of the patient. Consolidation resolved in 55.6%, remained unchanged in 22.2%, decreased in 11.1% and increased in 11.1% of the patients. Similarly to PFT indices, there were no statistically significant changes in any of the CT scores over all of the whole group over 2 years.In searching for predictors of sarcoidosis progression by the logistic regression model, only five markers had a significant negative association with the course of sarcoidosis—blood CD4+CD31+ and CD4+CD44+ T lymphocytes, BALF CD8+CD31+ and CD8+CD103+ T lymphocytes, and a number of lung nodules on chest CT at the time of the diagnosis .Although the course of sarcoidosis is highly variable , in mostThe biological mechanisms underlying sarcoidosis activity—persistent inflammation and the onset and development of fibrosis—are still not well characterized . We hypo1, TLC, VC, RV and DLCO [We also sought to evaluate whether objective chest CT findings and PFT indices present at the time of disease manifestation can be prognostic factors for the course of sarcoidosis. For that purpose, the following CT and PFT markers were chosen for the evaluation and long-term monitoring: lung nodules, linear opacities, consolidation and ground glass scores, FVC, FEVand DLCO .We found that of all indices tested, two immune blood T lymphocytes markers (CD4+CD31+ and CD4+CD44+), two BALF T lymphocytes markers (CD8+CD31+ and CD8+CD103+) and one chest CT sign (a number of lung nodules) are potential prognostic factors for the course of sarcoidosis. Surprisingly, none of the PFT indices, lung tissue immune markers or other  indicators proved suitable for prediction in our study population. To the best of our knowledge, none of our selected immune indices were analyzed as sarcoidosis prognostic markers. Due to the novelty of our data, it was not possible to directly compare our results with the results of other studies. Therefore, the interpretation of the results of our study is challenging.p = 0.02). Moreover, the odds ratio for the probability of sarcoidosis progression was 10.00 (p = 0.01) when BALF CD8+CD31+ T lymphocytes were ≥13.5%. CD31 is an integral membrane protein expressed by endothelial cells, dendritic cells, platelets and other blood cells, including T lymphocytes. CD31 is a co-modulator of T cell immunity, involved in leukocyte–leukocyte interactions, as well as in interactions between lymphocytes and the vascular endothelium, leukocyte extravasation, and migration to the inflamed tissues through intercellular junctions. CD31 plays a role in the regulation of vascular stability [Using logistic regression analysis, we found that if blood CD4+CD31+ T lymphocytes were ≤14.5%, the odds ratio for sarcoidosis progression was 13.78  ,31. Ziorp < 0.001). CD44 is a family of cell surface glycoproteins, also termed hyaladherin (HA), belonging to the group of cell adhesion molecules. The cluster of differentiation 44 (CD44) is a multi-structural and multi-functional transmembrane glycoprotein, involved in cell-to-cell and cell-to-matrix interactions and participates in the regulation of hyaluronic metabolism, activation and migration of lymphocytes, as well as the release of cytokines in areas of inflammation. CD44 participates in a wide variety of cellular functions, including lymphocyte activation, recirculation and homing [Our study showed that if blood CD4+CD44+ T cells were ≤37.5%, the probability of disease progression was 15.31 . CD103 is integrin αEβ7, an adhesion molecule expressed on most of the intraepithelial CD4+ lymphocytes in the mucosa [Our last revealed potential immune prognostic factor is BALF CD8+CD103+ T cells. We found that when BALF CD8+CD103+ T lymphocytes were ≥15.5%, the odds ratio for disease progression was 8.75  pieces of the lung, about 2 mm in size each, are usually obtained. BAL, on the other hand, washes out immune cells from approximately one million alveoli .p < 0.001). CT appearances of sarcoidosis mirror the perilymphatic spreading of the granulomatous process observed pathologically. Nodules represent aggregates of granulomas [The number of lung nodules on chest CT is a single non-immunological prognostic factor for the sarcoidosis course revealed in our study. We found that the odds ratio for sarcoidosis progression was 18.46 at ≥15.0 nodules in the lungs on chest CT (anulomas . Pulmonaanulomas . Severalanulomas . Distefaanulomas . Howeveranulomas . Althouganulomas ,55.None of the PFT indices at the time of manifestation of sarcoidosis were found to be a possible prognostic marker of disease course in our study. Unlike our study results, McDonnell et al., in their retrospective observational study, found that low DLCO at sarcoidosis presentation may identify patients without Löfgren’s syndrome who are more likely to develop physiological progression . HoweverOther specific potential prognostic factors found in other studies, but not confirmed or not investigated in our study, are older patients’ age ,56,57, COur study has strengths and limitations. The first strength is that it was a comprehensive study, including clinical, radiological, lung function, immune markers in the blood, BALF and lung biopsy tissue. The second strength is that it was a prospective study with the main primary objective to search for prognostic markers ,21. The The limitation of the study is that this was a single-center study. However, our center is the primary center for interstitial lung disease in our country; therefore, these results may reflect the sarcoidosis patients in our population. The second limitation is that there was no genetic testing of the subjects . AnotherOur results show that some blood and BAL fluid immunological markers and lung CT patterns have been associated with a different course of sarcoidosis. The blood CD4+CD31+ T lymphocyte and CD4+CD44+ T lymphocyte counts, the BAL fluid CD8+CD31+ T lymphocyte and CD8+ CD103+ T lymphocyte counts, and the number of lung nodules on chest CT may be reasonable predictors of sarcoidosis progression. Further studies are needed to consolidate these findings.


The American Society of Heating, Refrigeration, and Air-Conditioning Engineers (ASHRAE) recommends that hospital operating rooms (OR) are controlled for temperature and humidity with established ranges but does allow for exceedances for surgeons and surgical procedures. There is currently no clear consensus or established thresholds for out-of-range temperature and humidity ranges in relation to risk for surgical site infections (SSI). A study was performed at Memorial Sloan Kettering Cancer Center (MSKCC) to further examine if temperature and humidity deviations pose a patient safety risk.p < 0.05.The study included 5600 surgical procedures that were performed at MSKCC between September 2021 and January 2022 where temperature and humidity logs were available. Procedures were broken into groups based on in- (n=4419) and out-of-range (n=1187) temperatures and in- (n=5225) and out-of-range (n=381) humidity. SSIs following the procedure were identified using targeted positive microbiology cultures and within NHSN  surveillance periods. Chi-square and Fisher’s exact statistical tests were used to determine if there was a significant difference between groups where Breakdown of eligible procedures and follow upTable represents the total number of eligible procedures with environmental parameters and SSI follow up period.p=0.15). There was a significantly higher SSI rate observed for out-of-range temperatures (p=0.04) more specifically low out- of-range temperatures (p=0.02). A sub-analysis was performed for low temperatures based on procedures by duration. Significance of the finding was lost when surgery duration was 4 hours or greater.There was no significant impact on SSI for out-of-range humidity (If there was a true correlation between SSI and low ambient temperature, we would have expected to see a strengthening of SSI risk with longer procedures. This study suggests that temperature and humidity deviations out of the recommended guidelines in the operating room do not pose additional risks for surgical site infections and limited exceedances can be permitted without risking patient safety.All Authors: No reported disclosures


The pulmonary function test (PFT) has been widely used in sarcoidosis. It may vary due to the severity, extent, and the presence of complications of the disease. Although the PFT of most sarcoidosis patients is normal, there are still 10–30% of cases who may experience a decrease in the PFT, with a progressive involvement of lungs. Restrictive ventilatory impairment due to parenchymal involvement has been commonly reported, and an obstructive pattern can also be present related to airway involvement. The PFT may influence treatment decisions. A diffusing capacity for carbon monoxide (DLCO) < 60% as well as a forced vital capacity (FVC) < 70% portends clinically significant pulmonary sarcoidosis pathology and warrants treatment. During follow-up, a 5% decline in FVC from baseline or a 10% decline in DLCO has been considered significant and reflects the disease progression. FVC has been recommended as the favored objective endpoint for monitoring the response to therapy, and an improvement in predicted FVC percentage of more than 5% is considered effective. Sarcoidosis is a systemic granulomatous disorder of unknown etiology that may affect almost every body organ. The most commonly involved organs remain the lung and mediastinal lymph nodes. The diagnosis of it depends on a compatible clinical and imaging feature, histologic evidence of non-necrotizing epithelial granuloma, and exclusion of alternative causes of granulomatous diseases . CliniciThe PubMed database was searched for the period from January 2012 to December 2022 using the terms: “Sarcoidosis[title]”. The inclusion criteria included: (1) the article was about pulmonary sarcoidosis rather than other organs’ sarcoidosis; and (2) the article contained the content of the FPT. The exclusion criteria included: (1) the article was written in languages other than English; (2) case reports, study designs, comments or letters; (3) animal or laboratory studies; and (4) the full text was unavailable. According to the inclusion and exclusion criteria, there were 45 articles selected by investigators. An additional 39 articles were found by searching the reference lists of previously selected articles. The PFT, as well as radiographic and laboratory biomarkers tests, is useful for initial assessment in sarcoidosis diagnosis . The AmeThe PFT in sarcoidosis patients may vary due to the severity, extent, and the presence of complications of the disease. Most sarcoidosis patients have a normal PFT, whereas 10–30% of cases may experience a decrease in the PFT, with progressive involvement of the lungs and progress to chronic disease . An impaThe clinical course of sarcoidosis is usually evaluated and tracked with objective clinical outcome measures, including radiographic findings and a PFT . The PFTX-ray is the most common radiologic technique for assessing pulmonary involvement in sarcoidosis. There are differences in PFT parameters of sarcoidosis patients at different imaging stages . The PFTHigh-resolution computed tomography (HRCT) is an accurate modality to identify mediastinal lymphadenopathy and subtle pulmonary parenchymal changes. In clinical practice, it is widely used for the initial evaluation of sarcoidosis and monitoring of disease progression. Compared with CXR stages, HRCT findings of sarcoidosis have a better correlation with the severity of PFT changes ,28. PFT Airflow limitation was observed in patients with thickening of bronchovascular bundles (BVBs), air trapping, and reticular shadow ,30,31. HFluorodeoxyglucose positron emission tomography (FDG-PET) is a useful tool to evaluate inflammatory activity. The metabolic activity of pulmonary parenchyma displayed by FDG-PET was associated with PFT parameters and may represent an impaired pulmonary function ,33,34. ISevere sarcoidosis may lead to significant disability or reduced life expectancy. Pulmonary fibrosis, impaired lung function, extensive disease on HRCT, and pulmonary hypertension are related to poor clinical outcomes in sarcoidosis patients . Most saSarcoidosis-associated pulmonary hypertension (SAPH), a late complication of sarcoidosis, is most common in stage IV or advanced disease, but can also occur in the condition of relatively normal lung function and preserved parenchymal architecture. Approximately 5–6% of pulmonary sarcoidosis patients will develop SAPH, and it is a predictor of a worse outcome with a five-year survival rate of 55% ,42. PatiSeveral comprehensive scoring methods have been developed to assess the severity of pulmonary sarcoidosis and guide treatment. Wells and his colleagues designed a composite physiological index (CPI), which is a weighted index of pulmonary function variables, and is related to the extent of disease on HRCT in idiopathic pulmonary fibrosis (IPF), and they confirmed that a CPI can predict mortality more than any single pulmonary function variable in IPF . The calThe sarcoidosis treatment score (STS) system has been developed to assess treatment efficacy based on multiple factors of pulmonary sarcoidosis. This STS system integrates six variables, including 5% of absolute FVC change, 10% of absolute DLCO change, HRCT variations, King’s sarcoidosis questionnaire, the fatigue assessment scale, and changes of daily glucocorticoid dose ,51. EachPulmonary function parameters can also be applied to clinical phenotype identification. A cluster analysis has been studied to phenotype sarcoidosis subjects with slight or severe manifestation . Six pheThe 6MWD is a simple indicator for measuring pulmonary and cardiac status of patients with sarcoidosis, and it is useful for evaluating exercise tolerance and oxygen demand. It has been confirmed that the 6MWD decreases in some patients with pulmonary sarcoidosis. The 6MWD is most commonly used in the initial assessment, and it is also often used as one of the secondary endpoint indicators in clinical trials of sarcoidosis and as a predictive indicator of the patient survival rate. In a prospective study with 142 patients, Baughman and his colleagues assessed the role of the 6MWD in impairment and prognosis of disease, and found that 73 (51%) patients had a 6MWD < 400 m and 32 (22%) patients had a 6MWD < 300 m. Meanwhile, they found that the active ingredients of the St George’s Respiratory Questionnaire (SGRQ), FVC, as well as minimum oxygen saturation were independent predictors of 6MWD . In anotp = 0.032) after specific therapies [The 6MWT has been usually tested as one of the secondary endpoints in sarcoidosis therapy clinical research. The 6MWD improved from 227 m to 240 m after six months’ treatment in some patients with SAPH . In anotherapies . This waherapies . Howeverherapies . The CPET has been considered as a useful tool for assessing exercise tolerance, and it offers added value in detecting impaired PFT in pulmonary sarcoidosis patients . A compaThe PFT may influence treatment decisions. Most sarcoidosis patients do not require treatment when they have no obvious symptoms, normal PFT parameters, or a high possibility of remission. A cohort study demonstrated that oral glucocorticoids, disease-modifying antirheumatic agents (DMARDs), or biologic agents were required only in 104/311 of pulmonary sarcoidosis cases . HoweverOf the PFT parameters, FVC is recommended as a favored objective indicator for evaluating the response to therapy . The comOral glucocorticoids are the first-line therapeutic approach for sarcoidosis patients ,71. The Methotrexate (MTX) is a preferred second-line medication for sarcoidosis patients . AccordiBiologic agents are considered as the third-line treatment for patients with refractory diseases or those who cannot tolerate glucocorticoids and other immunosuppressants ,71. InflThe PFT is a widely available and useful method for evaluating and managing sarcoidosis. The review of available data suggested the baseline PFT could provide an estimate of disease severity, and a series of PFTs provide valuable information for monitoring disease progression as well as assessing the response to treatment. DLCO < 60% as well as FVC < 70% portends clinically significant pulmonary sarcoidosis pathology, which warrants treatment. During follow-up, a 5% decline in FVC from baseline or a 10% decline in DLCO is considered significant and reflects the disease progression. The improvement in the predicted FVC percentage by more than 5% is considered effective to therapy. In the future, the STS as a key endpoint should be widely used and further optimized in a sarcoidosis clinical study.


Large language models (LLMs) have broad potential applications in medicine, such as aiding with education, providing reassurance to patients, and supporting clinical decision-making. However, there is a notable gap in understanding their applicability and performance in the surgical domain and how their performance varies across specialties. This paper aims to evaluate the performance of LLMs in answering surgical questions relevant to clinical practice and to assess how this performance varies across different surgical specialties.We used the MedMCQA dataset, a large-scale multi-choice question-answer (MCQA) dataset consisting of clinical questions across all areas of medicine. We extracted the relevant 23,035 surgical questions and submitted them to the popular LLMs Generative Pre-trained Transformers (GPT)-3.5 and GPT-4 . Generative Pre-trained Transformer is a large language model that can generate human-like text by predicting subsequent words in a sentence based on the context of the words that come before it. It is pre-trained on a diverse range of texts and can perform a variety of tasks, such as answering questions, without needing task-specific training. The question-answering accuracy of GPT was calculated and compared between the two models and across surgical specialties. Both GPT-3.5 and GPT-4 achieved accuracies of 53.3% and 64.4%, respectively, on surgical questions, showing a statistically significant difference in performance. When compared to their performance on the full MedMCQA dataset, the two models performed differently: GPT-4 performed worse on surgical questions than on the dataset as a whole, while GPT-3.5 showed the opposite pattern. Significant variations in accuracy were also observed across different surgical specialties, with strong performances in anatomy, vascular, and paediatric surgery and worse performances in orthopaedics, ENT, and neurosurgery.Large language models exhibit promising capabilities in addressing surgical questions, although the variability in their performance between specialties cannot be ignored. The lower performance of the latest GPT-4 model on surgical questions relative to questions across all medicine highlights the need for targeted improvements and continuous updates to ensure relevance and accuracy in surgical applications. Further research and continuous monitoring of LLM performance in surgical domains are crucial to fully harnessing their potential and mitigating the risks of misinformation. Large language models (LLMs) are artificial intelligence (AI) models designed for language processing tasks requiring the analysis of text-based data . The utiLarge language models have broad potential medical and surgical applications for doctors, patients, and students . These iFirst, the use of LLMs in surgery is less understood . HoweverThe second gap is that existing work evaluating LLM performance on medical question-and-answer datasets tends to assess accuracy across the dataset as a whole, masking any variation present in relevant subgroups of the data, such as medical specialty ,10. ThisPresently, there is limited published research on AI’s ability to answer surgical questions and no stratified evaluations of LLMs on surgical subspecialties. Here, we explore the performance of the LLM GPT in answering surgical questions. GPT is one of the most well-known and easily accessible LLMs to medical professionals and the general public due to its conversational interface, ChatGPT . To maxiThe study was conducted at Chelsea and Westminster Hospital in London, UK. An overview of our methodology is summarised in Figure We selected MedMCQA as our question bank, a publicly available large-scale multi-choice question answering (MCQA) dataset for AI testing consisting of clinically-based questions covering 21 diverse subject areas . QuestioOf the 21 categories of questions in MedMCQA, four relate to the clinical practice of surgery and correlate with the knowledge of surgeons: surgery , ear, nose, and throat (ENT), orthopaedics, and anatomy. We therefore filtered MedMCQA into these four question categories. This reduced the size of the dataset to 36,341 questions. We then subsetted the data to questions where the ‘choice_type’ was ‘single’. There is only one other ‘choice_type’ in the dataset, which is ‘multi’. ‘Single’ refers to questions where there is a single best answer; ‘multi’ refers to questions where there are multiple correct answers. We chose to focus on 'single', as only a single correct answer is provided by the MedMCQA question bank for each question. This reduced the dataset to 23,035 questions.Questions were fed to GPT via OpenAI’s API (Application Programming Interface) OpenAI, LLC, San Francisco, CA) using the OpenAI Python package. Note that this is a zero-shot method; the respective LLMs have no prior training or fine-tuning for the task at hand. To prevent possible data leakage, only the question, possible answers, and question ID were submitted to the OpenAI API. We submitted questions to two LLMs: GPT-3.5 and GPT-4. We asked each model for a letter-only response to questions .A random set of 1,000 MedMCQA questions and answers generated by GPT-4 were extracted from the dataset. Of this subset, question content was manually categorised into surgical specialties by two independent clinician reviewers. Surgical specialty categorisations were based on the UK Surgical Royal Colleges’ surgical specialties. The two reviewers are practicing doctors in the UK, with clinical experience in medicine and surgery and specialist knowledge in medical education and assessment. Following review by both clinicians, categorisation was compared, and, where there was discordance, a collective agreement was reached to give a standardised outcome. While some questions within the MedMCQA database had been assigned a subtopic, this field was sporadically completed and was non-standardised; therefore, the existing subtopic field on MedMCQA was disregarded.Overall accuracy measures for GPT-3.5 and GPT-4 were calculated as percentage accuracy  and compared to the recently published zero-shot accuracy of GPT-3.5 and GPT-4 on the MedMCQA dataset as a whole, which is 50.1% and 69.5%, respectively . To asse2 = 585.53, df = 1, p-value < 0.01).Of 23,025 surgical multiple-choice questions (MCQs), the zero-shot results for GPT-3.5 and GPT-4 were 53.3% and 64.4%, respectively. These accuracies were significantly different .We found statistically significant differences in accuracy between our results using GPT-3.5 to answer surgical questions (53.3% accurate) and published results of the accuracy of GPT-3.5 on the MedMCQA dataset as a whole (50.1% accurate) . We also found statistically significant differences in the accuracy between our results using GPT-4 to answer surgical questions (64.4% accurate) and published results of the accuracy of GPT-4 on the MedMCQA dataset as a whole (69.5% accurate) . We found strong performances in anatomy, vascular, and paediatric surgery, but worse performances in orthopaedics, ENT, dermatology, and neurosurgery.We found there was a significant difference in accuracy between specialties  . We alsoThese results suggest that LLMs, like GPT-4, can perform well in specialised fields, such as surgery, with a zero-shot approach that is without the need for domain-specific or task-specific training. The model's capacity to handle a wide range of queries and prompts demonstrates how rapidly LLMs are closing the gap with contextualised language models , 17. MorThe significant improvement in performance between GPT-3.5 and GPT-4 could be credited to more extensive training data and enhanced training methodologies used to develop GPT-4, which contribute to the model’s improved language comprehension and contextualisation. Much like how, in the medical field, guidelines are constantly reviewed and updated, GPT’s knowledge base must consistently be refreshed to utilise emerging information. The need to supply sequential models with larger and more far-reaching datasets must be critically considered when referring to GPT’s medical and surgical knowledge; up-to-date knowledge is essential for informed surgical decision-making and practice, and delays between accepted changes in practice and updates to GPT training data could potentially be disastrous. Recent developments to provide ChatGPT with internet access through Microsoft’s Bing search engine could help resolve this by ensuring ChatGPT has access to current knowledge . EquallyThe latest model, GPT-4, had significantly lower performance on surgical questions compared to the MedMCQA dataset as a whole . RestricWe found significant variability in model accuracy between surgical specialties, suggesting that some areas might be covered more than others in GPT’s training data. It is possible that this variance relates to how specialised a given field is and thus how much information is readily available; this could explain, for example, why GPT performs better on questions about general surgery than neurosurgery . HoweverIt is important to note the limitations of our study. First, if there is a relationship between the question ‘choice_type’ and specialty, focusing on ‘single’ type questions could introduce a bias. While this is theoretically possible, we do not expect such a relationship a priori.Second, for some specialties, we have a small sample size. Given the significant time cost of manually categorising questions, a random sample of 1,000 questions was the best approach for the analysis of surgical specialties. A uniform distribution of questions across specialties would ensure more certainty around accuracy scores. However, achieving this would require manually categorising many thousands of questions to ensure a sufficient number of ‘rare’ specialty questions were encountered. For example, if a rare specialty made up 1% of the questions, approximately 10,000 questions would have to be categorised in order to obtain 100 questions for just that specialty. Given that five specialties make up less than 5% of the data, this was infeasible for this study.Third, the MedMCQA dataset contains questions targeted at recent graduates. However, some surgical specialties are more specialised than others; for example, a recent medical graduate would be expected to know more about general surgery than neurosurgery. This means that the questions in the dataset might require more advanced decision-making for general surgery than neurosurgery. Thoroughly testing more specialised areas, such as neurosurgery, may therefore require focused datasets designed specifically to test advanced knowledge in these more niche fields. However, we note that studies assessing LLM accuracy using the MedMCQA dataset are still relevant for testing LLMs' ability to reproduce the knowledge expected of more junior doctors.Fourth, OpenAI recently released a new version of GPT , after our analysis was completed. This new version (GPT-4 Turbo) is a mid-generation update to GPT-4 rather than a major new release , and so results are likely to not be substantially different from those presented here. However, it is possible that results may differ somewhat using this new version. We therefore encourage future research to benchmark GPT-4 Turbo to quantify its performance.Fifth, LLMs are stochastic, and thus it is possible for GPT to respond differently to questions if asked on multiple occasions. In this study, we asked GPT each question once, as is common in other papers assessing LLM performance . Future Sixth, the comparison between our results and the published results in Toma et al.'s study  should bThe value of LLMs in the time- and resource-strained setting of surgery lies in their ability to complete a myriad of tasks almost instantaneously, thus relieving pressure on the surgeon and enabling them to prioritise their craft specialty. Here we show the capabilities and limitations of GPT-3.5 and GPT-4 in addressing surgical questions. While both models showcased a good ability to interpret and apply surgical knowledge without specialised training, the performance varied significantly between different fields of surgery. This uneven proficiency underscores the need for more extensive and balanced training datasets to ensure consistency across surgical domains.There are legitimate concerns regarding the premature use of LLMs in the patient-safety-oriented field of healthcare. While we endorse their ongoing development, we caution that LLMs must be truly ready for use in surgery, confirmed through accurate evaluation. We therefore advocate for robust validation through stratified evaluation, enabling targeted enhancements.


In this work, we report a low-cost and highly sensitive electrochemical sensor for detecting As(III) in water. The sensor uses a 3D microporous graphene electrode with nanoflowers, which enriches the reactive surface area and thus enhances its sensitivity. The detection range achieved was 1–50 ppb, meeting the US-EPA cutoff criteria of 10 ppb. The sensor works by trapping As(III) ions using the interlayer dipole between Ni and graphene, reducing As(III), and transferring electrons to the nanoflowers. The nanoflowers then exchange charges with the graphene layer, producing a measurable current. Interference by other ions, such as Pb(II) and Cd(II), was found to be negligible. The proposed method has potential for use as a portable field sensor for monitoring water quality to control hazardous As(III) in human life. Human activities, such as mining, the production of pigments and pesticides, and others, have altered the levels of arsenic (As) in nature. Of importance, arsenic is a hazardous element to human health, and its poisoning causes fatal diseases, including cancer, liver damage, kidney disease, and disturbances of the nervous system . Arsenic−1 LOD) compared to other methods. They are mainly suitable for the semi-quantitative determination of high concentrations of arsenic in water. In addition, the colorimetric method cannot be used to make a real-time measurement on the AS(III) level, as in chronoamperometry.There are several methods for determining the level of arsenic contamination. High-Performance Liquid Chromatography (HPLC) and Inductively Coupled Plasma Mass Spectrometry (ICP-MS) are the traditional methods, with the limit of detection (LOD) down to microgram levels or less . LikewisElectrochemical methods are notable for arsenic determination. Despite this expense, hybrid gold-platinum nanoparticles with polyaniline have been proposed as an electrode for As(III) detection via anodic stripping voltammetry and achieve 19.7 nM or 1.48 ppb LOD . ReducedIn this work, we aimed to develop a low-cost and highly sensitive electrochemical sensor composed of three-dimensional graphene foam (GF) and composite ferrous-carbon nanoflowers (GNF)—the electrode material was then abbreviated as GF/GNFs—to determine arsenic levels in the water. Earlier, the GF/Ni-based electrochemical sensor was revealed to have ultra-high sensitivity ,16. Addi2H2/H2 (3/24) mixtures were flowed through the vacuum tube furnace (0.2 Torr pressure) at 700 °C for 3 min. The tube temperature then underwent rapid cooling (−10 °C/min) with hydrogen flow under 1 Torr pressure, and a graphene layer was formed on the 3D microporous surface. Carbon atoms were dissolved on the Ni Foam scaffold surface, forming graphene/Ni foam. Ni was etched using a 3 M HCl solution at 60 °C for 30 min.The GF was fabricated by chemical vapor deposition (CVD), where Ni foam was used as the catalyst. C4) with 97% purity was purchased from Loba Chemie Pvt. Ltd., Mumbai, India, and iron sulfate heptahydrate (FeSO4·7H2O) was obtained from Quality Reagent Chemicals (QReC), Wellington, New Zealand. All solutions were freshly prepared with deionized water.Sodium borohydride .The active electrode materials of the sensor were GF and metal-organic nanoflowers. The nanoflower decoration was initiated by diluting FeSOThe sensor material was characterized by FE-SEM in −3, and the detection process. The negative charges (−3e) can be described according to ferrous ions and C valence properties and will be explained in the mechanism section. The redox process occurred at the GF/GNF electrode, causing a measurable current proportional to As(III) concentrations. p denotes holes after losing electrons from the electrode material, causing a positive current.The whole experiment is summarized in The surface morphology of GF after the addition of ferrous nanoparticles and a flower-folded internal structure, as characterized by FE-SEM, are illustrated in 2SO4 [The active electrode used was GF/GNFs, whereas Pt-wire and Ag/AgCl electrodes were used as the counter and reference electrodes, respectively. When a cyclic voltammetry (CV) of the GF/GNFs electrode was plotted in response to different concentrations of As(III) ranging from 1 ppb to 10 ppm, the sensor system showed a linear relationship between the redox current and As(III) concentrations . HNO3 (02SO4 . The CV y-axis/slope = 3.3 · 1.51 (μA)/5 (μA/ppb) = 1 ppb.Chronoamperometric performance analysis of the sensor showed that the measured current was proportional to the arsenic concentration. When the arsenic solution was dropped into the experimental setup, it resulted in a step current . A drop The current detected by the sensor electrode in response to other heavy metals, such as Cd(II) and Pb(II), was negligible . The intdlC). Its equivalent circuit is composed of a capacitor and charge transfer resistance (ctR). The radii in the Nyquist plot correspond to the charge transfer resistance of each material. The two-layer fractal microporous graphene proposed in this work showed the lowest impedance compared to flat graphene (2D) and bare microporous graphene. This implies the claim that microporous graphene decorated with a nanoflower structure yields the highest sensitivity among the three methods.The behavior of the system can be analyzed by Electrochemical Impedance Spectroscopy (EIS). Usually, the EIS Nyquist plot is used to illustrate the impedance characteristics. Nyquist plots for each case are shown in The mechanism of high sensitivity can be described in two aspects. First, there is a two-level reactive surface area due to the 3D microporous graphene layer and the nanoflowers. These two magnificently increase the surface area in comparison with a flat graphene electrode. Second, the interlayer dipole-dipole enhancement greatly catalyzes the interaction at the electrode of the G-Ni foam . Dipole 3+ greatly support the selectivity for As(III) rather than As(V) (3+), once dissolved in water and moving near the electrode, is reduced into As0, resulting in a reduction current of 3e at the working electrode. Each As3+ ion gains 2 free electrons from Fe and a free electron from graphene, where they formed as graphene-ferrous composites (Fe : G)3− in the shape of nanoflowers.For specificity aspects, the hybrid carbon-ferrous nanoflowers (Fe: G)an As(V) . GF/GNFsFor reproducibility testing, we prepared 6 different pieces of GF/GNFs electrodes where the same amperometric measurement was carried out. The results yielded RSD% = 6 on day 1 and kept increasing until RSD% reached 10 on day 7 . It thusWe sampled 5 natural water sources where the reference value of As(III) was evaluated by the official authority using the standard ICP-MS method. The results are shown in 4 and GF was kept at 1:10 in the experiment. As a result, the structure determined by FE-SEM appeared to be metal-organic nanoflowers folded on the microporous graphene surface. These nanoflowers greatly enhance the reactive surface area of the working electrode. Graphene nanoflowers give a hierarchical structure to the graphene foam surface. This nanostructure could be said to be fractal, literally. According to several articles relating to metalloorganic structures, it normally yields a flower-like structure [4) on the graphene surface and forming metalloorganic compounds. Iron (ferrous) has been reported to catalyze the reaction to As(III) [Nanoflower-based microporous graphene was fabricated successfully using Chemical Vapor Deposition (CVD). A ferrous layer on graphene was formed and deposited by iron (ii) sulfate and sodium borohydride as precursors for reactions. The mass ratio between FeSOtructure . In our  As(III) . TherefoTo determine the potential for amperometric detection, we carried out cyclic voltammetry with varying As(III) concentrations from 1–50 ppb. The redox potential was found in the cyclic voltammogram at 0.15 V. This potential was selected for chronoamperometry. In For the selectivity test, Cd(II), Pb(II), and Cu(II) solutions were dropped onto the test solution and gave an insignificant current. Thus, the specificity of this sensor to As(III) can be concluded against at least two sources of interference. Further tests can also be conducted; however, the reaction is specific to the redox potential of our focused analyte, i.e., As(III).Electrochemical impedance spectroscopy was carried out, and the Nyquist plots are included in A comparison between the other methods and our developed nanoflower-based nano-microporous graphene sensor for arsenic measurements is shown in The key findings in this work are listed below.Novel nanoflowers grown on a microporous graphene foam surface formed a gigantic surface area enrichment and a highly sensitive electrode.LOD achieved was 1 ppb, comparable to lab-scale methods, such as ICP-MS, HPLC, and AAS.−1 (response current/As(III) concentration), which was 50–60 times greater than that of bare microporous graphene and flat graphene.Sensitivity was measured as 5000 μA/mgLIt was highly specific to As(III) under Cd(II), Pb(II), and Cu(II) interference.It had a low cost compared to the AuNPs-based method and other large laboratory-scale methods.Portable devices and on-site investigation of As(III) contamination are possible for the offensive prevention of As(III) contamination in agricultural water and drinking water.It required a smaller sample size in comparison with other spectroscopic-based approaches, such as AAS, ICP MS, and AFS.Amperometric detection supports rapid readout and is suitable for field experiments for actual As(III) screening.Reproducibility was tested, and RSD% gradually increased from 6% to 10% within 1 week.The reproducibility of the proposed nanoflowers/GF electrode was tested using a 20-time repeated experiment, and the standard deviation (SD) of each method is reported in A highly sensitive electrochemical sensor based on metal-organic nanoflowers on microporous graphene was developed and tested for As(III) sensing in water. This method yields the greatest sensitivity in comparison with flat graphene and microporous graphene. An explanation of greater sensitivity could be the larger reactive surface area due to nanoflower structure folding on a microporous graphene foam surface. In addition, a catalytic mechanism due to dipole-dipole enhancement between graphene and the nickel layer within the porous further increases the electron transfer . The pro


Candida species directly from a whole blood specimen within 3-5 hours . The objective of this study is to identify predictors of 30-day mortality in patients with candidemia identified by T2Candida Panel.Candidemia is associated with mortality rates exceeding 40%. However, prior studies indicate mortality may be reduced when antifungal therapy is initiated within 12 hours. The T2Candida Panel is a diagnostic assay that detects This is a retrospective, multicenter study of critically ill patients with candidemia identified by T2Candida Panel from January 2016 - December 2022. Critically ill patients were defined as those who developed candidemia during an intensive care unit (ICU) stay or within 72 hours of ICU admission or discharge. T2Candida sites were chosen across the United States based on T2Candida utilization. Exclusion criteria were patients < 18 years of age, those with prophylactic indications for antifungal therapy, prisoners and pregnant patients. Multivariate logistic regression was conducted to identify factors associated with 30-day mortality measured from the T2Candida draw time.There were 171 ICU patients from seven institutions with candidemia identified by T2Candida panel. The mean (standard deviation [SD]) age was 59.7 (14.8) years and 52.1% were male. Mean (SD) APACHE II and Charlson Comorbidity Index scores were 20.6 (7.1) and 4.9 (2.8), respectively. Empiric antifungal therapy was administered to 36.8% of patients and the majority received infectious diseases (ID) consult (92.4%). Echinocandins were the most common agents used for empiric (72.7%) and definitive therapy (62.6%). Overall, 30-day mortality occurred in 36.0% and was not associated with antifungal de-escalation. Administration of empiric therapy  and ID consult  were associated with reduced odds of 30-day mortality.Empiric antifungal administration and ID consult were independently associated with reduced odds of 30-day mortality in patients with candidemia identified by T2Candida Panel. Future studies are needed to evaluate the impact of the T2Candida panel on antifungal stewardship.Ryan K. Shields, PharmD, MS, Allergan: Advisor/Consultant|Cidara: Advisor/Consultant|Entasis: Advisor/Consultant|GSK: Advisor/Consultant|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Menarini: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Roche: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Utility: Advisor/Consultant|Venatorx: Advisor/Consultant|Venatorx: Grant/Research Support Michael J. Rybak, PharmD, PhD, MPH, Abbvie, Merck, Paratek, Shionogi, Entasis, La Jolla, T2 Biosystems: Advisor/Consultant


Chat Generative Pre-trained Transformer (ChatGPT) is an artificial intelligence (AI)-based language processing model using deep learning to create human-like text dialogue. It has been a popular source of information covering vast number of topics including medicine. Patient education in head and neck cancer (HNC) is crucial to enhance the understanding of patients about their medical condition, diagnosis, and treatment options. Therefore, this study aims to examine the accuracy and reliability of ChatGPT in answering questions regarding HNC.154 head and neck cancer-related questions were compiled from sources including professional societies, institutions, patient support groups, and social media. These questions were categorized into topics like basic knowledge, diagnosis, treatment, recovery, operative risks, complications, follow-up, and cancer prevention. ChatGPT was queried with each question, and two experienced head and neck surgeons assessed each response independently for accuracy and reproducibility. Responses were rated on a scale: (1) comprehensive/correct, (2) incomplete/partially correct, (3) a mix of accurate and inaccurate/misleading, and (4) completely inaccurate/irrelevant. Discrepancies in grading were resolved by a third reviewer. Reproducibility was evaluated by repeating questions and analyzing grading consistency.ChatGPT yielded “comprehensive/correct” responses to 133/154 (86.4%) of the questions whereas, rates of “incomplete/partially correct” and “mixed with accurate and inaccurate data/misleading” responses were 11% and 2.6%, respectively. There were no “completely inaccurate/irrelevant” responses. According to category, the model provided “comprehensive/correct” answers to 80.6% of questions regarding “basic knowledge”, 92.6% related to “diagnosis”, 88.9% related to “treatment”, 80% related to “recovery – operative risks – complications – follow-up”, 100% related to “cancer prevention” and 92.9% related to “other”. There was not any significant difference between the categories regarding the grades of ChatGPT responses (p=0.88). The rate of reproducibility was 94.1% (145 of 154 questions).ChatGPT generated substantially accurate and reproducible information to diverse medical queries related to HNC. Despite its limitations, it can be a useful source of information for both patients and medical professionals. With further developments in the model, ChatGPT can also play a crucial role in clinical decision support to provide the clinicians with up-to-date information. The Chat Generative Pre-trained Transformer (ChatGPT) is a recent AI model, designed to generate human-like conversational dialogue in response to textual input by predicting answers from a vast database of publicly undisclosed resources including websites, books, and articles up to 2021 . It is fHead and neck cancer (HNC) ranks as the seventh most common form of malignancy globally, with an annual incidence of approximately 660,000 new cases , 12. Ala2Institutional review board approval was not sought for this prospective study due to the absence of patient-level data. Authors have no affiliation or involvement with OpenAI Inc., the developer of ChatGPT.2.1The data set of questions was compiled from queries frequently posted by professional institutions and societies such as the American Head & Neck Society (AHNS), National Cancer Institute, and the Medline Plus Medical Encyclopedia. In the interest of inclusivity and patient representation, questions sourced from patient support groups and social media posts were incorporated. These questions underwent a rigorous screening process by three authors to evaluate their eligibility for inclusion in the study. The selected questions pertained specifically to HNC. Exclusion criteria were implemented to disqualify questions with similar meanings, questions that were subjective or could vary between patients , vague inquiries , and non-medical questions related to the condition   basic knowledge, (2) diagnosis, (3) treatment, (4) recovery, operative risks, complications and follow-up (5) cancer prevention, and (6) other. Grammatical adjustments were made to certain questions to ensure clarity and precision.The selection was predominantly patient-oriented, seeking to evaluate the AI model’s ability to provide information to potential patient inquiries . Additionally, we included questions featuring technical medical terminology to simulate scenarios that patients might encounter during their medical journey . Complex questions were also included to assess the model’s capacity to assist medical professionals .2.2In this study, we used ChatGPT Plus , an advanced subscription-based version of ChatGPT that was released in November 2022. The questions were submitted on June 13, 2023. Each question was entered independently using the “New Chat” function. In alignment with previous studies, each question was entered twice to assess the reproducibility of ChatGPT’s responses , 10. Cha2.3Two experienced head and neck surgeons, currently active in academic practice, independently reviewed and graded the responses to questions for accuracy and reproducibility. The reviewers evaluated the accuracy of responses according to the following scale2.3.1Data is accurate and comprehensive; a head and neck surgeon would add no further information if asked by a patient.2.3.2The provided data is correct; however, additional pertinent information could be provided if asked by a patient.2.3.3Contains accurate and inaccurate data, potentially misleading.2.3.4The data provided is completely inaccurate or irrelevant.Reproducibility was assessed based on the consistency of the two responses to each individual question. If the responses were similar, only the first response from ChatGPT was graded. In cases where the responses differed, both were independently graded by the reviewers. If the grades differed, the responses were deemed non-reproducible. Any discrepancies in the accuracy and reproducibility of responses between the two reviewers were independently reviewed and resolved by a third reviewer, a highly experienced academic head and neck surgeon, who was blinded to the initial reviews. Reproducibility was evaluated for each category of questions and compared between categories.2.4The proportions of each grade among the responses were calculated and reported as percentages. Categorical variables were examined using the χ2 test and Fisher’s exact test. The kappa statistic was used to measure inter-rater agreement, revealing a substantial agreement between Reviewers 1 and 2 . All analyses were performed using IBM SPSS v.25.0 (IBM Corp.).3A total of 154 inquiries pertaining to HNC were directed to ChatGPT. The model provided “comprehensive/correct” responses to 133 out of 154 (86.4%) questions. Meanwhile, the rates of “incomplete/partially correct” and “mixed with accurate and inaccurate data/misleading” responses were noted to be 11% and 2.6%, respectively. It is significant to note that there were no instances of “completely inaccurate/irrelevant” responses.Questions were categorized as follows: basic knowledge , diagnosis , treatment , recovery - operative risks – complications – follow-up , cancer prevention  and other .Overall, the reproducibility rate of the model was 94.1% (145 questions). Reproducibility was 100% for the categories of basic knowledge, cancer prevention, and other. However, this rate decreased to 88.9% for diagnosis, 88.9% for treatment, and 92.5% for recovery – operative risks – complications – follow-up categories  to the same queries . The finOur findings indicate that the majority of responses from ChatGPT were accurate, with 86.4% of receiving a “comprehensive/correct” rating on our grading scale. Importantly, none of the responses were classified as “completely inaccurate/irrelevant”. Furthermore, the model demonstrated high reproducibility across all topics, and performed commendably without any significant differences between them. Our study may provide an early evidence base demonstrating the immense potential of this innovative platform in the field of AI-driven medical information, specifically concerning HNC. With additional validation, ChatGPT or similar tools could serve as invaluable resources for rapid medical information retrieval in high-speed clinical settings, thereby enhancing efficiency and aiding clinicians in their complex decision-making processes. However, we are only in the early stages of the era of AI-provided medical services, and it is currently not advisable to rely solely on the existing version of ChatGPT as the only source of medical information. With the advent of newer versions that are appropriately trained by medical experts using the most current medical literature, accurate medical information could be rapidly disseminated to both patients and medical professionals.To the best of our knowledge, this is the first study investigating the application of ChatGPT in the field of HNC as of July 2023. The questions incorporated in our study were sourced from reputable institutions and societies, as well as patient support groups. The assessment of accuracy and reproducibility was conducted by independent evaluators. However, it is necessary to acknowledge the limitations inherent in both the ChatGPT model and our study. Pertaining to ChatGPT, the current version’s knowledge cutoff is up to September 2021. Omission of data from the past two years could potentially impact the precision of the responses. Furthermore, the reliability of ChatGPT is fundamentally contingent upon the quality of the training data. Hence, given the undisclosed sources of the model, it remains questionable whether the training was based on the most reliable and accurate medical literature. Thirdly, the latest version of ChatGPT, which exhibits superior performance compared to the publicly available version, is accessible only via paid subscription, potentially constraining the public’s access to more accurate knowledge.In relation to our study, we utilized a grading method similar to those employed in previous studies , 10. How5ChatGPT has proven to generate markedly accurate and reproducible responses to a wide range of medical inquiries pertaining to HNC. Despite its inherent limitations, it may serve as a beneficial source of information for both patients and healthcare professionals. As the model undergoes further refinement, ChatGPT could potentially assume a vital role in clinical decision support, equipping clinicians with current information. It is imperative that future research efforts strive to delineate the risks and benefits of employing this AI model in the context of HNC, as well as in diverse medical domains.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.OK: Conceptualization, Project administration, Resources, Supervision, Validation, Visualization, Writing – review & editing. AP: Conceptualization, Data curation, Formal Analysis, Investigation, Methodology, Writing – original draft, Writing – review & editing. NS: Project administration, Supervision, Validation, Visualization, Writing – review & editing. SH: Investigation, Project administration, Resources, Supervision, Validation, Visualization, Writing – review & editing.


Interestingly, the non-equidistant and nonlinear properties of LLs of graphene in the presence of a magnetic field which make it a promising material for various optoelectronic applications arises from its linear energy dispersion relation4. It is well-known that the zero-gap Dirac cones in the linear energy spectrum of graphene give rise to observation of the unconventional quantum Hall conductivity in the presence of a magnetic bias applied normally to its surface5.Under a normally applied magnetic field, unlike conventional 2D electron gas (2DEG) systems, the Landau levels (LLs) in 2D Dirac materials are not equally spaced and vary non-linearly with the field modulations. This could significantly affect the absorption properties of 2DEG systems with Dirac spectrum. Graphene, a 2D material composed of carbon atoms arranged in a honeycomb pattern, has attracted huge attention due to its exceptional electronic and optical properties10, the primary phenomenon is the absorption of incoming electromagnetic waves through materials and converting them to electrical current. The absorption of materials could be considered due to the electronic excitations in near-infrared and visible, phonons’ local vibrational modes in mid-infrared, and collective modes in terahertz regime11. However, the absorption of electromagnetic waves in a atomically 2D materials is generally insufficient for real-world applications. Therefore, developing innovative methods to enhance the absorption of them is an essential step toward improving its optical absorption properties.Now, the absorption of light is being studied to understand how electromagnetic waves can be harvested to stimulate electrons in materials. For instance, in optical sensors and solar cells16 to trap waves in an optical cavity and excitation surface plasmonic resonances19. Now, since these approaches are highly dependent on the structure, absorption is typically limited to a narrow electromagnetic spectrum. As a result, additional techniques are needed to achieve perfect absorption in a more straightforward and tunable manner. Here, coherent perfect absorption (CPA) is a promising concept to address these challenges. The underlying principle behind CPA is making standing waves by interfering with two beams with tuned frequency to trap electromagnetic energy onto the absorber and surpassing the scattering matrix. Therefore, the perfect absorption could be accessible by tuning the phase modulation of two incident beams21. Graphene, as a one-atom-thick 2D material, in the visible and near-IR zone under normal incidence could absorb only From a theoretical standpoint, the maximum absorption of a 2D material is 22. Fan et al., calculated the CPA frequency required to maintain perfect absorption. They considered monolayer graphene and illuminated it with two coherent beams. By finding the appropriate values for |r| and |t| to suppress the scattering matrix, they obtained a CPA frequency of 1.735 THz for doped monolayer graphene  in the mid-infrared and terahertz ranges. Rao et al., showed 80% modulation of light through the CPA concept. They employed unstructured multilayer graphene as an absorber in their setup and employed a continuous wave laser source  situation. To be more, specific, applying a magnetic field to the surface of graphene can introduce nonlinear Landau energy levels in its linear spectrum. This leads to a Hall term in the tensor of its magneto-optical conductivity which could significantly alter CPA conditions in QHE regime. In this work, for the first time, we propose that introducing a magnetic bias field into the unstructured monolayer graphene results in a magneto-tunable CPA at both sub-tesla and high field levels for RHC and LHC polarizations in THz regime. Our results could pave the way for magnetically tunable perfect absorber devices and ultrafast graphene-based quantum magnetometers.Up to now, the coherent absorption in graphene can be tuned substantially by varying the gate-controlled Fermi energy level which control the optical transitions of graphene. Optical conductivity of graphene is also a function of the illuminating frequency and the electron relaxation time. Some efforts have been made to change the Fermi level of graphene through chemical doping or applying voltagez-direction by two circularly-polarized coherent counter-propagating beams, 28. Both longitudinal and Hall conductivity terms could be obtained by the use of the Kubo formula:3:Our model is schematically proposed in Fig. In order to investigate the effect of magnetic field on magneto-CPA properties of graphene, we first calculate the transmission and reflection intensities for two sets of magnetostatic bias fields. As it is shown in Figs. Considering LHC polarized modes, as shown in Fig. entclass1pt{minimaentclass1pt{minimaentclass1pt{minimaentclass1pt{minimaFor the magnetic bias below The absorption of two LHC polarized coherent electromagnetic beams is shown in Fig. Now, we turn our attention to the low field limit for highly doped graphene. As illustrated in Fig. In conclusion, we prove that monolayer graphene could exhibit THz CPA in the QHE regime for circularly polarized radiations. Also, tunable property of quasi-CPA frequency corresponding to right- and left-handed modes by the intensity of the applied magnetic field was simulated. Moreover, at CPA frequencies, the two circularly polarizations revealed different phase modulations for an applied magnetic field intensity. It was demonstrated that two or even more CPA frequencies with different properties could be emerged for left-handed modes. Interestingly, it was shown that increasing the magnetic field bias for right-handed (left-handed) polaized beam red-shift (blu-shift) the CPA frequency. We also examined CPA properties at subtesla magnetic fields and found that the CPA frequency could be modulated ranging from about 1.4 to 2 THz. It was then revealed that our results at low magnetic field could recover earlier CPA conditions reported for graphene in the absence of an applied magnetostatic bias. The physics behind our results could be much more clear by analyzing Supplementary Figures.