The PO activated carbons have a surface area of up to 1760 m2 g−1 and are highly microporous with virtually all of the surface area arising from micropores. The porosity of the PO activated carbons can be readily tailored towards having pores of size 6–8 Å, which are highly suited for CO2 storage at low pressure . At 25 °C, the PO activated carbons can store up to 1.8 and 5.0 mmol g−1 of CO2 at 0.15 bar and 1 bar, respectively. On the other hand, KOH activated carbons reach a higher surface area of up to 2700 m2 g−1, and store up to 1.0 and 4.0 mmol g−1 of CO2. This work demonstrates that PO may be used as a mild, less corrosive and less toxic activating agent for the rational and targeted synthesis of biomass-derived activated carbons with tailored porosity. The targeted synthesis may be aided by careful selection of the biomass starting material as guided by the O/C ratio of the biomass.This work explores the use of a less corrosive activating agent, potassium oxalate (PO), in combination with difficult to activate carbonaceous matter for the preparation of activated carbons. The design of the study allowed a fuller understanding of the workings of PO compared to hydroxide (KOH) activation, and also optimised the preparation of highly microporous carbons with exceptional CO 2 uptake.Rational combination of a mild activating agent  and air carbonised biomass, which is resistant to activation, yields highly microporous carbons with enhanced post-combustion CO This increase is a significant global challenge as CO2 is a greenhouse gas in terms of contributing to global warming. Carbon capture and storage (CCS) is among the few remaining options for halting global warming.1–5 Activated porous carbons have long been used in environmental remediation applications, including removal of water pollutants, sewage treatment, air purification, and more recently have attracted attention in energy storage applications.6–11 As a result of their suitable chemical and thermal stability, and high and controllable porosity, activated carbons are amongst the most promising porous materials for CO2 capture and storage.12–21 In recent years, new ways of preparing porous carbons with properties directly targeted at energy-related applications have been a focus of intense research efforts.22–33The concentration of CO2SO4, and H3PO4), alkali hydroxides , ZnCl2, and K2CO3.14–16 KOH is one of the best-studied activating agent, as it can generate activated carbon with defined pore size distribution and high surface area from a wide range of carbon starting materials .27–31 However, the use of KOH has disadvantages associated with its toxic and corrosive nature. Milder activating agents that yield carbons with comparable or superior textural properties compared to KOH activation are therefore a key research target.34–44 In particular, in the search for activating agents beyond hydroxides, the use of potassium oxalate (PO) as activator for a range of precursors has been explored.34–38,40–44 Previous studies on PO activated carbons have shown that, in general, carbons with low to medium surface area  are obtained at activation temperature below 800 °C.34–38,44The most frequently used chemical activating agents for the preparation of activated carbons are inorganic acids  and the activation parameters. For thermal activation with an activating agent, the parameters include duration of activation, type and flow rate of the inert gas used to create a non-oxidising atmosphere, heating ramp rate and, most importantly, the temperature and amount of activating agent. Additionally, as demonstrated recently,Phoenix dactylifera), once air-carbonised in a process that is simpler than conventional hydrothermal carbonisation (HTC)46–48 or pyrolysis,49–52 generate carbonaceous matter with low O/C ratio that may be used as precursor to generate KOH-activated carbons with properties suited for methane storage.45 We demonstrated that the low O/C ratio of air-carbonised date seed plays a key role in determining the porosity of the resulting KOH-activated carbons.45 In the present study, milder PO activation of air carbonised date seed was performed and compared to KOH activation. This work focussed on exploration of the possibility of generating highly microporous activated carbons by combining a mild activating agent (PO) with a precursor that has low O/C ratio and is therefore resistant to activation. The expectation was that this will limit the level of activation (compared to the use of KOH) and thus hinder the formation of mesopores, while at the same time offering high yields of activated carbons that only possess micropores. Given the expectation of highly microporous carbons, this study targeted their application towards the uptake of CO2 at low pressures that mimic post-combustion capture from the flue gas streams of fossil fuel power stations.Biomass sources are widely available as a renewable resource, are generally affordable and may be considered as being ‘carbon neutral’. We have previously shown that date seeds  carbon. For activation, the ACDS carbon was mixed with the required amount of potassium oxalate (PO) at predetermined PO/ACDS carbon ratios in an agate mortar. The PO + ACDS carbon mixture was placed in an alumina boat and heated in a furnace to 700 or 800 °C at a heating ramp rate of 3 °C min−1 under an atmosphere of nitrogen gas and held at the final temperature for 1 h, after which the sample was allowed to cool under a flow of nitrogen. The resulting activated samples were then washed by stirring in 20% aqueous HCl at room temperature, and then repeatedly with deionised water until the filtrate was neutral (pH ∼ 7). The samples were then dried in an oven at 120 °C, and designated as ACDSxT(PO), where x is the PO/ACDS carbon ratio, T is the activation temperature (in °C) and PO indicates the use of potassium oxalate as activating agent. Thus, a carbon activated at a PO/ACDS carbon ratio of 2 and at 800 °C is designated as ACDS2800(PO) or ACDS2800P(PO), where P indicates that the PO + ACDS mixture was compacted before the activation step . The compaction into pellets prior to activation was performed in a 1.3 cm die for ca. 5 min at 740 MPa.After thorough washing with water and drying, date seed (5 g) were placed in an alumina boat and heated in a horizontal tube furnace, at a heating ramp rate of 10 °C min2 uptake in order to make a clear comparison between KOH and PO activation. A carbon activated at a KOH/ACDS carbon ratio of 2 and at 800 °C is designated as ACDS2800 for a powder sample and ACDS2800P for a compactivated sample.Carbons activated at a KOH/ACDS carbon ratio of 2 or 4 and at 700 or 800 °C were also explored for CO2.2−1). A PANalytical X'Pert PRO diffractometer was used to perform powder XRD analysis using Cu-Kα light source  with step size of 0.02° and 50 s time step. Elemental, CHN, analysis was performed on an Exeter Analytical CE-440 Elemental Analyser. Nitrogen sorption (at −196 °C) with a Micromeritics 3FLEX sorptometer was used for porosity analysis and to determine textural properties. Prior to analysis the carbon samples were degassed under vacuum at 200 °C for 12 h. Surface area was calculated using the Brunauer–Emmett–Teller (BET) method applied to adsorption data in the relative pressure (P/P0) range of 0.02–0.22, and pore volume was estimated from the total nitrogen uptake at close to saturation pressure (P/P0 ≈ 0.99). The micropore surface area and micropore volume were determined via t-plot analysis. The pore size distribution was determined using non-local density functional theory (NL-DFT) applied to nitrogen adsorption data. Scanning electron microscopy (SEM) images were recorded using an FEI Quanta200 microscope, operating at a 5 kV accelerating voltage. Transmission electron microscopy (TEM) images were obtained using a JEOL 2100F instrument operating at 200 kV equipped with a Gatan Orius CCD for imaging. Prior to analysis, the carbon samples were suspended in distilled water and dispersed onto lacey carbon support films.Thermogravimetric analysis (TGA) was performed using a TA Instruments Discovery analyser or TA Instruments SDT Q600 analyser under flowing air conditions , the yield from the hydrochar was in the range of 36% to 41%, which is significantly lower than for PO activation of ACDS carbon.34 This comparison clearly demonstrates the benefits, in terms of greater yield, of utilizing air-carbonised date seed as a precursor; the genesis of this benefit arises from the nature of the ACDS carbon as occasioned by its low O/C ratio and associated resistance to activation.45Following flash air-carbonisation, the carbon content increased from 49 wt% for raw date seeds to 78.5 wt% for ACDS carbon, whereas the H content decreased from 7 wt% to 4 wt%. This was accompanied by a significant decrease in the apparent O content from 42.4 wt% (raw date seed) to 16.3 wt% for ACDS carbon. The elemental C content of the PO activated carbons increases from 78.5 wt% for the ACDS carbon to as high as 87.0 wt% (ACDS2800P(PO)), while the content of both N and H reduces to trace or nil amounts for some of the activated samples. KOH activated carbons Table S1 show a si.e., non-graphitic) nature of the carbons. The activated carbons display nil or <2 wt% residual mass, suggesting that they may be considered as being essentially fully carbonaceous with only trace or nil inorganic matter. This is confirmed by XRD patterns , with hardly any further adsorption at P/P0 above 0.1. Pelletization (compaction) before activation has little effect on the porosity generated. This is related to the fact that the key determinant in the porosity of PO activated carbons is the activation temperature rather than the amount of PO.34,44 Compactivation has previously been shown to improve the efficiency of KOH as an activating agent but such improvement does not appear to apply to PO at PO/ACDS carbon ratio of 2 and 4. In a sense, the amount of PO can be considered to be already tending towards being ‘in excess’ at PO/ACDS carbon ratio of 2 and thus any process modification to improve the action of PO will have little effect. On the other hand, as shown in The ACDS carbon was found to be nearly non-porous, with a surface area of 2.5 mi.e., pore channels of size 7–20 Å) and some small mesopores.45 Clearly, KOH activation generates a greater proportion of larger pores compared to PO activation, and the proportion of these larger pores  is higher at KOH/ACDS carbon ratio of 4. Indeed, KOH activation, especially at 800 °C and/or KOH/ACDS ratio of 4, generates carbons . This is followed by a reaction, at 700 °C and above, between C within the precursor and the generated carbonate, which results in the etching of C atoms  according to the reaction K2CO3 + 2C → 2K + 3CO. Moreover, the carbonate can also decompose (K2CO3 → K2O + CO2), generating CO2 gas that can cause pore formation (at ≥700 °C) via gasification (C + CO2 → 2CO) of the ACDS carbon. Activation via oxalate decomposition explains the mild nature of PO compared to the more direct action of KOH with respect to interaction with the precursor. Thus using potassium oxalate as an activating agent allows for porosity control by simply changing the activation temperature, and benefits from being a less corrosive and less toxic activating agent than KOH. For the present activation of the ACDS carbon, the overall trends in porosity that emerge from the PO and KOH comparison are that, at temperatures of 700 to 800 °C, the former (PO) generates carbons with a surface area of up to ca. 1800 m2 g−1, whereas KOH activation achieves carbons with a surface area of up to 2700 m2 g−1. However, carbons with a higher proportion of micropore surface area, which is preferred for CO2 uptake at low pressure, are generated with PO.The differences in porosity described above are related to the action of KOH and PO. For KOH, the hydroxide reacts directly with C to generate carbonates, meaning that activation (C etching) can occur even at low temperatures. On the other hand, PO activation occurs 3.32 storage at low pressures that mimic post-combustion capture from flue gas streams of fossil fuel power stations. 2 uptake isotherms for PO and KOH activated carbons, respectively, and −1) at 0.15, 1 and 20 bar. The PO activated carbons have very high uptake of between 1.5 and 1.8 mmol g−1 at 0.15 bar. This uptake pressure was chosen as an indicator of the storage capacity from a flue gas stream (at 1 bar) that typically contains ca. 15% CO2. The uptake capacity places the PO carbons at the top end of porous materials given that for most previously reported activated carbons, the uptake at 0.15 bar is typically lower than 1 mmol g−1.19–40,53 The narrow range of the uptake capacity at 0.15 bar is a reflection of the similarity in pore size of the PO activated carbons regardless of their overall surface area and pore volume. Indeed, the magnitude of the surface area and pore volume does not have any effect on the uptake. As shown in −1, which is a reflection of their lower levels of microporosity and presence of wider micropores and small mesopores . This is despite the KOH activated carbons having higher surface area and pore volume, which emphasizes the absence of a link between low pressure CO2 uptake and total porosity. The lower uptake (at ≤1 bar) of the KOH carbons is due to their wider pores compared to PO activated equivalents  outperforms that of analogous KOH activated samples. At 0.15 bar, the uptake of PO carbons is more than double that of KOH samples, while at 1 bar the improvement is as high as 60% for some samples. Thus despite the PO carbons being prepared with a milder and much easier to handle activating agent, they are very attractive for CO2 capture and storage and compare favorably with current benchmark porous carbons.12–25,53–76At 1 bar  and S9†,2 uptake of the samples. Therefore, changing the PO/ACDS ratio between 2 to 4 does not significantly affect the CO2 uptake. For instance, the CO2 uptake at 1 bar is ca. 5.0 mmol g−1 for both sample ACDS2800P(PO) and ACDS4800P(PO). Additionally, the CO2 uptake at 20 bar is 11 mmol g−1 for both sample ACDS2800P(PO) and ACDS4800P(PO) and is very similar (9.5–10.5 mmol g−1) for sample ACDS2800(PO) and ACDS4800(PO). This means that there is no need to use the higher amount of PO as a means to optimising the CO2 uptake. Use of a lower amount of PO is attractive as it reduces the costs of activation thus making the process more affordable and sustainable. This is in addition to the milder nature (in terms of corrosion) of PO activation, which will translate to lower costs with respect to equipment maintenance. In contrast, the activation temperature has an essential role in determining the CO2 uptake. Higher activation temperature does in some cases translate to greater CO2 uptake especially at pressures above 1 bar. In a sense, the activation temperature can be used to tailor the porosity of the PO activated carbons so as to target optimised CO2 uptake at low or high pressure. In this regard, temperature variations combined with a meagre PO/ACDS ratio of 2 can be employed to synthesise a suite of carbons with a wide range of porosity. In this scenario, a more environmentally friendly and sustainable activation procedure is allowed, along with easier porosity control, by adjusting the activation temperature.Moreover, according to the uptake data in 4.2 g−1 and pore volumes up to 0.75 cm3 g−1. Thus at temperatures of 700–800 °C, the surface area of PO activated carbons is limited to below 1800 m2 g−1, while surface area of up to 2700 m2 g−1 may be obtained under similar activation conditions from KOH activation. However, due to their greater microporosity, PO activated carbons have high CO2 uptake at low pressure (i.e. post-combustion CO2 capture conditions). At 25 °C, the PO activated carbons capture up to 1.8 and 5.0 mmol g−1 of CO2 at 0.15 bar and 1 bar, respectively compared to a maximum of 1.0 and 4.0 mmol g−1 for equivalent KOH activated carbons. Unlike what is observed for KOH activation, changes in the amount of PO have no significant influence on the porosity of the PO activated carbons; the activation temperature is the more critical variable in controlling the porosity of the PO activated carbons. As a result, a low amount of PO, coupled with variations in the activation temperature, may be used to generate a suite of carbons with a wide range of targeted porosity.We have demonstrated that a less corrosive and less toxic activating agent, potassium oxalate (PO), may be used to produce activated carbons from biomass in a targeted manner. By carefully choosing activation conditions, is it possible to obtain highly microporous activated carbons with surface areas up to 1767 mThere are no conflicts to declare.RA-012-D2RA02661A-s001


An elevated adenosine deaminase (ADA) level in the cerebrospinal fluid (CSF) is considered a reliable marker of tuberculous meningitis (TBM). However, CSF-ADA levels can also be elevated in other diseases. We aimed to find the most common diagnosis of patients with elevated CSF-ADA levels for the last 10 years.We retrospectively investigated the diagnoses of all patients with elevated CSF-ADA (ADA ≥ 10 IU/L) levels between 2010 and 2019 at the Samsung Medical Center. Definite TBM was defined based on microbiological evidence. Clinical TBM was defined based on the brain imaging and response to the standard TB treatment. We compared the laboratory characteristics of the three most common diagnoses.CSF-ADA levels were elevated in 137 (5.6%) of 2,600 patients. The most common diagnoses included hematologic malignancy , TBM , and viral meningitis . CSF-ADA levels did not differ significantly between TBM  and HM [16.5 (12.8–24.0)]. However, CSF-ADA levels were lower in VM [14.0 (11.0–16.1)] than in TBM (p = 0.027). Lymphocyte-dominant pleocytosis was more common in VM [77.0% (70.8–81.5)] than in TBM  or HM . Interestingly, the CSF characteristics of clinical TBM were similar to those of VM but not definite TBM.The most common diagnoses with elevated CSF-ADA levels were HM, followed by TBM and VM. Clinicians should carefully consider the differential diagnoses in patients with elevated CSF-ADA levels, especially those in the early stage of meningitis without microbiological evidence for TBM. Tuberculous meningitis (TBM) is one of the most lethal and debilitating forms of TB that presents with few specific symptoms but needs an early diagnosis . As a diNevertheless, CSF-ADA levels are frequently elevated in various meningitis forms caused by other infectious or non-infectious etiologies including malignancies . ConsequTherefore, it is necessary to know how common other etiologies of meningitis with elevated CSF-ADA rather than TBM. Herein, we evaluated the diversity of diagnoses and their contribution to the patients with meningitis with elevated CSF-ADA levels. Moreover, we compared the clinical and laboratory characteristics of meningitis with different diagnoses. This study will help clinicians diagnose and decide treatment plans for those patients.th edition,” which reported the cutoff as 5–10 IU/L in Korea  ≥10,000/mmmorrhage .The included patients’ diagnoses were reviewed with the medical records and classified according to criteria set based on the former guidelines and studies. In our medical institution, the tests for a patient with meningitis included the following: CSF cytology, Gram stain and culture, acid-fast stain and culture, fungus culture, PCR for TB, PCR for the virus , PCR for protozoa (toxoplasma), and serologic test .The definite TBM were defined as meningitis with positive Acid Fast Bacilli culture for TB or positive nucleic acid amplification test (NAAT) for TB. The NAAT for TB was performed using the GENEDIA MTB/NTM Detection Kit  or Xpert MTB/RIF . Clinical TBM was defined as follows: 1) meningitis with brain MRI findings suggestive of TBM  or evidence of extra-neural TB , 2) negative results in a biological test of all other etiologies, and 3) responded well to at least 6 months of empirical TB treatment . DefinitDefinite meningeal involvement of hematologic malignancy (HM) or solid cancer was defined as meningitis with positive malignant cells in CSF or brain biopsy. Clinical meningitis due to malignancy was defined as meningitis in patients with hematologic malignancy or solid cancer without positive malignant cells in CSF or brain biopsy and without any evidence of all other meningitis etiology.Moreover, the following data were collected from the study population’s electronic medical records: age, sex, and CSF analyses .The primary aim of this study was to investigate the various possible diagnoses in patients with meningitis with elevated CSF-ADA levels. Subsequently, the sensitivity, specificity, negative predictive value (NPV), and PPV of CSF-ADA for TBM were calculated. The secondary aim of this study was to compare the clinical and laboratory characteristics of the three most common diagnoses: considering that the clinical diagnosis could be biased, only the definitive diagnoses with microbiological evidence were compared. Moreover, the CSF characteristics of definite TBM, clinical TBM, and definite VM were compared, since each of these diseases can present with lymphocyte-dominant pleocytosis in the CSF and can mimic the clinical manifestations of the others .http://www.R-project.org). Student’s t-test or the Mann–Whitney U test was used to compare the continuous variables of the two groups, and the one-way ANOVA or Kruskal–Wallis test was used to compare the continuous variables of multiple groups. The chi-squared test or Fisher’s exact test was used to compare categorical variables. The Bonferroni method was used to conduct post-hoc analysis for multiple comparisons. All p-values were two-tailed, and p-values <0.05 were considered statistically significant.All statistical analyses were performed using a commercially available software package R 4.0.2 , TBM , and VM  (Elevated CSF-ADA (≥10 IU/L) levels were observed only in 144 (5.6%) of the 2,600 eligible patients Figure 1The proportion of clinical and definitive TBM was significantly higher (p < 0.001) in the patients with elevated CSF-ADA  than in the patients without CSF-ADA . The calculated PPV of CSF-ADA for TBM was only 19.2%. The sensitivity, specificity, and NPV of CSF-ADA for TBM diagnosis were calculated as 65%, 95.4%, and 99.4%, respectively. We have specified the sensitivity, specificity, PPV, and NPV of CSF-ADA for the three most common diagnoses  in No significant difference was observed in the level of CSF-ADA between TBM  and HM [16.05 (12.80–24.02)], while the CSF-ADA levels were significantly lower in VM [14.00 (10.95–16.07)] than in TBM (p = 0.027). Regarding the cell count of the CSF, the prevalence of lymphocyte-dominant pleocytosis was higher in VM [77.0% (70.8–81.5)] than in TBM  or HM , while the prevalence of polymorphonuclear neutrophil-dominant pleocytosis was higher in TBM [58.0% (23.5–89.3)] than in VM [1.0% (0.0–1.0)] or HM [0.0% (0.0–4.3)]. As expected, CSF glucose levels were lower in TBM [34.5 (25.3–48.0)] than in VM  (CSF-ADA levels were higher in definite TBM [20.20 IU/L (13.78–29.30)] than in clinical TBM . Moreover, CSF glucose was lower in definite TBM [59 mg/dl (49.25–76)] than in clinical TBM . In general, the CSF characteristics of clinical TBM were similar to those of definite VM, rather than definite TBM Table 2.Our study found that HM, TBM, and VM were the three most common diagnoses in patients with elevated CSF-ADA levels for the past 10 years in our institution, which is the major tertiary hospital in Korea. More than two-thirds of patients with meningitis with elevated CSF-ADA levels did not have TBM. Moreover, the CSF findings of clinical TBM were similar to those of definite VM and not definite TBM. Therefore, this study suggests that clinicians should consider various diagnoses in patients with elevated CSF-ADA levels without any determined etiology.In our study, meningeal involvement in HM, especially lymphoma, was the most common cause of CSF-ADA elevation. As mentioned above, ADA is a marker of lymphocytic activation associated with the CMI . TherefoVM was the third most common cause of meningitis in patients with elevated CSF-ADA levels in our study. The VM's level of CSF-ADA overlapped with the TBM's. Moreover, the CSF findings of clinical TBM were similar to those of definite VM, and not definite TBM. This finding is not unusual because cell-mediated immunity plays a pivotal role in the defense against viral infections in humans . Also, tMeanwhile, our study showed that Japanese encephalitis was the most common etiology of definite VM with elevated CSF-ADA levels. This finding is interesting since CSF-ADA elevation has not been studied in patients with Japanese encephalitis. We suggest considering Japanese encephalitis as a differential diagnosis in patients with elevated CSF-ADA levels with meningitis with an undiscovered etiology.In this study, the PPV of CSF-ADA for TBM was 18.1% . The PPV was even lower for definite TBM, at only 8.3%. The low PPV of CSF-ADA in this study is a salient finding considering PPV depends on the prevalence of a given disease in the study population: TB is endemic to the Republic of Korea , which has a 23-fold higher incidence of TB as compared to the United States  . TherefoSeventy percent of the TBM has been diagnosed between 2010 and 2014, while 70% of the HM and VM has been diagnosed between 2015 and 2019. This reflects the constant decrement in TB prevalence  during the past 10 years in Korea; the prevalence was 152 in 2010, 101 in 2015, and 59 in 2019 . In contOur study has some limitations. First, it was a single-center, retrospective study: the differential diagnosis could have been different depending on the type of hospital and geographical characteristics. However, our medical center is the third largest tertiary referral center in South Korea for all serious illnesses, making it a suitable representation of the whole nation. Therefore, low prevalence or pretest probability of TBM is a major factor to decrease the diagnostic performance of ADA in general clinical situations, not limited to our medical institution. Second, clinical diagnoses may possibly differ from the actual underlying etiology. Twenty-eight percent (39/137) of patients were provided only with clinical diagnoses, without specific microbiological evidence on CSF analysis. Therefore, the true prevalence of each etiology should be cautiously interpreted. Finally, the similarity between the CSF findings of TBM and definite VM does not represent direct evidence of the possibility of misdiagnosing VM as TBM. Further studies are needed to examine the definitive microbiological evidence of patients diagnosed with clinical TBM. In addition, definitive TBM cases in our study showed relatively neutrophil-dominant pleocytosis. Although lymphocyte-dominant pleocytosis is known for characteristic findings in patients with TB meningitis, neutrophil-dominant pleocytosis can be frequently observed in TB meningitis, especially in the early stage of disease progression . SeveralIn conclusion, patients with meningitis and elevated CSF-ADA levels could have a variety of diagnoses: elevated CSF-ADA levels in these patients were not specific to TBM, as evidenced by the low PPV. Moreover, patients with clinical TBM who improved with standard TB treatment showed CSF findings that were similar to those with definite VM, but not akin to those with definite TBM. Hence, non-TBM patients may undergo unnecessary TB treatment if clinicians depend on CSF-ADA to diagnose TBM. Clinicians should consider the overall clinical and laboratory findings and sufficient alternative diagnoses in meningitis with elevated CSF-ADA levels.All data generated or analysed during this study are included in this published article (and its supplementary information files).This study was approved by the Institutional Review Board of the Samsung Medical Center (IRB number: SMC 2021-01-122). Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.JS and S-HK equally conceived the study; acquired, analyzed, and interpreted the data; and drafted and revised the manuscript. J-HM conceived, designed, and supervised the study; interpreted the data; and drafted and revised the manuscript for intellectual content. Y-rJ interpreted and analyzed the data. JC revised the manuscript for intellectual content. C-IK revised the manuscript for intellectual content and supervised the study. All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.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.


The final analysis showed anastomotic time to be significantly associated with DGF with odds ratio of 1.04 per minute corresponding to 4% increase in DGF incidence with every minute increment in anastomotic time. Other variables that had significant impact on DGF were DCD donor (odds ratio – 8.7) and donor terminal creatinine. We concluded that anastomotic time had significant impact on the development of DGF and hence should be minimized.The impact of anastomotic time in renal transplant is under recognized and not well studied. It is one of the few controllable factors that affect the incidence of delayed graft function (DGF). Our study aimed at quantifying the impact of anastomotic time. We performed a retrospective review of 424 renal transplants between the years 2006 and 2020. A total of 247 deceased donor renal transplants formed the study cohort. Patients were divided into two groups based on the presence or absence of DGF. Variables with  Renal transplant outcomes have come of age since its inception. With the improved immunosuppression and better understanding of the factors that affect the transplanted graft, the 5-year graft survival in deceased donor renal transplant has improved from 35–40% in the mid-1980s to 85–90% in the last decade –9.The deleterious effects of DGF on graft survival are well established since the first reference paper published by Anderson et al. in 1979 showing inferior long-term graft survival in patients with DGF  still hoThe cause of DGF is multifactorial and includes many non-modifiable donor and recipient factors . IschemiThe objective of our study was to evaluate the impact of AT on the incidence of DGF.Our study design was a retrospective chart review of consecutive renal transplant recipients at our center from 2006 to 2020. Data were extracted from prospectively recorded electronic health records of our departmental “Transnet” and other data repositories in our hospital. Ethics approval was obtained from our hospital ethics committee.Recipient and donor data were extracted that included demographic, comorbidities, donor type, kidney donor profile index (KDPI), CIT, AT, human leucocyte antigen mismatch (HLA MM), post-transplant dialysis incidence, and glomerular filtration rate (GFR) at 1 month and 1 year (mean GFR between 180 and 365 days).Inclusion criteria—All deceased donor renal allograft transplants performed at John hunter hospital (JHH) between 2006 and 2020 were included in the study.Exclusion criteria—Recipients of dual kidney transplants including en bloc kidneys and patients who suffered early graft loss within the first 7 days post-transplant were excluded.Standard induction immunosuppression included basiliximab 20 mg on day 0 and day 4 and methylprednisolone 500 mg at induction of anesthesia. Anti-thymocyte globulin (ATG) was used only in high immunological-risk patients. Standard maintenance immunosuppression included tacrolimus, mycophenolate mofetil, and prednisolone. All patients received pneumocystis and cytomegalovirus (CMV) prophylaxis.U-test, were used to compare continuous variables, and the Pearson chi-square test was used for categorical variables between groups. Binary log regression was used to analyze the impact of AT on DGF. Other variables used in the model were chosen based on prior knowledge and a p-value of < 0.3 on univariate tests to account for potential confounders. The other covariates included in the model were the age and sex of the recipient, donor age, CIT, and donation after cardiac death (DCD) donor status. There were only 14 missing values, which were imputed by the “maximum likelihood estimation method.” Model fitting was tested using the Hosmer and Lemeshow goodness-of-fit test. The c-statistic of the final model was 0.8.Delayed graft function was defined as the requirement of hemodialysis in the first-week post-transplant. Patients were divided into two groups based on the presence or absence of DGF. All analyses were done using SAS academic edition. Continuous variables were presented as the median and interquartile range (IQR) as they were not normally distributed. Categorical variables were expressed as numbers and percentages. Non-parametric tests, such as Mann–Whitney p = 0.108. Median CIT was 840 min . Around 46% of recipients were well matched with the donors having 0–2/6 HLA MM.A total of 279 deceased donor renal transplants were done between 2006 and 2020. The final study cohort consisted of 247 transplant after excluding 32 patients  . The chap = < 0.001. Anastomotic time was found to be significantly longer in the DGF group, p = 0.008. In total, 43.3% (107/247) of DD renal transplants developed DGF. p = 0.002). DCD transplants had an 8.7% higher chance of developing DGF as compared to DBD transplants. Other confounders that had a significant effect on the outcome were donor age and terminal donor creatinine. CIT and recipient sex were not found to have significant differences  .A more detailed analysis was published by Heylen et al. where they analyzed 669 renal transplantation from brain dead donors and showed a similar increase in the DGF odds ratio of 1.05 per minute. They also showed an increased risk of intestinal fibrosis and tubular atrophy on protocol biopsies at 3, 12, and 18 months post-transplant , 21. TheKhan et al. reinstated similar findings and showed AT of >45 min as a risk factor for poor EGF but had a statistically significant difference only beyond 60 min . More reIn our study, DGF occurred in a significant percentage of DD transplants (44%) with a much higher incidence in DCD transplants (75%) as compared to DBD transplants (32%).The adverse impact of DGF has been well established. A recently published study in 2021 showed DGF to be the greatest predictor of graft failure at 3 years, after analyzing UNOS/OPTN data of 42,736 living donor transplants .Incerti et al. evaluated the overall lifetime health burden of DGF as a loss of 3.01 quality adjusted life-years for a typical 56-year-old transplant recipient with DGF as compared to a non-DGF recipient of the same age . DGF is Our sub-analysis of serum creatinine at 1 month and 1 year was found to be significantly different in the DGF and non-DGF groups. We did not compound the rejection data or biopsy findings in analyzing the graft function as it was not the primary aim of our study, but similar findings have been reported in other studies , 16, 28.In our logistic regression analysis, CIT was not found to be significantly associated with DGF as opposed to the findings in various other studies , 29–32. The factors influencing anastomotic time include the complexity of the surgery, number of arteries, number of warm anastomosis, body habitus of the recipient, previous transplants, and expertise of the surgeon. Based on our findings and existing evidence, all attempts should be made to reduce the AT along with utilizing techniques to maintain hypothermia during anastomosis.Kidney warming speed is estimated to be around 0.48°C/min once out of ice, reaching >20°C for 30 min of AT . ProtectThe strength of our study is that we have analyzed the impact of AT as a continuous variable as compared to other studies which have described it as a threshold effect based on time interval groups. Our study signifies anastomotic time as an independent factor affecting immediate graft function and demonstrates the incremental effect of time taken for vascular anastomosis on the occurrence of DGF, with every minute adding to a 4% increase in the incidence of DGF in deceased donor transplants.There are some limitations to this study. First, this is a retrospective review with a small cohort. In addition, there was variability in the surgical technique as the transplants were done by different surgeons across the study period.Anastomotic time had a significant impact on the development of DGF and hence should be minimized. The impact is approximately 4% increment in the incidence of DGF with every minute increase in anastomotic time. Further study to address the factors leading to increased anastomotic time would help to identify the potentially modifiable factors to reduce DGF rates.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Hunter New England Human Research Ethics Committee. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.All authors listed have made a substantial, direct, and intellectual contribution to the work, and approved it for publication.


Sedative premedication with benzodiazepines has been linked with prolonged recovery and inadequate emergence during the immediate postoperative period. We aimed to analyze the association between postanesthesia care unit (PACU) delirium and sedative premedication with oral midazolam.We performed a secondary analysis of prospectively collected data before (midazolam cohort) and after (non-midazolam cohort) implementation of a restrictive strategy for oral premedication with midazolam. From March 2015 until July 2018, we included patients 60 years and older, who underwent elective radical prostatectomy for prostate cancer. Exclusion criteria were contraindications to premedication with midazolam, preoperative anxiety, and a history of neurological disorders. Patients, who were scheduled for postoperative admission to the intensive care unit, were excluded. Between 2015 and 2016, patients received 7.5 mg oral midazolam preoperatively (midazolam cohort). Patients included between 2017 and 2018 did not receive any sedative medication preoperatively (non-midazolam cohort). The primary endpoint was the incidence of PACU delirium.n = 214) and 33% in the non-midazolam cohort (n = 218). This difference was not statistically significant on multivariable logistic regression analysis . Age , the cumulative dose of sufentanil , and propofol-sufentanil for anesthesia maintenance  were significantly associated with PACU delirium.PACU delirium rates were 49% in the midazolam cohort (Midazolam for sedative premedication was not significantly associated with PACU delirium. The reduction in the incidence of PACU delirium throughout the study period may be attributable to improvements in perioperative management other than a more restrictive preoperative benzodiazepine administration.The online version contains supplementary material available at 10.1186/s13741-022-00253-4. Postoperative delirium (POD) is a common complication after surgery and anesthesia that particularly affects patients older than 60 years  delirium is one subtype of POD that occurs early after surgery in the PACU  and patients who did not receive any sedative medication preoperatively (study 2: non-midazolam cohort). The midazolam cohort represents a convenience sample of 347 patients who had been enrolled in a prospective observational study (study 1) between January 2015 and March 2016 to compare the incidence of PACU delirium between open retropubic and robot-assisted radical prostatectomy , propofol (2–3 mg kg−1), and rocuronium (0.6 mg kg−1). Anesthesia was maintained with sufentanil and sevoflurane (MAC target 0.8–1.2) or total intravenous anesthesia with sufentanil and propofol (4–7 mg kg−1 h−1). The choice of the anesthetic maintenance agent was at the discretion of the attending anesthesiologist. Anesthesia depth was monitored targeting a bispectral index  between 30 and 40. In the PACU, monitoring was continued  and supplementary oxygen was administered as needed to maintain a peripheral oxygen saturation ≥ 94% (88–92% in patients with chronic obstructive pulmonary disease). If the numeric rating scale was 3 or higher, metamizole and/or piritramide were administered  was used to determine the presence of PACU delirium. The CAM-ICU was performed 15, 30, 45, and 60 min after extubation by six members of the study team, who were trained in CAM-ICU assessment. The Richmond Agitation-Sedation Scale (RASS) was applied at the same time points to evaluate the severity of agitation or sedation. The RASS is a 10-point scale ranging from − 5 (unarousable) to + 4 (combative). The CAM-ICU was only applied in patients with a RASS score of − 3 or higher. We defined PACU delirium as a positive CAM-ICU at any one time point between 15 and 60 min after extubation.On the day before surgery, patients were screened for depressive disorders with the Patient Health Questionnaire (PHQ-9). To screen for preexisting cognitive impairment, the Mini-mental Status Examination was administered preoperatively. Information on baseline demographic and clinical variables  physical status, and education), were obtained during baseline assessment on the day before surgery. Variables related to anesthesia and surgery were collected from the anesthesia protocol on the day of surgery. Patients with one or more missing variables were excluded from analysis Fig. .U tests, χ2 tests, or Fisher’s exact tests, as appropriate. CAM-ICU positivity at different time points was compared with χ2 tests or Fisher’s exact tests and Bonferroni corrected for multiple comparisons. We analyzed the association between preoperative medication with midazolam and PACU delirium using binary logistic regression. The multivariable model included ‘PACU delirium’ as the dependent variable and ‘midazolam cohort’ as the independent variable of primary interest. Other clinically relevant variables were included in the model as possible confounders: anesthetic agent for anesthesia maintenance (propofol vs. sevoflurane), type of surgery , age, ASA physical status, estimated blood loss (ml), duration of surgery (min), sufentanil (μg kg−1 h−1), and the year of enrollment. With exception of ‘midazolam cohort’ and ‘year of enrollment’, which remained in the model, variables were eliminated stepwise backwards. ‘Duration of surgery’ and ‘estimated blood loss’ were transformed to their binary logarithm (ln(x)/ln(2)).Data are presented as mean ± standard deviation (SD) or absolute numbers and percentages, according to the measurement level of the data. Demographic and clinical characteristics as well as the incidence of PACU delirium in the historical and the new midazolam policy were compared with Mann-Whitney We performed a subgroup analysis to assess the association between premedication with midazolam and PACU delirium in patients who had received inhalational anesthesia with sevoflurane in combination with sufentanil. The multivariable model included the same variables as the main analysis except for the variable ‘type of anesthesia’ (propofol vs. sevoflurane).SPSS Statistics 24 (IBM Deutschland GmbH) was used for statistical analyses. Figures were designed with GraphPad Prism 8 . This manuscript adheres to the STROBE reporting guidelines for observational studies.n = 214; non-midazolam cohort: n = 218) were included in the final analysis. Details on the flow of participants throughout the study are presented in Fig. n = 373/432, 86.3%) fulfilled the criteria for ASA physical status I–II with significantly more ASA I and III patients in the midazolam cohort (p < 0.001). The duration of anesthesia (p < 0.001) and surgery (p = 0.002) and the estimated blood loss (p = 0.015) were significantly higher in the midazolam cohort compared with the non-midazolam cohort. Compared with participants from the midazolam cohort, patients in the non-midazolam cohort received sevoflurane for anesthesia maintenance more frequently (p < 0.001) and received significantly higher doses of sufentanil (p = 0.003). Scores from the Mini-mental status examination differed significantly between cohorts, without being clinically relevant. Details on baseline demographic and clinical characteristics of the study population are listed in Table A total of 569 patients had been enrolled. Of these, 454 completed the assessment for PACU delirium and 432  tested positive for delirium at any one time point during the PACU stay. In the non-midazolam cohort 72/218 patients (33.0%) showed delirium signs in the PACU (Table P = 0.842). Age , the cumulative dose of sufentanil , and total intravenous anesthesia (TIVA) for anesthesia maintenance  were significantly associated with PACU delirium . Age  and duration of surgery  were associated with the development of PACU delirium  patients tested positive for PACU delirium. A total of 71/337 (32.9%) patients in the non-midazolam cohort showed signs of PACU delirium. Multivariable analysis did not reveal a significant association between midazolam and PACU delirium  delirium in patients who received midazolam for sedative premedication (midazolam cohort) and patients without preoperative midazolam administration (non-midazolam cohort).


Listening to groovy music is an enjoyable experience and a common human behavior in some cultures. Specifically, many listeners agree that songs they find to be more familiar and pleasurable are more likely to induce the experience of musical groove. While the pleasurable and dance-inducing effects of musical groove are omnipresent, we know less about how subjective feelings toward music, individual musical or dance experiences, or more objective musical perception abilities are correlated with the way we experience groove. Therefore, the present study aimed to evaluate how musical and dance sophistication relates to musical groove perception. One-hundred 24 participants completed an online study during which they rated 20 songs, considered high- or low-groove, and completed the Goldsmiths Musical Sophistication Index, the Goldsmiths Dance Sophistication Index, the Beat and Meter Sensitivity Task, and a modified short version of the Profile for Music Perception Skills. Our results reveal that measures of perceptual abilities, musical training, and social dancing predicted the difference in groove rating between high- and low-groove music. Overall, these findings support the notion that listeners’ individual experiences and predispositions may shape their perception of musical groove, although other causal directions are also possible. This research helps elucidate the correlates and possible causes of musical groove perception in a wide range of listeners. Musical sophistication is the possession of heightened music skills and engagement, and contains attributes such as musical understanding, appreciation, evaluation, and communication alongside skills such as playing an instrument, improvisation, and possessing a sense of rhythm and pitch  of 0.95 to detect a medium effect size (f2 = 0.15) at a statistical significance level of α = 0.05. Most participants were UNLV undergraduates enrolled in a psychology course (n = 146). The remaining participants were recruited by word of mouth, email, or by announcements posted on social media platforms . Twenty-three participants were excluded due to poor performance on the initial headphone check (see “Headphone check” for details); eight participants were excluded due to incorrect answers on compliance checks (see “Compliance check” for details); one participant was excluded due to an excessively noisy environment while completing the study; and 15 participants were excluded due to issues loading the stimuli. The final 124 participants were between the ages of 18–44 years old  and had no history of learning, neurological, or motor disorders. Power analyses using G*Power (β) of 0.885 to detect a medium effect size (f2 = 0.15) at a statistical significance level of α = 0.05. While musicians and dancers were not actively recruited for the present study, participants reported varying degrees of music and dance experience  and LimeSurvey . Participants followed an internet link to access the experiment (link can be found on the project’s Open Science Foundation Repository).To ensure that participants were using headphones as requested, and could hear the auditory stimuli clearly, they completed a short assessment prior to beginning the experiment. In each trial, participants were presented with three tones and asked to indicate which was the quietest: the correct answer could only be discerned if the individual was wearing headphones rather than listening in free-field . We exclFirst, participants completed the short version of the Profile for Music Perception Skills PROMS; . This muThe Melody subtest assessed the ability to recognize either tonal (easy) or atonal (difficult) melodies. Two-bar, eighth-note melodies were played by a MIDI harpsicord monophonically in 4/4 time. In different trials, one note of the comparison melody would differ from the reference melody by one semitone. The Rhythm subtest assessed the ability to recognize percussive rhythmic motifs. Two-bar phrases played equally accented in 4/4 time were composed of quarter, eighth, and sixteenth notes. Trials varied in difficulty by where the rhythmic deviant was located between the reference and comparison stimuli . The Embedded Rhythm subtest assesses the ability to recognize a percussive rhythmic motif when it is presented as part of a melody. Two-bar monophonically played and equally accented phrases in 4/4 time were composed of eighth and quarter notes. The reference stimulus was presented as a simple rhythm while the comparison stimulus was presented as a tonal melody. Participants were asked to identify whether the rhythm of the melody in the comparison stimulus matched the rhythm of the reference stimulus. The Tempo subtest assessed the ability to discriminate the speed at which music is played. Reference and comparison stimuli were polyphonically played in 4/4 time. The comparison stimuli ranged in difficulty by being 1 BPM (difficult) to 7 BPM (easy) different from the reference stimulus. The Accent subtest assessed the ability to discriminate the relative emphasis given to certain notes in a rhythmic pattern. Across two identical rhythmic motifs presented in 4/4 time monophonically by a MIDI drum sound, accented notes were presented as 3 dB louder than non-accented notes. Easy trials had more accent variations between reference and comparison stimuli compared to moderate and difficult trials. More detailed information on these subtests can be found in via Qualtrics. The BMS uses naturalistic music stimuli to assess auditory beat and meter sensitivity in individuals with varying levels of musical expertise, and does not require familiarity with musical terms, theory, or notation. In the Short BMS, participants listened to brief excerpts of commercially-recorded ballroom dance music overlaid with a custom click track that either matched or mismatched the music at the beat and measure levels . The musical excerpts were taken from six ballroom dance pieces, three of which were scored in 3/4 time (triple meter) and three of which were scored in 4/4 time (duple meter). The click track could fully match the beat and measure of the musical excerpt , match the beat but not the measure , match the measure of the music but not the beat , or not match either the beat or measure of the music . Please consult the Open Science Foundation RepositoryIn the next task, participants completed the Short BMS, a brief version of the beat sensitivity score that indicates participants’ ability to distinguish between beat-matching and beat-mismatching metronomes, and a meter sensitivity score that indicates participants’ ability to distinguish between metronomes that fully match the beat and measure of the music and those metronomes that match the beat of the music but not the measure.After listening to each musical excerpt and click track pairing, participants rated the fit of the click track to the music using a four-point Likert-type scale ranging from 1 (“Not Well at All”) to 4 (“Very Well”). Participants were given four practice trials to experience the stimuli and the rating scale prior to starting the experimental portion of the Short BMS. The Short BMS consists of 30 pairs of musical excerpts/click tracks. The musical excerpt/click track pairings were three musical measures long, which translated to approximately 6–8 s per trial. The task took approximately 10 min for participants to complete. The Short BMS results in two scores per participant, a groovy was defined as how much a song makes you want to dance. On a seven-point Likert scale, they answered the following questions: (1) “Is this song groovy? ,” (2) “Did you enjoy this song?,” and (3) “Are you familiar with this song?.” Likert scale choices ranged from Not groovy at all, I do not like it at all, and This song is not familiar at all to Very groovy, I like it very much, and This song is very familiar, respectively. Stimuli were truncated to 15-s segments using Audacity 2.1.2 . Participants listened to 15-s clips of 10 high-groove (HG) and 10 low-groove (LG) songs and made judgments on what they heard. The ten songs rated highest in groove and the ten songs rated lowest in groove were chosen for this study from the ty 2.1.2  and normty 2.1.2 .Completely disagree to Completely agree. The composite score of these five subscales makes up an individual’s General Musical Sophistication score , a 39-item psychometric instrument used to quantify the amount of musical engagement, skill, and behavior of an individual . The queon score . More deCompletely disagree to Completely agree. More details about the Gold-DSI can be found in After the Gold-MSI, participants completed the Goldsmiths Dance Sophistication Index (Gold-DSI), a 26-item standardized self-report instrument used to quantify individual differences in doing dance , watching dance , and one’s knowledge about dance . Like thThe final task participants completed was a demographics questionnaire that asked questions about health history, music experience, dance experience, exercise, and engagement with music listening.Throughout the study, we utilized a set of previously published questions to ensure participants were adequately attending to the experimental task . Within After the completion of the experiment, participants were asked to answer compliance questions to ensure that the experiment was completed with effort in an environment with minimal distraction. The first question stated, “People are working on this task in many different places. Please tell us about the place you were at when working on this task. Please answer honestly.” Response options were (1) “I worked on this study in a very noisy place,” (2) “I worked on this study in a somewhat noisy place,” (3) “I worked on this study in a somewhat quiet place,” or (4) “I worked on this study in a very quiet place”. Those who answered the question with “I worked on this study in a very noisy place” or “I worked on this study in a somewhat noisy place” were excluded from analysis. The second question asked, “Please tell us if you had difficulty loading the sounds. Please answer honestly.” From “Yes” or “No” response choices, any participant who responded with “Yes” was excluded from analysis. The final question asked, “How carefully did you complete this experiment? Please answer honestly.” From the response options of (1) “Not at all carefully,” (2) “Slightly carefully,” (3) “Moderately carefully,” (4) “Quite carefully,” and (5) “Very carefully,” those who answered with “Not at all carefully,” “Slightly carefully,” or “Moderately carefully” were excluded from analysis.https://osf.io/g3y7c/. The main analysis was a stepwise multiple linear regression that predicted musical groove sensitivity score, which is the difference between mean high-groove music ratings and mean low-groove music ratings (Mhigh-groove music – Mlow-groove music). Musical groove sensitivity scores can range from – 6 to + 6. Those with higher musical groove sensitivity scores (score = 4–6) perceive greater differences between high- and low-groove songs. Those with lower musical groove sensitivity scores (score = 1–3) either perceive less differences between high-and low-groove songs or no differences (score = 0) between the two groove types. A score evaluating the difference between high- and low-groove music was employed rather than separately regressing ratings on high- and low-groove songs for two reasons. First, a difference score uses all the groove rating data in a single outcome measure. Second, a difference score controls for response bias or how individual participants use the subjective rating scale for “grooviness.” For example, two participants might provide different numbers for the same subjective amount of groove for a low-groove song, but it is assumed that the increased rating they would each provide for a high-groove song would reflect an accurate measure of their sensitivity for the difference between low-groove and high-groove songs. Overall, this allows for a more nuanced measurement of musical groove that captures how individuals differently rate high- and low-groove music.All data for this study can be found here: stepAIC function from the MASS package to choose predictors for a best-fit model based on the Akaike Information Criterion (AIC): a measure of fit that estimates the quality of each model. This automatic function evaluates models in parallel to avoid overfitting of data and cherry-picking of predictors . The ANOVA for musical groove, likeability, and familiarity ratings was replicated from Analysis of variance (ANOVA) evaluating musical groove, familiarity, and likeability ratings and Pearson’s M = 5.42, CI = 5.05, 5.79) than to low-groove excerpts , F1,18 = 226.02, p < 0.001, η2 = 0.926 (see r (18) = 0.79, p < 0.001; groove and familiarity ratings, r (18) = 0.70, p < 0.001; and familiarity and likeability ratings, r (18) = 0.88, p < 0.001 . The selected model for analysis contained seven predictors: three predictors from the Gold-MSI , two predictors from the Gold-DSI , one predictor from the PROMS (Accent), and one predictor from the Short BMS (beat sensitivity). We regressed these predictors using the lm function to find that Perceptual Abilities, Musical Training, and Social Dancing scores significantly predicted musical groove sensitivity, F  = 5.091, p < 0.001, R2 = 0.24, adj. R2 = 0.19 , the total scores of each of the Gold-DSI subscales , the total scores of each PROMS subtest , and the total scores on each of the Short BMS measures . After running the 0.19 see . Emotioninearity . The accmusical groove sensitivity score, which can be used in a regression framework to examine the relationship between an individual’s groove perception and other individual difference measures.The present study investigated individual differences in music and dance characteristics that may contribute to musical groove perception. Specifically, this online experiment examined 17 potential predictors and assessed how facets of musical sophistication, dance sophistication, and performance on music-based perceptual tasks influenced individuals’ sensitivity to musical groove. Although previous studies focused on the acoustic components of music , 2018 anIn general, our participants agreed on ratings of musical groove, familiarity, and likeability. Songs previously rated as high and low in musical groove by listeners in Using an AIC-based stepwise model selection, seven out of 17 possible predictors from subtest scores of the Gold-MSI, Gold-DSI, PROMS, and Short BMS were chosen to predict the musical groove sensitivity score. The seven selected predictors  together accounted for 24% of the variance in musical groove sensitivity score. Of these predictors, self-reported Perceptual Abilities, Musical Training, and Social Dancing scores separately predicted musical groove difference ratings compared to the other predictors in the model. Emotions, Dance Training, Accent, and beat sensitivity scores did not significantly predict the difference between high-and low-groove music ratings.r correlations reflected a positive relationship between Perceptual Abilities and musical groove sensitivity scores indicating that those who think they are good at judging others’ musical abilities, identifying musical genres, recognizing familiar music, and spotting mistakes in performances tend to rate high-and low-groove music more distinctly. Perceptual Abilities also had significant positive correlations with Gold-MSI Musical Training, Gold-MSI Emotions, Gold-DSI Dance Training, Gold-DSI Social Dancing, PROMS Accent, and Short BMS beat sensitivity.The Perceptual Abilities subtest of the Gold-MSI is comprised of self-reported views of song recognition, tonal perception, genre identification, and how well one can judge others’ musical abilities . Pearsonr correlations reflected a barely positive relationship between Musical Training and musical groove sensitivity scores indicating those that consider themselves to be musicians, those that are complimented more often on performance quality, and those who report more hours of daily practice, greater years of formal music training, and increased numbers of instruments played rated high-and low-groove music more distinctly. Musical Training also had significant positive correlations with Gold-MSI Perceptual Abilities, Gold-MSI Emotions, Gold-DSI Dance Training, PROMS Accent, and Short BMS beat sensitivity, but was not significantly correlated with Gold-DSI Social Dancing.The Musical Training subtest of the Gold-MSI is comprised of self-reported views of musicianship as well as quantitative measurements of practice time, formal training, and instrument type . Pearsonnegative predictor of musical groove sensitivity score. This regression result was surprising considering that when correlated on its own, Music Training score has a barely positive association with musical groove sensitivity score. It is only when other predictors are considered in the regression model, however, that Musical Training has a negative regression coefficient.In the stepwise regression model, the Perceptual Abilities score was a significant positive predictor of musical groove sensitivity score. Interestingly, Musical Training score was a significant These unpredicted results may be connected to the positive association found between Gold-MSI Perceptual Abilities and Musical Training subtest scores. Individuals who possess more honed perceptual abilities may have more musical training. Five out of seven questions on the Gold-MSI Musical Training subtest ask about quantitative hours of practice and years of training. Therefore, it seems that music training quantity is highly weighted in the final subscale score and is designed to identify individuals with formal music training. Questions that comprise the Gold-MSI Perceptual Abilities subtest, such as judging musical abilities and spotting mistakes during performances, are also some of the many skills that are taught and honed when formally learning to sing or play an instrument at a high level.type of music these musicians play. While this specific examination did not collect sufficient demographic data about the type of genre musicians claimed expertise in, future research should consider comparing musical groove sensitivity scores across a variety of musicians with different types of expertise to see if familiarity with a certain genre can drive musical groove ratings.Additionally, those with formal music training may rate songs with groove differently from those without formal training. Previous research has shown that musicians have rated more complex music, like jazz and funk, to be “groovier”  while noexperience with music , or associated with self-taught, informal training , but may not be indicative of formal music training . Conversely, possessing greater perceptual abilities may be linked to more informal music training may make greater distinctions between high- and low-groove music compared those with formal music training. For instance, the questions that make up the Gold-MSI Perceptual Abilities subtest ask about genre identification and recognition of familiar and novel songs. While these abilities can be learned through formal music training, they can also be refined through frequent music listening or informal music training. The high-and low-groove songs that were selected for this study belonged to differing genres: high-groove songs were previously categorized as belonging to soul and jazz genres while low-groove songs were previously identified as belonging to rock and folk genres  tend to hear greater differences between high- and low-groove music than those with more formal dance training . This seems to contradict our original prediction that Dance Training would be a significant predictor of musical groove sensitivity score. Those who scored higher on Social Dancing may not be formal dancers, but experienced non-trained dancers or dance appreciators who enjoy dancing with others as a form of bonding and socialization. Because songs with groove are often danced to in social settings, those who feel more comfortable dancing socially may have more familiarity with musical groove and as a result, are better at identifying differences between high- and low-groove music. Those who enjoy social dancing may also be people who have greater openness to experience or are more extraverted. Previous research has found that those who report more openness to experience also have more episodes of pleasurable esthetic chills to music  can be found at: The studies involving human participants were reviewed and approved by the University of Nevada, Las Vegas Institutional Review Board. The participants provided their written informed consent to participate in this study.SO’C, EH, and JS: conceptualization. SO’C, JN-B, and JS: methodology. SO’C: formal analysis and data collection. SO’C and GW: investigation setup. SO’C and JN-B: writing—original draft preparation. SO’C, JN-B, EH, and JS: writing—review and editing. All authors contributed to the article and approved the submitted version.This research was supported in part by the University of Nevada, Las Vegas Foundation Board of Trustees Fellowship awarded to SO’C. The publication fees for this article were supported by the UNLV MSI Open Article Fund.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.


After surgery, tonsils pulsatility decreased significantly (323 ± 175 μL/cardiac cycle (CC) vs. 194 ± 130 μL/CC, p = 0.008) and subarachnoid CSF pulsatility at the foramen magnum increased significantly . After surgery, we found a decrease in venous flow amplitude  and venous correction factor . Conclusions: Phase-contrast MRI could be a useful additional tool for postoperative evaluation and follow-up, and is complementary to morphological imaging.Background: We propose that the appearance of a ptosis of the cerebellar tonsils and syringomyelia is linked to its own hemohydrodynamic mechanisms. We aimed to quantify cerebrospinal fluid (CSF) and cerebral blood flow to highlight how neurofluid is affected by Chiari malformations type 1(CMI) and its surgery. Methods: We retrospectively included 21 adult patients with CMI who underwent pre- and postoperative phase contrast MRI (PCMRI) during the period from 2001 to 2017. We analyzed intraventricular CSF, subarachnoid spaces CSF, blood, and tonsils pulsatilities. Results: In preoperative period, jugular venous drainage seems to be less preponderant in patients with syringomyelia than other patients (venous correction factor: 1.49 ± 0.4 vs. 1.19 ± 0.1,  Chiari malformations (CMI) are defined radiologically and from a purely morphological point of view. They consist of ptosis of the cerebellar tonsils through the foramen magnum of greater than 3  or 5 mm The treatment of symptomatic CMI is surgical  and consCMI suggests by its name a malformation of a congenital nature. The pathophysiology of CMI is not clear but recent advances indicate that it is related to problems with intracranial pressure (ICP) and neurofluid dynamics.Indeed, elevated cerebral spinal fluid (CSF) velocities at the level of the foramen magnum, associated with so-called compensatory pulsatility of the tonsils, have been described, but non-quantitatively. CMI decreases the subarachnoid space in the plane of the foramen magnum. Consequently, higher CSF velocities have been observed to preserve the flow rate at the level of the foramen magnum ,11,12,13ICP is defined by the pressure of the CSF. In 1926, ICP was conceptualized by Cushing as being subject to the Monro–Kellie doctrine . This doThe relevance of hydrodynamic analyses is a subject of debate. For some authors, tonsils pulsatility appears to be the main diagnostic marker of CMI  but therWe propose that the appearance of a ptosis of the cerebellar tonsils and syringomyelia is linked to its own hemohydrodynamic mechanisms. We aimed to quantify CSF and cerebral blood flow to highlight how neurofluid is affected by CMI and its surgery.We retrospectively included 21 adult patients with CMI who underwent pre- and postoperative MRI during the period from 2010 to 2017. The mean age of the subjects was 41 ± 16 (21–72) years.The symptomatology was attributed by the neurosurgeon to be exclusively due to CMI. Patients with associated spina bifida (Chiari type 2) and those <18 years of age were excluded.Patients were treated by either simple bone decompression or bone decompression associated with duraplasty. No patient was treated by tonsil excision. Inclusion was independent of the type of surgery performed.Twelve patients presented with a syringomyelia cavity.The surgical indication was determined based on symptoms related to the malformation, as well as on its radiological definition . We added phase-contrast MRI (PCMRI) sequences to the usual clinical morphology protocol .All patients underwent MRI as part of their conventional clinical assessment. MRI was performed distant from any lumbar puncture (more than three months). In addition to conventional clinical sequences, we added two PCMRI sequences.2, matrix = 256 mm2 or 128 × 256 mm2, slice thickness = 5 mm, flip angle = 30°, two excitations, and two views per segment. Peripheral cardiac synchronization was achieved with retrospective gating to reconstruct 32 temporal phases of one mean cardiac cycle calculated from all cardiac cycles during the acquisition. For CSF flow, we selected velocity encoding, (VENC) = 5 cm/s at the level of the cervical, foramen magnum, and syrinx (if present). Pulsatility of the tonsils were also quantified through the foramen magnum. The Venc was increased to 10 cm/s for the Sylvius aqueduct and if aliasing occurred. Internal carotid, vertebral, and jugular artery flow at the cervical level was quantified using VENC = 80 cm/s. CSF and blood flow acquisition slices were positioned perpendicular to the presumed direction of the flow . PCMRI was performed with the following parameters: the repetition time (TR) and echo time (TE) were selected with the minimum value depending on heart rate, field-of-view = 16 cmthe flow .a) was defined as the sum of the flow through the internal carotid and vertebral arteries.Data were analyzed using in-house software for the semi-automatic delineation of the blood vessels and CSF regions. Velocities and segmented areas were calculated through each of the 32 cardiac phases to produce the flow curves during the cardiac cycle. Stroke volumes were defined as the average of the cranio-caudal and caudo-cranial volumes displaced through the region of interest during the cardiac cycle . CerebracorrectedCBFv flow curve = venous correction factor × CBJF flow. When this venous factor is equal to 1, the correctedCBFv is equal to the CBFv. This corresponds to exclusive jugular venous drainage. When the correction factor is >1, it shows the magnitude of accessory drainage paths.Cerebral jugular blood flow (CBJF) was measured as the sum of the flow of the two internal jugular veins. As CBJF does not drain all the CBF itself  a venous correction factor was calculated equal to the mean (CBFa)/mean(CBJF). It was thus possible to provide a theorical a and correctedCBFv. The arteriovenous stroke volume was calculated as the CSF stroke volume.To evaluate how the cerebral blood volume increases during the cardiac cycle, the cerebral arteriovenous flow curve was calculated by subtraction of the CBFThe peak amplitude of the flow curves was calculated.The complete postprocessing takes between 10 and 15 min to obtain all hemodynamic and hydrodynamic physiology of the patient.t-test was used to compare hemodynamic parameters between patients with syringomyelia and those without. The threshold of significance was set to p = 0.05.Wilcoxon’s signed rank test for paired samples was used to compare the various hemodynamic and hydrodynamic parameters between the pre- and postoperative periods. Student’s Twelve patients underwent duraplasty enlargement and nine underwent bone decompression . Twelve All patients who underwent surgery stated that they felt better after surgery (100%). The symptoms remained less intense than preoperatively for three (25%), compatible with an optimal quality of life. Two patients with residual signs underwent extradural surgery and one underwent enlargement surgery.Only three patients showed complete disappearance of their syringomyelic cavity (25%). Nine (75%) showed a persistent cavity but of much lower volume. For these patients, the syringomyelic cavity extended an average of 4.75 levels preoperatively and 2.5 postoperatively. Similarly, the mean maximum anteroposterior diameter of the cavities was 6.75 mm preoperatively and 3.5 mm postoperatively. On average, the syringomyelic cavities decreased by half after treatment. Only two patients in the syringomyelic population were operated by extradural approach.No postoperative complications were described. One radiological complication without any clinical consequences, meningocele, was described. No surgical revision was reported.No significant difference was found in the comparison of hemodynamic and hydrodynamic parameters between the groups of patients with syrinx and patients without syrinx . Only thAfter surgery, there was a significant decrease in stroke volume measured at the level of the foramen magnum but not at the cervical level or at the level of the mesencephalic aqueduct . We alsoThe analysis of the variations of the parameters after surgery did not reveal any difference between the two techniques .The study of CSF dynamics and hemodynamics is possible by PCMRI for patients with CMI in 10 min complementary to the morphological sequences. Here, we show an alteration of both CSF dynamics and cerebral hemodynamics, particularly at the venous level.CMI, by definition, decrease the surface of subarachnoid spaces at the cranio-cervical junction and thus decrease or block the local flow of CSF. Our current knowledge of the physiology of intracranial flow makes it possible to understand the crucial role of the flush of CSF towards the spinal subarachnoid spaces during systole ,25,26,27However, the cranial box is rigid and inextensible . This inIn CMI, CSF intracranial “mobile compliance” is more or less restricted due to the decrease in the area of CSF circulation at the level of the foramen magnum. Pulsatility of the CSF measured at the level of the foramen magnum is strongly altered, as suggested by our results and those of previous studies ,31. ManyParadoxically, we found no decrease in CSF dynamics measured at the upper cervical level in our population compared to a control population from the literature . We explThere was no significant difference in the hemodynamic parameters with the presence of syringomyelia but patients with syringomyelia have a significantly higher venous correction factor. The venous correction factor reflects the participation of the jugular veins in cerebral blood drainage. When this factor is 1, drainage is exclusively jugular. When this factor tends towards 2, cerebral blood drainage is 50% jugular and 50% from alternative drainage routes. Therefore, patients with syringomyelia showed an important accessory venous drainage pathway that may be secondary to the greater alteration of craniospinal neurofluid interactions. This finding is borderline significant and needs to be explored by further specific analysis. Such a mechanism of the redistribution of venous drainage through small veins with a higher resistance to flow than the large jugular veins could produce barometric alterations. Such alterations in hemodynamics have also been shown to be present in idiopathic intracranial hypertension , in whicOur results are not compared to a control population. This should be done in order to allow a better understanding of the physiopathological mechanisms. An analysis of this type would also allow us to observe if there are diagnostic markers complementary to the clinical and radiological morphological observations.The pre- and postoperative comparison of the craniospinal hemohydrodynamics of CMI showed the ventricular CSF flow measured in the aqueduct to be normal and unaffected by CMI. No patients showed hydrocephalus, which is not common in CMI.The stroke volume of the tonsils was analyzed by a semi-automatic segmentation of the bulbar-medullary junction and the amygdala according to the same method as the CSF, this allows a quantification of the pulsatility of the tonsils during one cardiac cycle. The stroke volume of the tonsils, or pulsatility of tonsils, is the volume of tonsils displaced during one cardiac cycle. This displacement is in a craniocaudal direction during the systolic phase and in a caudocranial direction during the diastolic phase. Here, we show low CSF oscillations at the cranio-cervical junction and the existence of pulsatility of the tonsils, which decreased after surgery, associated with an increase in CSF volume pulsatility. Previous studies have shown higher CSF velocities at the cranio-cervical junction in Chiari populations than in a control population  and a deMoreover, duraplasty has been reported to allow for a greater decrease in pulsatility of the tonsils . NeverthThe pulsatility of the tonsils, not present in control populations, is a major marker of this pathology . The decHemodynamic analysis shows that the venous correction factor makes it possible to assess the venous drainage pathways . Postoperatively, we observed a decrease in the correction factor that trended towards 1, showing that the involvement of jugular venous drainage is elevated in CMI. Decompression of the cranio-cervical junction made it possible to locally restore more physiological drainage. In addition, there was a decrease in venous flow amplitude after surgery. A number of studies have indeed shown a link between ICP disorders and this finding ,32. DuriThese results show the existence of a modification of the craniospinal hemodynamics and hydrodynamics after decompression surgery. There are cases of symptomatic recurrence which may lead to the question of a new surgery. The analysis of the neuro fluid dynamics may allow to observe if there is an alteration of the intracranial flows accompanying this recurrence of the symptomatology. This is an additional help to the decision of an often-difficult surgical indication.Phase-contrast MRI is easy to use in clinical practice but requires quantitative post processing to be completely interpreted. In CMI, we observed an exclusive alteration in CSF dynamics at the foramen magnum plane accompanied by tonsils pulsatility. We observed a reduction in the amplitude of jugular blood outflow and modification of the cerebral venous drainage pathway. We also observed that surgery had a quantitative hemodynamic and hydrodynamic impact. Phase-contrast MRI could be a useful additional tool for postoperative evaluation and follow-up and is complementary to morphological imaging. These results could be used to reevaluate the classification of CMI by not only taking into account morphology but also information concerning neurofluid dynamics.


Non-polio Enteroviruses (EV) are important neonatal CNS pathogens. Multiple EV genotypes have been detected in pediatric CSF, e.g. Echovirus (E) 6 and E30. CSF innate immune responses to EV genotypes remain poorly defined. Most data are from EV-A71 or E30 CNS infections and do not compare responses between these or other EV types. We sought to better define innate immune responses to EV genotypes in CSF.Salvaged standard of care CSF samples from ≤6 month olds  or EV PCR(-) controls) from Jan 2010 - Dec 2020 were tested in duplicate on a 21- cytokine bead panel (MilliporeSigma). EV positive samples were previously genotyped by sequencing the viral capsid gene. Cytokine levels calculated from the standard curve were compared by Kruskal-Wallis and post-hoc analysis (GraphPad Prism 8.4.3). Natural partitioning of participants was explored using principal component analysis and cluster analysis (IBM SPSS v27). The utility of cytokine signatures in predicting EV status was explored using discriminant analysis and ROC analysis (IBM SPSS v27).Data from 72 CSF with E6 (N=16), E9 (N= 9), E18 (N=9), and E30 (N=21) showed significant differences among EV genotypes vs. controls for 20 cytokines (IL-17 was excluded). Significant differences in cytokine levels in EV CSF vs controls were seen: E6 for all 20 cytokines; E9 for Fractalkine, IP10, and MCP1; E18 for Fractalkine and MCP1; E30 19 cytokines (not GM-CSF). PCA revealed only minor overlap of controls and EV positives; EV types overlapped, except E30, differing most from E9 and E18 but overlapping E6. The most important type-differentiating cytokines by PCA were MCP1, Fractalkine, IL-8, and IL-10. Patterns in DA resembled PCA; controls clearly separated from EV CSF, E30 being the most distinct. Overall, the discriminant model correctly classified EV type or controls at a 63% rate - highest for controls (94.1%) and E30 (74.1%). In the DA model, the most important cytokines were IP-10, IL-2, IL-1Ra, and Fractalkine. Discriminant scores had the largest area under the curve (AUC), 0.990. Among cytokines, IFNa2 had the largest AUC, 0.987.Preliminary data show significant EV-genotype differences in innate immune response to CNS infections. Cytokine patterns may serve as a key predictor for discerning EV genotypes.Brian R. Lee, PhD, MPH, CDC: Grant/Research Support|Merck: Grant/Research Support Christopher J Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric news: Honoraria|Pfizer: Grant/Research Support Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support.