bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knee Extensor and Flexor Torque Variability During Maximal Strength Testing and Change in Knee Pain and Physical Function at 60-Mo Follow-Up
Authors: Schroeder Allison , Wang Na , Felson David T. , Lewis Cora E. , Nevitt Michael C. , Segal Neil A. 
Published: September 2020

Abstract
As the population ages, there is a growing burden owing to musculoskeletal diseases, such as knee osteoarthritis, and subsequent functional decline. In the absence of a cure, there is a need to identify factors amenable to intervention to prevent or slow this process. The Multicenter Osteoarthritis Study cohort was developed for this purpose. In this study, associations between variability in peak knee flexor and extensor torque at baseline and worsening of pain and physical function over the subsequent 60 mos were assessed in a cohort of 2680 participants. The highest quartile of baseline knee flexor torque variability was found to be associated longitudinally with worsening pain (fourth quartile ß estimate, mean ± SE, 0.49 ± 0.19; P = 0.0115; with R
2 = 0.28 and P for trend across quartiles = 0.0370) and physical function scores (fourth quartile ß estimate, mean ± SE, 1.39 ± 0.64; P = 0.0296; with R
2 = 0.25 and P for trend across quartiles = 0.0371), after adjusting for baseline knee osteoarthritis and maximum knee flexor torque. There were no associations between baseline knee extensor torque and worsening pain or physical function by 60 mos. The presence of greater variability in maximum knee flexor strength may identify patients who may benefit from therapies aimed at preventing worsening knee pain and physical function.
The Effect of Age and Competition Level on Subtle Motor Performance in Adolescents Medically Cleared Postconcussion
Authors: Crasta Jewel E. , Raja Altamash E. , Caffo Brian S. , Hluchan Christine M. , Suskauer Stacy J. 
Published: September 2020

ObjectiveThe aim of this study was to examine the effect of age and level of competition on subtle motor performance in adolescents who have recently been medically cleared postconcussion and never-injured controls.DesignThirty adolescents who were recently medically cleared postconcussion (12–18 yrs) and 30 never-concussed, typically developing controls were examined using the Revised Physical and Neurological Examination of Subtle Signs (PANESS) and the Immediate Post-Concussion Assessment and Cognitive Testing.ResultsOlder age was associated with better Immediate Post-Concussion Assessment and Cognitive Testing scores in both groups, whereas only the control group showed improved motor performance on the PANESS with increasing age. Adolescents across both groups participating at a higher level of competition (school or travel level) had better motor performance on the PANESS than those participating at a lower level of competition (recreational level or no sports participation). Adolescents medically cleared postconcussion had greater motor deficits on the PANESS than controls did.ConclusionAfter medical clearance, adolescents with a history of recent concussion demonstrate alterations in the relationship between motor function and age. The PANESS merits further exploration as a measure that is sensitive to factors affecting motor performance, such as age and level of athletic competition, as well as to persistent subtle motor deficits in adolescents medically cleared postconcussion.
Multicenter validation of the American Association for the Surgery of Trauma grading scale for acute cholecystitis
Authors: Schuster Kevin M. , O’Connor Rick , Cripps Michael , Kuhlenschmidt Kali , Taveras Luis , Kaafarani Haytham M. , El Hechi Majed , Puri Ruchir , Mull Jennifer , Schroeppel Thomas J. , Rodriquez Jennifer , Cullinane Daniel C. , Cullinane Laura M. , Enniss Toby M. , Sensenig Rachel , Zilberman Brian , Crandall Marie 
Published: September 2020

BACKGROUND
The American Association for the Surgery of Trauma (AAST) patient assessment committee has created grading systems for emergency general surgery diseases to assist with clinical decision making and risk adjustment during research. Single-institution studies have validated the cholecystitis grading system as associated with patient outcomes. Our aim was to validate the grading system in a multi-institutional fashion and compare it with the Parkland grade and Tokyo Guidelines for acute cholecystitis.

METHODS
Patients presenting with acute cholecystitis to 1 of 8 institutions were enrolled. Discrete data to assign the AAST grade were collected. The Parkland grade was collected prospectively from the operative surgeon from four institutions. Parkland grade, Tokyo Guidelines, AAST grade, and the AAST preoperative grade (clinical and imaging subscales) were compared using linear and logistic regression to the need for surgical “bailout” (subtotal or fenestrated cholecystectomy, or cholecystostomy), conversion to open, surgical complications (bile leak, surgical site infection, bile duct injury), all complications, and operative time.

RESULTS
Of 861 patients, 781 underwent cholecystectomy. Mean (SD) age was 51.1 (18.6), and 62.7% were female. There were six deaths. Median AAST grade was 2 (interquartile range [IQR], 1–2), and median Parkland grade was 3 (interquartile range [IQR], 2–4). Median AAST clinical and imaging grades were 2 (IQR, 2–2) and 1 (IQR, 0–1), respectively. Higher grades were associated with longer operative times, and worse outcomes although few were significant. The Parkland grade outperformed the AAST grade based on area under the receiver operating characteristic curve.

CONCLUSION
The AAST cholecystitis grading schema has modest discriminatory power similar to the Tokyo Guidelines, but generally lower than the Parkland grade, and should be modified before widespread use.

LEVEL OF EVIDENCE
Diagnostic study, level IV.
Predicting Early Extubation After Liver Transplantation: External Validation and Improved Generalizability of a Proposed Fast-track Score
Authors: Haque Mohammed E. , Badenoch Adam D. , Orlov David , Selzner Markus , McCluskey Stuart A. 
Published: September 2020

Background.
Early extubation of liver transplantation recipients is a cornerstone of fast-track (FT) pathways. Identifying suitable candidates has previously been accomplished using perioperative variables to develop a FT probability score. The objective of this study was to externally validate a proposed FT score.

Methods.
Following Research Ethics Board approval, data were extracted on liver transplants conducted at a single center from 2009 to 2017. Data extracted included patient characteristics, intraoperative variables, and postoperative outcome variables. The proposed FT score utilized 9 variables: age, gender, body mass index, model of end-stage liver disease, retransplant, preoperative hospital admission, blood transfusion, operative time, and vasopressor use. We calculated the FT score in our cohort, and assessed the discrimination and calibration of the model. Score performance was explored by subgroup analyses, customization and altering the outcome definition.

Results.
The FT score was found to predict higher rates of successful FT than was observed in the external cohort (n = 1385) and had reduced discrimination (area under the receiver operating curve, 0.711; 95% confidence interval, 0.682-0.741) compared with the original internal validation cohort (area under the receiver operating curve, 0.830; 95% confidence interval, 0.789-0.871; P < 0.0001). Discrimination was improved by customizing the transfusion (P < 0.0001) components of the simplified score or by level 1 customization of all regression model coefficients (P < 0.0001). A time-based definition of FT (early extubation) did not alter the accuracy of the prediction score (P = 0.914), improving the model’s generalizability.

Conclusions.
The proposed FT score may help identify patients suitable for early extubation and FT pathways after liver transplantation in conjunction with clinical judgment.
Treatment with an Anti-CK2 Synthetic Peptide Improves Clinical Response in Covid-19 Patients with Pneumonia. A Randomized and Controlled Clinical Trial
Authors: Cruz Leticia R. , Baladrón Idania , Rittoles Aliusha , Díaz Pablo A. , Valenzuela Carmen , Santana Raúl , Vázquez Maria M. , García Ariadna , Chacón Deyli , Thompson Delvin , Perera Gustavo , González Ariel , Reyes Rafael , Torres Loida , Pérez Jesus , Valido Yania , Rodriguez Ralysmay , Vázquez Dania M. , Rosales Mauro , Ramón Ailyn C. , Pérez George V. , Guillén Gerardo , Muzio Verena , Perera Yasser , Perea Silvio E. ,   for the ATENEA-Co-300 group
Published: September 2020

ABSTRACTPurposeThe instrumental role of CK2 in the SARS-Cov2 infection has pointed out this protein kinase as a promising therapeutic target in Covid-19. Anti-SARS-Cov2 activity has been reported by CK2 inhibitors in vitro; however, any anti-CK2 clinical approach has been investigated in Covid-19. This exploratory trial aimed to explore safety and putative clinical benefit of CIGB-325, an anti-CK2 peptide previously assessed in cancer.MethodsA monocentric, parallel group design, therapeutic exploratory trial of intravenous CIGB-325 in adults hospitalized with Covid-19 was performed. Twenty patients were randomly assigned to receive CIGB-325 (2.5 mg/kg/day during 5-consecutive days) plus standard-of-care (10 patients) or standard-of-care (10 patients). Adverse events were classified by the WHO Adverse Reaction Terminology. Parametric and non-parametric statistical analyses were performed according to the type of variable. Considering the small sample size, differences between groups were estimated by Bayesian analysis.FindingsCIGB-325 induced transient mild and/or moderate adverse events like pruritus, flushing and rash in some patients. Both therapeutic regimens were similar respect to SARS-Cov2 clearance in nasopharynx swabs over the time. However, CIGB-325 significantly reduced the median number of pulmonary lesions (9.5 to 5.5, p = 0.042) at day 7 and proportion of patients with such effect was also higher according to Bayesian analysis (pDif > 0; 0.951). Additionally, CIGB-325 significantly reduced the CPK (p = 0.007) and LDH (p = 0.028) plasma levels at day 7.ImplicationsOur preliminary findings suggest that this anti-CK2 clinical approach could be combined with standard-of-care in Covid-19 thus warranting larger studies.
A dual antigen ELISA allows the assessment of SARS-CoV-2 antibody seroprevalence in a low transmission setting
Authors: Hicks Sarah M. , Pohl Kai , Neeman Teresa , McNamara Hayley A. , Parsons Kate M. , He Jin-shu , Ali Sidra A. , Nazir Samina , Rowntree Louise C. , Nguyen Thi H. O. , Kedzierska Katherine , Doolan Denise L. , Vinueas Carola G. , Cook Matthew C. , Coatsworth Nicholas , Myles Paul S. , Kurth Florian , Sander Leif E. , Mann Graham J. , Gruen Russell L. , George Amee J. , Gardiner Elizabeth E. , Cockburn Ian A. ,   the SARS-CoV-2 Testing in Elective Surgery Collaborators
Published: September 2020

AbstractEstimates of seroprevalence of SARS-CoV-2 antibodies have been hampered by inadequate assay sensitivity and specificity. Using an ELISA-based approach to that combines data about IgG responses to both the Nucleocapsid and Spike-receptor binding domain antigens, we show that near-optimal sensitivity and specificity can be achieved. We used this assay to assess the frequency of virus-specific antibodies in a cohort of elective surgery patients in Australia and estimated seroprevalence in Australia to be 0.28% (0 to 0.72%). These data confirm the low level of transmission of SARS-CoV-2 in Australia before July 2020 and validate the specificity of our assay.
Impact of sleep fragmentation, heart failure, and their combination, on the gut microbiome
Authors: Khannous-Lleiffe Olfat , Willis Jesse R. , Saus Ester , Cabrera-Aguilera Ignacio , Almendros Isaac , Farré Ramon , Gozal David , Farré Nuria , Gabaldón Toni 
Published: September 2020

ABSTRACTHeart failure (HF) is a common condition associated with a high rate of hospitalizations and adverse outcomes. HF is characterized by impairments of the cardiac ventricular filling and/or ejection of blood capacity. Sleep fragmentation (SF) involves a series of short sleep interruptions that lead to fatigue and contribute to cognitive impairments and dementia. Both conditions are known to be associated with increased inflammation and dysbiosis of the gut microbiota. In the present study, male mice were distributed into four groups, and subjected for four weeks to either HF, SF, both HF and SF, or left unperturbed as controls. We used 16S metabarcoding to assess fecal microbiome composition before and after the experiments. Evidence for distinct alterations in several bacterial groups and an overall decrease in alpha diversity emerged in HF and SF treatment groups. Combined HF and SF conditions, however, showed no synergism, and observed changes were not always additive, suggesting that some of the individual effects of either HF or SF cancel each other out when applied concomitantly.IMPORTANCEThe study demonstrates the potential of the gut microbiome as a source of molecular markers for the diagnosis, prevention, and treatment of both heart failure and sleep fragmentation conditions in isolation. Our results provide the first evidence of an antagonistic effect of the presence of both conditions in the gut microbiome dysbiosis, showing an attenuation of the alterations that are observed when considering them separately.
Impact of SARS-CoV-2 antibodies at delivery in women, partners and newborns
Authors: Egerup Pia , Olsen Line Fich , Christiansen Ann-Marie Hellerung , Westergaard David , Severinsen Elin Rosenbek , Hviid Kathrine Vauvert Römmelmayer , Kolte Astrid Marie , Boje Amalie Dyhrberg , Bertelsen Marie-Louise Mathilde Friis , Prætorius Lisbeth , Zedeler Anne , Nielsen Josefine Reinhardt , Bang Didi , Berntsen Sine , Ethelberg-Findsen Jeppe , Storm Ditte Marie , Bello-Rodríguez Judith , Ingham Andreas , Ollé-López Joaquim , Hoffmann Eva R , Wilken-Jensen Charlotte , Krebs Lone , Jørgensen Finn Stener , Westh Henrik , Jørgensen Henrik Løvendahl , Freiesleben Nina la Cour , Svarre Nielsen Henriette 
Published: September 2020

AbstractBackgroundOnly few studies have focused on serological testing for SARS-CoV-2 in pregnant women and no previous study has investigated the frequency in partners. The aim was to investigate the frequency and impact of SARS-CoV-2 in parturient women, their partners and newborns.MethodsFrom April 4thto July 3rd, 2020, all parturient women, their partners and newborns were invited to participate in the study. Participating women and partners had a pharyngeal swab and a blood sample taken at admission and immediately after delivery a blood sample was drawn from the umbilical cord. The swabs were analyzed for SARS-CoV-2 RNA by PCR and the blood samples were analyzed for SARS-CoV-2 antibodies. Full medical history, obstetric- and neonatal information were available.ResultsA total of 1,361 parturient women, 1,236 partners and 1,342 newborns participated in the study. No associations between previous COVID-19 disease and obstetric- or neonatal complications were found. The adjusted serological prevalence was 2.9% in women and 3.8% in partners. The frequency of blood type A was significantly higher in women with antibodies compared to women without antibodies. 17 newborns had SARS-CoV-2 IgG antibodies, and none had IgM antibodies. Full serological data from 1,052 families showed an absolute risk of infection of 0.37 if the partner had antibodies. Only 55% of individuals with antibodies reported symptoms.ConclusionThis large prospective cohort study reports no association between COVID-19 and obstetric- or neonatal complications. The family pattern showed a substantial increase in absolute risk for women living with a partner with antibodies.
Saliva cell type DNA methylation reference panel for epidemiology studies in children
Authors: Middleton Lauren Y. M. , Dou John , Fisher Jonah , Heiss Jonathan A. , Nguyen Vy K. , Just Allan C. , Faul Jessica , Ware Erin B. , Mitchell Colter , Colacino Justin A. , Bakulski Kelly M. 
Published: September 2020

AbstractSaliva is a widely used biological sample, especially in pediatric research, containing a heterogenous mixture of immune and epithelial cells. Associations of exposure or disease with saliva DNA methylation can be influenced by cell-type proportions. Here, we developed a saliva cell-type DNA methylation reference panel to estimate interindividual cell-type heterogeneity in whole saliva studies. Saliva was collected from 22 children (7-16 years) and sorted into immune and epithelial cells, using size exclusion filtration and magnetic bead sorting. DNA methylation was measured using the Illumina MethylationEPIC BeadChip. We assessed cell-type differences in DNA methylation profiles and tested for enriched biological pathways. Immune and epithelial cells differed at 164,793 (20.7%) DNA methylation sites (t-test p < 10-8). Immune cell hypomethylated sites mapped to genes enriched for immune pathways (p < 3.2 × 10-5). Epithelial cell hypomethylated sites were enriched for cornification (p = 5.2 × 10-4), a key process for hard palette formation. Saliva immune and epithelial cells have distinct DNA methylation profiles which can drive whole saliva DNA methylation measures. A primary saliva DNA methylation reference panel, easily implemented with an R package, will allow estimates of cell proportions from whole saliva samples and improve epigenetic epidemiology studies by accounting for measurement heterogeneity by cell-type proportions.
SARS-CoV-2 N-antigenemia: A new COVID-19 marker and a potential alternative to nucleic acid amplification techniques
Authors: Le Hingrat Quentin , Visseaux Benoit , Laouenan Cédric , Tubiana Sarah , Bouadma Lila , Yazdanpanah Yazdan , Duval Xavier , Ichou Houria , Damond Florence , Bertine Mélanie , Benmalek Nabil ,   French COVID cohort management committee,   CoV-CONTACT study group, Choquet Christophe , Timsit Jean-François , Ghosn Jade , Charpentier Charlotte , Descamps Diane , Houhou-Fidouh Nadhira 
Published: September 2020

ABSTRACTBackgroundMolecular assays on nasopharyngeal swabs remain the cornerstone of COVID-19 diagnostic. Despite massive worldwide efforts, the high technicalities of nasopharyngeal sampling and molecular assays, as well as scarce resources of reagents, limit our testing capabilities. Several strategies failed, to date, to fully alleviate this testing process (e.g. saliva sampling or antigen testing on nasopharyngeal samples). We assessed the performances of a new ELISA microplate assay quantifying SARS-CoV-2 nucleocapsid antigen (N-antigen) in serum or plasma.MethodsThe specificity of the assay, determined on 63 non-COVID patients, was 98.4% (95% confidence interval [CI], 85.3 to 100). Performances were determined on 227 serum samples from 165 patients with RT-PCR confirmed SARS-CoV-2 infection included in the French COVID and CoV-CONTACT cohorts.FindingsSensitivity was 132/142, 93.0% (95% CI, 84.7 to 100), within the first two weeks after symptoms onset. A subset of 73 COVID-19 patients had a serum collected within 24 hours following or preceding a positive nasopharyngeal swab. Among patients with high nasopharyngeal viral loads, Ct value below 30 and 33, only 1/50 and 4/67 tested negative for N-antigenemia, respectively. Among patients with a negative nasopharyngeal RT-PCR, 8/12 presented positive N-antigenemia. The lower respiratory tract was explored for 6/8 patients, showing positive PCR in 5 cases.InterpretationThis is the first demonstration of the N-antigen antigenemia during COVID-19. Its detection presented a robust sensitivity, especially within the first 14 days after symptoms onset and high nasopharyngeal viral loads. These findings have to be confirmed with higher representation of outpatients. This approach could provide a valuable new option for COVID-19 diagnosis, only requiring a blood draw and easily scalable in all clinical laboratories.
Predicting clinical outcome with phenotypic clusters in COVID-19 pneumonia: an analysis of 12,066 hospitalized patients from the Spanish registry SEMI-COVID-19
Authors: Rubio-Rivas Manuel , Corbella Xavier , Mora-Luján José María , Amigo Jose Loureiro , Sampalo Almudena López , Bergua Carmen Yera , Atiénzar Pedro Jesús Esteve , Díez García Luis Felipe , Ferrer Ruth Gonzalez , Canteli Susana Plaza , Piñeiro Antía Pérez , Rodríguez Begoña Cortés , Vidal Leyre Jorquer , Catalán Ignacio Pérez , Tellez Marta Leon , Martín Oterino José Ángel , González María Candelaria Martín , Serrano Carrillo de Albornoz José Luis , Sardon Eva Garcia , Pedrajas José Nicolás Alcalá , Diez-Canseco Anabel Martin-Urda , Giner MaJosé Esteban , Gómez Pablo Tellería , Gómez-Huelgas Ricardo , Ramos-Rincón José Manuel ,   for the SEMI-COVID-19 Network
Published: September 2020

Abstract(1) BackgroundThis study aims to identify different clinical phenotypes in COVID-19 pneumonia using cluster analysis and to assess the prognostic impact among identified clusters in such patients.(2) MethodsCluster analysis including 11 phenotypic variables was performed in a large cohort of 12,066 COVID-19 patients, collected and followed-up from March 1, to July 31, 2020, from the nationwide Spanish SEMI-COVID-19 Registry.(3) ResultsOf the total of 12,066 patients included in the study, most were males (7,052, 58.5%) and Caucasian (10,635, 89.5%), with a mean age at diagnosis of 67 years (SD 16). The main pre-admission comorbidities were arterial hypertension (6,030, 50%), hyperlipidemia (4,741, 39.4%) and diabetes mellitus (2,309, 19.2%). The average number of days from COVID-19 symptom onset to hospital admission was 6.7 days (SD 7). The triad of fever, cough, and dyspnea was present almost uniformly in all 4 clinical phenotypes identified by clustering. Cluster C1 (8,737 patients, 72.4%) was the largest, and comprised patients with the triad alone. Cluster C2 (1,196 patients, 9.9%) also presented with ageusia and anosmia; cluster C3 (880 patients, 7.3%) also had arthromyalgia, headache, and sore throat; and cluster C4 (1,253 patients, 10.4%) also manifested with diarrhea, vomiting, and abdominal pain. Compared to each other, cluster C1 presented the highest in-hospital mortality (24.1% vs. 4.3% vs. 14.7% vs. 18.6%; p<0.001). The multivariate study identified phenotypic clusters as an independent factor for in-hospital death.(4) ConclusionThe present study identified 4 phenotypic clusters in patients with COVID-19 pneumonia, which predicted the in-hospital prognosis of clinical outcomes.