bluuebunny/crossref_metadata_2025_split huggingface dataset:
Filgotinib decreases both vertebral body and posterolateral spine inflammation in ankylosing spondylitis: results from the TORTUGA trial
Authors: Maksymowych Walter P , Østergaard Mikkel , Landewé Robert , Barchuk William , Liu Ke , Gilles Leen , Hendrikx Thijs , Besuyen Robin , Baraliakos Xenofon 
Published: October 2021

Abstract

Objectives
To assess the effects of filgotinib on inflammatory and structural changes at various spinal locations, based on MRI measures in patients with active AS in the TORTUGA trial.

Methods
In the TORTUGA trial, patients with AS received filgotinib 200 mg (n = 58) or placebo (n = 58) once daily for 12 weeks. In this post hoc analysis, spine MRIs were evaluated using the Canada–Denmark (CANDEN) MRI scoring system to assess changes from baseline to week 12 in total spine and subscores for inflammation, fat, erosion and new bone formation (NBF) at various anatomical locations. Correlations were assessed between CANDEN inflammation and clinical outcomes and Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scores and between baseline CANDEN NBF and baseline BASFI and BASMI scores.

Results
MRIs from 47 filgotinib- and 41 placebo-treated patients were evaluated. There were significantly larger reductions with filgotinib vs placebo in total spine inflammation score and most inflammation subscores, including posterolateral elements (costovertebral joints, transverse/spinous processes, soft tissues), facet joints and vertebral bodies. No significant differences were observed for corner or non-corner vertebral body inflammation subscores, spine fat lesion, bone erosion or NBF scores. In the filgotinib group, the change from baseline in the total inflammation score correlated positively with the SPARCC spine score. Baseline NBF scores correlated with baseline BASMI but not BASFI scores.

Conclusions
Compared with placebo, filgotinib treatment was associated with significant reductions in MRI measures of spinal inflammation, including in vertebral bodies, facet joints and posterolateral elements.

Trial registration
ClinicalTrials.gov (https://clinicaltrials.gov), NCT03117270.
Systemic autoimmune myopathies: a prospective phase 4 controlled trial of an inactivated virus vaccine against SARS-CoV-2
Authors: Shinjo Samuel K , de Souza Fernando H C , Borges Isabela B P , dos Santos Alexandre M , Miossi Renata , Misse Rafael G , Medeiros-Ribeiro Ana C , Saad Carla G S , Yuki Emily F N , Pasoto Sandra G , Kupa Léonard V K , Ceneviva Carina , Seraphim Júlia C , Pedrosa Tatiana N , Vendramini Margarete B G , Silva Clóvis A , Aikawa Nádia E , Bonfá Eloisa 
Published: October 2021

Abstract

Objectives
To evaluate immunogenicity and safety of an inactivated SARS-CoV-2 vaccine in systemic autoimmune myopathies (SAMs) and the possible influence of baseline disease parameters, comorbidities and therapy on immune response.

Methods
This prospective controlled study included 53 patients with SAMs and 106 non-immunocompromised control group (CTRL). All participants received two doses of the Sinovac-CoronaVac vaccine (28-day interval). Immunogenicity was assessed by anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC), anti-S1/S2 IgG geometric mean titre (GMT), factor increase GMT (FI-GMT), neutralizing antibodies (NAb) positivity, and median neutralizing activity after each vaccine dose (D0 and D28) and six weeks after the second dose (D69). Participants with pre-vaccination positive IgG serology and/or NAb and those with RT-PCR confirmed COVID-19 during the protocol were excluded from immunogenicity analysis.

Results
Patients and CTRL had comparable sex (P&gt;0.99) and age (P=0.90). Immunogenicity of 37 patients and 79 CTRL-naïve participants revealed at D69, a moderate but significantly lower SC (64.9% vs 91.1%, P&lt;0.001), GMT [7.9 (95%CI 4.7–13.2) vs 24.7 (95%CI 30.0–30.5) UA/ml, P&lt;0.001] and frequency of NAb (51.4% vs 77.2%, P&lt;0.001) in SAMs compared with CTRL. Median neutralizing activity was comparable in both groups [57.2% (interquartile range (IQR) 43.4–83.4) vs 63.0% (IQR 40.3–80.7), P=0.808]. Immunosuppressives were less frequently used among NAb+ patients vs NAb- patients (73.7% vs 100%, P=0.046). Type of SAMs, disease status, other drugs or comorbidities did not influence immunogenicity. Vaccine-related adverse events were mild with similar frequencies in patients and CTRL (P&gt;0.05).

Conclusion
Sinovac-CoronaVac is safe and has a moderate short-term immunogenicity in SAMs, but reduced compared with CTRL. We further identified that immunosuppression is associated with diminished NAb positivity.

Trial registration
COVID-19 CoronaVac in Patients With Autoimmune Rheumatic Diseases and HIV/AIDS (CoronavRheum), http://clinicaltrials.gov/ct2/show/NCT04754698
Baseline Fecal Microbiota in Pediatric Patients With Celiac Disease Is Similar to Controls But Dissimilar After 1 Year on the Gluten-Free Diet
Authors: Sample Dory , Fouhse Janelle , King Seema , Huynh Hien Q. , Dieleman Levinus A. , Willing Benjamin P. , Turner Justine 
Published: October 2021

Objectives:
The objectives of this pilot study were to examine fecal microbiota composition of pediatric patients with celiac disease (CD) before and after a 1-year gluten-free diet (GFD) and to determine the association with symptoms and anti-tissue transglutaminase (aTTG) antibody.

Methods:
Stool samples were obtained from pediatric patients with CD and from healthy controls. Patients were classified by the presence (diarrhea, abdominal pain, weight loss) or absence (asymptomatic, headache, fatigue, etc.) of typical CD gastrointestinal symptoms and by aTTG normalization post-GFD intervention (< 7 U/mL). Fecal microbial composition was measured using 16S ribosomal RNA gene amplicon sequencing of the V3–V4 region.

Results:
At diagnosis, 13 of 22 patients with CD had typical gastrointestinal symptoms, the remaining patients having atypical or asymptomatic presentations. After a 1-year GFD, all symptomatic patients improved and 9 of 19 had normalized aTTG. Prior to GFD, no distinct microbial signature was observed between patients and controls (P = 0.39). Post-GFD, patients with CD had a unique microbial signature with reductions in known fiber-degrading bacteria, including Blautia, Dorea, Lactobacillus, and Prevotella compared with controls. Within the patients with CD, microbial composition was not associated with reported symptom presentation or aTTG normalization.

Conclusions:
Pediatric patients with CD only had a unique microbial signature compared with healthy controls when placed on the GFD. These results suggest that pediatric patients with CD may not have a unique fecal microbial signature indicative of inherent dysbiosis, in contrast to that suggested for older patients. In children with CD, diet may play a role in shaping microbial composition more so than disease status.
Association of Fecal Calprotectin With Endoscopic and Histologic Activity in Pediatric Inflammatory Bowel Disease
Authors: Crawford Erin , Gestrich Catherine , Malay Sindhoosha , Young Denise , Perry Sharon , Splawski Judy , Sferra Thomas J. , Saab Shahrazad , Moses Jonathan 
Published: October 2021

Objectives:
Fecal calprotectin (FC) is a noninvasive marker of intestinal inflammation used for screening and ongoing monitoring of inflammatory bowel disease (IBD); it is unclear the association of specific FC values with disease activity. The aim of our study was to examine the association of FC values with endoscopic and histologic severity.

Methods:
We performed a retrospective chart review of patients who had FC done between 30 days and 1 day before colonoscopy at our institution. IBD patients were graded using the simple endoscopic score for Crohn’s disease or Mayo endoscopic score for ulcerative colitis. Histologic slides were graded using the Geboes method.

Results:
Three-hundred thirty-one patients were included in the study and 107 had IBD. For endoscopy, median FC was lowest for all IBD patients with no disease (181 μg/g) and highest in severe disease (921 μg/g), with significant difference between no disease and moderate and severe disease (P = 0.019, 0.003), and between mild and severe disease (P = 0.012). For histology, median FC was lowest with no disease (328 μg/g) and highest in severe disease (895 μg/g), with significant difference between no disease and moderate and severe disease (P = 0.021, 0.018). The control population had a significantly lower median FC than the IBD population in endoscopic remission (35.5 versus 181 μg/g; P = 0.018).

Conclusions:
There was a linear increase in FC values associated with increasing disease severity in the undifferentiated IBD cohort. Values for IBD patients in endoscopic remission were significantly different from our control population. FC may be a useful noninvasive marker to assess disease severity.
The Role of Endonasal Endoscopic Skull Base Repair in Posttraumatic Tension Pneumocephalus
Authors: Dalolio Martina , Cordier Dominik , Al-Zahid Saif , Bennett Warren O. , Prepageran Narayanan , Waran Vicknes , Mariani Luigi , Koeppl Ruth , Brand Yves , Roethlisberger Michel 
Published: October 2021

Objectives:
Information about the endonasal endoscopic approach (EEA) for the management of posttraumatic tension pneumocephalus (PTTP) remains scarce. Concomitant rhinoliquorrhea and posttraumatic hydrocephalus (PTH) can complicate the clinical course.

Methods:
The authors systematically reviewed pertinent articles published between 1961 and December 2020 and identified 6 patients with PTTP treated by EEA in 5 reports. Additionally, the authors share their institutional experience including a seventh patient, where an EEA resolved a recurrent PTTP without rhinoliquorrhea.

Results:
Seven PTTP cases in which EEA was used as part of the treatment regime were included in this review. All cases presented with a defect in the anterior skull base, and 3 of them had concomitant rhinoliquorrhea. A transcranial approach was performed in 6/7 cases before EEA was considered to treat PTTP. In 4/7 cases, the PTTP resolved after the first intent; in 2/ 7 cases a second repair was necessary because of recurrent PTTP, 1 with and 1 without rhinoliquorrhea, and 1/7 case because of recurrent rhinoliquorrhea only. Overall, PTTP treated by EEA resolved with a mean radiological resolution time of 69 days (range 23–150 days), with no late recurrences. Only 1 patient developed a cerebrospinal fluid diversion infection probably related to a first incomplete EEA skull base defects repair. A permanent cerebrospinal fluid diversion was necessary in 3/7 cases.

Conclusions:
Endonasal endoscopic approach repair of air conduits is a safe and efficacious second-line approach after failed transcranial approaches for symptomatic PTTP. However, the strength of recommendation for EEA remains low until further evidence is presented.
The Biomedical Research Hub: A Federated Platform for Patient Research Data
Authors: Barnes Craig , Bajracharya Binam , Cannalte Matthew , Gowani Zakir , Haley Will , Kass-Hout Taha , Hernandez Kyle , Ingram Michael , Juvvala Hara Prasad , Kuffel Gina , Martinov Plamen , Maxwell J. Montgomery , McCann John , Malhotra Ankit , Metoki-Shlubsky Noah , Meyer Chris , Paredes Andre , Qureshi Jawad , Ritter Xenia , Schumm L. Philip , Shao Mingfei , Sheth Urvi , Simmons Trevar , VanTol Alexander , Zhang Zhenyu , Grossman Robert L. 
Published: October 2021

AbstractObjectiveThe objective was to develop and operate a cloud-based federated system for managing, analyzing and sharing patient data for research purposes, while allowing each resource sharing patient data to operate their component based upon their own governance rules. The federated system is called the Biomedical Research Hub (BRH).MethodsThe BRH is a cloud-based federated system built over a core set of software services called framework services. BRH framework services include authentication and authorization, services for generating and assessing FAIR data, and services for importing and exporting bulk clinical data. The BRH includes data resources providing data operated by different entities and workspaces that can access and analyze data from one or more of the data resources in the BRH.ResultsThe BRH contains multiple data commons that in aggregate provide access to over 6 PB of research data from over 400,000 research participants.Discussion and conclusionWith the growing acceptance of using public cloud computing platforms for biomedical research, and the growing use of opaque persistent digital identifiers for datasets, data objects, and other entities, there is now a foundation for systems that federate data from multiple independently operated data resources that expose FAIR APIs, each using a separate data model. Applications can be built that access data from one or more of the data resources.
A Standardized Protocol for Quantifying the Behavioral Dynamics of Food-seeking in Mice
Authors: Ha Dong-Soo , Lee Young Hee , Kim Kyu Sik , Kim You Bin , Choi Hyung Jin 
Published: October 2021

ABSTRACTFood is generally hidden in a natural environment and require free-living animals to search for it. Although such food-seeking behaviors involve motivation and exploration, previous studies examined food-seeking simply by measuring the time spent in the food zone or the frequency of pursuing food-cued context. Moreover, after discovering food, animals need to taste and smell it in order to evaluate their nutritional value or possible toxicity. However, researchers could not easily distinguish food-seeking from food-evaluating behaviors because food was visible or accessible throughout each test. Herein, we describe a behavioral protocol that triggers animals to show the behavioral dynamics of food-seeking (e.g., navigation, nose-digging, and paw-digging) and that exclusively elicits food-seeking without provoking any other food-evaluating behaviors. First, we prepared an open-field box with the floor covered with bedding. After we hid foods under the bedding of each corner, the test mice were habituated in this arena for four days (pre-test phase). On the next day (test phase), they were placed under the same conditions, but the foods previously hidden were removed. This process enabled the mice to perceive their surroundings as a food-hidden environment, which induced the animal to exhibit sustained food-seeking. In conclusion, the protocol presented here is a powerful method for provoking multiple forms of food-seeking and quantifies food-seeking independently from other food-related behavioral stages.
Modelling the effect of COVID-19 mass vaccination on acute admissions in a major English healthcare system
Authors: Booton RD , Powell AL , Turner KME , Wood RM 
Published: October 2021

AbstractBackgroundManaging high levels of severe COVID-19 in the acute setting can impact upon the quality of care provided to both affected patients and those requiring other hospital services. Mass vaccination has offered a route to reduce societal restrictions while protecting hospitals from being overwhelmed. Yet, early in the mass vaccination effort, the possible effect on future bed pressures remained subject to considerable uncertainty. This paper provides an account of how, in one healthcare system, operational decision-making and bed planning was supported through modelling the effect of a range of vaccination scenarios on future COVID-19 admissions.MethodsAn epidemiological model of the Susceptible-Exposed-Infectious-Recovered (SEIR) type was fitted to local data for the one-million resident healthcare system located in South West England. Model parameters and vaccination scenarios were calibrated through a system-wide multi-disciplinary working group, comprising public health intelligence specialists, healthcare planners, epidemiologists, and academics. From 4 March 2021 (the time of the study), scenarios assumed incremental relaxations to societal restrictions according to the envisaged UK Government timeline, with all restrictions to be removed by 21 June 2021.ResultsAchieving 95% vaccine uptake in adults by 31 July 2021 would not avert a third wave in autumn 2021 but would produce a median peak bed requirement approximately 6% (IQR: 1% to 24%) of that experienced during the second wave (January 2021). A two-month delay in vaccine rollout would lead to significantly higher peak bed occupancy, at 66% (11% to 146%) of that of the second wave. If only 75% uptake was achieved (the amount typically associated with vaccination campaigns) then the second wave peak for acute and intensive care beds would be exceeded by 4% and 19% respectively, an amount which would seriously pressure hospital capacity.ConclusionModelling provided support to senior managers in setting the number of acute and intensive care beds to make available for COVID-19 patients, as well as highlighting the importance of public health in promoting high vaccine uptake among the population. Forecast accuracy has since been supported by actual data collected following the analysis, with observed peak bed occupancy falling comfortably within the inter-quartile range of modelled projections.
Effects of Age, Sex, Serostatus and Underlying Comorbidities on Humoral Response Post-SARS-CoV-2 Pfizer-BioNTech Vaccination – A Systematic Review
Authors: Notarte Kin Israel , Ver Abbygail Therese , Velasco Jacqueline Veronica , Pastrana Adriel , Catahay Jesus Alfonso , Salvagno Gian Luca , Yap Eric Peng Huat , Martinez-Sobrido Luis , Torrelles Jordi , Lippi Giuseppe , Henry Brandon Michael 
Published: October 2021

ABSTRACTWith the advent of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, several vaccines have been developed to mitigate its spread and prevent adverse consequences of the Coronavirus Disease 2019 (COVID-19). The mRNA technology is an unprecedented vaccine, usually given in two doses to prevent SARS-CoV-2 infections. Despite effectiveness and safety, inter-individual immune response heterogeneity has been observed in recipients of mRNA-based vaccines. As a novel disease, the specific immune response mechanism responsible for warding off COVID-19 remains unclear at this point. However, significant evidence suggests that humoral response plays a crucial role in affording immunoprotection and preventing debilitating sequelae from COVID-19. As such this paper focused on the possible effects of age, sex, serostatus, and comorbidities on humoral response (i.e., total antibodies, IgG and/or IgA) of different populations post-mRNA-based Pfizer-BioNTech vaccination. A systematic search of literature was performed through PubMed, Cochrane CENTRAL, and Google Scholar. Studies were included if they reported humoral response to COVID-19 mRNA vaccines. A total of 32 studies was identified and reviewed, and the percent difference of means of reported antibody levels were calculated for comparison. Findings revealed that older individuals, the male sex, seronegativity, and those with more comorbidities mounted less humoral immune response. Given these findings, several recommendations were proposed regarding the current vaccination practices. These include giving additional doses of vaccination for immunocompromised and elderly populations. Another recommendation is conducting clinical trials in giving a combined scheme of mRNA vaccines, protein vaccines, and vector-based vaccines.
Quantitative chest CT combined with plasma cytokines predict outcomes in COVID-19 patients
Authors: Carbonell Guillermo , Del Valle Diane Marie , Gonzalez-Kozlova Edgar , Marinelli Brett , Klein Emma , Homsi Maria El , Stocker Daniel , Chung Michael , Bernheim Adam , Simons Nicole W. , Xiang Jiani , Nirenberg Sharon , Kovatch Patricia , Lewis Sara , Merad Miriam , Gnjatic Sacha , Taouli Bachir 
Published: October 2021

ABSTRACTDespite extraordinary international efforts to dampen the spread and understand the mechanisms behind SARS-CoV-2 infections, accessible predictive biomarkers directly applicable in the clinic are yet to be discovered. Recent studies have revealed that diverse types of assays bear limited predictive power for COVID-19 outcomes. Here, we harness the predictive power of chest CT in combination with plasma cytokines using a machine learning approach for predicting death during hospitalization and maximum severity degree in COVID-19 patients. Patients (n=152) from the Mount Sinai Health System in New York with plasma cytokine assessment and a chest CT within 5 days from admission were included. Demographics, clinical, and laboratory variables, including plasma cytokines (IL-6, IL-8, and TNF-α) were collected from the electronic medical record. We found that chest CT combined with plasma cytokines were good predictors of death (AUC 0.78) and maximum severity (AUC 0.82), whereas CT quantitative was better at predicting severity (AUC 0.81 vs 0.70) while cytokine measurements better predicted death (AUC 0.70 vs 0.66). Finally, we provide a simple scoring system using plasma IL-6, IL-8, TNF-α, GGO to aerated lung ratio and age as novel metrics that may be used to monitor patients upon hospitalization and help physicians make critical decisions and considerations for patients at high risk of death for COVID-19.
Investigating trends in those who experience menstrual bleeding changes after SARS-CoV-2 vaccination
Authors: Lee Katharine MN , Junkins Eleanor J , Luo Chongliang , Fatima Urooba A , Cox Maria L , Clancy Kathryn BH 
Published: October 2021

AbstractEarly in 2021, many people began sharing that they experienced unexpected menstrual bleeding after SARS-CoV-2 inoculation. We investigated this emerging phenomenon of changed menstrual bleeding patterns among a convenience sample of currently and formerly menstruating people using a web-based survey. In this sample, 42% of people with regular menstrual cycles bled more heavily than usual while 44% reported no change after being vaccinated. Among respondents who typically do not menstruate, 71% of people on long-acting reversible contraceptives, 39% of people on gender-affirming hormones, and 66% of post-menopausal people reported breakthrough bleeding. We found increased/breakthrough bleeding was significantly associated with age, systemic vaccine side effects (fever, fatigue), history of pregnancy or birth, and ethnicity. Generally, changes to menstrual bleeding are not uncommon nor dangerous, yet attention to these experiences is necessary to build trust in medicine.TeaserIncreased bleeding can occur post SARS-CoV-2 vaccines; this study investigates patterns in who experiences these changes.
Regenerative and non-regenerative transcriptional states of the human epicardium: from foetus to adult and back again
Authors: Knight-Schrijver Vincent R. , Davaapil Hongorzul , Ross Alexander , He Xiaoling , Vallier Ludovic , Gambardella Laure , Sinha Sanjay 
Published: October 2021

ABSTRACTEpicardial activation appears to be required for cardiac regeneration. Although reverting quiescent adult epicardium to an active neonatal or foetal state will likely represent a key therapeutic approach for human cardiac regeneration, the exact molecular differences between human adult and foetal epicardium are not understood. We used single-cell RNA sequencing to compare epicardial cells from both foetal and adult hearts. We found two foetal epicardial cell types, mesothelial and fibroblast-like, with only the mesothelial population present in adults. We also identified foetal-specific epicardial genes associated with regeneration and angiogenesis, and found that adult epicardium may be primed for immune and inflammatory responses. We predict that restoring the foetal epicardial state in human hearts would increase adult angiogenic potential. Finally, we demonstrated that human embryonic stem-cell derived epicardium is a valid model for the foetal epicardium and for investigating epicardial-mediated cardiac regeneration in humans. Our study defines regenerative programs in human foetal epicardium that are absent in the adult, brings human context to animal studies, and provides a roadmap for directing the epicardium in human heart regeneration.