bluuebunny/crossref_metadata_2025_split huggingface dataset:
Day-to-day fluctuations of fatigue severity in individuals with knee osteoarthritis: an ecological momentary assessment approach
Authors: Heijman Michelle W J , van den Ende Cornelia H M , Peters Yvonne A S , Mahler Elien A M , Popa Calin D , Vriezekolk Johanna E 
Published: July 2023

Abstract

Objective
The variable course of fatigue adds to the disease burden of patients with OA yet it has been poorly understood. This study aimed to describe within-person fluctuations of fatigue severity and explore its associations with pain, positive affect, negative affect, sleep, and perceived exertion of physical activity.

Methods
Individuals with chronic knee pain or a clinical diagnosis of knee OA ≥40 years of age completed daily assessments about fatigue, pain, positive affect, negative affect, sleep, perceived exertion of physical activity (numeric rating scale 0–10), and overwhelming fatigue (yes/no) on a smartphone over 14 days. Within-person fluctuations of fatigue severity were described by the probability of acute changes (PACs) and s.d.s. Associations with pain, positive affect, negative affect, sleep, and perceived exertion of physical activity were explored using multilevel models.

Results
Forty-nine individuals were included (mean age 63.4 years; 82% female). PACs and s.d.s of within-person daily fatigue fluctuations ranged from 0.00 to 0.80 and 0.35 to 2.95, respectively. Within-person associations of fatigue severity were moderate for positive affect [β = −0.57 (95% CI −0.67, −0.47)], weak for pain [β = 0.41 (95% CI 0.29, 0.53)] and negative affect [β = 0.40 (95% CI 0.21, 0.58)], and negligible for sleep [β = −0.13 (95% CI −0.18, −0.08)] and perceived exertion of physical activity [β = 0.18 (95% CI 0.09, 0.26)].

Conclusion
Some individuals showed almost stable day-to-day levels of fatigue severity, whereas others experienced a substantial number of clinically relevant fluctuations. To reduce the burden of daily fatigue fluctuations, our results suggest that pain, positive and negative affect rather than sleep and perceived exertion of physical activity should be considered as potential targets.
Twenty-five years of novel drug approvals in rheumatology
Authors: Henry Kathryn , Anumolu Natalie , Putman Michael 
Published: July 2023

Abstract
The field of rheumatology has experienced dozens of novel drug approvals in the past two and a half decades, but the regulatory mechanisms underpinning these decisions are not well understood. In the USA, the Food and Drug Administration (FDA) evaluates the safety and efficacy of novel drugs through the New Drug Application (NDA) process. When additional content expertise is required to evaluate scientific or technical matters, the FDA may convene Human Drug Advisory Committees. To better understand the landscape of rheumatology NDAs and the FDA use of advisory committees, we performed a review of all rheumatic disease drug applications from 1996 to 2021 that were granted approval by the FDA. Our review identified 31 NDAs, seven of which utilized an advisory committee. The indications for using advisory committees and their influence on ultimate approvals was not clear. Recommendations to improve transparency and increase public trust in FDA decisions are provided.
Anti-survival motor neuron complex antibodies as a novel biomarker for pulmonary arterial hypertension and interstitial lung disease in mixed connective tissue disease
Authors: Todoroki Yasuyuki , Satoh Minoru , Kubo Satoshi , Kosaka Shunpei , Fukuyo Shunsuke , Nakatsuka Keisuke , Saito Kazuyoshi , Tanaka Shin , Nakayamada Shingo , Tanaka Yoshiya 
Published: July 2023

Abstract

Objective
The presence of anti-U1 RNP antibodies (Abs) is critical for diagnosing MCTD. The aim of this study is to evaluate the clinical relevance of anti-survival motor neuron (SMN) complex Abs, which often coexist with anti-U1 RNP Abs.

Methods
A total of 158 newly diagnosed consecutive cases of SLE, SSc or MCTD with anti-U1 RNP Abs were enrolled in this multicentre observational study between April 2014 and August 2022. Serum anti-SMN complex Abs were screened by immunoprecipitation of 35S-methionine-labelled cell extracts, and associations between anti-SMN complex Abs positivity and clinical characteristics were analysed.

Results
Anti-SMN complex Abs were detected in 36% of MCTD patients, which was significantly higher than that in SLE (8%) or SSc (12%). Among MCTD patients classified based on the combination of the clinical features of SLE, SSc and idiopathic inflammatory myopathies, anti-SMN complex Abs showed the highest prevalence in a subset with clinical features of all three components. Anti-SMN complex Abs–positive MCTD had a higher prevalence of pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD), which are related to poor prognosis, than negative patients. Moreover, all three cases of death within 1 year of the treatment were positive for anti-SMN complex Abs.

Conclusions
Anti-SMN complex Abs is the first biomarker of a typical subset of MCTD which bears organ damages such as PAH and ILD.
“I was called everything but a student”: Blackness and the Social Death of Student Status
Authors: Lofton Richard 
Published: July 2023

Abstract
Using the conceptual tools of anti-Blackness and the Black habitus to analyze the interviews of 38 Black youth who lived and grew up in Baltimore City, this study contends that the negative associations placed on Black youth continue to dehumanize them and prevent them from the full embodiment of student status. This article explores Blackness and its relationship with the privileges and immunities of student status within America’s collective consciousness. Through the voices of Black youth, this article provides evidence that Black students in Baltimore have not been fully granted the immunity of student status. Instead, Black youth participants describe harm in their schools and neighborhoods, as well as a tenuous relationship between Blackness and “studentness.”
Looks Matter: Are U.S. Schools of Social Work Representing Diversity on Their Websites?
Authors: Ogbonnaya Ijeoma Nwabuzor , Wike Traci L , Bouchard Leah M , Carver Ann Turnlund 
Published: July 2023

Abstract
Public administration researchers have found that passive diversity leads to active diversity. However, whether this relationship holds in schools of social work is uncertain. Understanding this relationship in schools of social work can inform methods used by schools of social work to foster diversity and inclusion. Authors examined the relationship between passive and active diversity representation among 31 randomly selected school of social work websites. Quantitative content analysis revealed that the three most common passive diversity characteristics were (1) having tenure-track faculty of color, (2) images of diverse persons, and (3) faculty with diversity-focused research. The top three active diversity characteristics were (1) no GRE admissions requirement, (2) a woman dean/director, and (3) scholarship/fellowships opportunities. Least represented were student demographics and pronouns in faculty profiles. Most notable bivariate findings were the positive associations between a dean/director of color and tenured faculty of color and the relationship between faculty with diversity-focused research and tenured faculty of color. Greater representation of deans/directors of color in schools of social work is critical for the career advancement of faculty of color. To attract more faculty of color, schools of social work should use their websites to promote hiring opportunities for scholars conducting diversity-focused research. Future research exploring additional diversity characteristics on schools of social work websites and whether these characteristics translate to more inclusive environments is needed.
Fluid resuscitation in acute pancreatitis
Authors: Yang Allison L. , Vege Santhi Swaroop 
Published: July 2023

Purpose of review
The purpose of the review is to critically evaluate the evidence from the literature to establish the current perspective on fluid resuscitation (FR) in acute pancreatitis (AP). We will review the rationale, type of fluid, rate of administration, total volume, duration, monitoring, ideal outcomes to be studied in clinical trials and recommendations for future studies.

Recent findings
FR remains the key component of supportive therapy in AP. The paradigm has shifted from administration of aggressive fluid resuscitation towards more moderate FR strategies. Lactated Ringer's remains the preferred fluid for resuscitation. There remain critical gaps in knowledge regarding the end point(s) to indicate adequate resuscitation, and accurate assessments of fluid sequestration and intravascular volume deficit in AP.

Summary
There is insufficient evidence to state that goal-directed therapy, using any of the parameters to guide fluid administration, reduces the risk of persistent organ failure, infected pancreatic necrosis, or mortality in AP, as well as the most appropriate method for the same.
Beyond the hype: large language models propagate race-based medicine
Authors: Omiye Jesutofunmi A. , Lester Jenna , Spichak Simon , Rotemberg Veronica , Daneshjou Roxana 
Published: July 2023

ImportanceLarge language models (LLMs) are being integrated into healthcare systems; but these models recapitulate harmful, race-based medicine.ObjectiveThe objective of this study is to assess whether four commercially available large language models (LLMs) propagate harmful, inaccurate, race-based content when responding to eight different scenarios that historically included race-based medicine or widespread misconceptions around race.Evidence ReviewQuestions were derived from discussion among 4 physician experts and prior work on race-based medical misconceptions of medical trainees.FindingsWe assessed four large language models with eight different questions that were interrogated five times each with a total of forty responses per a model. All models had examples of perpetuating race-based medicine in their responses. Models were not always consistent in their responses when asked the same question repeatedly.Conclusions and RelevanceLLMs are being proposed for use in the healthcare setting, with some models already connecting to electronic health record systems. However, this study shows that based on our findings, these LLMs could potentially cause harm by perpetuating debunked, racist concepts.
Alterations of the gut microbiome are associated with epigenetic age acceleration and physical fitness
Authors: Torma Ferenc , Kerepesi Csaba , Jokai Matyas , Bakonyi Peter , Koltai Erika , Babszki Gergely , Ligeti Balazs , Kalcsevszki Regina , McGreevy Kristen M. , Horvath Steve , Radak Zsolt 
Published: July 2023

AbstractEpigenetic clocks can measure aging and predict the incidence of diseases and mortality. Higher levels of physical fitness are associated with a slower aging process and a healthier lifespan. Microbiome alterations occur in various diseases and during the aging process, yet their relation to epigenetic clocks is not explored. To fill this gap, we collected metagenomic, epigenetic and exercise-related data from physically fit individuals and applying epigenetic clocks, we examined the relationship between gut flora, epigenetic age acceleration and physical fitness. We revealed that an increased entropy in the gut microbiome is associated with accelerated epigenetic aging, lower fitness or impaired health status. We also observed that, in general, accelerated epigenetic aging can be linked to the abundance of pro-inflammatory and other pathogenic bacteria and decelerated epigenetic aging or high fitness level can be linked to the abundance of anti-inflammatory bacteria. Overall our data suggest that alterations in the microbiome can be associated with epigenetic age acceleration and physical fitness.
RNA-sequencing first approach generates new diagnostic candidates in Mendelian disorders
Authors: Jaramillo Oquendo Carolina , Wai Htoo A , Rich Will , Bunyan David J. , Thomas N. Simon , Hunt David , Lord Jenny , Douglas Andrew G L , Baralle Diana 
Published: July 2023

AbstractBackgroundRNA-sequencing is increasingly being used as a complementary tool to DNA sequencing in diagnostics where DNA analysis has been uninformative. RNA-sequencing allows us to identify alternative splicing and aberrant gene expression allowing for improved interpretation of variants of unknown significance (VUS). Additionally, RNA-sequencing provides the opportunity not only to look at the splicing effects of known VUSs but also to scan the transcriptome for abnormal splicing events and expression abnormalities in other relevant genes that may be the cause of a patient’s phenotype.MethodsUsing RNA from patient blood, we have systematically assessed transcriptomic profiles of 87 patients with suspected Mendelian disorders, 38% of which did not have a candidate sequence variant. Cases with VUSs and known events were assessed first followed by assessment of cases with no VUS. Each VUS was visually inspected using the Integrative Genomics Viewer (IGV) to search for splicing abnormalities. Once aberrant splicing was identified in cases with VUS, multiple open-source alternative splicing tools (MAJIQ, rMATS-turbo, FRASER2 and LeafCutterMD) were used to investigate if they would identify what was observed in IGV. Expression outliers were detected using OUTRIDER. To find diagnoses in cases without a VUS or gene of interest, two separate strategies were used. The first was a genotype to phenotype approach using variant calls obtained from the RNA-sequencing and overlapping those calls with results from splicing tools. The second strategy involved using phenotype information available to filter results from splicing tools.ResultsUsing RNA-sequencing only, we were able to assess 71% of VUSs and detect aberrant splicing in 14/48 patients with a VUS. Furthermore, we identified four new diagnoses by detecting novel aberrant splicing events in patients with no candidate sequence variants from prior genomic DNA testing (n=33) or those in which the candidate VUS did not affect splicing (n=23) and identified one additional diagnosis through detection of skewed X-inactivation.ConclusionWe demonstrate the identification of novel diagnoses using an RNA-sequencing first approach in patients without candidate VUSs. Furthermore, we demonstrate the utility of blood-based RNA analysis in improving diagnostic yields and highlight optimal approaches for such analysis.
The Influence of the Amino Acid Transporter LAT1 on Patient Prognosis and the Relationships between Tumor Immunometabolic and Proliferative Features Depend on Menopausal Status in Breast Cancer
Authors: Ramshankar Gautham , Liu Ryan , Perry Rachel J. 
Published: July 2023

AbstractL-type Amino Acid Transporter 1 (LAT1) facilitates the uptake of specific essential amino acids, and due to this quality, it has been correlated to worse patient outcomes in various cancer types. However, the relationship between LAT1 and various clinical factors, including menopausal status, in mediating LAT1’s prognostic effects remains incompletely understood. This is particularly true in the unique subset of tumors that are both obesity-associated and responsive to immunotherapy, including breast cancer. To close this gap, we employed 6 sets of transcriptomic data using the Kaplan-Meier model in the Xena Functional Genomics Explorer, demonstrating that higher LAT1 expression diminishes breast cancer patients’ survival probability.Additionally, we analyzed 3′-Deoxy-3′-18F-Fluorothymidine positron emission tomography-computed tomography (18F-FLT PET-CT) images found on The Cancer Imaging Archive (TCIA). After separating all patients based on menopausal status, we correlated the measured18F-FLT uptake with various clinical parameters quantifying body composition, tumor proliferation, and immune cell infiltration. By analyzing a wealth of deidentified, open-access data, the current study investigates the impact of LAT1 expression on breast cancer prognosis, along with the menopausal status-dependent associations between tumor proliferation, immunometabolism, and systemic metabolism.
A 3’UTR Insertion Is a Candidate Causal Variant at theTMEM106BLocus Associated with Increased Risk for FTLD-TDP
Authors: Chemparathy Augustine , Le Guen Yann , Zeng Yi , Gorzynski John , Jensen Tanner , Yang Chengran , Kasireddy Nandita , Talozzi Lia , Belloy Michael E. , Stewart Ilaria , Gitler Aaron D. , Wagner Anthony D. , Mormino Elizabeth , Henderson Victor W. , Wyss-Coray Tony , Ashley Euan , Cruchaga Carlos , Greicius Michael D. 
Published: July 2023

AbstractBackground and ObjectivesSingle nucleotide variants nearTMEM106Bassociate with risk of frontotemporal lobar dementia with TDP-43 inclusions (FTLD-TDP) and Alzheimer’s disease (AD) in genome-wide association studies (GWAS), but the causal variant at this locus remains unclear. Here we asked whether a novel structural variant onTMEM106Bis the causal variant.MethodsAn exploratory analysis identified structural variants on neurodegeneration-related genes. Subsequent analyses focused on anAluelement insertion on the 3’UTR ofTMEM106B. This study included data from longitudinal aging and neurogenerative disease cohorts at Stanford University, case-control cohorts in the Alzheimer’s Disease Sequencing Project (ADSP), and expression and proteomics data from Washington University in St. Louis (WUSTL). 432 individuals from two Stanford aging cohorts were whole-genome long-read and short-read sequenced. 16,906 samples from ADSP were short-read sequenced. Genotypes, transcriptomics, and proteomics data were available in 1,979 participants from an aging and dementia cohort at WUSTL. Selection criteria were specific to each cohort. In primary analyses, the linkage disequilibrium between theTMEM106Blocus variants in the FTLD-TDP GWAS and the 3’UTR insertion was estimated. We then estimated linkage by ancestry in the ADSP and evaluated the effect of theTMEM106Blead variant on mRNA and protein levels.ResultsThe primary analysis included 432 participants (52.5% females, age range 45-92 years old). We identified a 316 bpAluinsertion overlapping theTMEM106B3’UTR tightly linked with top GWAS variants rs3173615(C) and rs1990622(A). In ADSP European-ancestry participants, this insertion is in equivalent linkage with rs1990622(A) (R2=0.962, D’=0.998) and rs3173615(C) (R2=0.960, D’=0.996). In African-ancestry participants, the insertion is in stronger linkage with rs1990622(A) (R2=0.992, D’=0.998) than with rs3173615(C) (R2=0.811, D’=0.994). In public datasets, rs1990622 was consistently associated with TMEM106B protein levels but not with mRNA expression. In the WUSTL dataset, rs1990622 is associated with TMEM106B protein levels in plasma and cerebrospinal fluid, but not withTMEM106BmRNA expression.DiscussionWe identified a novelAluelement insertion in the 3’UTR ofTMEM106Bin tight linkage with the lead FTLD-TDP risk variant. The lead variant is associated with TMEM106B protein levels, but not expression. The 3’UTR insertion is a lead candidate for the causal variant at this complex locus, pending confirmation with functional studies.
Comparison of Adverse Effects Related to the Use of Epidural Anesthesia versus Spinal Anesthesia in Cesarean Section Patients at the Plaza de la Salud General Hospital in Santo Domingo, Dominican Republic, During the Period January-December 2021: A Retrospective Study
Authors: Alcántara Mariam , Hernández Alba Rebecca 
Published: July 2023

ABSTRACTObjectivesThis study aimed to investigate the two different types of regional anesthesia for a cesarean section and to analyze the various perioperative and postoperative side effects related to them.DesignWe retrospectively included those patients who required a cesarean section under regional anesthesiaSettingHospital General Plaza de la Salud from January 2021 to December 2021.ParticipantsA total of 202 cesarean sections were analyzed. Spinal anesthesia was used in 195 participants and epidural anesthesia in 7; both groups were then compared.ResultsPerioperative results revealed that spinal anesthesia had a shorter total anesthesia time, more frequent hypotensive episodes, and a higher perioperative ephedrine administration rate. Regarding the postoperative results, the Apgar scores of the newborns recorded at one minute and at 5 minutes were similar in both groups.ConclusionsFor patients who required a cesarean section under regional anesthesia, the use of spinal anesthesia led to a shorter anesthetic time, however it is associated with greater hemodynamic changes and ephedrine administration compared with epidural anesthesia.
Classification of the Attempted Arm and Hand Movements of Patients with Spinal Cord Injury Using Deep Learning Approach
Authors: Makouei Sahar Taghi Zadeh , Uyulan Caglar 
Published: July 2023

AbstractThe primary objective of this research is to improve the average classification performance for specific movements in patients with cervical spinal cord injury (SCI). The study utilizes a low-frequency multi-class electroencephalography (EEG) dataset obtained from the Institute of Neural Engineering at Graz University of Technology. The research combines convolutional neural network (CNN) and long-short-term memory (LSTM) architectures to uncover strong neural correlations between temporal and spatial aspects of the EEG signals associated with attempted arm and hand movements.To achieve this, three different methods are used to select relevant features, and the proposed model’s robustness against variations in the data is validated using 10-fold cross-validation (CV). Furthermore, the study explores the potential for subject-specific adaptation in an online paradigm, extending the proof-of-concept for classifying movement attempts.In summary, this research aims to make valuable contributions to the field of neuro-technology by developing EEG-controlled assistive devices using a generalized brain-computer interface (BCI) and deep learning (DL) framework. The focus is on capturing high-level spatiotemporal features and latent dependencies to enhance the performance and usability of EEG-based assistive technologies.