bluuebunny/crossref_metadata_2025_split huggingface dataset:
It doesn't hurt as long as I don't move: Aligning pain assessment in patients with rib fractures with mobilization needed for recovery
Authors: Bauman Zachary M. , Phillips Jakob , Tian Yuqian , Cavlovic Lindsey , Raposo-Hadley Ashley , Khan Hason , Evans Charity H. , Kamien Andrew , Cemaj Samuel , Sheppard Olabisi , Lamb Gina , Veatch Jessica , Matos Mike , Cantrell Emily 
Published: October 2024

BACKGROUND
Rib fracture pain is a major issue but likely underappreciated, given that patients avoid activity due to the pain. Pain is one criterion used to determine if someone is a candidate for surgical stabilization of rib fractures (SSRF). The purpose of this study was to assess pain for rib fracture patients, hypothesizing pain from rib fractures is underappreciated in current practice.

METHODS
A prospective study analyzing patients with one or more rib fractures admitted to our Level I trauma center from March 2023 through February 2024. Exclusion criteria included refusal to participate, ventilator dependent, younger than 18 years, moderate/severe traumatic brain injury, spinal cord injury, pregnancy, or incarceration. Basic demographics were obtained. Participants rated their pain on an 11-point Numerical Rating Scale while resting in bed and performing a series of movements (0, no pain; 10, worst pain imaginable). Movements included incentive spirometer, flexion, extension, bilateral side bending, bilateral rotation, and holding a 5-pound dumbbell. Patients undergoing SSRF were surveyed pre- and postoperatively. Outcomes included the difference between pain scores at rest versus performing all movements, difference between pain scores pre- and post-SSRF, and incentive spirometry pre- and postoperatively. Nonparametric analysis was completed with the Wilcoxon signed-rank test with statistical significance set at p < 0.05.

RESULTS
One-hundred two patients were enrolled. The mean age was 60 ± 15 years; 57.8% were male. The median pain score at rest was 3 (interquartile range [IQR], 2–5.5). Pain scores significantly increased to >5 for all movements. Thirty-one patients underwent SSRF. Resting pain prior to SSRF was 3 (IQR, 1–6) and postoperatively was 2 (IQR, 1.5–3) (p = 0.446). For all movements, median Numerical Rating Scale score was significantly less after SSRF (p < 0.001). The median incentive spirometry was 1,100 mL (IQR, 625–1,600 mL) preoperatively and 2,000 mL (IQR, 1,475–2,250 mL) postoperatively.

CONCLUSION
Traditional assessment of pain in patients with rib fractures significantly underappreciates true pain severity caused by movements involving the chest wall and should be considered when evaluating for SSRF.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level II.
Functional Natural Killer-cell Genetics and Microvascular Inflammation After Kidney Transplantation: An Observational Cohort Study
Authors: Diebold Matthias , Vietzen Hannes , Schatzl Martina , Mayer Katharina A. , Haindl Susanne , Heinzel Andreas , Hittmeyer Philip , Herz Carsten T. , Hopfer Helmut , Menter Thomas , Kühner Laura M. , Berger Sarah M. , Puchhammer-Stöckl Elisabeth , Doberer Konstantin , Steiger Jürg , Schaub Stefan , Böhmig Georg A. 
Published: October 2024

Background.
Recent evidence highlights the pivotal role of natural killer (NK) cells in allograft rejection.

Methods.
We explored associations of missing self and gene polymorphisms determining the phenotype and/or functionality of NK cells with microvascular inflammation (MVI) in a single-center cohort of 507 consecutive kidney transplant recipients. Patients were genotyped for killer cell Ig-like receptors and polymorphisms in 4 selected genes (FCGR3A
V/F158 [rs396991], KLRC2
wt/del, KLRK1
HNK/LNK [rs1049174], and rs9916629-C/T).

Results.
MVI was detected in 69 patients (13.6%). In a proportional odds model, the KLRC2
del/del variant reduced MVI risk (odds ratio [OR] 0.26; 95% confidence interval [CI], 0.05-0.93; P = 0.037) independent of donor-specific antibodies, HLA class II eplet mismatch, and number of biopsies. Conversely, missing self (OR 1.40; 95% CI, 1.08-1.80; P = 0.011) and the rs9916629 T/T gene variant increased the risk (OR 1.70; 95% CI, 1.08-2.68; P = 0.021). Graft loss tended to be more frequent among patients with missing self ≥2 (hazard ratio 1.97; 95% CI, 0.89-4.37; P = 0.097), without influence on estimated glomerular filtration trajectories. FCGR3A variants were associated with MVI only in patients with preformed and/or de novo donor-specific antibodies (OR 4.14; 95% CI, 0.99-17.47; P = 0.052).

Conclusions.
Missing self and NK-cell genetics may contribute to MVI, underscoring the important role of NK cells in transplant rejection.
Diffuse fibrosis, coronary microvascular dysfunction and systolic dysfunction in Wilson disease
Authors: Steffen Johansson Rebecka , Fogarasi Csenge , Kellman Peter , Kindmark Andreas , Nickander Jannike 
Published: October 2024

AbstractBackgroundWilson disease (WD) causes intracellular copper accumulation in the body due to a genetic defect in the protein ATP7B. Cardiac involvement such as electrocardiographic abnormalities, rhythm abnormalities, heart failure and cardiac death have been reported, however pathophysiological mechanisms remain unclear.ObjectivesThis study aimed to comprehensively assess the myocardium in WD patients without cardiac symptoms using multiparametric cardiovascular magnetic resonance imaging (CMR), including quantitative stress perfusion mapping and strain analysis.MethodsWD patients (n=17, 41±16 years, 47% female) and volunteers (n=17, 39±15 years, 47% female) underwent multiparametric mapping at 1.5 T CMR including cine, native T1, native T2, adenosine stress perfusion mapping, late gadolinium enhancement (LGE), and extracellular volume (ECV) imaging. Symptoms of myocardial ischemia were quantified using Seattle Angina Questionnaire-7 (SAQ-7) and cardiovascular risk factors and medications were recorded.ResultsBoth stress perfusion and MPR were lower in WD patients (2.95±0.58 vs 3.67±1.01 ml/min/g, and 3.4±0.8 vs 4.4±1.9), while ECV was higher, (29±3% vs 27±2%), p<0.05 for all. Left ventricular ejection fraction (LVEF) was lower in WD patients, (56±6% vs 61±6%,p=0.02), and LV ventricular global circumferential strain (LV GCS) was higher (-18±2% vs - 20±2%,p=0.005). Late gadolinium enhancement (LGE) was present in the right ventricular insertion point (RVIP) in 12/17 (71%) of the WD patients.ConclusionsIn this small mechanistic study, WD patients on stable treatment without apparent cardiac symptoms have early signs of diffuse fibrosis, coronary microvascular dysfunction (CMD) and systolic dysfunction, shedding light on pathophysiological mechanisms of cardiac dysfunction in copper accumulation.
Radiotherapy triggers pro-angiogenic signaling in human lung
Authors: Soulier Juliette , Curras-Alonso Sandra , Dubail Maxime , Laporte Hugo , Mallick Ayan , Lafouasse Chloé , Colin Delphine , Côté Jean-François , Didier Jérôme , Pouliquen Christelle , Benali Abdelali , Alifano Marco , Durdux Catherine , Damotte Diane , Lefèvre Marine , Bohec Mylène , Cao Kim , Créhange Gilles , Verrelle Pierre , Girard Nicolas , Seguin-Givelet Agathe , Londoño-Vallejo Arturo , Fouillade Charles 
Published: October 2024

AbstractRadiotherapy is one of the main therapeutic options for the treatment of lung cancer. Although highly efficient, radiation cause severe damages to normal tissue and radio-induced toxicities vary from mild pneumonitis to pulmonary fibrosis. The mechanism leading to these toxicities remain unclear. To investigate the molecular responses of human lung to radiotherapy, we analyzed, by single cell RNAseq, lung tissue resected in the vicinity of the tumor (i.e. treated with radiation) and compared the transcriptional profiles of the distinct lung populations from the same patient removed at distance from the tumor (i.e. non-treated with radiation).Analysis of six lung samples from patients suffering from Pancoast tumor, a rare lung malignancy that requires neo-adjuvant radiotherapy before surgery, revealed a strong induction of VEGF signaling after radiotherapy. Expression of VEGFA, one of the canonical pro-angiogenic ligands, was found upregulated in multiple cell populations in lung exposed to high doses of radiation. Irradiated capillaries, particularly gCap cells, expressing KDR/VEGFR2, present transcriptional profile similar to tip cells, characterized by sprouting and motility capacities. In addition, we identified a sub-population of alveolar macrophages expressing FLT1/VEGFR1, a receptor for VEGFA, in lung tissues treated by radiotherapy. Cell-Cell communication analysis revealed that FLT1/VEGFR1 positive macrophages interact with tip cells after radiotherapy through IL1B-IL1R signaling. Lastly, analysis of mouse single cell dataset confirmed the increase in the proportion of gCap cells presenting a tip-like phenotype after radiation injury.Altogether, this study describes, at the single cell level, the pro-angiogenic responses of human lung after radiotherapy. These results will lead to a better understanding of the physiopathology of lung radiation injury and may pave the way to optimize treatments to improve patients’ quality of life.
Comparative assessment of machine learning algorithms to predict severity of disease in COVID-19 patients based on eight cofactors
Authors: Patel Tanvi S. , Patel Daxesh P. , El-Sayed Hoda , Sanyal Mallika , Shrivastav Pranav S. 
Published: October 2024

AbstractMachine learning is one of the important tools to diagnose and predict the diseased state accurately and effectively. The COVID-19 pandemic caused due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become one of the most researched healthcare topics worldwide. Machine learning algorithms can find efficient and reliable ways to predict the COVID-19 from vast amounts of existing health care data, allowing faster, effective, and more accurate diagnosis with lower risk based on the symptoms. Based on the countrywide data published by the Israeli Ministry of Health, we propose a system that detects COVID-19 instances using simple variables. The COVID-19 dataset used in the study consisted of 278848 patients samples with five different symptoms, namely cough, fever, sore throat, shortness of breath, and headache, apart from other basic information like age, gender, and test indication excluding confirmed COVID-19 result. The data was analyzed using traditional supervised machine learning algorithms namely, Decision tree, Support vector machine, Random Forest, Logistic regression, k-nearest neighbor, and Naive Bayes based on eight cofactors with high accuracy rate (≥ 0.9450). Apart from Support vector machine, all other algorithms displayed better performance based on the AUC score calculated using the receiver operator characteristic (ROC) curve. This study also highlights the significant differences between precision, recall and accuracy for each model.Abstract FigureGraphical Abstract
Neuroinflammation and Spinal Cord Pathology Associated with Hypertension in Spontaneously Hypertensive Stroke-Prone Rats
Authors: Noyan H. , Juurlink B.H.J. 
Published: October 2024

ABSTRACTHypertension is a major contributor to cardiovascular and cerebrovascular disease, leading to significant central nervous system (CNS) damage, including in the spinal cord. This study examines the spinal cord in uncontrolled hypertension of stroke-prone spontaneously hypertensive rats (SHRsp) compared to normotensive Wistar-Kyoto rats (WKY). Histological analyses, including Sudan Black B staining, NADPH-diaphorase histochemistry, immunohistochemistry, and Western blotting, were used to assess inflammation, gliosis, oxidative stress, and axonal injury.SHRsp rats displayed extensive spinal cord pathology, including macrophage infiltration, astrocyte hypertrophy, and demyelination. ED1 immunostaining revealed significant microglial activation in SHTsp, particularly in the ventrolateral white matter, while Sudan Black B staining showed edema and lipid-laden macrophages in dilated perivascular spaces. Increased NADPH-diaphorase activity in SHRsp indicated heightened nitric oxide synthase activity. Glial fibrillary acidic protein (GFAP) immunostaining confirmed significant astrogliosis, with hypertrophic astrocytes more prominent in SHRsp. Western blot analysis showed elevated amyloid precursor protein (APP) levels in SHRsp, associated with axonal injury and oxidative stress. APP-positive phagocytes in white matter further suggested active axonal degeneration.These findings demonstrate significant neuroinflammation, gliosis, and spinal cord tissue damage in hypertensive rats, highlighting the spinal cord’s vulnerability to hypertension. This underscores the importance of addressing hypertensive damage in the CNS, particularly in patients at risk of neurodegenerative or motor impairments.
Single-Cell Antigen Receptor Sequencing in Pigs with Influenza
Authors: Gu Weihong , Madrid Darling Melany de Carvahlo , Clements Sadie , Touchard Laurie , Bivins Nathan , Zane Grant , Zhou Mingyi , Lee Kiho , Driver John P. 
Published: October 2024

AbstractUnderstanding the pulmonary adaptive immune system of pigs is important as respiratory pathogens present a major challenge for swine producers and pigs are increasingly used to model human pulmonary diseases. Single-cell RNA sequencing (scRNAseq) has accelerated the characterization of cellular phenotypes in the pig respiratory tract under both healthy and diseased conditions. However, combining scRNAseq with recovery of paired T cell receptor (TCR) α and β chains as well as B cell receptor (BCR) heavy and light chains to interrogate their repertoires has not to our knowledge been demonstrated for pigs. Here, we developed primers to enrich porcine TCR α and β chains along with BCR κ and λ light chains and IgM, IgA, and IgG heavy chains that are compatible with the 10x Genomics VDJ sequencing protocol. Using these pig-specific assays, we sequenced the T and B cell receptors of cryopreserved lung cells fromCD1D-expressing and -deficient pigs after one or two infections with influenza A virus (IAV) to examine whether natural killer T (NKT) cells alter pulmonary TCR and BCR repertoire selection. We also performed paired single-cell RNA and receptor sequencing of FACS-sorted T cells longitudinally sampled from the lungs of IAV-vaccinated and -infected pigs to track clonal expansion in response to IAV exposure. All pigs presented highly diverse repertoires. Pigs re-exposed to influenza antigens from either vaccination or infection exhibited higher numbers of expanded CD4 and CD8 T cell clonotypes with activated phenotypes, suggesting potential IAV reactive T cell populations. Our results demonstrate the utility of high throughput single-cell TCR and BCR sequencing in pigs.
Illicit Cigarette Trade and Tax evasion in Zambia: Findings from the Tobacco Control Data Initiative 2023
Authors: Zyambo Cosmas , Phiri Masauso Moses , Mwamulela Webby , Zulu Richard , Maka Mbaita , Camara Aminata , Ogolla Sharon , Ali Seember Joy , Pokothoane Retselisitsoe , Ross Hana , Goma Fastone Matthew , Mdege Noreen Dadirai 
Published: October 2024

AbstractBackgroundIllicit cigarette trade has significant economic and public health implications. It leads to governments tax revenue losses due to the evasion of tobacco taxes, and often these cigarettes are cheaper ones therefore increasing cigarette consumption.ObjectiveTo estimate the Illicit cigarette trade and tax evasion in Zambia and establish its associated factorsMethods and analysisA cross sectional survey was used to collect empty cigarette packs from the retailers and street/bins in 25 districts covering 10 Provinces of Zambia. We used a descriptive analysis to calculate the proportion of illicit cigarette packs and other specific criteria. Logistic regression was used to model the factors associated with the prevalence of the illicit cigarette market in Zambia.ResultsOf the 118, 344 empty cigarette packs collected (82.0% from the retailers and 18.0% the street/bins), Rothmans accounted for 40.7% and Stuyvesant 13.1%, both manufactured by British American Tobacco. 14,428 (12.2%) were deemed illicit. Out of the total packs, 1792 (1.5%) did not have a textual health warning, 343 (0.3%) packs did not have a textual health warning in english, 1490 (1.3%) had duty-free stamps even though they were purchased from retail outlets that were not duty-free shops and, 11,939 (10.1%) did not have a ZRA stamp. Factors associated with reduced odds of illicit cigarettes sales were non-boarder [AOR 0.17 (CI; 0.13 – 0.23)] and local manufactured AOR 0.44 (CI; 0.37 – 0.53).ConclusionsOur study demonstrated that 12.2% of the cigarettes sold on the Zambian market is illicit, with 10.1% evading tax. We found that cigarettes from Lusaka province, urban regions, border towns, and those that are imported had higher odds of being illicit. This finding underscores the fact that Zambia should ratify and implement the WHO Protocol on Illicit Tobacco Trade (ITP) to counter the supply of illicit cigarettes.
Body composition as a biomarker for assessing future lung cancer risk
Authors: Wang Jing , Leader Joseph K. , Meng Xin , Yu Tong , Wang Renwei , Herman James , Yuan Jian-min , Wilson David , Pu Jiantao 
Published: October 2024

ABSTRACTPurposeTo investigate if body composition is a biomarker for assessing the risk of developing lung cancer.Materials and MethodsLow-dose computed tomography (LDCT) scans from the Pittsburgh Lung Screening Study (PLuSS) (n=3,635, 22 follow-up years) and NLST-ACRIN (n=16,435, 8 follow-up years) cohorts were used in the study. Artificial intelligence (AI) algorithms were developed to automatically segment and quantify subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), intramuscular adipose tissue (IMAT), skeletal muscle (SM), and bone. Cause-specific Cox proportional hazards models were used to evaluate the hazard ratios (HRs). Standard time-dependent receiver operating characteristic (ROC) analysis was used to evaluate the prognostic ability of different models over time.ResultsThe final composite models were formed by seven variables: age (HR=1.20), current smoking status (HR=1.59), bone volume (HR=1.79), SM density (HR=0.29), IMAT ratio (HR=0.33), IMAT density (HR=0.56), and SAT volume (HR=0.56). The models trained on the PLuSS cohort achieved a mean AUC of 0.76 (95% CI: 0.74-0.79) over 21 follow-up years and 0.70 (95% CI: 0.66-0.74) over the first 7 follow-up years for predicting lung cancer development within the PLuSS cohort. In contrast, models trained on the PLuSS cohort alone, as well as in combination with the NLST cohorts, achieved an AUC ranging from 0.61 to 0.68 in the NLST cohort over a 7-year follow-up period.ConclusionBody composition assessed on LDCT is a significant predictor of lung cancer risk and could improve the effectiveness of LDCT lung cancer screening by optimizing the screening eligibility and frequency.Summary statementBody composition assessed on LDCT is a significant predictor of lung cancer risk and could improve the effectiveness of LDCT lung cancer screening by optimizing the screening eligibility and frequency.Key PointsThis study unveils the significant associations between body tissues and lung cancer risk.The prediction models based on body composition alone, as well as the combination of demographics and body composition features can effectively identify patients at higher risk of developing lung cancer.
The Hexosamine Biosynthetic Pathway alters the cytoskeleton to modulate cell proliferation and migration in metastatic prostate cancer
Authors: Shakya Rajina , Suraneni Praveen , Zaslavsky Alexander , Rahi Amit , Magdongon Christine B. , Gajjela Raju , Mattamana Basil B. , Varma Dileep 
Published: October 2024

AbstractCastration-resistant prostate cancer (CRPC) progresses despite androgen deprivation therapy, as cancer cells adapt to grow without testosterone, becoming more aggressive and prone to metastasis. CRPC biology complicates the development of effective therapies, posing challenges for patient care. Recent gene-expression and metabolomics studies highlight the Hexosamine Biosynthetic Pathway (HBP) as a critical player, with key components like GNPNAT1 and UAP1 being downregulated in metastatic CRPC. GNPNAT1 knockdown has been shown to increase cell proliferation and metastasis in CRPC cell lines, though the mechanisms remain unclear.To investigate the cellular basis of these CRPC phenotypes, we generated a CRISPR-Cas9 knockout model of GNPNAT1 in 22Rv1 CRPC cells, analyzing its impact on metabolomic, glycoproteomic, and transcriptomic profiles of cells. We hypothesize that HBP inhibition disrupts the cytoskeleton, altering mitotic progression and promoting uncontrolled growth. GNPNAT1 KO cells showed reduced levels of cytoskeletal filaments, such as actin and microtubules, leading to cell structure disorganization and chromosomal mis-segregation. GNPNAT1 inhibition also activated PI3K/AKT signaling, promoting proliferation, and impaired cell adhesion by mislocalizing EphB6, enhancing migration via the RhoA pathway and promoting epithelial-to-mesenchymal transition. These findings suggest that HBP plays a critical role in regulating CRPC cell behavior, and targeting this pathway could provide a novel therapeutic approach.
Liver CYP4A autophagic-lysosomal degradation (ALD): A major role for the autophagic receptor SQSTM1/p62 through an uncommon target interaction site
Authors: He Liang , Kwon Doyoung , Trnka Michael J. , Liu Yi , Yang Jade , Li Kathy , Totah Rheem A. , Johnson Eric F. , Burlingame A. L. , Correia Maria Almira 
Published: October 2024

ABSTRACTThe hepatic P450 hemoproteins CYPs 4A are typical N-terminally anchored Type I endoplasmic reticulum (ER)-proteins, that are inducible by hypolipidemic drugs and other “peroxisome proliferators”. They are engaged in the ω-/ω-1-oxidation of various fatty acids including arachidonic acid, prostaglandins and leukotrienes and in the biotransformation of some therapeutic drugs. Herein we report that of the mammalian liver CYPs 4A, human CYP4A11 and mouse Cyp4a12a are preferential targets of the ER-lysosome-associated degradation (ERLAD). Consequently, these proteins are stabilized both as 1%Triton X100-soluble and -insoluble species in mouse hepatocytes and HepG2-cells deficient in the autophagic initiation ATG5-gene. Although these proteins exhibit surface LC3-interacting regions (LIRs) that would target them directly to the autophagosome, they nevertheless interact intimately with the autophagic receptor SQSTM1/p62. Through structural deletion analyses and site-directed mutagenesis, we have identified the Cyp4A-interacting p62 subdomain to lie between residues 170 and 233, which include its Traf6-binding and LIM-binding subdomains. Mice carrying a liver-specific genetic deletion of p62 residues 69-251 (p62Mut) that includes the CYP4A-interacting subdomain also exhibit Cyp4a-protein stabilization both as Triton X100-soluble and -insoluble species. Consistently, p62Mut mouse liver microsomes exhibit enhanced ω- and ω-1-hydroxylation of arachidonic acid to its physiologically active metabolites 19- and 20-HETEs relative to the corresponding wild-type mouse liver microsomes. Collectively, our findings suggest that any disruption of CYP4A ERLAD results in functionally active P450 protein and consequent production of proinflammatory metabolites on one hand, and insoluble aggregates on the other, which may contribute to pathological aggregates i.e. Mallory-Denk bodies/inclusions, hallmarks of many liver diseases.