bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebral hemodynamics as biomarkers for neuropathic pain in rats: a longitudinal study using a spinal nerve ligation model
Authors: Jin Seokha , Cho Hyung Joon 
Published: July 2024

Abstract
Neuropathic pain is one of the most challenging types of pain to diagnose and treat, a problem exacerbated by the lack of a quantitative biomarker. Recently, several clinical and preclinical studies have shown that neuropathic pain induces cerebral hemodynamic changes as a result of neuroplasticity in the brain. Our hypothesis in this study is that neuropathic pain leads to cerebral hemodynamic changes over postoperative time in a spinal nerve ligation (SNL) rat model, which has not been longitudinally explored previously. Furthermore, by identifying multiple regional hemodynamic features that are the most distinct between SNL and sham groups, where the sham group underwent only an incision without SNL, it may be possible to classify the SNL group regardless of when the onset of pain occurs. We investigate cerebral hemodynamic changes using dynamic susceptibility contrast magnetic resonance imaging in a rat model up to 28 days after ligating L5/L6 spinal nerves. We trained a linear support vector machine with relative cerebral blood volume data from different brain regions and found that the prediction model trained on the nucleus accumbens, motor cortex, pretectal area, and thalamus classified the SNL group and sham group at a 79.27% balanced accuracy, regardless of when the onset of pain occurred (SNL/sham: 60/45 data points). From the use of the SNL model without prior knowledge of the onset time of pain, the current findings highlight the potential of relative cerebral blood volume in the 4 highlighted brain regions as a biomarker for neuropathic pain.
Course-based intra-articular injection of medical chitosan mitigates excessive deposition of triacylglycerides in the synovial tissue of the knee osteoarthritis
Authors: Su Qi-Hang , Chen Li-Yang , Cai Qiu-Chen , Ge Heng-An , Li Jun , Liu Cen-Tao , Xue Chao , Huang Jing-Biao , Huang Cheng-Long , Feng Xiao-Fei , Cheng Biao 
Published: July 2024

Background:
This study aimed to investigate the clinical efficacy of intra-articular injections of medical chitosan for treating knee osteoarthritis (KOA) and measure the lipid metabolism profiles of the synovial tissue.

Methods:
Sixty patients with KOA undergoing conservative treatment were recruited and randomized into two groups: one without pharmacological intervention (OA group) and the other receiving course-based intra-articular medical chitosan injections (CSI group). Quantitative lipidomic profile of synovial tissue was analyzed. Functional scores, including Kellgren-Lawrence rating (K-L), Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scoring, and American Knee Society (AKS) scoring were conducted.

Results:
Survival from the initial conservative treatment to final knee arthroplasty was significantly longer in the CSI group compared to the OA group. Except for the presurgery VAS score, no statistically significant differences were observed in the other scores, including K-L, initial VAS, WOMAC, and AKS. However, the CSI group experienced more reductions in AKS-Knee subscores compared to the OA group. Compared to the CSI group, the OA group exhibited a significant upregulation in most differential lipids, particularly triacylglycerides (TAGs, 77%). The OA group had notably higher levels of long-chain unsaturated fatty acids.

Conclusion:
Intra-articular injection of medical chitosan significantly prolongs the survival period before knee arthroplasty and reduces the deposition of TAGs metabolites.
Lidocaine patch for treatment of acute localized pain in the emergency department: a systematic review and meta-analysis
Authors: Felemban Abdullah , Allan Salsabeel , Youssef Elias , Verma Rajesh , Zehtabchi Shahriar 
Published: July 2024

Lidocaine patches are commonly prescribed for acute localized pain. Most of the existing evidence is, however, derived from postoperative or chronic pain. The objective of this study is to assess the efficacy and safety of lidocaine patch compared to placebo patch or nonsteroidal anti-inflammatory drugs (NSAIDs) for acute localized pain.
This was a systematic review and meta-analysis of trials randomizing patients with acute localized pain to lidocaine patch versus placebo patch or NSAIDs.
The outcomes were change in pain score (any validated scale) from baseline to a specific time endpoint (primary efficacy); adverse events (primary harm), and time to exit the study due to reaching a pain relief target (secondary). We used Cochrane revised tool to assess the risk of bias and GRADE to rate the quality of evidence. The meta-analysis was performed using a random-effects model and Cochrane Q test for heterogeneity. Data were summarized as risk ratios and weighted mean differences with 95% confidence interval (CI).
We conducted a comprehensive search of MEDLINE, EMBASE, and other major databases, identifying 10 randomized controlled trials with a total of 523 patients. These trials collectively found that lidocaine patches were more effective in controlling both musculoskeletal and neuropathic pain compared to placebo patches. Due to heterogeneity among the studies, we did not pool the efficacy data. The risk of adverse events was similar between the groups (risk ratio: 0.90; 95% CI: 0.48–1.67; moderate-quality evidence). In the two trials comparing lidocaine patches with NSAIDs, there was no statistically significant difference in pain relief between the treatments.
Low to moderate-quality evidence from small trials supports the efficacy and safety of lidocaine patch for the treatment of acute localized pain.
Surgical closure versus transcatheter closure for ventricular septal defect post-infarction: a meta-analysis
Authors: Aramin Mohamed A. S. , Abuhashem Shadi , Faris Khalid Jamal , Omar Belal M. M. , Burhanuddin Mohd , Teja Puli Sai , Ibraheim Mark 
Published: July 2024

Background:
Surgical correction of post-infarct ventricular septal defect (PIVSD) is associated with a significant incidence of morbidity and mortality. The authors aimed to evaluate the effectiveness and safety of surgical versus transcatheter approaches in the management of PIVSD.

Methods:
A systematic review and meta-analysis of retrospective from five databases including the Cochrane Library, PubMed, Web of Science, Ovid, and Scopus) until 9 March 2024 was conducted. Risk ratio (RR) for dichotomous outcomes was used and data with a 95% CI are presented.

Results:
A total of 7 retrospective observational studies with 603 patients were included in the analysis. Surgical closure was associated with a significantly lower short-term mortality and lower number of residual shunt or re-intervention rate compared to percutaneous closure, with a relative risk (RR) of 1.21 (95% CI:1:00–1.46, P = 0.05) and 2.68 (95% CI: 1.46–4.91, P = 0.001), respectively. Surgical closure was associated with a non-significantly lower long-term mortality rate compared to percutaneous closure, with a relative risk (RR) of 1.10 (95% CI: 0.82–1.48, P = 0.52). No difference is reported when time from acute myocardial infarction (AMI) or PIVSD to intervention is compared groups, with a relative risk (RR) of -0.24 (95% CI: −4.49 to 4.2, P = 0.91).

Conclusion:
Our meta-analysis shied the light on the significance of surgical closure in terms of short-term mortality and the need for re-intervention. However, no significant difference was observed in terms of long-term mortality and time to intervention.
A case report of breast cancer metastasis to the bladder from invasive ductal carcinoma
Authors: Hou Tian , Shen Guangtai , Hu Xin , Bai Tubuxin , He Heping , Zhang Zhipeng , Bao Wenqi , Tian Ruibo , Yu Xiaoqiang , Sun Tianyang , Ding Xiaoli , Wang Xin , Zhang Yuhai 
Published: July 2024

Introduction and importance:
Breast cancer is the most common malignancy among women worldwide, predominantly manifesting as invasive ductal carcinoma (IDC), which usually metastasizes to the bones, lungs, and liver. However, metastasis to the bladder is exceedingly rare, with few documented cases and limited understanding in the existing literature.

Case presentation:
A 57-year-old woman with a history of IDC presented with a lump in her left breast and was initially treated with chemotherapy and a modified radical mastectomy. Years later, she developed urinary symptoms, which upon investigation revealed multiple bladder tumors and right kidney hydronephrosis. Diagnostic imaging, including ultrasound and computed tomography (CT) scans, supported these findings.

Clinical discussion:
The discovery of bladder metastasis from IDC highlights significant diagnostic challenges due to the atypical presentation. The case underscores the importance of considering unusual metastatic sites in patients with known breast cancer, especially when they present with non-specific urinary symptoms. This report explores the potential pathophysiological mechanisms of such rare metastatic occurrences and discusses the implications for clinical practice.

Conclusion:
This case exemplifies the critical need for heightened awareness and thorough evaluation in patients with unusual symptoms and a history of breast cancer. It calls for more comprehensive diagnostic approaches and possibly adjusted treatment protocols to better manage atypical metastases, ultimately aiming to improve patient outcomes and contribute to a deeper understanding of metastatic breast cancer behavior.
Cluster Analysis Methods to Support Population Health Improvement Among US Counties
Authors: Pollock Elizabeth A. , Gangnon Ronald E. , Gennuso Keith P. , Givens Marjory L. 
Published: July 2024

Context:
Population health rankings can be a catalyst for the improvement of health by drawing attention to areas in need of relative improvement and summarizing complex information in a manner understood by almost everyone. However, ranks also have unintended consequences, such as being interpreted as “hard truths,” where variations may not be significant. There is a need to improve communication about uncertainty in ranks, with accurate interpretation. The most common solutions discussed in the literature have included modeling approaches to minimize statistical noise or borrow strength from covariates. However, the use of complex models can limit communication and implementation, especially for broad audiences.

Objectives:
Explore data-informed grouping (cluster analysis) as an easier-to-understand, empirical technique to account for rank imprecision that can be effectively communicated both numerically and visually.

Design:
Cluster analysis, specifically k-means clustering with Wasserstein (earth mover’s) distance, was explored as an approach to identify natural and meaningful groupings and gaps in the data distribution for the County Health Rankings’ (CHR) health outcomes ranks.

Setting:
County-level health outcomes from the 2022 CHR.

Participants:
3082 counties that were ranked in the 2022 CHR.

Main Outcome Measure:
Data-informed health groups.

Results:
Cluster analysis identified 30 health groupings among counties nationwide, with cluster size ranging from 9 to 184 counties. On average, states had 16 identified clusters, ranging from 3 in Delaware and Hawaii to 27 in Virginia. Number of clusters per state was associated with number of counties per state and population of the state. The method helped address many of the issues that arise from providing rank estimates alone.

Conclusions:
Public health practitioners can use this information to understand uncertainty in ranks, visualize distances between county ranks, have context around which counties are not meaningfully different from one another, and compare county performance to peer counties.
A Quality Improvement Project to Improve After-visit Summary Patient Instructions in a Pediatric Multidisciplinary Neuromuscular Program
Authors: de Pins Agathe M. , Adu-Amankwah Dorothy , Shadman Kristin A. , Hess Skylar M. , Elaiho Cordelia R. , Butler Liam R. , Ranade Sheena C. , Shah Brijen J. , Fields Robert , Lin Elaine P. 
Published: July 2024

Introduction:Multidisciplinary clinics aim to coordinate care between multiple specialties for children with medical complexity yet may result in information overload for caregivers. The after-visit summary (AVS) patient instruction section offers a solution by summarizing visit details and recommendations. No known studies address patient instruction optimization and integration within a multidisciplinary clinic setting. This project aimed to improve the quality of patient instructions to support better postvisit communication between caregivers and providers in a multidisciplinary pediatric neuromuscular program.Methods:A multidisciplinary stakeholder team created a key driver diagram to improve postvisit communication between caregivers and providers in the clinic. The first specific aim was to achieve an 80% completion rate of AVS patient instructions within 6 months. To do so, a standardized electronic medical record “text shortcut” was created for consistent information in each patient’s instructions. Feedback on AVS from caregivers was obtained using the Family Experiences with Coordination of Care survey and open-ended interviews. This feedback informed the next specific aim: to reduce medical jargon within patient instructions by 25% over 3 months. Completion rates and jargon use were reviewed using control charts.Results:AVS patient instruction completion rates increased from a mean of 39.4%–85.0%. Provider education reduced mean jargon usage in patient instructions, from 8.2 to 3.9 jargon terms.Conclusions:Provider education and caregiver feedback helped improve patient communication by enhancing AVS compliance and diminishing medical jargon. Interventions to improve AVS patient instructions may enhance patient communication strategies for complex medical visits.
Prevalence and Correlates of Frailty Among Older Adults Living With HIV in the CHANGE HIV Cohort
Authors: Zhabokritsky Alice , Klein Marina , Harris Marianne , Loutfy Mona , Guillemi Silvia , Tan Darrell H. S. , Falutz Julian , Andany Nisha , Guaraldi Giovanni , Lovblom Leif Erik , Walmsley Sharon 
Published: July 2024

Background:
Advancements in treatment have resulted in improved survival among people living with HIV. However, additional years of life are not necessarily spent in good health, as frailty tends to develop at a younger age among people living with HIV. We set out to examine the prevalence of frailty and its correlates among older adults living with HIV in Canada, with a primary interest in nadir CD4 count.

Methods:
We performed a cross-sectional analysis of the Correlates of Healthy Aging in Geriatric HIV (CHANGE HIV) study, a Canadian cohort of people living with HIV aged 65 years or older. Participants were assessed using the Fried Frailty Phenotype at cohort entry, and those meeting ≥3 criteria were characterized as frail. We used Poisson regression with robust standard errors to estimate the association between nadir CD4 count and frailty, as well as age, gender, time since HIV diagnosis, comorbidities, marital status, and loneliness.

Results:
Among 439 participants included in this analysis (median age 69 years, interquartile ranges 67–73), prevalence of frailty was 16.6%. Frailty was not associated with nadir CD4 count. Not being in a relationship (aRR 2.09, 95% CI 1.01 to 4.30) and greater degree of loneliness (aRR 1.25 per 10 point increase on UCLA loneliness scale, 95% CI 1.09 to 1.44) were associated with frailty.

Conclusions:
Frailty occurred in 16.6% of older adults living with HIV in this cohort. While nadir CD4 count did not correlate with frailty, being single and lonely did, highlighting the importance of recognizing and addressing these social vulnerabilities among people aging with HIV.
Late Ordovician eurypterid preserves oldest euchelicerate musculature in pyrite
Authors: Bicknell Russell D. C. , Gaines Robert R. , Hopkins Melanie J. 
Published: July 2024

Pyritization of soft tissues of invertebrates is rare in the fossil record. In New York State, it occurs in black shales of the Lorraine Group (Late Ordovician), the best-known example of which is Beecher's Trilobite Bed. Exceptional preservation at the quarry where this bed is exposed allowed detailed examination of trilobite and ostracod soft-tissue anatomy. Here, we present the first example of a eurypterid (sea scorpion) currently ascribed to Carcinosomatidae from this deposit that also preserves the first evidence for mesosomal musculature in eurypterids. This specimen demonstrates that eurypterid musculature can be preserved in pyrite and evidences the oldest example of euchelicerate muscles within the fossil record. Sulfur isotope data illustrate that pyrite rapidly replicated muscle tissue in the early burial environment, prior to the pyritization of biomineralized exoskeleton and cuticular trilobite limbs. This discovery therefore expands the limited fossil record of euchelicerate musculature, while extending the taphonomic scope for preservation of detailed internal structures, more broadly, within arthropods.
Antibody optimization enabled by artificial intelligence predictions of binding affinity and naturalness
Authors: Bachas Sharrol , Rakocevic Goran , Spencer David , Sastry Anand V. , Haile Robel , Sutton John M. , Kasun George , Stachyra Andrew , Gutierrez Jahir M. , Yassine Edriss , Medjo Borka , Blay Vincent , Kohnert Christa , Stanton Jennifer T. , Brown Alexander , Tijanic Nebojsa , McCloskey Cailen , Viazzo Rebecca , Consbruck Rebecca , Carter Hayley , Levine Simon , Abdulhaqq Shaheed , Shaul Jacob , Ventura Abigail B. , Olson Randal S. , Yapici Engin , Meier Joshua , McClain Sean , Weinstock Matthew , Hannum Gregory , Schwartz Ariel , Gander Miles , Spreafico Roberto 
Published: July 2024

Abstract

Traditional antibody optimization approaches involve screening a small subset of the available sequence space, often resulting in drug candidates with suboptimal binding affinity, developability or immunogenicity. Based on two distinct antibodies, we demonstrate that deep contextual language models trained on high-throughput affinity data can quantitatively predict binding of unseen antibody sequence variants. These variants span a
K

D

range of three orders of magnitude over a large mutational space. Our models reveal strong epistatic effects, which highlight the need for intelligent screening approaches. In addition, we introduce the modeling of “naturalness”, a metric that scores antibody variants for similarity to natural immunoglobulins. We show that naturalness is associated with measures of drug developability and immunogenicity, and that it can be optimized alongside binding affinity using a genetic algorithm. This approach promises to accelerate and improve antibody engineering, and may increase the success rate in developing novel antibody and related drug candidates.
Tumor Subtype Classification Tool for HPV-associated Head and Neck Cancers
Authors: Li Shiting , Garb Bailey F. , Qin Tingting , Soppe Sarah , Lopez Elizabeth , Patil Snehal , D’Silva Nisha J. , Rozek Laura S. , Sartor Maureen A. 
Published: July 2024

ABSTRACTImportanceMolecular subtypes of HPV-associated Head and Neck Squamous Cell Carcinoma (HNSCC), named IMU (immune strong) and KRT (highly keratinized), are well-recognized and have been shown to have distinct mechanisms of carcinogenesis, clinical outcomes, and potentially differing optimal treatment strategies. Currently, no standardized method exists to subtype a new HPV+ HNSCC tumor. Our paper introduces a machine learning-based classifier and webtool to reliably subtype HPV+ HNSCC tumors using the IMU/KRT paradigm and highlights the importance of subtype in HPV+ HNSCC.ObjectiveTo develop a robust, accurate machine learning-based classification tool that standardizes the process of subtyping HPV+ HNSCC, and to investigate the clinical, demographic, and molecular features associated with subtype in a meta-analysis of four patient cohorts.Data SourcesWe conducted RNA-seq on 67 HNSCC FFPE blocks from University of Michigan hospital. Combining this with three publicly available datasets, we utilized a total of 229 HPV+ HNSCC RNA-seq samples. All participants were HPV+ according to RNA expression. An ensemble machine learning approach with five algorithms and three different input training gene sets were developed, with final subtype determined by majority vote. Several additional steps were taken to ensure rigor and reproducibility throughout.Study SelectionThe classifier was trained and tested using 84 subtype-labeled HPV+ RNA-seq samples from two cohorts: University of Michigan (UM; n=18) and TCGA-HNC (n=66). The classifier robustness was validated with two independent cohorts: 83 samples from the HPV Virome Consortium and 62 additional samples from UM. We revealed 24 of 39 tested clinicodemographic and molecular variables significantly associated with subtype.ResultsThe classifier achieved 100% accuracy in the test set. Validation on two additional cohorts demonstrated successful separation by known features of the subtypes. Investigating the relationship between subtype and 39 molecular and clinicodemographic variables revealed IMU is associated with epithelial-mesenchymal transition (p=2.25×10−04), various immune cell types, and lower radiation resistance (p=0.0050), while KRT is more highly keratinized (p=2.53×10−08), and more likely female than IMU (p=0.0082).Conclusions and RelevanceThis study provides a reliable classifier for subtyping HPV+ HNSCC tumors as either IMU or KRT based on bulk RNA-seq data, and additionally, improves our understanding of the HPV+ HNSCC subtypes.
Extracellular ISG15 triggers ISGylation via a type-I interferon independent non-canonical mechanism to regulate host response during virus infection
Authors: Miller Lindsay Grace , Chiok Kim , Mariasoosai Charles , Mohanty Indira , Pandit Sudiksha , Deol Pallavi , Mehari Liyon , Teng Michael N. , Haas Arthur L. , Natesan Senthil , Miura Tanya A. , Bose Santanu 
Published: July 2024

AbstractType-I interferons (IFN) induce cellular proteins with antiviral activity. One such protein is Interferon Stimulated Gene 15 (ISG15). ISG15 is conjugated to proteins during ISGylation to confer antiviral activity and regulate cellular activities associated with inflammatory and neurodegenerative diseases and cancer. Apart from ISGylation, unconjugated free ISG15 is also released from cells during various conditions, including virus infection. The role of extracellular ISG15 during virus infection was unknown. We show that extracellular ISG15 triggers ISGylation and acts as a soluble antiviral factor to restrict virus infection via an IFN-independent mechanism. Specifically, extracellular ISG15 acts post-translationally to markedly enhance the stability of basal intracellular ISG15 protein levels to support ISGylation. Furthermore, extracellular ISG15 interacts with cell surface integrin (α5β1 integrins) molecules via its RGD-like motif to activate the integrin-FAK (Focal Adhesion Kinase) pathway resulting in IFN-independent ISGylation. Thus, our studies have identified extracellular ISG15 protein as a new soluble antiviral factor that confers IFN-independent non-canonical ISGylation via the integrin-FAK pathway by post-translational stabilization of intracellular ISG15 protein.