bluuebunny/crossref_metadata_2025_split huggingface dataset:
Testing a candidate composite serum protein marker of skin severity in systemic sclerosis
Authors: Roblin Elen , Clark Kristina E N , Beesley Claire , Ong Voon H , Denton Christopher P 
Published: March 2024

Abstract

Objectives
Using an integrated multi-omic analysis, we previously derived a candidate marker that estimates the modified Rodnan Skin Score (mRSS) and thus the severity of skin involvement in SSc. In the present study we explore technical and biological validation of this composite marker in a well-characterized cohort of SSc patients.

Methods
Cartilage oligomeric matrix protein (COMP), collagen type IV (COL4A1), tenascin-C (TNC) and spondin-1 (SPON1) were examined in serum samples from two independent cohorts of patients with dcSSc. The BIOlogical Phenotyping of diffuse SYstemic sclerosis cohort had previously been used to derive the composite marker and Molecular Determinants to Improve Scleroderma (SSc) treatment (MODERNISE) was a novel validation cohort. Multiple regression analysis derived a formula to predict the mRSS based on serum ELISA protein concentration.

Results
The serum concentration of two of the proteins—COMP and TNC—positively correlated with the mRSS, particularly in early dcSSc patients. Interpretable data could not be obtained for SPON1 due to technical limitations of the ELISA. COL4A1 showed a correlation with disease duration but not overall mRSS. Patients receiving MMF showed lower serum concentrations of COMP, COL4A1 and TNC and a lower composite biomarker score not established on treatment. A revised ELISA-based three-protein composite formula was derived for future validation studies.

Conclusions
Although more validation is required, our findings represent a further step towards a composite serum protein assay to assess skin severity in SSc. Future work will establish its utility as a predictive or prognostic biomarker.
Research advances in Peyronie’s disease: a comprehensive review on genomics, pathways, phenotypic manifestation, and therapeutic targets
Authors: Chi Junpeng , Bi Wenhua , Lou Keyuan , Ma Jian , Wu Jitao , Cui Yuanshan 
Published: March 2024

Abstract

Introduction
Penile induration disease, commonly known as Peyronie’s disease (PD), is a connective tissue disorder that affects the penis, leading to the development of fibrous plaques, penile curvature, and erectile dysfunction. PD is a common male reproductive system disease with a complex etiology involving multiple genes, signaling pathways, and different phenotypes.

Objectives
The etiology and pathogenesis of PD remain poorly understood, hindering the development of effective treatment strategies. By understanding the underlying mechanisms of PD, we can pave the way for targeted therapies and improved patient outcomes.

Methods
We reviewed the epidemiology and pathophysiology of PD. We performed database searches on Google Scholar, PubMed, Medline, and Web of Science from inception to September 2023. The literature reviewed included priapism guidelines, review articles, current trial studies, and various literature related to PD.

Results
This article provides a comprehensive overview of the current research progress on the disease, focusing on its genetic factors, signaling pathways, cellular mechanisms, phenotypic manifestations, and therapeutic targets. It can help identify individuals at higher risk, aid in early detection and intervention, and provide insights into fibrosis and tissue remodeling. It can also reveal potential therapeutic targets, guide accurate diagnoses and treatment strategies, and address the impact of the disease on patients’ quality of life.

Conclusion
By integrating insights from genomics, molecular pathways, clinical phenotypes, and therapeutic potentials, our research aims to achieve a deeper and more comprehensive understanding of PD, propelling the field toward innovative strategies that enhance the lives of those affected by PD. The complex manifestations and pathogenesis of PD necessitate the use of multiple treatment methods for personalized care.
‘My feet cannot stand on their own’: podoconiosis patient healthcare expenditures and income impacts in Rwanda
Authors: Schurer Janna M , Bayisenge Ursin , Hakizimana Dieudonne , Rafferty Ellen 
Published: March 2024

Abstract

Background
Podoconiosis is a progressive and debilitating form of tropical lymphoedema endemic to Rwanda. Although the physical and psychological consequences are well known, few studies have evaluated the financial burden of podoconiosis.

Methods
This cross-sectional, quantitative study aimed to characterize direct treatment costs and impacts on annual earnings among individuals living with podoconiosis. Participants from two highly endemic districts were invited to complete a survey focused on health-seeking history, insurance status, out-of-pocket costs and income changes. Direct treatment costs included medical expenditures (consultation, diagnostics, medication) and non-medical expenditures (food, transportation, accommodation).

Results
Overall, 226 adults (≥18 y of age) diagnosed with podoconiosis participated. Most had access to community-based health insurance (91.6%) but were unable to work (71.7%). Respondents sought care from health centres/posts (61.9%), hospitals (25.1%), traditional healers (5.8%) and/or community health workers (4.0%). On average, study participants paid US$32.50 (range US$0–779.23) annually, or 11.7% of their household salary, on podoconiosis treatments.

Conclusions
This study demonstrates the significant financial burden of podoconiosis on individuals and their communities. Increased attention on integrating podoconiosis management into primary care systems and testing cost-effective solutions is needed to protect those who are most vulnerable.
Bone Quality in Spinal Surgery: Evaluation, Implications, and Treatments
Authors: Raad Micheal , Satin Alexander , Derman Peter B. 
Published: March 2024

AbstractBone mineral density (BMD) is generally defined as the concentration or density of bone minerals in bone tissue. It is an indicator of bone quality and is used in the diagnosis of osteopenia or osteoporosis. Poor bone quality has been demonstrated to be associated with significantly higher risk of fragility fractures including those of the hip, distal radius, and spine. It is important for spinal surgeons to understand the implications of BMD on outcomes after spinal surgery, learn the various methods to evaluate it, and be aware of treatment options in the perioperative period.
“Block and lock” viral integration sites in persons with drug-free control of HIV-1 infection
Authors: Bone Benjamin , Lichterfeld Mathias 
Published: March 2024

Purpose of review
Elite controllers (ECs) and Posttreatment controllers (PTCs) represent a small subset of individuals who are capable of maintaining drug-free control of HIV plasma viral loads despite the persistence of a replication-competent viral reservoir. This review aims to curate recent experimental studies evaluating viral reservoirs that distinguish EC/PTC and may contribute to their ability to maintain undetectable viral loads in the absence of antiretroviral therapy.

Recent findings
Recent studies on ECs have demonstrated that integration sites of intact proviruses in EC/PTC are markedly biased towards heterochromatin regions; in contrast, intact proviruses in accessible and permissive chromatin were profoundly underrepresented. Of note, no such biases were noted when CD4+ T cells from EC were infected directly ex vivo, suggesting that the viral reservoir profile in EC is not related to altered integration site preferences during acute infection, but instead represents the result of immune-mediated selection mechanisms that can eliminate proviruses in transcriptionally-active euchromatin regions while promoting preferential persistence of intact proviruses in nonpermissive genome regions. Proviral transcription in such “blocked and locked” regions may be restricted through epigenetic mechanisms, protecting them from immune-recognition but presumably limiting their ability to drive viral rebound. While the exact immune mechanisms driving this selection process remain undefined, recent single-cell analytic approaches support the hypothesis that HIV reservoir cells are subject to immune selection pressure by host factors.

Summary
A “blocked and locked” viral reservoir profile may constitute a structural virological correlate of a functional cure of HIV-1 infection. Further research into the immunological mechanism promoting HIV-1 reservoir selection and evolution in EC/PTC is warranted and could inform foreseeable cure strategies.
Strategies to target the central nervous system HIV reservoir
Authors: Mastrangelo Andrea , Gama Lucio , Cinque Paola 
Published: March 2024

Purpose of the review
The central nervous system (CNS) is an hotspot for HIV persistence and may be a major obstacle to overcome for curative strategies. The peculiar anatomical, tissular and cellular characteristics of the HIV reservoir in the CNS may need to be specifically addressed to achieve a long-term HIV control without ART. In this review, we will discuss the critical challenges that currently explored curative strategies may face in crossing the blood–brain barrier (BBB), targeting latent HIV in brain-resident myeloid reservoirs, and eliminating the virus without eliciting dangerous neurological adverse events.

Recent findings
Latency reversing agents (LRA), broadly neutralizing monoclonal antibodies (bNabs), chimeric antigen receptor (CAR) T-cells, and adeno-associated virus 9-vectored gene-therapies cross the BBB with varying efficiency. Although brain penetration is poor for bNAbs, viral vectors for in vivo gene-editing, certain LRAs, and CAR T-cells may reach the cerebral compartment more efficiently. All these approaches, however, may encounter difficulties in eliminating HIV-infected perivascular macrophages and microglia. Safety, including local neurological adverse effects, may also be a concern, especially if high doses are required to achieve optimal brain penetration and efficient brain cell targeting.

Summary
Targeting the CNS remains a potential problem for the currently investigated HIV curing strategies. In vivo evidence on CNS effectiveness is limited for most of the investigated strategies, and additional studies should be focused on evaluating the interplay between the cerebral HIV reservoir and treatment aiming to achieve an ART-free cure.
Harnessing natural killer cells to target HIV-1 persistence
Authors: Joshi Vinita R. , Altfeld Marcus 
Published: March 2024

Purpose of review
The purpose of this article is to review recent advances in the role of natural killer (NK) cells in approaches aimed at reducing the latent HIV-1 reservoir.

Recent findings
Multiple approaches to eliminate cells harboring latent HIV-1 are being explored, but have been met with limited success so far. Recent studies have highlighted the role of NK cells and their potential in HIV-1 cure efforts. Anti-HIV-1 NK cell function can be optimized by enhancing NK cell activation, antibody dependent cellular cytotoxicity, reversing inhibition of NK cells as well as by employing immunotherapeutic complexes to enable HIV-1 specificity of NK cells. While NK cells alone do not eliminate the HIV-1 reservoir, boosting NK cell function might complement other strategies involving T cell and B cell immunity towards an HIV-1 functional cure.

Summary
Numerous studies focusing on targeting latently HIV-1-infected cells have emphasized a potential role of NK cells in these strategies. Our review highlights recent advances in harnessing NK cells in conjunction with latency reversal agents and other immunomodulatory therapeutics to target HIV-1 persistence.
Perineural Inflammation as a Novel Feature in Lichen Sclerosus: A Case Series of Histologic and Clinical Features
Authors: Del Papa Joshua , Pucchio Aine Celestina , Schneider Mark , Wang Ami 
Published: March 2024

Abstract:
Lichen sclerosus (LS) is a frequently encountered inflammatory skin disorder characterized by whitened, atrophic patches that can cause pain and pruritus. The underlying cause of this condition remains unknown. Primarily affecting the genital area, this condition carries an increased risk of developing cutaneous cancers and frequently co-occurs with autoimmune disorders. Our retrospective study aimed to explore histologic features of LS, with a particular focus on a newly established finding and its potential implications. We examined 53 histologic cases of LS collected over 2 years. Experienced pathologists evaluated and reached a consensus on the assignment of histologic features. Patient charts were manually reviewed to gather relevant demographic and clinical data. Statistical analysis was performed using IBM SPSS Statistics (2021). Of the 53 total patients identified as meeting criteria for inclusion in this study, only 8 (15%) were male. Eight cases (15%) demonstrated perineural inflammatory infiltrate. Notably, half of all samples from male patients exhibited perineural inflammatory infiltrate. A statistically significant increase (P < 0.01) in the presence of dermal plasma cells was identified in cases with perineural inflammation versus cases without this feature. The findings of our study highlight the recurrent nature of perineural inflammation in LS, providing valuable insights into this condition. Furthermore, we observed a notable correlation between perineural inflammation, male patients, and the presence of dermal plasma cells. These discoveries contribute to a better understanding of the underlying mechanisms of LS and suggest avenues for future research into the condition.
Comparison of 2 T-Cell Receptor-γ Clonality Assays on Skin Biopsies Suspicious for Mycosis Fungoides
Authors: Miller Stan , Vandergriff Travis , Woodworth Goff Heather , Xu Jing , Oliver Dwight 
Published: March 2024

Abstract:
PCR-based fragment analysis of the T-cell receptor (TCR) gene is used extensively in diagnostic labs to assess clonality in T-cell populations in multiple tissue sites. Of the numerous TCR assays that have been reported, studies assessing use on biopsies suspicious for mycosis fungoides specifically are lacking. We compared clonality findings from a previously run 2-tube/2-fluorochrome dye assay to a redesigned 1-tube/1-fluorochrome dye assay on formalin-fixed skin biopsies. Overall, the accuracy of the 2-tube assay was marginally better (75.7% vs. 71.4%), when using clinical history combined with histologic diagnosis as the gold standard. The 2-tube assay had better sensitivity (73.7% vs. 65.8%), while the 1-tube assay had superior specificity (93.8% vs. 87.5%). Clonality results were easier to interpret with the 1-tube assay. In nearly 19% of cases, a change of assays on the same biopsy resulted in a change of clonality interpretation. For laboratories that change TCR-γ clonality assays, follow-up biopsies for mycosis fungoides assessment may result in a change of diagnosis.
Intraoperative Cardiac Arrest During Liposuction: A Case Report
Authors: Shu Lu , Zhou Jian , He Xue 
Published: March 2024

Background:With the popularity of liposuction surgery, more awareness should be obtained regarding complications. Liposuction has been thought of as a safe procedure with a very low incidence of major complications. However, life-threatening risks of liposuction have rarely been reported.Methods:We present a case of a 36-year-old woman who developed cardiac arrest during a liposuction procedure, and we present a literature review.Results:She was previously healthy and had no risk factors for pulmonary embolism. The diagnosis was made based on clinical presentation and the presence of an electrolyte disorder and a positive sign on computed tomography pulmonary angiogram (CTPA). Mild hypothermia treatment, symptomatic treatment, and supportive therapy were applied. As the respiratory and circulation were smooth, she was discharged to a rehabilitation hospital. Seven months after discharge, the patient was still in a coma with eye opening.Conclusions:Spinal anesthesia, pulmonary embolism, and hyperkalemia are the most probable contributors to the cardiac arrest observed during the liposuction procedure in this specific case. There is a heightened imperative to vigilantly monitor for critical incidents during these operations and to meticulously identify associated risk factors during liposuction.
Outcomes of Residency Education: Insights Into the Professional Formation of the Physical Therapist Resident
Authors: Peterson Julie A. , Black Lisa , Christensen Nicole , Hartley Gregory W. , Jensen Gail M. 
Published: March 2024

Introduction.
The definition of excellence in physical therapy (PT) education is evolving, yet the role of postprofessional residency education remains uncertain. Arguments in favor of required residency have emerged through the re-visioning of PT education across the continuum. Yet, little evidence exists whether residency education further develops clinical skills, clinical knowledge, and clinical reasoning abilities.

Review of Literature.
Previous studies have explored the development of the novice physical therapist in the first 2 years of practice; however, there is little evidence about the outcomes of PT residency education. Thus, this study looked to explore the development of learners through their residency education and to identify the critical elements of the teaching and learning environment in residency education.

Subjects.
Eleven PT residency programs and 13 residents participated in a qualitative study to explore the learner development through residency. Each residency program consisted of a residency program director, one or more mentors identified by the residency program director, and at least one physical therapist resident. Semistructured interviews were conducted with program participants, and journal entries were collected from residents.

Methods.
Using a purposeful sample of convenience, an exploratory, multiple-site/specialty area qualitative case study design was conducted.

Results.
Three emerging themes were identified including growth of self, becoming a member of the community of practice, and facilitation of learning through mentoring. Through the transformative journey of residency education, there are critical elements of the learning environment supporting deep learning within the community of practice. These elements include the provision of opportunities and adequate time and space for learning to occur.

Discussion and Conclusion.
The intentional design of the community of practice through residency education facilitates the development of the novice clinician to experienced clinician in an accelerated period of time. In addition, residency graduates develop characteristics similar to adaptive learners through planned teaching and learning opportunities. Finally, the structure of residency education mattered to the resident participants such that the learning environment enhanced peer learning and the development of professional relationships.
A Deep Learning Application of Capsule Endoscopic Gastric Structure Recognition Based on a Transformer Model
Authors: Li Qingyuan , Xie Weijie , Wang Yusi , Qin Kaiwen , Huang Mei , Liu Tianbao , Chen Zefeiyun , Chen Lu , Teng Lan , Fang Yuxin , Ye Liuhua , Chen Zhenyu , Zhang Jie , Li Aimin , Yang Wei , Liu Side 
Published: March 2024

Background:
Gastric structure recognition systems have become increasingly necessary for the accurate diagnosis of gastric lesions in capsule endoscopy. Deep learning, especially using transformer models, has shown great potential in the recognition of gastrointestinal (GI) images according to self-attention. This study aims to establish an identification model of capsule endoscopy gastric structures to improve the clinical applicability of deep learning to endoscopic image recognition.

Methods:
A total of 3343 wireless capsule endoscopy videos collected at Nanfang Hospital between 2011 and 2021 were used for unsupervised pretraining, while 2433 were for training and 118 were for validation. Fifteen upper GI structures were selected for quantifying the examination quality. We also conducted a comparison of the classification performance between the artificial intelligence model and endoscopists by the accuracy, sensitivity, specificity, and positive and negative predictive values.

Results:
The transformer-based AI model reached a relatively high level of diagnostic accuracy in gastric structure recognition. Regarding the performance of identifying 15 upper GI structures, the AI model achieved a macroaverage accuracy of 99.6% (95% CI: 99.5-99.7), a macroaverage sensitivity of 96.4% (95% CI: 95.3-97.5), and a macroaverage specificity of 99.8% (95% CI: 99.7-99.9) and achieved a high level of interobserver agreement with endoscopists.

Conclusions:
The transformer-based AI model can accurately evaluate the gastric structure information of capsule endoscopy with the same performance as that of endoscopists, which will provide tremendous help for doctors in making a diagnosis from a large number of images and improve the efficiency of examination.
Coxsackie B virus-induced myocarditis in a patient with a history of lymphoma: A case report and review of literature
Authors: Zhang Qian , Yuan Jia , Zhao Wei , Ouyang Weiwei , Chen Bowen , Li Yehong , Tao Junling , Chen Xianjun , Li Guangsu , Guo Zhendong , Liu Ying 
Published: March 2024

Introduction:
In rare occasions, coxsackievirus infections can cause serious illness, such as encephalitis and myocarditis. The immunotherapies of cancer could increase the risk of myocarditis, especially when applying immune checkpoint inhibitors. Herein, we report a rare case of Coxsackie B virus-induced myocarditis in a patient with a history of lymphoma.

Case presentation:
A 32-year-old woman was admitted to the hospital with recurrent fever for more than 20 days, and she had a history of lymphoma. Before admission, the positron emission tomography/computed tomography result indicated that the patient had no tumor progression, and she was not considered the cancer-related fever upon arriving at our hospital. Patient’s red blood cell, platelet count, and blood pressure were decreased. In addition, she had sinus bradycardia and 3 branch blocks, which was consistent with acute high lateral and anterior wall myocardial infarction. During hospitalization, the patient had recurrent arrhythmia, repeated sweating, poor mentation, dyspnea, and Coxsackie B virus were detected in patient’s blood samples by pathogen-targeted next-generation sequencing. The creatine kinase, creatine kinase MB, and N-terminal pro-brain natriuretic peptide were persistently elevated. Consequently, the patient was diagnosed with viral myocarditis induced by Coxsackie B virus, and treated with acyclovir, gamma globulin combined with methylprednisolone shock therapy, trimetazidine, levosimendan, sildenan, continuous pump pressors with m-hydroxylamine, entecavir, adefovir, glutathione, pantoprazole, and low-molecular-weight heparin. Her symptoms worsened and died.

Conclusion:
We reported a case with a history of lymphoma presented with fever, myocardial injury, who was ultimately diagnosed with Coxsackie B virus-induced myocarditis. Moreover, pathogen-targeted next-generation sequencing indeed exhibited higher sensitivity compared to mNGS in detecting Coxsackie B virus.