bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

Bone 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.
Experience with pembrolizumab in a renal transplant patient with advanced lung cancer: a case report and review
Authors: Fernández Madrigal Laura , García Samblás Victoria , Sánchez Escudero Laura
Published: March 2024

The treatment of non-small cell lung cancer (NSCLC) has undergone a change because of the advancement of new therapies, like immune checkpoint inhibitors (ICIs), including pembrolizumab. A 64-year-old woman received a kidney transplant in 2012 because of chronic kidney disease secondary to glomerulosclerosis, diagnosed in 2020 with stage IV NSCLC because of metastasis in the contralateral lung, with programmed death ligand 1programmed death ligand 1 expression of 98%, starting treatment with ICIs, despite presenting a graft rejection risk around 40%. After three ICIs cycles, the patient presented a partial response, with good tolerance to treatment and no signs of graft failure. ICIs were maintained for 19 cycles, until disease progression was observed on a reassessment computed tomography, with a progression-free interval of 18 months, with no evidence of treatment rejection. In transplant patients diagnosed with some type of tumor, antineoplastic therapies may be less effective than in the general population. The current evidence derives from observational studies and case series, since this patient population was excluded from clinical trials, suggesting that the use of ICIs in patients with kidney transplants can lead to acute graft rejection. This is still a controversial issue, it is necessary to improve the quality of the data, with the implementation of clinical trials or prospective studies.
Machine Learning–Based Approach to Predict Last-Minute Cancellation of Pediatric Day Surgeries
Authors: Li Canping , Li Zheming , Huang Shoujiang , Chen Xiyan , Zhang Tingting , Zhu Jihua
Published: March 2024

The last-minute cancellation of surgeries profoundly affects patients and their families. This research aimed to forecast these cancellations using EMR data and meteorological conditions at the time of the appointment, using a machine learning approach. We retrospectively gathered medical data from 13 440 pediatric patients slated for surgery from 2018 to 2021. Following data preprocessing, we utilized random forests, logistic regression, linear support vector machines, gradient boosting trees, and extreme gradient boosting trees to predict these abrupt cancellations. The efficacy of these models was assessed through performance metrics. The analysis revealed that key factors influencing last-minute cancellations included the impact of the coronavirus disease 2019 pandemic, average wind speed, average rainfall, preanesthetic assessments, and patient age. The extreme gradient boosting algorithm outperformed other models in predicting cancellations, boasting an area under the curve value of 0.923 and an accuracy of 0.841. This algorithm yielded superior sensitivity (0.840), precision (0.837), and F1 score (0.838) relative to the other models. These insights underscore the potential of machine learning, informed by EMRs and meteorological data, in forecasting last-minute surgical cancellations. The extreme gradient boosting algorithm holds promise for clinical deployment to curtail healthcare expenses and avert adverse patient-family experiences.
A Microlearning-Based Self-directed Learning Chatbot on Medication Administration for New Nurses
Authors: Kim Ae Ran , Park Ae Young , Song Soojin , Hong Jeong Hee , Kim Kyeongsug
Published: March 2024

New nurses must acquire accurate knowledge of medication administration, as it directly affects patient safety. This study aimed to develop a microlearning-based self-directed learning chatbot on medication administration for novice nurses. Furthermore, the study had the objective of evaluating the chatbot feasibility. The chatbot covered two main topics: medication administration processes and drug-specific management, along with 21 subtopics. Fifty-eight newly hired nurses on standby were asked to use the chatbot over a 2-week period. Moreover, we evaluated the chatbot's feasibility through a survey that gauged changes in their confidence in medication administration knowledge, intrinsic learning motivation, satisfaction with the chatbot's learning content, and usability. After using the chatbot, participants' confidence in medication administration knowledge significantly improved in all topics (P < .001) except “Understanding a concept of 5Right” (P = .077). Their intrinsic learning motivation, satisfaction with the learning content, and usability scored above 5 out of 7 in all subdomains, except for pressure/tension (mean, 2.12; median, 1.90). They scored highest on ease of learning (mean, 6.69; median, 7.00). A microlearning-based chatbot can help new nurses improve their knowledge of medication administration through self-directed learning.
“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.

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.

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.

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

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

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.
Machine learning-based cell death signature for predicting the prognosis and immunotherapy benefit in stomach adenocarcinoma
Authors: Li Fan , Feng Qian , Tao Ran
Published: March 2024

Stomach adenocarcinoma (STAD) is a one of most common malignancies with high mortality-to-incidence ratio. Programmed cell death (PCD) exerts vital functions in the progression of cancer. The role of PCD-related genes (PRGs) in STAD are not fully clarified. Using TCGA, GSE15459, GSE26253, GSE62254 and GSE84437 datasets, PCD-related signature (PRS) was constructed with an integrative procedure including 10 machine learning methods. The role of PRS in predicting the immunotherapy benefits was evaluated by several predicting score and 3 immunotherapy datasets (GSE91061, GSE78220, and IMvigor210). The model developed by Lasso + CoxBoost algorithm having a highest average C-index of 0.66 was considered as the optimal PRS. As an independent risk factor for STAD patients, PRS had a good performance in predicting the overall survival rate of patients, with an AUC of 1-, 3-, and 5-year ROC curve being 0.771, 0.751 and 0.827 in TCGA cohort. High PRS score demonstrated a lower gene set score of some immune-activated cells and immune-activated activities. Patient with high PRS score had a higher TIDE score, higher immune escape score, lower PD1&CTLA4 immunophenoscore, lower TMB score, lower response rate and poor prognosis, indicating a less immunotherapy response. The IC50 value of some drugs correlated with chemotherapy and targeted therapy was higher in high PRS score group. Our investigation developed an optimal PRS in STAD and it acted as an indicator for predicting the prognosis, stratifying risk and guiding treatment for STAD patients.
A case control study of vNOTES hysterectomy with the da Vinci surgical system and conventional vNOTES hysterectomy
Authors: Zhang Chengling , Liu Dandan , Zhang Qiang , Li Qiaoqiao , He Li , Lin Yonghong , Ge Huisheng
Published: March 2024

The aim of the case control study was to compare surgical outcomes of transvaginal natural orifice transluminal endoscopic surgery (vNOTES) hysterectomy with the da Vinci surgical system (dVSS) and conventional vNOTES. A case control study was performed on 25 cases in our hospital. Patients (n = 8) who underwent vNOTES hysterectomy with dVSS were selected to compare with the control group (n = 17) consisted of patients who underwent conventional vNOTES. Patients in the 2 groups underwent different operations respectively, and no case was transferred to transabdominal laparoscopy. In the conventional vNOTES group, 1 patient happened intraoperative hemorrhage of about 1000 mL, and was treated with blood transfusion, and the other one of vNOTES hysterectomy with dVSS had poor incision healing within 1 month after surgery. The other patients had no intraoperative and postoperative complications. The difference of pain scores on the first day (P = .006) and the third day (P = .045) after the 2 surgical methods differed significantly. No statistical differences were observed in operation time, median hospital stay, blood loss, decreased hemoglobin 3 days after surgery, and postoperative white blood cell count. vNOTES hysterectomy with dVSS is safe and feasible, and can achieve the same effect as the conventional vNOTES hysterectomy. And this method may alleviate the pain of patients.
Association of white blood cell parameters with metabolic syndrome: A systematic review and meta-analysis of 168,000 patients
Authors: Mahmood Aysal , Haider Hoorain , Samad Saba , Kumar Danisha , Perwaiz Aimen , Mushtaq Rabeea , Ali Abraish , Farooq Muhammad Zain , Farhat Hadi
Published: March 2024

Background:

Leukocyte parameters are predicted to be affected in patients with metabolic syndrome (MetS). We conducted a systematic review and meta-analysis to study the association between white blood cell parameters (WBC) in people with and without MetS.

Methods:

PubMed, EMBASE, Scopus and Cochrane Library databases were searched according to the study protocol. The standardized mean difference (SMD) and 95% confidence intervals (CI) of leukocyte markers between individuals with and without MetS were pooled using an inverse variance model. Additionally, a subgroup analysis by sex was performed where possible. Methodological quality assessment was conducted using the Newcastle-Ottawa scale (NOS) for observational studies and the Cochrane Risk of Bias tool 2.0 for Randomized Controlled Trials (RCTs).

Results:

Of 6068 articles identified, 63 were eligible for the study. Compared to controls, individuals with MetS showed significantly higher concentrations of total leukocyte count (SMD [95% CI]: 0.60 [0.55–0.65]; P < .00001; I
2 = 100%), neutrophil counts (0.32 [0.28–0.37]; P < .00001; I
2 = 99%), lymphocyte counts (0.15 [0.07–0.23]; P = .0004; I
2 = 100%), basophil counts (0.01 [0.00–0.02]; P = .02; I
2 = 98%), monocyte counts (0.05 [0.02–0.09]; P = .003; I
2 = 99%), and neutrophil-to-lymphocyte ratio (0.24 [0.15–0.33]; P < .00001; I
2 = 98%). There were no significant differences in the eosinophil count (0.02 [−0.01 to 0.05]; P = .19; I
2 = 96%) and monocyte-to-lymphocyte ratio (0.06 [−0.05 to 0.17]; P = .27; I
2 = 100%) between patients with and without MetS, however, the lymphocyte-to-monocyte ratio (0.52 [−0.81 to −0.23]; P = .0005; I
2 = 52%) tended to be significantly lower in patients with MetS.

Conclusion:

Biomarkers such as total leukocyte count, neutrophil count, lymphocyte count, basophil count, monocyte count and neutrophil-to-lymphocyte ratio are associated with higher levels in patients in MetS and thus can potentially be used for early detection of MetS.
Chronological change of left ventricular global longitudinal strain in patients with maternally inherited diabetes and deafness: A case series
Authors: Seo Jeong-Sook
Published: March 2024

Rationale:

Maternally inherited diabetes and deafness (MIDD) is a rare genetic disorder arising from mitochondrial DNA mutations, characterized by a combination of diabetes mellitus and sensorineural deafness. It is known that MIDD patients with cardiomyopathy have a poor prognosis, but there are no established guidelines for the diagnosis and follow-up of cardiomyopathy in MIDD patients.

Patient concerns:

Patient 1 was a 48-year-old woman who visited the hospital with cardiomegaly and had been taking oral hypoglycemic agents for 8 years. Patient 2 was a 21-year-old man, the son of patient 1, who visited the hospital for genetic screening. Patient 2 was also diagnosed diabetes mellitus 2 years ago.

Diagnosis:

Patient 1 was found to have restrictive cardiomyopathy on echocardiography and underwent endomyocardial biopsy and genetic testing to determine the etiology. The m.3243A>G mutation was confirmed and she was diagnosed with MIDD accompanied with diabetes and hearing loss. Additionally, patient 2 had m.3243 A>G mutation and was diagnosed with MIDD due to diabetes and hearing loss.

Interventions:

Because MIDD does not have a specific treatment, patient 1 took ubidecarenone (coenzyme Q10), acetylcarnitine, and multivitamin along with the treatment for diabetes control and heart failure. Patient 2 was taking ubidecarenone (coenzyme Q10), acetylcarnitine, and multivitamin along with treatment for diabetes.

Outcomes:

She subsequently underwent routine transthoracic echocardiography, and a progressive decline in global longitudinal strain (GLS) was first observed, followed by a worsening of the patient’s clinical situation. Patient 2 had concentric remodeling and decreased GLS. On periodic echocardiography, GLS decreased at a very slow rate, and the patient’s clinical course was stable.

Lessons:

The findings of this report contribute to the understanding of the clinical course of MIDD-associated cardiomyopathy and highlight the potential of GLS as a sensitive marker for disease progression.
Hepatic hemangiomatosis: a case report from Morocco
Authors: Hamdaoui Yassine , Harouachi Abdelhakim , Kharkhach Ayoub , Bouhout Tariq , Serji Badr
Published: March 2024

Introduction:

Hepatic hemangiomas are benign liver tumors comprising clusters of blood-filled cavities, lined by endothelial cells, and supplied by the hepatic artery. The vast majority of hepatic hemangiomas (HH) are asymptomatic, often discovered incidentally during imaging studies for unrelated pathologies.

Case Report:

We present the clinical case of a 72-year-old patient admitted to our department due to a suspicious mass that emerged in the right hypochondrium a few months earlier. Laboratory studies were within normal limits, and diagnostic findings supported hepatic hemangiomatosis. Therapeutic abstention (with symptomatic treatment and close monitoring) was recommended.

Discussion:

Diffuse hepatic hemangiomatosis (DHH) is rare with an unclear etiology. In many cases, HH are small and asymptomatic at diagnosis with a stable progression. Asymptomatic patients typically undergo bservation with long-term follow-up, and imaging is generally unnecessary for lesions smaller than 5 cm, unless there is rapid growth or diagnostic uncertainty. Surgical resection may be considered for symptomatic patients or those with hemangiomas causing mass effects, after excluding other causes of pain.

Conclusion:

Ensuring an accurate diagnosis of hepatic hemangiomas is essential to differentiate them from other focal hepatic lesions, considering the possibility of coexisting diagnoses. While the majority of cases are asymptomatic and non-progressive, a subset may exhibit rapid growth or complications, requiring specific therapeutic approaches.
Cervical Ganglioneuroma Associated With Neurofibromatosis Type 1
Authors: Wang Chuang , Niu Deying , Zhai Naichi
Published: March 2024

Cervical ganglioneuroma combined with neurofibromatosis type I is very rare. This article reports a case of a 21-year-old male patient with a rare presentation of cervical ganglioneuroma and neurofibromatosis type I. In this patient, the tumors on both sides of the cervical spine were surgically removed with good results. The effects and advantages of surgery when both diseases coexist are discussed, as well as further investigation into possible causal relationships between these two pathologies.
Impact of Hospital Affiliation With a Flagship Hospital System on Surgical Outcomes
Authors: Ramadan Omar I. , Rosenbaum Paul R. , Reiter Joseph G. , Jain Siddharth , Hill Alexander S. , Hashemi Sean , Kelz Rachel R. , Fleisher Lee A. , Silber Jeffrey H.
Published: March 2024

Objective:

To compare general surgery outcomes at flagship systems, flagship hospitals, and flagship hospital affiliates versus matched controls.

Summary Background Data:

It is unknown whether flagship hospitals perform better than flagship hospital affiliates for surgical patients.

Methods:

Using Medicare claims for 2018 to 2019, we matched patients undergoing inpatient general surgery in flagship system hospitals to controls who underwent the same procedure at hospitals outside the system but within the same region. We defined a “flagship hospital” within each region as the major teaching hospital with the highest patient volume that is also part of a hospital system; its system was labeled a “flagship system.” We performed 4 main comparisons: patients treated at any flagship system hospital versus hospitals outside the flagship system; flagship hospitals versus hospitals outside the flagship system; flagship hospital affiliates versus hospitals outside the flagship system; and flagship hospitals versus affiliate hospitals. Our primary outcome was 30-day mortality.

Results:

We formed 32,228 closely matched pairs across 35 regions. Patients at flagship system hospitals (32,228 pairs) had lower 30-day mortality than matched control patients [3.79% vs. 4.36%, difference=−0.57% (−0.86%, −0.28%),P<0.001]. Similarly, patients at flagship hospitals (15,571/32,228 pairs) had lower mortality than control patients. However, patients at flagship hospital affiliates (16,657/32,228 pairs) had similar mortality to matched controls. Flagship hospitals had lower mortality than affiliate hospitals [difference-in-differences=−1.05% (−1.62%, −0.47%),P<0.001].

Conclusions:

Patients treated at flagship hospitals had significantly lower mortality rates than those treated at flagship hospital affiliates. Hence, flagship system affiliation does not alone imply better surgical outcomes.
Can We Predict Kidney Graft Function and Graft Survival Using Hypothermic Machine Perfusion Parameters From Donors After Circulatory Death?
Authors: Offerni Juliano C. M. , Ai Li Erica , Matti Danny , Luke Grant , Luke Patrick P. , Sener Alp
Published: March 2024

Background.

Hypothermic machine perfusion (HMP) reduces renal injury in donation after circulatory death donors with a high Kidney Donor Profile Index (KDPI). This study aims to characterize the correlation between KDPI, HMP parameters, and donor vitals during the withdrawal period in predicting short- and long-term graft outcomes.

Methods.

ANOVA with Tukey’s honestly significant difference tests compared the relationship between average flow, average resistance, peak resistance, flow slope, and resistance slope on day 30, 1-y, and 3-y eGFR, and days of delayed graft function. Graft and recipient survival rates were assessed using Kaplan-Meier analysis.

Results.

The data for 72 grafts were suitable for analysis. Kidneys with KDPI >50% had a significantly higher day 30, and 1-y posttransplant eGFR, if HMP average flow was >150 mL/min, or the average resistance was <0.15 mm Hg/mL/min, compared with kidneys with also KDPI >50% but had not achieved the same pump parameters. There were no significant differences in the Kaplan-Meier analysis, considering recipient or graft survival, regardless of the KPDI score with 3- or 5-y outcomes.

Conclusions.

Use of average resistance and average flow from a HMP, in conjunction with KDPI, may be predictive of the short- and long-term function of donation after circulatory death kidney transplants.
Impact of COVID-19 on the Incidence of Fragility Fracture in South Korea
Authors: Baek Seungjin , Kim Ye-Jee , Kim Beom-Jun , Hong Namki
Published: March 2024

Background: The coronavirus disease 2019 (COVID-19) pandemic and the consequent social distancing period are thought to have influenced the incidence of osteoporotic fracture in various ways, but the exact changes have not yet been well elucidated. The purpose of this study was to investigate the impact of the COVID-19 pandemic on the incidence of osteoporotic fracture using a nationwide cohort.Methods: The monthly incidence rates of vertebral; hip; and non-vertebral, non-hip fractures were collected from a nationwide database of the Korean National Health Insurance Review and Assessment from July 2016 to June 2021. Segmented regression models were used to assess the change in levels and trends in the monthly incidence of osteoporotic fractures.Results: There was a step decrease in the incidence of vertebral fractures for both males (6.181 per 100,000, P=0.002) and females (19.299 per 100,000, P=0.006). However, there was a negative trend in the incidence of hip fracture among both males (-0.023 per 100,000 per month, P=0.023) and females (-0.032 per 100,000 per month, P=0.019). No impact of COVID-19-related social distancing was noted.Conclusions: In conclusion, during the early days of the COVID-19 pandemic, vertebral fracture incidence considerably decreased with the implementation of social distancing measures.
DCAF16-Based Covalent Handle for the Rational Design of Monovalent Degraders
Authors: Lim Melissa , Cong Thang Do , Orr Lauren M. , Toriki Ethan S. , Kile Andrew C. , Papatzimas James W. , Lee Elijah , Nomura Daniel K.
Published: March 2024

Targeted protein degradation with monovalent molecular glue degraders is a powerful therapeutic modality for eliminating disease causing proteins. However, rational design of molecular glue degraders remains challenging. In this study, we sought to identify a transplantable and linker-less covalent handle that could be appended onto the exit vector of various protein-targeting ligands to induce the degradation of their respective targets. Using the BET family inhibitor JQ1 as a testbed, we synthesized and screened a series of covalent JQ1 analogs and identified a vinylsulfonyl piperazine handle that led to the potent and selective degradation of BRD4 in cells. Through chemoproteomic profiling, we identified DCAF16 as the E3 ligase responsible for BRD4 degradation—an E3 ligase substrate receptor that has been previously covalently targeted for molecular glue-based degradation of BRD4. Interestingly, we demonstrated that this covalent handle can be transplanted across a diverse array of protein-targeting ligands spanning many different protein classes to induce the degradation of CDK4, the androgen receptor, BTK, SMARCA2/4, and BCR-ABL/c-ABL. Our study reveals a DCAF16-based covalent degradative and linker-less chemical handle that can be attached to protein-targeting ligands to induce the degradation of several different classes of protein targets.
Genetic susceptibility to acute viral bronchiolitis
Authors: Pasanen Anu , Karjalainen Minna K. ,   FinnGen, Korppi Matti , Hallman Mikko , Rämet Mika
Published: March 2024

Acute viral bronchiolitis is a major cause of infant hospitalizations worldwide. Childhood bronchiolitis is considered a risk factor for asthma, suggesting shared genetic factors and biological pathways. Genetic risk loci may provide new insights into disease pathogenesis. Here, we examined the genetic contributions to bronchiolitis susceptibility by analyzing 1,465 infants hospitalized for bronchiolitis and 356,404 individuals without a history of acute lower respiratory tract infections in the FinnGen project data. Genome-wide analysis identified associations (p<5×10-8) for variants in gasdermin B (GSDMB) and a missense variant in cadherin-related family member 3 (CDHR3). Children with bronchiolitis in infancy were more likely to develop asthma later in life compared to controls. The two associated loci were previously linked to asthma and susceptibility to wheezing illness by other causative agents than RSV. Our analysis discovered associations with overall bronchiolitis, with larger effects in non-RSV than RSV-induced infection. Our results suggest that genetic variants inCDHR3andGSDMBmodulate susceptibility to bronchiolitis, especially when caused by viruses other than RSV, and that severe bronchiolitis in infancy may trigger the development of asthma in genetically susceptible individuals determined by these loci.
WITHDRAWN: Radiation-induced non-neoplastic cells senescence promoting the proliferation and invasiveness of GBM through SASP/JAK2-STAT3 Pathway
Authors: Nie Pan , Chen Jincao , Zhang Jibo
Published: March 2024

Withdrawal statement

The authors have withdrawn their manuscript owing to [The authors have conducted further in-depth research on this study and updated the previous data.]. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Unravelling the effects of individual heterogeneity on connectivity estimates: Insights from Spatial Capture-Recapture modelling
Authors: Kervellec Maëlis , Gimenez O. , Vanpé C. , Quenette P.-Y. , Sentilles J. , Palazón S. , Jordana I. Afonso , Jato R. , Irurtia M. M. Elósegui , Milleret C.
Published: March 2024

Abstract

Spatial Capture-Recapture (SCR) models, parametrized with least cost path distance, provide a unifying framework for explicitly estimating landscape connectivity and population size from individual detection data. However, we frequently encounter individuals with larger apparent space use than the rest of the population. To avoid biased population size estimates, it is common practice to remove these outliers from the analysis. Yet such individuals are likely to be very important when the aim is to estimate connectivity. We therefore investigated how unmodelled individual heterogeneity in space use affects population size and connectivity estimates from SCR models.

We first conducted a simulation study. We varied the proportion of the population whose space use is most constrained by landscape structure. We fit four SCR models, increasing the degree of modelled individual heterogeneity to assess its effect on parameter estimates. Secondly, we applied these models to the Pyrenean brown bear population, examining the effects of removing outliers or modelling explicitly heterogeneity on parameter estimates.

Our simulation study showed that population size was underestimated when no individual heterogeneity was modelled and increased with increasing the level of individual heterogeneity modelled. Moreover, unmodeled individual heterogeneity led to biased connectivity estimates towards the group, which is the most detected. In our case study, modelling individual heterogeneity was key to unravel the patterns in population space use. Female brown bear movements were restricted by road density (estimated resistance:α2= 0.27 [0.01, 0.43]), whereas a small group of males were not affected by road density (α2= - 0.16 [-0.64, 0.24]).

Our study provides valuable insights for optimizing the application of SCR models. When the primary objective is to accurately estimate population size, we recommend removing outlier individuals with larger home range sizes to avoid the risk of underestimating population size. Conversely, when the aim is to assess landscape population-level connectivity, modelling individual heterogeneity is essential. Our findings underscore the importance of tailoring the SCR model to the specific research goal, ensuring more precise and meaningful ecological inferences.