An approach to determine the net predictive multivariate association pattern between cardiorespiratory fitness and a high-resolution physical activity spectrum in the presence of multicollinear covariates.

Multivariate pattern analysis was recently extended with covariate projections to solve the challenging task of modelling and interpreting associations in the presence of linear dependent multivariate covariates. Within a joint model, this approach allows quantification of the net association pattern between the outcome and the explanatory variables and between the individual covariates and these variables. The aim of this paper is to apply this methodology to establish the net multivariate association pattern between cardiorespiratory fitness (CRF) and a high-resolution linear dependent physical activity (PA) intensity descriptor derived from accelerometry in children and to validate the crucial sub-regions in the PA spectrum predicting CRF.

Validating a clinically based MS-MLPA threshold through comparison with Sanger sequencing in glioblastoma patients.

Background: Glioblastoma is the commonest malignant brain tumor and has a very poor prognosis. Reduced expression of the MGMT gene (10q26.3), influenced primarily by the methylation of two differentially methylated regions (DMR1 and DMR2), is associated with a good response to temozolomide treatment.

N7-methylguanosine modification in cancers: from mechanisms to therapeutic potential.

N7-methylguanosine (m7G) is an important RNA modification involved in epigenetic regulation that is commonly observed in both prokaryotic and eukaryotic organisms. Their influence on the synthesis and processing of messenger RNA, ribosomal RNA, and transfer RNA allows m7G modifications to affect diverse cellular, physiological, and pathological processes. m7G modifications are pivotal in human diseases, particularly cancer progression.

Gardnerella vaginalis-binding IgA in the urethra of sexually experienced males.

Background: Genital inflammation increases HIV susceptibility and is associated with the density of pro-inflammatory anaerobes in the vagina and coronal sulcus. The penile urethra is a critical site of HIV acquisition, although correlates of urethral HIV acquisition are largely unknown. While Streptococcus mitis is a consistent component of the urethral flora, the presence of Gardnerella vaginalis has been linked with prior penile-vaginal sex and urethral inflammation.

Understanding retinal tau pathology through functional 2D and 3D iPSC-derived in vitro retinal models.

The generation of retinal models from human induced pluripotent stem cells holds significant potential for advancing our understanding of retinal development, neurodegeneration, and the in vitro modeling of neurodegenerative disorders. The retina, as an accessible part of the central nervous system, offers a unique window into these processes, making it invaluable for both study and early diagnosis. This study investigates the impact of the Frontotemporal Dementia-linked IVS 10 + 16 MAPT mutation on retinal development and function using 2D and 3D retinal models derived from human induced pluripotent stem cells.

λ-cyhalothrin induced sex-specific inflammation, glia activation and GABAergic interneuron disruption in the hippocampus of rats.

Background: Glia mediated neuroinflammation and degeneration of inhibitory GABAergic interneurons are some of the hall marks of pyrethroid neurotoxicity. Here we investigated the sex specific responses of inflammatory cytokines, microglia, astrocyte and parvalbumin positive inhibitory GABAergic interneurons to λ-cyhalothrin (LCT) exposures in rats.

Methods: Equal numbers of male and female rats were given oral corn oil, 2 mg/kg.

Molecular and cellular characteristics of cerebrovascular cell types and their contribution to neurodegenerative diseases.

Many diseases and disorders of the nervous system suffer from a lack of adequate therapeutics to halt or slow disease progression, and to this day, no cure exists for any of the fatal neurodegenerative diseases. In part this is due to the incredible diversity of cell types that comprise the brain, knowledge gaps in understanding basic mechanisms of disease, as well as a lack of reliable strategies for delivering new therapeutic modalities to affected areas. With the advent of single cell genomics, it is now possible to interrogate the molecular characteristics of diverse cell populations and their alterations in diseased states.

Diagnostic utility of LEF1 and β-catenin in WNT pathway tumors with CTNNB1 mutation.

Objective: This study aimed to compare the expression of lymphoid enhancer factor 1 (LEF1) and β-catenin in basal cell adenoma (BA), desmoid-type fibromatosis (DF), and pancreatic solid pseudopapillary neoplasm (SPN) to evaluate their diagnostic utility in tumors associated with the WNT/β-catenin signaling pathway harboring the mutation of CTNNB1 gene 3 exon.

Methods: Eighty tumor patients, including 26 BAs, 30 DFs, and 24 SPNs, were analyzed. Immunohistochemical staining was identified positive (nuclear staining of LEF1 and β-catenin in > 50% of tumor cells).

Therapeutic exercise protocol for the prevention of anterior cruciate ligament injuries in female soccer players with dynamic knee valgus (RCT).

Background: Women's football has experienced exponential growth over the last 10 years. Its popularity is associated with an increase in ACL injuries. They constitute a major current problem as they account for 43% of the injury burden during the sports season.

Epidermal stem cell derived exosomes-induced dedifferentiation of myofibroblasts inhibits scarring via the miR-203a-3p/PIK3CA axis.

Hypertrophic scar (HS) is a common fibroproliferative disorders with no fully effective treatments. The conversion of fibroblasts to myofibroblasts is known to play a critical role in HS formation, making it essential to identify molecules that promote myofibroblast dedifferentiation and to elucidate their underlying mechanisms. In this study, we used comparative transcriptomics and single-cell sequencing to identify key molecules and pathways that mediate fibrosis and myofibroblast transdifferentiation.

Assessing the disconnect between student interest and education in artificial intelligence in medicine in Saudi Arabia.

Background: Although artificial intelligence (AI) has gained increasing attention for its potential future impact on clinical practice, medical education has struggled to stay ahead of the developing technology. The question of whether medical education is fully preparing trainees to adapt to potential changes from AI technology in clinical practice remains unanswered, and the influence of AI on medical students' career preferences remains unclear. Understanding the gap between students' interest in and knowledge of AI may help inform the medical curriculum structure.

Evaluation of undergraduate forensic medicine education in Nepal: a critical analysis using Schwab's five commonplaces and Schubert's curriculum images.

Following the establishment of Nepal's first medical college in 1972, forensic medicine was introduced in 1978. To date, 25 medical colleges in the country have included forensic medicine as a compulsory subject in the undergraduate medical curriculum. Although this subject has been introduced into the medical curriculum, the outcome is unsatisfactory, as reflected by the poor medico-legal reports prepared by newly graduated medical students.

Comparative evaluation of calretinin immunohistochemical expression in calcifying odontogenic cyst and ameloblastoma.

Background: Calretinin is a 29 kilodalton (KDa) calcium-binding protein that is expressed in normal and tumoral tissues. The expression of calretinin has been shown in the dental epithelium during odontogenesis and in different odontogenic cysts and tumors such as ameloblastoma. Since the epithelium of calcifying odontogenic cyst (COC) is similar to ameloblastoma and in both lesions, an arrangement of loose cells similar to stellate reticulum is seen, we aimed to investigate the comparative expression of calretinin in COC and ameloblastoma.

Primary extraskeletal osteosarcoma of rectal mesentery: a rare case and literature review.

Background: Extraskeletal osteosarcoma (ESOS) is a rare kind of sarcoma with a low preoperative diagnosis and a poor prognosis. ESOS arising from abdominal mesentery is extremely rare. Increasing diagnostic methods and standardizing treatment protocols are crucial issues of ESOS.

The histone demethylase KDM5C enhances the sensitivity of acute myeloid leukemia cells to lenalidomide by stabilizing cereblon.

Background: The protein cereblon (CRBN) mediates the antileukemia effect of lenalidomide (Len). Len binds to CRBN, recruits IKZF1/IKZF3, and promotes their ubiquitination and degradation, through which Len exhibits its antileukemia and antimyeloma activity. Therefore, the protein level of CRBN might affect the antiproliferative effect of Len.

Cecropin AD ameliorates pneumonia and intestinal injury in mice with mycoplasma pneumoniae by mediating gut microbiota.

Animals infected with mycoplasma pneumoniae not only develop respiratory diseases, but also cause digestive diseases through the lung-gut axis mediated by the intestinal flora, and vice versa. Antimicrobial peptides are characterized by their bactericidal, anti-inflammatory, and intestinal flora-regulating properties. However, the effect of cecropin AD (CAD) against mycoplasma pneumonia remains unclear.

Vitamin D3/VDR alleviates double-stranded RNA virus -induced biliary epithelial cell damage by inhibiting autophagy.

Background: The increased apoptosis of bile duct epithelial cells (BECs) due to some damage factors is considered the initiating factor in the occurrence and progression of biliary atresia (BA). Vitamin D receptor (VDR) is thought to play a crucial role in maintaining the intrinsic immune balance and integrity of bile duct epithelial cells (BECs). To investigate the role of VDRs in the pathogenesis and progression of BA using in vitro and in vivo models.

Influence of the metabolic control in patients with type 1 diabetes on their oral health status and the need for orthodontic treatment in a group of Spanish children (aged 6-12 years): a cross-sectional study.

Background: The aim of this study was to analyze the influence of good metabolic control, based on glycosylated hemoglobin (HbA1c) levels, on oral health status and the need for orthodontic treatment in children.

Methods: This cross-sectional study was carried out at the Dental Clinic of the University of Salamanca (Spain) during the years 2020 and 2024. A total of 260 children with type 1 diabetes (aged between 6 and 12 years) participated.

Associations between sedentary behaviour and sarcopenia among patients aged 40 and older with chronic obstructive pulmonary disease: a cross-sectional study.

Background: Patients with chronic obstructive pulmonary disease (COPD) and sarcopenia experience poorer clinical prognosis. Although sedentary behaviour (SB) is common risk factor for COPD, its relationship with sarcopenia in this specific population remains unclear.

Methods: This is a cross-sectional survey of participants aged 40 and above with COPD, involving 27 communities and 2 hospitals' outpatient departments.

Tegaserod maleate exerts anti-tumor effects on prostate cancer via repressing sonic hedgehog signaling pathway.

Prostate cancer (PCa) is a highly common type of malignancy and affects millions of men in the world since it is easy to recur or emerge therapy resistance. Therefore, it is urgent to find novel treatments for PCa patients. In the current study, we found that tegaserod maleate (TM), an FDA-approved agent, inhibited proliferation, colony formation, migration as well as invasion, caused the arrest of the cell cycle, and promoted apoptosis of PCa cells in vitro.

Ectopic thyroid tissue in the airway: a case report.

Background: Ectopic thyroid tissue (ETT) is a rare congenital anomaly caused by the abnormal embryonic migration of thyroid tissue, leading to its presence outside its usual pretracheal location. This condition can lead to diagnostic challenges, especially when located within the airway, as it mimics other respiratory disorders such as asthma.

Case Presentation: We report the case of a 69-year-old man with endotracheal ETT presenting with severe dyspnea, and the lesion was initially suspected to be malignant.

Silent witnesses: unveiling the epidemic of femicides in North-west Tshwane, South Africa - a decade of analysis.

Background: Femicides, defined as the gender-based killing of women, are a pressing public health issue worldwide, with South Africa experiencing some of the highest rates globally. This study focuses on the North-west region of Tshwane, particularly the Garankuwa area, aiming to address gaps in understanding the epidemiology, demographics, circumstances, and pathology associated with femicides. The Garankuwa mortuary serves as the primary site for this investigation, providing a detailed analysis over a ten-year period, shedding light on contributing risk factors in the context of systemic gender inequality.

An autopsy case with tubular obstruction by impacted swollen blebs due to ischemic acute kidney injury.

Background: Oliguric acute kidney injury (AKI) is one of the critical conditions which needs emergent treatment due to the lack of the capacity of excreting toxins and fluids, and plasma membrane bleb formation is considered as one of the characteristic morphologic alterations in ischemic AKI in both animal models and human. We present here an autopsy case with clear electron microscopy images capturing a definitive instance of blebbing in ischemic AKI.

Case Presentation: A 66-year-old man was admitted for oliguric AKI with nephrotic syndrome (NS).

Solving unknown primary cancer with earlier diagnosis - the SUPER-ED trial: study protocol for a stepped-wedge cluster randomised controlled trial to support earlier diagnosis for people presenting with malignancy of undefined primary origin.

Background: People with malignancy of undefined primary origin (MUO) have a poor prognosis and may undergo a protracted diagnostic workup causing patient distress and high cancer related costs. Not having a primary diagnosis limits timely site-specific treatment and access to precision medicine. There is a need to improve the diagnostic process, and healthcare delivery and support for these patients.

Dioscin pretreatment ameliorates ferroptosis in cardiomyocytes after myocardial infarction via inhibiting endoplasmic reticulum stress.

Background: Myocardial infarction (MI) remains a leading cause of mortality globally, often resulting in irreversible damage to cardiomyocytes. Ferroptosis, a recently identified form of regulated cell death driven by iron-dependent lipid peroxidation, has emerged as a significant contributor to post-MI cardiac injury. The endoplasmic reticulum (ER) stress response has been implicated in exacerbating ferroptosis.