Altered chromatin landscape and 3D interactions associated with primary constitutional MLH1 epimutations.

Background: Lynch syndrome (LS), characterised by an increased risk for cancer, is mainly caused by germline pathogenic variants affecting a mismatch repair gene (MLH1, MSH2, MSH6, PMS2). Occasionally, LS may be caused by constitutional MLH1 epimutation (CME) characterised by soma-wide methylation of one allele of the MLH1 promoter. Most of these are "primary" epimutations, arising de novo without any apparent underlying cis-genetic cause, and are reversible between generations.

Unveiling the molecular profile of a prostate carcinoma: implications for personalized medicine.

Background: Prostate cancer is the most common diagnosed tumor and the fifth cancer related death among men in Europe. Although several genetic alterations such as ERG-TMPRSS2 fusion, MYC amplification, PTEN deletion and mutations in p53 and BRCA2 genes play a key role in the pathogenesis of prostate cancer, specific gene alteration signature that could distinguish indolent from aggressive prostate cancer or may aid in patient stratification for prognosis and/or clinical management of patients with prostate cancer is still missing. Therefore, here, by a multi-omics approach we describe a prostate cancer carrying the fusion of TMPRSS2 with ERG gene and deletion of 16q chromosome arm.

Patient-derived response estimates from zero-passage organoids of luminal breast cancer.

Background: Primary luminal breast cancer cells lose their identity rapidly in standard tissue culture, which is problematic for testing hormone interventions and molecular pathways specific to the luminal subtype. Breast cancer organoids are thought to retain tumor characteristics better, but long-term viability of luminal-subtype cases is a persistent challenge. Our goal was to adapt short-term organoids of luminal breast cancer for parallel testing of genetic and pharmacologic perturbations.

Health checks for autistic adults: study protocol for a cluster randomised controlled trial.

Background: Autistic people commonly have physical and mental health conditions. They also frequently experience barriers to accessing healthcare, contributing to problems identifying and treating health conditions. These factors may lead to increased and earlier morbidity and lower average life expectancy for autistic people.

The efficacy of platelet-rich plasma in ankle disease: a systematic review and meta-analysis.

Objective: Ankle osteoarthritis is a debilitating condition that significantly impairs patients' quality of life. Platelet-rich plasma has emerged as a novel cellular therapy in clinical practice. This study evaluates the clinical efficacy of platelet-rich plasma (PRP) after intervention in ankle disorders, so as to provide strong evidence in support of clinical treatment.

Reassessing the roles of oxidative DNA base lesion 8-oxoGua and repair enzyme OGG1 in tumorigenesis.

ROS cause multiple forms of DNA damage, and among them, 8-oxoguanine (8-oxoGua), an oxidized product of guanine, is one of the most abundant. If left unrepaired, 8-oxoGua may pair with A instead of C, leading to a mutation of G: C to T: A during DNA replication. 8-Oxoguanine DNA glycosylase 1 (OGG1) is a tailored repair enzyme that recognizes 8-oxoGua in DNA duplex and initiates the base excision repair (BER) pathway to remove the lesion and ensure the fidelity of the genome.

Chili pepper consumption and duration of fissure symptoms onset are associated with perianal fistula development among patients with anal fissure: a case-control study.

Background: Perianal fistula is one of the complications of deepened anal fissure. The present case-control study aimed to assess the risk factors of fissure-associated fistulas due to the limited available evidence.

Methods: Patients with fissure-associated fistulas were considered as case, and patients with anal fissure who were undergoing medical treatment without any previous anorectal surgeries were considered as control group.

GRK6 palmitoylation dictates triple-negative breast cancer metastasis via recruiting the β-Arrestin 2/MAPKs/NF-κB signaling axis.

Background: Triple negative breast cancer (TNBC) belongs to the worst prognosis of breast cancer subtype probably because of distant metastasis to other organs, e.g. lungs.

Association of continuous renal replacement therapy downtime with fluid balance gap and clinical outcomes: a retrospective cohort analysis utilizing EHR and machine data.

Background: Fluid balance gap (FBgap-prescribed vs. achieved) is associated with hospital mortality. Downtime is an important quality indicator for the delivery of continuous renal replacement therapy (CRRT).

Si-Wu-Tang improves liver fibrosis by restoring liver sinusoidal endothelial cell functionality and reducing communication with hepatic stellate cells.

Background: Liver fibrosis is a complex reparative process in response to chronic liver injuries, with limited effective therapeutic options available in clinical practice. During liver fibrosis, liver sinusoidal endothelial cells (LSECs) undergo phenotypic changes and also play a role in modulating cellular communications. Si-Wu-Tang (SWT), a traditional Chinese herbal remedy, has been extensively studied for its effectiveness in treating hematological, gynecological and hepatic diseases.

Crosstalk between fat tissue and muscle, brain, liver, and heart in obesity: cellular and molecular perspectives.

A high-fat diet and physical inactivity are key contributors to obesity, predisposing individuals to various chronic diseases, such as cardiovascular disease and diabetes, which involve multiple organs and tissues. To better understand the role of multi-organ interaction mechanisms in the rising incidence of obesity and its associated chronic conditions, treatment and prevention strategies are being extensively investigated. This review examines the signaling mechanisms between different tissues and organs, with a particular focus on the crosstalk between adipose tissue and the muscle, brain, liver, and heart, and potentially offers new strategies for the treatment and management of obesity and its complications.

Talent management intervention towards performance outcomes of Jordanian telecommunication companies: mediating role of perceived organizational support.

Background: Grounding on the Resource-Based View (RBV) and organization support theory (OST), this study examines the effect of talent management practice (TMP) on perceived organizational support (POS), organizational performance (OP), and employee performance (EP) within the Jordanian telecom sector, with a specific focus on the mediating effect of POS's between TMP-EP and OP relationship.

Methods: This study uses a cross-sectional method to collect data from 397 personnel at three Jordanian telecom enterprises. The Smart-PLS application assisted with structural equation modeling, which was used to examine the data.

A case of subcutaneous metastatic malignant melanoma of the left medial ankle: a case report and review of literature.

Background: Although rare, melanoma confined to the dermis or subcutaneous tissue without evidence of a primary cutaneous site should provoke consideration of melanoma of unknown primary. This diagnosis carries a favorable prognosis when compared with cutaneous metastatic melanoma. Several hypotheses have been proposed for how melanoma of unknown primary develops, two of which were considered in our patient case: (1) spontaneous regression of the primary tumor following metastasis or (2) the traumatic implantation of ectopic melanocytic cells in other tissues, such as the subcutaneous tissue.

The association of cigarette smoking with the development and progression of diabetic retinopathy: based on cross-sectional survey and mendelian randomization.

Background: The relationship between cigarette smoking and diabetic retinopathy (DR) remains controversial, as existing studies have yielded inconsistent results. This study aimed to investigate the association between smoking and both the development and progression of DR.

Methods: This study encompassed two complementary approaches.

"It's a delicate balance": clinicians' experiences of providing heroin-assisted treatment.

Background: Little attention has been paid to the experiences of clinicians and health personnel who provide heroin-assisted treatment (HAT). This study provides the first empirical findings about the clinicians' experiences of providing HAT in the Norwegian context.

Methods: 23 qualitative interviews were conducted with 31 clinicians shortly after HAT clinics opened in Norway's two largest cities: Oslo and Bergen.

Application of additive manufacturing TaBw01 porous tantalum rod in ARCO stage II osteonecrosis of the femoral head.

Purpose: This study aims to investigate the suitable surgical strategies for applying TaBw01 porous tantalum rod across different stages of osteonecrosis of the femoral head (ONFH).

Methods: TaBw01 tantalum rods were fabricated using type FTaY-1 tantalum powder via the foam impregnation-sintering method. Mechanical testing with the Instron 8801 universal testing machine and finite element analysis (FEA) assessed single tantalum rod implantation and impaction bone grafting combined with rod implantation.

Prediction of Ki-67 expression in gastric gastrointestinal stromal tumors using histogram analysis of monochromatic and iodine images derived from spectral CT.

Purpose: To assess and compare the diagnostic efficiency of histogram analysis of monochromatic and iodine images derived from spectral CT in predicting Ki-67 expression in gastric gastrointestinal stromal tumors (gGIST).

Methods: Sixty-five patients with gGIST who underwent spectral CT were divided into a low-level Ki-67 expression group (LEG, Ki-67 < 10%, n = 33) and a high-level Ki-67 expression group (HEG, Ki-67 ≥ 10%, n = 32). Conventional CT features were extracted and compared.

Reoperation for chronological complete dislodgement of the bioprosthetic aortic valve into the left ventricle due to Takayasu arteritis.

Background: Takayasu arteritis is a large-vessel vasculitis, in addition to giant cell arteritis. Various post-operative complications associated with the cardiac macrovasculature have been reported. Detachment of the prosthetic valve, pseudoaneurysm formation, and dilatation of the aortic root are well-known post-operative complications associated with vasculitis syndromes, including Takayasu arteritis.

Efficacy of uterine flushing with human chorionic gonadotropin (hCG) on pregnancy rates in primary unexplained infertility: a randomized controlled trial.

Background: There are limited and controversial findings concerning ovulation induction using intrauterine and intramuscular human chorionic gonadotropin (hCG) injection compared to intramuscular hCG alone. The study aimed to examine the impact of intrauterine hCG injection, which is used to induce ovulation, on the efficacy of the intrauterine insemination (IUI) technique in patients with unexplained infertility.

Methods: A randomized controlled clinical trial was conducted involving 80 subjects with unexplained primary infertility at the infertility clinic of Al-Zahra Hospital in northwest Iran.

Gut microbial 'TNFα-sphingolipids-steroid hormones' axis in children with autism spectrum disorder: an insight from meta-omics analysis.

Background: Autism spectrum disorder (ASD) is a persistent neurodevelopmental disorder affecting brains of children. Mounting evidences support the associations between gut microbial dysbiosis and ASD, whereas detailed mechanisms are still obscure.

Methods: Here we probed the potential roles of gut microbiome in ASD using fecal metagenomics and metabolomics.

The predictive value of endplate morphology and pedicle screw bone quality score on screw loosening after single-level lumbar spinal fusion surgery.

Objective: This study aims to explore the predictive value of endplate morphology and pedicle screw bone quality score on screw loosening after single-level lumbar spinal fusion surgery.

Methods: A retrospective analysis was conducted on the clinical data of 207 patients who underwent single-level lumbar spinal fusion (34 in the screw loosening group and 173 in the non-screw loosening group). Univariate analysis and binary logistic regression model analysis were performed using SPSS 27.

Interpretation and classification of FBN1 variants associated with Marfan syndrome: consensus recommendations from the Clinical Genome Resource's FBN1 variant curation expert panel.

Background: In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) developed standardized variant curation guidelines for Mendelian disorders. Although these guidelines have been widely adopted, they are not gene- or disease-specific. To mitigate classification discrepancies, the Clinical Genome Resource FBN1 variant curation expert panel (VCEP) was established in 2018 to develop adaptations to the ACMG/AMP criteria for FBN1 in association with Marfan syndrome.

Assessment of the efficacy of palliative sedation in advanced cancer patients by evaluating discomfort levels: a prospective, international, multicenter observational study.

Background: Palliative sedation involves the intentional proportional lowering of the level of consciousness in patients with life-limiting disease who are experiencing refractory suffering. The efficacy of palliative sedation needs to be monitored to ensure patient comfort. The aim of this study was to evaluate the efficacy using discomfort levels combined with sedation/agitation levels.