Revisiting the model for coactivator recruitment: Med15 can select its target sites independent of promoter-bound transcription factors.

Activation domains (ADs) within transcription factors (TFs) induce gene expression by recruiting coactivators such as the Mediator complex. Coactivators lack DNA binding domains (DBDs) and are assumed to passively follow their recruiting TFs. This is supported by direct AD-coactivator interactions seen in vitro but has not yet been tested in living cells.

Diagnostic Modalities for Early Detection of Anastomotic Leak After Colorectal Surgery.

Introduction: Anastomotic leak (AL) remains a severe complication following colorectal surgery, leading to increased morbidity and mortality, particularly in cases of delayed diagnosis. Existing diagnostic methods, including computed tomography (CT) scans, contrast enemas, endoscopic examinations, and reoperations can confirm AL but lack strong predictive value. Early detection is crucial for improving patient outcomes, yet a definitive and reliable predictive test, or "gold standard," is still lacking.

Autotrophic growth of is achieved by a small number of genetic changes.

Synthetic autotrophy is a promising avenue to sustainable bioproduction from CO. Here, we use iterative laboratory evolution to generate several distinct autotrophic strains. Utilising this genetic diversity, we identify that just three mutations are sufficient for to grow autotrophically, when introduced alongside non-native energy (formate dehydrogenase) and carbon-fixing (RuBisCO, phosphoribulokinase, carbonic anhydrase) modules.

Genomic Selection Signals in Andean Highlanders Reveal Adaptive Placental Metabolic Phenotypes That Are Disrupted in Preeclampsia.

Background: The chronic hypoxia of high-altitude residence poses challenges for tissue oxygen supply and metabolism. Exposure to high altitude during pregnancy increases the incidence of hypertensive disorders of pregnancy and fetal growth restriction and alters placental metabolism. High-altitude ancestry protects against altitude-associated fetal growth restriction, indicating hypoxia tolerance that is genetic in nature.

Developing a privacy-preserving deep learning model for glaucoma detection: a multicentre study with federated learning.

Background: Deep learning (DL) is promising to detect glaucoma. However, patients' privacy and data security are major concerns when pooling all data for model development. We developed a privacy-preserving DL model using the federated learning (FL) paradigm to detect glaucoma from optical coherence tomography (OCT) images.

Variations in the Branching Pattern and Course of the Left Axillary Artery: A Cadaveric Case Report.

The axillary artery is the primary arterial supply of the upper limb and functions as a key landmark in the region of the axilla. Anatomical variations in the axillary artery may arise from abnormal angiogenesis in the upper limb bud during embryological development. The routine dissection of the upper limb of an 88-year-old male cadaver revealed unilateral variations in the left axillary artery, including an abnormal anteromedial course with respect to the divisions and cords of the brachial plexus, while no variations were observed in the right axillary artery.

Protocol for culturing the endocrine junctional zone of the mouse placenta in serum-free medium.

The lack of a suitable explant culture system restricts the study of factors secreted by the mouse placenta into maternal circulation. Here, we present a protocol for culturing the endocrine junctional zone of the mouse placenta, free from the decidua and labyrinthine layers in serum-free medium. We describe steps for dissecting and separating layers, dicing tissue, and culture setup.

Perturbation of placental protein glycosylation by endoplasmic reticulum stress promotes maladaptation of maternal hepatic glucose metabolism.

Placental hormones orchestrate maternal metabolic adaptations to support pregnancy. We hypothesized that placental ER stress, which characterizes early-onset pre-eclampsia (ePE), compromises glycosylation, reducing hormone bioactivity and these maladaptations predispose the mother to metabolic disease in later life. We demonstrate ER stress reduces the complexity and sialylation of trophoblast protein N-glycosylation, while aberrant glycosylation of vascular endothelial growth factor reduced its bioactivity.

Perspective of smokers and healthcare professionals toward real-time video counseling smoking cessation program in general out-patient clinics in Hong Kong: a qualitative study.

Objective: This study aimed to explore the perceptions and experiences of individuals that currently smoke and healthcare professionals on using real-time video counseling in the Smoking Cessation and Counselling Program in General Out-patient Clinics in Hong Kong.

Design: This was a qualitative study using face-to-face semi-structured interviews based on the extended technology acceptance model. All interviews were audiotaped and transcribed verbatim.

Elevated homocysteine activates unfolded protein responses and causes aberrant trophoblast differentiation and mouse blastocyst development.

Hyperhomocysteinemia may arise from folate/vitamin B deficiency, genetic polymorphisms, kidney disease, or hypothyroidism. It is associated with an increased risk of early pregnancy loss and placenta-related complications of pregnancy, including pre-eclampsia and fetal growth restriction. While the majority of studies of hyperhomocysteinemia focus on epigenetic changes secondary to metabolic disruption, the effects of homocysteine toxicity on placental development remain unexplored.

Interventions for the prevention or treatment of epidural-related maternal fever: a systematic review and meta-analysis.

Background: Epidural-related maternal fever in women in labour has consequences for the mother and neonate. There has been no systematic review of preventive strategies.

Methods: RCTs evaluating methods of preventing or treating epidural-related maternal fever in women in active labour were eligible.

The reliability of symptom assessment by telepsychiatry compared with face to face psychiatric interviews.

Introduction: With the start of the COVID-19 pandemic, the various social distancing policies imposed have mandated psychiatrists to consider the option of using telepsychiatry as an alternative to face-to-face interview in Hong Kong. Limitations over sample size, methodology and information technology were found in previous studies and the reliability of symptoms assessment remained a concern.

Aim: To evaluate the reliability of assessment of psychiatric symptoms by telepsychiatry comparing with face-to-face psychiatric interview.

Three-Dimensional Multi-Task Deep Learning Model to Detect Glaucomatous Optic Neuropathy and Myopic Features From Optical Coherence Tomography Scans: A Retrospective Multi-Centre Study.

Purpose: We aim to develop a multi-task three-dimensional (3D) deep learning (DL) model to detect glaucomatous optic neuropathy (GON) and myopic features (MF) simultaneously from spectral-domain optical coherence tomography (SDOCT) volumetric scans.

Methods: Each volumetric scan was labelled as GON according to the criteria of retinal nerve fibre layer (RNFL) thinning, with a structural defect that correlated in position with the visual field defect (i.e.

Chronic Hypoxia in Ovine Pregnancy Recapitulates Physiological and Molecular Markers of Preeclampsia in the Mother, Placenta, and Offspring.

Background: Preeclampsia continues to be a prevalent pregnancy complication and underlying mechanisms remain controversial. A common feature of preeclampsia is utero-placenta hypoxia. In contrast to the impact of hypoxia on the placenta and fetus, comparatively little is known about the maternal physiology.

Excessive endoplasmic reticulum stress drives aberrant mouse trophoblast differentiation and placental development leading to pregnancy loss.

Key Points: Endoplasmic reticulum (ER) stress promotes placental dysmorphogenesis and is associated with poor pregnancy outcomes. We show that unfolded protein response signalling pathways located in the ER drive differentiation of mouse trophoblast stem cells into trophoblast subtypes involved in development of the placental labyrinth zone and trophoblast invasion. In a mouse model of chronic ER stress (Eif2s1 ), higher ER stress in homozygous blastocysts is accompanied by reduced trophectoderm cell number and developmental delay and also is associated with an increased incidence of early pregnancy loss.

Biological basis for novel mesothelioma therapies.

Mesothelioma is an aggressive cancer that is associated with exposure to asbestos. Although asbestos is banned in several countries, including the UK, an epidemic of mesothelioma is predicted to affect middle-income countries during this century owing to their heavy consumption of asbestos. The prognosis for patients with mesothelioma is poor, reflecting a failure of conventional chemotherapy that has ultimately resulted from an inadequate understanding of its biology.

Defective folate metabolism causes germline epigenetic instability and distinguishes Hira as a phenotype inheritance biomarker.

The mechanism behind transgenerational epigenetic inheritance is unclear, particularly through the maternal grandparental line. We previously showed that disruption of folate metabolism in mice by the Mtrr hypomorphic mutation results in transgenerational epigenetic inheritance of congenital malformations. Either maternal grandparent can initiate this phenomenon, which persists for at least four wildtype generations.

Stromal Cell-Derived Factor (SDF) 2 and the Endoplasmic Reticulum Stress Response of Trophoblast Cells in Gestational Diabetes Mellitus and Hyperglycaemic Condition.

Background And Aim: The endoplasmic reticulum (ER) stress response and the unfolded protein response (UPR) are essential cellular mechanisms to ensure the proper functioning of ER in adverse conditions. However, activation of these pathways has also been associated with insulin resistance and cell death in pathological conditions such as diabetes mellitus. In the present study, we investigated whether stromal cell-derived factor 2 (SDF2)-an ER stress-responsive factor-is related to ER response in placental cells exposed to maternal gestational diabetes mellitus (GDM) or to a hyperglycaemic in vitro condition.

HYPOXIA AND REPRODUCTIVE HEALTH: Oxygen and development of the human placenta.

Development of the human placenta takes place in contrasting oxygen concentrations at different stages of gestation, from ~20 mmHg during the first trimester rising to ~60 mmHg at the start of the second trimester before gradually declining to ~40 mmHg at term. In view of these changes, the early placenta has been described as 'hypoxic'. However, placental metabolism is heavily glycolytic, supported by the rich supply of glucose from the endometrial glands, and there is no evidence of energy compromise.

Food for Thought: Dietary Intervention in a Rare Cause of Severe Ventilatory Failure.

Unlabelled: Plastic bronchitis is a rare condition characterised by endobronchial cast formation. We report the case of a 53-year-old women who deteriorated following an elective bronchoscopy procedure. She developed refractory ventilatory failure and required repeated bronchoscopy, which identified thick tenacious casts as the cause of her airway compromise.

Artificial intelligence deep learning algorithm for discriminating ungradable optical coherence tomography three-dimensional volumetric optic disc scans.

Spectral-domain optical coherence tomography (SDOCT) is a noncontact and noninvasive imaging technology offering three-dimensional (3-D), objective, and quantitative assessment of optic nerve head (ONH) in human eyes . The image quality of SDOCT scans is crucial for an accurate and reliable interpretation of ONH structure and for further detection of diseases. Traditionally, signal strength (SS) is used as an index to include or exclude SDOCT scans for further analysis.

High-definition transcranial direct current stimulation-An open-label pilot intervention in alleviating depressive symptoms and cognitive deficits in late-life depression.

The efficacy of high-definition transcranial direct current stimulation (HD-tDCS) in late-life depression (LLD) remains unknown due to limited research on its therapeutic effects on the hallmarks of LLD-the depressive and cognitive symptoms. The present open-label pilot study aimed to examine the effectiveness of HD-tDCS as an augmentation therapy with antidepressants in improving the depressive and cognitive symptoms for LLD. Significant improvements were hypothesized in the depressive, cognitive, and daily functioning outcomes over time.

Noncanonical mitochondrial unfolded protein response impairs placental oxidative phosphorylation in early-onset preeclampsia.

Preeclampsia (PE) is a dangerous complication of pregnancy, especially when it presents at <34 wk of gestation (PE < 34 wk). It is a major cause of maternal and fetal morbidity and mortality and also increases the risk of cardiometabolic diseases in later life for both mother and offspring. Placental oxidative stress induced by defective placentation sits at the epicenter of the pathophysiology.