Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.

Quantitative natural history modeling of HPDL-related disease based on cross-sectional data reveals genotype-phenotype correlations.

Objectives: Biallelic HPDL variants have been identified as the cause of a progressive childhood-onset movement disorder, with a broad clinical spectrum from severe neurodevelopmental disorder to juvenile-onset pure hereditary spastic paraplegia type 83. This study aims at delineating the geno- and phenotypic spectra of patients with HPDL-related disease, quantitatively modelling the natural history, and uncovering genotype-phenotype associations.

Methods: A cross-sectional analysis of 90 published and one novel case was performed, employing a Human Phenotype Ontology-based approach.

A Firing Cannon: Bilateral Lower Limb Ischemia as a Manifestation of Cardiac Myxoma.

 Cardiac myxomas are the most common primary cardiac neoplasms.  We present a case of a middle-aged lady with cardiac myxoma in her left atrium awaiting semi-elective surgery. During the preoperative period, the patient presented emergently with acute bilateral lower limb ischemia.

is implicated in central nervous system, orofacial and maxillofacial anomalies.

Background: Previous studies in mouse, and zebrafish embryos show strong expression in progenitor cells of neuronal and neural crest tissues suggesting its involvement in neural crest specification. However, the role of human transcription factor activator protein 2 ( in human embryonic central nervous system (CNS), orofacial and maxillofacial development is unknown.

Methods: Through a collaborative work, exome survey was performed in families with congenital CNS, orofacial and maxillofacial anomalies.

Application comparison of paediatric myocardial protection procedures in arterial switch surgery.

Background: Reliable myocardial protection is essential for a good outcome after arterial switch operation.

Patients And Methods: We evaluated 56 neonates with arterial switch operation in this retrospective study. Three types of cardioplegia were used: antegrade Custodiol® (CCC) = 22, antegrade Custodiol® plus paediatric microplegia (mix) = 14, and antegrade plus retrograde intermittently paediatric microplegia (blood) = 20.

Random forest algorithm identifies miRNA signatures for breast cancer detection and classification from patient urine samples.

Background And Objectives: Breast cancer is the most common cancer in women, with one in eight women suffering from this disease in her lifetime. The implementation of centrally organized mammography screening for women between 50 and 69 years of age was a major step in the direction of early detection. However, the participation rate reaches approximately 50% of the eligible women, one reason being the painful compression of the breast, cited as a major issue for not participating in this very important program.

Donor-derived cell-free DNA monitoring for early diagnosis of antibody-mediated rejection after kidney transplantation: a randomized trial.

Background And Hypothesis: Donor-derived cell-free DNA (dd-cfDNA) shows good diagnostic performance for the detection of antibody-mediated rejection (AMR) in kidney transplant recipients (KTR). However, the clinical benefits of dd-cfDNA monitoring need to be established. Early diagnosis of AMR at potentially reversible stages may be increasingly important due to emerging treatment options for AMR.

Activation of STAT6 in Intestinal Epithelial Cells Predisposes to Gut Inflammation.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) often associated with a Type 2 immune response. Although previous reports hint at a role for signal transducer and activator of transcription (STAT) 6 signaling in non-immune cells, the contribution of STAT6-activation particularly in intestinal epithelial cells (IECs) is still unknown. Dextran sodium sulfate (DSS)-induced colitis is a model for UC in mice that we applied here on animals with expression of a constitutively active version of STAT6 in IECs (VillinCre_STAT6vt mice).

Automated discovery of experimental designs in super-resolution microscopy with XLuminA.

Driven by human ingenuity and creativity, the discovery of super-resolution techniques, which circumvent the classical diffraction limit of light, represent a leap in optical microscopy. However, the vast space encompassing all possible experimental configurations suggests that some powerful concepts and techniques might have not been discovered yet, and might never be with a human-driven direct design approach. Thus, AI-based exploration techniques could provide enormous benefit, by exploring this space in a fast, unbiased way.

Characterizing and targeting glioblastoma neuron-tumor networks with retrograde tracing.

Glioblastomas are invasive brain tumors with high therapeutic resistance. Neuron-to-glioma synapses have been shown to promote glioblastoma progression. However, a characterization of tumor-connected neurons has been hampered by a lack of technologies.

Endoscopic papillectomy versus surgical ampullectomy for adenomas and early cancers of the papilla: a retrospective Pancreas2000/European Pancreatic Club analysis.

Objective: Ampullary neoplastic lesions can be resected by endoscopic papillectomy (EP) or transduodenal surgical ampullectomy (TSA) while pancreaticoduodenectomy is reserved for more advanced lesions. We present the largest retrospective comparative study analysing EP and TSA.

Design: Of all patients in the database, lesions with prior interventions, benign histology advanced malignancy (T2 and more), patients with hereditary syndromes and those undergoing pancreatoduodenectomy were excluded.

Group 2 innate lymphoid cells are a non-redundant source of interleukin-5 required for development and function of murine B1 cells.

Tissue-resident immune cells, such as innate lymphoid cells, mediate protective or detrimental immune responses at barrier surfaces. Upon activation by stromal or epithelial cell-derived alarmins, group 2 innate lymphoid cells (ILC2s) are a rapid source of type 2 cytokines, such as IL-5. However, due to the overlap in effector functions, it remains unresolved whether ILC2s are an essential component of the type 2 response or whether their function can be compensated by other cells, such as T cells.

Less Pain with Intra-Articular Hyaluronic Acid Injections for Knee Osteoarthritis Compared to Placebo: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

The present meta-analysis investigated the efficacy of intra-articular hyaluronic acid (HA) injections for knee osteoarthritis. The outcomes of interest were the visual analogue scale (VAS) and Western Ontario McMaster Osteo-Arthritis Index (WOMAC) scores. This study was conducted according to the 2020 PRISMA statement.

Quantitative Macromolecular Modeling Assay of Biopolymer-Based Hydrogels.

The rubber elasticity theory has been lengthily applied to several polymeric hydrogel substances and upgraded from idealistic models to consider imperfections in the polymer network. The theory relies solely on hyperelastic material models in order to provide a description of the elastic polymer network. While this is also applicable to polymer gels, such hydrogels are rather characterized by their water content and visco-elastic mechanical properties.

Triskelion-Shaped Hexabenzocoronenes: Synthesis and Characterization of Tris-Substituted HBC Derivatives.

The synthesis of unprecedented triskelion-shaped hexa-peri-hexabenzocoronenes with C, C or D symmertry is reported. We present a new, five step synthetic access to tris-iodinated HBC derivatives carrying different solubilizing moieties (tert-butyl and mesityl), which serve as suitable building blocks for further functionalization. These molecules can undergo Sonogashira cross coupling reactions to obtain a series of seven ethynyl tris-substituted HBCs.

The Delay of Recanalisation of Acutely Thrombosed Dialysis Arteriovenous Access Until the Next Workday has No Negative Impact on Clinical Outcome.

Purpose: The necessity of providing endovascular recanalization of acutely thrombosed arteriovenous access (AV access) during weekend is questionable, since hemodialysis can alternatively be achieved by temporarily placed non-tunneled central venous catheters (CVC). Interventional therapy of acutely thrombosed AV access is provided only on weekdays in the study center. This study aimed to compare outcomes in patients admitted on weekdays and on the weekend.

IgG Glycosylation: Biomarker, Functional Modulator, and Structural Component.

The family of IgG Abs is a crucial component of adaptive immunity. Glycosylation of IgG maintains its structural integrity and modulates its effector functions. In this review, we discuss IgG glycosylation covering cell biological as well as therapeutic and disease-related aspects, focusing on the glycan structures in distinct IgG regions (Fab versus Fc).

The Role of Intermittent Fasting on Metabolic Syndrome: A Systematic Review and Meta-Analysis.

Intermittent fasting has gained popularity as a dietary intervention to improve metabolic health. Metabolic syndrome may benefit from intermittent fasting by improving weight, cholesterol levels, blood pressure (BP), and glucose control. This study aims to assess the effects of intermittent fasting on weight, BMI, cholesterol levels, BP, and glucose in individuals with metabolic syndrome.

Management of the Expected Difficult Airway with Planned One-Lung Ventilation: A Retrospective Analysis of 44 Cases.

Background:  Difficult airway management is essential in anesthesia practice. Particular challenges are posed to patients who require intraoperative one-lung ventilation. Specific guidelines for these scenarios have been lacking.

Analysis of abiotic and biotic stress-induced Ca transients in the crop species Solanum tuberosum.

Secondary messengers, such as calcium ions (Ca), are integral parts of a system that transduces environmental stimuli into appropriate cellular responses. Different abiotic and biotic stresses as well as developmental processes trigger temporal increases in cytosolic free Ca levels by an influx from external and internal stores. Stimulus-specificity is obtained by a certain amplitude, duration, oscillation and localisation of the response.

Predicting blood pressure response to renal denervation based on a new approach.

Background: Identifying predictors of blood pressure (BP) response to renal denervation (RDN) is crucial for patient selection. According to Wilder's principle, baseline BP predicts BP change after any antihypertensive intervention. Thus, any observed BP change after RDN is the sum of the BP change depending on the baseline BP and the specific BP reduction due to RDN.

Dysplastic crypts with lateral buddings in tubular adenomas.

Tubular adenomas (TA) are the most frequent of all colorectal adenomas. Current definitions of TA do not include the phenotype of the dysplastic crypts. We report a novel crypt phenotype characterized by dysplastic crypts with lateral buddings (DCLB).