Higher-order transient membrane protein structures.

This study shows that five membrane proteins-three GPCRs, an ion channel, and an enzyme-form self-clusters under natural expression levels in a cardiac-derived cell line. The cluster size distributions imply that these proteins self-oligomerize reversibly through weak interactions. When the concentration of the proteins is increased through heterologous expression, the cluster size distributions approach a critical distribution at which point a phase transition occurs, yielding larger bulk phase clusters.

Distinct gut microbial signature and altered short chain fatty acid metabolism at disease onset in a rat preclinical model of superimposed preeclampsia.

Chronic hypertension is an increasingly prevalent condition that constitutes a risk factor for superimposed preeclampsia during pregnancy. In this study, we assessed the gut microbiome in a rat model of superimposed preeclampsia to characterize the microbial signature associated with defective placentation processes identified at the preclinical disease stage. The blood pressure profile, renal function parameters and fetal phenotype were evaluated in pregnant Stroke-prone Spontaneously Hypertensive Rats (SHRSP) and their normotensive controls.

Evaluating a computer-based body exposure paradigm for the treatment of body image disturbance in adolescent Anorexia Nervosa: effects on the attentional bias and emotions.

Background: A diagnostic criterion of Anorexia Nervosa (AN) is body image disturbance. Body exposure therapy is a widely used approach to treat this; however, it is unclear which part of body exposure therapy is relevant for regaining a realistic perspective on the own body. This study aimed to examine the role of the attentional bias (AB), which AN patients exhibit to the most disliked parts of their body.

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.

Compensating elastic faults in a torque-assisted knee exoskeleton: functional evaluation and user perception study.

Wearable robots are often powered by elastic actuators, which can mimic the intrinsic compliance observed in human joints, contributing to safe and seamless interaction. However, due to their increased complexity, when compared to direct drives, elastic actuators are susceptible to faults, which pose significant challenges, potentially compromising user experience and safety during interaction. In this article, we developed a fault-tolerant control strategy for torque assistance in a knee exoskeleton and investigated user experience during a walking task while emulating faults.

A crucial active site network of titratable residues guides catalysis and NAD binding in human succinic semialdehyde dehydrogenase.

Human succinic semialdehyde dehydrogenase is a mitochondrial enzyme fundamental in the neurotransmitter γ-aminobutyric acid catabolism. It catalyzes the NAD-dependent oxidative degradation of its derivative, succinic semialdehyde, to succinic acid. Mutations in its gene lead to an inherited neurometabolic rare disease, succinic semialdehyde dehydrogenase deficiency, characterized by mental and developmental delay.

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.

Hyperreactive B cells instruct their elimination by T cells to curb autoinflammation and lymphomagenesis.

B cell immunity carries the inherent risk of deviating into autoimmunity and malignancy, which are both strongly associated with genetic variants or alterations that increase immune signaling. Here, we investigated the interplay of autoimmunity and lymphoma risk factors centered around the archetypal negative immune regulator TNFAIP3/A20 in mice. Counterintuitively, B cells with moderately elevated sensitivity to stimulation caused fatal autoimmune pathology, while those with high sensitivity did not.

Addressing the role of surgery in brain tumour trials: A report from the neurosurgery committee of the EORTC brain tumour group.

The Brain Tumor Group (BTG) of the European Organization for Research and Treatment of Cancer (EORTC) conducts academic clinical trials and translational research to improve clinical management of patients with primary and secondary brain tumors. The EORTC BTG has traditionally played an important role in providing evidence and thus advancing the field, albeit with a main focus on radiotherapy and pharmacotherapy in gliomas. Although examples of well-designed neuro-oncological surgical trials can be found, evidence in surgical neuro-oncology predominantly includes data from uncontrolled prospective series or retrospective cohorts.

Reduction in Renal Heme Oxygenase-1 Is Associated with an Aggravation of Kidney Injury in Shiga Toxin-Induced Murine Hemolytic-Uremic Syndrome.

Hemolytic-uremic syndrome (HUS) is a systemic complication of an infection with Shiga toxin (Stx)-producing enterohemorrhagic , primarily leading to acute kidney injury (AKI) and microangiopathic hemolytic anemia. Although free heme has been found to aggravate renal damage in hemolytic diseases, the relevance of the heme-degrading enzyme heme oxygenase-1 (HO-1, encoded by ) in HUS has not yet been investigated. We hypothesized that HO-1 also important in acute phase responses in damage and inflammation, contributes to renal pathogenesis in HUS.

Contrastive Learning Approach for Assessment of Phonological Precision in Patients with Tongue Cancer Using MRI Data.

Magnetic Resonance Imaging (MRI) allows analyzing speech production by capturing high-resolution images of the dynamic processes in the vocal tract. In clinical applications, combining MRI with synchronized speech recordings leads to improved patient outcomes, especially if a phonological-based approach is used for assessment. However, when audio signals are unavailable, the recognition accuracy of sounds is decreased when using only MRI data.

Long-Term Safety and Effectiveness of Canakinumab in Patients with MKD/HIDS: Interim Analysis of the RELIANCE Registry.

Introduction: Interim analysis of the long-term safety and effectiveness of canakinumab, at a patient level, in the mevalonate kinase deficiency/hyperimmunoglobulin-D syndrome (MKD/HIDS) cohort of the RELIANCE registry.

Methods: From June 2018, the RELIANCE registry enrolled paediatric (aged ≥ 2 years) and adult patients (aged ≥ 18 years) with MKD/HIDS who were receiving canakinumab as part of their routine medical care. Safety, physician- and patient-reported measures of disease activity and dosing patterns were evaluated at baseline and every 6 months until end-of-study visit.

Tagless LysoIP for immunoaffinity enrichment of native lysosomes from clinical samples.

Lysosomes are implicated in a wide spectrum of human diseases including monogenic lysosomal storage disorders (LSDs), age-associated neurodegeneration and cancer. Profiling lysosomal content using tag-based lysosomal immunoprecipitation (LysoTagIP) in cell and animal models has substantially moved the field forward, but studying lysosomal dysfunction in human patients remains challenging. Here, we report the development of the 'tagless LysoIP' method, designed to enable the rapid enrichment of lysosomes, via immunoprecipitation, using the endogenous integral lysosomal membrane protein TMEM192, directly from clinical samples and human cell lines (e.

Disturbed spatial WNT activation - a potential driver of the reticularized skin phenotype in Systemic Sclerosis (SSc).

Objectives: Little is known on the mechanisms necessary to maintain the physiological adult human skin integrity. This study aims to quantitatively describe anatomical changes in systemic sclerosis (SSc)-skin compared to controls and investigate the underlying mechanisms.

Methods: Skin morphology was histologically assessed in twenty-three SSc-patients, eighteen controls and fifteen patients with hypertrophic scars.

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.

Signaling events driving Aspergillus fumigatus-induced eosinophil activation.

Allergic bronchopulmonary aspergillosis is an incurable disease caused by the environmental mold Aspergillus fumigatus. This hypersensitivity pneumonia is characterized by an inflammatory type 2 immune response, accompanied by influx of eosinophils into the lung. To investigate the mode of action of eosinophils and the signaling events triggered by A.

Benefit of the Omental Flap in Breast Reconstruction for Oncoplastic Treatment: A Systematic Review and Single-Arm Meta-Analysis.

Background: Oncoplastic surgery for breast cancer patients poses the challenge of achieving optimal aesthetic outcomes without increasing the risk of complications. Omental flap has emerged as n reconstructive option in breast surgery, yet the efficacy and safety of large omental flaps remain uncertain. This study aims to conduct a systematic review and single-arm meta-analysis to comprehensively evaluate the effectiveness, safety, and cosmetic outcomes of large omental flap breast reconstruction, providing updated evidence for clinical practice.

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.

Persistent humid climate favored the Qin and Western Han Dynasties in China around 2,200 y ago.

The Qin and Western Han dynasties (221 BCE to 24 CE) represent an era of societal prosperity in China. However, due to a lack of high-resolution paleoclimate records it is still unclear whether the agricultural boost documented for this period was associated with more favorable climatic conditions. Here, multiparameter analysis of annually resolved tree-ring records and process-based physiological modeling provide evidence of stable and consistently humid climatic conditions during 270 to 77 BCE in northern China.

Optimized monitoring for immune checkpoint inhibitor induced myocarditis using high-sensitivity troponin-T.

Background: Immune checkpoint inhibitor (ICI)-induced Myocarditis (irMyocarditis) is a rare adverse event with a high mortality rate of 40-50 % and which is mostly not diagnosed until clinical symptoms emerge.

Objectives: This study aims to screen patients for irMyocarditis using high-sensitivity cardiac troponin-T (hs-TnT) before and regularly during therapy with ICI.

Methods: A cohort of 280 cancer patients were prospectively screened for levels of hs-TnT at baseline and prior to every ICI infusion.

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.

CAR T-cells in autoimmunity: game changer or stepping stone?

The advent of chimeric antigen receptor (CAR) T-cells has revolutionized the treatment landscape for hematologic malignancies, and emerging evidence suggests their potential in autoimmune diseases (AIDs). This article examines the early successes and future implications of B-cell-targeting CAR T-cell therapy in AIDs. Initial applications, particularly in refractory systemic lupus erythematosus (SLE), have demonstrated significant and durable clinical remissions, with accompanying evaluation of the immune system suggesting a so-called "reset" of innate inflammation and adaptive autoimmunity.

Photon counting CT versus energy-integrating CT: A comparative evaluation of advances in image resolution, noise, and dose efficiency.

Background: Photon counting computed tomography (PCCT) employs direct and spectrally resolved counting of individual x-ray quanta, enhancing image quality compared to the standard energy-integrating CT (EICT).

Purpose: To evaluate the quantitative improvements in CT image quality metrics by comparing the first medical PCCT with a state-of-the-art EICT.

Methods: The PCCT versus EICT noise improvement ratio R was derived from the quantum statistics of the measurement process and measured across the clinical x-ray flux range for both systems.

Correction: Podolska et al. Graphene Oxide Nanosheets for Localized Hyperthermia-Physicochemical Characterization, Biocompatibility, and Induction of Tumor Cell Death. 2020, , 776.

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