Ritlecitinib, a JAK3 /TEC inhibitor, modulates the markers of celiac autoimmunity in alopecia areata and vitiligo patients.

Background: Celiac disease (CeD) has shown an association with autoimmune disorders including vitiligo and alopecia areata (AA). Ritlecitinib, a JAK3 and TEC kinase family inhibitor, has been approved for treatment of patients with AA and is in late-stage development for vitiligo. Ritlecitinib inhibits cytotoxic T cells, NK cells, and B cells which play a role in the pathogenesis of CeD.

Upper cervical spinal cord atrophy in MS: Sex, menopause, and neurodegeneration.

Background: Spinal cord (SC) atrophy is a key imaging biomarker of progressive multiple sclerosis (MS). Progressive MS is more common in men and postmenopausal women.

Objective: Investigate the impact of sex and menopause on SC measurements in persons with MS (pwMS).

Functional variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are associated with increased risk of colorectal cancer.

Background: Individuals with cystic fibrosis (CF; a recessive disorder) have an increased risk of colorectal cancer (CRC). Evidence suggests individuals with a single CFTR variant may also have increased CRC risk.

Methods: Using population-based studies (GECCO, CORECT, CCFR, and ARIC; 53 785 CRC cases and 58 010 controls), we tested for an association between the most common CFTR variant (Phe508del) and CRC risk.

The epitope of the antibody used in the REAADS VWF activity assay is quaternary.

The REAADS VWF activity assay is often assumed to be specific for the A1 domain, the portion of VWF that binds platelet GPIbα. We tested this assay on the A1A2A3 region of VWF with each domain expressed independently of one another and together in combination as a tri-domain. The monoclonal antibody used in this assay is found to be insensitive to the single A domains and does not recognize free A1 domains as it is often assumed.

Outcome and complications in postcardiotomy cardiogenic shock treated with extracorporeal life support - a systematic review and meta-analysis.

Background: Postcardiotomy cardiogenic shock (PCCS) in cardiac surgery is associated with a high rate of morbidity and mortality. Beside other therapeutic measures (e.g.

Estimation of factorial expressions and its improvement through calibration: A replication and extension of Tversky and Kahneman (1973).

Fifty years ago, Tversky and Kahneman (Cognitive Psychology, 5[2], 207-232, 1973) reported that people's speeded estimations of 8 × 7 × 6 × 5 × 4 × 3 × 2 × 1 were notably higher than their estimations for the equivalent expression in the opposite order, 1 × 2 × 3 × 4 × 5 × 6 × 7 × 8 (Median = 2,250 vs. 512, respectively). On top of this order effect, both groups grossly underestimated the correct value (40,320).

Propagation of neuronal micronuclei regulates microglial characteristics.

Microglia-resident immune cells in the central nervous system-undergo morphological and functional changes in response to signals from the local environment and mature into various homeostatic states. However, niche signals underlying microglial differentiation and maturation remain unknown. Here, we show that neuronal micronuclei (MN) transfer to microglia, which is followed by changing microglial characteristics during the postnatal period.

Structural basis for metal ion transport by the human SLC11 proteins DMT1 and NRAMP1.

Iron and manganese are essential nutrients whose transport across membranes is catalyzed by members of the SLC11 family. In humans, this protein family contains two paralogs, the ubiquitously expressed DMT1, which is involved in the uptake and distribution of Fe and Mn, and NRAMP1, which participates in the resistance against infections and nutrient recycling. Despite previous studies contributing to our mechanistic understanding of the family, the structures of human SLC11 proteins and their relationship to functional properties have remained elusive.

Manganese Intercalation Enabling High-Performance Aqueous Fe-VO Batteries.

The aqueous iron ion batteries (AIIBs) are an attractive option for large-scale energy storage applications. However, the inadequate plating and stripping of Fe ions underscore the need to explore more suitable cathode materials. Herein, we optimize the structure of tunnel-like VO nanosheets by introducing Mn ion intercalation as a cathode material to enhance their performance in AIIBs.

A Phase II Trial of Onapristone and Fulvestrant for Patients With ER+ and HER2- Metastatic Breast Cancer.

Background: The SMILE study is a multi-institutional phase II clinical trial to determine the efficacy and safety of an antiprogestin, onapristone, in combination with fulvestrant as second-line therapy for patients with ER+, PgR+/-, HER2- metastatic breast cancer. This study was terminated early and herein, we report patient characteristics, and outcomes.

Methods: Eligibility criteria included disease progression on ≥2 lines of prior therapy, ECOG performance status ≤ 2, measurable disease per RECIST 1.

Guidance on the assessment of the functionality of biomaterials for periodontal tissue regeneration: Methodologies and testing procedures.

Innovative biomaterials and tissue engineering strategies show great promise in regenerating periodontal tissues. This guidance provides an overview and detailed recommendations for evaluating the biological functionality of these new biomaterials in vitro, focusing on mineralization, immunomodulatory effects, cellular differentiation, and angiogenesis. Additionally, it discusses the use of in vivo experimental models that mimic periodontitis and scrutinizes methods such as osteogenic differentiation, immunomodulation, and anti-inflammatory responses to assess the effectiveness of these biomaterials in promoting periodontal tissue reconstruction.

Racial disparities in lung transplantation for cystic fibrosis in the era of highly effective modulator therapy.

Background: Highly effective modulator therapies (HEMT) including ivacaftor (IVA) and elexacaftor/tezacaftor/ivacaftor (ETI) have transformed treatment for people with cystic fibrosis (pwCF). However, non-HEMT-responsive mutations are more common in pwCF of non-White race/ethnicity; introduction of HEMT might have exacerbated racial/ethnic disparities in CF care.

Methods: Using the Scientific Registry of Transplant Recipients, we identified all lung transplant candidates and recipients 05/2005-12/2022 and categorized them by diagnosis (CF/non-CF), race/ethnicity (non-Hispanic White/Black/Hispanic) and era [Pre-HEMT (2005-1/30/2012), IVA (1/31/2012-10/30/2019), ETI (10/31/2019-12/31/2022)].

Estradiol Levels are Differentially Associated with Pulse Wave Velocity in Trauma-exposed Premenopausal Women with and without PTSD.

Arterial stiffness is a well-known risk factor for cardiovascular disease. Although estradiol (E2) is known to be cardioprotective, the available data point to a growing cardiovascular disease risk in women before menopause due to post-traumatic stress disorder (PTSD). The present study aimed to investigate the effects of E2 on arterial compliance in trauma-exposed premenopausal women, with and without a clinical diagnosis PTSD.

A high throughput assay for phosphoribosylformylglycinamidine synthase.

Metabolic reprogramming of purine biosynthesis is a hallmark of cancer metabolism and represents a critical vulnerability. The enzyme phosphoribosylformylglycinamidine synthase (PFAS) catalyzes the fourth step in de novo purine biosynthesis and has been demonstrated to be prognostic for survival of liver cancer. Despite the importance of this protein as a drug target, there are no known specific inhibitors of PFAS activity.

Metal ion transport in maize: survival in a variable stress environment.

Maize (Zea mays) is the most widely cultivated crop in the world. Maize production is closely linked to the extensive uptake and utilization of various mineral nutrients. Potassium (K), calcium (Ca), and magnesium (Mg) are essential metallic macronutrients for plant growth and development.

Effective pretreatment of tea stem via poly-deep eutectic solvent for promoting platform molecule production and obtaining fluorescent lignin.

In this study, polyethylene glycol 200 (PEG200) was employed as hydrogen bond acceptor, while organic acids served as hydrogen bond donors, to formulate poly-deep eutectic solvents (PDESs), which were utilized to pretreat tea stem. Specially, combining PEG200 and oxalic acid (OA) exhibited a notably high cellulose retention (82.03 %) and most efficient hemicellulose (97.

Eliminating osmotic stress during cryoprotectant loading: A mathematical investigation of solute-solvent transport.

Osmotic stresses during cryoprotectant loading induce changes in cellular volume, leading to membrane damage or even cell death. Appropriate model-guided mitigation of these osmotic gradients during cryoprotectant loading is currently lacking, but would be highly beneficial in reducing viability loss during the loading process. To address this need, we reformulate the two-parameter formalism described by Jacobs and Stewart for cryoprotectant loading under the constraint of constant cell volume.

Association of Impaired Relaxation Mitral Inflow Pattern (Grade 1 Diastolic Function) with Long-term Non-Cardiovascular and Cardiovascular Mortality.

Background: Abnormalities of left ventricular (LV) diastolic function are established independent predictors of heart failure (HF) and mortality.

Objectives: To determine whether the association of diastolic function with all-cause mortality is driven by cardiovascular or non-cardiovascular death and if impaired relaxation mitral inflow filling pattern is a risk marker.

Methods: Diastolic function was graded by the Mayo Clinic algorithm utilizing the well characterized prospective Olmsted County Heart Function Study.

Outcomes after medical treatment for primary aldosteronism: an international consensus and analysis of treatment response in an international cohort.

Background: Primary aldosteronism can be treated medically but there is no standardised method to evaluate treatment outcomes. We aimed to develop criteria for assessing the outcomes of targeted medical treatment of primary aldosteronism, analyse outcomes across an international cohort, and identify factors associated with a complete treatment response.

Methods: An international panel of 31 primary aldosteronism experts used the Delphi method to reach consensus on the definition of complete, partial, or absent biochemical and clinical outcomes of medical treatment of primary aldosteronism.

Charting the epitranscriptomic landscape across RNA biotypes using native RNA nanopore sequencing.

RNA modifications are conserved chemical features found in all domains of life and across diverse RNA biotypes, shaping gene expression profiles and enabling rapid responses to environmental changes. Their broad chemical diversity and dynamic nature pose significant challenges for studying them comprehensively. These limitations can now be addressed through direct RNA nanopore sequencing (DRS), which allows simultaneous identification of diverse RNA modification types at single-molecule and single-nucleotide resolution.

An online segmented continuous flow analysis system for rapid determining chemical oxygen demand in seawater to assess organic pollution levels.

By integrating ultraviolet (UV) photocatalytic oxidation digestion with segmented continuous flow analysis technology, an online measurement method and analysis system for the alkaline chemical oxygen demand (COD) in seawater, based on the color-change reaction of potassium permanganate, has been established. This represents the first application of UV photocatalytic oxidation technology in the measurement of COD in seawater. The system effectively overcomes the limitations of high-temperature and high-pressure digestion methods employed in traditional COD analysis.

Blue-Green space seasonal influence on land surface temperatures across different urban functional zones: Integrating Random Forest and geographically weighted regression.

As climate change and urbanization progress, the urban heat island issue will affect more people. Urban blue-green spaces can effectively mitigate the urban heat island effect, and their structure and morphology significantly impact the degree of mitigation. To identify the most effective blue-green space distribution for mitigating the heat island effect across different urban function zones (UFZ), we selected 14 landscape metrics of blue-green spaces in the main urban area of Nanjing.