Hypomorphic RAG2 Deficiency Promotes Selection of Self-Reactive B Cells.

Reduced function or hypomorphic variants in recombination-activating genes (RAG) 1 or 2 result in a broad clinical phenotype including common variable immunodeficiency (CVID) and even adult-onset disease. Milder RAG variants are less characterized. Here we describe the longitudinal course of a milder combined RAG deficiency in 3 of 7 siblings sharing the same RAG2 mutations over a 50-year study.

Clinical and economic effects of the transformation from an open to a laparoscopic center for colorectal surgery.

Purpose: The purpose of this study was to assess the feasibility of transitioning from open to laparoscopic surgery for colorectal carcinoma in a primary care hospital setting. Despite the recognized benefits of laparoscopic surgery in postoperative recovery and its demonstrated oncological equivalence, only a minority of patients (30-40%) in Germany undergo laparoscopic procedures, primarily due to concerns which, in addition to the perioperative quality data and economic aspects, focus on patient safety.

Methods: Over a three-year period (2012-2014), the transformation process was observed in a colorectal cancer center.

Subclonal TP53 and KRAS variants combined with poor treatment response identify ultra-high-risk pediatric T-ALL patients.

Variations in the TP53 and KRAS genes indicate a particularly adverse prognosis in relapsed pediatric T-ALL. We hypothesized that these variations might be subclonally present at disease onset and contribute to relapse risk. To test this, we examined two cohorts of children diagnosed with T-ALL: one with 81 patients who relapsed and 79 matched non-relapsing controls, and another with 226 consecutive patients, 30 of whom relapsed.

The Transcription Factor SOX18 Inhibitor Small Molecule 4 Is a Potential Treatment of Cancer-Induced Lymphatic Metastasis and Lymphangiosarcoma.

Background: Malignant tumors release growth factors, promoting lymphangiogenesis in primary tumors and draining sentinel lymph nodes, ultimately facilitating lymph node metastasis. As a malignant lymphatic tumor entity, lymphangiosarcomas are characterized by low survival rates and limited treatment options. The transcription factor SOX18 plays a crucial role in both lymphatic endothelial cell differentiation and cancer-induced lymphangiogenesis.

Electrospun adsorbent membrane of PLA containing chitosan for toxic metal ions removal from aqueous solution: Effect of chitosan incorporation.

The scarcity of water resources and their pollution are vital to modern civilization. Thus, adsorptive membranes are promising candidates to be applied in the filtration systems to improve the water quality. In summary, this study investigated the effect of chitosan (CS) in the morphological, chemical, and physical aspects of PLA-based membranes incorporating chitosan obtained by electrospinning process, their adsorption behavior in multielement aqueous systems containing Cr, Cu, Zn, Mn , Ni, and Cd in pH 4, and the possible removal mechanism on the composite electrospun membrane's surface.

A sentinel survey in remote Western Thailand indicates that school-aged children and reproductive-aged women of the Indigenous Pwo Karen community are iodine sufficient.

Indigenous peoples are often not routinely included in iodine programmes because of language barriers and remote access and may thus be at higher risk of iodine deficiency disorders, which could adversely impact their quality of life. We conducted this cross-sectional study in the remote Pwo Karen community of Thailand to determine the urinary iodine concentration of school-aged children and women of reproductive age and investigate the iodine content in household salt. We measured urinary iodine concentration in spot urine samples from healthy school-aged children and women of reproductive age, administered a questionnaire, estimated daily iodine intake and collected household salt samples to determine salt iodine concentration.

The International Bathymetric Chart of the Arctic Ocean Version 5.0.

Knowledge about seafloor depth, or bathymetry, is crucial for various marine activities, including scientific research, offshore industry, safety of navigation, and ocean exploration. Mapping the central Arctic Ocean is challenging due to the presence of perennial sea ice, which limits data collection to icebreakers, submarines, and drifting ice stations. The International Bathymetric Chart of the Arctic Ocean (IBCAO) was initiated in 1997 with the goal of updating the Arctic Ocean bathymetric portrayal.

Maintenance therapy with trofosfamide, idarubicin and etoposide in patients with rhabdomyosarcoma and other high-risk soft tissue sarcomas (CWS-2007-HR): a multicentre, open-label, randomised controlled phase 3 trial.

Background: Rhabdomyosarcoma and other soft tissue sarcomas (STS) with high-risk features are still associated with an unsatisfactory outcome. We evaluated the efficacy of oral maintenance therapy added at the end of standard therapy in patients with high-risk rhabdomyosarcoma and STS.

Methods: CWS-2007-HR was a multicentre, open-label, randomised controlled, phase 3 trial done at 87 centers in 5 countries.

Metabolomic analysis of 18th-19th pipes from the kingdom of Dahomey (actual Benin) indicates smoking of caffeine-bearing plants.

Increasingly, molecular chemistry and pharmacology are complementing classical studies in the field of archaeology. In this case, we present the results of the chemical study of pipe residues found in the context of an archaeological mission (AROMA mission: Archaeology of the Exercise of Royal and Magico-Religious Power) in the royal palaces of Abomey (Benin), dating from the 17th-19th century. The search for many products was carried out (mainly tobacco, cannabis) but surprisingly only highlighted the presence of caffeine residues.

2,6-Hepta-O-tert-butyldimethylsilyl α-cyclodextrin - A carbohydrate undecaol with all OH groups visible in NMR indicative of a partially disrupted hydrogen bond network.

During a synthesis of the well-known and useful building block 6-hexa-O-tert-butyldimethylsilyl α-cyclodextrin (2) by silylation of α-cyclodextrin (1) we isolated as a byproduct the oversilylated 2,6-hepta-O-tert-butyldimethylsilyl α-cyclodextrin (3) where one 2-OH group has also been silylated. This unsymmetrical new compound has a remarkable H NMR spectrum in CDCl where all 11 alcohol groups are visible. We have analyzed the spectrum of 3 using 1D and 2D 800 MHz NMR and are able to assign all the 11 alcohol protons.

Sustained response to guselkumab regardless of baseline characteristics in patients with active psoriatic arthritis and inadequate response to TNF inhibitors: results from the phase 3b COSMOS clinical trial.

Objectives: To prospectively evaluate the effect of guselkumab through 48 weeks across various clinical outcomes in subgroups of patients with psoriatic arthritis (PsA) and inadequate response to tumour necrosis factor inhibitors (TNFi-IR) from the phase 3b COSMOS trial. Subgroups were defined by baseline demographics, disease characteristics and prior/ongoing therapies.

Methods: Patients with active PsA (tender joint count (TJC) and swollen joint count (SJC) both ≥3) and TNFi-IR were randomised 2:1 to receive guselkumab 100 mg at week 0, week 4, then every 8 weeks through week 44 or to placebo with cross-over to guselkumab 100 mg at week 16 (early escape) or week 24 (planned).

Frequency and neuropathology of HTT repeat expansions in FTD/ALS: co-existence rather than causation.

Introduction: While ≥ 40 CAG repeat expansions in HTT present a well-established cause of Huntington's disease (HD), an enrichment of HTT repeat expansions was recently reported also in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), including FTD/ALS patients with additional HD neuropathology. This raises the question whether the phenotypic spectrum of HTT expansions can be extended to ALS and FTD, and whether HTT should be considered as a new causative gene of FTD/ALS. If HTT repeat expansions were indeed systematically related to FTD/ALS, one would expect an increased frequency of HTT carriers in FTD/ALS, who can clinically/neuropathologically not be explained better than by the presence of the HTT repeat expansions.

Growth and Cognitive Outcome in Very Preterm Infants with Postnatal Cytomegalovirus Infection.

Introduction: There are conflicting data on the association between postnatal cytomegalovirus (CMV) infection and growth and cognitive outcome in very preterm infants. The aim of the current study was to systematically evaluate the effect of postnatal CMV infection on growth and cognitive outcome in an unselected, contemporary cohort of very preterm infants.

Methods: Infants <32 gestational weeks (2011-2018) were screened for postnatal CMV infection.

An Analytical Approach that Combines Knowledge from Germline and Somatic Mutations Enhances Tumor Genomic Reanalyses in Precision Oncology.

Expanded analysis of tumor genomics data enables current and future patients to gain more benefits, such as improving diagnosis, prognosis, and therapeutics. Here, we report tumor genomic data from 1146 cases accompanied by simultaneous expert analysis from patients visiting our oncological clinic. We developed an analytical approach that leverages combined germline and cancer genetics knowledge to evaluate opportunities, challenges, and yield of potentially medically relevant data.

Emergent properties of the lysine methylome reveal regulatory roles via protein interactions and histone mimicry.

Aims: Epigenomics has significantly advanced through the incorporation of Systems Biology approaches. This study aims to investigate the human lysine methylome as a system, using a data-science approach to reveal its emergent properties, particularly focusing on histone mimicry and the broader implications of lysine methylation across the proteome.

Methods: We employed a data-science-driven OMICS approach, leveraging high-dimensional proteomic data to study the lysine methylome.

Assessing Protein Surface-Based Scoring for Interpreting Genomic Variants.

Clinical genomics sequencing is rapidly expanding the number of variants that need to be functionally elucidated. Interpreting genetic variants (i.e.

Targeting mitochondrial metabolism by the mitotoxin bromoxib in leukemia and lymphoma cells.

Targeting mitochondrial metabolism represents a promising approach for cancer treatment. Here, we investigated the mitotoxic potential of the polybrominated diphenyl ether bromoxib, a natural compound isolated from the marine sponge Dysidea family. We could show that bromoxib comprised strong cytotoxicity in different leukemia and lymphoma cell lines (such as HL60, HPBALL, Jurkat, K562, KOPTK1, MOLT4, SUPB15 and Ramos), but also in solid tumor cell lines (such as glioblastoma cell lines SJ-GBM2 and TP365MG).

plaque formation model to unravel biofilm formation dynamics on implant abutment surfaces.

Background: Biofilm formation on implant-abutment surfaces can cause inflammatory reactions. Ethical concerns often limit intraoral testing, necessitating preliminary in vitro or animal studies. Here, we propose an in vitro model using human saliva and hypothesize that this model has the potential to closely mimic the dynamics of biofilm formation on implant-abutment material surfaces in vivo.

Correlation between serum and saliva sex hormones in young female athletes.

Background: Saliva sampling provides a practical noninvasive way for biological monitoring of steroid hormones but few studies have focused on saliva sex hormones in female athletes, and it is still unknown whether salivary concentrations are an accurate reflection of blood concentrations in this population. The aim of this study was therefore to evaluate the correlation between serum and saliva estradiol (E2) and progesterone (PG) in 10 young female athletes with normal menstrual cycle.

Methods: Thirty blood and saliva samples were taken at rest in a fasting state in order to analyze E2 and PG concentrations, during 3 different hormonal periods: Status 1: low E2 and low PG (end luteal/early follicular); Status 2: high E2 and low PG (end follicular/peri-ovulatory); Status 3: high PG (mid-luteal).

Inhibition of the Notch signal transducer CSL by Pkc53E-mediated phosphorylation to fend off parasitic immune challenge in .

Notch signalling activity regulates hematopoiesis in and vertebrates alike. Parasitoid wasp infestation of larvae, however, requires a timely downregulation of Notch activity to allow the formation of encapsulation-active blood cells. Here, we show that the CSL transcription factor Suppressor of Hairless [Su(H)] is phosphorylated at Serine 269 in response to parasitoid wasp infestation.

Developing personas to inform the design of digital interventions for perinatal mental health.

Objectives: Digital interventions are increasingly in demand to address mental health concerns, with significant potential to reach populations that disproportionately face barriers to accessing mental health care. Challenges with user engagement, however, persist. The goal of this study was to develop user personas to inform the development of a digital mental health intervention (DMHI) for a perinatal population.