Society of American Gastrointestinal and Endoscopic Surgeons guidelines development: patient engagement update to standard operating procedure.

Introduction: The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Guidelines Committee develops evidence-based surgical guidelines. Involvement of patient partners is important to ensure patient concerns and values are adequately addressed and incorporated. This standard operating procedure (SOP) for the process of patient partner involvement within the guidelines is described here.

Identification of potent TMPRSS4 inhibitors through structural modeling and molecular dynamics simulations.

TMPRSS4, a transmembrane serine protease type II, is associated with various pathological illnesses. It has been found to activate SARS-CoV-2, enhance viral infection of human small-intestinal enterocytes and is overexpressed in different types of cancers. Therefore, this study aims to disover potential TMPRSS4 inhibitors that have better binding affinity than the approved inhibitors: 2-hydroxydiarylamide and tyroserleutide.

Neoadjuvant nivolumab and chemotherapy in early estrogen receptor-positive breast cancer: a randomized phase 3 trial.

Patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) primary breast cancer (BC) have low pathological complete response (pCR) rates with neoadjuvant chemotherapy. A subset of ER+/HER2- BC contains dense lymphocytic infiltration. We hypothesized that addition of an anti-programmed death 1 agent may increase pCR rates in this BC subtype.

Pembrolizumab and chemotherapy in high-risk, early-stage, ER/HER2 breast cancer: a randomized phase 3 trial.

Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER/HER2) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER/HER2 grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1-2 or T3-4, cN0-2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W.

Temporal and regional X-linked gene reactivation in the mouse germline reveals site-specific retention of epigenetic silencing.

Random X-chromosome inactivation is a hallmark of female mammalian somatic cells. This epigenetic mechanism, mediated by the long noncoding RNA Xist, occurs in the early embryo and is stably maintained throughout life, although inactivation is lost during primordial germ cell (PGC) development. Using a combination of single-cell allele-specific RNA sequencing and low-input chromatin profiling on developing mouse PGCs, we provide a detailed map of X-linked gene reactivation.

Cholesterol mobilization regulates dendritic cell maturation and the immunogenic response to cancer.

Maturation of conventional dendritic cells (cDCs) is crucial for maintaining tolerogenic safeguards against auto-immunity and for promoting immunogenic responses to pathogens and cancer. The subcellular mechanism for cDC maturation remains poorly defined. We show that cDCs mature by leveraging an internal reservoir of cholesterol (harnessed from extracellular cell debris and generated by de novo synthesis) to assemble lipid nanodomains on cell surfaces of maturing cDCs, enhance expression of maturation markers and stabilize immune receptor signaling.

Incomplete elimination of viral genomes is associated with chronic inflammation in nonhuman primate livers after AAV-mediated gene transfer.

The liver is a unique organ where immunity can be biased toward ineffective response notably in the context of viral infections. Chronic viral hepatitis depends on the inability of the T-cell immune response to eradicate antigen. In the case of recombinant Adeno-Associated-Virus, used for therapeutic gene transfer, conflicting reports describe tolerance induction to different transgene products while other studies have shown conventional cytotoxic CD8 T cell responses with a rapid loss of transgene expression.

TLE4 is a repressor of the oncogenic activity of TLX3 in T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological disease originating from the malignant transformation of T-cell progenitors, caused by the accumulation of genetic aberrations. One-fifth of T-ALL patients are characterized by ectopic expression of the homeobox transcription factor TLX3. However, the role of TLX3 in T-ALL remains elusive, partly due to the lack of suitable study models.

Insights from a century of data reveal global trends in ex situ living plant collections.

Ex situ living plant collections play a crucial role in providing nature-based solutions to twenty-first century global challenges. However, the complex dynamics of these artificial ecosystems are poorly quantified and understood, affecting biodiversity storage, conservation and utilization. To evaluate the management of ex situ plant diversity, we analysed a century of data comprising 2.

One carbon metabolism supplementation in maturation medium but not embryo culture medium improves the yield of blastocysts from bovine oocytes.

Optimizing oocyte maturation and embryo culture media could enhance in vitro embryo production. The purpose of the present study was to investigate the role of supplementing one carbon metabolism (OCM) substrates and its cofactors (Cystine, Zinc, Betaine, B2, B3, B6, B12 and 5-methyltetrahydrofolate) in maturation and/or embryo culture media on the rate of blastocyst formation and pregnancy outcomes following the transfer of the resulting blastocysts in bovines. In the first experiment, 2537 bovine oocytes were recovered from slaughterhouse ovaries and then matured either in conventional maturation medium (IVM) or IVM supplemented with OCM substrates (Sup-IVM).

The association of origin and environmental conditions with performance in professional IRONMAN triathletes.

We have (i) little knowledge about where the fastest professional IRONMAN triathletes originate from and where the fastest races take place and (ii) we have no knowledge of the optimal weather conditions for an IRONMAN triathlon. The aims of the present study were, therefore, (i) to investigate the origin and the fastest IRONMAN race courses for professional triathletes and (ii) to evaluate the best environmental conditions (i.e.

Comprehensive evaluation of pure and hybrid collaborative filtering in drug repurposing.

Drug development is known to be a costly and time-consuming process, which is prone to high failure rates. Drug repurposing allows drug discovery by reusing already approved compounds. The outcomes of past clinical trials can be used to predict novel drug-disease associations by leveraging drug- and disease-related similarities.

FGFR antagonists restore defective mandibular bone repair in a mouse model of osteochondrodysplasia.

Gain-of-function mutations in fibroblast growth factor receptor (FGFR) genes lead to chondrodysplasia and craniosynostoses. FGFR signaling has a key role in the formation and repair of the craniofacial skeleton. Here, we analyzed the impact of Fgfr2- and Fgfr3-activating mutations on mandibular bone formation and endochondral bone repair after non-stabilized mandibular fractures in mouse models of Crouzon syndrome (Crz) and hypochondroplasia (Hch).

Quantum machine learning with Adaptive Boson Sampling via post-selection.

The implementation of large-scale universal quantum computation represents a challenging and ambitious task on the road to quantum processing of information. In recent years, an intermediate approach has been pursued to demonstrate quantum computational advantage via non-universal computational models. A relevant example for photonic platforms has been provided by the Boson Sampling paradigm and its variants, which are known to be computationally hard while requiring at the same time only the manipulation of the generated photonic resources via linear optics and detection.

Time to HIV viral rebound and frequency of post-treatment control after analytical interruption of antiretroviral therapy: an individual data-based meta-analysis of 24 prospective studies.

The only current strategy to test efficacy of novel interventions for sustained HIV control without antiretroviral therapy (ART) among people with HIV (PWH) is through an analytical treatment interruption (ATI). Inclusion of 'placebo' controls in ATIs poses ethical, logistical, and economic challenges. To understand viral dynamics and rates of post-treatment control (PTC) after ATI among PWH receiving either placebo or no intervention, we undertook an individual-participant data meta-analysis.

Ligand-Directed Actinide Oxo-Bond Manipulation in Actinyl Thiacalix[4]arene Complexes.

Understanding the chemistry of the inert actinide oxo bond in actinyl ions AnO22+ is important for controlling actinide behavior in the environment, during separations, and in nuclear waste (An = U, Np, Pu). The thioether calixarene TC4A (4-tert-butyltetrathiacalix[4]arene) binds equatorially to [AnO2]n+ (An = U, Np) forming a conical pocket that differentiates the two trans-oxo groups. The 'ate' complexes, [A]2[UO2(TC4A)] (A = [Li(DME)2], HNEt3) and [HNEt3]2[NpO2(TC4A)], enable selective oxo chemistry.

The Phenotypic and Genotypic Spectrum of BRPF1-Related Disorder: 29 New Patients and Literature Review.

Intellectual Developmental Disorder with Dysmorphic Facies and Ptosis (IDDDFP) is a rare autosomal dominant syndrome caused by pathogenic variants in the BRPF1 gene, which is critical for chromatin regulation. This study expands the clinical and molecular spectrum of IDDDFP by analysing 29 new patients from 20 families with confirmed BRPF1 variants. Our cohort presented with a wide range of clinical features including developmental delay, intellectual disability (ID) and characteristic dysmorphic facial features such as ptosis, blepharophimosis and a broad nasal bridge.

Therapeutic potential of cannabidiol polypharmacology in neuropsychiatric disorders.

Cannabidiol (CBD), the primary non-intoxicating compound in cannabis, is currently approved for treating rare, treatment-resistant seizures. Recent preclinical research suggests that CBD's multifaceted mechanisms of action in the brain, which involve multiple molecular targets, underlie its neuroprotective, anti-inflammatory, anxiolytic, and antipsychotic effects. Clinical trials are also exploring CBD's therapeutic potential beyond its current uses.

Calretinin-expressing neurons in the basal forebrain specifically contact granule cells in the olfactory bulb and modulate odor learning.

GABAergic neurons in basal forebrain (BF) nuclei project densely to all layers of the mouse main olfactory bulb (OB), the first relay in odor information processing. However, BF projection neurons are diverse and the contribution of each subtype to odor information processing is not known. In the present study, we used retrograde and anterograde tracing methods together with whole-brain light-sheet analyses, patch-clamp recordings coupled with optogenetic and chemogenetic approaches during spontaneous odor discrimination, and go/no-go odor discrimination/learning tests to characterize the synaptic targets in the OB of BF calretinin-expressing (CR+) GABAergic cells and to reveal their functional implications.

Radiation Exposure Analysis on 274 Patients With Vertebral Augmentation Using the Surgivisio Intraoperative Navigation System.

Background: Surgeons' reliance on intraoperative fluoroscopy during vertebroplasty procedures has raised concerns regarding the level of patient and surgeon radiation. Navigation systems have shown a potential to reduce the overall patient and medical staff exposure during dose exposure studies. The main objective of this study was to determine whether the Surgivisio platform (eCential Robotics, France), a unified imaging and navigation platform, lowers the patient dose during routine clinical usage as compared with published fluoroscopy and other navigation options that are published in the literature.

A novel, dominant disease mechanism of distal renal tubular acidosis with specific variants in ATP6V1B1.

Background And Hypothesis: ATP6V1B1 encodes a subunit of the vacuolar H+-ATPase and pathogenic variants are associated with autosomal recessive distal renal tubular acidosis (dRTA) with deafness. Heterozygous variants predicted to affect a specific amino acid, Arg394, have been recurrently reported in dRTA but their significance has been unclear. We hypothesised that these variants are associated with a dominant disease mechanism.

Influence of DOAC Levels and Thrombin Generation on Postoperative Bleeding [SONAR]: A Nested Case-Control Study.

A DOAC concentration threshold above which an impact on surgical hemostasis starts to occur is unknown. Thrombin generation assays (TGAs) provide a measure of the coagulation phenotype. This study aimed to determine whether preoperative TGA parameters are associated with postoperative bleeding, and whether this is partly due to residual DOAC levels.