Histidine limitation alters plant development and influences the TOR network.

Plant growth depends on growth regulators, nutrient availability, and amino acids levels, all of which influence cell wall formation and cell expansion. Cell wall integrity and structures are surveyed and modified by a complex array of cell wall integrity sensors, including LRR-extensins (LRXs) that bind RALF (rapid alkalinization factor) peptides with high affinity and help to compact cell walls. Expressing the Arabidopsis root-hair specific LRX1 without the extensin domain, which anchors the protein to the cell wall, has a negative effect on root hair development.

Resistance to spindle inhibitors in glioblastoma depends on STAT3 and therapy induced senescence.

While mitotic spindle inhibitors specifically kill proliferating tumor cells without the toxicities of microtubule poisons, resistance has limited their clinical utility. Treating glioblastomas with the spindle inhibitors ispinesib, alisertib, or volasertib creates a subpopulation of therapy induced senescent cells that resist these drugs by relying upon the anti-apoptotic and metabolic effects of activated STAT3. Furthermore, these senescent cells expand the repertoire of cells resistant to these drugs by secreting an array of factors, including TGFβ, which induce proliferating cells to exit mitosis and become quiescent-a state that also resists spindle inhibitors.

A global sensitivity analysis of a mechanistic model of neoadjuvant chemotherapy for triple negative breast cancer constrained by in vitro and in vivo imaging data.

Unlabelled: Neoadjuvant chemotherapy (NAC) is a standard-of-care treatment for locally advanced triple negative breast cancer (TNBC) before surgery. The early assessment of TNBC response to NAC would enable an oncologist to adapt the therapeutic plan of a non-responding patient, thereby improving treatment outcomes while preventing unnecessary toxicities. To this end, a promising approach consists of obtaining in silico personalized forecasts of tumor response to NAC via computer simulation of mechanistic models constrained with patient-specific magnetic resonance imaging (MRI) data acquired early during NAC.

Effects of sodium-glucose co-transporter inhibitors on individual clinical endpoints and quality of life.

Aims: Sodium-glucose co-transporter inhibitors (SGLTis) have cardiovascular protective effects. We aimed to assess the effects of SGLTis on individual hard clinical endpoints and quality of life (QoL) in patients with cardiovascular risk factors.

Methods And Results: Data was searched in PubMed, Embase, Cochrane Library and clinicaltrials.

Safety and efficacy of pembrolizumab, radiation therapy, and surgery versus radiation therapy and surgery for stage III soft tissue sarcoma of the extremity (SU2C-SARC032): an open-label, randomised clinical trial.

Background: Approximately half of patients with localised, high-risk soft tissue sarcoma of the extremity develop metastases. We aimed to assess whether the addition of pembrolizumab to preoperative radiotherapy and surgery would improve disease-free survival.

Methods: We completed an open-label, randomised clinical trial in patients with grade 2 or 3, stage III undifferentiated pleomorphic sarcoma or dedifferentiated or pleomorphic liposarcoma of the extremity and limb girdle.

Proposal and clinical validation of a perioperative algorithm enhancing antimicrobial stewardship in substitution urethroplasty.

Objective: To evaluate the impact of a standardized antibiotic stewardship protocol on three subsequent endpoints in patients undergoing urethroplasty.

Methods: Men undergoing bulbar substitution urethroplasty between January 2009 and December 2016 were stratified by urine culture (UCx) at the time of surgery (sterile non-sterile) and were subjected to a standardized algorithm for urinalysis and antimicrobial therapy. We performed quantitative and qualitative exploration of UCx results and the microbial spectrum.

Application of the 5th WHO Guidelines for the Diagnosis of Lung Carcinoma in Small Lung Biopsies in a Tertiary Care Center: Is Insecurity of Pathologists for the Accurate Diagnosis Justified?

Background/objectives: The diagnosis of lung carcinoma (LC) is currently performed in small biopsies and according to the WHO classification by using limited stains to spare tissue for molecular testing. This procedure, however, often causes diagnostic uncertainty among pathologists.

Methods: In this retrospective analysis, we compared the diagnosis made by these guidelines in 288 lung biopsies with that using more stains, as retrieved from our archive.

Interactions of contact force, impedance, and power during repeated atrial arrhythmia ablation after previous atrial fibrillation ablation.

Background: Acutely effective repeated radiofrequency catheter ablation (RFCA) after previous atrial fibrillation ablation depends on several parameters including local impedance (LI), contact force (CF), and power.

Objective: We aimed to investigate the relationship of LI, CF, and power to the LI drop in a repeated atrial RFCA environment.

Methods: Consecutive patients undergoing repeated atrial RFCA were studied.

Expanded profiling of WD repeat domain 5 inhibitors reveals actionable strategies for the treatment of hematologic malignancies.

WD40 Repeat Domain 5 (WDR5) is a highly conserved nuclear protein that recruits MYC oncoprotein transcription factors to chromatin to stimulate ribosomal protein gene expression. WDR5 is tethered to chromatin via an arginine-binding cavity known as the "WIN" site. Multiple pharmacological inhibitors of the WDR5-interaction site of WDR5 (WINi) have been described, including those with picomolar affinity and oral bioavailability in mice.

[Long-term courses of alcohol dependence].

Background: Descriptions of long-term histories of alcohol dependence provide insight into the etiology, prevention and care.

Objective: Report of empirical findings about the development into and remission from alcohol dependence.

Method: Narrative literature review, analysis of findings from cohort studies in the general population.

Context-sensitivity and context-productivity: notions of "practice" and "practicality" in ethnomethodology and conversation analysis.

The text reconstructs the concepts of practice and practicality used in ethnomethodology and conversation analysis and examines their internal similarities and differences as well as similarities and differences to other practice theories. After a description of the characteristics of practice theories, the ethnomethodological perspective on practice and practicality is presented. Then, the use of the terms in conversation analysis is examined.

Outcomes After Definitive Surgery for Spinal and Sacral Chordoma in 101 Patients Over 20 Years.

Background And Objectives: Spinal chordomas are primary bone tumors where surgery remains the primary treatment. However, their low incidence, lack of evidence, and late disease presentation make them challenging to manage. Here, we report the postoperative outcomes of a large cohort of patients after surgical resection, investigate predictors for overall survival (OS) and local recurrence-free survival (LRFS) times, and trend functional outcomes over multiple time periods.

Cardioneuroablation for the treatment of reflex syncope and functional bradyarrhythmias: A Scientific Statement of the European Heart Rhythm Association (EHRA) of the ESC, the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS) and the Latin American Heart Rhythm Society (LAHRS).

Cardioneuroablation has emerged as a potential alternative to cardiac pacing in selected cases with vasovagal reflex syncope, extrinsic vagally induced sinus bradycardia-arrest or atrioventricular block. The technique was first introduced decades ago, and its use has risen over the past decade. However, as with any intervention, proper patient selection and technique are a prerequisite for a safe and effective use of cardioneuroablation therapy.

Ocular adnexal sebaceous carcinoma in a patient with Li-Fraumeni syndrome.

Li-Fraumeni syndrome (LFS) is caused by a pathogenic germline variant at the locus and is associated with an increased predisposition to a variety of cancers. The neoplasms most frequently associated with LFS are sarcomas, breast cancer, brain tumors, and adrenocortical carcinomas. In this case report, we present a 43-year-old male diagnosed with an ocular adnexal sebaceous carcinoma of the right upper eyelid who was confirmed to have LFS with subsequent genetic testing.

Pulmonary Vein Isolation or Pace and Ablate in Elderly Patients With Persistent Atrial Fibrillation (ABLATE Versus PACE)-Rationale, Methods, and Design.

Age is a major risk-factor for atrial fibrillation (AF) and associated hospitalisations. With increasing emphasis on rhythm control, pulmonary vein isolation (PVI) is often suggested, even to elderly patients (≥ 75 years of age). Efficacy of PVI aiming at rhythm control is limited in persistent AF.

The predictive validity of MCAT scores and undergraduate GPA for COMLEX-USA licensure exam performance of students enrolled in osteopathic medical schools.

Context: Osteopathic (Doctor of Osteopathic Medicine [DO]) medical students account for more than 25 % of all medical students in the United States.

Objectives: This study examined the predictive validity of Medical College Admission Test (MCAT) total scores and cumulative undergraduate grade point averages (UGPAs) for performance on the Comprehensive Osteopathic Medical Licensing Examination of the United States (COMLEX-USA) Level 1 and Level 2-CE (Cognitive Evaluation) licensure examinations administered by the National Board of Osteopathic Medical Examiners (NBOME). Additionally, the study examined the degree to which MCAT total scores and UGPAs provide comparable prediction of student performance by key sociodemographic variables.

App-Based Addiction Prevention at German Vocational Schools: Implementation and Reach for a Cluster-Randomized Controlled Trial.

This article examines the implementation, participation rates, and potential determinants of participation in the digital addiction prevention program "ready4life." A two-arm cluster-randomized trial recruited German vocational students via class-based strategies. Intervention group received 16 weeks of in-app coaching; the control group received health behavior information, with coaching offered after 12 months.

Natural variation in response to combined water and nitrogen deficiencies in Arabidopsis.

Understanding plant responses to individual stresses does not mean that we understand real-world situations, where stresses usually combine and interact. These interactions arise at different levels, from stress exposure to the molecular networks of the stress response. Here, we built an in-depth multiomic description of plant responses to mild water (W) and nitrogen (N) limitations, either individually or combined, among 5 genetically different Arabidopsis (Arabidopsis thaliana) accessions.