Allosteric CDC37 Inhibitor Disrupts Chaperone Complex to Block CDK4/6 Maturation.

Cell division cycle 37 (CDC37) is a member of the molecular chaperone family and acts as a cochaperone of heat shock protein 90 (HSP90), which is overexpressed in many cancer types as a regulator of protein kinase maturation. In this process, CDC37 selectively recognizes and stabilizes protein kinases by forming a HSP90-CDC37-kinase chaperone complex. The protein-protein interactions (PPIs) of HSP90-CDC37 and CDC37-kinase complexes contribute to malignant tumors, as oncogenic kinases in malignant cells depend upon CDC37 expression.

Interval Advanced Adenomas and Neoplasia in Patients with Negative Colonoscopy Following Positive Stool-Based Colorectal Cancer Screening Test.

Background/aims: Fecal occult blood test (FOBT) and fecal immunohistochemical test (FIT) are used for colorectal cancer (CRC) screening. However, when no adenomas are found following a positive FOBT/FIT, the future risk of advanced adenomas or colorectal cancer (CRC) is unclear. We determined the incidence and determinants of advanced adenomas or CRC after a negative index colonoscopy following a positive FOBT/FIT.

Intra-individual radiomic analysis of pericoronary adipose tissue: Photon-counting detector vs energy-integrating detector CT angiography.

Background: The impact of novel photon-counting detector (PCD)-CT technology on in-vivo radiomics is not fully understood. This study aimed to compare the intra-individual stability and reproducibility of pericoronary adipose tissue (PCAT) radiomic features between PCD-CT and energy-integrating detector (EID)-CT in patients undergoing coronary CT angiography (CCTA) on both systems.

Methods: Patients undergoing clinically indicated CCTA on an EID-CT were prospectively enrolled for research PCD-CCTA within 30 days.

Patient-psychologist telemedicine interactions in an intensive care unit recovery clinic: Qualitative secondary analysis.

Objectives: We aimed to describe the content of patient-psychologist mental health related dialogues during a telemedicine intensive care unit recovery clinic visit.

Research Methodology/design: Qualitative descriptive study nested within a randomized controlled pilot trial to assess a telemedicine intensive care unit recovery clinic feasibility and preliminary efficacy. Participants included adults hospitalized with sepsis and/or respiratory failure.

Veterans' Lung Cancer Risk Conceptualizations versus Lung Cancer Screening Shared Decision-Making Conversations with Clinicians: A Qualitative Study.

Background: The Veterans Health Administration (VA) recommends lung cancer screening (LCS), including shared decision making between clinicians and veteran patients. We sought to characterize 1) veteran conceptualization of lung cancer risk and 2) veteran and clinician accounts of shared decision-making discussions about LCS to assess whether they reflect veteran concerns.

Methods: We conducted qualitative interviews at 6 VA sites, with 48 clinicians and 34 veterans offered LCS in the previous 6 mo.

Evaluating a predictive model of avoidable hospital events for race- and sex-based bias.

Objective: To evaluate whether race- and sex-based biases are present in a predictive model of avoidable hospital (AH) events.

Study Setting And Design: We examined whether Medicare fee-for-service (FFS) beneficiaries in Maryland with similar risk scores differed in true AH event risk on the basis of race or sex (n = 324,834). This was operationalized as a logistic regression of true AH events on race or sex with fixed effects for risk score percentile.

Novel approach to bone comorbidity in resistant acromegaly.

Active acromegaly may lead to irreversible complications. Among them, acromegaly osteopathy and fragility (vertebral and hip) fractures have emerged as frequent and precocious events in the natural history of the disease, being correlated with longer disease duration and higher growth hormone (GH) levels, accounting for patients' reported poor quality of life, physical performance and other life-impacting complications. Differently from primary osteoporosis, bone mineral density is not a reliable tool to predict fracture risk in this clinical setting, as patients with active disease frequently have normal or slightly reduced bone mass; whereas bone quality is particularly compromised, as determined by low trabecular bone score (TBS) in patients with active disease as compared to healthy controls or patients with cured/controlled disease.

External Physical Demands during Official Under-18 Basketball Games: Consideration of Overtime Periods.

The purpose of this study was to identify the external demands during official under-18 basketball matches that included four quarters (Q1, Q2, Q3, Q4) and/or overtime (OT) periods. Variables included: 1) distance covered and distance covered within four intensity zones (standing-walking S-W, jogging JOG, running RUN, and high-speed running HSR); 2) explosive efforts per minute (EEs); 3) PlayerLoad (PL); 4) the number of jumps per minute; 5) the number of accelerations above 2 m·s2 (ACCs); and 6) the number of decelerations above -2 m·s2 per minute (DECs). The values for total distance, JOG, RUN, HSR, PL, ACC, and DEC were significantly smaller during periods Q2, Q3, Q4, and OT compared to Q1.

Mixed comparison of intervention with eccentric, isometric, and heavy slow resistance for Victorian Institute of Sport Assessment Patella Questionnaire in adults with patellar tendinopathy: A systematic review and network meta-analysis.

Background: PT (Patellar Tendinopathy) is a degenerative disorder of the tendons induced via extended overstretching or overuse of the tendons instead than usual inflammation. In the past, humans have centered on a number of strategies of treating PT such as ultrasound and surgical treatment. However, they did no longer genuinely consider the effectiveness of eccentric, isometric, or HSR (Heavy Slow Resistance Training) education for PT; They did now not really outline the stage of PT to beautify the uniformity of the find out about participants; They did no longer immediately examine the affects of isometric, eccentric, and HSR training.

Impacts of sugar and sweetener warning labels on substitution between sugar- and non-sugar-sweetened beverages in a non-hypothetical selection task.

Background: Front-of-pack (FOP) warning labels have demonstrated effectiveness for reducing sugar-sweetened beverage (SSB) consumption and switching to water. However, an unintended consequence is that they may also increase switching to non-sugar-sweetened beverages (NSSBs). A non-hypothetical experimental study examined the effectiveness of combining sugar and sweetener FOP warning labels to reduce sugary drink consumption and prevent NSSB substitution.

Addressing social and health needs in health care: Characterizing case managers' work to address patient-defined goals.

Objective: To test quantitative process measures characterizing the work of social needs case managers as they assisted patients with diverse health-related needs-spanning both medical and social domains.

Study Setting And Design: The study analyzed secondary data on 7076 patients working with 147 case managers from the CommunityConnect social needs case management program in Contra Costa County, California from 2018 to 2021. The service-designed to be holistic with a focus on social determinants as root causes of health issues-helped patients navigate social services, health care, and mental health care.

Gut microbiota in very early systemic sclerosis: the first case-control taxonomic and functional characterisation highlighting an altered butyric acid profile.

Objectives: In systemic sclerosis (SSc), gastrointestinal involvement is one of the earliest events. We compared the gut microbiota (GM), its short-chain fatty acids (SCFAs) and host-derived free fatty acids (FFAs) in patients with very early diagnosis of SSc (VEDOSS) and definite SSc.

Methods: Stool samples of 26 patients with SSc, 18 patients with VEDOSS and 20 healthy controls (HC) were collected.

Joint optimization of overbooking and seat allocation for high-speed railways considering stochastic demand.

To mitigate empty seat loss caused by random passenger no-show behavior, this study extends seat allocation to joint optimization of overbooking and seat allocation for high-speed railways (HSR). Assuming that stochastic passenger demand follows a specific distribution and considering various constraints, including train capacity, demand, and denied boarding rate constraints, a nonlinear stochastic programming model for joint optimization of overbooking and seat allocation for HSR is constructed with the aim of maximizing railway expected revenue. To solve this optimization model, a multi-level optimization algorithm is designed.

The new ice age: the promise and challenges of rapid oocyte warming protocols.

Oocyte cryopreservation has transformed assisted reproductive technology, providing enhanced flexibility and efficacy in assisted reproductive technology treatments. The shift from traditional slow freezing to vitrification has markedly improved survival rates by preventing ice crystal formation, which can damage cellular structures. Despite these advances, rapid warming of vitrified oocytes remains a challenge due to the unique sensitivity of oocytes to thermal and osmotic stress, which can compromise spindle integrity and developmental competence.

An approach to evaluation of digital data in public health campaigns.

Unlabelled: Mass media campaigns for public health often rely heavily on digital media and advertising tools that are customarily the domain of marketing professionals and primarily used for commercial purposes. Digital campaigns also generate a myriad of metrics, which can pose both a challenge and opportunity for scientists wishing to leverage these data for research and evaluation.

Objective: The aim of this article is to provide practical guidance for the evaluation of paid media campaigns, with a focus on analyzing digital data generated directly by the campaign.

Preserve or destroy: Orphan protein proteostasis and the heat shock response.

Most eukaryotic genes encode polypeptides that are either obligate members of hetero-stoichiometric complexes or clients of organelle-targeting pathways. Proteins in these classes can be released from the ribosome as "orphans"-newly synthesized proteins not associated with their stoichiometric binding partner(s) and/or not targeted to their destination organelle. Here we integrate recent findings suggesting that although cells selectively degrade orphan proteins under homeostatic conditions, they can preserve them in chaperone-regulated biomolecular condensates during stress.

Comparative analysis of IRE1s in plants: insights into heat stress adaptation in Triticum aestivum.

Background: The unfolded protein response (UPR) pathway serves as a crucial mechanism enabling plants to perceive, respond to, and shield themselves from adverse environmental conditions. Inositol-requiring enzyme 1 (IRE1) is one of the key players of the UPR, and resides in the endoplasmic reticulum (ER) within the cell. This study provides a comprehensive analysis of 195 IRE1 genes across 90 diverse plant species, with a focus on their identification and characterization.

Frailty screening with comprehensive geriatrician-led multidisciplinary assessment for older adults during emergency hospital attendance in Ireland (SOLAR): a randomised controlled trial.

Background: Multidisciplinary comprehensive geriatric assessment (CGA) improves outcomes in hospitalised older adults but there is limited evidence on its effectiveness in the emergency department. We aimed to assess the benefits of CGA in the emergency department for older adults living with frailty.

Methods: In this randomised controlled trial, we enrolled older adults (≥75 years) who presented to the emergency department with medical complaints at University Hospital Limerick (Limerick, Ireland).

Optimizing TDP-43 silencing with siRNA-loaded polymeric nanovectors in neuronal cells for therapeutic applications: balancing knockdown and function.

TAR DNA-binding protein 43 (TDP-43) is a ubiquitously expressed DNA/RNA binding protein critical for regulating gene expression, including transcription, splicing, mRNA stability, and protein translation. Aggregation of pathological TDP-43 proteins in the cytoplasm of neurons and glial cells appears to be a common feature of amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases such as frontotemporal dementia (FTD), contributing to motor neuron degeneration and clinical symptoms. Downregulation of TDP-43 expression to prevent or reduce the formation of pathological aggregates is a potential therapeutic approach for treating TDP-43-related diseases.