The Hao-Fountain syndrome protein USP7 regulates neuronal connectivity in the brain via a novel p53-independent ubiquitin signaling pathway.

Mutation or deletion of the deubiquitinase USP7 causes Hao-Fountain syndrome (HAFOUS), which is characterized by speech delay, intellectual disability, and aggressive behavior and highlights important unknown roles of USP7 in the nervous system. Here, we conditionally delete USP7 in glutamatergic neurons in the mouse forebrain, triggering disease-relevant phenotypes, including sensorimotor deficits, impaired cognition, and aggressive behavior. Although USP7 deletion induces p53-dependent neuronal apoptosis, most behavioral abnormalities in USP7 conditional knockout mice persist following p53 loss.

Protocol for identifying Dicer as dsRNA binding and cleaving reagent in response to transfected dsRNA.

Mammalian Dicer has been proved to be functional on double-stranded RNAs (dsRNAs) and involved in antiviral immunity or immune regulation. Here, we present a protocol for identifying Dicer as a dsRNA binding and cleaving factor to transfected dsRNA in cell lines, based on small RNA sequencing (RNA-seq) and dsRNA-immunoprecipitation (dsRNA-IP). We detail both experimental processes and analysis on small RNA-seq data.

Identification of GBN5 as a molecular biomarker of pan-cancer species by integrated multi-omics analysis.

Introduction: We conducted a panoramic analysis of GBN5 expression and prognosis in 33 cancers, aiming to deepen the systematic understanding of GBN5 in cancer.

Materials And Methods: We employed a multi-omics approach, including transcriptomic, genomic, proteomic, single-cell cytomic, spatial transcriptomic, and genomic data, to explore the prognostic value and potential oncogenic mechanisms of GBN5 across pan-cancers from multiple perspectives.

Results: We found that GBN5 was differentially expressed in multiple tumors and showed early diagnostic value.

What does the patients' perception of alignment tell us about alignment targets in total knee arthroplasty?

Introduction: Knee alignment significantly impacts the outcome of total knee arthroplasty (TKA). Understanding patient perceptions of their knee alignment in relation to objective measurements is essential to ensure optimal surgical outcomes and to meet patients' expectations. This study reports patients' perception of pre- and postoperative knee alignment in relation to radiographic alignment measurements.

Extreme heat risk and the potential implications for the scheduling of football matches at the 2026 FIFA World Cup.

Climate change is making extreme heat events more frequent and intense. This negatively impacts many aspects of society, including organised sport. As the world's most watched sporting event, the FIFA World Cup commands particular attention around the threat of extreme heat.

Abdominopelvic imaging in the follow-up of testicular germ-cell tumors in adults: recommendations of the Scrotal and Penile Imaging Working Group of the European Society of Urogenital Radiology.

Objectives: The Scrotal and Penile Imaging Working Group (SPIWG) of the European Society of Urogenital Radiology (ESUR) aimed to formulate recommendations on the imaging modalities and minimal technical requirements for abdominopelvic imaging in the follow-up of adult patients treated for testicular germ-cell tumors (TGCT).

Methods: The SPIWG members performed an extensive literature search, reviewed the current clinical practice, and reached a consensus based on the opinions of experts in the field.

Results: Recurrence in patients treated for TGCT mainly occurs in retroperitoneal lymph nodes (LNs).

Bimekizumab efficacy and safety through 3 years in patients with moderate to severe plaque psoriasis: Long-term results from the BE RADIANT phase 3b trial open-label extension period.

Background: Overexpression of interleukin (IL)-17A and IL-17F significantly influences psoriasis pathology. Until recently, biologics targeting IL-17A alone, like secukinumab, were used to treat psoriasis. Bimekizumab is a monoclonal IgG1 antibody that targets both IL-17A and IL-17F.

High Modified 5 Factor Frailty Index is Associated With Worse PROMs and Decreased Return to Activities After 1 or 2 Level MI-TLIF.

Study Design: Retrospective cohort study.

Objective: Frailty is defined as a state of minimal "physiologic reserve." The modified 5 factor frailty index (mFI-5) is a recently proposed metric for assessing frailty and has been previously studied as a predictor of morbidity and mortality.

Task activation results in regional C-lactate signal increase in the human brain.

Hyperpolarized-C magnetic resonance imaging (HP-C MRI) was used to image changes in C-lactate signal during a visual stimulus condition in comparison to an eyes-closed control condition. Whole-brain C-pyruvate, C-lactate and C-bicarbonate production was imaged in healthy volunteers (N = 6, ages 24-33) for the two conditions using two separate hyperpolarized C-pyruvate injections. BOLD-fMRI scans were used to delineate regions of functional activation.

Virtual screening: hope, hype, and the fine line in between.

Introduction: Technological advancements in virtual screening (VS) have rapidly accelerated its application in drug discovery, as reflected by the exponential growth in VS-related publications. However, a significant gap remains between the volume of computational predictions and their experimental validation. This discrepancy has led to a rise in the number of unverified 'claimed' hits which impedes the drug discovery efforts.

The silent pandemic of stress: impact on menstrual cycle and ovulation.

In the current age of technological advancement, stress has emerged as a silent pandemic affecting individuals, especially young generations, globally. Factors such as increased competition, social pressures fueled by social media and smartphones, and a sense of diminished control in the face of modern challenges contribute to rising stress levels. In addition to the negative implications on mental well-being, stress affects physiological processes such as the menstrual cycle.

Analysis of "Dose Accuracy and Reliability of a Connected Insulin Pen System".

In an article in the , Backfish and coauthors examined the dose accuracy and reliability of the Tempo Pen and Tempo Smart Button connected insulin pen system. This study sponsored by Eli Lilly and Company found that this system met the International Organization for Standardization 11608-1:2014 requirements for dose accuracy at a range of doses, as well as the data transfer requirements after all injections. While these results are very encouraging, they were based on simulated human factors data while data from a human factors validation study where individuals successfully dialed and administered correct doses was not reported.

Evaluation of the Pediatric Regional Anesthesia Time-Out Checklist: A Simulation Study.

Introduction: The Society for Pediatric Anesthesia Quality and Safety Committee developed the Pediatric Regional Anesthesia Time-Out Checklist, consisting of 14 safety items intended to be reviewed by an anesthesia team prior to a regional anesthetic. Primarily, we hypothesized that use of this Checklist would increase the number of safety items performed compared with no checklist, evaluating the usefulness of this tool. Secondarily, we hypothesized that, after checklist training, subjects would show better clinical judgment by electing to perform a regional anesthetic in scenarios in which no programmed error existed and electing to not perform a regional anesthetic in scenarios in which a programmed error did exist.

Probability of Achieving Bone Mineral Density Treatment Goals with Denosumab Treatment in Postmenopausal Women with Osteoporosis.

Bone mineral density (BMD) levels achieved on osteoporosis treatment are predictive of subsequent fracture risk, and T-score > -2.5 has been proposed as a minimum treatment target for women with osteoporosis. Knowing the likelihood of attaining target T-scores with different medications for different baseline BMD levels can help determine appropriate initial treatment for individual patients.

Flunarizine as a Candidate for Drug Repurposing Against Human Pathogenic Mammarenaviruses.

Lassa fever (LF), a viral hemorrhagic fever disease with a case fatality rate that can be over 20% among hospitalized LF patients, is endemic to many West African countries. Currently, no vaccines or therapies are specifically licensed to prevent or treat LF, hence the significance of developing therapeutics against the mammarenavirus Lassa virus (LASV), the causative agent of LF. We used in silico docking approaches to investigate the binding affinities of 2015 existing drugs to LASV proteins known to play critical roles in the formation and activity of the virus ribonucleoprotein complex (vRNP) responsible for directing replication and transcription of the viral genome.

Expanding the Diversity of : A Novel Genus from .

Six novel phages belonging to the family were isolated using as a host. Phages MuffinTheCat, Badulia, DesireeRose, Bee17, SCoupsA, and LuzDeMundo were purified from environmental samples by students participating in the Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) program at Alliance University, New York. The phages have linear dsDNA genomes 15,438-15,636 bp with 112-120 bp inverted terminal repeats.

Plant Compounds Inhibit the Growth of W12 Cervical Precancer Cells Containing Episomal or Integrant HPV DNA; Tanshinone IIA Synergizes with Curcumin in Cervical Cancer Cells.

This study explores the effects of plant compounds on human papillomavirus (HPV)-induced W12 cervical precancer cells and bioelectric signaling. The aim is to identify effective phytochemicals, both individually and in combination, that can prevent and treat HPV infection and HPV associated cervical cancer. Phytochemicals were tested using growth inhibition, combination, gene expression, RT PCR, and molecular docking assays.

Investigations of Long-Acting Formulations in Children, Adolescents, and Pregnant Women: A Systematic Review.

Long-acting and extended-release drug delivery strategies have greatly improved treatment for a variety of medical conditions. Special populations, specifically infants, children, young people, and pregnant and postpartum women, could greatly benefit from access to these strategies but are often excluded from clinical trials. We conducted a systematic review of all clinical studies involving the use of a long-acting intramuscular injection or implant in infants, children, young people, and pregnant and postpartum people.

Dietary Interventions, Supplements, and Plant-Derived Compounds for Adjunct Vitiligo Management: A Review of the Literature.

Vitiligo is a chronic autoimmune pigmentation disorder shaped by a complex interplay of genetic predispositions and environmental triggers. While conventional therapies-phototherapy, corticosteroids, and immunosuppressants-can be effective, their benefits are often partial and temporary, with recurrence common once treatment stops. As such, there is increasing interest in exploring complementary approaches that may offer a more sustainable impact.

Associations of Maternal Prenatal Zinc Consumption with Infant Brain Tissue Organization and Neurodevelopmental Outcomes.

Background/objectives: While studies in rat pups suggest that early zinc exposure is critical for optimal brain structure and function, associations of prenatal zinc intake with measures of brain development in infants are unknown. This study aimed to assess the associations of maternal zinc intake during pregnancy with MRI measures of brain tissue microstructure and neurodevelopmental outcomes, as well as to determine whether MRI measures of the brain mediated the relationship between maternal zinc intake and neurodevelopmental indices.

Methods: Forty-one adolescent mothers were recruited for a longitudinal study during pregnancy.

Real-Time Pharmacovigilance: Transforming Population-Based Monitoring of Post-Approval Vaccine Safety Through Rapid Cycle Analysis (RCA)-A Review of the Published Literature.

: Rapid cycle analysis (RCA) is an established and efficient methodology that has been traditionally utilized by United States health authorities to monitor post-approval vaccine safety. Initially developed in the Vaccine Safety Datalink (VSD) in early 2000s, RCA has evolved into a valuable approach for timely post-approval signal detection. Due to the availability of additional near real-time data sources and enhanced analytic approaches, the use of RCA has expanded.

Facilitation of Tumor Stroma-Targeted Therapy: Model Difficulty and Co-Culture Organoid Method.

Tumors, as intricate ecosystems, comprise oncocytes and the highly dynamic tumor stroma. Tumor stroma, representing the non-cancerous and non-cellular composition of the tumor microenvironment (TME), plays a crucial role in oncogenesis and progression, through its interactions with biological, chemical, and mechanical signals. This review aims to analyze the challenges of stroma mimicry models, and highlight advanced personalized co-culture approaches for recapitulating tumor stroma using patient-derived tumor organoids (PDTOs).

Seroprevalence of in White-Tailed Deer () in New York State.

The parasitic protozoa, (), is a model organism for one health because of its wide-ranging impacts on humans, wildlife, and domestic animals. Intermediate hosts, including white-tailed deer (), have been implicated in its maintenance. Prior analysis of seroprevalence in New York State deer focused on rural areas; however, the high density of domestic cats () in urban areas has been implicated in its spread amongst deer.

State of the Art of Primary PCI: Present and Future.

Primary percutaneous coronary intervention (PCI) has revolutionized the management of ST-elevation myocardial infarction (STEMI), markedly improving patient outcomes. Despite technological advancements, pharmacological innovations, and refined interventional techniques, STEMI prognosis remains burdened by a persistent incidence of cardiac death and heart failure (HF), with mortality rates plateauing over the last decade. This review examines current practices in primary PCI, focusing on critical factors influencing patient outcomes.