Malate initiates a proton-sensing pathway essential for pH regulation of inflammation.

Metabolites can double as a signaling modality that initiates physiological adaptations. Metabolism, a chemical language encoding biological information, has been recognized as a powerful principle directing inflammatory responses. Cytosolic pH is a regulator of inflammatory response in macrophages.

Localized molecular chaperone synthesis maintains neuronal dendrite proteostasis.

Proteostasis is maintained through regulated protein synthesis and degradation and chaperone-assisted protein folding. However, this is challenging in neuronal projections because of their polarized morphology and constant synaptic proteome remodeling. Using high-resolution fluorescence microscopy, we discover that hippocampal and spinal cord motor neurons of mouse and human origin localize a subset of chaperone mRNAs to their dendrites and use microtubule-based transport to increase this asymmetric localization following proteotoxic stress.

Neurotransmitter-bound bestrophin channel structures reveal small molecule drug targeting sites for disease treatment.

Best1 and Best2 are two members of the bestrophin family of anion channels critically involved in the prevention of retinal degeneration and maintenance of intraocular pressure, respectively. Here, we solved glutamate- and γ-aminobutyric acid (GABA)-bound Best2 structures, which delineate an intracellular glutamate binding site and an extracellular GABA binding site on Best2, respectively, identified extracellular GABA as a permeable activator of Best2, and elucidated the co-regulation of Best2 by glutamate, GABA and glutamine synthetase in vivo. We further identified multiple small molecules as activators of the bestrophin channels.

Longitudinal network changes and phenoconversion risk in isolated REM sleep behavior disorder.

Isolated rapid eye movement sleep behavior disorder is a prodrome of α-synucleinopathies. Using positron emission tomography, we assessed changes in Parkinson's disease-related motor and cognitive metabolic networks and caudate/putamen dopaminergic input in a 4-year longitudinal imaging study of 13 male subjects with this disorder. We also correlated times to phenoconversion with baseline network expression in an independent validation sample.

Rapid nongenomic estrogen signaling controls alcohol drinking behavior in mice.

Ovarian-derived estrogen can signal non-canonically at membrane-associated receptors in the brain to rapidly regulate neuronal function. Early alcohol drinking confers greater risk for alcohol use disorder in women than men, and binge alcohol drinking is correlated with high estrogen levels, but a causal role for estrogen in driving alcohol drinking has not been established. We found that female mice displayed greater binge alcohol drinking and reduced avoidance when estrogen was high during the estrous cycle than when it was low.

Global mean sea level likely higher than present during the holocene.

Global mean sea-level (GMSL) change can shed light on how the Earth system responds to warming. Glaciological evidence indicates that Earth's ice sheets retreated inland of early industrial (1850 CE) extents during the Holocene (11.7-0 ka), yet previous work suggests that Holocene GMSL never surpassed early industrial levels.

Direct perception of affective valence from vision.

Subjective feelings are thought to arise from conceptual and bodily states. We examine whether the valence of feelings may also be decoded directly from objective ecological statistics of the visual environment. We train a visual valence (VV) machine learning model of low-level image statistics on nearly 8000 emotionally charged photographs.

High-performance 2D electronic devices enabled by strong and tough two-dimensional polymer with ultra-low dielectric constant.

As the feature size of microelectronic circuits is scaling down to nanometer order, the increasing interconnect crosstalk, resistance-capacitance (RC) delay and power consumption can limit the chip performance and reliability. To address these challenges, new low-k dielectric (k < 2) materials need to be developed to replace current silicon dioxide (k = 3.9) or SiCOH, etc.

PSCA-targeted BPX-601 CAR T cells with pharmacological activation by rimiducid in metastatic pancreatic and prostate cancer: a phase 1 dose escalation trial.

Here we report results of a phase 1 multi-institutional, open-label, dose-escalation trial (NCT02744287) of BPX-601, an investigational autologous PSCA-directed GoCAR-T® cell product containing an inducible MyD88/CD40 ON-switch responsive to the activating dimerizer rimiducid, in patients with metastatic pancreatic (mPDAC) or castration-resistant prostate cancer (mCRPC). Primary objectives were to evaluate safety and tolerability and determine the recommended phase 2 dose/schedule (RP2D). Secondary objectives included the assessment of efficacy and characterization of the pharmacokinetics of rimiducid.

Neoadjuvant anti-PD1 immunotherapy for surgically accessible recurrent glioblastoma: clinical and molecular outcomes of a stage 2 single-arm expansion cohort.

Glioblastoma is immunologically "cold" and resistant to single-agent immune-checkpoint inhibitors (ICI). Our previous study of neoadjuvant pembrolizumab in surgically-accessible recurrent glioblastoma identified a molecular signature of response to ICI and suggested that neoadjuvant pembrolizumab may improve survival. To increase the power of this observation, we enrolled an additional 25 patients with a primary endpoint of evaluating the cell cycle gene signature associated with neoadjuvant pembrolizumab and performed bulk-RNA seq on resected tumor tissue (NCT02852655).

Moving Towards the Outpatient DIEP Flap: Factors Influencing Early Discharge.

Background: Enhanced Recovery After Surgery (ERAS) protocols can reduce the length of stay (LOS) for surgical patients, including those undergoing unilateral deep inferior epigastric artery perforator (DIEP) flap breast reconstruction, allowing most patients to be discharged by postoperative day 2. However, some patients require a prolonged inpatient stay due to difficulty completing postoperative milestones. This study aims to identify factors associated with increased LOS after DIEP flap breast reconstruction and assess safety of earlier discharge.

Three Decades of Outpatient Plastic Surgery Safety: A Review of 42,720 Consecutive Cases.

Background: Outpatient plastic surgery offers cost-effective solutions and enhanced privacy but demands careful patient assessment for suitability and vigilant anticipation of adverse events. This study provides recommendations to enhance patient safety in outpatient settings by analyzing over 40,000 consecutive cases spanning across three decades.

Methods: We retrospectively reviewed all consecutive cases completed by board-certified plastic surgeons at an accredited outpatient surgical center between 1995-2023.

Management of Spontaneous Epidural Hematoma in the Setting of Vaso-occlusive Crisis Among Pediatric Patients With Sickle Cell Disease: A Case Series and Scoping Literature Review.

Spontaneous epidural hematoma (EDH) is a rare sickle cell disease (SCD) complication. We report 3 pediatric cases with SCD and spontaneous EDH and 1 with subgaleal hematomas in the setting of vaso-occlusive crises and elaborate on their presentation and management. Through a scoping review, we identified 71 additional cases reported from 1970 to 2024 and highlighted notable features.

Machine learning-enabled virtual screening indicates the anti-tuberculosis activity of aldoxorubicin and quarfloxin with verification by molecular docking, molecular dynamics simulations, and biological evaluations.

Drug resistance in Mycobacterium tuberculosis (Mtb) is a significant challenge in the control and treatment of tuberculosis, making efforts to combat the spread of this global health burden more difficult. To accelerate anti-tuberculosis drug discovery, repurposing clinically approved or investigational drugs for the treatment of tuberculosis by computational methods has become an attractive strategy. In this study, we developed a virtual screening workflow that combines multiple machine learning and deep learning models, and 11 576 compounds extracted from the DrugBank database were screened against Mtb.

A comprehensive benchmark study of methods for identifying significantly perturbed subnetworks in cancer.

Network-based methods utilize protein-protein interaction information to identify significantly perturbed subnetworks in cancer and to propose key molecular pathways. Numerous methods have been developed, but to date, a rigorous benchmark analysis to compare the performance of existing approaches is lacking. In this paper, we proposed a novel benchmarking framework using synthetic data and conducted a comprehensive analysis to investigate the ability of existing methods to detect target genes and subnetworks and to control false positives, and how they perform in the presence of topological biases at both gene and subnetwork levels.

"The Heart of the Center": Exploring the Role of the Patient Care Technician in US Dialysis Care.

Rationale & Objective: Dialysis patient care technicians (PCTs) provide essential, frontline care for patients receiving in-center hemodialysis. We qualitatively explored perceptions of the PCT job role, responsibilities, and training among current PCTs, non-PCT dialysis staff, and patients receiving hemodialysis.

Study Design: Focus group study.

Bias-Based Bullying Among Sexual and Gender Minority Youth Living With Disabilities.

Both sexual and gender minority youth (SGMY) and youth living with disabilities are disproportionately impacted by bias-based bullying in school settings. While research has separately examined how sexual and gender minority status and disability status are associated with experiences of bullying, very little research has explored the experiences of youth living with these identities simultaneously. This study examined to what extent SGMY report differential experiences of bias-based bullying depending on various identities and the type of disability an individual reports.

A phase I study using bortezomib (Velcade), cladribine, and rituximab in treating patients over 50 years old with mantle cell lymphoma.

Unlabelled: Cladribine indirectly downregulates methylation of DNA, RNA, and histones by blocking the transfer of methyl groups from -adenosyl-methionine. The cladribine and rituximab combination showed a synergetic effect in treating B-cell lymphomas. Bortezomib (Velcade) is a Food and Drug Administration (FDA)-approved proteasome inhibitor for treating mantle cell lymphoma (MCL).

The Impact of Headaches in Young Adults: An Analysis of Types, Triggers, and Daily Functioning Through the Headache-Attributed Restriction, Disability, Social Handicap, and Impaired Participation (HARDSHIP) Questionnaire.

Background:  Headaches affect people's social, intellectual, and personal lives and are quite common worldwide, especially among young adults. Primary headaches that cause significant impairment, such as tension-type headaches (TTH) and migraines, frequently start in adolescence and early adulthood. Research on the incidence and consequences of headache problems among young people in India is scarce, especially when it comes to a variety of academic fields.

Iris Avulsion During Corneal Wound Hydration After Uneventful Cataract Extraction.

We report a case of spontaneous total iris avulsion that occurred during corneal wound hydration following an uneventful phacoemulsification procedure. An 86-year-old woman underwent cataract surgery on her right eye, during which a single-piece acrylic intraocular lens (Bausch and Lomb Akreos Adapt Advanced Optics, Bausch and Lomb Incorporated, Rochester, NY, USA) was implanted in the bag, and the viscoelastic material was removed. During corneal wound hydration, total iris avulsion was observed, with the iris prolapsing out of the anterior chamber through the main wound.

Bibliometric Analysis of Peer-Reviewed Literature on Erosive Tooth Wear From 1945 to 2023.

Erosive tooth wear (ETW) is a prevalent oral condition with varying etiology, including erosion, abrasion, abfraction, and attrition. It is reported in the literature in different nomenclatures, hindering the ability to identify the emerging trends and influential scholarly works and bodies within this field. Using a bibliometric analysis approach, this study aims to evaluate the trends, themes, and productivity of the research on ETW condition while respecting its different terminologies.

Immediate postplacental intrauterine device placement: retrospective cohort study of expulsion and associated risk factors.

Background: Postpartum contraception is typically provided during postpartum visits. When desired and accessible, the immediate postpartum period provides an additional opportunity to increase the use of more effective contraceptive methods to potentially reduce subsequent unintended pregnancies and improve pregnancy outcomes. In New York State, recent policy changes expanded Medicaid coverage to include immediate postplacental intrauterine device insertion.

Lipidomic analysis of plant-derived extracellular vesicles for guidance of potential anti-cancer therapy.

Plant-derived extracellular vesicles (PEVs) have been regarded as a superior source for nanomedicine and drug delivery systems. Nevertheless, their clinical translation is hindered by the lack of clarity and even contradiction in their biomedical applications. Herein, we conducted a comprehensive compositional analysis of four commonly used PEVs to fully understand their functional lipid contents and assess their potential therapeutic applications.

Impact of steroid-sparing immunosuppressive agents on tumor outcome in the context of cancer immunotherapy with highlight on melanoma: a systematic literature review and meta-analysis.

Background: The impact of steroid-sparing immunosuppressive agents (SSIAs) for immune-related adverse events (irAEs) on tumor outcome is not well-known. This systematic review evaluates tumor outcomes for corticosteroid (CS) monotherapy versus CS with SSIA (CS-SSIA) for irAE treatment with a focus on melanoma.

Methods: Search was conducted through 1/5/23 using PubMed, Embase, Cochrane CENTRAL, and Web of Science.

The ADHD Assessment Quality Assurance Standard for Children and Teenagers (CAAQAS).

Around 5% of the children and teenagers worldwide are affected by Attention-Deficit/Hyperactivity Disorder [ADHD], making it a major public health concern. Recently, demand for assessments has substantially increased, putting strain on healthcare and waiting lists. There is concern that pressure to clear service bottlenecks is leading to variable quality and reliability of ADHD assessments in this population.