Severe Lymphopenia Predicts Poorer Survival in Patients With Rectal Cancer Undergoing Neoadjuvant Chemoradiation.

Purpose: Chemoradiation-induced lymphopenia is common and associated with poorer survival in multiple solid malignancies. However, the association between chemoradiation-related lymphopenia and survival outcomes in rectal cancer is yet unclear. The objective of this study was to evaluate the prognostic impact of lymphopenia and its predictors in patients with rectal cancer undergoing neoadjuvant chemoradiation.

Evidence of Rapid Infection of Four Sweetpotato Potyviruses in a Commercial Field in California.

Sweetpotato ( Lam.) is grown worldwide and is a staple food in many countries. One of the main constraints for sweetpotato production is cultivar decline, caused by the accumulation of viruses and subsequent losses of storage root yield and quality over years of vegetative propagation.

N-detected TROSY for H-N heteronuclear correlation to study intrinsically disordered proteins: strategies to increase spectral quality.

Intrinsically disordered proteins and protein regions are central to many biological processes but difficult to characterize at atomic resolution. Nuclear magnetic resonance is particularly well-suited for providing structural and dynamical information on intrinsically disordered proteins, but existing NMR methodologies need to be constantly refined to provide greater sensitivity and resolution, particularly to capitalise on the potential of high magnetic fields to investigate large proteins. In this paper, we describe how N-detected 2D NMR experiments can be optimised for better performance.

The paradoxical GH response at OGTT does not predict Pasireotide efficacy but matters for glucose metabolism.

Purpose: A paradoxical increase in GH after oral glucose load (GH-Par) characterizes about one-third of acromegaly patients and is associated with a better response to first-generation somatostatin receptor ligands (fg-SRLs). Pasireotide is typically considered as a second-/third-line treatment. Here, we investigated the predictive role of GH-Par in pasireotide response and adverse event development.

Witchcraft, Envy, and Norm Enforcement in Mauritius.

Recent research has shown that an array of religious beliefs can be used to enforce socially normative behaviour, but the application of these theories to other supernatural beliefs, including witchcraft, is still nascent. Across two pre-registered studies in Mauritius, we examine how witchcraft is believed to be caused by envy and how this belief can create and enforce social norms around not causing envy. Data was collected in-person in Mauritius.

Empagliflozin Reduces High Glucose-Induced Cardiomyopathy in hiPSC-Derived Cardiomyocytes : Glucose-induced Lipotoxicity in hiPSC-Derived Cardiomyocytes.

Human-induced pluripotent stem cell (hiPSC) technology has been applied in pathogenesis studies, drug screening, tissue engineering, and stem cell therapy, and patient-specific hiPSC-derived cardiomyocytes (hiPSC-CMs) have shown promise in disease modeling, including diabetic cardiomyopathy. High glucose (HG) treatment induces lipotoxicity in hiPSC-CMs, as evidenced by changes in cell size, beating rate, calcium handling, and lipid accumulation. Empagliflozin, an SGLT2 inhibitor, effectively mitigates the hypertrophic changes, abnormal calcium handling, and contractility impairment induced by HG.

Novel pain management strategy for uterine fibroid embolization.

Background: Uterine fibroid embolization can be associated with significant pain due to fibroid ischemia and interventions of the procedure itself. Fentanyl and midazolam are commonly provided for sedation and pain relief, but are not tolerated by all patients. This report outlines a novel pain management strategy for uterine fibroid embolization in a patient who could not receive either opioids or benzodiazepines.

Predicting Postoperative Infection After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy with Splenectomy.

Background: Hematologic changes after splenectomy and hyperthermic intraperitoneal chemotherapy (HIPEC) can complicate postoperative assessment of infection. This study aimed to develop a machine-learning model to predict postoperative infection after cytoreductive surgery (CRS) and HIPEC with splenectomy.

Methods: The study enrolled patients in the national TriNetX database and at the Johns Hopkins Hospital (JHH) who underwent splenectomy during CRS/HIPEC from 2010 to 2024.

Attenuated cardiac autonomic function in patients with long-COVID with impaired orthostatic hemodynamics.

Purpose: Long-coronavirus disease (long-COVID) is associated with initial orthostatic hypotension and postural orthostatic tachycardia syndrome. Whether altered autonomic tone underlies these abnormalities is unknown. We compared autonomic function between patients with long-COVID and healthy controls, and within patients with long-COVID with different orthostatic hemodynamic phenotypes.

GABA mitigates mitochondrial apoptosis induced by high temperature stress in the Pacific oyster (Crassostrea gigas).

Background: High temperature is a critical environmental factor leading to mass mortality in oyster aquaculture in China. Recent advancements highlight the physiological regulation function of γ-aminobutyric acid (GABA) in the adaptation of environmental stress.

Methods And Results: This study examined the physiological responses of the Pacific oyster (Crassostrea gigas) upon high temperature exposure, focusing on the histopathological changes in gill, the GABA concentration, the mRNA expression and activities of apoptosis-related genes.

Phase I trial of ATR inhibitor elimusertib with FOLFIRI in advanced or metastatic gastrointestinal malignancies (ETCTN 10406).

Background: ATR is an apical DDR kinase activated at damaged replication forks. Elimusertib is an oral ATR inhibitor and potentiates irinotecan in human colorectal cancer models.

Methods: To establish dose and tolerability of elimusertib with FOLFIRI, a Bayesian Optimal Interval trial design was pursued.

Transcriptome Analysis Reveals the Key Genes and Pathways for Growth, Ion Transport, and Oxidative Stress in Post-Larval Black Tiger Shrimp (Penaeus monodon) Under Acute Low Salt Stress.

As an abiotic stress factor, salinity significantly affects the physiological activities of crustaceans. In this study, transcriptome sequencing was used to evaluate the mechanism of ion transport and the physiological response of black tiger shrimp (Penaeus monodon) under low salt stress. Four hundred post larval (PL) stage P.

The arabidopsis phytoglobin 1 (Pgb1) involvement in somatic embryogenesis is linked to changes in ethylene and the class VII ethylene transcription factor HRE2.

Phytoglobin1 promotes Arabidopsis somatic embryogenesis through the mediation of ethylene and the ERFVII HRE2. Generation of somatic embryos in Arabidopsis (Arabidopsis thaliana) is a two-step process, encompassing an induction phase where embryogenic tissue (ET) is formed followed by a developmental phase encouraging the growth of the embryos. Using previously characterized transgenic lines dysregulating the class 1 Phytoglobin (Pgb1) we show that suppression of Pgb1 decreases somatic embryogenesis (SE).

De novo proliferative glomerulonephritis with monoclonal IgG deposits in an adolescent kidney transplant recipient.

Proliferative Glomerulonephritis with Monoclonal IgG Deposits (PGNMID) is a glomerular disease characterized by membranoproliferative and mesangioproliferative lesions, with granular capillary wall monoclonal IgG positivity and immunoglobulin light chain restriction. Most commonly a disease of older adults, we present the case of an 18-year-old patient who developed de novo PGNMID in a kidney allograft three years after kidney transplantation. There was minimal proteinuria and no serum paraproteinemia was detected, so the patient was managed conservatively.

Efficacy of complement inhibition with pegcetacoplan in children with C3 glomerulopathy.

Background: C3 glomerulopathy (C3G) is a rare kidney disease due to a dysregulation of the alternative complement pathway, orphan of specific treatment. Pegcetacoplan is an inhibitor of the third complement component C3, currently on a phase III registration protocol in C3G. Here we describe our experience with the off-label use of pegcetacoplan in pediatric patients with C3G.

The anti-dyskinetic effect of the clinic-ready mGluRpositive allosteric modulator AZD8529 in the 6-OHDA-lesioned rat.

L-3,4-dihydroxyphenylalanine (L-DOPA) remains the main treatment for motor symptoms of Parkinson's disease (PD). However, chronic use is associated with the development of complications such as L-DOPA-induced dyskinesia. We previously demonstrated that LY-487,379, a highly selective metabotropic glutamate receptor 2 (mGluR2) positive allosteric modulator (PAM), reduces the severity of L-DOPA-induced abnormal involuntary movements (AIMs) in the 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD, without interfering with the anti-parkinsonian action of L-DOPA.

The association between pain, analgesia, and delirium among critically ill adults: a systematic review and meta-analysis.

Purpose: We performed a systematic review with meta-analysis examining the relationship between pain or pain medications and delirium occurence, duration, and severity.

Methods: We searched MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials from inception to May 15, 2023. We included randomised or observational studies among critically ill adults, that reported data on pain or exposure to analgesics, and reported delirium presence, duration, or severity with no language or region restrictions.

[New methods at the transition from research to routine diagnostics].

Background: Pathology, traditionally focused on classification and diagnosis, is continuously evolving through new technologies. Advances in proteomics, epigenetics, tissue staining, and 3D imaging expand the possibilities of classical morphology.

Aim Of The Study: The aim of this study was to investigate how modern technologies can improve diagnostic accuracy and therapy selection and how they can be integrated into pathologic routine diagnostics.

Ravulizumab demonstrates long-term efficacy, safety and favorable patient survival in patients with paroxysmal nocturnal hemoglobinuria.

Ravulizumab is a second-generation complement component 5 (C5) inhibitor (C5i) approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) following positive results from two pivotal trials in patients with PNH originally naive to C5i treatment and eculizumab-experienced patients with PNH. In both trials, after the 26week primary evaluation period, all patients received ravulizumab for up to 6 years. To report ravulizumab treatment outcomes in patients with PNH originally naive to C5i treatment and eculizumab-experienced patients with PNH treated for up to 6 years.

Evolution of long scalp hair in humans.

The ability to grow long scalp hair is a distinct human characteristic. It probably originally evolved to aid in cooling the sun-exposed head, although the genetic determinants of long hair are largely unknown. Despite ancestral variations in hair growth, long scalp hair is common to all extant human populations, which suggests its emergence before or concurrently with the emergence of anatomically modern humans (AMHs), approximately 300 000 years ago.

Healthy Aging and the Gut Microbiome in People With and Without HIV.

Background: Aging-related comorbidities are more common in people with human immunodeficiency virus (HIV) compared to people without HIV. The gut microbiome may play a role in healthy aging; however, this relationship remains unexplored in the context of HIV.

Methods: 16S rRNA gene sequencing was conducted on stool from 1409 women (69% with HIV; 2304 samples) and 990 men (54% with HIV; 1008 samples) in the MACS/WIHS Combined Cohort Study.

Intercellular mRNA transfer alters the human pluripotent stem cell state.

Intercellular transmission of messenger RNA (mRNA) is being explored in mammalian species using immortal cell lines. Here, we uncover an intercellular mRNA transfer phenomenon that allows for the adaptation and reprogramming of human primed pluripotent stem cells (hPSCs). This process is induced by the direct cell contact-mediated coculture with mouse embryonic stem cells under the condition impermissible for primed hPSC culture.

BCL6 coordinates muscle mass homeostasis with nutritional states.

Nutritional status is a determining factor for growth during development and homeostatic maintenance in adulthood. In the context of muscle, growth hormone (GH) coordinates growth with nutritional status; however, the detailed mechanisms remain to be fully elucidated. Here, we show that the transcriptional repressor B cell lymphoma 6 (BCL6) maintains muscle mass by sustaining GH action.

The XCL1-XCR1 axis supports intestinal tissue residency and antitumor immunity.

Tissue-resident memory T cells (TRM) provide frontline protection against pathogens and emerging malignancies. Tumor-infiltrating lymphocytes (TIL) with TRM features are associated with improved clinical outcomes. However, the cellular interactions that program TRM differentiation and function are not well understood.

Novel clinical trial designs emerging from the molecular reclassification of cancer.

Next-generation sequencing has revealed the disruptive reality that advanced/metastatic cancers have complex and individually distinct genomic landscapes, necessitating a rethinking of treatment strategies and clinical trial designs. Indeed, the molecular reclassification of cancer suggests that it is the molecular underpinnings of the disease, rather than the tissue of origin, that mostly drives outcomes. Consequently, oncology clinical trials have evolved from standard phase 1, 2, and 3 tissue-specific studies; to tissue-specific, biomarker-driven trials; to tissue-agnostic trials untethered from histology (all drug-centered designs); and, ultimately, to patient-centered, N-of-1 precision medicine studies in which each patient receives a personalized, biomarker-matched therapy/combination of drugs.