Tumour-infiltrating Lymphocytes and Radiation Therapy in Rectal Cancer: Systematic Review and Meta-analysis.

Aim: Tumour-infiltrating lymphocytes (TILs) represent a promising cancer biomarker. Different TILs, including CD8+, CD4+, CD3+, and FOXP3+, have been associated with clinical outcomes. However, data are lacking regarding the value of TILs for patients receiving radiation therapy (RT).

Coordinated immune networks in leukemia bone marrow microenvironments distinguish response to cellular therapy.

Understanding how intratumoral immune populations coordinate antitumor responses after therapy can guide treatment prioritization. We systematically analyzed an established immunotherapy, donor lymphocyte infusion (DLI), by assessing 348,905 single-cell transcriptomes from 74 longitudinal bone marrow samples of 25 patients with relapsed leukemia; a subset was evaluated by both protein- and transcriptome-based spatial analysis. In acute myeloid leukemia (AML) DLI responders, we identified clonally expanded CD8 cytotoxic T lymphocytes with in vitro specificity for patient-matched AML.

Improved daily PM estimates in India reveal inequalities in recent enhancement of air quality.

Poor ambient air quality poses a substantial global health threat. However, accurate measurement remains challenging, particularly in countries such as India where ground monitors are scarce despite high expected exposure and health burdens. This lack of precise measurements impedes understanding of changes in pollution exposure over time and across populations.

Diverse and highly differentiated lava suite in Jezero crater, Mars: Constraints on intracrustal magmatism revealed by Mars 2020 PIXL.

The Jezero crater floor features a suite of related, iron-rich lavas that were examined and sampled by the Mars 2020 rover Perseverance, and whose textures, minerals, and compositions were characterized by the Planetary Instrument for X-ray Lithochemistry (PIXL). This suite, known as the Máaz formation (fm), includes dark-toned basaltic/trachy-basaltic rocks with intergrown pyroxene, plagioclase feldspar, and altered olivine and overlying trachy-andesitic lava with reversely zoned plagioclase phenocrysts in a K-rich groundmass. Feldspar thermal disequilibrium textures indicate that they were carried from their crustal staging area.

Synthesis and preclinical evaluation of tigilanol tiglate analogs as latency-reversing agents for the eradication of HIV.

Tigilanol tiglate (EBC-46) is a selective modulator of protein kinase C (PKC) isoforms that is Food and Drug Administration (FDA) approved for the treatment of mast cell tumors in canines with up to an 88% cure rate. Recently, it has been FDA approved for the treatment of soft tissue sarcomas in humans. The role of EBC-46 and, especially, its analogs in efforts to eradicate HIV, treat neurological and cardiovascular disorders, or enhance antigen density in antigen-targeted chimeric antigen receptor-T cell and chimeric antigen receptor-natural killer cell immunotherapies has not been reported.

Romosozumab Improves Tissue Thickness-Adjusted Trabecular Bone Score in Women With Osteoporosis and Diabetes.

Context: Trabecular bone score (TBS), a gray-level texture index derived from lumbar spine (LS) dual-energy x-ray absorptiometry (DXA) scans, is decreased in patients with diabetes and is associated with increased fracture risk, independent of areal bone mineral density (aBMD), but potentially influenced by abdominal fat tissue.

Objective: Evaluate effect of romosozumab (210 mg monthly) for 12 months followed by alendronate (70 mg weekly) for 24 months vs alendronate alone (70 mg weekly) for 36 months on LS aBMD and TBS in women with type 2 diabetes (T2D) enrolled in the ARCH study.

Methods: This post hoc analysis included women from ARCH who had T2D at baseline and LS DXA scans at baseline and ≥1 postbaseline visit (romosozumab-to-alendronate, n = 165; alendronate-to-alendronate, n = 195).

An alternatively translated isoform of PPARG proposes AF-1 domain inhibition as an insulin sensitization target.

PPARγ is the pharmacological target of thiazolidinediones (TZDs), potent insulin sensitizers that prevent metabolic disease morbidity but are accompanied by side effects such as weight gain, in part due to non-physiological transcriptional agonism. Using high throughput genome engineering, we targeted nonsense mutations to every exon of PPARG, finding an ATG in Exon 2 (chr3:12381414, CCDS2609 c.A403) that functions as an alternative translational start site.

Iodinated Contrast Adsorption in Cartridges With Styrene-Divinylbenzene Sorbent.

Background: Contrast-associated acute kidney injury (CA-AKI) is frequent in patients with chronic kidney disease who are submitted to cardiac endovascular procedures using iodinated contrast. In hemoadsorption, cartridges containing styrene-divinylbenzene sorbent resin are applied to remove substances from the blood through an extracorporeal circuit. Importantly, iodinated contrast is also removed via adsorption.

Sex-specific activation of platelet purinergic signaling is key in local cytokine release and phagocytosis in the peritoneal cavity in intra-abdominal sepsis.

Intra-abdominal sepsis is a life-threatening complex syndrome caused by microbes in the gut microbiota invading the peritoneal cavity. It is one of the major complications of intra-abdominal surgery. To date, only supportive therapies are available.

MaTableGPT: GPT-Based Table Data Extractor from Materials Science Literature.

Efficiently extracting data from tables in the scientific literature is pivotal for building large-scale databases. However, the tables reported in materials science papers exist in highly diverse forms; thus, rule-based extractions are an ineffective approach. To overcome this challenge, the study presents MaTableGPT, which is a GPT-based table data extractor from the materials science literature.

Phase 2 Randomised Study of Bulevirtide as Monotherapy or Combined With Peg-IFNα-2a as Treatment for Chronic Hepatitis Delta.

Background And Aim: Bulevirtide (BLV) leads to beneficial virologic and biochemical responses when given alone to treat hepatitis delta virus (HDV) infection, which causes the most severe form of chronic viral hepatitis. We evaluated 48 weeks of BLV monotherapy, BLV + tenofovir disoproxil fumarate (TDF) and BLV + pegylated interferon alfa-2a (Peg-IFNα-2a), with 24-week follow-up.

Methods: Ninety patients were enrolled into six arms of 15 each (A-F); 60 patients were included in the main randomisation (arms A-D), and 30 patients (arms E-F) were randomised to the extension phase: (A) Peg-IFNα-2a 180 μg once weekly (QW); (B) BLV 2 mg once daily (QD) + Peg-IFNα-2a 180 μg QW; (C) BLV 5 mg QD + Peg-IFNα-2a 180 μg QW; (D) BLV 2 mg QD; (E) BLV 10 mg QD + Peg-IFNα-2a 180 μg QW and (F) BLV 10 mg (5 mg twice daily) + TDF QD.

Extended Treatment Duration of Artemether-Lumefantrine in Ugandan Children with HIV on Efavirenz-Based Antiretroviral Therapy: A Randomized Controlled Pharmacokinetic and Pharmacodynamic Trial.

Malaria and HIV co-infection are prevalent in sub-Saharan Africa causing significant drug interactions with co-treatment. We previously reported a 30%-70% reduction in exposure to the standard 3-day (6-dose) artemether-lumefantrine (AL) treatment for malaria when given with efavirenz-based HIV therapy, impacting malaria reinfection risk. We conducted a prospective, randomized study comparing the 3-day regimen to an extended 5-day (10-dose) regimen with pharmacokinetic sampling for artemether, dihydroartemisinin, lumefantrine, and desbutyl-lumefantrine (DBL) over 42 days.

Relationships for Social Change: The Value of the Promotora Framework in Navigating Systems of Employment.

In the United States, socioeconomic disparities are a reality that shapes the challenges many communities of color experience. Throughout the globe, community-based initiatives have been explored as a way to reduce several barriers that contribute to social inequalities. One in particular, the Promotora framework, has been widely used to improve health outcomes.

Inhibition of acyl-CoA synthetase long-chain isozymes decreases multiple myeloma cell proliferation and causes mitochondrial dysfunction.

Multiple myeloma (MM) is an incurable cancer of plasma cells with a 5-year survival rate of 59%. Dysregulation of fatty acid (FA) metabolism is associated with MM development and progression; however, the underlying mechanisms remain unclear. Herein, we explore the roles of long-chain fatty acid coenzyme A ligase (ACSL) family members in MM.

A phase 2 basket study of talabostat, a small-molecule inhibitor of dipeptidyl peptidases, administered in combination with pembrolizumab in patients with advanced solid cancers.

Background: Talabostat, an oral small molecule inhibitor of dipeptidyl peptidases (DPP4 and DPP8/9), has shown synergistic activity with immune checkpoint inhibitors in preclinical studies. This open label, phase 2 basket trial assessed the antitumor activity of combining talabostat and pembrolizumab (anti-programmed death-1 antibody) in advanced solid tumor patients.

Methods: The primary objective was assessment of dose-limiting toxicity (DLT) rates in the first six patients (lead-in stage) and response rate (efficacy stage; included cohort A [checkpoint inhibitor (ICI) naive] and cohort B [ICI pretreated]) for the study treatment using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.

Anxiety Symptoms Predict Subsequent Depressive Symptoms in Neurodivergent Youth: A 10-Year Longitudinal Study.

Neurodivergent youth often experience anxiety and depressive symptoms that may hamper adaptive functioning and well-being. There is little knowledge of how anxiety and depression are related in neurodivergent youth. Therefore, we aimed to examine whether the relationship between anxiety and depressive symptoms is uni- or bidirectional in neurodiverse youth.

Proximal remote sensing: an essential tool for bridging the gap between high-resolution ecosystem monitoring and global ecology.

A new proliferation of optical instruments that can be attached to towers over or within ecosystems, or 'proximal' remote sensing, enables a comprehensive characterization of terrestrial ecosystem structure, function, and fluxes of energy, water, and carbon. Proximal remote sensing can bridge the gap between individual plants, site-level eddy-covariance fluxes, and airborne and spaceborne remote sensing by providing continuous data at a high-spatiotemporal resolution. Here, we review recent advances in proximal remote sensing for improving our mechanistic understanding of plant and ecosystem processes, model development, and validation of current and upcoming satellite missions.

Predictive strength of inflammatory scores for in-hospital mortality in infective endocarditis.

Background: Inflammatory markers have been proposed as prognostic tools for predicting in-hospital mortality in infective endocarditis (IE). Nonetheless, it is unclear whether these markers provide additional prognostic value over established indicators. This study compared nine different inflammation scores to assess their effectiveness in enhancing the prediction of in-hospital mortality.

Surgeon attitudes toward risk stratification in emergency surgery for the elderly: an ESTES cross-sectional survey.

Purpose: Our study explores the utilization of objective tools for preoperative assessment of elderly patients by Emergency General Surgeons (EGS).

Methods: A descriptive cross-sectional survey was conducted via the European Society for Trauma and Emergency Surgery (ESTES) Research Committee. EGS were invited through the ESTES members' mailing list and social media platforms.

Influence of Preoperative Depression on Cervical Spine Surgery Outcomes: A Systematic Review and Meta-Analysis.

Study Design: Systematic review and Meta-analysis.

Objectives: To quantify the association of preoperative depression on patient reported outcome measures (PROMS) after cervical spine surgery.

Methods: We systematically searched PubMed, Cochrane, Embase, Scopus, PsychInfo, Web of Science, and ClinicalTrials.

RNase T2 deficiency promotes TLR13-dependent replenishment of tissue-protective Kupffer cells.

Lysosomal stress due to the accumulation of nucleic acids (NAs) activates endosomal TLRs in macrophages. Here, we show that lysosomal RNA stress, caused by the lack of RNase T2, induces macrophage accumulation in multiple organs such as the spleen and liver through TLR13 activation by microbiota-derived ribosomal RNAs. TLR13 triggered emergency myelopoiesis, increasing the number of myeloid progenitors in the bone marrow and spleen.

Optimized genetic tools for neuroanatomical and functional mapping of the Aedes aegypti olfactory system.

The mosquito Aedes aegypti is an emerging model insect for invertebrate neurobiology. We detail the application of a dual transgenesis marker system that reports the nature of transgene integration with circular donor template for CRISPR-Cas9-mediated homology-directed repair at target mosquito chemoreceptor genes. Employing this approach, we demonstrate the establishment of cell-type-specific T2A-QF2 driver lines for the A.

Talin, a Rap1 effector for integrin activation at the plasma membrane, also promotes Rap1 activity by disrupting sequestration of Rap1 by SHANK3.

Talin regulates the adhesion and migration of cells in part by promoting the affinity of integrins for extracellular matrix proteins, a process that in cells such as endothelial cells and platelets requires the direct interaction of talin with both the small GTPase, Rap1-GTP, and the integrin β3 cytoplasmic tail. To study this process in more detail, we employed an optogenetic approach in living, immortalized endothelial cells to be able to regulate talin interaction with the plasma membrane. Previous studies identified talin as the Rap1-GTP effector for β3 integrin activation.