Effective cancer immunotherapy combining mRNA-encoded bispecific antibodies that induce polyclonal T cell engagement and PD-L1-dependent 4-1BB costimulation.

Background: Immune checkpoint inhibitors have revolutionized cancer therapy, but many patients fail to respond or develop resistance, often due to reduced T cell activity. Costimulation via 4-1BB has emerged as a promising approach to enhance the effector function of antigen-primed T cells. Bispecific T cell-engaging (TCE) antibodies are an effective way to provide tumor-specific T cell receptor-mediated signaling to tumor-infiltrating lymphocytes.

Genomic, transcriptomic, and T cell receptor profiling in stratifying response to first-line chemoradiotherapy or radiotherapy for esophageal squamous cell carcinoma.

Introduction: Esophageal squamous cell carcinoma (ESCC) accounts for 80% of esophageal cancer (EC) worldwide. The molecular characteristics of locally advanced ESCC have been extensively studied.

Methods: In this study, we investigate the genomic and transcriptomic characteristics and try to provide the basic T-cell receptors (TCRs) dynamics and its genomic and transcriptome association during the radiochemotherapy of ESCC using multi-omics analysis.

Restraint stress effects on glutamate signaling protein levels in the rats' frontal cortex: Does β1 adrenoceptor activity matter?

Introduction: Stress-evoked dysfunctions of the frontal cortex (FC) are correlated with changes in the functioning of the glutamatergic system, and evidence demonstrates that noradrenergic transmission is an important regulator of this process. In the current study, we adopted a restraint stress (RS) model in male Wistar rats to investigate whether the blockade of β1 adrenergic receptors (β1AR) with betaxolol (BET) in stressed animals influences the body's stress response and the expression of selected signaling proteins in the medial prefrontal cortex (mPFC).

Methods: The study was divided into two parts.

Mild drought conditions at the tillering stage promote dry matter accumulation and increase grain weight in drip-irrigated spring wheat ( L.).

Introduction: In order to elucidate the physiological mechanism of post-flowering assimilate transport regulating the formation of yields in arid regions and to provide technological support for further water-saving and high yields in the wheat region in Xinjiang, we conducted a study on the effects of different fertility periods and different degrees of drought and re-watering on the post-flowering dry matter accumulation and transport of spring wheat and the characteristics of grain filling.

Methods: In two spring wheat growing seasons in 2023 and 2024, a split-zone design was used, with the drought-sensitive variety Xinchun 22 (XC22) and drought-tolerant variety Xinchun 6 (XC6) as the main zones and a fully irrigated control during the reproductive period [CK, 75%~80% field capacity (FC)], with mild drought at the tillering stage (T1, 60%~65% FC), moderate drought at the tillering stage (T2, 45%~50% FC), mild drought at the jointing stage (J1, 60%~65% FC), and mild drought at the jointing stage (J2, 45%~50% FC) as the sub-zones.

Results: The dry matter accumulation of the aboveground parts of wheat (stem sheaths, leaves, and spikes), the transfer rate and contribution rate of nutrient organs, the maximum filling rate (V), and the mean filling rate (V) increased significantly after re-watering in the T1 treatment, and decreased with the deepening of the degree of water stress.

Efficacy and safety of dapagliflozin in patients with CKD: real-world experience in 93 Italian renal clinics.

Background: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are recommended for reducing the renal and cardiovascular risk in patients with chronic kidney disease (CKD) based on the positive results reported by clinical trials. However, real-world data on the efficacy and the safety of these drugs in CKD population followed in nephrology setting are lacking.

Methods: We report the effects of dapagliflozin in CKD patients by using data collected during a learning program in which 105 nephrologists added dapagliflozin (10 mg/day) to consecutive patients referred to their renal clinics.

Dysfunctional large-scale brain networks in drug-naïve depersonalization-derealization disorder patients.

Background: Depersonalization-Derealization Disorder (DPRD) presents challenges in understanding its neurobiological underpinnings. Several neuroimaging studies have revealed altered brain function and structure in DPRD. However, the knowledge about large-scale dysfunctional brain networks in DPRD remains unknown.

Circulating tumour DNA in early stage and locally advanced NSCLC: ready for clinical implementation?

Circulating tumour DNA (ctDNA) can be released by cancer cells into biological fluids through apoptosis, necrosis or active release. In patients with non-small-cell lung cancer (NSCLC), ctDNA levels correlate with clinical and pathological factors, including histology, tumour size and proliferative status. Currently, ctDNA analysis is recommended for molecular profiling in patients with advanced-stage NSCLC.

Physiochemical and functional evaluation of the first-in-class anti-cancer IgE antibody drug, MOv18, through process development and good manufacturing practice production.

Antibodies used for cancer therapy are monoclonal IgGs, but tumor-targeting IgE antibodies have shown enhanced effector cell potency against cancer in preclinical models. Research-grade recombinant IgE antibodies have been generated and studied for several decades. The recent Phase 1 clinical trial of the first-in-class MOv18 IgE, however, necessitated the inaugural process development and scaled manufacture of a recombinant IgE to clinical quality standards.

Understanding good communication in ambulance pre-alerts to the emergency department: findings from a qualitative study of UK emergency services.

Objectives: Prehospital notifications (pre-alerts) enable emergency department (ED) staff to prepare for the arrival of patients requiring a time-critical response. Effective communication of the pre-alert is key to enabling the ED to prepare appropriately, but evidence on communication practices is lacking. We undertook qualitative research to understand how pre-alert communication may be improved to optimise the ED response for pre-alerted patients.

Emulation of ARISTOTLE and ROCKET AF trials in real-world atrial fibrillation patients results in similar efficacy and safety as original landmark trials: insights from the GARFIELD-AF registry.

Aims: This study aimed to determine the robustness, reproducibility and representativeness of the landmark Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (AF) (ARISTOTLE) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in AF (ROCKET AF) randomised trials through replication in an observational AF patient registry.

Methods And Results: Patients from the Global Anticoagulant Registry in the FIELD (GARFIELD)-AF registry treated with apixaban, rivaroxaban or vitamin K antagonist (VKA) were assessed for eligibility for the ARISTOTLE and ROCKET AF trials. HRs of apixaban and rivaroxaban versus comparator for stroke/systemic embolism, major bleeding and all-cause mortality within 2 years follow-up were calculated using propensity score overlap-weighted Cox models.

Structural and functional connectivity coupling as an imaging marker for bone metastasis pain in lung cance patients.

Background: Cancer pain is a common symptom in patients with malignant tumors and associated with poor prognosis and a high risk of death. Structural connectivity (SC) and functional connectivity (FC) couplings have not yet been explored in lung cancer patients with bone metastasis pain.

Methods: In total, 51 patients with lung cancer without bone metastasis pain (BMP-), 52 patients with lung cancer with bone metastasis pain (BMP+), and 28 healthy controls (HC) were prospectively enrolled in our study.

Potential associations between altered brain function, cognitive deficits and gene expressing profiles in bipolar disorder across three clinical stages.

Aims: We aimed to determine the relationship between altered brain imaging characteristics, cognitive function and profiles of gene expression of bipolar disorder (BD).

Methods: Functional magnetic resonance imaging (fMRI) was presented in three groups of BD participants (depressed, manic and euthymic) and healthy controls. Regional Homogeneity (ReHo) and region of interest based functional analysis combining with neuroimaging-transcription association analysis were utilized to investigate abnormalities and their correlation with clinical symptoms.

The magneto-mechanical coupling of multiphase magnetorheological elastomers.

Magnetorheological elastomers (MREs) are soft magnetic composites that achieve tunable changes in stiffness and energy response in the presence of a magnetic field. Rigid particle composite (RC) MREs have been studied for decades for their potential applications to automotive dampers and robotic systems. Recently, magnetic fluid composite (FC) MREs have been developed which utilize magnetic fluids as inclusions to elastomers.

Helicobacter pylori infection is associated with significant elevations to fecal calprotectin, systemic inflammatory markers.

Objectives: Fecal calprotectin (FC) is a marker commonly used in the diagnosis and follow-up of inflammatory bowel diseases (IBD). However, other gastrointestinal conditions, like H. pylori (HP) infection, can result in increased neutrophil activity as well.

Relationship Between Structural and Functional Network Connectivity Changes for Patients With Traumatic Brain Injury and Chronic Health Symptoms.

Combination of structural and functional brain connectivity methods provides a more complete and effective avenue into the investigation of cortical network responses to traumatic brain injury (TBI) and subtle alterations in brain connectivity associated with TBI. Structural connectivity (SC) can be measured using diffusion tensor imaging to evaluate white matter integrity, whereas functional connectivity (FC) can be studied by examining functional correlations within or between functional networks. In this study, the alterations of SC and FC were assessed for TBI patients, with and without chronic symptoms (TBIcs/TBIncs), compared with a healthy control group (CG).

Optimizing Medical Pretreatment for Balloon Pulmonary Angioplasty: Overshoot or Stride Toward Optimal Multimodal Treatment.

In patients with chronic thromboembolic pulmonary hypertension (CTEPH) who undergo balloon pulmonary angioplasty (BPA), pretreatment with PH-targeted medical therapy may be beneficial to improve clinical parameters and pulmonary hemodynamics. This study aims to describe clinical results of PH-targeted therapy prior to BPA. All consecutive patients with CTEPH who underwent BPA treatment were selected from our CTEPH database.

Pancreatic Fistula and Intraabdominal Fluid Collections after Distal Pancreatectomy: Incidence, Implications, and Natural History.

Objective: To investigate the incidence and management of pancreatic fistula and fluid collections (FC) after distal pancreatectomy (DP).

Summary Background Data: Pancreatic fistula and FC are common after DP. The relationship between pancreatic fistula, FC, and surgical drain placement remains unclear.

In ovo delivery of carvacrol triggers expression of chemotactic factors, antimicrobial peptides and pro-inflammatory pathways in the yolk sac of broiler chicken embryos.

Background: Broiler chickens are most vulnerable immediately after hatching due to their immature immune systems, making them susceptible to infectious diseases. The yolk plays an important role in early immune defence by showing relevant antioxidant and passive immunity capabilities during broiler embryonic development. The immunomodulatory effects of phytogenic compound carvacrol have been widely reported.

Alterations in resting-state EEG functional connectivity in patients with major depressive disorder receiving electroconvulsive therapy: A systematic review.

Electroconvulsive therapy (ECT) is highly efficacious for the treatment of major depressive disorder (MDD), but its mechanisms still require clarification. Even though depression is associated with alterations in functional connectivity (FC), EEG studies investigating effects of ECT on FC have not been systematically reviewed. Understanding these effects may help to identify the role of functional brain circuits in depression and its remission.

Identification of correlation relationships and establishment of regression models among multiple microbial indicators in reclaimed waters.

Monitoring and controlling microbial water quality is crucial for ensuring water reuse safety. In particular, existing water reuse guidelines and regulations normally prescribed coliform bacteria as microbial indicators. However, the use of non-unified coliform groups may bring difficulties to compare and optimize the conformity efforts on microbial surveillance.

An engineered Palivizumab IgG2 subclass for synthetic gp130 and fas mediated signaling.

Recently, we phenocopied Interleukin (IL-)6 signaling using the dimerized single-chain variable fragment (scFv) derived from the respiratory syncytial virus (RSV) IgG1-antibody Palivizumab (PLHFc) to activate a Palivizumab anti-idiotypic nanobody (AIP)-gp130 receptor fusion protein. Palivizumab was unable to activate STAT3 signaling, so we aimed to create a similar ligand capable of triggering this pathway. Here, we created three variants of the ligand called PLH0Fc, PLH4Fc and PLH8Fc by shortening the spacer region connecting PLH and Fc from 23 amino acids in PLHFc to 0 amino acids or expanding it by rigid linkers of 4 or 8 alpha helical loops, respectively.

Sustained Improvement in Medical Students' Academic Performance in Renal Physiology Through the Application of Flipped Classroom.

Background: Teaching renal physiology is problematic in many medical schools since conventional passive learning might not be effective. Active learnings including flipped classroom (FC) have been introduced to medical education including renal physiology topic recently, but no study regarding long-term outcomes has been reported.

Approach: Two classes of second-year medical students were compared.

Abnormal alterations in structure-function coupling at the modular level in patients with postherpetic neuralgia.

To investigate the presence of modular loss of coupling and abnormal alterations in functional and structural networks in the brain networks of patients with postherpetic neuralgia (PHN). We collected resting-state functional magnetic resonance imaging data and diffusion tensor imaging data from 82 healthy controls (HCs) and 71 PHN patients, generated structural connectivity (SC) and functional connectivity (FC) networks, and assessed the corresponding clinical information assessment. Based on AAL(90) mapping, the brain network was divided into 9 modules, and the structural-functional connectivity (SC-FC) coupling was compared at the whole-brain level and within the modules, as well as alterations in the topological properties of the brain network in the patient group.

Safety and humoral immunogenicity of the ChAdOx1 nCoV-19 vaccine administered as a fourth dose booster following two doses of ChAdOx1 nCoV-19 and a third dose of BNT162b2 (COV009): a prospective cohort study.

Objectives: Evaluation of the safety and humoral immunogenicity of ChAdOx1 nCoV-19 as a fourth dose booster in individuals who have had two initial doses of the vaccine and a third dose of BNT162b2.

Methods: COV009 is a safety follow-up study of volunteers enrolled in the pivotal pre-licensure ChAdOx1 nCoV-19. In this sub-study 149 eligible participants were given a fourth dose of ChAdOx1 nCoV-19.

Association of Care Fragmentation and Hospital Cancer Designation with Survival in Gastroesophageal Junction Cancer: A State-Wide Study.

Background: Fragmentation of care (FC) is healthcare provided by different providers and/or facilities. FC has been associated with inferior outcomes, yet it improves access to specialized cancer care. We aim to identify the association of fragmented gastroesophageal junction cancer (GEJ) care with survival.