Prolgolimab with chemotherapy as first-line treatment for advanced non-squamous non-small-cell lung cancer.

Background: Prolgolimab is an IgG1 anti-PD-1 monoclonal antibody with the Fc-silencing 'LALA' mutation. The phase III DOMAJOR study assessed efficacy and safety of prolgolimab in combination with pemetrexed and platinum-based chemotherapy vs placebo in combination with pemetrexed and platinum-based chemotherapy as first-line treatment for advanced non-small cell lung cancer (NSCLC).

Methods: 292 patients with advanced non-squamous NSCLC were randomized 1:1 to receive 4 cycles of pemetrexed, platinum-based drug and either prolgolimab (3 mg/kg Q3W) or placebo followed by prolgolimab/placebo with pemetrexed until disease progression or toxicity (≤36 months).

Users´ perspectives and preferences on using wearables in epilepsy: A critical review.

Seizure detection devices (SDDs) offer promising technological advancements in epilepsy management, providing real-time seizure monitoring and alerts for patients and caregivers. This critical review explores user perspectives and experiences with SDDs to better understand factors influencing their adoption and sustained use. An electronic literature search identified 34 relevant studies addressing common themes such as usability, motivation, comfort, accuracy, barriers, and the financial burden of these devices.

Temporal transcriptional profiling of host cells infected by a veterinary alphaherpesvirus using nanopore sequencing.

In our research, we performed temporal transcriptomic profiling of host cells infected with Equid alphaherpesvirus 1 (EHV-1) by utilizing direct cDNA sequencing based on nanopore MinION technology. The sequencing reads were harnessed for transcript quantification at various time points. Viral infection-induced differential gene expression was identified through the edgeR package.

Bacteriophage Treatment Induces Phenotype Switching and Alters Antibiotic Resistance of ESBL .

Bacteriophage therapy represents a promising strategy to combat multidrug-resistant pathogens, such as . In this study, we explored the effects of a bacteriophage infection on an Extended Spectrum Beta-Lactamase (ESBL) positive isolate. We used next generation sequencing, proteomics and phenotypic screens to investigate the effect of bacteriophage infections on metabolism and resistance phenotypes.

Changes in Locomotor Activity Observed During Acute Nicotine Withdrawal Can Be Attenuated by Ghrelin and GHRP-6 in Rats.

Ghrelin and growth hormone-releasing peptide 6 (GHRP-6) are peptides which can stimulate GH release, acting through the same receptor. Ghrelin and its receptor have been involved in reward sensation and addiction induced by natural and artificial drugs, including nicotine. The present study aimed to investigate the impacts of ghrelin and GHRP-6 on the horizontal and vertical activity in rats exposed to chronic nicotine treatment followed by acute nicotine withdrawal.

The effects of corticotropin-releasing factor (CRF) and urocortins on the serotonin (hydroxytryptamine, 5HT) released from the raphe nuclei (RN).

Corticotropin-releasing factor (CRF) and urocortins (UCN1, UCN2 and UCN3) belong to the same CRF family of neuropeptides. They regulate the neuroendocrine, autonomic and behavioral responses to stress via two CRF receptors (CRF1 and CRF2). Stress, anxiety and depression affects the activity of the hypothalamic-pituitary-adrenal (HPA) axis and the serotoninergic neurotransmission, both being regulated by CRF and CRF-related peptides.

Prospective validation of ORACLE, a clonal expression biomarker associated with survival of patients with lung adenocarcinoma.

Human tumors are diverse in their natural history and response to treatment, which in part results from genetic and transcriptomic heterogeneity. In clinical practice, single-site needle biopsies are used to sample this diversity, but cancer biomarkers may be confounded by spatiogenomic heterogeneity within individual tumors. Here we investigate clonally expressed genes as a solution to the sampling bias problem by analyzing multiregion whole-exome and RNA sequencing data for 450 tumor regions from 184 patients with lung adenocarcinoma in the TRACERx study.

Knowledge, attitude, and practice toward vocal fatigue among occupational voice users: a cross-sectional study.

Background: Occupational voice users frequently face the challenge of vocal fatigue, impacting their overall well-being and job performance. This study aimed to investigate the knowledge, attitude, and practice (KAP) toward vocal fatigue among occupational voice users.

Methods: This web-based cross-sectional study was conducted among occupational voice users between July and October 2023 in Shenzhen People's Hospital, utilizing a self-administered questionnaire to examine the KAP of vocal fatigue.

Invasive lobular carcinoma of the breast: we diagnose it, but do we know what it is?

Invasive lobular carcinoma of the breast is the most common special type breast cancer. It has been defined using morphological features, has a characteristic immunophenotype associated with the loss of E-cadherin mediated intercellular adhesion, and the background of this immunohistochemistry and morphology is generally a biallelic genetic alteration of the CDH-1 gene coding E-cadherin. However, the morphology may often deviate from the classical, and immunohistochemistry may also deviate from the typical, and then the diagnosis of invasive lobular carcinoma becomes less straight forward.

Onset of pancreatic cancer before and after acute pancreatitis: A multicenter longitudinal cohort study.

Background: Pancreatic cancer (PC) is a leading cause of cancer mortality, often diagnosed at advanced stages. Acute pancreatitis (AP), particularly idiopathic cases, may serve as an early indicator of PC.

Objective: This multicenter cohort study investigated the incidence of PC before and after an AP episode, focusing on idiopathic AP and the role of pseudocysts as potential early markers for PC development.

Hemoglobin decrease predicts untoward outcomes better than severity of anemia.

Patients with gastrointestinal bleeding (GIB) exhibit varying tolerances to acute blood loss. We aimed to investigate the effect of relative Hb decrease (ΔHb%) on GIB outcomes. Participants enrolled in the Hungarian GIB Registry between 2019 and 2022 were analyzed.

Unbiased Drug Target Prediction Reveals Sensitivity to Ferroptosis Inducers, HDAC and RTK Inhibitors in Melanoma Subtypes.

Background: The utilization of PD1 and CTLA4 inhibitors has revolutionized the treatment of malignant melanoma (MM). However, resistance to targeted and immune-checkpoint-based therapies still poses a significant problem.

Objective: Here, we mine large-scale MM proteogenomic data to identify druggable targets and forecast treatment efficacy and resistance.

Respiratory Viruses in Patients With Hematological Malignancy in Boreal Autumn/Winter 2023-2024: EPICOVIDEHA-EPIFLUEHA Report.

Community-acquired respiratory viral infections (CARV) significantly impact patients with hematological malignancies (HM), leading to high morbidity and mortality. However, large-scale, real-world data on CARV in these patients is limited. This study analyzed data from the EPICOVIDEHA-EPIFLUEHA registry, focusing on patients with HM diagnosed with CARV during the 2023-2024 autumn-winter season.

Acid Reflux Management with the RefluxStop Implant: A Prospective Multicenter Trial with 3-Year Outcomes.

Background: RefluxStop is a unique implant for laparoscopic treatment of gastroesophageal reflux disease (GERD). It restores normal function of the gastroesophageal junction without the unwanted effects of encircling the esophagus, circumventing adverse events (AEs) associated with conventional anti-reflux surgeries.

Methods: Three-year follow-up of 50 patients with chronic GERD treated by RefluxStop was achieved in a prospective, single-arm, multicentric clinical trial analyzing safety and effectiveness of the procedure.

Particularities of deposition of two ICS-LABA fixed dose combination dry powder aerosol drugs in the airways of COPD patients.

The aim of this study was to analyse the effect of breathing parameters, age, gender and disease status on the lung doses of the two ICS + LABA fixed combination dry powder drugs. Breathing parameters of 113 COPD patients were measured while inhaling through emptied NEXThaler® and Ellipta® inhalers and the corresponding lung doses were calculated. Lung dose of Foster® NEXThaler® was superior to the lung dose of Relvar® Ellipta® in around 85 % of the patients.

Individualised Positive End-Expiratory Pressure Settings Reduce the Incidence of Postoperative Pulmonary Complications: A Systematic Review and Meta-Analysis.

Progressive atelectasis regularly occurs during general anaesthesia; hence, positive end-expiratory pressure (PEEP) is often applied. Individualised PEEP titration may reduce the incidence of postoperative pulmonary complications (PPCs) and improve oxygenation as compared to fixed PEEP settings; however, evidence is lacking. This systematic review and meta-analysis was registered on PROSPERO (CRD42021282228).

The effects of corticotropin-releasing factor (CRF) and urocortins on the noradrenaline (NA) released from the locus coeruleus (LC).

Corticotropin-releasing factor (CRF) activates the hypothalamic-pituitary-adrenal (HPA) axis and stimulates the noradrenergic neurotransmission, both processes being implicated in the pathogenesis of anxiety and depression, but the intimate site and mechanism of interaction of CRF and CRF-related peptides, named urocortins (UCN1, UCN2, UCN3), with noradrenaline (NA) was not fully elucidated yet. Therefore, the aim of the present study was to investigate the actions of CRF and urocortins on the NA released from the rat locus coeruleus (LC), the primary source of NA in the brain, and the participation of CRF receptors (CRF1 and CRF2) in these actions. In order to do so, male Wistar rats were used, their LC were isolated and dissected, and the LC slices were incubated with tritium-labelled NA, superfused and stimulated electrically.

The prognostic value of histological grade determined after neoadjuvant chemotherapy of breast cancer.

Histological grade is a validated prognostic factor of breast cancer but may show alterations following neoadjuvant chemotherapy (NACT). Its reporting after NACT is recommended by several guidelines, but evidence of its retained prognostic impact is scarce. Patients treated with NACT followed by surgery and having sufficient residual tumour for the determination of grade were analysed for the survival effects of posttreatment grade (yG).

New pedagogical tools for vaccine education: preparing future healthcare workers for the next pandemic.

Vaccine hesitancy (VH) is an issue for healthcare students, influenced by safety concerns and misinformation. The need for better communication training and understanding sociocultural factors in VH was highlighted in a European University Alliance seminar. Practical exercises like simulation role-playing, interprofessional collaboration, and digital literacy may improve vaccine education.

Evaluation of the Effectiveness and Safety of Mesenchymal Stem Cell Treatment in Fistulising Crohn's Disease: An International Real-Life Retrospective Multicentre Cohort Study.

Background: Perianal fistulas of Crohn's disease (CD) create a significant burden on patients' lives. However, the efficacy and safety of adipose-derived mesenchymal stem cell treatment are contradicting, and real-world evidence is lacking.

Aims: To examine the usability of darvadstrocel therapy in managing perianal CD.

An Artificial Intelligent System for Prostate Cancer Diagnosis in Whole Slide Images.

In recent years a significant demand to develop computer-assisted diagnostic tools to assess prostate cancer using whole slide images has been observed. In this study we develop and validate a machine learning system for cancer assessment, inclusive of detection of perineural invasion and measurement of cancer portion to meet clinical reporting needs. The system analyses the whole slide image in three consecutive stages: tissue detection, classification, and slide level analysis.