Escalation

BACKGROUND: Belantamab mafodotin (belamaf) has shown promising antimyeloma activity in relapsed or refractory multiple myeloma (RRMM) as a single agent. It was hypothesized that its multimodal activity may be enhanced by programmed cell death protein 1 pathway inhibition and activation of T cell-mediated antitumor responses. This study investigated the efficacy and safety of belamaf with pembrolizumab in patients with RRMM. METHODS: DREAMM-4 (NCT03848845) was an open-label, single-arm, phase 1/2 study divided into dose-escalation (part 1) and dose-expansion (part 2) phases...

PURPOSE: Simlukafusp alfa (FAP-IL2v), a tumor-targeted immunocytokine, comprising an interleukin-2 variant moiety with abolished CD25 binding fused to human immunoglobulin G1, is directed against fibroblast activation protein-α. This phase I, open-label, multicenter, dose-escalation and extension study (NCT02627274) evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of FAP-IL2v in patients with advanced/metastatic solid tumors. METHODS: Participants received FAP-IL2v intravenously once weekly...

Genomic epidemiology enhances the ability to detect and refute methicillin-resistant Staphylococcus aureus (MRSA) outbreaks in healthcare settings, but its routine introduction requires further evidence of benefits for patients and resource utilization. We performed a 12 month prospective study at Cambridge University Hospitals NHS Foundation Trust in the UK to capture its impact on hospital infection prevention and control (IPC) decisions. MRSA-positive samples were identified via the hospital microbiology laboratory between November 2018 and November 2019...

BACKGROUND: Understanding the factors influencing individuals' health decisions is a dynamic research question. Particularly, after China announced the deregulation of the COVID-19 epidemic, health risks escalated rapidly. The convergence of "no longer controlled" viruses and the infodemic has created a distinctive social period during which multiple factors may have influenced people's decision-making. Among these factors, the precautionary intentions of older individuals, as a susceptible health group, deserve special attention...

This study aims to examine the health effects of smog on different age groups in Gujranwala and its associated health effects. To achieve this, primary data was gathered through a questionnaire survey focused on health issues faced by elderly individuals during the smog season. The results of the survey revealed that older adults in Gujranwala are particularly vulnerable to a range of health problems during this period, including coughing, throat infections, irritated eyes, runny noses, shortness of breath, chest pain while breathing, wheezing, asthma, heart problems, and respiratory issues...

An increasing body of research suggests that promoting microglial autophagy hinders the neuroinflammation initiated though the NLRP3 inflammasome activation in Alzheimer's disease (AD). The function of FoxG1, a crucial transcription factor involved in cell survival by regulating mitochondrial function, remains unknown during the AD process and neuroinflammation occurs. In the present study, we firstly found that Aβ peptides induced AD-like neuroinflammation upregulation and downregulated the level of autophagy...

Casein (CN) is the primary allergenic protein in cow's milk, contributing to the worldwide escalating prevalence of food allergies. However, there remains limited knowledge regarding the effect of structural modifications on CN allergenicity. Herein, we prepared three modified CNs (mCN), including sodium dodecyl sulfate and dithiothreitol-induced linear CN (LCN), transglutaminase-cross-linked CN (TCN), and glucose-glycated CN (GCN). The electrophoresis results indicated widespread protein aggregation among mCN, causing variations in their molecular weights...

In the contemporary era, heightened emphasis on health and safety has emerged as a paramount concern among individuals with food. The concepts of "natural" and "green" have progressively asserted dominance in the food consumption market. Consequently, through continuous exploration and development, an escalating array of natural bioactive ingredients is finding application in both nutrition delivery and the broader food industry. Chlorogenic acid (CGA), a polyphenolic compound widely distributed in various plants in nature, has garnered significant attention...

Human challenge studies, in which human research subjects are intentionally exposed to pathogens to contribute to scientific knowledge, raise many ethical complexities. One controversial question is whether it is ethically permissible to include children as participants. Commentary of the past decades endorses the exclusion of children, while new guidance suggests that pediatric human challenge studies can be ethically permissible. This paper argues that neither children's exclusion nor their inclusion are well justified...

BACKGROUND AND AIMS: To assess the 10-year cardiovascular disease (CVD) risk among Thai physicians. The risk compared to the general population and their relationship with the current coronary artery disease (CAD) were also examined. METHODS: This retrospective study collected data of Thai physicians who underwent cardiovascular assessments between February 14, 2022, and October 31, 2022. The CVD risk was calculated using the Thai CVD risk (TCVR) score, which incorporated variables of age, gender, smoking, diabetes mellitus, blood pressure, and total cholesterol...

BACKGROUND: Fosfomycin treatment of urinary tract infections is increasingly attractive due to escalating antibiotic resistance rates among urinary pathogens. Standard antibiotic susceptibility testing methods perform poorly for fosfomycin as there is poor correlation between susceptibility results and clinical outcomes in urinary pathogens other than Escherichia coli . OBJECTIVE: We evaluated the performance of fosfomycin susceptibility testing in E. coli and Klebsiella pneumoniae to determine whether fosfomycin susceptibility is associated with molecular resistance mechanisms...

OBJECTIVE: Determine the impact of limited implementation of a rapid blood culture identification (BCID) panel. DESIGN: Retrospective cohort study. METHODS: From February to April 2022, positive blood cultures identified via e-Plex BCID (Roche, Carlsbad, CA) were compared to those identified using standard microbial identification techniques. The primary outcomes assessed were time to optimal therapy, time to de-escalation of anti-MRSA (methicillin-resistant Staphylococcus aureus) agents, and time to de-escalation of anti-pseudomonal agents...

OBJECTIVE: Audit and feedback is an antimicrobial stewardship (AMS) strategy, with the potential to also optimize antimicrobial use in non-audited patients. This study aimed to determine whether audit and feedback reduce antimicrobial use in both audited and non-audited patients. DESIGN: Before-after trial with a 1-year intervention period and 2.5-year historical cohort. SETTING: 750-bed community hospital in the Netherlands. PATIENTS: All patients admitted to the urology wards during the 3...

BACKGROUND: Midwifery specialisation was introduced in 1993 as a response to escalating maternal and neonatal mortalities and shortage of physicians in rural parts of South Africa. Basic midwives enrolled into a postgraduate midwifery qualification to extend their knowledge and skills which enabled them to manage complicated obstetric conditions. The postgraduate midwifery qualification rendered them midwife specialists upon completion of the course. Yet, MS remain underutilised in clinical facilities due to limiting practice regulations and fear of medico-legal litigations, leading to forfeiture of skills...

The rise of psychedelics in contemporary medicine has sparked interest in their potential therapeutic applications. While traditionally associated with countercultural movements and recreational use, recent research has shed light on the potential benefits of psychedelics in various mental health conditions. In this review, we explore the possible role of psychedelics in the management of chronic pain and opioid use disorder (OUD), 2 critical areas in need of innovative treatment options. Pain control remains a significant clinical challenge, particularly for individuals with OUD and those who receive long-term opioid therapy who develop marked tolerance to opioid-induced analgesia...

Hybrid nanozyme graphene quantum dots (GQDs) deposited TiO2 nanotubes (NTs) on titanium foil (Ti/TiO2 NTs-GQDs) were manufactured by bestowing the hybrid with the advantageous porous morphology, surface valence states, high surface area, and copious active sites. The peroxidase-like activity was investigated through the catalytic oxidation of chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2 O2 , which can be visualized by the eyes. TiO2 NTs and GQDs comprising oxygen-containing functional groups can oxidize TMB in the presence of H2 O2 by mimicking peroxidase enzymes...

INTRODUCTION: Gonorrhoea, the sexually transmissible infection caused by Neisseria gonorrhoeae , has a substantial impact on sexual and reproductive health globally with an estimated 82 million new infections each year worldwide. N. gonorrhoeae antimicrobial resistance continues to escalate, and disease control is largely reliant on effective therapy as there is no proven effective gonococcal vaccine available. However, there is increasing evidence from observational cohort studies that the serogroup B meningococcal vaccine four-component meningitis B vaccine (4CMenB) (Bexsero), licensed to prevent invasive disease caused by Neisseria meningitidis , may provide cross-protection against the closely related bacterium N...

In this work, we propose that humor violates norms that can build consensus or escalate conflict in negotiations. Drawing on social identity theory, we propose that humor commits norm violations that are more likely to be perceived as benign among ingroup observers in negotiations, but perceived as offensive to outgroup observers in negotiations. We introduce the Comedy, Consensus, and Conflict Framework to shed light on the interpersonal effect of humor on negotiations. When humor is expressed to an ingroup observer, relative to neutral communication, humor is more likely to violate weak norms that govern social group membership resulting in the violation as being perceived as benign, which promotes cooperative behaviors in negotiations such as concessions and collaborative problem-solving...

With the escalating global awareness of air quality management, the need for continuous and reliable monitoring of toxic gases by using low-power operating systems has become increasingly important. One of which, semiconductor metal oxide gas sensors have received great attention due to their high/fast response and simple working mechanism. More specifically, self-heating metal oxide gas sensors, wherein direct thermal activation in the sensing material, have been sought for their low power-consuming characteristics...

Antimicrobial de-escalation refers to reducing the spectrum of antibiotics used in treating bacterial infections. This strategy is widely recommended in many antimicrobial stewardship programs and is believed to reduce patients' exposure to broad-spectrum antibiotics and prevent resistance. However, the ecological benefits of de-escalation have not been universally observed in clinical studies. This paper conducts computer simulations to assess the ecological effects of de-escalation on the resistance prevalence of Pseudomonas aeruginosa-a frequent pathogen causing nosocomial infections...