Rely trial

The human gut hosts numerous ecological niches for microbe-microbe and host-microbe interactions. Gut lactate homeostasis in humans is crucial and relies on various bacteria. Veillonella spp., gut lactate-utilizing bacteria, and lactate-producing bacteria were frequently co-isolated. A recent clinical trial has revealed that lactate-producing bacteria in humans cross-feed lactate to Veillonella spp.; however, their interspecies interaction mechanisms remain unclear. Veillonella dispar, an obligate anaerobe commonly found in the human gut and oral cavity, ferments lactate into acetate and propionate...

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, which has a high recurrence rate and is incurable due to a lack of effective treatment. Mesenchymal stromal cells (MSCs) are a class of pluripotent stem cells that have recently received a lot of attention due to their strong self-renewal ability and immunomodulatory effects, and a large number of experimental and clinical models have confirmed the positive therapeutic effect of MSCs on IBD. In preclinical studies, MSC treatment for IBD relies on MSCs paracrine effects, cell-to-cell contact, and its mediated mitochondrial transfer for immune regulation...

The increasing number of bacterial infections globally that do not respond to any available antibiotics indicates a need to invest in-and ensure access to-new antibiotics, vaccines, and diagnostics. The traditional model of drug development, which depends on substantial revenues to motivate investment, is no longer economically viable without push and pull incentives. Moreover, drugs developed through these mechanisms are unlikely to be affordable for all patients in need, particularly in low-income and middle-income countries...

BACKGROUND: Quality study monitoring is fundamental to patient safety and data integrity. Regulators and industry consortia have increasingly advocated for risk-based monitoring (RBM) and central statistical monitoring (CSM) for more effective and efficient monitoring. Assessing which statistical methods underpin these approaches can best identify unusual data patterns in multi-center clinical trials that may be driven by potential systematic errors is important. METHODS: We assessed various CSM techniques, including cross-tests, fixed-effects, mixed-effects, and finite mixture models, across scenarios with different sample sizes, contamination rates, and overdispersion via simulation...

During development, the zebrafish embryo relies on its yolk sac as a nutrient source. Here, we present a protocol for modifying the free fatty acid (FFA) and triacylglycerol (TAG) content of the zebrafish yolk sac by microinjection. We describe steps for needle and injection mold preparation, FFA and TAG solution preparation, and microinjection. This protocol can elucidate how excesses of FFA and TAG affect development and modify the transcriptome of zebrafish embryos. For complete details on the use and execution of this protocol, please refer to Konadu et al...

The blood-brain-barrier (BBB) is made up of blood vessels whose permeability enables the passage of some compounds. A predictive model of BBB permeability is important in the early stages of drug development. The predicted BBB permeabilities of drugs have been confirmed using a variety of in vitro methods to reduce the quantities of drug candidates needed in preclinical and clinical trials. Most prior studies have relied on animal or cell-culture models, which do not fully recapitulate the human BBB. The development of microfluidic models of human-derived BBB cells could address this issue...

Immunotherapy with checkpoint inhibitors, albeit commonly used against tumors, is still at its infancy against chronic virus infections. It relies on the reinvigoration of exhausted T lymphocytes to eliminate virus-infected cells. Since T cell exhaustion is a physiological process to reduce immunopathology, the reinvigoration of these cells might be associated with an augmentation of pathological changes. To test this possibility, we here analyzed in the model system of chronic lymphocytic choriomeningitis virus (LCMV)-infected mice whether treatment with the checkpoint inhibitor anti-PD-L1 antibody would increase CD8 T cell-dependent fibrosis...

Vulvar carcinoma is a rare cancer affecting the genital tract, constituting 4% of gynecological tumors. Vulvar squamous cell carcinoma (VSCC) is the most common type. Diagnosis relies on biopsy during vulvoscopy, plus imaging such as ultrasonography (USG), magnetic resonance imaging (MRI) and positron emission tomography (PET). This review aims to lay out a thorough overview as to the current preoperative management of VSCC, both in case of vulvar and lymph node involvement. The data research was conducted using the following databases: MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial...

Time-to-event analysis often relies on prior parametric assumptions, or, if a semiparametric approach is chosen, Cox's model. This is inherently tied to the assumption of proportional hazards, with the analysis potentially invalidated if this assumption is not fulfilled. In addition, most interpretations focus on the hazard ratio, that is often misinterpreted as the relative risk (RR), the ratio of the cumulative distribution functions. In this paper, we introduce an alternative to current methodology for assessing a treatment effect in a two-group situation, not relying on the proportional hazards assumption but assuming proportional risks...

BACKGROUND: Signal peptide (SP) engineering has proven able to improve production of many proteins yet is a laborious process that still relies on trial and error. mRNA structure around the translational start site is important in translation initiation and has rarely been considered in this context, with recent improvements in in silico mRNA structure potentially rendering it a useful predictive tool for SP selection. Here we attempt to create a method to systematically screen candidate signal peptide sequences in silico based on both their nucleotide and amino acid sequences...

In the post-Moore's law era, the progress of electronics relies on discovering superior semiconductor materials and optimizing device fabrication. Computational methods, augmented by emerging data-driven strategies, offer a promising alternative to the traditional trial-and-error approach. In this Perspective, we highlight data-driven computational frameworks for enhancing semiconductor discovery and device development by elaborating on their advances in exploring the materials design space, predicting semiconductor properties and optimizing device fabrication, with a concluding discussion on the challenges and opportunities in these areas...

For a long time, the reliability of medical-scientific research was, without further verification, based on real data. It is becoming increasingly clear that this assumption is unjustified and that probably at least 25% of published randomized clinical trials are based on unreliable and sometimes even fabricated data. After giving a number of examples, it is discussed what the reader can do about this problem. More importantly, editors and publishers should no longer rely on whistle-blowers but take action themselves...

BACKGROUND: Recruitment and retention are common challenges in clinical trials, particularly with older adults and their caregivers who often benefit from palliative care but have significant strain from caregiving. In recent years, there has been an expansion in home-based palliative care programs, especially for patients with dementia. Because these programs often rely on physicians or advanced practice nurses, they are quite costly and may be difficult to staff due to workforce shortages...

Streptococcus pyogenes (Group A Streptococcus; GAS) is a Gram-positive bacterium responsible for substantial human mortality and morbidity. Conventional diagnosis of GAS pharyngitis relies on throat swab culture, a low-throughput, slow, and relatively invasive 'gold standard'. While molecular approaches are becoming increasingly utilized, the potential of saliva as a diagnostic fluid for GAS infection remains largely unexplored. Here, we present a novel, high-throughput, sensitive, and robust speB qPCR assay that reliably detects GAS in saliva using innovative 3base™ technology (Genetic Signatures Limited, Sydney, Australia)...

While the exertion of mental effort improves performance on cognitive tasks, the neural mechanisms by which motivational factors impact cognition remain unknown. Here, we used fMRI to test how changes in cognitive effort, induced by changes in task difficulty, impacts neural representations of working memory. Participants (both sexes) were precued whether working memory difficulty would be hard or easy. We hypothesized that hard trials demanded more effort as a later decision required finer mnemonic precision...

OBJECTIVE: To evaluate whether the continuous support provided by doulas influences the endogenous release of serotonin in parturients. METHODS: This pilot study included 24 primigravidae at term. Of these, 12 women received continuous doula support (Experimental Group), whereas the other 12 received the usual assistance without doula support (Control Group). Blood samples were collected from all the women at the active and expulsion stages of labor and at the fourth period of labor (Greenberg period) for evaluation of their serotonin levels using high-performance liquid chromatography...

BACKGROUND: Pharmacotherapy is one of the primary treatment modalities for depression. However, there is considerable variability in the individual response to antidepressant medications. Personalized medicine guided by pharmacogenomic testing may hold promise in addressing this issue. METHODS: In this study, 665 depressive patients were randomly enrolled into two groups: the pharmacogenomic testing group (n = 333) and the control group (n = 332)...

Eyes are active in memory recall and visual imagination, yet our grasp of the underlying qualities and factors of these internally coupled eye movements is limited. To explore this, we studied 50 participants, examining how workload, spatial reference availability, and imagined movement direction influence internal coupling of eye movements. We designed a visuospatial working memory task in which participants mentally moved a black patch along a path within a matrix and each trial involved one step along this path (presented via speakers: up, down, left, or right)...

BACKGROUND: Iliofemoral Venous Stent Placement (IVS) has evolved to a well-established endovascular treatment modality for chronic iliofemoral venous obstruction (CIVO). Dedicated venous stents gained FDA approval in 2019 and solidified IVS as a defined intervention with clear indications, contraindications, risks, benefits, and procedural management principles. This review focuses on the indications, technical aspects and outcomes of stenting for CIVO. Other aspects pertaining to IVS are covered in manuscripts that are part of this series...

BACKGROUND: Hundreds of millions of doses of Praziquantel (PZQ) have been administered to persons with and without schistosomiasis living in schistosomiasis endemic settings, through the mass drug administration (MDA) strategy which started in the early 2000s. A recent publication suggested high risk of PZQ-related visual disorders, raising public health concerns. We aim to systematically synthesize evidence on the magnitude of PZQ-related visual disorders. METHODS: We will search PubMed, Google Scholar, CINAHL, SCOPUS, CENTRAL and LILACS from 1977 (when the first human clinical trials on PZQ started) to 31st May 2024, with no language restrictions...