Continuous Measurement of Lactate Concentration in Human Subjects through Direct Electron Transfer from Enzymes to Microneedle Electrodes.

Microneedle lactate sensors may be used to continuously measure lactate concentration in the interstitial fluid in a minimally invasive and pain-free manner. First- and second-generation enzymatic sensors produce a redox-active product that is electrochemically sensed at the electrode surface. Direct electron transfer enzymes produce electrons directly as the product of enzymatic action; in this study, a direct electron transfer enzyme specific to lactate has been immobilized onto a microneedle surface to create lactate-sensing devices that function at low applied voltages (0.

NEMoE: a nutrition aware regularized mixture of experts model to identify heterogeneous diet-microbiome-host health interactions.

Background: Unrevealing the interplay between diet, the microbiome, and the health state could enable the design of personalized intervention strategies and improve the health and well-being of individuals. A common approach to this is to divide the study population into smaller cohorts based on dietary preferences in the hope of identifying specific microbial signatures. However, classification of patients based solely on diet is unlikely to reflect the microbiome-host health relationship or the taxonomic microbiome makeup.

Homotopic local-global parcellation of the human cerebral cortex from resting-state functional connectivity.

Resting-state fMRI is commonly used to derive brain parcellations, which are widely used for dimensionality reduction and interpreting human neuroscience studies. We previously developed a model that integrates local and global approaches for estimating areal-level cortical parcellations. The resulting local-global parcellations are often referred to as the Schaefer parcellations.

Learning meaningful latent space representations for patient risk stratification: Model development and validation for dengue and other acute febrile illness.

Background: Increased data availability has prompted the creation of clinical decision support systems. These systems utilise clinical information to enhance health care provision, both to predict the likelihood of specific clinical outcomes or evaluate the risk of further complications. However, their adoption remains low due to concerns regarding the quality of recommendations, and a lack of clarity on how results are best obtained and presented.

Angioinvasive Fungal Thyroidits.

Fungal thyroiditis is an uncommon cause of thyroid inflammation and infection. This condition is typically observed within immunosuppressed patients, such as those with a hematologic malignancy or those receiving corticosteroids or chemo-radiation therapies. This report describes a case of a 66-year-old male with underlying high-risk myelodysplastic syndrome who presents with complaints of fever, right anterior neck pain, severe dysphagia, dysphonia, and difficulty managing upper airway secretions.

KMT2D acetylation by CREBBP reveals a cooperative functional interaction at enhancers in normal and malignant germinal center B cells.

Heterozygous inactivating mutations of the KMT2D methyltransferase and the CREBBP acetyltransferase are among the most common genetic alterations in B cell lymphoma and co-occur in 40 to 60% of follicular lymphoma (FL) and 30% of EZB/C3 diffuse large B cell lymphoma (DLBCL) cases, suggesting they may be coselected. Here, we show that combined germinal center (GC)-specific haploinsufficiency of and synergizes in vivo to promote the expansion of abnormally polarized GCs, a common preneoplastic event. These enzymes form a biochemical complex on select enhancers/superenhancers that are critical for the delivery of immune signals in the GC light zone and are only corrupted upon dual / loss, both in mouse GC B cells and in human DLBCL.

Development and Optimization of Imiquimod-Loaded Nanostructured Lipid Carriers Using a Hybrid Design of Experiments Approach.

Background: Imiquimod (IMQ) is an immunomodulating drug that is approved for the treatment of superficial basal cell carcinoma, actinic keratosis, external genital warts and perianal warts. However, IMQ cream (Aldara) has several drawbacks including poor skin permeation, local toxicity, and compromised patient compliance as a topical pharmacological option.

Methods: Our research aimed to develop and optimize nanostructured lipid carriers (NLCs) containing IMQ for the first time using a hybrid design of experiments approach.

Macrocystic ductal adenocarcinoma, a good outcome for a rare cancer in an elderly comorbid patient.

Ductal adenocarcinoma is an aggressive prostate cancer often presenting late due to low serum PSA. A variant presentation of ductal adenocarcinoma occurs with formation of large cystic structures in the prostate, often associated with lower urinary tract symptoms. We present a case illustrating investigation and successful management of a macrocytic ductal carcinoma in a 90 year old patient.

Seborrheic dermatitis: topical therapeutics and formulation design.

Seborrheic dermatitis (SD) is a common dermatological disorder with symptoms that include skin flaking, erythema and pruritus. This review discusses the topical products available for treating SD, which target several aspects of disease pathobiology, including cutaneous microbial dysbiosis (driven by Malassezia yeast), inflammation, sebum production and skin barrier disruption. Among the various treatments available, zinc pyrithione (ZnPT) based products that exhibit anti-fungal action are the market leaders.

Harnessing the Collective Expertise of Patients, Care Partners, Clinical Teams, and Researchers Through a Coproduction Learning Health System: A Case Study of the Dartmouth Health Promise Partnership.

The coproduction learning health system (CLHS) model extends the definition of a learning health system to explicitly bring together patients and care partners, health care teams, administrators, and scientists to share the work of optimizing health outcomes, improving care value, and generating new knowledge. The CLHS model highlights a partnership for coproduction that is supported by data that can be used to support individual patient care, quality improvement, and research. We provide a case study that describes the application of this model to transform care within an oncology program at an academic medical center.

Associations of physical and social workplace characteristics with movement behaviors at work.

Introduction/purpose: Sedentary behavior (SB) is common in desk-based work and prolonged periods of SB are associated with negative health outcomes. This study assessed associations between workplace characteristics and setting and movement patterns during working hours.

Methods: This secondary analysis used baseline data from the Reducing Sedentary Behavior to Decrease Blood Pressure (RESET BP) clinical trial which enrolled inactive, desk-based workers with elevated blood pressure (=271; mean age: 45.

Transcranial direct current stimulation (tDCS) to dorsolateral prefrontal cortex influences perceived pleasantness of food.

The ability to regulate the intake of unhealthy foods is critical in modern, calorie dense food environments. Frontal areas of the brain, such as the dorsolateral prefrontal cortex (DLPFC), are thought to play a central role in cognitive control and emotional regulation. Therefore, increasing activity in the DLPFC may enhance these functions which could improve the ability to reappraise and resist consuming highly palatable but unhealthy foods.

Applied machine learning for the risk-stratification and clinical decision support of hospitalised patients with dengue in Vietnam.

Background: Identifying patients at risk of dengue shock syndrome (DSS) is vital for effective healthcare delivery. This can be challenging in endemic settings because of high caseloads and limited resources. Machine learning models trained using clinical data could support decision-making in this context.

Invader at the edge - Genomic origins and physiological differences of round gobies across a steep urban salinity gradient.

Species invasions are a global problem of increasing concern, especially in highly connected aquatic environments. Despite this, salinity conditions can pose physiological barriers to their spread, and understanding them is important for management. In Scandinavia's largest cargo port, the invasive round goby () is established across a steep salinity gradient.

Virtual Fly Brain-An interactive atlas of the nervous system.

As a model organism, is uniquely placed to contribute to our understanding of how brains control complex behavior. Not only does it have complex adaptive behaviors, but also a uniquely powerful genetic toolkit, increasingly complete dense connectomic maps of the central nervous system and a rapidly growing set of transcriptomic profiles of cell types. But this also poses a challenge: Given the massive amounts of available data, how are researchers to Find, Access, Integrate and Reuse (FAIR) relevant data in order to develop an integrated anatomical and molecular picture of circuits, inform hypothesis generation, and find reagents for experiments to test these hypotheses? The Virtual Fly Brain (virtualflybrain.

An analysis of existing national action plans for antimicrobial resistance-gaps and opportunities in strategies optimising antibiotic use in human populations.

At the 2015 World Health Assembly, UN member states adopted a resolution that committed to the development of national action plans (NAPs) for antimicrobial resistance (AMR). The political determination to commit to NAPs and the availability of robust governance structures to assure sustainable translation of the identified NAP objectives from policy to practice remain major barriers to progress. Inter-country variability in economic and political resilience and resource constraints could be fundamental barriers to progressing AMR NAPs.

Mapping patient pathways and understanding clinical decision-making in dengue management to inform the development of digital health tools.

Background: Dengue is a common viral illness and severe disease results in life-threatening complications. Healthcare services in low- and middle-income countries treat the majority of dengue cases worldwide. However, the clinical decision-making processes which result in effective treatment are poorly characterised within this setting.

A rapid, simple, high-performance liquid chromatography method for the clinical measurement of beta-lactam antibiotics in serum and interstitial fluid.

: enhanced methods of therapeutic drug monitoring are required to support the individualisation of antibiotic dosing based on pharmacokinetics (PK) parameters. PK studies can be hampered by limited total serum volume, especially in neonates, or by sensitivity in the case of critically ill patients. We aimed to develop a liquid chromatography-mass spectrometry (LC/MS) analysis of benzylpenicillin, phenoxymethylpenicillin and amoxicillin in single low volumes of human serum and interstitial fluid (ISF) samples, with an improved limit of detection (LOD) and limit of quantification (LOQ), compared with previously published assays.

The effectiveness of various strategies to improve DNA analysis of formaldehyde-damaged tissues from embalmed cadavers for human identification purposes.

Formalin-fixed tissues provide the medical and forensic communities with alternative and often last resort sources of DNA for identification or diagnostic purposes. The DNA in these samples can be highly degraded and chemically damaged, making downstream genotyping using short tandem repeats (STRs) challenging. Therefore, the use of alternative genetic markers, methods that pre-amplify the low amount of good quality DNA present, or methods that repair the damaged DNA template may provide more probative genetic information.

The elephant in the room: Exploring the influence and participation of patients in infection-related care across surgical pathways in South Africa and India.

Objective: The irrational use of antibiotics is a leading contributor to antibiotic resistance. Antibiotic stewardship (AS) interventions predominantly focus on prescribers. This study investigated the influence and participation of inpatients in infection-related care, including antibiotic decision-making, within and across two tertiary hospitals in South Africa (Cape Town) and India (Kerala).

Importance of timely metadata curation to the global surveillance of genetic diversity.

Genetic diversity within species represents a fundamental yet underappreciated level of biodiversity. Because genetic diversity can indicate species resilience to changing climate, its measurement is relevant to many national and global conservation policy targets. Many studies produce large amounts of genome-scale genetic diversity data for wild populations, but most (87%) do not include the associated spatial and temporal metadata necessary for them to be reused in monitoring programs or for acknowledging the sovereignty of nations or Indigenous peoples.

A cross-sectional and longitudinal study of human brain development: The integration of cortical thickness, surface area, gyrification index, and cortical curvature into a unified analytical framework.

Brain maturation studies typically examine relationships linking a single morphometric feature with cognition, behavior, age, or other demographic characteristics. However, the coordinated spatiotemporal arrangement of morphological features across development and their associations with behavior are unclear. Here, we examine covariation across multiple cortical features (cortical thickness [CT], surface area [SA], local gyrification index [GI], and mean curvature [MC]) using magnetic resonance images from the NIMH developmental cohort (ages 5-25).