Roseburia intestinalis-derived butyrate alleviates neuropathic pain.

Approximately 20% of patients with shingles develop postherpetic neuralgia (PHN). We investigated the role of gut microbiota in shingle- and PHN-related pain. Patients with shingles or PHN exhibited significant alterations in their gut microbiota with microbial markers predicting PHN development among patients with shingles.

A novel 4,4-dimethylcytidine in the archaeal ribosome enhances hyperthermophily.

Ribosome structure and activity are challenged at high temperatures, often demanding modifications to ribosomal RNAs (rRNAs) to retain translation fidelity. LC-MS/MS, bisulfite-sequencing, and high-resolution cryo-EM structures of the archaeal ribosome identified an RNA modification, 4,4-dimethylcytidine (mC), at the universally conserved C918 in the 16S rRNA helix 31 loop. Here, we characterize and structurally resolve a class of RNA methyltransferase that generates mC whose function is critical for hyperthermophilic growth.

Three-Dimension Sawbone Models and Shadow-Play: A Low-Cost Approach to Improve Orthopedic Plain Radiograph Reading in Medical Students.

Background: The usage of 3D sawbone models and shadow-play is a novel teaching method in orthopedic education. The aim of this study was to evaluate the effectiveness of 3D sawbone models and shadow-play in improving medical student orthopedic knowledge and interpretation of plain radiographs.

Methods: Ninety-three medical students with no prior clinical orthopaedic experience were recruited into 2 groups: Group 1 underwent conventional education methods and Group 2 underwent a sawbone and shadow-play education.

Scanning the aged to minimize missed injury: An Eastern Association for the Surgery of Trauma multicenter study.

Background: Despite the high incidence of blunt trauma in older adults, there is a lack of evidence-based guidance for computed tomography (CT) imaging in this population. We aimed to identify an algorithm to guide use of a pan-scan (head/cervical spine [C-spine]/torso) or a selective scan (head/C-spine ± torso). We hypothesized that a patient's initial history and examination could be used to guide imaging.

Polymeric Nanoparticles Enable mRNA Transfection and Its Translation in Intervertebral Disc and Human Joint Cells, Except for M1 Macrophages.

Chronic lower back pain caused by intervertebral disc degeneration and osteoarthritis (OA) are highly prevalent chronic diseases. Although pain management and surgery can alleviate symptoms, no disease-modifying treatments are available. mRNA delivery could halt inflammation and degeneration and induce regeneration by overexpressing anti-inflammatory cytokines or growth factors involved in cartilage regeneration.

Characterization of Individuals With Apparent Resistant Hypertension Using Contemporary Guidelines: Insights From CV-QUIC.

Background: Apparent resistant hypertension (aRH) carries excess cardiovascular risk beyond nonresistant forms of hypertension; however, our understanding of this at-risk population, as defined by current US practice guidelines, is limited. Accordingly, we sought to evaluate the prevalence, clinical characteristics, and pharmacotherapeutic patterns of patients with aRH using contemporary blood pressure guidance.

Methods: We classified patients at 3 large healthcare systems by hypertensive status using contemporary hypertension guidelines.

Anterior cruciate ligament rupture and associated Segond fracture: Incidence and effect on associated ligamentous and meniscal injuries.

Introduction: The Segond fracture is an avulsion fracture of the lateral tibial plateau and is widely considered to be pathognomonic of anterior cruciate ligament (ACL) rupture. In addition to ACL rupture, Segond fractures have also been noted to be associated with significant intra-articular pathology such as meniscal injuries as well as extra-articular pathology such as collateral ligament injuries. This is likely due to the fact that the presence of a Segond fracture may represent increased rotatory instability.

Stroke genetics informs drug discovery and risk prediction across ancestries.

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.

Plasma Markers of Neurologic Injury and Inflammation in People With Self-Reported Neurologic Postacute Sequelae of SARS-CoV-2 Infection.

Background And Objectives: The biologic mechanisms underlying neurologic postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) are incompletely understood.

Methods: We measured markers of neurologic injury (glial fibrillary acidic protein [GFAP], neurofilament light chain [NfL]) and soluble markers of inflammation among a cohort of people with prior confirmed SARS-CoV-2 infection at early and late recovery after the initial illness (defined as less than and greater than 90 days, respectively). The primary clinical outcome was the presence of self-reported CNS PASC symptoms during the late recovery time point.

Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution.

Tumor evolution is driven by the progressive acquisition of genetic and epigenetic alterations that enable uncontrolled growth and expansion to neighboring and distal tissues. The study of phylogenetic relationships between cancer cells provides key insights into these processes. Here, we introduced an evolving lineage-tracing system with a single-cell RNA-seq readout into a mouse model of Kras;Trp53(KP)-driven lung adenocarcinoma and tracked tumor evolution from single-transformed cells to metastatic tumors at unprecedented resolution.

Answer ALS, a large-scale resource for sporadic and familial ALS combining clinical and multi-omics data from induced pluripotent cell lines.

Answer ALS is a biological and clinical resource of patient-derived, induced pluripotent stem (iPS) cell lines, multi-omic data derived from iPS neurons and longitudinal clinical and smartphone data from over 1,000 patients with ALS. This resource provides population-level biological and clinical data that may be employed to identify clinical-molecular-biochemical subtypes of amyotrophic lateral sclerosis (ALS). A unique smartphone-based system was employed to collect deep clinical data, including fine motor activity, speech, breathing and linguistics/cognition.

A Slam-dependent hemophore contributes to heme acquisition in the bacterial pathogen Acinetobacter baumannii.

Nutrient acquisition systems are often crucial for pathogen growth and survival during infection, and represent attractive therapeutic targets. Here, we study the protein machinery required for heme uptake in the opportunistic pathogen Acinetobacter baumannii. We show that the hemO locus, which includes a gene encoding the heme-degrading enzyme, is required for high-affinity heme acquisition from hemoglobin and serum albumin.

Text Message Medication Adherence Reminders Automated and Delivered at Scale Across Two Institutions: Testing the Nudge System: Pilot Study.

Background: Medication refill behavior in patients with cardiovascular diseases is suboptimal. Brief behavioral interventions called Nudges may impact medication refill behavior and can be delivered at scale to patients using text messaging.

Methods: Patients who were prescribed and filled at least one medication for hypertension, hyperlipidemia, diabetes, atrial fibrillation, and coronary artery disease were identified for the pilot study.

Towards motor evaluation of Parkinson's Disease Patients using wearable inertial sensors.

Parkinson's disease (PD) patients require frequent office visits where they are assessed for health state changes using Unified Parkinson's Disease Rating Scale (UPDRS). Inertial wearable sensor devices present a unique opportunity to supplement these assessments with continuous monitoring. In this work, we analyze kinematic features from sensor devices located on feet, wrists, lumbar and sternum for 35 PD subjects as they performed walk trials in two clinical visits, one for each of their self-reported ON and OFF motor states.

Tenofovir Alafenamide for HIV Prevention: Review of the Proceedings from the Gates Foundation Long-Acting TAF Product Development Meeting.

The ability to successfully develop a safe and effective vaccine for the prevention of HIV infection has proven challenging. Consequently, alternative approaches to HIV infection prevention have been pursued, and there have been a number of successes with differing levels of efficacy. At present, only two oral preexposure prophylaxis (PrEP) products are available, Truvada and Descovy.

Deep Multi-Magnification Networks for multi-class breast cancer image segmentation.

Pathologic analysis of surgical excision specimens for breast carcinoma is important to evaluate the completeness of surgical excision and has implications for future treatment. This analysis is performed manually by pathologists reviewing histologic slides prepared from formalin-fixed tissue. In this paper, we present Deep Multi-Magnification Network trained by partial annotation for automated multi-class tissue segmentation by a set of patches from multiple magnifications in digitized whole slide images.

The Cardiovascular Quality Improvement and Care Innovation Consortium: Inception of a Multicenter Collaborative to Improve Cardiovascular Care.

Despite decades of improvement in the quality and outcomes of cardiovascular care, significant gaps remain. Existing quality improvement strategies are often limited in scope to specific clinical conditions and episodic care. Health services and outcomes research is essential to inform gaps in care but rarely results in the development and implementation of care delivery solutions.

A Carbohydrate-Binding Protein from the Edible Lablab Beans Effectively Blocks the Infections of Influenza Viruses and SARS-CoV-2.

The influenza virus hemagglutinin (HA) and coronavirus spike (S) protein mediate virus entry. HA and S proteins are heavily glycosylated, making them potential targets for carbohydrate binding agents such as lectins. Here, we show that the lectin FRIL, isolated from hyacinth beans (Lablab purpureus), has anti-influenza and anti-SARS-CoV-2 activity.

Speech-based characterization of dopamine replacement therapy in people with Parkinson's disease.

People with Parkinson's (PWP) disease are under constant tension with respect to their dopamine replacement therapy (DRT) regimen. Waiting too long between doses results in more prominent symptoms, loss of motor function, and greater risk of falling per step. Shortened pill cycles can lead to accelerated habituation and faster development of disabling dyskinesias.

Longitudinal biomarkers in amyotrophic lateral sclerosis.

Objective: To investigate neurodegenerative and inflammatory biomarkers in people with amyotrophic lateral sclerosis (PALS), evaluate their predictive value for ALS progression rates, and assess their utility as pharmacodynamic biomarkers for monitoring treatment effects.

Methods: De-identified, longitudinal plasma, and cerebrospinal fluid (CSF) samples from PALS (n = 108; 85 with samples from ≥2 visits) and controls without neurological disease (n = 41) were obtained from the Northeast ALS Consortium (NEALS) Biofluid Repository. Seventeen of 108 PALS had familial ALS, of whom 10 had C9orf72 mutations.

Multi-Field-of-View Deep Learning Model Predicts Nonsmall Cell Lung Cancer Programmed Death-Ligand 1 Status from Whole-Slide Hematoxylin and Eosin Images.

Background: Tumor programmed death-ligand 1 (PD-L1) status is useful in determining which patients may benefit from programmed death-1 (PD-1)/PD-L1 inhibitors. However, little is known about the association between PD-L1 status and tumor histopathological patterns. Using deep learning, we predicted PD-L1 status from hematoxylin and eosin (H and E) whole-slide images (WSIs) of nonsmall cell lung cancer (NSCLC) tumor samples.

Tunable Hyperbolic Metamaterials Based on Self-Assembled Carbon Nanotubes.

We show that packed, horizontally aligned films of single-walled carbon nanotubes are hyperbolic metamaterials with ultrasubwavelength unit cells and dynamic tunability. Using Mueller matrix ellipsometry, we characterize the films' optical properties, which are doping level dependent, and find a broadband hyperbolic region tunable in the mid-infrared. To characterize the dispersion of in-plane hyperbolic plasmon modes, we etch the nanotube films into nanoribbons with differing widths and orientations relative to the nanotube axis, and we observe that the hyperbolic modes support strong light localization.