Regulation of PD-L1 glycosylation and advances in cancer immunotherapy.

Protein glycosylation plays a versatile role in regulating homeostasis, such as cell migration, protein sorting, and the immune response. Drugs aimed at targeting glycosylation have strong implications for immunity enhancement, diagnosis, and cancer regression. Programmed death-ligand 1 (PD-L1), expressed in cancer or antigen-presenting cells, binds to programmed cell death protein 1 (PD-1) and suppresses T cells.

Long term outcomes post-ICD in Chagas cardiomyopathy and non-ischemic cardiomyopathy: A comparative analysis.

Background: Chagas cardiomyopathy (CCM) is a significant cause of ventricular arrhythmias and sudden cardiac death (SCD). Although, implantable cardiac defibrillators (ICD) have been used for all forms of non-ischemic cardiomyopathy (NICM), studies on ICD efficacy in CCM are scarce.

Objective: The present study aims to compare the long-term outcomes, mortality rates, and the occurrence of tachycardia therapies after ICD implantation in patients with CCM and NICM.

Effect of one prophylactic dose of Azithromycin on Bifidobacterium infantis colonization in infants from the Mumta Trial.

Objectives: The effects of antibiotics on the microbiome remain incompletely understood. Azithromycin (AZ) has been shown to improve child survival and infant growth outcomes. This study aimed to assess the impact of AZ on B.

Therapeutic potential of siRNA PMP22-SQ nanoparticles for Charcot-Marie-Tooth 1A neuropathy in rodents and non-human primates.

Small interfering RNA (siRNA) has shown promising results for the treatment of Charcot-Marie-Tooth disease 1A (CMT1A) caused by overexpression of peripheral myelin protein (PMP22), leading to myelin dysfunction and axonal damage. Recently, we developed siRNA PMP22-squalene (SQ) nanoparticles (NPs) for intravenous use. Three consecutive injections of siRNA PMP22-SQ NPs at a cumulative dose of 1.

Causal Estimands for Analyses of Averted and Avertible Outcomes due to Infectious Disease Interventions.

During the coronavirus disease (COVID-19) pandemic, researchers attempted to estimate the number of averted and avertible outcomes due to vaccination campaigns to quantify public health impact. However, the estimands used in these analyses have not been previously formalized. It is also unclear how these analyses relate to the broader framework of direct, indirect, total, and overall causal effects under interference.

Designed mosaic nanoparticles enhance cross-reactive immune responses in mice.

Nanoparticle vaccines displaying combinations of SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) could protect against SARS-CoV-2 variants and spillover of zoonotic sarbecoviruses into humans. Using a computational approach, we designed variants of SARS-CoV-2 RBDs and selected 7 natural sarbecovirus RBDs, each predicted to fold properly and abrogate antibody responses to variable epitopes. RBDs were attached to 60-mer nanoparticles to make immunogens displaying two (mosaic-2s), five (mosaic-5), or seven (mosaic-7) different RBDs for comparisons with mosaic-8b, which elicited cross-reactive antibodies and protected animals from sarbecovirus challenges.

Necrotizing enterocolitis vs bowel ischemia of congenital heart disease: Apples and oranges.

Necrotizing enterocolitis (NEC) is a devastating illness with mortality rates approaching 26 ​%, with 4 ​% of patients with congenital heart disease (CHD) receiving this diagnosis. In this retrospective cohort study, the Pediatric Health Information System database was used to compare outcomes among patients with NEC diagnoses between 2019 and 2021 by CHD. The association of clinical factors with the outcomes of interest were compared using multivariable logistic regression.

A low-cost transhumeral prosthesis operated via an ML-assisted EEG-head gesture control system.

Objective Key challenges in upper limb prosthetics include a lack of effective control systems, the often invasive surgical requirements of brain-controlled limbs, and prohibitive costs. As a result, disuse rates remain high despite potential for increased quality of life. To address these concerns, this project developed a low cost, noninvasive transhumeral neuroprosthesis-operated via a combination of electroencephalography (EEG) signals and head gestures.

Impact of disease duration and surgical intervention on arousal networks in temporal lobe epilepsy.

Objective: Epilepsy is a common neurological disease affecting nearly 1% of the global population, and temporal lobe epilepsy (TLE) is the most common type. Patients experience recurrent seizures and chronic cognitive deficits that can impact their quality of life, ability to work, and independence. These cognitive deficits often extend beyond the temporal lobe and are not well understood.

Lewis Base-Enhanced C-H Bond Functionalization Mediated by a Diiron Imido Complex.

Herein, we investigate the effects of ligand design on the nuclearity and reactivity of metal-ligand multiply bonded (MLMB) complexes to access an exclusively bimetallic reaction pathway for C-H bond functionalization. To this end, the diiron alkoxide [Fe(Dbf)] () was treated with 3,5-bis(trifluoromethyl)phenyl azide to access the diiron imido complex [Fe(Dbf)(μ-NCHF)] () that promotes hydrogen atom abstraction (HAA) from a variety of C-H and O-H bond containing substrates. A diiron bis(amide) complex [Fe(Dbf)(μ-NHCHF)(NHCHF)] () was generated, prompting the isolation of the analogous bridging amide terminal alkoxide [Fe(Dbf)(μ-NHCHF)(OCH)] () and the asymmetric pyridine-bound diiron imido [Fe(Dbf)(μ-NCHF)(NCH)] ().

Management of Insomnia in the General Hospital.

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.

Myelin ensheathment and drug responses of oligodendrocytes are modulated by stiffness of artificial axons.

Myelination is a key biological process wherein glial cells such as oligodendrocytes wrap myelin around neuronal axons, forming an insulative sheath that accelerates signal propagation down the axon. A major obstacle to understanding myelination is the challenge of visualizing and reproducibly quantifying this inherently three-dimensional process in vitro. To this end, we previously developed artificial axons (AAs), a biocompatible platform consisting of 3D-printed hydrogel-based axon mimics designed to more closely recapitulate the micrometer-scale diameter and sub-kilopascal mechanical stiffness of biological axons.

Successful Healing After Minimally Invasive Subtalar Fusion Following Comminuted Open Calcaneus Fracture: A Case Report.

Case: A 51-year-old male polytrauma patient presented with bilateral calcaneus fractures after a fall. This report describes treatment of his right comminuted Sanders IV calcaneus fracture with percutaneous open reduction internal fixation (ORIF) and minimally invasive surgery (MIS) primary subtalar fusion to restore alignment and preserve soft tissue.

Conclusion: Unlike traditional open approaches, which are prone to wound complications due to larger incisions, our approach of maintaining fracture alignment during joint preparation using an MIS burr for acute posttrauma subtalar arthrodesis and percutaneous ORIF appears to have reduced these risks, resulting in successful radiological healing and functional recovery at 1-year follow-up.

Development of a unique crosslinked glycosaminoglycan for soft tissue repair: Treatment of interstitial cystitis/bladder pain syndrome.

Chemical modification of naturally derived glycosaminoglycans (GAGs) expands their potential utility for applications in soft tissue repair and regenerative medicine. Here we report the preparation of a novel crosslinked chondroitin sulfate (~200 to 2000 kilodaltons) that is both soluble in aqueous solution and microfilterable. We refer to these materials as "SuperGAGs.

Romosozumab Improves Tissue Thickness-Adjusted Trabecular Bone Score in Women With Osteoporosis and Diabetes.

Context: Trabecular bone score (TBS), a gray-level texture index derived from lumbar spine (LS) dual-energy x-ray absorptiometry (DXA) scans, is decreased in patients with diabetes and is associated with increased fracture risk, independent of areal bone mineral density (aBMD), but potentially influenced by abdominal fat tissue.

Objective: Evaluate effect of romosozumab (210 mg monthly) for 12 months followed by alendronate (70 mg weekly) for 24 months vs alendronate alone (70 mg weekly) for 36 months on LS aBMD and TBS in women with type 2 diabetes (T2D) enrolled in the ARCH study.

Methods: This post hoc analysis included women from ARCH who had T2D at baseline and LS DXA scans at baseline and ≥1 postbaseline visit (romosozumab-to-alendronate, n = 165; alendronate-to-alendronate, n = 195).

Automating alloy design and discovery with physics-aware multimodal multiagent AI.

The design of new alloys is a multiscale problem that requires a holistic approach that involves retrieving relevant knowledge, applying advanced computational methods, conducting experimental validations, and analyzing the results, a process that is typically slow and reserved for human experts. Machine learning can help accelerate this process, for instance, through the use of deep surrogate models that connect structural and chemical features to material properties, or vice versa. However, existing data-driven models often target specific material objectives, offering limited flexibility to integrate out-of-domain knowledge and cannot adapt to new, unforeseen challenges.

Biofield Therapies Clinical Research Landscape: A Scoping Review and Interactive Evidence Map.

Biofield Therapies, with a historical lineage spanning millennia and continuing relevance in contemporary practices, have been used to address various health conditions and promote wellbeing. The scientific study and adoption of these therapies have been hindered by cultural challenges and institutional barriers. In addition, the current research landscape for Biofield Therapies is insufficiently documented.

Testing One Primary and Two Secondary Endpoints in a Two-Stage Group Sequential Trial With Extensions.

We study the problem of testing multiple secondary endpoints conditional on a primary endpoint being significant in a two-stage group sequential procedure, focusing on two secondary endpoints. This extends our previous work with one secondary endpoint. The test for the secondary null hypotheses is a closed procedure.

Non-Ablative Fractional 1940-nm Diode Laser for Skin Resurfacing and Treatment of Benign Pigmented Lesions.

Background: The non-ablative 1940-nm laser induces controlled thermal damage at superficial depths without ablating the epidermis.

Objective: We evaluated a new 1940-nm fractional diode laser for improving pigmentation and skin texture.

Materials And Methods: Participants with mild to severe benign pigmented lesions received up to three laser treatments.

Benefit Design and Access to Dental Care Among Seniors With Medicare Advantage Dental Benefits.

Importance: Although Medicare Advantage plans frequently offer dental benefits, enrollees report lower rates of dental care use and higher rates of unmet dental need compared with individuals with employer-sponsored benefits. It is unknown which attributes of Medicare Advantage dental plans are associated with enhanced dental care access.

Objective: To determine attributes of Medicare Advantage dental plans associated with higher rates of dental care use and lower rates of unmet dental need.