Dual Inhibitors of SARS-CoV-2 3CL Protease and Human Cathepsin L Containing Glutamine Isosteres Are Anti-CoV-2 Agents.

SARS-CoV-2 3CL protease (Main protease) and human cathepsin L are proteases that play unique roles in the infection of human cells by SARS-CoV-2, the causative agent of COVID-19. Both proteases recognize leucine and other hydrophobic amino acids at the P position of a peptidomimetic inhibitor. At the P position, cathepsin L accepts many amino acid side chains, with a partial preference for phenylalanine, while 3CL-PR protease has a stringent specificity for glutamine or glutamine analogues.

A propensity score-matched comparison between single-stage and multistage anterior/posterior lumbar fusion surgery: a Michigan Spine Surgery Improvement Collaborative study.

Objective: Patients undergoing anterior/posterior lumbar fusion surgery can undergo either a single-stage or multistage operation, depending on surgeon preference. The goal of this study was to assess different patient outcomes between single-stage and multistage lumbar fusion procedures in a multicenter setting.

Methods: The Michigan Spine Surgery Improvement Collaborative database was queried for anterior/posterior lumbar fusion surgeries between July 2018 and January 2022.

Sportizumab - Multimodal progressive exercise over 10 weeks decreases Th17 frequency and CD49d expression on CD8 T cells in relapsing-remitting multiple sclerosis: A randomized controlled trial.

Background: Multiple Sclerosis (MS) represents a neuroinflammatory autoimmune disease characterized by the predominance of circulating T cell subsets with proinflammatory characteristics and increased central nervous system (CNS)-homing potential. Substantial evidence confirms various beneficial effects of chronic exercise interventions in MS, but it is unknown how long-term multi-modal intense exercise affects MS-associated lymphocytes that are commonly targeted by medication in persons with relapsing remitting MS (pwRRMS).

Methods: A total of 45 participants with defined RRMS were randomized to either the exercise (n = 22) or passive waitlist-control group (n = 23).

Laser Interstitial Thermal Therapy for Intra-Axial Brain Tumors: Everything the Neuroradiologist Should Know.

Laser interstitial thermal therapy (LITT) is a minimally invasive cytoreductive treatment option for patients with intracranial tumors. Utilizing real-time MR thermometry, LITT delivers tailored, targeted, and permanent cytotoxic thermal injury to intra-axial pathology. As a minimally invasive and nonionizing treatment option proved to be an effective, less morbid, and more efficient alternative to surgery, the utility of LITT has rapidly expanded.

The impact of serum albumin levels on postoperative complications in lumbar and cervical spine surgery: an analysis of the Michigan Spine Surgery Improvement Collaborative registry.

Objective: Patients with serum albumin levels < 3.5 g/dL are considered malnourished, but there is a paucity of data regarding the outcomes of patients with albumin levels > 3.5 g/dL.

Longitudinal relations of prematurity and fetal growth restrictions with hyperactivity/inattention and aggression/delinquency.

Background: It is the aim of this study to analyze the longitudinal relationship between premature birth and low birth weight and the reciprocal influence between hyperactive/inattentive behavior and aggressive/delinquent behavior problems in children from early to late childhood.

Methods: This study contains data from the German Erlangen-Nuremberg Development and Prevention Study. It applies prospective longitudinal path analyses on data obtained from postnatal pediatric assessments as well as later psychosocial behavior assessments by teachers and parents on N = 667 children, out of which n = 83 children (12.

Measurement invariance of the inventory of Callous‑Unemotional traits in different age groups from preschool age to late adolescence in Germany.

Background: Callous-unemotional traits are associated with the development of severe behavior problems, delinquency, and psychopathy. Previous studies have repeatedly shown that CU traits may be present as early as preschool age, and they have consistently used the Inventory of Callous-Unemotional Traits (ICU) to assess CU traits in children and adolescents. A three-factor structure for the ICU has been widely endorsed.

Compartments in medulloblastoma with extensive nodularity are connected through differentiation along the granular precursor lineage.

Medulloblastomas with extensive nodularity are cerebellar tumors characterized by two distinct compartments and variable disease progression. The mechanisms governing the balance between proliferation and differentiation in MBEN remain poorly understood. Here, we employ a multi-modal single cell transcriptome analysis to dissect this process.

Bone Grafting Options for Single-Level TLIF: So Many Options, What Is the Evidence?

Background: This review seeks to investigate the clinically relevant bone graft materials in single-level transforaminal lumbar interbody fusion (TLIF) procedures as defined by (1) primary outcomes (ie, fusion rates and complication rates) and (2) patient-reported outcomes (ie, visual analog scale [VAS] and Oswestry disability index [ODI]). Because of the advantages in stimulating bone growth, autologous bone grafts such as the iliac crest bone graft (ICBG) have been the gold standard. Numerous alternatives to ICBG have been introduced.

Physical activity is related to disease severity and fatigue, but not to relapse rate in persons with relapsing remitting multiple sclerosis - a self-reported questionnaire based study.

Introduction: Based on theoretical models, physical activity has been introduced as a promoting method to mitigate the disease severity, fatigue and relapse rate in multiple sclerosis. The primary objective of the study was to investigate the relation between self-reported physical activity level and disease severity, fatigue and relapse rate in persons with relapsing remitting multiple sclerosis (RRMS).

Methods: A survey was offered to persons with RRMS from March 2019 to August 2021 ( = 253).

Cycling in primary progressive multiple sclerosis (CYPRO): study protocol for a randomized controlled superiority trial evaluating the effects of high-intensity interval training in persons with primary progressive multiple sclerosis.

Background: Primary progressive multiple sclerosis (PPMS) is the least prevalent multiple sclerosis (MS) phenotype. For persons with PPMS (pwPPMS), pharmacological treatment options are limited. As a complementary non-pharmacological treatment, endurance training improves the health-related quality of life (HRQoL), numerous MS symptoms, and MS-related performance impediments.

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance.

Multimodal Agility-Based Exercise Training for Persons With Multiple Sclerosis: A New Framework.

Introduction: Multimodal agility-based exercise training (MAT) has been described as a framework for fall prevention in the elderly but might also be a valuable concept for exercise training in persons with Multiple Sclerosis (pwMS).

The Problem: Current recommendations advise pwMS to perform a multitude of different exercise training activities, as each of these has its separate evidence. However, pwMS struggle even more than the general population to be physically active.

Assessing the Phase Separation Propensity of Proteins in Living Cells Through Optodroplet Formation.

Phase separation is emerging as a key mechanism to describe the formation of membraneless organelles in the cell. It depends on the multivalent (self-) interaction properties of the macromolecules involved and can be observed in aqueous solutions under controlled conditions in vitro with purified components. However, to experimentally demonstrate that this process indeed occurs in the complex environment of living cells remains difficult.

Systems in Flames: Dynamic Coproduction of Social-Ecological Processes.

Ecologists who study human-dominated places have adopted a social-ecological systems framework to recognize the coproduced links between ecological and social processes. However, many social scientists are wary of the way ecologists use the systems concept to represent such links. This wariness is sometimes due to a misunderstanding of the contemporary use of the systems concept in ecology.

Transcription activation is enhanced by multivalent interactions independent of phase separation.

Transcription factors (TFs) consist of a DNA-binding domain and an activation domain (AD) that are frequently considered to be independent and exchangeable modules. However, recent studies report that the physicochemical properties of the AD can control TF assembly at chromatin by driving phase separation into transcriptional condensates. Here, we dissected transcription activation by comparing different synthetic TFs at a reporter gene array with real-time single-cell fluorescence microscopy.

DNA sequence-dependent formation of heterochromatin nanodomains.

The mammalian epigenome contains thousands of heterochromatin nanodomains (HNDs) marked by di- and trimethylation of histone H3 at lysine 9 (H3K9me2/3), which have a typical size of 3-10 nucleosomes. However, what governs HND location and extension is only partly understood. Here, we address this issue by introducing the chromatin hierarchical lattice framework (ChromHL) that predicts chromatin state patterns with single-nucleotide resolution.

ALT-FISH quantifies alternative lengthening of telomeres activity by imaging of single-stranded repeats.

Alternative lengthening of telomeres (ALT) occurs in ∼10% of cancer entities. However, little is known about the heterogeneity of ALT activity since robust ALT detection assays with high-throughput in situ readouts are lacking. Here, we introduce ALT-FISH, a method to quantitate ALT activity in single cells from the accumulation of single-stranded telomeric DNA and RNA.

Fitness, physical activity, and exercise in multiple sclerosis: a systematic review on current evidence for interactions with disease activity and progression.

Background: A moderate to high level of physical activity, including regular exercise, represents an established behavioral and rehabilitative approach for persons with multiple sclerosis (pwMS). Although being increasingly proposed to limit disease activity and progression, high-quality evidence is lacking.

Objective: The objective of the study is to provide valuable information for MS clinicians and researchers by systematically evaluating the current state of evidence (i) whether exercise interventions affect established clinical measures of disease activity and progression in pwMS (i.

The aerobic capacity - fatigue relationship in persons with Multiple Sclerosis is not reproducible in a pooled analysis of two randomized controlled trials.

Background: Fatigue is one of the most frequent symptoms of persons with Multiple Sclerosis (pwMS) but has limited treatment options. Aerobic capacity and endurance training have been discussed as relevant factors to improve fatigue. However, over the last decades, results have been equivocal.

Patients' lived experiences and recommendations for enhanced awareness and use of integrative oncology services in cancer care.

Background: Consuming educational content, adhering to treatment plans and managing symptoms and side-effects can be overwhelming to new oncology patients.

Objective: The purpose of this study is to engage patients in conceptualization of enhanced clinic processes and digital health tools to support awareness and use of integrative oncology services.

Patient Involvement: We engaged patients in participatory design to understand lived experiences surrounding use of integrative oncology services during and after conventional cancer treatment.