Accessing Rehabilitation after Upper Limb Reconstructive Surgery in Cervical Spinal Cord Injury: A Qualitative Study.

Objectives: To investigate the barriers and facilitators to rehabilitation experienced by individuals with cervical SCI after upper limb (UL) reconstructive surgery.

Methods: We conducted a prospective cohort study with a follow-up period of up to 24 months. Data collection occurred at two academic and two Veterans Affairs medical centers in the United States.

Toward a Radically Simple Multi-Modal Nasal Spray for Preventing Respiratory Infections.

Nasal sprays for pre-exposure prophylaxis against respiratory infections show limited protection (20-70%), largely due to their single mechanism of action-either neutralizing pathogens or blocking their entry at the nasal lining, and a failure to maximize the capture of respiratory droplets, allowing them to potentially rebound and reach deeper airways. This report introduces the Pathogen Capture and Neutralizing Spray (PCANS), which utilizes a multi-modal approach to enhance efficacy. PCANS coats the nasal cavity, capturing large respiratory droplets from the air, and serving as a physical barrier against a broad spectrum of viruses and bacteria, while rapidly neutralizing them with over 99.

Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency.

The use of modified nucleotides to suppress the interferon response and maintain translation of self-amplifying RNA (saRNA), which has been achieved for mRNA, has not yet succeeded. We identify modified nucleotides that, when substituted at 100% in saRNA, confer innate immune evasion and robust long-term protein expression, and when formulated as a vaccine, protect against lethal SARS-CoV-2 challenge in mice. This discovery advances saRNA therapeutics by enabling prolonged protein expression at low doses.

Aging is associated with an insufficient early inflammatory response of lung endothelial cells in SARS-CoV-2 infection.

Advanced age is associated with an increased susceptibility to Coronavirus Disease (COVID)-19 and more severe outcomes, although the underlying mechanisms are understudied. The lung endothelium is located next to infected epithelial cells and bystander inflammation may contribute to thromboinflammation and COVID-19-associated coagulopathy. Here, we investigated age-associated SARS-CoV-2 pathogenesis and endothelial inflammatory responses using humanized K18-hACE2 mice.

Evasion of NKG2D-mediated cytotoxic immunity by sarbecoviruses.

SARS-CoV-2 and other sarbecoviruses continue to threaten humanity, highlighting the need to characterize common mechanisms of viral immune evasion for pandemic preparedness. Cytotoxic lymphocytes are vital for antiviral immunity and express NKG2D, an activating receptor conserved among mammals that recognizes infection-induced stress ligands (e.g.

Immune Signatures of SARS-CoV-2 Infection Resolution in Human Lung Tissues.

While human autopsy samples have provided insights into pulmonary immune mechanisms associated with severe viral respiratory diseases, the mechanisms that contribute to a clinically favorable resolution of viral respiratory infections remain unclear due to the lack of proper experimental systems. Using mice co-engrafted with a genetically matched human immune system and fetal lung xenograft (fLX), we mapped the immunological events defining successful resolution of SARS-CoV-2 infection in human lung tissues. Viral infection is rapidly cleared from fLX following a peak of viral replication, histopathological manifestations of lung disease and loss of AT2 program, as reported in human COVID-19 patients.

Sarcoma microenvironment cell states and ecosystems are associated with prognosis and predict response to immunotherapy.

Characterization of the diverse malignant and stromal cell states that make up soft tissue sarcomas and their correlation with patient outcomes has proven difficult using fixed clinical specimens. Here, we employed EcoTyper, a machine-learning framework, to identify the fundamental cell states and cellular ecosystems that make up sarcomas on a large scale using bulk transcriptomes with clinical annotations. We identified and validated 23 sarcoma-specific, transcriptionally defined cell states, many of which were highly prognostic of patient outcomes across independent datasets.

Opportunistic hand radiographs to screen for low forearm bone mineral density: a prospective and retrospective cohort study.

Background: Low bone mineral density affects 53% of women over age 65 in the US, yet many are unaware and remain untreated. Underdiagnosis of forearm osteoporosis and related fragility fractures represent missed warning signs of more deadly, future fractures. This study aimed to determine if hand radiographs could serve as early, simple screening tools for predicting low forearm bone mineral density (BMD).

Peripheral nerve stimulation for saphenous neuralgia.

Background: Injury to saphenous nerve branches is frequent during knee surgery and can result in chronic pain. This saphenous neuralgia remains challenging to treat. Peripheral nerve stimulation (PNS) is a new potential non-pharmacologic treatment option.

Complete substitution with modified nucleotides suppresses the early interferon response and increases the potency of self-amplifying RNA.

Self-amplifying RNA (saRNA) will revolutionize vaccines and therapeutics by enabling protein expression for longer duration at lower doses. However, a major barrier to saRNA efficacy is the potent early interferon response triggered upon cellular entry, resulting in saRNA degradation and translational inhibition. Substitution of mRNA with modified nucleotides (modNTPs), such as N1-methylpseudouridine (N1mΨ), reduce the interferon response and enhance expression levels.

Assessment of the Interval to Diagnosis in Pediatric Bone Sarcoma.

Objectives: The timely diagnosis of primary bone malignancies in pediatric patients is critical to clinical outcomes. The purpose of this study is to investigate the initial presentation of pediatric bone sarcoma patients to an academic health care system and assess the current interval to diagnosis.

Methods: We conducted a retrospective review of pediatric patients (aged 1-18) with biopsy-proven diagnosis of osteosarcoma or Ewing sarcoma presenting between 2004 and 2020.

Positive-strand RNA viruses-a Keystone Symposia report.

Positive-strand RNA viruses have been the cause of several recent outbreaks and epidemics, including the Zika virus epidemic in 2015, the SARS outbreak in 2003, and the ongoing SARS-CoV-2 pandemic. On June 18-22, 2022, researchers focusing on positive-strand RNA viruses met for the Keystone Symposium "Positive-Strand RNA Viruses" to share the latest research in molecular and cell biology, virology, immunology, vaccinology, and antiviral drug development. This report presents concise summaries of the scientific discussions at the symposium.

Dimensionally reduced machine learning model for predicting single component octanol-water partition coefficients.

MF-LOGP, a new method for determining a single component octanol-water partition coefficients ([Formula: see text]) is presented which uses molecular formula as the only input. Octanol-water partition coefficients are useful in many applications, ranging from environmental fate and drug delivery. Currently, partition coefficients are either experimentally measured or predicted as a function of structural fragments, topological descriptors, or thermodynamic properties known or calculated from precise molecular structures.

Spike and nsp6 are key determinants of SARS-CoV-2 Omicron BA.1 attenuation.

The SARS-CoV-2 Omicron variant is more immune evasive and less virulent than other major viral variants that have so far been recognized. The Omicron spike (S) protein, which has an unusually large number of mutations, is considered to be the main driver of these phenotypes. Here we generated chimeric recombinant SARS-CoV-2 encoding the S gene of Omicron (BA.

The biomechanics of osteoarthritis in the hand: Implications and prospects for hand therapy.

Background: The unique anatomy of the human hand makes it possible to carefully manipulate tools, powerfully grasp objects, and even throw items with precision. These apparent contradictory functions of the hand, high mobility for manual dexterity vs high stability during forceful grasping, imply that daily activities impose a high strain on a relatively instable joint. This makes the hand susceptible to joint disorders such as osteoarthritis.

Purification of Bone Marrow Precursors to T Cells and ILCs.

T cells and innate lymphoid cells (ILCs) share expression of many key transcription factors during development and at mature stage, resulting in striking functional similarities between these lineages. Taking into account ILC contribution is thus necessary to appreciate T cell functions during immune responses. Furthermore, understanding ILC development and functions helps to understand T cells.

Role of spike in the pathogenic and antigenic behavior of SARS-CoV-2 BA.1 Omicron.

The recently identified, globally predominant SARS-CoV-2 Omicron variant (BA.1) is highly transmissible, even in fully vaccinated individuals, and causes attenuated disease compared with other major viral variants recognized to date. The Omicron spike (S) protein, with an unusually large number of mutations, is considered the major driver of these phenotypes.

Surgery to restore upper extremity function in tetraplegia-Preferences for early and frequent access to information.

Introduction: People with cervical spinal cord injury (SCI) identify improving upper extremity (UE) function as a top priority. In addition to comprehensive rehabilitation, UE surgeries, including nerve and tendon transfers, enhance function. However, barriers exist to disseminating information about surgical options to enhance UE function.

Evaluation of the PROMIS Upper Extremity Against Validated Patient-Reported Outcomes in Patients With Early Carpometacarpal Osteoarthritis.

Purpose: Internal consistency, construct, and criterion validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) upper extremity (UE) v1.2 were evaluated in patients with early-stage carpometacarpal (CMC) osteoarthritis (OA). We hypothesized that in patients with early CMC OA, PROMIS UE scores would: (1) be lower than those in asymptomatic controls; (2) correlate with established patient-reported outcomes; (3) correlate with pinch and grip strengths; and (4) not correlate with radiographic disease progression.

Humanized mice reveal a macrophage-enriched gene signature defining human lung tissue protection during SARS-CoV-2 infection.

The human immunological mechanisms defining the clinical outcome of SARS-CoV-2 infection remain elusive. This knowledge gap is mostly driven by the lack of appropriate experimental platforms recapitulating human immune responses in a controlled human lung environment. Here, we report a mouse model (i.