Advances in manufacturing chimeric antigen receptor immune cell therapies.

Biomedical research has witnessed significant strides in manufacturing chimeric antigen receptor T cell (CAR-T) therapies, marking a transformative era in cellular immunotherapy. Nevertheless, existing manufacturing methods for autologous cell therapies still pose several challenges related to cost, immune cell source, safety risks, and scalability. These challenges have motivated recent efforts to optimize process development and manufacturing for cell therapies using automated closed-system bioreactors and models created using artificial intelligence.

Long-read sequencing and profiling of RNA-binding proteins reveals the pathogenic mechanism of aberrant splicing of an poison exon in epilepsy.

Pathogenic loss-of-function variants cause a spectrum of seizure disorders. We previously identified variants in individuals with -related epilepsy that fall in or near a poison exon (PE) in intron 20 (20N). We hypothesized these variants lead to increased PE inclusion, which introduces a premature stop codon, and, therefore, reduced abundance of the full-length transcript and Na 1.

Racialised experiences of Black and Brown nurses and midwives in UK health education: A qualitative study.

Background: Institutional racism within the United Kingdom's (UK) Higher Education (HE) sector, particularly nurse and midwifery education, has lacked empirical research, critical scrutiny, and serious discussion. This paper focuses on the racialised experiences of nurses and midwives during their education in UK universities, including their practice placements. It explores the emotional, physical, and psychological impacts of these experiences.

Data crowdsourcing on psychomotor and cognitive effects of cannabis via mobile app.

In an effort to educate consumers of cannabis, we created a downloadable application (app) for mobile phones that collects data on the neuropsychological effects related to cannabis use. In particular, the app assessed four domains, these being: (i) psychomotor compensation, (ii) time estimation, (iii) sustained attention, and (iv) response inhibition. These tests were presented as a sequence of video games to be completed in under 10 min.

Precision medicine for developmental and epileptic encephalopathies in Africa-strategies for a resource-limited setting.

Purpose: Sub-Saharan Africa bears the highest burden of epilepsy worldwide. A presumed proportion is genetic, but this etiology is buried under the burden of infections and perinatal insults in a setting of limited awareness and few options for testing. Children with developmental and epileptic encephalopathies (DEEs) are most severely affected by this diagnostic gap in Africa, because the rate of actionable findings is highest in DEE-associated genes.

Production and characterization of virus-free, CRISPR-CAR T cells capable of inducing solid tumor regression.

Background: Chimeric antigen receptor (CAR) T cells have demonstrated high clinical response rates against hematological malignancies (e.g., CD19+ cancers) but have shown limited activity in patients with solid tumors.

Handgrip strength: A simple and effective tool to predict mortality after liver transplantation.

Introduction: Malnutrition is a widely prevalent yet unrecognized problem of patients with end-stage liver disease (ESLD) awaiting liver transplant (LT). The aim of this study was to ascertain pre-LT nutritional status of adult Asian Indian patients with ESLD including functional deficit (frailty) and determine predictor/s of poor post-LT outcome (futility).

Methods: A prospective, longitudinal, single-center study which enrolled adults listed for LT between October 2014 and April 2018.

Spinal cord associative plasticity improves forelimb sensorimotor function after cervical injury.

Associative plasticity occurs when two stimuli converge on a common neural target. Previous efforts to promote associative plasticity have targeted cortex, with variable and moderate effects. In addition, the targeted circuits are inferred, rather than tested directly.

Acute Graft Versus Host Disease Following Liver Transplantation: Case Report With Review of Current Literature.

Graft verus host disease (GVHD) following Liver transplantation is rare life threatening complication with very high mortality rate around 85%. Due to increased recognition of this condition management approach is rapidly evolving due to newer diagnostic methods and drugs. Etiology, risk factors, pathogenesis, preventive strategies, management approach and newer drugs are discussed.

Fibromyalgia Pain and Depression: An Update on the Role of Repetitive Transcranial Magnetic Stimulation.

Fibromyalgia is a musculoskeletal pain of different parts of the body, which is also associated with fatigue, lack of sleep, cognition deficits, family history, gender bias, and other disorders such as osteoarthritis and rheumatoid arthritis. It is generally initiated after trauma, surgery, infection, or stress. Fibromyalgia often coexists with several other conditions or disorders such as temporomandibular joint disorders, bowel and bladder syndrome, anxiety, depression, headaches, and interstitial cystitis.

Alzheimer's Disease and Related Disorders Prevalence Differs by Appalachian Residence in Ohio.

Background: Areas within the Appalachian region may have a greater burden of under diagnosed Alzheimer's disease and related disorders (ADRD).

Objective: To estimate the prevalence of ADRD in the Appalachian counties of Ohio, and to determine if differences exist by geographic location (Appalachian/non-Appalachian and rural/urban) and across time among Medicare beneficiaries.

Methods: Centers for Medicare and Medicaid Services Public Use Files from 2007-2017 were used to estimate county-level ADRD prevalence among all fee-for-service beneficiaries in Ohio.

Liver transplantation and COVID-19 (Coronavirus) infection: guidelines of the liver transplant Society of India (LTSI).

The Liver Transplant Society of India (LTSI) has come up with guidelines for transplant centres across the country to deal with liver transplantation during this evolving pandemic of COVID-19 infection. The guidelines are applicable to both deceased donor as well as living donor liver transplants. In view of the rapidly changing situation of COVID-19 infection in India and worldwide, these guidelines will need to be updated according to the emerging data.

Mevalonate pathway activity as a determinant of radiation sensitivity in head and neck cancer.

Radioresistance is a major hurdle in the treatment of head and neck squamous cell carcinoma (HNSCC). Here, we report that concomitant treatment of HNSCCs with radiotherapy and mevalonate pathway inhibitors (statins) may overcome resistance. Proteomic profiling and comparison of radioresistant to radiosensitive HNSCCs revealed differential regulation of the mevalonate biosynthetic pathway.

Repair-independent functions of DNA-PKcs protect irradiated cells from mitotic slippage and accelerated senescence.

The binding of DNA-dependent protein kinase catalytic subunit (DNA-PKcs, also known as PRKDC) to Ku proteins at DNA double-strand breaks (DSBs) has long been considered essential for non-homologous end joining (NHEJ) repair, providing a rationale for use of DNA-PKcs inhibitors as cancer therapeutics. Given lagging clinical translation, we reexamined mechanisms and observed instead that DSB repair can proceed independently of DNA-PKcs. While repair of radiation-induced DSBs was blocked in cells expressing shRNAs targeting Ku proteins or other NHEJ core factors, DSBs were repaired on schedule despite targeting DNA-PKcs.

Independent replication of motor cortex and cervical spinal cord electrical stimulation to promote forelimb motor function after spinal cord injury in rats.

Cervical spinal cord injury (SCI) impairs arm and hand function largely by interrupting descending tracts. Most SCI spare some axons at the lesion, including the corticospinal tract (CST), which is critical for voluntary movement. We targeted descending motor connections with paired electrical stimulation of motor cortex and cervical spinal cord in the rat.

Combating hospital malnutrition: Dietitian-led quality improvement initiative.

Background & Aim: Malnutrition is serious but under-diagnosed problem among hospitalized patients as approximately one-third patients may become malnourished during their stay. We audited our clinical nutrition practice (CNP) to understand the gaps and planned quality improvement initiatives to strengthen CNP through early delivery of oral nutrition supplement (ONS) prescribed.

Method: A prospective study was conducted in a tertiary care hospital in three phases between Dec'15 and Feb'17.

O-GlcNAcylation Enhances Double-Strand Break Repair, Promotes Cancer Cell Proliferation, and Prevents Therapy-Induced Senescence in Irradiated Tumors.

The metabolic reprogramming associated with characteristic increases in glucose and glutamine metabolism in advanced cancer is often ascribed to answering a higher demand for metabolic intermediates required for rapid tumor cell growth. Instead, recent discoveries have pointed to an alternative role for glucose and glutamine metabolites as cofactors for chromatin modifiers and other protein posttranslational modification enzymes in cancer cells. Beyond epigenetic mechanisms regulating gene expression, many chromatin modifiers also modulate DNA repair, raising the question whether cancer metabolic reprogramming may mediate resistance to genotoxic therapy and genomic instability.

Aberrant Inclusion of a Poison Exon Causes Dravet Syndrome and Related SCN1A-Associated Genetic Epilepsies.

Developmental and epileptic encephalopathies (DEEs) are a group of severe epilepsies characterized by refractory seizures and developmental impairment. Sequencing approaches have identified causal genetic variants in only about 50% of individuals with DEEs. This suggests that unknown genetic etiologies exist, potentially in the ∼98% of human genomes not covered by exome sequencing (ES).

Customized nutrition intervention and personalized counseling helps achieve nutrition targets in perioperative liver transplant patients.

Background And Aim: Nutritional therapy is an integral part of care in all phases of liver transplantation (LTx). However, there are several factors that make it a challenge to manage malnutrition in these patients including, but not limited to, loss of appetite, dietary restrictions and dietary habits. Dietary habits are guided by personal choice, social, cultural and regional background with diversity ranging from veganism to vegetarianism with the latter predominant in Indian population.

HMG-CoA Reductase Inhibition Delays DNA Repair and Promotes Senescence After Tumor Irradiation.

Despite significant advances in combinations of radiotherapy and chemotherapy, altered fractionation schedules and image-guided radiotherapy, many cancer patients fail to benefit from radiation. A prevailing hypothesis is that targeting repair of DNA double strand breaks (DSB) can enhance radiation effects in the tumor and overcome therapeutic resistance without incurring off-target toxicities. Unrepaired DSBs can block cancer cell proliferation, promote cancer cell death, and induce cellular senescence.

Enterococcal meningitis in association with hyperinfection syndrome.

Introduction: Strongyloidiasis can cause hyperinfection or disseminated infection in an immunocompromised host, and is an important factor linked to enterococcal bacteremia and meningitis.

Case Reports: We report two cases highlighting the importance of suspecting hyperinfection syndrome in patients with enterococcal meningitis.

Conclusion: Our cases highlight the importance of suspecting hyperinfection syndrome in cases of community acquired enterococcal bacteremia and meningitis.

Supra Hepatic Inferior Vena Cava Thrombosis-Surgical Challenges.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a chronic affliction characterized by numerous liver and kidney cysts. There is a gradual but progressive renal and liver impairment which may require combined liver-kidney transplantation. Compression of the retrohepatic Inferior Vena Cava (IVC) by an enlarged polycystic liver may impede clear visualization on pre-operative imaging and miss an underlying thrombosis or obliteration.