Protocol for mitochondrial variant enrichment from single-cell RNA sequencing using MAESTER.

Single-cell RNA sequencing (scRNA-seq) enables detailed characterization of cell states but often lacks insights into tissue clonal structures. Here, we present a protocol to probe cell states and clonal information simultaneously by enriching mitochondrial DNA (mtDNA) variants from 3'-barcoded full-length cDNA. We describe steps for input library preparation, mtDNA enrichment, PCR product cleanup, and paired-end sequencing.

Brain aging rejuvenation factors in adults with genetic and sporadic neurodegenerative disease.

The largest risk factor for dementia is age. Heterochronic blood exchange studies have uncovered age-related blood factors that demonstrate 'pro-aging' or 'pro-youthful' effects on the mouse brain. The clinical relevance and combined effects of these factors for humans is unclear.

Opportunities and limitations of B cell depletion approaches in SLE.

B cell depletion with rituximab, a chimeric monoclonal antibody that selectively targets B cells by binding CD20, has been used off label in severe and resistant systemic lupus erythematosus (SLE) for over two decades. Several biological mechanisms limit the efficacy of rituximab, including immunological reactions towards the chimeric molecule, increased numbers of residual B cells, including plasmablasts and plasma cells, and a post-treatment surge in B cell-activating factor (BAFF) levels. Consequently, rituximab induces remission in only a proportion of patients, and safety issues limit its use.

De novo designed proteins neutralize lethal snake venom toxins.

Snakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually and causing severe complications and long-lasting disabilities for many more. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including severe tissue damage and inhibition of nicotinic acetylcholine receptors, resulting in life-threatening neurotoxicity. At present, the only available treatments for snakebites consist of polyclonal antibodies derived from the plasma of immunized animals, which have high cost and limited efficacy against 3FTxs.

Improving Newborn Professional Billing at a Community Hospital.

Introduction: In community hospital medicine programs, newborns often represent a large patient population with diverse clinical needs. Capturing the care provided through professional billing provides the foundation for division revenue; however, provider knowledge on how to optimally bill is often lacking. Our group underused Hospital Care current procedural terminology (CPT) evaluation and management (E/M) codes for newborns requiring increased monitoring, diagnostic interventions, or therapy.

CD137 agonism enhances anti-PD1 induced activation of expanded CD8 T cell clones in a neoadjuvant pancreatic cancer clinical trial.

Successful pancreatic ductal adenocarcinoma (PDAC) immunotherapy requires therapeutic combinations that induce quality T cells. Tumor microenvironment (TME) analysis following therapeutic interventions can identify response mechanisms, informing design of effective combinations. We provide a reference single-cell dataset from tumor-infiltrating leukocytes (TILs) from a human neoadjuvant clinical trial comparing the granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting allogeneic PDAC vaccine GVAX alone, in combination with anti-PD1 or with both anti-PD1 and CD137 agonist.

Enabling next-generation engineered TCR-T therapies based on high-throughput TCR discovery from diagnostic tumor biopsies.

Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) can mediate tumor regression, including complete and durable responses, in a range of solid cancers, most notably in melanoma. However, its wider application and efficacy has been restricted by the limited accessibility, proliferative capacity and effector function of tumor-specific TIL. Here, we develop a platform for the efficient identification of tumor-specific TCR genes from diagnostic tumor biopsies, including core-needle biopsies frozen in a non-viable format, to enable engineered T cell therapy.

Predicting Mortality in Patients Hospitalized With Acute Myocardial Infarction: From the National Cardiovascular Data Registry.

Background: In-hospital mortality risk prediction is an important tool for benchmarking quality and patient prognostication. Given changes in patient characteristics and treatments over time, a contemporary risk model for patients with acute myocardial infarction (MI) is needed.

Methods: Data from 313 825 acute MI hospitalizations between January 2019 and December 2020 for adults aged ≥18 years at 784 sites in the National Cardiovascular Data Registry Chest Pain-MI Registry were used to develop a risk-standardized model to predict in-hospital mortality.

Challenges and opportunities for high-quality battery production at scale.

As the world electrifies, global battery production is expected to surge. However, batteries are both difficult to produce at the gigawatt-hour scale and sensitive to minor manufacturing variation. As a result, the battery industry has already experienced both highly-visible safety incidents and under-the-radar reliability issues-a trend that will only worsen if left unaddressed.

Assessing the risk of heart failure in type 2 diabetes: a prediction algorithm to sustain the evaluation of NT-proBNP in primary care.

Purpose: Heart failure (HF) is a disease that leads to approximately 300,000 fatalities annually in Europe and 250,000 deaths each year in the United States. Type 2 Diabetes Mellitus (T2DM) is a significant risk factor for HF, and testing for N-terminal (NT)-pro hormone BNP (NT-proBNP) can aid in early detection of HF in T2DM patients. We therefore developed and validated the HFriskT2DM-HScore, an algorithm to predict the risk of HF in T2DM patients, so guiding NT-proBNP investigation in a primary care setting.

No Difference in External Rotation Loss After Isolated Bankart Repair, Remplissage, or Latarjet: A Systematic Review and Meta-analysis.

Background: Despite the effectiveness of remplissage in reducing instability recurrence, debate remains about the loss of external rotation (ER) after this procedure.

Purpose: To compare the loss of ER after primary isolated arthroscopic Bankart repair alone (BR), Bankart with remplissage (REMP), and Latarjet (LAT) procedures.

Study Design: Meta-analysis; Level of evidence, 3.

A multilevel framework for recruitment and retention in implementation trials: An illustrative example.

Background: Implementation and hybrid effectiveness-implementation trials aspire to speed the translation of science into practice by generating crucial evidence for improving the uptake of effective health interventions. By design, they pose unique recruitment and retention challenges due to their aims, units of analysis, and sampling plans, which typically require many clinical sites (i.e.

Diseases of Economic Importance in Feedlot Cattle in Sub-Saharan Africa: A Review with a Focus on Existing and Potential Options for Control.

A large number of livestock are found in sub-Saharan Africa (SSA), including 20-25% of the world's ruminants [...

Translational and clinical comparison of whole genome and transcriptome to panel sequencing in precision oncology.

Precision oncology offers new cancer treatment options, yet sequencing methods vary in type and scope. In this study, we compared whole-exome/whole-genome (WES/WGS) and transcriptome sequencing (TS) with broad panel sequencing by resequencing the same tumor DNA and RNA as well as normal tissue DNA for germline assessment, from 20 patients with rare or advanced tumors, who were originally sequenced by WES/WGS ± TS within the DKFZ/NCT/DKTK MASTER program from 2015 to 2020. Molecular analyses resulted in a median number of 2.

Impact of American College of surgeons trauma verification on statewide collaborative outcomes.

Background: American College of Surgeons (ACS) trauma center verification has demonstrated improved outcomes at individual centers, but its impact on statewide Trauma Quality Improvement Program (TQIP) Collaboratives is unknown. A statewide TQIP Collaborative, founded in 2011, noted underperformance in six of eight patient cohorts identified in the TQIP Collaborative report. We hypothesized that requiring ACS verification for level I and II trauma centers would result in improved outcomes for the state collaborative.

Performance of the High-STEACS Early Rule Out Pathway Using hs-cTnT at 30 Days in a Multisite US Cohort.

Background: The High-STEACS (High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome) pathway risk stratifies emergency department patients with possible acute coronary syndrome. This study aims to determine if the High-STEACS hs-cTnT (high-sensitivity cardiac troponin T) pathway can achieve the ≥99% negative predictive value (NPV) safety threshold for 30-day cardiac death or myocardial infarction (CDMI) in a multisite US cohort of patients with and without known coronary artery disease (CAD).

Methods: A secondary analysis of the STOP-CP (High-Sensitivity Cardiac Troponin T [Gen 5 STAT Assay] to Optimize Chest Pain Risk Stratification) cohort, which enrolled adult emergency department patients with possible acute coronary syndrome at 8 US sites (January 25, 2017-September 6, 2018).

Prior thermal acclimation gives White Sturgeon a fin up dealing with low oxygen.

Assessing how at-risk species respond to co-occurring stressors is critical for predicting climate change vulnerability. In this study, we characterized how young-of-the-year White Sturgeon () cope with warming and low oxygen (hypoxia) and investigated whether prior exposure to one stressor may improve the tolerance to a subsequent stressor through "cross-tolerance". Fish were acclimated to five temperatures within their natural range (14-22°C) for one month prior to assessment of thermal tolerance (critical thermal maxima, CTmax) and hypoxia tolerance (incipient lethal oxygen saturation, ILOS; tested at 20°C).

Machine learning-derived multivariable predictors of postcardiotomy cardiogenic shock in high-risk cardiac surgery patients.

Objective: To develop a model for preoperatively predicting postcardiotomy cardiogenic shock (PCCS) in patients with poor left ventricular (LV) function undergoing cardiac surgery.

Methods: From the Society of Thoracic Surgeons Adult Cardiac Database, 11,493 patients with LV ejection fraction ≤35% underwent isolated on-pump surgery from 2018 through 2019, of whom 3428 experienced PCCS. In total, 68 preoperative clinical variables were considered in machine-learning algorithms trained and optimized using scikit-learn software.

Biomass carbon emissions from nickel mining have significant implications for climate action.

Global nickel demand is projected to double by 2050 to support low-carbon technologies and renewable energy production. However, biomass carbon emissions from clearing vegetation for nickel mining are rarely included in corporate sustainability reports or considered in mineral sourcing decisions. Here, we compiled data for 481 nickel mines and undeveloped deposits to show that the footprint of nickel mining could be 4 to 500 times greater than previously reported (depending on the mine site), and thus the environmental impacts of nickel products, including batteries, have been underestimated to date.

Talquetamab plus Teclistamab in Relapsed or Refractory Multiple Myeloma.

Background: Talquetamab (anti-G protein-coupled receptor family C group 5 member D) and teclistamab (anti-B-cell maturation antigen) are bispecific antibodies that activate T cells by targeting CD3 and that have been approved for the treatment of triple-class-exposed relapsed or refractory multiple myeloma.

Methods: We conducted a phase 1b-2 study of talquetamab plus teclistamab in patients with relapsed or refractory multiple myeloma. In phase 1, we investigated five dose levels in a dose-escalation study.

Who will benefit from vorasidenib? Review of data from the literature and open questions.

The clinical efficacy of isocitrate dehydrogenase (IDH) inhibitors in the treatment of patients with grade 2 IDH-mutant (mIDH) gliomas is a significant therapeutic advancement in neuro-oncology. It expands treatment options beyond traditional radiation therapy and cytotoxic chemotherapy, which may lead to significant long-term neurotoxic effects while extending patient survival. The INDIGO study demonstrated that vorasidenib, a pan-mIDH inhibitor, improved progression-free survival for patients with grade 2 mIDH gliomas following surgical resection or biopsy compared to placebo and was well tolerated.

Rotator Cuff Repair Study Designs Correlate With Revision Shoulder Surgery Rates: A Systematic Review.

Purpose: To identify arthroscopic rotator cuff repair study groups and evaluate if study design or other study characteristics correlate with a repeat ipsilateral shoulder surgery.

Methods: A systematic search of the PubMed, Embase, and Cochrane Library databases was conducted on March 20, 2021, and April 2, 2021. The following search terms were used by 2 different researchers: ((Rotator cuff repair[Title/Abstract]) AND (Revision[Title/Abstract]) NOT (Systematic Review[Title/Abstract]) NOT (arthroplasty[Title/Abstract]).

Simulated Cam Morphology of the Hip Changes Sacroiliac Motion During Hip Motion and Loading in a Cadaveric Model.

Purpose: To determine the relationship between cam morphology of the hip and ipsilateral sacroiliac motion compared to the native hip in a cadaveric model.

Methods: A simulated cam state was created using a 3-dimensional printed cam secured to the head-neck junction of 5 cadaveric hips. Hips were studied using a computed tomography-based optic metrology system and a 6 degree-of-freedom robot to exert an internal rotation torque at 3 different torque levels (6 N-m, 12 N-m, 18 N-m).

Pelvic Organ Prolapse Repair Using Robotic-Assisted Sacral Hysterocolpopexy vs Vaginal Surgery with the Uphold™ System: 1-Year Clinical Outcomes.

Introduction And Hypothesis: The aim of the study was to compare clinical outcomes when using robotic-assisted sacral hysterocolpopexy (RASC) and vaginal surgery using the Uphold™ Vaginal Support System mesh for pelvic organ prolapse repair.

Methods: This was a nonrandomized, prospective, multicenter study in which 72 women underwent RASC, and 73 Uphold™ surgery, for apical prolapse (POP-Q C ≥ stage II). Anatomical outcomes were assessed using the Pelvic Organ Prolapse Quantification (POP-Q) system.