Duvelisib is a novel NFAT inhibitor that mitigates adalimumab-induced immunogenicity.

Introduction: TNFα inhibitor (TNFi) immunogenicity in rheumatoid arthritis (RA) is a major obstacle to its therapeutic effectiveness. Although methotrexate (MTX) can mitigate TNFi immunogenicity, its adverse effects necessitate alternative strategies. Targeting nuclear factor of activated T cells (NFAT) transcription factors may protect against biologic immunogenicity.

Multisensory naturalistic decoding with high-density diffuse optical tomography.

Significance: Decoding naturalistic content from brain activity has important neuroscience and clinical implications. Information about visual scenes and intelligible speech has been decoded from cortical activity using functional magnetic resonance imaging (fMRI) and electrocorticography, but widespread applications are limited by the logistics of these technologies.

Aim: High-density diffuse optical tomography (HD-DOT) offers image quality approaching that of fMRI but with the silent, open scanning environment afforded by optical methods, thus opening the door to more naturalistic research and applications.

Ethnic and racial differences in children and young people with respiratory and neurological post-acute sequelae of SARS-CoV-2: an electronic health record-based cohort study from the RECOVER Initiative.

Background: Children from racial and ethnic minority groups are at greater risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they have increased risk for post-acute sequelae of SARS-CoV-2 (PASC). Our objectives were to assess whether the risk of respiratory and neurologic PASC differs by race/ethnicity and social drivers of health.

Methods: We conducted a retrospective cohort study of individuals <21 years seeking care at 24 health systems across the U.

Contraceptive use and pregnancy in cystic fibrosis: Survey findings from 10 cystic fibrosis centers.

Background: Reproductive life planning is key, now that people with cystic fibrosis (pwCF) may live into their 60s. This study explores contraceptive use, pregnancy trends, and whether concomitant cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy reduces contraceptive effectiveness.

Methods: Females with CF aged 18-45 years from 10 U.

How Do Clinicians Use Quotations in Goals of Care Notes?

Background: Quoting patients in electronic medical record (EMR) notes is controversial. Quotations may be used to promote accuracy in documentation. However they also may be used to cast skepticism on patient speech.

Practice patterns for acquiring neuroimaging after pediatric in-hospital cardiac arrest.

Aims: To determine which patient and cardiac arrest factors were associated with obtaining neuroimaging after in-hospital cardiac arrest, and among those patients who had neuroimaging, factors associated with which neuroimaging modality was obtained.

Methods: Retrospective cohort study of patients who survived in-hospital cardiac arrest (IHCA) and were enrolled in the ICU-RESUS trial (NCT02837497).

Results: We tabulated ultrasound (US), CT, and MRI frequency within 7 days following IHCA and identified patient and cardiac arrest factors associated with neuroimaging modalities utilized.

The Role of Sex and Gender in Acute Kidney Injury - Consensus Statements from the 33 Acute Disease Quality Initiative.

Sex differences exist in acute kidney injury (AKI), and the role that sex and gender play along the AKI care continuum remains unclear. The 33 Acute Disease Quality Initiative meeting evaluated available data on the role of sex and gender in AKI and identified knowledge gaps. Data from experimental models, pathophysiology, epidemiology, clinical care, gender, social determinants of health, education, and advocacy were reviewed.

Alterations in Prefrontal Cortical Somatostatin Neurons in Schizophrenia: Evidence for Weaker Inhibition of Pyramidal Neuron Dendrites.

Background: Certain cognitive processes require inhibition provided by the somatostatin (SST) class of gamma-aminobutyric acid (GABA) neurons in the dorsolateral prefrontal cortex (DLPFC). This inhibition onto pyramidal neuron dendrites depends on both SST and GABA signaling. Although SST mRNA levels are lower in the DLPFC in schizophrenia, it is not known if SST neurons exhibit alterations in the capacity to synthesize GABA, principally via the 67-kilodalton isoform of glutamic acid decarboxylase (GAD67).

Lysosomal dysfunction and inflammatory sterol metabolism in pulmonary arterial hypertension.

Vascular inflammation regulates endothelial pathophenotypes, particularly in pulmonary arterial hypertension (PAH). Dysregulated lysosomal activity and cholesterol metabolism activate pathogenic inflammation, but their relevance to PAH is unclear. Nuclear receptor coactivator 7 () deficiency in endothelium produced an oxysterol and bile acid signature through lysosomal dysregulation, promoting endothelial pathophenotypes.

Use of Intraoperative Frozen Section to Assess Surgical Margins in HPV-Related Oropharyngeal Carcinoma.

Importance: Given the favorable overall prognosis of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) and the morbidity of increased adjuvant therapy associated with positive surgical margins, large-scale studies on the accuracy of frozen sections in predicting final surgical margin status in HPV-related OPSCC are imperative. Final surgical margin status is the definitive assessment of tumor clearance as determined through surgeon-pathologist collaboration based on permanent analysis of frozen section margins, main specimens, and supplemental resections.

Objectives: To assess the accuracy and testing properties of intraoperative frozen section histology (IFSH) in assessing final surgical margin status in patients undergoing transoral surgery for HPV-related OPSCC.

Tendon Inversion Improves Tendon-to-Bone Healing in a Rat Bicep Tenodesis Model.

Purpose: Tendon-to-bone repair remains a surgical challenge. Although bone tunnel fixation is a common surgical technique whereby soft tissue is expected to heal against a bone tunnel interface, contemporary methods have yet to recapitulate biomechanical similarity to the native enthesis. In this study, we aimed to understand how inside-out longitudinal tendon inversion affects bone tunnel healing with the hypothesis that inversion removes the gliding epitenon surface to facilitate interface healing.

A nuanced scrutiny of the segmental renal artery spectral Doppler in "Pickering" the right diagnosis.

Approximately 5-10% of patients with hypertension have secondary hypertension. We describe a case of secondary hypertension from bilateral renal artery stenosis (RAS): "Pickering syndrome." This is a case of hypertension secondary to bilateral RAS which provides an opportunity to review secondary hypertension with a specific focus on RAS, in terms of when to consider work up, causes of secondary hypertension, diagnostic testing, and treatment.

CD209d/e promotes inflammation and lung injury during influenza virus infection.

Influenza virus infects millions each year, contributing greatly to human morbidity and mortality. Upon viral infection, pathogen-associated molecular patterns activate pattern recognition receptors on host cells, triggering an immune response. The CD209 protein family, homologs of DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin), is thought to modulate immune responses to viruses.

A proteogenomic analysis of the adiposity colorectal cancer relationship identifies GREM1 as a probable mediator.

Background: Adiposity is an established risk factor for colorectal cancer (CRC). The pathways underlying this relationship, and specifically the role of circulating proteins, are unclear.

Methods: Utilizing two-sample univariable Mendelian randomization (UVMR), multivariable Mendelian randomization (MVMR), and colocalization, based on summary data from large sex-combined and sex-specific genetic studies, we estimated the univariable associations between: (i) body mass index (BMI) and waist-hip ratio (WHR) and overall and site-specific (colon, proximal colon, distal colon, and rectal) CRC risk, (ii) BMI and WHR and circulating proteins, and (iii) adiposity-associated circulating proteins and CRC risk.

High-grade liver injury: outcomes with a trauma surgery-liver surgery collaborative approach.

Background: Operative mortality for high-grade liver injury (HGLI) remains 42% to 66%, with near-universal mortality after retrohepatic caval injury. The objective of this study was to evaluate mortality and complications of operative and nonoperative management (OM and NOM) of HGLI at our institution, characterized by a trauma surgery-liver surgery collaborative approach to trauma care.

Methods: This was an observational cohort study of adult patients (age ≥16) with HGLI (The American Association for Surgery of Trauma (AAST) grades IV and V) admitted to an urban level I trauma center from January 2010 to November 2021.

Identify biological Alzheimer's disease using a novel nucleic acid-linked protein immunoassay.

Blood-based biomarkers have been revolutionizing the detection, diagnosis and screening of Alzheimer's disease. Specifically, phosphorylated-tau variants (p-tau, p-tau and p-tau) are promising biomarkers for identifying Alzheimer's disease pathology. Antibody-based assays such as single molecule arrays immunoassays are powerful tools to investigate pathological changes indicated by blood-based biomarkers and have been studied extensively in the Alzheimer's disease research field.

Operating room times differ for surgical fixation of metacarpal fractures: An analysis of two principally different techniques.

Introduction: Time spent in the operating room (OR) has ramifications that impact patient outcomes and the economics of patients, physicians, surgery centers, and insurance industry. For that reason, there is an incentive to seek approaches that allow shorter times to be spent in the OR. To what extent varying routine techniques impact on operating times has not been extensively studied in metacarpal fixation literature, specifically investigating retrograde threaded intramedullary nail fixations (RTNF) and comparing it to open plating fixations (OPF).

Optimizing brain mapping: integrating real-time neuropsychological assessment in awake craniotomy.

Intraoperative neuropsychological testing (IONT) is a sophisticated method of cognitive mapping during the resection of brain tumors in eloquent areas. Direct electrical stimulation during awake craniotomy is routinely utilized for mapping basic language and sensorimotor function, but the utilization of IONT offers an individualized approach that can yield real-time, comprehensive feedback on various cognitive functions, allowing for a tailored and more extensive tumor resection. In this video, the authors present the case of a 41-year-old male undergoing re-resection for a recurrent right temporal astrocytoma in which IONT played a crucial role.

A novel sensitizer reduces EGFR-TKI resistance by regulating the PI3K/Akt/mTOR pathway and autophagy.

Background: The incidence and mortality of lung cancer are high, and treatment with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is the preferred first-line treatment for patients suffering from non-small cell lung cancer (NSCLC) with EGFR mutations. However, EGFR-TKI resistance leads to treatment failure. Yifei-Sanjie pill (YFSJ) is a novel type of Chinese patent medicine for lung cancer.

Advancements and Future Directions of Dual-Target Chimeric Antigen Receptor T-Cell Therapy in Preclinical and Clinical Studies.

In recent years, chimeric antigen receptor T-cell (CAR-T) therapy has made groundbreaking progress in the treatment of various cancer types, particularly hematological malignancies. In the meantime, various preclinical and clinical studies have extensively explored dual-target CAR-T therapies which can be designed to recognize two antigens simultaneously based on the immunophenotype of tumor cells. Compared with single-target CAR-T approach, dual-target CAR-T therapies demonstrate varying degrees of superior antitumor CAR effects, prevent antigen escape and relapse, reduce on-target off-tumor effects, and ensure durable responses in different types of cancer.

Virulence and pathogenicity of group B : Virulence factors and their roles in perinatal infection.

This review summarizes key virulence factors associated with group B (GBS), a significant pathogen particularly affecting pregnant women, fetuses, and infants. Beginning with an introduction to the historical transition of GBS from a zoonotic pathogen to a prominent cause of human infections, particularly in the perinatal period, the review describes major disease manifestations caused by GBS, including sepsis, meningitis, chorioamnionitis, pneumonia, and others, linking each to specific virulence mechanisms. A detailed exploration of the genetic basis for GBS pathogenicity follows, emphasizing the roles of capsules in pathogenesis and immune evasion.

Obesity Is Associated With Worsened Outcomes in Patients With Ulcerative Colitis on Advanced Therapies: A Propensity Matched Cohort Study From the U.S.

Background: Obesity has been linked to a more severe phenotype in patients with ulcerative colitis (UC).

Aim: To evaluate the impact of obesity on outcomes of advanced therapies in UC.

Methods: We conducted a retrospective cohort study utilising the TriNetX database comparing the composite score of corticosteroid use, change in advanced therapy or colectomy within two years between two cohorts of patients with UC-those with obesity (BMI ≥ 30 kg/m) and those without (BMI 18.

Genomic sequencing: the case for equity of care in the era of personalized medicine.

Over the past two decades, genomic sequencing (exome and genome) has proven to be critical in providing a faster and more accurate diagnosis as well as tailored treatment plans for a variety of populations. Despite its potential, disparities in access to genomic sequencing persist, predominantly among underrepresented and socioeconomically disadvantaged groups and populations. This inequity stems from factors such as: 1) high costs of sequencing, 2) significant gaps in insurance coverage, 3) limited availability of genetic services in many healthcare institutions and geographic areas, and 4) lack of diversity in genetic research and databases.