Design of pseudosymmetric protein hetero-oligomers.

Pseudosymmetric hetero-oligomers with three or more unique subunits with overall structural (but not sequence) symmetry play key roles in biology, and systematic approaches for generating such proteins de novo would provide new routes to controlling cell signaling and designing complex protein materials. However, the de novo design of protein hetero-oligomers with three or more distinct chains with nearly identical structures is a challenging unsolved problem because it requires the accurate design of multiple protein-protein interfaces simultaneously. Here, we describe a divide-and-conquer approach that breaks the multiple-interface design challenge into a set of more tractable symmetric single-interface redesign tasks, followed by structural recombination of the validated homo-oligomers into pseudosymmetric hetero-oligomers.

Combined Cytokine Blockade Therapy (CCBT) Using Basiliximab and Infliximab for Treatment of Steroid-Refractory Graft-Versus-Host Disease (SR-GvHD).

Background: The standard first-line treatment for acute graft-versus-host disease (aGvHD) is systemic, high-dose glucocorticoids which have historically had limited responses. Combined cytokine blockade therapy (CCBT) with the monoclonal antibodies infliximab (a TNF-α inhibitor) and basiliximab (an IL-2 receptor blocker) has had limited discussion in the literature.

Methods: Sixty patients with steroid-refractory aGVHD were analyzed.

Potent antitumor activity of a designed interleukin-21 mimic.

Long-standing goals of cancer immunotherapy are to activate cytotoxic antitumor T cells across a broad range of affinities while dampening suppressive regulatory T (Treg) cell responses, but current approaches achieve these goals with limited success. Here, we report a IL-21 mimic, 21h10, designed to have augmented stability and high signaling potency in both humans and mice. In multiple animal models and in human melanoma patient derived organotypic tumor spheroids (PDOTS), 21h10 showed robust antitumor activity.

Living in a food desert in Louisiana and its effects on gynecologic cancer outcomes.

Objective: Food insecurity is becoming recognized as an important measure of public health. Louisiana has a poorer health index and a higher food insecurity rate than the national average. This study aims to investigate how living in a food desert affects the stage at diagnosis and 5-year overall survival in patients with gynecologic cancers.

Inborn errors of immunity reveal molecular requirements for generation and maintenance of human CD4 IL-9-expressing cells.

Background: CD4 T cells play essential roles in adaptive immunity. Distinct CD4 T-cell subsets-T1, T2, T17, T22, T follicular helper, and regulatory T cells-have been identified, and their contributions to host defense and immune regulation are increasingly well defined. IL-9-producing T9 cells were first described in 2008 and appear to play both protective and pathogenic roles in human immunity.

Delaying pegaspargase during induction in adults with acute lymphoblastic leukaemia is associated with lower risk of high-grade hepatotoxicity without adversely impacting outcomes.

Pegaspargase is a key drug for the treatment of younger adults with acute lymphoblastic leukaemia (ALL). Pegaspargase-associated hepatotoxicity is most common during induction, and its incidence increases with age and body mass index (BMI). We hypothesized that the delayed administration of pegaspargase during induction is associated with lower risk of hepatotoxicity while retaining efficacy.

Remote blood pressure management for postpartum hypertension: a cost-effectiveness analysis.

Background: Recognizing the importance of close follow-up after hypertensive disorders of pregnancy, many centers have initiated programs to support postpartum remote blood pressure management.

Objective: This study aimed to evaluate the cost-effectiveness of remote blood pressure management to determine the scalability of these programmatic interventions.

Study Design: This was a cost-effectiveness analysis of using remote blood pressure management vs usual care to manage postpartum hypertension.

A Phenomenological Qualitative Exploration of Mind-Body Therapy Use and Effectiveness Among Young, Middle, and Older Adult Cancer Survivors.

Background: Having been diagnosed with and treated for cancer can have negative psychosocial repercussions that may differ across the lifespan. Mind-body therapies (MBTs), such as tai-chi/qigong (TCQ) or mindfulness-based cancer recovery (MBCR), have shown promise in decreasing negative psychosocial outcomes in cancer survivors, but few studies have explored potential differences in MBT use and effectiveness across age groups.

Methods: A descriptive phenomenological qualitative design was used.

Discovery and preclinical development of a therapeutically active nanobody-based chimeric antigen receptor targeting human CD22.

Chimeric antigen receptor (CAR) T cell therapies targeting B cell-restricted antigens CD19, CD20, or CD22 can produce potent clinical responses for some B cell malignancies, but relapse remains common. Camelid single-domain antibodies (sdAbs or nanobodies) are smaller, simpler, and easier to recombine than single-chain variable fragments (scFvs) used in most CARs, but fewer sdAb-CARs have been reported. Thus, we sought to identify a therapeutically active sdAb-CAR targeting human CD22.

The constitutively active form of a key cholesterol synthesis enzyme is lipid droplet-localized and upregulated in endometrial cancer tissues.

Cholesterol is essential for both normal cell viability and cancer cell proliferation. Aberrant activity of squalene monooxygenase (SM, also known as squalene epoxidase), the rate-limiting enzyme of the committed cholesterol synthesis pathway, is accordingly implicated in a growing list of cancers. We previously reported that hypoxia triggers the truncation of SM to a constitutively active form, thus preserving sterol synthesis during oxygen shortfalls.

Blood-Brain Barrier Dysfunction Predicts Microglial Activation After Traumatic Brain Injury in Juvenile Rats.

Traumatic brain injury (TBI) disrupts the blood-brain barrier (BBB), which may exacerbate neuroinflammation post-injury. Few translational studies have examined BBB dysfunction and subsequent neuroinflammation post-TBI in juveniles. We hypothesized that BBB dysfunction positively predicts microglial activation and that vulnerability to BBB dysfunction and associated neuroinflammation are dependent on age at injury.

Smartwatch detection of new-onset monomorphic ventricular tachycardia in pregnancy.

Smartwatches provide health tracking in various ways and there has been a recent rise in reporting cardiac arrhythmias. While original studies focused on atrial fibrillation, fewer reports have been made on other arrhythmias especially in pregnancy. We report a pregnant patient who presented at 34 weeks' gestation with palpitations.

ChatGPT in Medical Education: A Precursor for Automation Bias?

Artificial intelligence (AI) in health care has the promise of providing accurate and efficient results. However, AI can also be a black box, where the logic behind its results is nonrational. There are concerns if these questionable results are used in patient care.

Isolated Chronic Mucocutaneous Candidiasis due to a Novel Duplication Variant of IL17RC.

Purpose: Inborn errors of the IL-17A/F-responsive pathway lead to chronic mucocutaneous candidiasis (CMC) as a predominant clinical phenotype, without other significant clinical manifestations apart from mucocutaneous staphylococcal diseases. Among inborn errors affecting IL-17-dependent immunity, autosomal recessive (AR) IL-17RC deficiency is a rare disease with only three kindreds described to date. The lack of an in vitro functional evaluation system of IL17RC variants renders its diagnosis difficult.

Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency.

Patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1) caused by autosomal recessive AIRE deficiency produce autoantibodies that neutralize type I interferons (IFNs), conferring a predisposition to life-threatening COVID-19 pneumonia. Here we report that patients with autosomal recessive NIK or RELB deficiency, or a specific type of autosomal-dominant NF-κB2 deficiency, also have neutralizing autoantibodies against type I IFNs and are at higher risk of getting life-threatening COVID-19 pneumonia. In patients with autosomal-dominant NF-κB2 deficiency, these autoantibodies are found only in individuals who are heterozygous for variants associated with both transcription (p52 activity) loss of function (LOF) due to impaired p100 processing to generate p52, and regulatory (IκBδ activity) gain of function (GOF) due to the accumulation of unprocessed p100, therefore increasing the inhibitory activity of IκBδ (hereafter, p52/IκBδ).

Corrigendum: The relationship between metamotivational knowledge and performance.

[This corrects the article DOI: 10.3389/fpsyg.2023.

Standardized Clinical Assessment and Management Plan to Reduce Readmissions for Postpartum Hypertension.

Objective: To evaluate the effect of a postpartum hypertension standardized clinical assessment and management plan on postpartum readmissions and emergency department (ED) visits.

Methods: We conducted a prospective cohort study of patients with postpartum hypertension (either chronic hypertension or hypertensive disorders of pregnancy) who delivered at a single tertiary care center for 6 months after enacting an institution-wide standardized clinical assessment and management plan (postintervention group). Patients in the postintervention group were compared with patients in a historical control group.

Merging public health and automated approaches to address online hate speech.

The COVID-19 pandemic sparked a rise in misinformation from various media sources, which contributed to the heightened severity of hate speech. The upsurgence of hate speech online has devastatingly translated to real-life hate crimes, which saw an increase of 32% in 2020 in the United States alone (U.S.