Made to move: A review of measurement strategies to characterize heterogeneity in normal fetal movement.

Fetal movement is a crucial indicator of fetal well-being. Characteristics of fetal movement vary across gestation, posing challenges for researchers to determine the most suitable assessment of fetal movement for their study. We summarize the current measurement strategies used to assess fetal movement and conduct a comprehensive review of studies utilizing these methods. We critically evaluate various measurement approaches including subjective maternal perception, ultrasound, Doppler ultrasound, wearable technology, magnetocardiograms, and magnetic resonance imaging, highlighting their strengths and weaknesses. We discuss the challenges of accurately capturing fetal movement, which is influenced by factors such as differences in recording times, gestational ages, sample sizes, environmental conditions, subjective perceptions, and characterization across studies. We also highlight the clinical implications of heterogeneity in fetal movement assessment for monitoring fetal behavior, predicting adverse outcomes, and improving maternal attachment to the fetus. Lastly, we propose potential areas of future research to overcome the current gaps and challenges in measuring and characterizing abnormal fetal movement. Our review contributes to the growing body of literature on fetal movement assessment and provides insights into the methodological considerations and potential applications for research.

Primary extrahepatic biliary neuroendocrine tumor: a case report.

Extrahepatic biliary neuroendocrine tumors (EBNETs) are extremely rare and difficult to diagnose. The vast majority are diagnosed postoperatively on histological evaluation of surgical specimens. Workup and treatment principles are largely based on retrospective series and case reports. Complete surgical resection is the gold standard treatment for these lesions. Here we present a case of a 77-year-old male with a biopsy-proven EBNET incidentally discovered during evaluation for fatty liver disease. Further workup did not show any other suspicious lesions. Resection of the tumor and multiple Roux-en-Y hepaticojejunostomy was performed. Final pathology revealed grade 1, well-differentiated neuroendocrine tumor. This is the third case reported in the literature with a confirmed preoperative EBNET diagnosis based on endoscopic biopsy results. This case highlights the feasibility of preoperative diagnosis of EBNETs and emphasizes the importance of complete surgical resection.

Autologous regeneration of blood vessels in urinary bladder matrices provides early perfusion after transplant to the bladder.

Large animal testing and clinical trials using bioengineered bladder for augmentation have revealed that large grafts fail due to insufficient blood supply. To address this critical issue, an in vivo staged implant strategy was developed and evaluated to create autologous, vascularized bioengineered bladder tissue with potential for clinical translation. Pig bladders were used to create acellular urinary bladder matrices (UBMs), which were implanted on the rectus abdominus muscles of rats and pigs to generate cellular and vascular grafts. Rectus-regenerated bladder grafts (rrBGs) were highly cellularized and contained an abundance of CD31-positive blood vessels, which were shown to be functional by perfusion studies. Muscle patterns within grafts showed increased smooth muscle formation over time and specifically within the detrusor compartment, with no evidence of striated muscle. Large, autologous rrBGs were transplanted to the pig bladder after partial cystectomy and compared to transplantation of control UBMs at 2 weeks and 3 months post-transplant. Functional, ink-perfused blood vessels were found in the central portion of all rrBGs at 2 weeks, while UBM grafts were significantly deteriorated, contracted and lacked central cellularization and vascularization. By 3 months, rrBGs had mature smooth muscle bundles and were morphologically similar to native bladder. This staged implantation technique allows for regeneration and harvest of large bladder grafts that are morphologically similar to native tissue with functional vessels capable of inosculating with host bladder vessels to provide quick perfusion to the central area of the large graft, thereby preventing early ischemia and contraction.

SENTI-101, a Preparation of Mesenchymal Stromal Cells Engineered to Express IL12 and IL21, Induces Localized and Durable Antitumor Immunity in Preclinical Models of Peritoneal Solid Tumors.

Advanced peritoneal carcinomatosis including high-grade ovarian cancer has poor prognoses and a poor response rate to current checkpoint inhibitor immunotherapies; thus, there is an unmet need for effective therapeutics that would provide benefit to these patients. Here we present the preclinical development of SENTI-101, a cell preparation of bone marrow-derived mesenchymal stromal (also known as stem) cells (MSC), which are engineered to express two potent immune-modulatory cytokines, IL12 and IL21. Intraperitoneal administration of SENTI-101 results in selective tumor-homing and localized and sustained cytokine production in murine models of peritoneal cancer. SENTI-101 has extended half-life, reduced systemic distribution, and improved antitumor activity when compared with recombinant cytokines, suggesting that it is more effective and has lower risk of systemic immunotoxicities. Treatment of tumor-bearing immune-competent mice with a murine surrogate of SENTI-101 (mSENTI-101) results in a potent and localized immune response consistent with increased number and activation of antigen presenting cells, T cells and B cells, which leads to antitumor response and memory-induced long-term immunity. Consistent with this mechanism of action, co-administration of mSENTI-101 with checkpoint inhibitors leads to synergistic improvement in antitumor response. Collectively, these data warrant potential clinical development of SENTI-101 for patients with peritoneal carcinomatosis and high-grade ovarian cancer.Graphical abstract: SENTI-101 schematic and mechanism of actionSENTI-101 is a novel cell-based immunotherapeutic consisting of bone marrow-derived mesenchymal stromal cells (BM-MSC) engineered to express IL12 and IL21 intended for the treatment of peritoneal carcinomatosis including high-grade serous ovarian cancer. Upon intraperitoneal administration, SENTI-101 homes to peritoneal solid tumors and secretes IL12 and IL21 in a localized and sustained fashion. The expression of these two potent cytokines drives tumor infiltration and engagement of multiple components of the immune system: antigen-presenting cells, T cells, and B cells, resulting in durable antitumor immunity in preclinical models of cancer.

Challenges in Quantifying Cytosine Methylation in the HIV Provirus.

DNA methylation is an epigenetic mechanism most commonly associated with transcriptional repression. While it is clear that DNA methylation can silence HIV proviral expression in in vitro latency models, its correlation with HIV persistence and expression in vivo is ambiguous, particularly in persons living with HIV (PLWH) receiving antiretroviral therapy (ART). Several factors potentially contribute to discrepancies between results in the literature, including differences in integration sites, functional proviral load, sampling bias, and stochastic PCR amplification. Recent studies into genomic features of cytosine methylation sites in mammalian genes offer potentially significant insights into this mechanism. Here, we discuss the importance of these factors in the context of the HIV.

Herd Immunity Likely Protected the Men Who Have Sex With Men in the Recent Hepatitis A Outbreak in San Diego, California.

A high seroprevalence of hepatitis A virus (81%) among human immunodeficiency virus-negative high-risk men who have sex with men is likely why this community was largely spared from a recent hepatitis A virus outbreak in San Diego, California.