Unique Population Research Articles

Esophageal Lichen Planus: A Descriptive Multicenter Report.

To better understand the characteristics, treatment approaches, and outcomes of patients with esophageal lichen planus (ELP). ELP is a rare, often unrecognized and misdiagnosed disorder. Data on this unique patient population are currently limited to small, single-center series. A multicenter, retrospective descriptive study was conducted of adults diagnosed with ELP over a 5-year period, between January 1, 2015, and October 10, 2020, from 7 centers across the United States. Seventy-eight patients (average age 65y, 86% female, 90% Caucasian) were included. Over half had at least 1 extraesophageal manifestation. Esophageal strictures (54%) and abnormal mucosa (50%) were frequent endoscopic findings, with the proximal esophagus the most common site of stricture. Approximately 20% had normal endoscopic findings. Topical steroids (64%) and/or proton pump inhibitors (74%) dominated management; endoscopic response favored steroids (43% vs. 29% respectively). Almost half of the patients required switching treatment modalities during the study period. Adjunctive therapies varied significantly between centers. Given its at times subtle clinical and endoscopic signs, a high index of suspicion and biopsy will improve ELP diagnosis, especially in those with extraesophageal manifestations. Effective therapies are lacking and vary significantly. Prospective investigations into optimal treatment regimens are necessary.

Abstract 5443: Identifying key regulators of glioblastoma cancer stem cells

Abstract Glioblastoma multiforme (GBM) has a dire prognosis that has had little progress over the past three decades. The existence of a unique population of stem-like gene signature baring quiescent cells (GSCs) within GBM are important for GBM tumorigenesis, therapy-resistance and recurrence. Our lab has developed one of the most faithful genetically engineered mouse models, encompassing a Nestin promoter-enhancer driven CreERT2-H2BeGFP-hDTR cassette (hereafter as CGD), that allows us to accurately capture and isolate GSCs in mouse GBM. The next logical step is to leverage these tools to uncover therapeutic vulnerabilities of GSCs and make a meaningful impact on GBM patient outcomes. To our knowledge, very few studies have explored the functional regulators of GSCs using a CRISPR/Cas9 screening approach. Our GSC signature provides a strong foundation for performing targeted in vitro or in vivo screens. In this study, to identify functionally important genes that may regulate GSC self-renewal and tumorigenic properties, an in vitro CRISPR knockout screens using a gene library derived from the GSC signature. The viral library was applied to low passage primary cultures of FACS sorted CGD_GFP+ and CGD_GFP- GBM cells developed from CGD; Nf1f/+;Trp53f/f;Ptenf/+ mice, respectively. The result of our in vitro CRISPR knock-out screen demonstrated guide depletion of Atp1b2-sgRNA in CGD_GFP+ but not in CGD_GFP- cells. The main objective of this study is to utilize in vitro and in vivo functional assays to test the difference between Atp1b2 WT and Atp1b2 KO GSCs and Atp1b2 WT vs KO GSC-derived tumors. Having a targeted candidate gene list is also particularly helpful for designing an in vivo CRISPR knockout screen, which is more physiological relevant. Therefore, I propose to use the candidate gene list derived from the in vitro screen as a starting point. The in vivo screen can provide valuable insights for the selection of the most optimal candidates for anti-GSC therapies. Citation Format: Tao Wang, Xuanhua Xie, Luis F. Parada. Identifying key regulators of glioblastoma cancer stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5443.

ATG9 resides on a unique population of small vesicles in presynaptic nerve terminals

ABSTRACT In neurons, autophagosome biogenesis occurs mainly in distal axons, followed by maturation during retrograde transport. Autophagosomal growth depends on the supply of membrane lipids which requires small vesicles containing ATG9, a lipid scramblase essential for macroautophagy/autophagy. Here, we show that ATG9-containing vesicles are enriched in synapses and resemble synaptic vesicles in size and density. The proteome of ATG9-containing vesicles immuno-isolated from nerve terminals showed conspicuously low levels of trafficking proteins except of the AP2-complex and some enzymes involved in endosomal phosphatidylinositol metabolism. Super resolution microscopy of nerve terminals and isolated vesicles revealed that ATG9-containing vesicles represent a distinct vesicle population with limited overlap not only with synaptic vesicles but also other membranes of the secretory pathway, uncovering a surprising heterogeneity in their membrane composition. Our results are compatible with the view that ATG9-containing vesicles function as lipid shuttles that scavenge membrane lipids from various intracellular membranes to support autophagosome biogenesis. Abbreviations: AP: adaptor related protein complex: ATG2: autophagy related 2; ATG9: autophagy related 9; DNA PAINT: DNA-based point accumulation for imaging in nanoscale topography; DyMIN STED: dynamic minimum stimulated emission depletion; EL: endosome and lysosome; ER: endoplasmic reticulum; GA: Golgi apparatus; iBAQ: intensity based absolute quantification; LAMP: lysosomal-associated membrane protein; M6PR: mannose-6-phosphate receptor, cation dependent; Minflux: minimal photon fluxes; Mito: mitochondria; MS: mass spectrometry; PAS: phagophore assembly site; PM: plasma membrane; Px: peroxisome; RAB26: RAB26, member RAS oncogene family; RAB3A: RAB3A, member RAS oncogene family; RAB5A: RAB5A, member RAS oncogene family; SNARE: soluble N-ethylmaleimide-sensitive-factor attachment receptor; SVs: synaptic vesicles; SYP: synaptophysin; TGN: trans-Golgi network; TRAPP: transport protein particle; VTI1: vesicle transport through interaction with t-SNAREs.

Operative Volumes and Postoperative Outcomes After Elective Resection of Congenital Lung Malformations in Infants.

To determine whether hospital- and surgeon-level operative volumes are associated with differences in postoperative outcomes among infants undergoing elective lung surgery for a congenital lung malformation (CLM). Infant lung surgery is a relatively uncommon procedure performed by pediatric surgeons nationwide. The relationship between surgical volume and postoperative outcomes remains unknown. A retrospective cohort study of asymptomatic infants who underwent elective lung resection of a CLM was conducted using the Pediatric Health Information System database (2016-2020). Multivariable linear and poisson regressions were performed based on annual lung resection tertiles. There were 1420 infants managed by 48 hospitals and 309 primary surgeons. Institutions that performed seven or fewer CLM resections per year (56%) were associated with significantly higher postoperative complication rates compared to medium- and high-volume hospitals (low: 134 [34%], medium: 110 [21%], high: 144 [29%]; P<0.001). Surgeons who performed one or fewer CLM resections per year (82%) were associated with significantly higher complication rates compared to medium- and high-volume surgeons (low: 171 [31%], medium: 75 [26%], high: 119 [24%]; P=0.02). Multivariable analyses confirmed that low-volume hospitals were associated with higher complications (OR 1.81, CI 1.38-2.37; P<0.001), and low-volume surgeons had an increased risk of complications (overall: OR 1.37, CI 1.01-1.84; P=0.04). In this cohort study of infants undergoing elective lung resection for a CLM, lower volume providers were associated with higher postoperative patient morbidity. These findings represent an opportunity to inform quality improvement initiatives on pediatric lung resection and the debate on surgical subspecialization for this unique patient population.

Distinct Clinical Manifestations of COVID-19 in Multiple Sclerosis Patients: Unraveling the Clinical Nexus

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is a virus in the coronaviridae, has caused a global pandemic with various symptoms and complications. Among the groups affected by this virus are individuals with multiple sclerosis (MS), a chronic autoimmune disorder that affects the primary central nervous system (CNS). Understanding coronavirus disease 2019’s (COVID-19) impact on MS patients is crucial for optimizing patient management and developing targeted therapies due to the challenges it presents. Objectives: The primary purpose of this study was to investigate the respiratory and neurology symptoms of COVID-19 in patients with MS in comparison to the non-infected group. Furthermore, this study examined how age and gender might affect the symptoms of contracting COVID-19 and the mortality rate in patients with MS. Methods: The data were collected from six hospitals within the Iranian Network for Research in Viral Diseases (INRVD) between March 2020 and July 2021. A total of 63 individuals diagnosed with MS were examined, with 30 testing positive for both COVID-19 and MS; however, 33 individuals were positive only for MS. These individuals had presented at the hospital experiencing respiratory symptoms, including rhinorrhea, difficulty breathing, and cough. Various clinical aspects were evaluated, including age, gender, and the presence of COVID-19 symptoms. Statistical analyses included the Mann-Whitney t-test, Fisher’s exact test, and odds ratio calculations using SPSS-27 and R 4.2.3. Results: The study encompassed 63 MS patients, with 29 (46%) and 34 (54%) males and females, respectively. Of these patients, 30 individuals were positive for COVID-19. Most subjects were from Tehran province, Iran. Patients in the case group were significantly younger than those in the control group. Notably, dizziness, breath shortness, and vomiting were significantly more prevalent in MS patients following COVID-19. Conclusions: This study highlights the distinct clinical presentation of COVID-19 in individuals with MS. Dizziness, breath shortness, vomiting, and increased mortality were significantly associated with MS patients with COVID-19. The aforementioned findings underscore the importance of tailored management strategies for this unique patient population following the disease.

Acute opioid overdose in pediatric patients.

Recent increases in pediatric and adolescent opioid fatalities mandate an urgent need for early consideration of possible opioid exposure and specific diagnostic and management strategies and interventions tailored to these unique populations. In contrast to adults, pediatric methods of exposure include accidental ingestions, prescription misuse, and household exposure. Early recognition, appropriate diagnostic evaluation, along with specialized treatment for opioid toxicity in this demographic are discussed. A key focus is on Naloxone, an essential medication for opioid intoxication, addressing its unique challenges in pediatric use. Unique pediatric considerations include recognition of accidental ingestions in our youngest population, critical social aspects including home safety and intentional exposure, and harm reduction strategies, mainly through Naloxone distribution and education on safe medication practices. It calls for a multifaceted approach, including creating pediatric-specific guidelines, to combat the opioid crisis among children and to work to lower morbidity and mortality from opioid overdoses.

Psychometrics of the Children's Report of Parental Behavior Inventory among caregivers and youth with HIV.

Parenting has been implicated in a range of youth health outcomes. Positive parenting during adolescence, a critical period of developmental change, may equip youth with the necessary tools for their transition into adulthood and, for youth living with HIV, their transition from pediatric HIV care into adult HIV care. Yet, because few studies have carefully assessed the psychometric properties of parenting instruments applied cross-culturally, the validity of parenting research derived in these contexts remains unclear. This study tested the factor structure of the Children's Report of Parenting Behavior Inventory (CRPBI) in a novel setting (e.g., Rwanda), context (e.g., youth with HIV), and considering multiple informants (caregivers and youth). Youth (N = 330) were on average 16.78 years of age; 51% self-identified as female. Caregivers (N = 330) were on average 44.40 years of age; 80% self-identified as female. The factor structures for youth and caregiver CRPBIs appeared to be indicative of two dimensions: (a) acceptance and positive involvement, and (b) hostile detachment and rejection. The CRPBI worked well for youth reports and showed predictive validity. The CRPBI worked less well for caregivers, necessitating the removal of 10 items, seven of which were related to hostile detachment and rejection. The reliability of both CRPBIs was supported. The CRPBI appears to function well for youth, but not as well for caregivers, in this novel context with this unique population of youth with HIV. The findings support careful assessment of instruments developed in high-resource settings and then used in resource-constrained contexts. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Immune Checkpoint Inhibition in Pediatric Oncology Patients: A Single-Institution Experience

Immunotherapy has emerged as a promising treatment approach in oncology, as it is specifically designed to boost the strength and accuracy of the immune system, allowing it to target tumor cells but spare non-tumor tissue. This treatment not only demonstrates potential for improved clinical outcomes but may also be associated with fewer adverse effects compared to traditional therapies. Despite its early success, the application of immunotherapy has largely been limited to adult cancer patients, with slow adoption noted in the treatment of pediatric cancer patients. Our objective is to demonstrate a single institution’s experience with immunotherapy in pediatric cancer patients and to discuss the use of these treatment modalities in this unique patient population. We performed a retrospective chart review and identified patients who received immune checkpoint inhibitors (ICIs) and/or underwent immunohistochemistry (IHC) testing for programmed death ligand 1 (PD-L1), quantification of tumor mutational burden (TMB), and classification of microsatellite instability (MSI) status. In total, we identified seven pediatric cancer patients who received therapy with ICIs. Four of these patients demonstrated positive PD-L1 expression, high TMB, and/or MSI-high status. These patients were treated with nivolumab alone or in combination with ipilimumab or brentuximab. The diagnoses included: multifocal epithelioid and spindle cell hemangioma (n = 1); metastatic melanoma (n = 2); histiocytic sarcoma (n = 1); rectal adenocarcinoma in the setting of constitutional mismatch repair deficiency syndrome (CMMRD) (n = 1); and Hodgkin lymphoma (n = 2). The patients received between four and nineteen cycles of immunotherapy. Immunotherapy-related adverse events included: mild allergic reaction; prodromal symptoms; anemia; neutropenia; transaminitis; endocrinopathies; and self-limiting neuritis. Of the seven patients, three are still being treated with immunotherapy (the patients with rectal adenocarcinoma, metastatic melanoma, and multifocal epithelioid and spindle cell hemangioma) with positive treatment responses observed on imaging, one is being treated with other modalities (the patient with Hodgkin lymphoma), two have achieved remission (the patients with metastatic melanoma and Hodgkin lymphoma), and one has relapsed (the patient with histiocytic sarcoma). The three patients who completed their immunotherapy regimens have been followed for 1 month, 4 months, and 10 months, respectively. This report of a single-institution experience with immunotherapy in pediatric cancer patients highlights the positive impact immunotherapy can have, especially when utilized to treat relapsed/refractory malignancies, as tumor regression or stabilization of disease burden was achieved in six of the patients described (CR = 2; PR = 4). Further research is needed to accurately identify pediatric oncology patients who could benefit from immunotherapy.

Incorporating temporal information during feature engineering bolsters emulation of spatio-temporal emergence.

Emergent biological dynamics derive from the evolution of lower-level spatial and temporal processes. A long-standing challenge for scientists and engineers is identifying simple low-level rules that give rise to complex higher-level dynamics. High-resolution biological data acquisition enables this identification and has evolved at a rapid pace for both experimental and computational approaches. Simultaneously harnessing the resolution and managing the expense of emerging technologies-e.g. live cell imaging, scRNAseq, agent-based models-requires a deeper understanding of how spatial and temporal axes impact biological systems. Effective emulation is a promising solution to manage the expense of increasingly complex high-resolution computational models. In this research, we focus on the emulation of a tumor microenvironment agent-based model to examine the relationship between spatial and temporal environment features, and emergent tumor properties. Despite significant feature engineering, we find limited predictive capacity of tumor properties from initial system representations. However, incorporating temporal information derived from intermediate simulation states dramatically improves the predictive performance of machine learning models. We train a deep-learning emulator on intermediate simulation states and observe promising enhancements over emulators trained solely on initial conditions. Our results underscore the importance of incorporating temporal information in the evaluation of spatio-temporal emergent behavior. Nevertheless, the emulators exhibit inconsistent performance, suggesting that the underlying model characterizes unique cell populations dynamics that are not easily replaced. All source codes for the agent-based model, emulation, and analyses are publicly available at the corresponding DOIs: 10.5281/zenodo.10622155, 10.5281/zenodo.10611675, 10.5281/zenodo.10621244, respectively.

Analysis of single nuclear chromatin accessibility reveals unique myeloid populations in human pancreatic ductal adenocarcinoma.

A better understanding of the pancreatic ductal adenocarcinoma (PDAC) immune microenvironment is critical to developing new treatments and improving outcomes. Myeloid cells are of particular importance for PDAC progression; however, the presence of heterogenous subsets with different ontogeny and impact, along with some fluidity between them, (infiltrating monocytes vs. tissue-resident macrophages; M1 vs. M2) makes characterisation of myeloid populations challenging. Recent advances in single cell sequencing technology provide tools for characterisation of immune cell infiltrates, and open chromatin provides source and function data for myeloid cells to assist in more comprehensive characterisation. Thus, we explore single nuclear assay for transposase accessible chromatin (ATAC) sequencing (snATAC-Seq), a method to analyse open gene promoters and transcription factor binding, as an important means for discerning the myeloid composition in human PDAC tumours. Frozen pancreatic tissues (benign or PDAC) were prepared for snATAC-Seq using 10× Chromium technology. Signac was used for preliminary analysis, clustering and differentially accessible chromatin region identification. The genes annotated in promoter regions were used for Gene Ontology (GO) enrichment and cell type annotation. Gene signatures were used for survival analysis with The Cancer Genome Atlas (TCGA)-pancreatic adenocarcinoma (PAAD) dataset. Myeloid cell transcription factor activities were higher in tumour than benign pancreatic samples, enabling us to further stratify tumour myeloid populations. Subcluster analysis revealed eight distinct myeloid populations. GO enrichment demonstrated unique functions for myeloid populations, including interleukin-1b signalling (recruited monocytes) and intracellular protein transport (dendritic cells). The identified gene signature for dendritic cells influenced survival (hazard ratio=.63, p=.03) in the TCGA-PAAD dataset, which was unique to PDAC. These data suggest snATAC-Seq as a method for analysis of frozen human pancreatic tissues to distinguish myeloid populations. An improved understanding of myeloid cell heterogeneity and function is important for developing new treatment targets in PDAC.

Outcomes of upfront plerixafor use for mobilization in germ cell tumor patients

High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) improved 5-year overall survival rates in relapsed/refractory germ cell tumors (GCTs) from 10% to 52%. Nearly 30% of GCT patients are deemed poor mobilizers after receiving several lines of prior therapy. There is limited data available regarding upfront plerixafor use in GCT patients. We predicted upfront plerixafor use would increase the amount of stem cells collected preventing subsequent mobilizations and improve time to curative therapy. A retrospective, single center, chart review of adult GCT patients who received plerixafor upfront for mobilization at a single center between January 1, 2013 and August 31, 2021 was performed.The primary objective was to evaluate the rate of successful peripheral blood CD34+ cell collections. Secondary objectives consisted of describing the impact of plerixafor use on mobilization and assessing auto-HSCT related outcomes. Sixteen patients received plerixafor upfront after an average of three prior lines of therapy (range: 2-5 lines). Successful collection (≥4 × 106 CD34+ cells/Kg collected within four days) was achieved in 15 (94%) patients in a median of one apheresis day (interquartile range: 1-2 days). All patients proceeded to an initial auto-HSCT and 12 patients (75%) completed both transplants as planned. Survival at 12 months was 50%.The significantly higher amount of CD34+ cells collected over less apheresis days demonstrated the clinical utility of upfront plerixafor and its potential to facilitate more efficient stem cell mobilization. There is a need for larger randomized studies with upfront plerixafor use in this unique patient population.

Clinical outcomes and return to dance after total hip arthroplasty or hip resurfacing in professional dancers.

Professional dancers represent a unique patient population in the setting of hip arthroplasty, given the high degree of hip strength and mobility required by their profession. We sought to determine the clinical outcomes and ability to return to professional dance after total hip arthroplasty (THA) or hip resurfacing arthroplasty (HRA). Active professional dancers who underwent primary THA or HRA at a single institution with minimum one-year follow-up were included in the study. Primary outcomes included the rate of return to professional dance, three patient-reported outcome measures (PROMs) (modified Harris Hip Score (mHHS), Hip disability and Osteoarthritis Outcome Score for Joint Replacement (HOOS-JR), and Lower Extremity Activity Scale (LEAS)), and postoperative complications. A total of 49 hips in 39 patients (mean age 56 years (SD 13); 80% female (n = 39)) were included. Mean follow-up was 4.9 years (SD 5.1). Of these 49 hips, 37 THAs and 12 HRAs were performed. In all, 96% of hips returned to professional dance activities postoperatively. With regard to PROMs, there were statistically significant improvements in mHHS, HOOS-JR, and LEAS from baseline to ≥ one year postoperatively. There were complications in 7/49 hips postoperatively (14%), five of which required revision surgery (10%). There were no revisions for instability after the index procedure. Two complications (5.4%) occurred in hips that underwent THA compared with five (42%) after HRA (p = 0.007), though the difference by procedure was not significantly different when including only contemporary implant designs (p = 0.334). Active professional dancers experienced significant improvements in functional outcome scores after THA or HRA, with a 96% rate of return to professional dance. However, the revision rate at short- to mid-term follow-up highlights the challenges of performing hip arthroplasty in this demanding patient population. Further investigation is required to determine the results of THA versus HRA using contemporary implant designs in these patients.

On the Existence, Rareness, and Uniqueness of Quenched H i-rich Galaxies in the Local Universe

Using data from ALFALFA, xGASS, H i-MaNGA, and the Sloan Digital Sky Survey (SDSS), we identify a sample of 47 “red but H i-rich” (RR) galaxies with near-UV (NUV) − r > 5 and unusually high H i-to-stellar mass ratios. We compare the optical properties and local environments between the RR galaxies and a control sample of “red and H i-normal” (RN) galaxies that are matched in stellar mass and color. The two samples are similar in the optical properties typical of massive red (quenched) galaxies in the local Universe. The RR sample tends to be associated with slightly lower-density environments and has lower clustering amplitudes and smaller neighbor counts at scales from several hundred kiloparsecs to a few megaparsecs. The results are consistent with the RR galaxies being preferentially located at the center of low-mass halos, with a median halo mass ∼1012 h −1 M ⊙ compared to ∼1012.5 h −1 M ⊙ for the RN sample. This result is confirmed by the SDSS group catalog, which reveals a central fraction of 89% for the RR sample, compared to ∼60% for the RN sample. If assumed to follow the H i size–mass relation of normal galaxies, the RR galaxies have an average H i-to-optical radius ratio of R HI/R 90 ∼ 4, four times the average ratio for the RN sample. We compare our RR sample with similar samples in previous studies, and quantify the population of RR galaxies using the SDSS complete sample. We conclude that the RR galaxies form a unique but rare population, accounting for only a small fraction of the massive quiescent galaxy population. We discuss the formation scenarios of the RR galaxies.

Genetic formation of Sui populations in southwest China

AbstractThe Sui people living in Guizhou province have a unique ethnic culture and population history due to their long‐time isolation from other populations. To investigate the genetic structure of Sui populations in different regions of Guizhou, we genotyped 89 individuals from four Sui populations using genome‐wide single nucleotide polymorphisms arrays. We analyzed the data using principal component analysis, ADMIXTURE analysis, f‐statistics, qpWave/qpAdm, TreeMix analysis, fineSTRUCTURE, and GLOBETROTTER. We found that Sui populations in Guizhou were genetically homogeneous and had a close genetic affinity with Tai‐Kadai‐speaking populations, Hmong‐Mien‐speaking Hmong, and some ancient populations from southern China. The Sui populations could be modeled as an admixture of 33.5%–37.9% of Yellow River Basin farmer‐related ancestry and 62.1%–66.5% of Southeast Asian‐related ancestry, indicating that the southward expansion of northern East Asian‐related ancestry influenced the formation of the Tai‐Kadai‐speaking Sui people. Future publications of more ancient genomics in southern China could effectively provide further insight into the demographic history and population structure of the Sui people.

Persistently high HBsAg levels during HBeAg-seropositive stage predict lower risk of hepatocellular carcinoma in chronic hepatitis B patients.

High hepatitis B surface antigen (HBsAg) level predicts hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients with low viral load. The role of longitudinal HBsAg levels in predicting HCC in HBeAg-positive CHB patients remains unknown. HBeAg-positive CHB participants from the REVEAL-HBV cohort with ≥2 HBsAg measurements before HBeAg seroclearance were enrolled. Group-based trajectory modelling identified distinct HBsAg trajectory groups during a median of 11 years of HBeAg-positive status. Cox regression models were applied for investigating independent predictors of HCC and estimating adjusted hazard ratio (HRadj) with a 95% confidence interval (CI). A p-value less than 0.05 was considered statistically significant. A total of 319 patients were enrolled and classified by HBsAg trajectory patterns as (A) persistently high group (n = 72): HBsAg persistently ≥104 IU/mL, and (B) non-stationary group (n = 233): low HBsAg at baseline or declining to <104 IU/mL during the follow-up. Group B had higher proportions of abnormal ALT levels, HBV genotype C and basal core mutation than group A (p < 0.05); age at entry and gender were comparable. The annual incidence of HCC in group A and group B were 0.37% and 1.16%, respectively (p = 0.03). In multivariate analysis, age >40 years (HRadj [95% CI] = 4.11 [2.26-7.48]), genotype C (HRadj [95% CI] = 4.39 [1.96-9.81]) and the non-stationary group (HRadj [95% CI] = 3.50 [1.49-8.21]) were independent predictors of HCC. Basal core promoter mutation was the only risk factor of HCC in the persistently high HBsAg group (HRadj [95% CI] = 32.75 [5.41-198.42]). Patients with persistently high HBsAg levels during HBeAg-seropositive stage represent a unique population with low risk of HCC development.

Comet 81P/Wild 2 dust impactors of Stardust turnip-like tracks analogous to cluster IDPs

We measured oxygen isotope ratios of 16 silicate fragments from seven aerogel tracks (turnip-like type B tracks 77, 149, 172, 191, and 220; carrot-like type A tracks 22 and 175) of the comet 81P/Wild 2 collector from NASA’s Stardust mission using secondary ion mass spectrometry. Thirteen were prepared by ultramicrotomy; three from track 220 were prepared by sputtering resin blocks using a SIMS Kohler beam, a new procedure aiming to mine as many cometary particles encased in aerogel/resin as possible. Combining new and literature results, we recognized that most silicate fragments of individual type B tracks have diverse mineralogy but consistent mass-independent fractionation of oxygen isotopes (Δ17O = δ17O − 0.52 × δ18O). These observations suggest that their impactors are loosely bound aggregates of unequilibrated materials originating mainly from similar protoplanetary disk regions, resembling the cluster IDP U2-20-GCA. Furthermore, silicate fragments from type A track 22 have almost identical mineralogy and Δ17O values, confirming that its impactor is a single chondrule-like fragment. The terminal particle of type A track 175 is pure forsterite with Δ17O of ∼ –23 ‰.Six iron-rich fragments of this study have positive oxygen isotope ratios (Δ17O∼ +2 ‰) and ordinary chondrite chondrule-like olivine compositions. Together with five similar fragments in the literature, a unique population (Mg# ≤ 86) of Wild 2 fragments that resemble chondrules from the inner solar system (O-E-R) chondrites or the outer solar system CH-CB chondrites was identified. The remaining 16O-poor Wild 2 fragments are Mg# ≥ 79 silicates with Δ17O ∼ –2 ‰ and a small amount of Mg# ≤ 79 silicates with Δ17O ∼ 0 ‰, which are most consistent with CR chondrite chondrules. Thus, we conclude that in addition to the possible major source of CR chondrite chondrule-like materials, the inner solar system or CH-CB chondrule-like materials are a minor component of comet Wild 2, like the cluster IDP U2-20-GCA.

Medication Trends in the Military: A Comparative Analysis of Prescribing Patterns Among Service Members Seen by a Pharmacist and Implications for Medical Readiness.

Medications play a critical role supporting the health of military service members. Little is known about the broad use of medications prescribed to this population. Active duty service members (ADSMs), while often younger and having fewer diagnosed comorbid conditions, face unique health challenges that benefit from pharmacotherapy. Understanding prescribing patterns is instrumental to illuminate potential areas for research and to guide education so that military health care professionals can maintain competency, improve outcomes, and support medical readiness. This study aimed to characterize commonly dispensed medications among ADSMs and to compare these prescriptions with those of the general population. A retrospective, cross-sectional analysis using data extracted contained in the Military Health System Information Platform focused on ADSMs who consulted with a clinical pharmacist during the 2019 fiscal year. Descriptive statistics were used to summarize patient and prescription data. The 100 most frequently prescribed medications and 20 most frequently prescribed therapeutic classes were identified. Analyses were performed using Statistical Analysis System (SAS) software, and a non-metric multidimensional scaling plot was generated in R to illustrate the relationships between the 20 most frequently used therapeutic classes and the branches of service. The study analyzed 719,788 prescriptions for 30,012 service members, revealing a high prescription rate for pain, inflammation, and psychiatric condition treatments. Antidepressants and nonsteroidal anti-inflammatory drugs were among the most commonly prescribed across all military branches. Some medication uses varied, which may indicate distinct needs within different service branches. Understanding medication patterns among ADSMs may be able to help health care professionals proactively address pharmacological challenges and optimize pharmaceutical use in this unique population. This knowledge can also aid in the development of training modules focused on medication side effects, interactions, counseling, and implications on military deployment for the most commonly used medications. Future examination into prescribing cascades and medication use related to proton-pump inhibitors, docusate, benzonatate, and muscle relaxants may identify opportunities to provide better care or lower cost.

Stem Cells and Differentiation in Vascular Tissues.

Plant vascular tissues are crucial for the long-distance transport of water, nutrients, and a multitude of signal molecules throughout the plant body and, therefore, central to plant growth and development. The intricate development of vascular tissues is orchestrated by unique populations of dedicated stem cells integrating endogenous as well as environmental cues. This review summarizes our current understanding of vascular-related stem cell biology and of vascular tissue differentiation. We present an overview of the molecular and cellular mechanisms governing the maintenance and fate determination of vascular stem cells and highlight the interplay between intrinsic and external cues. In this context, we emphasize the role of transcription factors, hormonal signaling, and epigenetic modifications. We also discuss emerging technologies and the large repertoire of cell types associated with vascular tissues, which have the potential to provide unprecedented insights into cellular specialization and anatomical adaptations to distinct ecological niches.

Worst pattern of invasion: A prognostic indicator in early-stage oral tongue cancer: A single-center cohort study

IntroductionThe goal of prognostic studies in early-stage oral tongue cancer is to identify the subset of patients at risk of a poor prognosis and thus need more aggressive treatment, such as multimodality therapy. This study analyses the prognostic significance of worst pattern of invasion (WPOI) in a unique population of pathologically proven node-negative early-stage oral tongue cancer patients to see if the WPOI is a prognostic marker that may help guide options of adjuvant therapy. Materials and methodsWe analyzed prospectively collected data of 192 oral squamous cell carcinoma (OSCC) patients treated between 2017 and 2021. Patients underwent curative surgery with or without adjuvant therapy. The study included only pathologically proven early-stage tongue squamous cell carcinoma (pathological T1-T2) with node-negative (N0) and complete histological details such as WPOI, Lymphocyte host response (LHR), Perinueral invasion (PNI), and Lymphovascular invasion (LVI). Statistical analysis was done using chi-square, cox multivariate analysis and Kaplan-Meier survival analysis. ResultsIn 192 patients with a mean follow-up period of 22 months, there were 39 recurrences. out of these we had 20 patients in non-aggressive WPOI and 19 in aggressive WPOI groups. TNM staging and WPOI are significantly associated with postoperative recurrence (p-value 0.029 and 0.019 respectively). However, PNI (p-value-0.954), LVI (p-value - 0.7490) and adjuvant therapy (p-value-0.733) were found to have no significant association. In our study adjuvant radiation had no role in patients with aggressive WPOI. ConclusionWPOI is an independently significant prognostic factor for postoperative recurrences. This study also found that adjuvant radiation therapy did not help in reduction of post-operative recurrences.

The sacred deer conflict of management after a 1000‐year history: Hunting in the name of conservation or loss of their genetic identity

AbstractHuman–wildlife conflict involves diverse stakeholders with conflicting values. Resolving such conflicts necessitates the development of management plans rooted in scientific knowledge and establishing of social consensus. In Nara City, situated within the Japanese Archipelago, wild sika deer (Cervus nippon) hold sacred significance due to religious reasons and have been protected for over a millennium, resulting in a distinct genetic identity. However, the escalating deer population has caused significant agricultural damage in the areas surrounding the sanctuary. Consequently, a debate has arisen regarding the advantages and disadvantages of implementing lethal measures to address individuals that might be considered sacred deer but are regarded as pests in the vicinity of the sanctuary. Here, we used mitochondrial DNA (mtDNA) control region and nuclear simple sequence repeat (SSR) markers to detect the origin of deer in the areas neighboring the sanctuary (management areas). As a result, two genetic populations of deer were detected in Nara City. In the sanctuary, we detected only one specific mtDNA haplotype (S4). On the other hand, seven haplotypes, including S4, were detected in the management area. SSR analysis also suggested that the sika deer in the management area may be an admixed population of multiple origins from the sanctuary and out of Nara City. Interbreeding populations may expand into the sanctuary, and unique genetic populations for more than 1000 years may disappear. This study suggests that ordinary deer could soon replace the deer revered and protected by the people of Nara. Additionally, the proximity of sanctuary deer to tourists worldwide and the interaction with wild deer in other areas pose a potential risk of spreading zoonotic diseases. Urgent decisions are required to determine whether to advocate for extermination in managed areas for ‘conservation’ purposes or risk losing the genetic identity of the sacred deer.