Serum Calcium Levels in Patients with Essential Hypertension: A Cross-Sectional Study in a Tertiary Hospital of Bangladesh.

The exact cause of essential hypertension remains unclear. There is evidence to suggest that the development of essential hypertension is causally related to serum calcium levels. This study was designed to assess the status of serum calcium level in patients with essential hypertension and compared with healthy control. The research study was cross-sectional observational in nature. This study was done at the Department of Physiology in Sylhet MAG Osmani Medical College, Sylhet, Bangladesh. The duration of the research period was one year. All the known case of hypertension and newly diagnosed hypertensive patients were selected and compared with age-sex matched apparently healthy individual. Age below 18 years, pregnant women and patients taking supplementary calcium therapy were excluded from this study. Blood pressure was measured by auscultatory method; aneroid sphygmomanometer and standard stethoscope were used. Automated chemistry analyzer Vitrose-350, USA was used to estimate serum calcium level. Standard operating procedure strictly followed. There were 62 hypertensive (both known case of hypertension and newly diagnosed cases) were selected in hypertensive group (Group A) and 62 age-sex matched apparently healthy individuals were selected in normotensive group (Group B). The mean age of hypertensive and normotensive subjects was not statistically significant (p=0.814). There were 27(43.5%) male and 35(56.5%) female in hypertensive group, 32(51.8%) male and 30(48.4%) female in normotensive group. The distribution was statistically not significant (p=0.472). The mean value of the systolic blood pressure (SBP) was 146.45±5.82 mm Hg and the mean value of the diastolic blood pressure (DBP) was 92.90±7.66 mm Hg in hypertensive group. The mean value of the SBP was 112.74±6.88 mm Hg and the mean value of the DBP was 74.52±5.33 mm Hg of the normotensive group. The difference in mean blood pressure (BP) between the two groups was highly significant (p<0.001). The mean value of the serum calcium level was 8.59±0.55 mg/dl in hypertensive group and 9.12±0.93 mg/dl in normotensive group, which was statistically significant (p <0.001) between two groups. Serum calcium was significantly lower in hypertensive group than normotensive group. There was a negative correlation of the serum calcium level with both systolic and diastolic blood pressure.

Effects of racial teasing on adolescent marijuana use and nicotine vaping: An analysis of the Virginia Youth Risk Behavior Surveillance System.

BACKGROUND: Despite adverse effects of tobacco and marijuana use on the adolescent brain, its use among youth remains high. Previous research shows associations between bullying and risks of substance use; less is known about racial teasing. This study examines associations of racial teasing, marijuana and/or electronic vapor products (EVP) use among adolescents, using 2021 Virginia Youth Risk Behavior Surveillance System (VYRBSS). METHODS: VYRBSS is a self-reported survey which collects information on experiences with racial teasing and substance use. This analysis included 3,083 high school students ≥ 12 years old. Descriptive analysis and logistic regression models were performed for categorical variables. Multivariable models were adjusted for confounders. RESULTS: Racial teasing was associated with marijuana (AOR 1.89; CI 1.43-2.48) and EVP use (AOR 2.52; CI 1.91-3.31). Compared to Whites; Asians, Blacks, and Latinos were more likely to report racial teasing. Older heterosexual females reported higher use of marijuana and EVP. Blacks reported greater use of marijuana, whereas Whites were more likely to use EVP. EVP use was higher in females (AOR 1.73, CI 1.34-2.23), bisexual youth (AOR 1.68, CI 1.23, 2.30) and poor mental health (AOR 1.49, CI 1.16, 1.92). Marijuana use was associated with bisexuality (AOR 1.75, CI 1.28-2.39) and poor mental health (AOR 1.62, CI 1.27-2.07) as well. CONCLUSIONS: Every effort should be made by public health professionals in Virginia to prevent racial teasing among adolescents because it increases the odds of substance use, particularly in older females, youth who identify as bisexual, and those reporting poor mental health.

Public engagement with consumer sleep technology for obstructive sleep apnea screening: implications for equity, access, and practice.

STUDY OBJECTIVES: To characterize public practices and perspectives on the use of consumer sleep technology (CST) and evaluate perspectives on using CST as a screening tool for obstructive sleep apnea (OSA). METHODS: We designed a survey instrument incorporating content from validated instruments (STOP-BANG and the Epworth Sleepiness Scale) and hypothesis-generated questions. Survey development involved multidisciplinary collaboration among three board-certified sleep medicine experts, researchers, and consumers. The survey was disseminated across a national sample of adults living in the United States via an online platform. RESULTS: Among 897 respondents, the mean (SD) age was 47.5 (16.9) years; 73.1% were female, 81.8% were White, and 505 respondents (56.3%) reported having tracked sleep using CS. Factors associated with decreased odds of CST use included household income <$30,000 (OR 0.47, 95% CI 0.28-0.79; p=0.004), Medicaid insurance (OR 0.43, 95% CI 0.26-0.69; p=0.001), Medicare insurance (OR 0.59, 95% CI 0.41-0.84; p=0.004), and lack of a primary care physician (OR 0.55, 95% CI 0.33-0.91; p=0.021). Most respondents (91.1%) agreed or strongly agreed that screening for OSA would be a useful feature of CST, but respondents reporting an education of high school diploma or less (OR 0.48, 95% CI 0.29-0.79; p=0.004) were less likely to agree with this statement. CONCLUSIONS: Attitudes toward and use of CST differed based on demographic and socioeconomic factors. Further study is needed to understand and address barriers to CST adoption and to characterize implications for equitable access to care for sleep disorders.

The effects of the COVID-19 pandemic on pediatric dog bite injuries.

BACKGROUND/OBJECTIVE: Shortly after the onset of the COVID Pandemic, when many schools and outside activities were suspended, dog adoption rates increased. It is unknown if increased dog adoption rates along with stay-at-home orders resulted in changes to pediatric dog bite injuries. The objective of this study was to examine the incidence and characteristics of dog bites in children seen in a pediatric emergency department (PED) during the pandemic compared to before. METHODS: A retrospective review of children evaluated in the PED of a level 1 pediatric trauma center and its satellite PED from March 2018 through February 2022 who had a discharge diagnosis of dog bite (ICD-10 W54.0XXA) was conducted. Pre-pandemic cases, March 2018 through February 2020, were compared to those that occurred during the pandemic, March 2020 through February 2022. RESULTS: There were 2,222 patients included in the study. Compared to pre-pandemic cases, the incidence for the first 12 months of the pandemic was 1.5 times higher than the pre-pandemic 12-month periods but returned closer to the pre-pandemic rates during the second 12 months of the pandemic. More patients were admitted during the pandemic (6.1% vs. 3.7%, p < 0.05). Facial and multiple injuries occurred more frequently during the pandemic (face 35.9% vs. 33.5%: multiple 18.5% vs. 15.6% p < 0.05). CONCLUSIONS: There was a higher incidence of PED visits, higher admission rates, and an increase in multiple body part and facial injuries in children with dog bite injuries during the COVID pandemic compared to pre-pandemic. Pediatric providers should emphasize safe dog interactions with anticipatory guidance.

Obesity Promotes the Ceramide-Mediated NADPH Oxidase in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a type of blood cancer of the myeloid cell lineage. Obesity is characterized by an increase in body weight that results in excessive fat accumulation. Obesity has been associated with an increased incidence of many cancers, including blood cancers. This study evaluated the role obesity in AML progression in a novel transgenic mouse model developed by crossing Flt3ITD mice with Lepob/ob mice. Leukemia burden was augmented in obese AML mice. In addition, it was determined that obesity upregulated the ceramide-mediated and ceramide-1-phosphate-mediated NADPH oxidase 2 (NOX2). Notably, increased oxidative pathways has been attributed to disease progression in AML. Taken together, this study demonstrates a direct link between obesity and the progression of AML in part by augmenting the ceramide mediated NOX2.

Patient-Specific Nanoparticle Targeting in Human Leukemia Blood.

Antibody-directed targeting of chemotherapeutic nanoparticles to primary human cancers holds promise for improving efficacy and reducing off-target toxicity. However, clinical responses to targeted nanomedicines are highly variable. Herein, we prepared and examined a matrix of 9 particles (organic and inorganic particles of three surface chemistries with and without antibody functionalization) and developed an ex vivo model to study the person-specific targeting of nanoparticles in whole blood of 15 patients with chronic lymphocytic leukemia (CLL). Generally, anti-CD20-functionalized poly(ethylene glycol) (PEG) nanoparticles efficiently targeted CLL cells, leading to low off-target phagocytosis by granulocytes and monocytes in the blood. However, there was up to 164-fold patient-to-patient variability in the CLL targeting. This was further exemplified through using clinically relevant PEGylated doxorubicin-encapsulated liposomes, which showed high interpersonal differences in CLL targeting (up to 234-fold differences) and off-target phagocytosis (up to 65- and 112-fold differences in granulocytes and monocytes, respectively). Off-target phagocytosis led to almost all monocytes being killed within 24 h of treatment. Variance of the off-target association of PEGylated liposomes with granulocytes and monocytes significantly correlated to anti-PEG immunoglobulin G levels in the blood of CLL patients. A negative correlation between CLL targeting of PEG particles and anti-PEG immunoglobulin M levels was found in the blood. Taken together, our study identifies anti-PEG antibodies as key proteins in modulating patient-specific targeting of PEGylated nanoparticles in human leukemia blood. Other factors, such as the antigen expression of targeted cells and fouling properties of nanoparticles, also play an important role in patient-specific targeting. The human leukemia blood assay we developed provides an ex vivo model to evaluate interpersonal variances in response to targeted nanomedicines.

Implementing a Streamlined Hypoglossal Nerve Stimulator Pathway: Cost, Time to Surgery, and Outcomes.

Objective: To evaluate the costs, time to surgery, and clinical outcomes associated with implementing a streamlined hypoglossal nerve stimulator (HGNS) implantation pathway. Study Design: Retrospective cohort study. Setting: Single tertiary care center in the United States from 2016 to 2023. Methods: Patients with a lack of complete concentric collapse of the velum during volitional snore on in-office laryngoscopy qualified for the streamlined HGNS pathway. This pathway consisted of confirmatory drug-induced sleep endoscopy (DISE) followed immediately by HGNS implantation during the same surgical encounter. Outcomes were compared to patients in the traditional pathway (standalone DISE followed by HGNS implantation on a later date). Results: A total of 68 patients (13 streamlined, 55 traditional) with obstructive sleep apnea who underwent HGNS implantation were included. Patients were predominately male (70.6%) and White (95.6%) and had a mean (SD) age of 63.5 (10.0) years. The streamlined pathway was associated with a significant reduction in both hospital costs (mean difference $9258, 95% confidence interval [CI]: 3690-14,825; P = .002) and time to surgery (mean decrease of 3.82 months, 95% CI: 0.83-6.80 months; P = .013) compared to the traditional pathway. Patients in both groups had reduction in apnea-hypopnea index and Epworth Sleepiness Scale score, with no significant differences in comparisons between groups. Conclusion: In select patients, the streamlined HGNS pathway may expedite time to surgery and reduce hospital costs with comparable clinical outcomes to a traditional 2-stage pathway. Further research is warranted to validate patient selection and better understand longitudinal outcomes.

Targeting CD38 with monoclonal antibodies disrupts key survival pathways in paediatric Burkitt's lymphoma malignant B cells.

Objectives: Paediatric Burkitt's lymphoma (pBL) is the most common childhood non-Hodgkin B-cell lymphoma. Despite the encouraging survival rates for most children, treating cases with relapse/resistance to current therapies remains challenging. CD38 is a transmembrane protein highly expressed in pBL. This study investigates the effectiveness of CD38-targeting monoclonal antibodies (mAbs), daratumumab and isatuximab, in impairing crucial cellular processes and survival pathways in pBL malignant cells. Methods: In silico analyses of patient samples, combined with in vitro experiments using the Ramos cell line, were conducted to assess the impact of daratumumab and isatuximab on cellular proliferation, apoptosis and the phosphoinositide 3-kinase (PI3K) pathway. Results: Isatuximab was found to be more effective than daratumumab in disrupting B-cell receptor signalling, reducing cellular proliferation and inducing apoptosis. Additionally, isatuximab caused a significant impairment of the PI3K pathway and induced metabolic reprogramming in pBL cells. The study also revealed a correlation between CD38 and MYC expression levels in pBL patient samples, suggesting CD38 involvement in key oncogenic processes. Conclusion: The study emphasises the therapeutic potential of CD38-targeting mAbs, particularly isatuximab, in pBL.

Challenges and Opportunities in Transitioning Autistic Individuals Into Adulthood.

BACKGROUND AND OBJECTIVES: Approximately 1.2 million autistic youth will reach the legal age of adulthood over the next decade. Given dynamic changes in the socioecological context of the transition to adulthood, we produced an updated transitions research agenda reflecting the perspectives of autistic young adults, care partners (parents), and professionals who use autism research. METHODS: We conducted 9 focus groups: 4 young adult, 4 care partner, and 1 professional, with 59 total participants. Young adults were grouped by self-reported identity: (1) racial and ethnic minority, (2) lesbian, gay, bisexual, transgender, queer, intersex, asexual, and other identities, and (3) nonspeaking, in addition to a general group. We selected care partners who supported youth with varying intensity of support needs. We used rapid qualitative inquiry methods to extract key points from answers to semistructured interview questions. RESULTS: Delays in diagnosis and transition processes, and placement on wait lists resulted in significant obstacles to successful transitions. Parents assumed a dominant role by coordinating services, navigating systems and identifying opportunities for community participation, and providing direct supports. There was an overarching need for inclusion of autistic people in transitions research and consideration of cultural differences in priorities and values. Participants prioritized investigation of variation in transitions among autistic youth with intersecting identities, navigation support (eg, peer mentors), efficacy of services and supports (eg, transition and employment services), differences in available services by location, and problems within specific benefits programs. CONCLUSIONS: Research should focus on understanding population-level factors of system performance on outcomes and support needs, service delivery among marginalized groups, and transformation of complex service ecosystems.

Impaired diffusing capacity and COPD incidence in adults with symptoms and normal spirometry.

BACKGROUND: Impaired diffusing capacity of the lung (DLCO) in the absence of post-bronchodilator (BD) airflow obstruction has been proposed as a marker of 'Pre-COPD'. However, the relationship between impaired DLCO and subsequent lung function decline and COPD incidence has not been examined in-depth. METHODS: We conducted an observational study of adults aged between 40 and 70 years who were evaluated at a multi-centre lung function laboratory in Australia between 2014 and 2024. Adults referred with respiratory symptoms or a clinical suspicion of obstructive airways disease with follow-up spirometry obtained ≥12 months after the initial assessment were included. The relationship between impaired DLCO and subsequent lung function decline and COPD incidence was assessed among those with normal spirometry at baseline. RESULTS: A total of 266 patients with a mean age of 53.2 (SD 12.8) years were evaluated after a median follow-up of 2.3 [IQR 1.5 to 3.3] years. We found no evidence of an association between impaired DLCO (below the lower limit of normal) and annualised rate of decline in post-BD FEV1 (MD -0.1 % predicted per-year, 95%CI -1.3 to 1.2), FVC (-0.4 % predicted, 95%CI -1.6 to 0.8) or FEV1/FVC (-0.1 % per-year, 95%CI -0.1 to 0.1). The sensitivity of impaired DLCO for COPD incidence was 40 %, and specificity 82 %. Findings were similar in sub-samples limited to current and former smokers, and when impaired DLCO was defined as < 80 % predicted. CONCLUSION: Impaired DLCO was not an effective discriminator of lung function decline or COPD incidence in this real-world cohort.

Evolutionary origins of the lysosome-related organelle sorting machinery reveal ancient homology in post-endosome trafficking pathways.

The major organelles of the endomembrane system were in place by the time of the last eukaryotic common ancestor (LECA) (~1.5 billion years ago). Their acquisitions were defining milestones during eukaryogenesis. Comparative cell biology and evolutionary analyses show multiple instances of homology in the protein machinery controlling distinct interorganelle trafficking routes. Resolving these homologous relationships allows us to explore processes underlying the emergence of additional, distinct cellular compartments, infer ancestral states predating LECA, and explore the process of eukaryogenesis itself. Here, we undertake a molecular evolutionary analysis (including providing a transcriptome of the jakobid flagellate Reclinomonas americana), exploring the origins of the machinery responsible for the biogenesis of lysosome-related organelles (LROs), the Biogenesis of LRO Complexes (BLOCs 1,2, and 3). This pathway has been studied only in animals and is not considered a feature of the basic eukaryotic cell plan. We show that this machinery is present across the eukaryotic tree of life and was likely in place prior to LECA, making it an underappreciated facet of eukaryotic cellular organisation. Moreover, we resolve multiple points of ancient homology between all three BLOCs and other post-endosomal retrograde trafficking machinery (BORC, CCZ1 and MON1 proteins, and an unexpected relationship with the "homotypic fusion and vacuole protein sorting" (HOPS) and "Class C core vacuole/endosomal tethering" (CORVET) complexes), offering a mechanistic and evolutionary unification of these trafficking pathways. Overall, this study provides a comprehensive account of the rise of the LROs biogenesis machinery from before the LECA to current eukaryotic diversity, integrating it into the larger mechanistic framework describing endomembrane evolution.

Quantitative Measurement of Cooperative Binding in Partially Dissociated Water Dimers at the Hematite "R-Cut" Surface.

Water-solid interfaces pervade the natural environment and modern technology. On some surfaces, water-water interactions induce the formation of partially dissociated interfacial layers; understanding why is important to model processes in catalysis or mineralogy. The complexity of the partially dissociated structures often makes it difficult to probe them quantitatively. Here, we utilize normal incidence X-ray standing waves (NIXSW) to study the structure of partially dissociated water dimers (H2O-OH) at the α-Fe2O3(012) surface (also called the (11̅02) or "R-cut" surface): a system simple enough to be tractable yet complex enough to capture the essential physics. We find the H2O and terminal OH groups to be the same height above the surface within experimental error (1.45 ± 0.04 and 1.47 ± 0.02 Å, respectively), in line with DFT-based calculations that predict comparable Fe-O bond lengths for both water and OH species. This result is understood in the context of cooperative binding, where the formation of the H-bond between adsorbed H2O and OH induces the H2O to bind more strongly and the OH to bind more weakly compared to when these species are isolated on the surface. The surface OH formed by the liberated proton is found to be in plane with a bulk truncated (012) surface (-0.01 ± 0.02 Å). DFT calculations based on various functionals correctly model the cooperative effect but overestimate the water-surface interaction.

Cell-cell interaction determines cell fate of mesoderm-derived cell in tongue development through Hh signaling.

Dysfunction of primary cilia leads to genetic disorder, ciliopathies, which shows various malformations in many vital organs such as brain. Multiple tongue deformities including cleft, hamartoma, and ankyloglossia are also seen in ciliopathies, which yield difficulties in fundamental functions such as mastication and vocalization. Here, we found these tongue anomalies in mice with mutation of ciliary protein. Abnormal cranial neural crest-derived cells (CNCC) failed to evoke Hh signal for differentiation of mesoderm-derived cells into myoblasts, which resulted in abnormal differentiation of mesoderm-derived cells into adipocytes. The ectopic adipose subsequently arrested tongue swelling formation. Ankyloglossia was caused by aberrant cell migration due to lack of non-canonical Wnt signaling. In addition to ciliopathies, these tongue anomalies are often observed as non-familial condition in human. We found that these tongue deformities could be reproduced in wild-type mice by simple mechanical manipulations to disturb cellular processes which were disrupted in mutant mice. Our results provide hints for possible future treatment in ciliopathies.

Associations between maternal diet, family eating habits and preschool children's dietary patterns: insights from the UPBEAT trial.

BACKGROUND: Dietary behaviours in early life often track across the life course, influencing the development of adverse health outcomes such as obesity and cardiovascular disease. This study aimed to explore the between dietary patterns (DP) in preschool children and maternal DP and family eating habits. METHODS: We conducted a secondary analysis of 488 mother-child pairs from the UK pregnancy Better Eating and Activity Trial (UPBEAT) at 3-year follow-up. Previously published DP from mothers and children (derived from food-frequency questionnaires and exploratory factor analysis) were used. Mothers' DP were "Fruits-Vegetables", "African-Caribbean", "Processed and Snacks", and children's DP were "Prudent", "Processed-Snacking", and "African-Caribbean". Family meal environments were evaluated using a 5-point Likert scale. RESULTS: Linear regression models revealed that child's prudent pattern was positively associated with maternal Fruits-Vegetables (B = 0.18 (0.08, 0.27)), Snacks patterns (B = 0.10 (0.01, 0.18)), and eating the same foods during meals (B = 0.25 (0.07, 0.43)). Child's Processed-Snacking pattern was directly associated with maternal Processed (B = 0.22 (0.13, 0.30)) and Snacks (B = 0.27 (0.18, 0.36)) patterns, receiving food as reward (B = 0.22 (0.04, 0.39)) and watching TV during meals (B = 0.27 (0.09, 0.45)). Finally, the child African-Caribbean pattern was directly associated with that from the mother (B = 0.41 (0.33, 0.50)) and watching TV during meals (B = 0.15 (0.09, 0.30)), and inversely associated with maternal processed (B=-0.09 (-0.17, -0.02)) and snacking (B=-0.08 (-0.15, -0.04)) patterns. CONCLUSIONS: Unhealthy dietary patterns in childhood are directly linked to similar maternal patterns and family meal behaviours, such as television viewing and food rewards. These findings highlight targetable behaviours for public health interventions.

Inhibition of hepatic oxalate overproduction ameliorates metabolic dysfunction-associated steatohepatitis.

The incidence of metabolic dysfunction-associated steatohepatitis (MASH) is on the rise, and with limited pharmacological therapy available, identification of new metabolic targets is urgently needed. Oxalate is a terminal metabolite produced from glyoxylate by hepatic lactate dehydrogenase (LDHA). The liver-specific alanine-glyoxylate aminotransferase (AGXT) detoxifies glyoxylate, preventing oxalate accumulation. Here we show that AGXT is suppressed and LDHA is activated in livers from patients and mice with MASH, leading to oxalate overproduction. In turn, oxalate promotes steatosis in hepatocytes by inhibiting peroxisome proliferator-activated receptor-α (PPARα) transcription and fatty acid ß-oxidation and induces monocyte chemotaxis via C-C motif chemokine ligand 2. In male mice with diet-induced MASH, targeting oxalate overproduction through hepatocyte-specific AGXT overexpression or pharmacological inhibition of LDHA potently lowers steatohepatitis and fibrosis by inducing PPARα-driven fatty acid ß-oxidation and suppressing monocyte chemotaxis, nuclear factor-κB and transforming growth factor-ß targets. These findings highlight hepatic oxalate overproduction as a target for the treatment of MASH.

A study on the diversity of phlebotomine sand flies (Diptera, Psychodidae) in karstic limestone areas in Vientiane Province, Laos, with a description of two new species of Sergentomyia França and & Parrot.

BACKGROUND: Southeast Asia is well known as a hotspot of biodiversity. However, very little is known about cave-dwelling hematophagous insects that are medically important. Taxonomic knowledge and ecology of phlebotomine sand flies are very poorly studied in Laos, as well as in other countries in the region. Herein, we report species diversity data and some notes on the ecology of the detected species from these karstic limestone areas of Laos. METHODS: Phlebotomine sand flies were collected using Centers for Disease Control and Prevention (CDC) light traps from limestone cave locations in three districts of Vientiane Province, Laos. Both morphological and molecular techniques were used for sand fly identification. Species diversity and abundance were analyzed according to sites, locations, collection seasons, and trapping positions. RESULTS: A total of 6564 sand flies, of which 5038 were females and 1526 were males, were morphologically identified into 20 species belonging to five genera (Chinius, Idiophlebotomus, Phlebotomus, Sergentomyia, and Grassomyia). The most abundant species were Chinius eunicegalatiae, Phlebotomus stantoni, Sergentomyia hivernus, Se. siamensis, and Idiophlebotomus longiforceps. Cytochrome b analysis results supported the morphological identification and revealed that Se. siamensis was separated from other members of the Se. barraudi group. Two new species, Se. dvoraki n. sp. and Se. marolii n. sp., were described. Sand fly density was generally high except in a cave in Vangvieng, with species richness ranging from 14 to 18 across different caves. Outside caves had higher species richness (R = 20) and diversity (H = 2.50) than cave entrances (R = 18, H = 2.41) and interiors (R = 16, H = 2.13). Seasonal variations showed high sand fly density in Feung and Hinheup during both dry and rainy seasons, while Vangvieng had a notable decrease in density during the dry season (D = 6.29). CONCLUSIONS: This study revealed that the diversity of phlebotomine sand fly fauna in Laos, particularly in karstic limestone areas, is greater than previously known. However, the taxonomic status of many species in Laos, as well as Southeast Asia, still needs more in-depth study using both morphological characters and molecular methods. Many species could be found from inside, at the entrance, and outside of caves, indicating a wide range of host-seeking behavior or possible natural breeding in the karstic cave areas.

Probing the Shape of the Weyl Fermi Surface of NbP Using Transverse Electron Focusing.

Weyl semimetals are defined by their unique Fermi surface, comprising pairs of Weyl points of opposite chirality, connected through topological surface states. Angle-resolved photoemission spectroscopy (ARPES) has been used to verify the existence of the Weyl points and the Fermi arcs. However, ARPES is limited in resolution, leading to significant uncertainty when characterizing the shape of the Fermi surface of semimetals and measuring features such as the distance between the Weyl points. Here, to surpass the resolution of ARPES, we combine quantum oscillation measurements with transverse electron focusing experiments. These techniques offer complementary information, enabling the reconstruction of the distinctive peanut-shaped cross section of the Weyl Fermi surface and accurately determining the separation between Weyl points in the Weyl semimetal NbP. Our Letter showcases the integration of quantum oscillations and transverse electron focusing, allowing for the measurements of complex Fermi surface geometries, concurrently with carriers' transport properties, in high-mobility quantum materials.

Financial Hardship Among Patients With Early-Stage Colorectal Cancer.

Importance: The degree of cancer patients' financial hardship is dynamic and can change over time. Objective: To assess longitudinal changes in financial hardship among patients with early-stage colorectal cancer. Design, Setting, and Participants: In this prospective longitudinal cohort study, English-speaking adult patients with a new diagnosis of stage I to III colorectal cancer being treated with curative intent at National Cancer Institute (NCI) Community Oncology Research Program (NCORP) practices between May 2018 and July 2020 and who had not started chemotherapy and/or radiation were included. Data analysis was conducted from March to December 2023. Main Outcomes and Measures: Patients completed surveys at baseline as well as at 3, 6, 12, and 24 months after enrollment. Cost-related care nonadherence and material hardship, as adopted by Medical Expenditure Panel Survey, were measured. Factors associated with financial hardship were assessed using longitudinal multivariable logistic regression models with time interaction. Results: A total of 451 patients completed baseline questions, with 217 (48.1%) completing the 24-month follow-up. Mean (SD) age was 61.0 (12.0) years (210 [46.6%] female; 33 [7.3%] Black, 380 [84.3%] White, and 33 [7.3%] American Indian or Alaska Native, Asian, multiracial, or Native Hawaiian or Other Pacific Islander individuals or those who did not report race or who had unknown race). Among 217 patients with data at baseline and 24 months, 19 (8.8%) reported cost-related care nonadherence at baseline vs 20 (9.2%) at 24 months (P = .84), and 125 (57.6%) reported material hardship at baseline vs 76 (35.0%) at 24 months (P < .001). In multivariable analysis, lower financial worry (odds ratio [OR], 0.90; 95% CI, 0.87-0.93), higher education (OR, 0.34; 95% CI, 0.15-0.77), and older age (OR, 0.94; 95% CI, 0.91-0.98) were associated with lower nonadherence. Receipt of chemotherapy was associated with higher material hardship (OR, 2.68; 95% CI, 1.15-6.29), while lower financial worry was associated with lower material hardship (OR, 0.83; 95% CI, 0.80-0.96). Over 24 months, female sex was associated with lower nonadherence (OR, 0.90; 95% CI, 0.85-0.96), while higher education was associated with higher nonadherence (OR, 1.09; 95% CI, 1.03-1.17). Being employed was associated with lower material hardship (OR, 0.85; 95% CI, 0.78-0.93), while receipt of care at safety-net hospitals was associated with higher hardship (OR, 1.09; 95% CI, 1.01-1.17). Conclusions and Relevance: In patients with early-stage colorectal cancer, material hardship was more common than cost-related cancer care nonadherence and decreased over time, while nonadherence remained unchanged. Early and longitudinal financial screening and referral to intervention are recommended to mitigate financial hardship.

Phase 1b/2a Study Assessing the Safety and Efficacy of Felzartamab in Anti-Phospholipase A2 Receptor Autoantibody-Positive Primary Membranous Nephropathy.

Introduction: Primary membranous nephropathy (PMN) is most often caused by autoantibodies to phospholipase A2 receptor (PLA2R). M-PLACE (NCT04145440) is an open-label, phase 1b/2a study that assessed the safety and efficacy of the fully human anti-CD38 monoclonal antibody felzartamab in high-risk anti-PLA2R+ PMN. Methods: Patients with newly diagnosed or relapsed PMN (cohort 1 [C1]; n = 18) or PMN refractory to immunosuppressive therapy (IST) (cohort 2 [C2]; n = 13) received 9 infusions of felzartamab 16 mg/kg in the 24-week treatment period, followed by a 28-week follow-up. The primary end point was the incidence and severity of treatment-emergent adverse events (TEAEs). Results: A total of 31 patients were enrolled and received felzartamab. Twenty-seven patients (87.1%) had TEAEs, including infusion-related reactions (IRRs) (29.0%), hypogammaglobulinemia (25.8%), peripheral edema (19.4%), and nausea (16.1%). Five patients (16.1%) had serious TEAEs that all resolved. Immunologic response (anti-PLA2R titer reduction ≥50%) was achieved by 20 of 26 efficacy-evaluable patients (76.9%) (C1, 13/15 [86.7%]; C2, 7/11 [63.6%]). Anti-PLA2R titer reductions were rapid (week 1 response, 44.0%; response 7 months after last felzartamab dose [end of study, EOS], 53.8%). Partial proteinuria remission (urine protein-to-creatinine ratio [UPCR] reduction ≥50%, UPCR <3.0 g/g, and stable estimated glomerular filtration rate [eGFR]) was achieved by 9 of 26 patients (34.6%) (C1, 7/15 [46.7%]; C2, 2/11 [18.2%]) before or at EOS (median follow-up, 366 days). Serum albumin increased from baseline to EOS in 20 of 26 patients (76.9%) (C1, 12/15 [80.0%]; C2, 8/11 [72.7%]). Conclusion: In this population with high-risk anti-PLA2R+ PMN, felzartamab was tolerated and resulted in rapid partial and complete immunologic responses and partial improvements in proteinuria and serum albumin in some patients.

Elevated Plasma Matrix Metalloproteinases Are Associated With Mycobacterium tuberculosis Bloodstream Infection and Mortality in Human Immunodeficiency Virus-Associated Tuberculosis.

Mortality from human immunodeficiency virus (HIV)-associated tuberculosis (TB) is high, particularly among hospitalized patients. In 433 people with HIV hospitalized with symptoms of TB, we investigated plasma matrix metalloproteinases (MMP) and matrix-derived biomarkers in relation to TB diagnosis, mortality, and Mycobacterium tuberculosis (Mtb) bloodstream infection (BSI). Compared to other diagnoses, MMP-8 was elevated in confirmed TB and in Mtb-BSI, positively correlating with extracellular matrix breakdown products. Baseline MMP-3, -7, -8, -10, and PIIINP were associated with Mtb-BSI and 12-week mortality. These findings implicate MMP dysregulation in pathophysiology of advanced HIV-TB and support MMP inhibition as a host-directed therapeutic strategy for HIV-TB.