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California farmers who use reduced-disturbance tillage and winter cover cropping can boost production and improve soil health. However, some farmers are hesitant to try these conservation practices due to uncertainty about whether planting winter cover crops will deplete soil moisture in already drought-stricken regions. Our study addresses these concerns by looking at how long-term reduced-disturbance tillage and winter cover cropping, compared to fallowed soils with standard tillage, affected soil moisture. Although we found a statistical difference in total soil water content, the difference was only about 0.3 inches of water per foot of soil. On average, the soil water content of the top 0–96 inches was highest for the reduced-disturbance fields with winter cover crops. This was especially evident during our driest field season, from November 1, 2017, to March 15, 2018, when cumulative rainfall was only 1.9 inches. Our findings show that winter cover cropping and reduced-disturbance tillage can improve soil without depleting soil water levels in row crops.

This publication highlights the latest advancements in the field of energy and nutrient recovery from organics rich municipal and industrial waste and wastewater. Energy and carbon rich waste streams are multifaceted, including municipal solid waste, industrial waste, agricultural by-products and residues, beached or residual seaweed biomass from post-harvest processing, and food waste and are valuable resources to overcome current limitations with sustainable feedstock supply chains for biorefining approaches. The emphasis will be on the most recent scientific progress in the area, including the development of new and innovative technologies, such as microbial processes and the role of biofilms for the degradation of organic pollutants in wastewater, as well as the production of biofuels and value-added products from organic waste and wastewater streams. The carboxylate platform, which employs microbiomes to produce mixed carboxylic acids through methane-arrested anaerobic digestion, is the focus as a new conversion technology. Nutrient recycling from conventional waste streams such as wastewater and digestate, and the energetic valorization of such streams will also be discussed. The selected technologies significantly contribute to advanced waste and wastewater treatment and support the recovery and utilization of carboxylic acids as the basis to produce many useful and valuable products, including food and feed preservatives, human and animal health supplements, solvents, plasticizers, lubricants, and even biofuels such as sustainable aviation fuel.

Caloric restriction (CR) can extend the organism life- and health-span by improving glucose homeostasis. How CR affects the structure-function of pancreatic beta cells remains unknown. We used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis reveal that CR activates transcription factors important for beta cell identity and homeostasis, while imaging metabolomics demonstrates that beta cells upon CR are more energetically competent. In fact, high-resolution microscopy show that CR reduces beta cell mitophagy to increase mitochondria mass and the potential for ATP generation. However, CR beta cells have impaired adaptive proliferation in response to high fat diet feeding. Finally, we show that long-term CR delays the onset of beta cell aging hallmarks and promotes cell longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cell structure-function during aging and diabetes.

Centromeric localization of evolutionarily conserved CENP-A (Cse4 in Saccharomyces cerevisiae) is essential for chromosomal stability. Mislocalization of overexpressed CENP-A to noncentromeric regions contributes to chromosomal instability in yeasts, flies, and humans. Overexpression and mislocalization of CENP-A observed in many cancers are associated with poor prognosis. Previous studies have shown that F-box proteins, Cdc4 and Met30 of the Skp, Cullin, F-box ubiquitin ligase cooperatively regulate proteolysis of Cse4 to prevent Cse4 mislocalization and chromosomal instability under normal physiological conditions. Mck1-mediated phosphorylation of Skp, Cullin, F-box-Cdc4 substrates such as Cdc6 and Rcn1 enhances the interaction of the substrates with Cdc4. Here, we report that Mck1 interacts with Cse4, and Mck1-mediated proteolysis of Cse4 prevents Cse4 mislocalization for chromosomal stability. Our results showed that mck1Δ strain overexpressing CSE4 (GAL-CSE4) exhibits lethality, defects in ubiquitin-mediated proteolysis of Cse4, mislocalization of Cse4, and reduced Cse4-Cdc4 interaction. Strain expressing GAL-cse4-3A with mutations in three potential Mck1 phosphorylation consensus sites (S10, S16, and T166) also exhibits growth defects, increased stability with mislocalization of Cse4-3A, chromosomal instability, and reduced interaction with Cdc4. Constitutive expression of histone H3 (Δ16H3) suppresses the chromosomal instability phenotype of GAL-cse4-3A strain, suggesting that the chromosomal instability phenotype is linked to Cse4-3A mislocalization. We conclude that Mck1 and its three potential phosphorylation sites on Cse4 promote Cse4-Cdc4 interaction and this contributes to ubiquitin-mediated proteolysis of Cse4 preventing its mislocalization and chromosomal instability. These studies advance our understanding of pathways that regulate cellular levels of CENP-A to prevent mislocalization of CENP-A in human cancers.

BackgroundHepatitis-E virus (HEV), an etiologic agent of acute inflammatory liver disease, is a significant cause of morbidity and mortality in South Asia. HEV is considered endemic in Nepal; but data on population-level infection transmission is sparse.MethodsWe conducted a longitudinal serosurvey in central Nepal to assess HEV exposure. At each visit, capillary blood samples were collected and analyzed for the presence of anti-HEV IgG antibodies. The study took place between February 2019 and April 2021, with up to 4 visits per participant approximately 6 months apart.ResultsWe collected 2513 samples from 923 participants aged 0-25 years, finding a seroprevalence of 4.8% and a seroincidence rate of 10.9 per 1000 person-years. Young adults and individuals consuming surface water faced the highest incidence of infection. Geospatial analysis identified potential HEV clusters, suggesting a need for targeted interventions.SignificanceOur findings demonstrate that HEV is endemic in Nepal and that the risk of infection increases with age.

To meet the requirements of California's Sustainable Groundwater Management Act, there is a critical need for crop production strategies with less reliance on irrigation from surface and groundwater sources. One strategy for improving agricultural water use efficiency is reducing tillage and maintaining residues on the soil surface. We evaluated high residue no-till versus standard tillage in the San Joaquin Valley with and without cover crops on the yields of two crops, garbanzo and sorghum, for 4 years. The no-till treatment had no primary or secondary tillage. Sorghum yields were similar in no-till and standard tillage systems while no-till garbanzo yields matched or exceeded those of standard tillage, depending on the year. Cover crops had no effect on crop yields. Soil cover was highest under the no-till with cover crop system, averaging 97% versus 5% for the standard tillage without cover crop system. Our results suggest that garbanzos and sorghum can be grown under no-till practices in the San Joaquin Valley without loss of yield.

Introduction: Chronic kidney disease (CKD) is common cause of renal failure. It involves a progressive loss in the structure and function of the kidneys over the course of months, with or without decreased glomerular filtration rate (GFR). CKD can be diagnosed by its pathological abnormalities, changes in the levels of renal function markers in the blood or urine, or by imaging investigations (E.g. USG etc). Objectives: The purpose of our study is 1) To correlate renal echogenicity with serum creatinine in order to determine the significance of renal echogenicity for identifying the progression of chronic kidney disease (CKD) and for the sonographic grading of CKD, 2) To study association of blood pressure, renal cortical cysts and renal size with grade of chronic renal disease. Methods: This hospital based cross sectional study was carried out at National Kidney Centre, Banasthali Kathmandu. Two hundred patients above 20 years, diagnosed with CKD according to the guidelines of the National Kidney Foundation and referred for USG, were included in the study. Patients with kidney transplant, on dialysis, with liver disease and renal tumors were excluded. Ultrasound of kidneys was performed by senior consultant radiologist who was blind to the patients’ serum creatinine levels. The relationship between grade of CKD with serum creatinine, kidney size, blood pressure and cortical cysts were assessed. Statistical analysis was performed by Kruskal wallis test using SPSS version 17. P values less than 0.05 were considered statistically significant. Results: Mean serum creatinine was 1.7 mg/dl for Grade 1 (range: 1.1- 4.7 mg/dl, STD 0.44), 2.38 mg/dl for Grade 2 (range: 1.8-3.9 mg/dl STD 0.40), 4.18 mg/dl for Grade 3 (range: 2.6-6.0 mg/dl, STD 0.88), and 5.65 mg/dl for Grade 4 (range: 3.1-12 mg/dl, STD 2.0. Conclusion: Renal echogenicity and its grading correlates better with serum creatinine in CKD than other sonographic parameters. Hence, renal echogenicity is a better parameter than serum creatinine for estimating renal function in CKD, and has the added advantage of irreversibility.

Introduction: Amniotic fluid plays an important role in the development of fetus. Any abnormality in the production amniotic fluid may have adverse effect on the fetus and the mother. Polyhydraminos is one of the common complications occurring during pregnancy and complicates around 0.2 - 2% of pregnancies. Methods: It is a prospective study conducted in Manipal Teaching Hospital, Pokhara, Nepal from January 2013 to December 2015. All the pregnant ladies irrespective of gestational age with amniotic fluid index (AFI) 25 cm or more were enrolled for the study. According to the AFI, polyhydraminos was classified as mild (25 – 30 cm), moderate (30.1 - 35 cm) and severe (>35 cm). Fetal outcome, mode of delivery, presence of congenital anomalies, NICU admission and maternal glucose intolerance were recorded. Results: Out of 8232 deliveries, 24 were diagnosed and admitted with the diagnosis of polyhydraminos. Mild polyhydraminos, 50% (n=12) occurred after 37 weeks of gestation and 12.5% (n=3) had severe polyhydraminos. All pregnant ladies 50% (n=12), beyond 37 weeks gestation had cesarean section, whereas 25% (n=6) had vaginal deliveries. 33.3% (n=8) had preterm labor, 12.5% (n=3) had premature rupture of membrane, 25% (n=6) had congenital anomalies, one IUFD, one case of Rh isoimmunisation and one case of twin pregnancy. NICU admission needed in 20.5% (n=5). Pregnant ladies with impaired glucose intolerance were 8.3% (n=2). Conclusions: Polyhydraminos is associated with increased incidence of cesarean section, preterm labor, fetal malformation and NICU admission.

BACKGROUND: Uptake of mobile phone surveys (MPS) is increasing in many low- and middle-income countries, particularly within the context of data collection on non-communicable diseases (NCDs) behavioural risk factors. One barrier to collecting representative data through MPS is capturing data from older participants.Respondent driven sampling (RDS) consists of chain-referral strategies where existing study subjects recruit follow-up participants purposively based on predefined eligibility criteria. Adapting RDS strategies to MPS efforts could, theoretically, yield higher rates of participation for that age group. OBJECTIVE: To investigate factors that influence the perceived acceptability of a RDS recruitment method for MPS involving people over 45 years of age living in Colombia. METHODS: An MPS recruitment strategy deploying RDS techniques was piloted to increase participation of older populations. We conducted a qualitative study that drew from surveys with open and closed-ended items, semi-structured interviews for feedback, and focus group discussions to explore perceptions of the strategy and barriers to its application amongst MPS participants. RESULTS: The strategys success is affected by factors such as cultural adaptation, institutional credibility and public trust, data protection, and challenges with mobile phone technology. These factors are relevant to individuals willingness to facilitate RDS efforts targeting hard-to-reach people. Recruitment strategies are valuable in part because hard-to-reach populations are often most accessible through their contacts within their social network who can serve as trust liaisons and drive engagement. CONCLUSIONS: These findings may inform future studies where similar interventions are being considered to improve access to mobile phone-based data collection amongst hard-to-reach groups.

BACKGROUNDAndrogen receptor signaling inhibitors (ARSIs) have improved outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC), but their clinical benefit is limited by treatment resistance.METHODSTo investigate the mechanisms of ARSI resistance, we analyzed the whole-genome (n = 45) and transcriptome (n = 31) sequencing data generated from paired metastatic biopsies obtained before initiation of first-line ARSI therapy for mCRPC and after radiographic disease progression. We investigated the effects of genetic and pharmacologic modulation of SSTR1 in 22Rv1 cells, a representative mCRPC cell line.RESULTSWe confirmed the predominant role of tumor genetic alterations converging on augmenting androgen receptor (AR) signaling and the increased transcriptional heterogeneity and lineage plasticity during the emergence of ARSI resistance. We further identified amplifications involving a putative enhancer downstream of the AR and transcriptional downregulation of SSTR1, encoding somatostatin receptor 1, in ARSI-resistant tumors. We found that patients with SSTR1-low mCRPC tumors derived less benefit from subsequent ARSI therapy in a retrospective cohort. We showed that SSTR1 was antiproliferative in 22Rv1 cells and that the FDA-approved drug pasireotide suppressed 22Rv1 cell proliferation.CONCLUSIONOur findings expand the knowledge of ARSI resistance and point out actionable next steps, exemplified by potentially targeting SSTR1, to improve patient outcomes.FUNDINGNational Cancer Institute (NCI), NIH; Prostate Cancer Foundation; Conquer Cancer, American Society of Clinical Oncology Foundation; UCSF Benioff Initiative for Prostate Cancer Research; Netherlands Cancer Institute.

Scrub typhus, a vector-borne bacterial infection, is an important but neglected disease globally. Accurately characterizing the burden is challenging because of nonspecific symptoms and limited diagnostics. Prior seroepidemiology studies have struggled to find consensus cutoffs that permit comparisons of estimates across contexts and time. In this study, we present a novel approach that does not require a cutoff and instead uses information about antibody kinetics after infection to estimate seroincidence. We use data from three cohorts of scrub typhus patients in Chiang Rai, Thailand, and Vellore, India, to characterize antibody kinetics after infection and two population serosurveys in the Kathmandu Valley, Nepal, and Tamil Nadu, India, to estimate seroincidence. The samples were tested for IgM and IgG responses to Orientia tsutsugamushi-derived recombinant 56-kDa antigen using commercial enzyme-linked immunosorbent assay kits. We used Bayesian hierarchical models to characterize antibody responses after scrub typhus infection and used the joint distributions of the peak antibody titers and decay rates to estimate population-level incidence rates in the cross-sectional serosurveys. Median responses persisted above an optical density (OD) of 1.8 for 23.6 months for IgG and an OD of 1 for 4.5 months for IgM. Among 18- to 29-year-olds, the seroincidence was 10 per 1,000 person-years (95% CI, 5-19) in Tamil Nadu, India, and 14 per 1,000 person-years (95% CI: 10-20) in the Kathmandu Valley, Nepal. When seroincidence was calculated with antibody decay ignored, the disease burden was underestimated by more than 50%. The approach can be deployed prospectively, coupled with existing serosurveys, or leverage banked samples to efficiently generate scrub typhus seroincidence estimates.

The impact of variations in the three-dimensional structure of the genome has been recognized, but solid cancer tissue studies are limited. Here, we performed integrated deep Hi-C sequencing with matched whole-genome sequencing, whole-genome bisulfite sequencing, 5-hydroxymethylcytosine (5hmC) sequencing and RNA sequencing across a cohort of 80 biopsy samples from patients with metastatic castration-resistant prostate cancer. Dramatic differences were present in gene expression, 5-methylcytosine/5hmC methylation and in structural variation versus mutation rate between A and B (open and closed) chromatin compartments. A subset of tumors exhibited depleted regional chromatin contacts at the AR locus, linked to extrachromosomal circular DNA (ecDNA) and worse response to AR signaling inhibitors. We also identified topological subtypes associated with stark differences in methylation structure, gene expression and prognosis. Our data suggested that DNA interactions may predispose to structural variant formation, exemplified by the recurrent TMPRSS2-ERG fusion. This comprehensive integrated sequencing effort represents a unique clinical tumor resource.

Mobile technology growth in Nepal offers promising opportunities for using mobile health (mHealth) interventions to facilitate HIV prevention efforts. However, little is known about access and utilization of communication technology and their willingness to use mHealth for HIV prevention services in Nepal. We conducted a cross-sectional respondent-driven sampling survey of 250 MSM in Kathmandu Valley of Nepal from October to December 2022. We collected information on participant characteristics, HIV risk-related behaviors, ownership, or access to and frequency of use of communication technology (phones, tablets, laptops, and computers), and willingness to use mHealth to access HIV prevention services. Descriptive, bivariate, and multivariate linear regression analyses were performed. Almost all participants had smartphones with the internet (231/250, 92.4%) and accessed the internet daily (219/250, 87.6%) on the smartphone (236/250, 94.4%). The median score for willingness to use mHealth for HIV prevention was 10 (IQR: 3 to 17). Willingness to use mHealth was higher among those participants with a high school or above education (β = 0.223, p = < 0.001), had experienced violence (β = 0.231, p = 0.006), and had moderate to severe depressive symptoms (β = 0.223, p = < 0.001). However, monthly income above NPR 20,000 (USD 150) (β= -0.153, p = 0.008), disclosure of their sexual orientation to anyone (β= -0.159, p = < 0.007), and worry about being negatively judged by health care workers (β= -0.136, p = 0.023) were less willing to use mHealth strategies. The findings from this study suggest that there is a high willingness for utilizing mHealth interventions for HIV prevention in MSM population who are at higher risk of HIV acquisition.

The mechanisms of postacute medical conditions and unexplained symptoms after SARS-CoV-2 infection [Long Covid (LC)] are incompletely understood. There is growing evidence that viral persistence, immune dysregulation, and T cell dysfunction may play major roles. We performed whole-body positron emission tomography imaging in a well-characterized cohort of 24 participants at time points ranging from 27 to 910 days after acute SARS-CoV-2 infection using the radiopharmaceutical agent [18F]F-AraG, a selective tracer that allows for anatomical quantitation of activated T lymphocytes. Tracer uptake in the postacute COVID-19 group, which included those with and without continuing symptoms, was higher compared with prepandemic controls in many regions, including the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. T cell activation in the spinal cord and gut wall was associated with the presence of LC symptoms. In addition, tracer uptake in lung tissue was higher in those with persistent pulmonary symptoms specifically. Increased T cell activation in these tissues was also observed in many individuals without LC. Given the high [18F]F-AraG uptake detected in the gut, we obtained colorectal tissue for in situ hybridization of SARS-CoV-2 RNA and immunohistochemical studies in a subset of five participants with LC symptoms. We identified intracellular SARS-CoV-2 single-stranded spike protein-encoding RNA in rectosigmoid lamina propria tissue in all five participants and double-stranded spike protein-encoding RNA in three participants up to 676 days after initial COVID-19, suggesting that tissue viral persistence could be associated with long-term immunologic perturbations.

Single-cell assay for transposase-accessible chromatin by sequencing (scATAC-seq) has emerged as a powerful tool for dissecting regulatory landscapes and cellular heterogeneity. However, an exploration of systemic biases among scATAC-seq technologies has remained absent. In this study, we benchmark the performance of eight scATAC-seq methods across 47 experiments using human peripheral blood mononuclear cells (PBMCs) as a reference sample and develop PUMATAC, a universal preprocessing pipeline, to handle the various sequencing data formats. Our analyses reveal significant differences in sequencing library complexity and tagmentation specificity, which impact cell-type annotation, genotype demultiplexing, peak calling, differential region accessibility and transcription factor motif enrichment. Our findings underscore the importance of sample extraction, method selection, data processing and total cost of experiments, offering valuable guidance for future research. Finally, our data and analysis pipeline encompasses 169,000 PBMC scATAC-seq profiles and a best practices code repository for scATAC-seq data analysis, which are freely available to extend this benchmarking effort to future protocols.

BACKGROUND: Suicidal thoughts and behaviors (STBs) are prevalent within the Lesbian, Gay, Bisexual, Transgender, and Queers (LGBTQ) community, often exacerbated by challenges in accessing care and the perceived stigma and discrimination tied to disclosing ones identity. Digital health interventions that offer psychosocial self-help present a promising platform to reach individuals at risk of STBs, especially those who may not engage with conventional health services. This review aimed to assess the role of digital-based intervention in reducing STBs among LGBTQ individuals. METHODS: We conducted a systematic literature search from three databases, PsycINFO, PubMed, and CINHAL, from 1st Jan 1990 to 31st December 2023. The review encompassed studies investigating the feasibility, acceptability, and impact of digital interventions on STBs, employing randomized control trials (RCTs), pseudo-RCTs, observational pre-posttest designs, and qualitative studies. Potential bias was evaluated using the McGill Mixed Methods Appraisal Tool (MMAT). RESULTS: Five non-overlapping studies were included, reporting data from 777 participants. The studies featured diverse types of digital interventions, including videos, online writing, and mobile applications. The studies included three RCTs, and two qualitative studies. Across most of these studies, notable enhancements or reductions in the proportion of participants reporting STBs were observed post-intervention, alongside improvements in help-seeking intentions. The findings underscored that the applications used in the studies were engaging, acceptable, and deemed feasible in effectively addressing suicide prevention among the LGBTQ community. CONCLUSION: Overall, digital interventions were found to be feasible and acceptable in suicide prevention among LGBTQ communities, demonstrating preliminary efficacy in increasing help-seeking behavior when experiencing suicidal thoughts and in reducing STBs. Therefore, advocating for widespread promotion and dissemination of digital health interventions is crucial, particularly in low- and middle-income countries (LMICs) with limited access to health services and heightened barriers to obtaining such services. Further research using fully powered RCT is imperative to assess the efficacy of these interventions.