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The Diabetes Remission Clinical Trial (DiRECT) demonstrated that substantial weight loss and remission from type 2 diabetes can be achieved with low-energy total diet replacement and behavioural support. However, the acceptability of the DiRECT intervention in diverse populations with strong cultural emphases on food and shared eating remains unclear. We conducted a qualitative study nested within a pilot randomised controlled trial of DiRECT in one Māori (the Indigenous people of New Zealand) primary care provider in Aotearoa New Zealand. Participants with type 2 diabetes or prediabetes, obesity, and a desire to lose weight were randomised to either dietitian-supported usual care or the dietitian-supported DiRECT intervention for twelve months. The DiRECT intervention included three months of total diet replacement, then food reintroduction and supported weight loss maintenance. At three and twelve months, semi-structured interviews explored the acceptability of DiRECT and participants’ experiences of each intervention. Interview transcripts from 25 participants (aged 48 ± 10 years, 76% female, 78% Māori or Pacific) at three months and 15 participants at twelve months were analysed. Participants viewed their pre-enrolment selves as unhealthy people with poor eating habits and desired professional weight loss support. For DiRECT participants, the total diet replacement phase was challenging but well-received, due to rapid improvements in weight and health. Food reintroduction and weight loss maintenance each presented unique challenges requiring effective strategies and adaptability. All participants considered individualised and empathetic dietetic support crucial to success. Sociocultural factors influencing success were experienced in both interventions: family and social networks provided support and motivation; however, eating-related norms were identified as challenges. The DiRECT intervention was considered an acceptable approach to weight loss in participants with type 2 diabetes or prediabetes with strong cultural emphases on food and shared eating. Our findings highlight the importance of individualised and culturally relevant behavioural support for effective weight loss and weight loss maintenance.

This study aimed to understand how psychological factors affect regular exercise in older adults, hypothesising that trait self-control mediates the relationship between motivation types (intrinsic, extrinsic, and amotivation) and exercise time. In this cross-sectional study, 430 older adults (mean age = 68.8 ± 6.72) completed questionnaires regarding their perceived trait self-control, motivation towards leisure activities, and level of physical activity. A Bayesian mediation analysis was performed, controlling for demographics. We documented positive direct (c′ = 0.021, 95%CI [0.001, 0.043]) and indirect (ab = 0.028, 95%CI [0.014, 0.043]) effects of intrinsic motivation on exercise, a fully mediated indirect effect of extrinsic motivation on exercise (ab = 0.027, 95%CI [0.011, 0.046]), and negative direct (c′ = −0.281, 95%CI [−0.368, −0.194]) and indirect (ab = −0.161, 95%CI [−0.221, −0.105]) effects of amotivation on exercise. There was no direct association between extrinsic motivation and exercise (c′ = 0.013, 95% CI [−0.013, 0.037]). In conclusion, trait self-control mediates motivation to influence exercise behaviour in older adults. Intrinsically motivated individuals resist sedentary living and show higher self-control, while extrinsically motivated ones rely on self-control and are more susceptible to non-adherence during mental fatigue. High amotivation is linked to less exercise and reduced self-control, suggesting potential non-compliance with structured exercise interventions.

Understanding the recharge–discharge system of a catchment is key to the efficient use and effective management of groundwater resources. The present study focused on the estimation of groundwater recharge using Soil Moisture Balance (SMB) and Baseflow Separation (BFS) methods in the Gilgel Gibe catchment where water demand for irrigation, domestic, and industrial purposes is dramatically increasing. The demand for groundwater and the existing ambitious plans to respond to this demand will put a strain on the groundwater resource in the catchment unless prompt intervention is undertaken to ensure its sustainability. Ground-based hydrometeorological 36-years data (1985 to 2020) from 17 stations and satellite products from CHIRPS and NASA/POWER were used for the SMB method. Six BFS methods were applied through the Web-based Hydrograph Analysis Tool (WHAT), SepHydro, BFLOW, and Automated Computer Programming (PART) to sub-catchments and the main catchment to estimate the groundwater recharge. The streamflow data (discharge) obtained from the Ministry of Water and Energy were the main input data for the BFS methods. The average annual recharge of groundwater was estimated to be 313 mm using SMB for the years 1985 to 2020 and 314 mm using BFS for the years 1986 to 2003. The results from the SMB method revealed geographical heterogeneity in annual groundwater recharge, varying from 209 to 442 mm. Significant spatial variation is also observed in the estimated annual groundwater recharge using the BFS methods, which varies from 181 to 411 mm for sub-catchments. Hydrogeological conditions of the catchment were observed, and the yielding capacity of existing wells was assessed to evaluate the validity of the results. The recharge values estimated using SMB and BFS methods are comparable and hydrologically reasonable. The findings remarkably provide insightful information for decision-makers to develop effective groundwater management strategies and to prioritize the sub-catchments for immediate intervention to ensure the sustainability of groundwater.

The cause of childhood hearing impairment (excluding infectious pathology of the middle ear) can be extrinsic (embryofoetopathy, meningitis, trauma, drug ototoxicity, noise trauma, etc [...]

The emergence of remote health monitoring and increased at-home care emphasizes the importance of patient adherence outside the clinical setting. This is particularly pertinent in the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in pediatric patients, as the population inherently has difficulty remembering and initiating treatment tasks. Neurostimulation is an emerging treatment modality for pediatric ADHD and requires strict adherence to a treatment regimen to be followed in an at-home setting. Thus, to achieve the desired therapeutic effect, careful attention must be paid to design features that can passively promote and effectively monitor therapeutic adherence. This work describes instrumentation designed to support a clinical trial protocol that tests whether choice of color, or color itself, can statistically significantly increase adherence rates in pediatric ADHD patients in an extraclinical environment. This is made possible through the development and application of an internet-of-things approach in a remote adherence monitoring technology that can be implemented in forthcoming neurostimulation devices for pediatric patient use. This instrumentation requires minimal input from the user, is durable and resistant to physical damage, and provides accurate adherence data to parents and physicians, increasing assurance that neurostimulation devices are effective for at-home care.

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of prematurity. Postulated mechanisms leading to inflammatory necrosis of the ileum and colon include activation of the pathogen recognition receptor Toll-like receptor 4 (TLR4) and decreased levels of transforming growth factor beta (TGFβ). Extracellular nicotinamide phosphoribosyltransferase (eNAMPT), a novel damage-associated molecular pattern (DAMP), is a TLR4 ligand and plays a role in a number of inflammatory disease processes. To test the hypothesis that eNAMPT is involved in NEC, an eNAMPT-neutralizing monoclonal antibody, ALT-100, was used in a well-established animal model of NEC. Preterm Sprague–Dawley pups delivered prematurely from timed-pregnant dams were exposed to hypoxia/hypothermia and randomized to control—foster mother dam-fed rats, injected IP with saline (vehicle) 48 h after delivery; control + mAB—foster dam-fed rats, injected IP with 10 µg of ALT-100 at 48 h post-delivery; NEC—orally gavaged, formula-fed rats injected with saline; and NEC + mAb—formula-fed rats, injected IP with 10 µg of ALT-100 at 48 h. The distal ileum was processed 96 h after C-section delivery for histological, biochemical, molecular, and RNA sequencing studies. Saline-treated NEC pups exhibited markedly increased fecal blood and histologic ileal damage compared to controls (q < 0.0001), and findings significantly reduced in ALT-100 mAb-treated NEC pups (q < 0.01). Real-time PCR in ileal tissues revealed increased NAMPT in NEC pups compared to pups that received the ALT-100 mAb (p < 0.01). Elevated serum levels of tumor necrosis factor alpha (TNFα), interleukin 6 (IL-6), interleukin-8 (IL-8), and NAMPT were observed in NEC pups compared to NEC + mAb pups (p < 0.01). Finally, RNA-Seq confirmed dysregulated TGFβ and TLR4 signaling pathways in NEC pups that were attenuated by ALT-100 mAb treatment. These data strongly support the involvement of eNAMPT in NEC pathobiology and eNAMPT neutralization as a strategy to address the unmet need for NEC therapeutics.

The rat model of perinatal stress (PRS), in which exposure of pregnant dams to restraint stress reduces maternal behavior, is characterized by a metabolic profile that is reminiscent of the “metabolic syndrome”. We aimed to identify plasma metabolomic signatures linked to long-term programming induced by PRS in aged male rats. This study was conducted in the plasma and frontal cortex. We also investigated the reversal effect of postpartum carbetocin (Cbt) on these signatures, along with its impact on deficits in cognitive, social, and exploratory behavior. We found that PRS induced long-lasting changes in biomarkers of secondary bile acid metabolism in the plasma and glutathione metabolism in the frontal cortex. Cbt treatment demonstrated disease-dependent effects by reversing the metabolite alterations. The metabolomic signatures of PRS were associated with long-term cognitive and emotional alterations alongside endocrinological disturbances. Our findings represent the first evidence of how early life stress may alter the metabolomic profile in aged individuals, thereby increasing vulnerability to CNS disorders. This raises the intriguing prospect that the pharmacological activation of oxytocin receptors soon after delivery through the mother may rectify these alterations.

We report a straightforward alkane elimination strategy to prepare well-defined heterobimetallic Al/Mo species. Notably, the reaction of the monohydride complex of molybdenum, Cp*MoH(CO)3, with triisobutyl aluminum affords a new heterobimetallic [MoAl]2 tetranuclear compound, [Cp*Mo(CO)(µ-CO)2Al(iBu)2]2, (1), featuring a 12-membered C4O4Mo2Al2 ring in which isocarbonyls bridge the Mo and Al centers. The addition of pyridine to this complex successfully results in the dissociation of the dimer into a new discrete binuclear complex, [Cp*Mo(CO)2(µ-CO)Al(Py)(iBu)2], (2). Switching the nature of the Lewis base from pyridine to tetrahydrofuran does not lead to the THF analogue of adduct 2, but rather to a complex reaction where one of the identified products corresponds to a tetranuclear species, [Cp*Mo(CO)3(μ-CH2CH2CH2CH2O)Al(iBu)2]2, (3), featuring two bridging alkoxybutyl fragments originating from the C-O ring opening of THF. Compound 3 adds to the unusual occurrences of THF ring opening by heterobimetallic complexes, which is evocative of masked metal-only frustrated Lewis pair behavior and highlights the high reactivity of these Al/Mo assemblies.

The urgency of responding to climate change for corals necessitates the exploration of innovative methods to swiftly enhance our understanding of crucial processes. In this study, we employ an integrated chemical omics approach, combining elementomics, metabolomics, and volatilomics methodologies to unravel the biochemical pathways associated with the thermal response of the coral symbiont, Symbiodiniaceae Durusdinium trenchii. We outline the complimentary sampling approaches and discuss the standardised data corrections used to allow data integration and comparability. Our findings highlight the efficacy of individual methods in discerning differences in the biochemical response of D. trenchii under both control and stress-inducing temperatures. However, a deeper insight emerges when these methods are integrated, offering a more comprehensive understanding, particularly regarding oxidative stress pathways. Employing correlation network analysis enhanced the interpretation of volatile data, shedding light on the potential metabolic origins of volatiles with undescribed functions and presenting promising candidates for further exploration. Elementomics proves to be less straightforward to integrate, likely due to no net change in elements but rather elements being repurposed across compounds. The independent and integrated data from this study informs future omic profiling studies and recommends candidates for targeted research beyond Symbiodiniaceae biology. This study highlights the pivotal role of omic integration in advancing our knowledge, addressing critical gaps, and guiding future research directions in the context of climate change and coral reef preservation.

Scrapie is a neurodegenerative disease that impacts sheep and goats, characterized by gradual and progressive changes in neurological function. Recent research shows that the scrapie incubation period is significantly influenced by specific variations in amino acids within the prion protein gene (PRNP). The objective of this study was to estimate the national prevalence of caprine PRNP genetic variability at codons 146, 211, and 222 in goat populations across the United States. A total of 3052 blood, ear tissue, and brain tissue samples were collected from goats from 50 states. The participating states were categorized into four Veterinary Service (VS) district regions. The samples underwent DNA extraction, and the PRNP variants corresponding to codons 146, 211, and 222 were amplified and sequenced. The analysis of PRNP variants, when compared to the PRNP reference sequence, revealed seven alleles in twelve genotypes. The homozygous 146NN, 211RR, and 222QQ alleles, which have been linked to an increased risk of scrapie, were found to be the most prevalent among all the goats. The heterozygous 222QK, 211RQ, 146SD, 146ND, and 146NS alleles and the homozygous 222KK, 146SS, and 146DD alleles, known to be associated with reduced scrapie susceptibility and a prolonged incubation period after experimental challenge, were found in 1.098% (222QK), 2.33% (211RQ), 0.58% (146SD), 3.13% (146ND), 20.68% (146NS), 0.005% (222KK), 3.31% (146SS), and 0.67% (146DD) of goats, respectively. The 222QK allele was found most frequently in goats tested from the east (VS District 1, 1.59%) and southwest (VS District 4, 1.08%) regions, whereas the 211RQ allele was found most often in goats tested from the Midwest (VS District 2, 8.03%) and east (VS District 1, 6.53%) regions. The 146NS allele was found most frequently in goats tested from the northwest (VS District 3, 29.02%) and southwest (VS District 4, 20.69%) regions. Our results showed that the prevalence of less susceptible genotypes at PRNP codon 146 may be sufficient to use genetic susceptibility testing in some herds. This may reduce the number of goats removed as part of a herd clean-up plan and may promote the selective breeding goats for less susceptible alleles in high-risk herds at the national level.

UAVs need to communicate along three dimensions (3D) with other aerial vehicles, ranging from above to below, and often need to connect to ground stations. However, wireless transmission in 3D space significantly dissipates power, often hindering the range required for these types of links. Directional transmission is one way to efficiently use available wireless channels to achieve the desired range. While multiple-input multiple-output (MIMO) systems can digitally steer the beam through channel matrix manipulation without needing directional awareness, the power resources required for operating multiple radios on a UAV are often logistically challenging. An alternative approach to streamline resources is the use of phased arrays to achieve directionality in the analog domain, but this requires beam sweeping and results in search-time delay. The complexity and search time can increase with the dynamic mobility pattern of the UAVs in aerial networks. However, if the direction of the receiver is known at the transmitter, the search time can be significantly reduced. In this work, multi-antenna channels between two UAVs in A2A links are analyzed, and based on these findings, an efficient machine learning-based method for estimating the direction of a transmitting node using channel estimates of 4 antennas (2 × 2 MIMO) is proposed. The performance of the proposed method is validated and verified through in-field drone-to-drone measurements. Findings indicate that the proposed method can estimate the direction of the transmitter in the A2A link with 86% accuracy. Further, the proposed direction estimation method is deployable for UAV-based massive MIMO systems to select the directional beam without the need to sweep or search for optimal communication performance.

Dairy milk holds a prominent position as a widely consumed food, particularly among infants and children. However, it is crucial to address the presence of multiple natural toxic compounds that may co-occur in dairy milk to ensure its safety prior to consumption. Aflatoxin M1 (AFM1), an emerging mycotoxin of interest, is a potential contaminant in the milk of animals who ingest aflatoxin B1 (AFB1). The toxin is regulated in the European Union under Commission Regulation No 1881/2006. Unfortunately, there is a notable lack of data concerning the transfer of various emerging microbial contaminants into dairy milk and, therefore, their natural occurrences. In this study, a simple and sensitive LC-MS/MS method was developed and validated for the quantification of multiple cyanotoxins (microcystin congeners and nodularin) and AFM1 by the main analytical guidelines. Toxins are extracted with methanol 80%, followed by an SPE clean-up step before LC-MS/MS analysis. The LOQ was fixed at 1 µg/L for the nine cyanotoxins and 0.05 µg/L for AFM1. Recoveries were measured between 82.67% and 102%. To the best of our knowledge, there are no other LC-MS/MS methods available for the simultaneous quantification of cyanotoxins and mycotoxins in milk.

Engrailed (en) and invected (inv) encode paralogous transcription factors found as a closely linked tandem duplication within holometabolous insects. Drosophila en mutants segment normally, then fail to maintain their segments. Loss of Drosophila inv is viable, while loss of both genes results in asegmental larvae. Surprisingly, the knockdown of Oncopeltus inv can result in the loss or fusion of the entire abdomen and en knockdowns in Tribolium show variable degrees of segmental loss. The consequence of losing or knocking down both paralogs on embryogenesis has not been studied beyond Drosophila. To further investigate the relative functions of each paralog and the mechanism behind the segmental loss, Tribolium double and single knockdowns of en and inv were analyzed. The most common cuticular phenotype of the double knockdowns was small, limbless, and open dorsally, with all but a single, segmentally iterated row of bristles. Less severe knockdowns had fused segments and reduced appendages. The Tribolium paralogs appear to act synergistically: the knockdown of either Tribolium gene alone was typically less severe, with all limbs present, whereas the most extreme single knockdowns mimic the most severe double knockdown phenotype. Morphological abnormalities unique to either single gene knockdown were not found. inv expression was not affected in the Tribolium en knockdowns, but hh expression was unexpectedly increased midway through development. Thus, while the segmental expression of en/inv is broadly conserved within insects, the functions of en and inv are evolving independently in different lineages.

According to the Institute of Medicine, immediate steps must be taken across the United States to educate and train the healthcare workforce to work collaboratively to address the needs of the growing older adult population. The Geriatric Practice Leadership Institute (GPLI) was designed to support professional teams working in acute and post-acute care in transforming their organization into a designated Age-Friendly Health System. The program was built around the Institute for Healthcare Improvement’s Age-Friendly Health Systems 4Ms framework. This framework focuses on What Matters, Medication, Mentation, and Mobility (the 4Ms) in supporting care for older adults. The GPLI program is an online, seven-month team-based program with four to seven participants from one organization per team. Additionally, each team selected, developed, and completed a quality improvement project based on Age-Friendly Health Systems 4Ms. The curriculum also includes organizational culture, leadership, and interprofessional team-building modules. Using a post-completion survey, the experiences of 41 participants in the GPLI program were assessed. All respondents found the information in the program ‘very’ or ‘extremely’ valuable, and their executive sponsor ‘very’ or ‘extremely’ valuable in supporting their team’s involvement and project. The GPLI program has trained over 200 healthcare professionals and teams that have successfully implemented projects across their organizations.

The ability of Mycobacterium bovis (M. bovis) to survive in bovine milk has emerged as a serious public health concern. The first objective of this study was to evaluate the diagnostic utility of IS1081-targeted real-time PCR for the detection of M. bovis DNA in different fractions of bovine milk. In a model study, bovine milk samples were spiked with serially diluted M. bovis BCG to investigate the detection limit of M. bovis DNA in whole milk and milk fractions (cream, pellet, and pellet + cream combined) using IS1081 real-time PCR. The assay was then used to detect M. bovis DNA in whole milk and milk fractions from naturally infected animals. The results showed that the IS1081 real-time PCR was more sensitive when detecting M. bovis DNA in the cream layer alone and cream + pellet combined compared to whole milk or the pellet alone. While PCR-based diagnostic assays for the detection of M. bovis in milk samples provide a quicker diagnostic tool for bovine tuberculosis, safe processing, and handling of M. bovis-infected milk samples remain a challenge and pose a human health risk. PrimeStore Molecular Transport Medium (MTM) has been shown to rapidly inactivate infected specimens while preserving nucleic acid for subsequent Molecular analysis. Therefore, the secondary objective of this study was to evaluate the ability of MTM to inactivate M. bovis BCG in spiked milk samples as well as its ability to preserve BCG DNA for the PCR assay. The results showed that MTM can successfully inactivate BCG alone or in spiked milk samples while preserving DNA for the PCR assay. The CT values of M. bovis BCG alone and spiked milk samples aliquoted in MTM and without MTM were similar at various dilutions. Taken together, our results indicate that using DNA extracted from the milk cream fraction alone or combined milk cream and pellet improved the recovery rate of M. bovis DNA in bovine milk samples. MTM has the potential to provide a safe and rapid sample processing tool for M. bovis inactivation in milk samples and preserve DNA for molecular diagnostics.

Dual-task activities are essential within everyday life, requiring visual–spatial memory (VSM) and mobility skills. Navigational memory is an important component of VSM needed to carry out everyday activities, but this is often not included in traditional tests such as the Corsi block tapping test (CBT). The Walking Corsi Test (WalCT) allows both VSM and navigational memory to be tested together, as well as allowing measures of gait to be collected, thus providing a more complete understanding of dual-task function. The aim of this study was to investigate the effect of an increasingly complex cognitive task on gait in a healthy adult population, using the WalCT and body-worn inertial measurement unit (IMU) sensors. Participants completed both the CBT and WalCT, where they were asked to replicate increasingly complex sequences until they were no longer able to carry this out correctly. IMU sensors were worn on the shins throughout the WalCT to assess changes in gait as task complexity increased. Results showed that there were significant differences in several gait parameters between completing a relatively simple cognitive task and completing a complex task. The type of memory used also appeared to have an impact on some gait variables. This indicates that even within a healthy population, gait is affected by cognitive task complexity, which may limit function in everyday dual-task activities.

The present study aimed to compare NIRS results using freeze-dried ground or not ground (FDG or FDNG) faeces to predict faecal chemical composition and apparent total tract digestibility (ATTD) coefficients. Two different batches of pigs were used (n = 20 mixed sex pens/batch; 11 pigs/pen; Duroc × (Large White × Landrace)). The first batch of pigs (B1; 50.1 ± 3.44 kg body weight (BW)) was used at 13 wks of age and the second batch (B2; 87.0 ± 4.10 kg BW) was used at 18 wks of age. For both B1 and B2, pens were assigned to five diets formulated to obtain a control [10.03 MJ of net energy (NE), 160.0 g of crude protein (CP), and 9.5 g of standardized ileal digestive (SID) lysine (Lys) per kg of feed], low protein (132.0 g CP and 7.5 g SID Lys), high protein (188.0 g CP and 11.5 g SID Lys), low energy (9.61 MJ NE/kg), and high energy (10.45 MJ NE/kg) diets. After a 10-day adaptation period, one faecal sample was collected daily from each pen floor during 6 days in both B1 and B2 (n = 120/batch). Faecal samples were freeze-dried and analysed via NIRS as FDNG and FDG faeces. Dry matter (DM), organic matter (OM), CP, gross energy (GE), fat, and ATTD coefficients were analysed/calculated. The NIRS calibrations were evaluated by cross-validation, splitting the data in four random groups, or using the leave-one-out method. For both FDNG and FDG faeces, coefficients of determination for calibration (R2cv) and residual predictive deviation (RPD) values were: close to 0.9 and 3 for DM and CP, 0.7–0.8 and ≥2 for OM and GE, 0.6 and p < 0.05), while DM and OM ATTD were better predicted using FDNG faeces (p < 0.05). In conclusion, NIRS successfully predicts faeces’ chemical components and ATTD coefficients of nutrients using FDNG or FDG faeces.

The main mode of transmission of Middle East respiratory syndrome-related coronavirus (MERS-CoV) between dromedaries is likely via the respiratory route. However, there must be other modes to explain how the infection is brought to MERS-CoV-negative closed herds, such as transmission by ticks. Here, we present a study performed at three different locations in the United Arab Emirates (UAE) involving 215 dromedary camels (Camelus dromedarius) and the ticks attached to them. We tested the camels and ticks via RT-(q)PCR for the presence of MERS-CoV nucleic acids, as well as flaviviruses that may be present in the region (e.g., Alkhumra hemorrhagic fever virus). Camel sera were additionally analyzed for evidence of previous exposure to MERS-CoV. In total, 8 out of 242 tick pools were positive for MERS-CoV RNA (3.3%; Ct 34.6–38.3), 7 of which contained Hyalomma dromedarii ticks, and one contained a Hyalomma sp. tick (species not identified). All of the virus-positive ticks’ host camels were also positive for MERS-CoV RNA in their nasal swab samples. Short sequences established in the N gene region from two positive tick pools were identical to viral sequences from their hosts’ nasal swabs. In total, 59.3% of dromedaries at the livestock market had MERS-CoV RNA in their nasal swabs (Ct 17.7–39.5). While dromedaries at all locations were negative for MERS-CoV RNA in their serum samples, antibodies were detected in 95.2% and 98.7% of them (tested by ELISA and indirect immunofluorescence test, respectively). Given the probably transient and/or low level of MERS-CoV viremia in dromedaries and the rather high Ct values observed in the ticks, it seems unlikely that Hyalomma dromedarii is a competent vector for MERS-CoV; however, its role in mechanical or fomite transmission between camels should be investigated.

Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10−9) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46, IKBKE, PARK2, ULK4, ATG5, and CDKN2A associated with MM risk (p = 4.47 × 10−4−5.79 × 10−14). Mechanistically, we found that the ULK4rs6599175 SNP correlated with circulating concentrations of vitamin D3 (p = 4.0 × 10−4), whereas the IKBKErs17433804 SNP correlated with the number of transitional CD24+CD38+ B cells (p = 4.8 × 10−4) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (p = 3.6 × 10−4). We also found that the CD46rs1142469 SNP correlated with numbers of CD19+ B cells, CD19+CD3− B cells, CD5+IgD− cells, IgM− cells, IgD−IgM− cells, and CD4−CD8− PBMCs (p = 4.9 × 10−4−8.6 × 10−4) and circulating concentrations of interleukin (IL)-20 (p = 0.00082). Finally, we observed that the CDKN2Ars2811710 SNP correlated with levels of CD4+EMCD45RO+CD27− cells (p = 9.3 × 10−4). These results suggest that genetic variants within these six loci influence MM risk through the modulation of specific subsets of immune cells, as well as vitamin D3−, MCP-2−, and IL20-dependent pathways.

Racehorse welfare is a prominent, public issue which affects nearly every aspect of the racing industry. Thoroughbred care after race career completion has garnered increasing attention from the equine industry, general public, and animal welfare groups alike. As the average racehorse’s career lasts just 4.5 years, owner demand for thoroughbreds is essential for post-race careers and acceptable welfare standards. This study utilized data from and hedonic pricing models to analyze buyer demand for thoroughbreds sold in online auctions held from 2012 to 2020. The results indicate buyer preferences for age (p < 0.01), sex (p < 0.05), and organization registration (p < 0.05), with bid price premiums for age and registration status (USEF, USEA, USHJA, etc.) and price discounts for mares compared to geldings and horses listed for non-competition careers (trail, p < 0.01). The results of this study confirm and quantify the value potential buyers place on thoroughbreds offered for sale in sport disciplines. The findings may help non-profit organizations charged with rehoming off the track thoroughbreds and reduce the number of unwanted thoroughbreds by illustrating the desired traits and skills within the equine market, thus improving welfare optics overall.

Bacteria use an array of sigma factors to regulate gene expression during different stages of their life cycles. Full-length, atomic-level structures of sigma factors have been challenging to obtain experimentally as a result of their many regions of intrinsic disorder. AlphaFold has now supplied plausible full-length models for most sigma factors. Here we discuss the current understanding of the structures and functions of sigma factors in the model organism, Bacillus subtilis, and present an X-ray crystal structure of a region of B. subtilis SigE, a sigma factor that plays a critical role in the developmental process of spore formation.

Rare sugars have recently attracted attention as potential sugar replacers. Understanding the biochemical and biological behavior of these sugars is of importance in (novel) food formulations and prevention of type 2 diabetes. In this study, we investigated whether rare sugars may positively affect intestinal and liver metabolism, as well as muscle insulin sensitivity, compared to conventional sugars. Rare disaccharide digestibility, hepatic metabolism of monosaccharides (respirometry) and the effects of sugars on skeletal muscle insulin sensitivity (impaired glucose uptake) were investigated in, respectively, Caco-2, HepG2 and L6 cells or a triple coculture model with these cells. Glucose and fructose, but not l-arabinose, acutely increased extracellular acidification rate (ECAR) responses in HepG2 cells and impaired glucose uptake in L6 cells following a 24 h exposure at 28 mM. Cellular bioenergetics and digestion experiments with Caco-2 cells indicate that especially trehalose (α1-1α), D-Glc-α1,2-D-Gal, D-Glc-α1,2-D-Rib and D-Glc-α1,3-L-Ara experience delayed digestion and reduced cellular impact compared to maltose (α1-4), without differences on insulin-stimulated glucose uptake in a short-term setup with a Caco-2/HepG2/L6 triple coculture. These results suggest a potential for l-arabinose and specific rare disaccharides to improve metabolic health; however, additional in vivo research with longer sugar exposures should confirm their beneficial impact on insulin sensitivity in humans.

The majority of emerging viral infectious diseases in humans originate from wildlife reservoirs, such as rodents and bats. We investigated a possible reservoir, namely wild gerbils and mice trapped in a desert reserve within the emirate of Dubai, United Arab Emirates (UAE). In total, 52 gerbils and 1 jird (Gerbillinae), 10 house mice (Mus musculus), and 1 Arabian spiny mouse (Acomys dimidiatus) were sampled. Oro-pharyngeal swabs, fecal samples, attached ticks, and organ samples (where available) were screened by (RT-q)PCR for the following viruses: Middle East respiratory syndrome-related coronavirus, Crimean-Congo hemorrhagic fever orthonairovirus, Alkhumra hemorrhagic fever virus, hantaviruses, Lymphocytic choriomeningitis mammarenavirus, Rustrela virus, poxviruses, flaviviruses, and herpesviruses. All of the samples were negative for all investigated viruses, except for herpesviruses: 19 gerbils (35.8%) and seven house mice (70.0%) were positive. The resulting sequences were only partly identical to sequences in GenBank. Phylogenetic analysis revealed three novel betaherpesviruses and four novel gammaherpesviruses. Interestingly, species identification of the positive gerbils resulted in eight individuals clustering in a separate clade, most closely related to Dipodillus campestris, the North African gerbil, indicating either the expansion of the geographic range of this species, or the existence of a closely related, yet undiscovered species in the UAE. In conclusion, we could not find evidence of persistence or shedding of potentially zoonotic viruses in the investigated rodent cohorts of limited sample size.

Candida auris is a novel and emerging pathogenic yeast which represents a serious global health threat. Since its first description in Japan 2009, it has been associated with large hospital outbreaks all over the world and is often resistant to more than one antifungal drug class. To date, five C. auris isolates have been detected in Austria. Morphological characterization and antifungal susceptibility profiles against echinocandins, azoles, polyenes and pyrimidines, as well as the new antifungals ibrexafungerp and manogepix, were determined. In order to assess pathogenicity of these isolates, an infection model in Galleria mellonella was performed and whole genome sequencing (WGS) analysis was conducted to determine the phylogeographic origin. We could characterize four isolates as South Asian clade I and one isolate as African clade III. All of them had elevated minimal inhibitory concentrations to at least two different antifungal classes. The new antifungal manogepix showed high in vitro efficacy against all five C. auris isolates. One isolate, belonging to the African clade III, showed an aggregating phenotype, while the other isolates belonging to South Asian clade I were non-aggregating. In the Galleria mellonella infection model, the isolate belonging to African clade III exhibited the lowest in vivo pathogenicity. As the occurrence of C. auris increases globally, it is important to raise awareness to prevent transmission and hospital outbreaks.

Failure due to cracks is a major structural safety issue for engineering constructions. Human examination is the most common method for detecting crack failure, although it is subjective and time-consuming. Inspection of civil engineering structures must include crack detection and categorization as a key component of the process. Images can automatically be classified using convolutional neural networks (CNNs), a subtype of deep learning (DL). For image categorization, a variety of pre-trained CNN architectures are available. This study assesses seven pre-trained neural networks, including GoogLeNet, MobileNet-V2, Inception-V3, ResNet18, ResNet50, ResNet101, and ShuffleNet, for crack detection and categorization. Images are classified as diagonal crack (DC), horizontal crack (HC), uncracked (UC), and vertical crack (VC). Each architecture is trained with 32,000 images equally divided among each class. A total of 100 images from each category are used to test the trained models, and the results are compared. Inception-V3 outperforms all the other models with accuracies of 96%, 94%, 92%, and 96% for DC, HC, UC, and VC classifications, respectively. ResNet101 has the longest training time at 171 min, while ResNet18 has the lowest at 32 min. This research allows the best CNN architecture for automatic detection and orientation of cracks to be selected, based on the accuracy and time taken for the training of the model.

The management and monitoring of the quality of water resources in the Mekelle area are challenging, due to both geogenic and anthropogenic impacts. The extent of these impacts and the sources of pollution in this area have not been thoroughly investigated. In this article, a mapping of water resources vulnerability was carried out using the DRASTIC method and a modified DRASTIC vulnerability map was produced. Single-parameter and map-removal sensitivity analyses were performed on the relevant rates and weights. A final DRASTIC vulnerability index, varying from 54 to 140, was divided into four vulnerability classes: low (225.7 km2), medium (302.8 km2), high (307.2 km2), and very high (187.6 km2); the values in the parentheses indicate the corresponding areal coverage of each class. Similarly, a modified DRASTIC vulnerability index, ranging from 91 to 192, was divided into four vulnerability classes: low (166.4 km2), medium (266.8 km2), high (338.0 km2), and very high (252.2 km2) Nitrates were used to validate both models. in which moderate positive correlations (with Pearson’s correlation coefficient, r) of 0.681 and 0.702 were calculated for the DRASTIC and modified DRASTIC indices, respectively. A comparison of the two maps showed that significant sources of pollution are located in areas with high to very high vulnerability. The results of this research work can be used for the protection and monitoring of groundwater resources in the Mekelle area.

Urban environments represent unique ecosystems where dense human populations may come into contact with wildlife species, some of which are established or potential reservoirs for zoonotic pathogens that cause human diseases. Finding practical ways to monitor the presence and/or abundance of zoonotic pathogens is important to estimate the risk of spillover to humans in cities. As brown rats (Rattus norvegicus) are ubiquitous in urban habitats, and are hosts of several zoonotic viruses, we conducted longitudinal sampling of brown rats in Vienna, Austria, a large population center in Central Europe. We investigated rat tissues for the presence of several zoonotic viruses, including flaviviruses, hantaviruses, coronaviruses, poxviruses, hepatitis E virus, encephalomyocarditis virus, and influenza A virus. Although we found no evidence of active infections (all were negative for viral nucleic acids) among 96 rats captured between 2016 and 2018, our study supports the findings of others, suggesting that monitoring urban rats may be an efficient way to estimate the activity of zoonotic viruses in urban environments.

The objective of this scoping review was to describe and characterize the existing literature regarding umbilical health and identify gaps in knowledge. Six databases were searched for studies examining umbilical health in an intensively raised cattle population. There were 4249 articles initially identified; from these, 723 full text articles were then screened, with 150 articles included in the review. Studies were conducted in the USA (n = 41), Brazil (n = 24), Canada (n = 13), UK (n = 10), and 37 additional countries. Seventeen were classified as descriptive, 24 were clinical trials, and 109 were analytical observational studies. Umbilical outcomes evaluated in descriptive studies were infection (n = 11), parasitic infection (n = 5), and hernias (n = 2). Of the clinical trials, only one examined treatment of navel infections; the remainder evaluated preventative management factors for navel health outcomes (including infections (n = 17), myiasis (n = 3), measurements (n = 5), hernias (n = 1), and edema (n = 1)). Analytical observational studies examined risk factors for umbilical health (n = 60) and umbilical health as a risk factor (n = 60). Studies examining risk factors for umbilical health included navel health outcomes of infections (n = 28; 11 of which were not further defined), hernias (n = 8), scoring the navel sheath/flap size (n = 16), myiasis (n = 2), and measurements (n = 6). Studies examining umbilical health as a risk factor defined these risk factors as infection (n = 39; of which 13 were not further defined), hernias (n = 8; of which 4 were not further defined), navel dipping (n = 12), navel/sheath scores as part of conformation classification for breeding (n = 2), measurements (n = 3), and umbilical cord drying times (n = 2). This review highlights the areas in need of future umbilical health research such as clinical trials evaluating the efficacy of different treatments for umbilical infection. It also emphasizes the importance for future studies to clearly define umbilical health outcomes of interest, and consider standardization of these measures, including time at risk.

Human cytochrome P450 CYP3A4 is involved in the processing of more than 35% of current pharmaceuticals and therefore is responsible for multiple drug-drug interactions (DDI). In order to develop a method for the detection and prediction of the possible involvement of new drug candidates in CYP3A4-mediated DDI, we evaluated the application of midazolam (MDZ) as a probe substrate. MDZ is hydroxylated by CYP3A4 in two positions: 1-hydroxy MDZ formed at lower substrate concentrations, and up to 35% of 4-hydroxy MDZ at high concentrations. The ratio of the formation rates of these two products (the site of metabolism ratio, SOM) was used as a measure of allosteric heterotropic interactions caused by effector molecules using CYP3A4 incorporated in lipid nanodiscs. The extent of the changes in the SOM in the presence of effectors is determined by chemical structure and is concentration-dependent. MD simulations of CYP3A4 in the lipid bilayer suggest that experimental results can be explained by the movement of the F-F’ loop and concomitant changes in the shape and volume of the substrate-binding pocket. As a result of PGS binding at the allosteric site, several residues directly contacting MDZ move away from the substrate molecule, enabling the repositioning of the latter for minor product formation.

This study aimed to assess baseline levels of coughing on a farm free of respiratory disease, and to identify relationships between environmental conditions and coughing frequency in finisher pigs. Six replicates were conducted (690 pigs in total). A cross-correlation analysis was performed and lags of the predictor variables were carried forward for multivariable regression analysis when significant and showing r > 0.25. Results show that coughing frequency was overall low. In the first replicate, coughing was best predicted by exposure to higher ammonia concentrations that occurred with a lag of 1, 7, and 15 days (p = 0.003, p = 0.001, and p < 0.001, respectively), while in the sixth replicate coughing frequency was best predicted by the exposure to lower relative humidity and higher ventilation rates with a lag of 7 and 15 days (p < 0.001 and p = 0.003, respectively). Ammonia concentrations varied according to ventilation rates recorded on the same day (r > −0.70). In conclusion, guidelines on coughing levels in healthy pigs and calibration of the alarm systems of tools that measure coughing frequency can be extrapolated from this study. Environmental risk factors are associated with the respiratory health of finisher pigs.

This study investigates the effects of space allowance (SA), mixing and phase feeding (PF) on performance of grower-finisher pigs. Three trials (T) were conducted. In T1 and T2, 345 pigs/trial were moved to finisher stage at 11 weeks of age and assigned to two SAs: 0.96 (n = 15 pens; 10 pigs/pen) and 0.78 (n = 15; 13 pigs/pen) m2/pig. Mixing was applied to 5 pens of each SA leading to a 2 × 2 factorial arrangement (SA × Mixing). For PF, 2 diets with 0.95 and 0.82 g SID Lys/MJ NE were applied to 5 pens of each SA (not mixed) leading to another 2 × 2 factorial arrangement (SA × PF). In T3, 230 pigs were moved to the grower-finisher stage at 11 weeks of age, mixed, and assigned to 4 treatments (SA × PF; n = 5 pens). Data were analyzed using general linear mixed models. SA did not affect performance (p > 0.05). Non-mixed pigs were 5.40 (T1) and 5.25 (T2) kg heavier than mixed pigs at 21 weeks of age (p < 0.001). PF reduced performance of pigs by 3.45 (T1) and 4.05 (T2) kg at 21 weeks of age (p < 0.001). In conclusion, mixing and reducing SID Lys:NE ratio from 0.95 to 0.82 g/MJ at 15–16 weeks of age, have a more marked impact on performance than reducing SA from 0.96 to 0.78 m2/pig.

People in the southwestern (SW) coastal part of Bangladesh are suffering from a severe freshwater crisis due to saline groundwater at a shallow depth. Fresh groundwater below a 200 m depth is an option, but it is costly to construct deep tubewells for the local inhabitants. The processes of salinization and freshening were previously identified using conventional methods. In this study, we brought new insight into these processes by analyzing existing datasets using multivariate statistics to identify the factors affecting groundwater chemistry. Cluster analysis (CA) revealed three major clusters. Cluster A corresponded to saline (NaCl-type) water. Cluster B was also saline (NaCl-type) water but showed mixing effects. Cluster C was fresh groundwater (NaHCO3-type) and isolated. The hydrochemical characteristics of clusters A, B and C compared remarkably well with the groundwaters from the upper shallow aquifer (USA), lower shallow aquifer (LSA) and deep aquifer (DA), respectively. Factor analysis (FA) showed that 75% of the total variance was influenced by evaporate dissolution, carbonate dissolution/precipitation, cation exchange and anthropogenic pollution to some extent. Therefore, the integrated approach showed the validity of applying multivariate statistical techniques to infer the dominant hydrochemistry and to characterize and understand a complicated hydrogeological system.

Empirical formulas to estimate the radius of influence, such as the Sichardt formula, occasionally appear in studies assessing the environmental impact of groundwater extractions. As they are inconsistent with fundamental hydrogeological principles, the term “radius of influence myth” is used by analogy with the water budget myth. Alternative formulations based on the well-known de Glee and Theis equations are presented, and the contested formula that estimates the radius of influence by balancing pumping and infiltration rate is derived from an asymptotic solution of an analytical model developed by Ernst in 1971. The transient state solution of this model is developed applying the Laplace transform, and it is verified against the finite-difference solution. Examining drawdown and total storage change reveals the relations between the presented one-dimensional radial flow solutions. The assumptions underlying these solutions are discussed in detail to show their limitations and to refute misunderstandings about their applicability. The discussed analytical models and the formulas derived from it to estimate the radius of influence cannot be regarded as substitutes for advanced modeling, although they offer valuable insights on relevant parameter combinations.

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease worldwide and is impacted by an unhealthy diet with excessive calories, although the role of sugars in NAFLD etiology remains largely unexplored. Rare sugars are natural sugars with alternative monomers and glycosidic bonds, which have attracted attention as sugar replacers due to developments in enzyme engineering and hence an increased availability. We studied the impact of (rare) sugars on energy production, liver cell physiology and gene expression in human intestinal colorectal adenocarcinoma (Caco-2) cells, hepatoma G2 (HepG2) liver cells and a coculture model with these cells. Fat accumulation was investigated in the presence of an oleic/palmitic acid mixture. Glucose, fructose and galactose, but not mannose, l-arabinose, xylose and ribose enhanced hepatic fat accumulation in a HepG2 monoculture. In the coculture model, there was a non-significant trend (p = 0.08) towards higher (20–55% increased) median fat accumulation with maltose, kojibiose and nigerose. In this coculture model, cellular energy production was increased by glucose, maltose, kojibiose and nigerose, but not by trehalose. Furthermore, glucose, fructose and l-arabinose affected gene expression in a sugar-specific way in coculture HepG2 cells. These findings indicate that sugars provide structure-specific effects on cellular energy production, hepatic fat accumulation and gene expression, suggesting a health potential for trehalose and l-arabinose, as well as a differential impact of sugars beyond the distinction of conventional and rare sugars.

Prostate cancer (PCa) is the major cause of cancer-related death in males; however, effective treatments to prevent aggressive progression remain an unmet need. We have previously demonstrated that secreted extracellular nicotinamide phosphoribosyltransferase (eNAMPT) is a multifunctional innate immunity regulator that promotes PCa invasion. In the current study, we further investigate the therapeutic effects of an eNAMPT-neutralizing humanized monoclonal antibody (ALT-100 mAb) in preclinical PCa orthotopic xenograft models. We utilized human aggressive PCa cells (DU145 or PC3) for prostate implantation in SCID mice receiving weekly intraperitoneal injections of either ALT-100 mAb or IgG/PBS (control) for 12 weeks. Prostatic tumors and solid organs were examined for tumor growth, invasion, and metastasis and for biochemical and immunohistochemistry evidence of NFκB activation. ALT-100 mAb treatment significantly improved overall survival of SCID mice implanted with human PCa orthotopic prostate xenografts while inducing tumor necrosis, decreasing PCa proliferation and reducing local invasion and distal metastases. The ALT-100 mAb inhibits NFκB phosphorylation and signaling in PCa cells both in vitro and in vivo. This study demonstrates that eNAMPT neutralization effectively prevents human PCa aggressive progression in preclinical models, indicating its high potential to directly address the unmet need for an effective targeted therapy for patients with aggressive PCa.

Dromedaries are an important livestock, used as beasts of burden and for meat and milk production. However, they can act as an intermediate source or vector for transmitting zoonotic viruses to humans, such as the Middle East respiratory syndrome coronavirus (MERS-CoV) or Crimean–Congo hemorrhagic fever virus (CCHFV). After several outbreaks of CCHFV in the Arabian Peninsula, recent studies have demonstrated that CCHFV is endemic in dromedaries and camel ticks in the United Arab Emirates (UAE). There is no apparent disease in dromedaries after the bite of infected ticks; in contrast, fever, myalgia, lymphadenopathy, and petechial hemorrhaging are common symptoms in humans, with a case fatality ratio of up to 40%. We used the in-solution hybridization capture of 100 annotated immune genes to genotype 121 dromedaries from the UAE tested for seropositivity to CCHFV. Through univariate linear regression analysis, we identified two candidate genes belonging to the innate immune system: FCAR and CLEC2B. These genes have important functions in the host defense against viral infections and in stimulating natural killer cells, respectively. This study opens doors for future research into immune defense mechanisms in an enzootic host against an important zoonotic disease.

Several studies have shown that type IV fibrocytes, located in the spiral ligament, degenerate first after noise exposure. Interestingly, this is the region where Coch expression is most abundant. As it is suggested that cochlin plays a role in our innate immune system, our goal is to investigate hearing thresholds and inner ear inflammation after noise exposure in Coch knockout (Coch−/−) mice compared to Coch wildtype (Coch+/+) mice. Animals were randomly allocated to a noise exposure group and a control group. Vestibular and auditory testing was performed at 48 h and one week after noise exposure. Whole mount staining and cryosectioning of the cochlea was performed in order to investigate hair cells, spiral ganglion neurons, inner ear inflammation, Coch expression and fibrocyte degeneration. Hearing assessment revealed that Coch+/+ mice had significantly larger threshold shifts than Coch−/− mice after noise exposure. We were unable to identify any differences in hair cells, neurons, fibrocytes and influx of macrophages in the inner ear between both groups. Interestingly, Coch expression was significantly lower in the group exposed to noise. Our results indicate that the absence of Coch has a protective influence on hearing thresholds after noise exposure, but this is not related to reduced inner ear inflammation in the knockout.

The potential of supercritical CO2 (SC-CO2) for the extraction of bioactive compounds from mango by-products was assessed. Carotenoid extraction was optimized using a design of experiments based on temperature (35, 55 and 70 °C), pressure (10 and 35 MPa) and co-solvent addition (0%, 10% and 20% of ethanol or acetone). Moreover, the co-extraction of phenolic acids, flavonoids and xanthonoids was evaluated in a subset of parameters. Finally, a comparison was made between SC-CO2 and a two-step organic solvent extraction of the bioactive compounds from the pulp and peel fractions of two Ecuadorian varieties. The optimal extraction temperature was found to be dependent on the bioactive type, with phenolics requiring higher temperature than carotenoids. The optimal overall conditions, focused on maximal carotenoids recovery, were found to be 55 °C, 35 MPa and 20% of ethanol. The main carotenoid was β-carotene, while phenolics differed among the varieties. The bioactive content of the peel was up to 4.1-fold higher than in the pulp fraction. Higher antioxidant activity was found in the extracts obtained with organic solvents. SC-CO2 is a promising technology for the isolation of valuable compounds from mango by-products.

The global spread of ticks and various tick-borne viruses (TBVs) suggests the possibility of new tick-borne diseases emerging. Crimean-Congo hemorrhagic fever virus (CCHFV) is an emerging TBV of the Nairoviridae family that causes serious disease that can be fatal in humans. CCHFV endemic foci can be found in Africa, Asia, the Middle East, and South-Eastern Europe, and has spread to previously unaffected regions and nations, such as Spain, over the last two decades. In this review, we discuss the current situation of CCHFV in Asia, Africa and Europe based on existing knowledge, and we discuss driving factors in the distribution and transmission of the virus, such as the spread of tick vector species and host reservoirs.

Insufficiency of potable water is acute in southwest (SW) coastal areas of Bangladesh. The local population ignores the depth to saltwater/freshwater interface causing many unsuccessful waters wells drilling. In this context, a combined use of borehole logs, geophysical well logs, vertical electrical soundings (VES), electrical resistivity tomography (ERT) and electrical conductivity (EC) of sampled waters was performed to identify saltwater/freshwater interface depths in this coastal part. The study shows that the depth to freshwater/saltwater interface varies from place to place occurring commonly between 190 to 285 m, and locally as shallow as 146 m. The shallow freshwater/saltwater interface depth is greatly influenced by the upconing of fresh water from the deep aquifer (DA) near the major rivers and coast compared to the landward part and is mixed with more saline waters above. Vertically infiltrated saltwater is the main cause of brackish water in the upper shallow aquifer (USA), which is hydraulically connected with the lower shallow aquifer (LSA), and not directly recharged from the Bay of Bengal in the south. The study will contribute to find out the depth of the potential freshwater aquifer and assess the aquifer vulnerability in the coastal area of SW Bangladesh.

Many immunotherapies rely on CD8+ effector T cells to recognize and kill cognate tumor cells. These T cell-based immunotherapies include adoptive cell therapy, such as CAR T cells or transgenic TCR T cells, and anti-cancer vaccines which expand endogenous T cell populations. Tumor mutation burden and the choice of antigen are among the most important aspects of T cell-based immunotherapies. Here, we highlight various classes of cancer antigens, including self, neojunction-derived, human endogenous retrovirus (HERV)-derived, and somatic nucleotide variant (SNV)-derived antigens, and consider their utility in T cell-based immunotherapies. We further discuss the respective anti-tumor/anti-self-properties that influence both the degree of immunotolerance and potential off-target effects associated with each antigen class.

Rodents (order Rodentia), followed by bats (order Chiroptera), comprise the largest percentage of living mammals on earth. Thus, it is not surprising that these two orders account for many of the reservoirs of the zoonotic RNA viruses discovered to date. The spillover of these viruses from wildlife to human do not typically result in pandemics but rather geographically confined outbreaks of human infection and disease. While limited geographically, these viruses cause thousands of cases of human disease each year. In this review, we focus on three questions regarding zoonotic viruses that originate in bats and rodents. First, what biological strategies have evolved that allow RNA viruses to reside in bats and rodents? Second, what are the environmental and ecological causes that drive viral spillover? Third, how does virus spillover occur from bats and rodents to humans?

Alpha-synuclein (α-syn) and leucine-rich repeat kinase 2 (LRRK2) play crucial roles in Parkinson’s disease (PD). They may functionally interact to induce the degeneration of dopaminergic (DA) neurons via mechanisms that are not yet fully understood. We previously showed that the C-terminal portion of LRRK2 (ΔLRRK2) with the G2019S mutation (ΔLRRK2G2019S) was sufficient to induce neurodegeneration of DA neurons in vivo, suggesting that mutated LRRK2 induces neurotoxicity through mechanisms that are (i) independent of the N-terminal domains and (ii) “cell-autonomous”. Here, we explored whether ΔLRRK2G2019S could modify α-syn toxicity through these two mechanisms. We used a co-transduction approach in rats with AAV vectors encoding ΔLRRK2G2019S or its “dead” kinase form, ΔLRRK2DK, and human α-syn with the A53T mutation (AAV-α-synA53T). Behavioral and histological evaluations were performed at 6- and 15-weeks post-injection. Results showed that neither form of ΔLRRK2 alone induced the degeneration of neurons at these post-injection time points. By contrast, injection of AAV-α-synA53T alone resulted in motor signs and degeneration of DA neurons. Co-injection of AAV-α-synA53T with AAV-ΔLRRK2G2019S induced DA neuron degeneration that was significantly higher than that induced by AAV-α-synA53T alone or with AAV-ΔLRRK2DK. Thus, mutated α-syn neurotoxicity can be enhanced by the C-terminal domain of LRRK2G2019 alone, through cell-autonomous mechanisms.

Digital agriculture services can greatly assist growers to monitor their fields and optimize their use throughout the growing season. Thus, knowing the exact location of fields and their boundaries is a prerequisite. Unlike property boundaries, which are recorded in local council or title records, field boundaries are not historically recorded. As a result, digital services currently ask their users to manually draw their field, which is time-consuming and creates disincentives. Here, we present a generalized method, hereafter referred to as DECODE (DEtect, COnsolidate, and DElinetate), that automatically extracts accurate field boundary data from satellite imagery using deep learning based on spatial, spectral, and temporal cues. We introduce a new convolutional neural network (FracTAL ResUNet) as well as two uncertainty metrics to characterize the confidence of the field detection and field delineation processes. We finally propose a new methodology to compare and summarize field-based accuracy metrics. To demonstrate the performance and scalability of our method, we extracted fields across the Australian grains zone with a pixel-based accuracy of 0.87 and a field-based accuracy of up to 0.88 depending on the metric. We also trained a model on data from South Africa instead of Australia and found it transferred well to unseen Australian landscapes. We conclude that the accuracy, scalability and transferability of DECODE shows that large-scale field boundary extraction based on deep learning has reached operational maturity. This opens the door to new agricultural services that provide routine, near-real time field-based analytics.

Attention deficit hyperactivity disorder (ADHD) is a pervasive condition affecting persons across all age groups, although it is primarily diagnosed in children. This neurological condition affects behavior, learning, and social adjustment and requires specific symptomatic criteria to be fulfilled for diagnosis. ADHD may be treated with a combination of psychological or psychiatric therapeutic interventions, but it often goes unattended. People with ADHD face societal bias challenges that impact how they manage the disorder and how they view themselves. This paper summarizes the present state of understanding of this disorder, with particular attention to early diagnosis and innovative therapeutic intervention. Contemporary understanding of the mind–brain duality allows for innovative therapeutic interventions based on neurological stimulation. This paper introduces the concept of neurostimulation as a therapeutic intervention for ADHD and poses the question of the relationship between patient adherence to self-administered therapy and the aesthetic design features of the neurostimulation device. By fabricating devices that go beyond safety and efficacy to embrace the aesthetic preferences of the patient, it is proposed that there will be improvements in patient adherence to a device intended to address ADHD.

Dhaka city has emerged as the fastest-growing megacity, having more than 20 million inhabitants, with a growth rate of 3.62%. Unplanned and rapid urbanization, coupled with exponential population growth, has significantly altered the groundwater dynamics in Dhaka city. This study concentrates on the evolution of long-term piezometric heads of the Upper Dupi Tila aquifer (UDA) and the Middle Dupi Tila aquifer (MDA) based on long-term hydrographs, piezometric maps and synthetic graphical overviews of piezometric trends. Due to over-exploitation, the piezometric level (PL) has declined deeper than −85 and −65 m PWD (Public Works Department reference datum) in UDA and MDA, respectively. The highest rate of decline was observed in the south-central to southeastern parts of the city both in UDA (4.0 m/year) and MDA (5.74 m/year). The results clearly show that the rates of decline in PL vary from 2.25 to 5.74 m/year in both aquifers of the city, and urban expansion has greatly affected the shape and extent of the depression cone over the past four decades. The magnitudes of the depression cones in both aquifers seem to pose a considerable threat to groundwater resources, indicating that the current exploitation is not sustainable at all.

The recent SARS-CoV-2 pandemic has refocused attention to the betacoronaviruses, only eight years after the emergence of another zoonotic betacoronavirus, the Middle East respiratory syndrome coronavirus (MERS-CoV). While the wild source of SARS-CoV-2 may be disputed, for MERS-CoV, dromedaries are considered as source of zoonotic human infections. Testing 100 immune-response genes in 121 dromedaries from United Arab Emirates (UAE) for potential association with present MERS-CoV infection, we identified candidate genes with important functions in the adaptive, MHC-class I (HLA-A-24-like) and II (HLA-DPB1-like), and innate immune response (PTPN4, MAGOHB), and in cilia coating the respiratory tract (DNAH7). Some of these genes previously have been associated with viral replication in SARS-CoV-1/-2 in humans, others have an important role in the movement of bronchial cilia. These results suggest similar host genetic pathways associated with these betacoronaviruses, although further work is required to better understand the MERS-CoV disease dynamics in both dromedaries and humans.

The Lake Tana Basin, comprising the largest natural lake in Ethiopia, is the source and the uppermost part of the Upper Blue Nile Basin. In this review paper, research papers, mainly on the rainfall-runoff modeling and lake water balance, and on the hydrogeology, have been reviewed. The earlier water balance estimation attempts used simple conceptual and statistical approaches and calculate on a monthly timescale. More recent research has been using advanced semi-physically or physically based distributed hydrological models. Accordingly, mean annual precipitation over the lake was estimated in the range 36.1–53.1%; lake evaporation at 45.3–57.5%; river inflow (all gauged and estimated ungauged) at 43.6–63.9%; and river (lake) water outflow at 0–9.2%. With the few isotope studies, groundwater inflow and outflow are found insignificant. Different studies had estimated groundwater recharge, ranging from 57 mm to 850 mm. The basin has a heterogenous aquifer system consisting of different volcanic rocks and alluvio-lacustrine sediments. Generally, groundwater with low TDS, Ca–Mg–HCO3 type, isotopically relatively enriched, and high TDS, Na–HCO3 type, isotopically relatively depleted, water types have been identified. In this paper, major research gaps such as aquifer hydraulic characterization, surface-groundwater interaction, groundwater flow and groundwater balance have been identified. Hence, future research shall focus on the groundwater resources, so that existing surface water studies are updated and future water usage options are explored.

Chronic obstructive airway diseases are characterized by airflow obstruction and airflow limitation as well as chronic airway inflammation. Especially bronchial asthma and chronic obstructive pulmonary disease (COPD) cause considerable morbidity and mortality worldwide, can be difficult to treat, and ultimately lack cures. While there are substantial knowledge gaps with respect to disease pathophysiology, our awareness of the role of neurological and neuro-immunological processes in the development of symptoms, the progression, and the outcome of these chronic obstructive respiratory diseases, is growing. Likewise, the role of pathogenic and colonizing microorganisms of the respiratory tract in the development and manifestation of asthma and COPD is increasingly appreciated. However, their role remains poorly understood with respect to the underlying mechanisms. Common bacteria and viruses causing respiratory infections and exacerbations of chronic obstructive respiratory diseases have also been implicated to affect the local neuro-immune crosstalk. In this review, we provide an overview of previously described neuro-immune interactions in asthma, COPD, and respiratory infections that support the hypothesis of a neuro-immunological component in the interplay between chronic obstructive respiratory diseases, respiratory infections, and respiratory microbial colonization.

Puumala orthohantavirus (PUUV) has a wide distribution throughout Europe. Distinctive temporal patterns of spillover into the human population are related to population dynamics of the reservoir host, the bank vole (Clethrionomys glareolus). As the rodent host is tied to specific habitats with small individual ranges, PUUV genetic diversity is also highly correlated with geographic distance. Using sequenced portions of viral S and M segments, we determined whether geographic clusters were supported. Human cases of PUUV infections are concentrated in southeastern Austria. We detected four distinct genotypes: two genotypes of the Alpe-Adria (ALAD) lineage typically associated with southeast Europe, and two sublineages of the Central Europe (CE) lineage. One cluster of CE genotypes represents a phylogenetically distinct sublineage compared to previously reported CE clades, and extends the boundary of the CE lineage further south than previously reported.