Miracle-dz/UniFAR-FTUs huggingface dataset:
Extracellular vesicles from cerebrospinal fluid revealed changes in miR‐19a‐3p and miR‐4516 expression in Slovene male suicides

Suicide is an important public‐health concern, with more than 700,000 people dying by suicide yearly. It is a multifactorial phenomenon, shaped by the effects of sociodemographic, environmental and biological factors. The latter two factors can be linked through epigenetic studies, which examine differences in gene expression that are not due to changes in the DNA sequence itself. Epigenetic mechanisms include micro RNAs (miRNAs), which have a direct effect on already translated mRNA, leading to either decay or translational repression of the target mRNA. MiRNA molecules have been identified as cargo of extracellular vesicles (EVs) used by cells for long‐distance communication, and pathophysiological changes in miRNA in brain cells may be reflected in cerebrospinal fluid (CSF) vesicles. In this study we investigated the presence and differential expression of selected miRNAs in EVs from the CSF of male suicide completers and controls. Western blot and nanoparticle tracking analyses confirmed the presence of small and medium sized EVs. Of the miRNA analyzed (miR‐16‐5p, miR‐19a‐3p, miR‐34c‐5p, miR‐17‐5p, miR‐4286, miR‐26b‐5p, miR‐381‐3p, and miR‐4516) miR‐19a‐3p and miR‐4516 reached statistical significance with p‐values of 0.0408 and 0.0168, respectively. Mir‐4516 and miRNA‐19a‐3p have been previously studied in suicide, and target SLC6A4 and TNF‐α expression, correspondingly. Approximately 70% of known miRNAs are expressed in the central nervous system, and therefore represent an important biomarker potential. Investigating the cargo of CFS and blood EVs would further support the identification of miRNAs with clinical use potential.
Education‐related needs for children with cystic fibrosis: Perspectives of US pediatric care teams

Patients with cystic fibrosis (CF) often bring education‐related concerns to their medical teams. Concerns around the ability for CF care teams to identify and address these concerns exist. We sought to describe CF care team perceptions of (1) patient and family education‐related needs, (2) how these needs are identified, documented and addressed, and (3) education‐related resource gaps.
On the hydrological cycle under paleoclimatic conditions as derived from AGCM simulations

The atmospheric hydrological cycle is compared for different time slices of the late Quaternary. Simulations have been conducted with an atmospheric circulation model at T42 resolution, and we have performed a global evaluation of the atmospheric water vapor transport. The water export from the Atlantic catchment area, important for driving the large-scale thermohaline ocean circulation, is analyzed in detail. For the Last Glacial Maximum (LGM), we examine the model's sensitivity with respect to tropical cooling relative to the CLIMAP reconstruction which is motivated by recent data. We find that the LGM experiment with tropical cooling is in better agreement with proxy data available. Our experiments indicate that the water vapor transport is strongly affected by three mechanisms: continental drying, eddy moisture transport, and changes in the tropical circulation. Except for the continental drying and the blocking effect of the Laurentide ice sheet, the hydrological cycle is substancially different for both LGM experiments. We find that the hydrological system is rather sensitive to tropical temperature change which is important to understand paleoclimate and future climate changes.
Revisiting the Wintertime Intraseasonal SST Variability in the Tropical South Indian Ocean: Impact of the Ocean Interannual Variation*

Intraseasonal sea surface temperature (SST) variability over the Seychelles‐Chagos thermocline ridge (SCTR; 128‐48S, 558‐858E) induced by boreal wintertime Madden‐Julian oscillations (MJOs) is investigated with a series of OGCM experiments forced by the best available atmospheric data. The impact of the ocean interannualvariation(OIV),forexample,thethermoclinedepthchangesintheSCTR,isassessed.Theresults show that surface shortwave radiation (SWR), wind speed‐controlled turbulent heat fluxes, and wind stress‐ driven ocean processes are all important in causing the MJO-related intraseasonal SST variability. The effect of the OIV is significant in the eastern part of the SCTR (708‐858E), where the intraseasonal SSTs are strengthened by about 20% during the 2001‐11 period. In the western part (558‐708E), such effect is relatively small and not significant. The relative importance of the three dominant forcing factors is adjusted by the OIV, with increased (decreased) contribution from wind stress (wind speed and SWR). The OIV also tends to intensify the year-to-year variability of the intraseasonal SST amplitude. In general, a stronger (weaker) SCTR favors larger (smaller) SST responses to the MJO forcing. Because of the nonlinearity of the upper-ocean thermal stratification, especially the mixed layer depth (MLD), the OIV imposes an asymmetric impact on the intraseasonal SSTs between the strong and weak SCTR conditions. In the eastern SCTR, both the heat flux forcing and entrainment are greatly amplified under the strong SCTR condition, but only slightly suppressed under the weak SCTR condition, leading to an overall strengthening effect by the OIV.
MODELING WATER UTILITY FINANCIAL PERFORMANCE

ABSTRACT: The purpose of this paper is to present a theory and model for assessing the financial health of public water systems. Using financial information from 25 water utilities in Georgia, the paper seeks to identify the causal relationships between the financial performance of a water utility and its fiscal position. The need for a theoretical understanding of water utility financial health is the result of the increasingly stringent performance requirements under the Safe Drinking Water Act (SDWA). The issue has become particularly important for small water systems that will be exposed to significant financial demands. A set of financial ratios were developed and tested in a model that was based on liquid asset theory. The model contained five variables designed to account for the size of liquid assets, current debt, cash-flow, and the level of expenses. The variables fit the need of water utilities: to provide an adequate level of operation and maintenance to meet current and future system needs as well as SDWA standards.
Iron IIA Pottery from the Negev Highlands: Petrographic Investigation and Historical Implications

Abstract The article reports the results of a petrographic investigation of pottery from early Iron IIA settlements in the Negev Highlands. A substantial percentage of the vessels studied, most notably slag-tempered ware, originated in the copper districts of the Wadi Arabah. This provides us, for the first time, with conclusive proof of the profound connection between the Negev Highlands and the Arabah copper extraction system, which was operated by tribal desert groups. The data demonstrate that the subsistence economy of the Negev Highlands sites was supplemented by the participation of at least some of the local inhabitants in this enterprise.
A robust seizure detection and prediction method with feature selection and spatio-temporal casual neural network model

Objective. Epilepsy is a fairly common condition that affects the brain and causes frequent seizures. The sudden and recurring epilepsy brings a series of safety hazards to patients, which seriously affects the quality of their life. Therefore, real-time diagnosis of electroencephalogram (EEG) in epilepsy patients is of great significance. However, the conventional methods take in a tremendous amount of features to train the models, resulting in high computation cost and low portability. Our objective is to propose an efficient, light and robust seizure detecting and predicting algorithm. Approach. The algorithm is based on an interpretative feature selection method and spatial-temporal causal neural network (STCNN). The feature selection method eliminates the interference factors between different features and reduces the model size and training difficulties. The STCNN model takes both temporal and spatial information to accurately and dynamically track and diagnose the changing of the features. Considering the differences between medical application scenarios and patients, leave-one-out cross validation (LOOCV) and cross-patient validation (CPV) methods are used to conduct experiments on the dataset collected at the Children’s Hospital Boston (CHB-MIT), Siena and Kaggle competition datasets. Main results. In LOOCV-based method, the detection accuracy and prediction sensitivity have been improved. A significant improvement is also achieved in the CPV-based method. Significance. The experimental results show that our proposed algorithm exhibits superior performance and robustness in seizure detection and prediction, which indicates it has higher capability to deal with different and complicated clinical situations.
Abolishing β‐arrestin recruitment is necessary for the full metabolic benefits of G protein‐biased glucagon‐like peptide‐1 receptor agonists

Earlier studies have shown that peptide glucagon‐like peptide‐1 receptor (GLP‐1R) agonists with reduced β‐arrestin recruitment show enhanced anti‐hyperglycaemic efficacy through avoidance of GLP‐1R desensitization. However, the ligand modifications needed to decrease β‐arrestin recruitment usually also reduces GLP‐1R affinity, therefore higher doses are needed. Here we aimed to develop new, long‐acting, G protein‐biased GLP‐1R agonists with acute signalling potency comparable with semaglutide, to provide insights into specific experimental and therapeutic scenarios.
The impact of sea-level rise on mangrove shorelines

There are extensive mangrove forests along the tropical shorelines of the world; they are particularly well developed in, though not exclusively restricted to, areas that are sheltered and muddy. Stratigraphic studies of the sediments underlying both the mangrove forests themselves and associated wetlands indicate that there have been considerable changes in the extent of these wetlands as a result of past sea-level fluctuations. Further changes in the area covered by mangroves are to expected if the sea rises at the rates anticipated as a result of the greenhouse effect. The exact response of a mangrove coastline will depend upon shoreline topography, sources of sediment, rates of sediment supply, and the rate of sealevel rise. The stratigraphy and chronology of Holocene deposits on mangrove shorelines allow reconstruction of the way that mangrove forests have responded
Structure‐based design of new N‐benzyl‐piperidine derivatives as multitarget‐directed AChE/BuChE inhibitors for Alzheimer's disease

The pathogenic complexity of Alzheimer's disease (AD) demands the development of multitarget‐directed agents aiming at improving actual pharmacotherapy. Based on the cholinergic hypothesis and considering the well‐established role of butyrylcholinesterase (BuChE) in advanced stages of AD, the chemical structure of the acetylcholinesterase (AChE) inhibitor drug donepezil (1) was rationally modified for the design of new N‐benzyl‐piperidine derivatives (4a−d) as potential multitarget‐direct AChE and BuChE inhibitors. The designed analogues were further studied through the integration of in silico and in vitro methods. ADMET predictions showed that 4a−d are anticipated to be orally bioavailable, able to cross the blood‐brain barrier and be retained in the brain, and to have low toxicity. Computational docking and molecular dynamics indicated the formation of favorable complexes between 4a−d and both cholinesterases. Derivative 4a presented the lowest binding free energy estimation due to interaction with key residues from both target enzymes (−36.69 ± 4.47 and −32.23 ± 3.99 kcal/mol with AChE and BuChE, respectively). The in vitro enzymatic assay demonstrated that 4a was the most potent inhibitor of AChE (IC50 2.08 ± 0.16 µM) and BuChE (IC50 7.41 ± 0.44 µM), corroborating the in silico results and highlighting 4a as a novel multitarget‐directed AChE/BuChE inhibitor.
Spatial and temporal variability of tropospheric ozone (O3) in the boundary layer above the Aegean Sea (eastern Mediterranean)

[1] To study the spatial and temporal variability of tropospheric ozone in the marine boundary layer over the Aegean Sea (eastern Mediterranean), an O3 analyzer has been installed onboard of a passenger vessel traveling on a regular basis in the Aegean Sea (from Heraklion/Crete 35°30′N, 25°13′E to Thessaloniki 40°64′N, 22°97′E) during a period of 14 months (August 1999 to November 2000). In addition, O3 data have been obtained on a daily basis at the regional background station of Finokalia (Crete; 35°30′N, 25°70′E) since September 1997, short-term measurements of O3 were performed over Crete during the PAUR II campaign (May 1999), and the first O3 data from a rural area (40°32′N, 23°50′E) close to Thessaloniki at the north of Greece have been collected from March 2000 to January 2001. This survey extensive points out the existence of a well-defined seasonal cycle in boundary layer O3 with maximum in summer both above the Aegean Sea and at Finokalia. However, the seasonal signal (defined as the summer/winter ratio) is not constant and varies as a function of air mass origin from 1.33 to 1.15 for the N-NE and SW-S sectors, respectively, in line with the geographical location of the O3 precursor sources. Our data show the absence of any significant longitudinal gradient over Crete at least during spring and autumn and the absence of significant latitudinal gradient between the north and south Aegean Sea during all seasons for air masses having similar origin. The above results indicate that long-range transport is the main factor accounting for the elevated O3 levels above the eastern Mediterranean Sea. Thus (1) O3 data from Finokalia, where the longest time series are available for the area, have regional significance and (2) over the entire Aegean basin, ozone values are above the 32 ppbv European Union (EU) phytotoxicity limit throughout the year and above the 53 ppbv EU health protection limit most of the time during the dry season of the year. The very significant correlation between black carbon (BC) and O3 observed during an intensive campaign in May 2000 provides an indication that the high O3 concentrations at Finokalia resulted from ageing of air masses strongly affected by combustion processes.
Improvements in cardiorespiratory fitness, muscle strength and body composition to modest weight loss are similar in those with adult‐ versus childhood‐onset obesity

Adults who have had obesity from childhood are at greater risk of obesity‐related comorbidities compared to those who only develop obesity in adulthood. The main way of mitigating these risks in obesity is with weight loss, which has been shown to positively affect the cardiorespiratory fitness (CRF) and body composition of adults. However, it is unclear whether the response of these outcomes to weight loss may be influenced by age of obesity onset. The objective of our study was to investigate how age of obesity onset mitigates the responsiveness of CRF, muscle strength and body composition to modest weight loss. Measurements were conducted at baseline and 12 weeks. In total, 37 participants (childhood‐onset = 19, adult‐onset = 18) lost 3.7% ± 0.4% through aerobic exercise and diet. The YMCA cycle ergometer test (YMCA) and the 20‐m shuttle run test (20MSR) were used to estimate CRF (mL kg−1 min−1) and a handgrip dynamometer was used to estimate muscle strength. Total body composition was assessed by dual‐energy x‐ray absorptiometry (DEXA). Overall, CRF and body composition improved (time effect: p < 0.05) after 12 weeks. There was no group‐by‐time interaction for YMCA, 20MSR, muscle strength and body composition variables. Therefore, the present study suggests that individuals with childhood‐onset obesity and adult‐onset obesity can improve their CRF and body composition similarly after mild weight loss.
Proportion of Mesozoic sedimentary rock types: data from northern Eurasia reveal similarities to North American patterns

Abstract The Mesozoic stratigraphic record of northern Eurasia includes a total of 1,739 formations. The proportion of conglomerate, sandstone + siltstone, shale, carbonates, evaporites, siliceous rocks, and volcanics + volcaniclastics among sedimentary complexes are evaluated for each epoch of the Mesozoic. Sandstone, shale, and conglomerate occur in 86%, 71%, and 42% of formations respectively. Less common are carbonates (28%) and volcanics and volcaniclastics (24%), whereas evaporites and siliceous rocks are rare (< 5%). The proportion of particular sedimentary rock types fluctuates throughout the Mesozoic. The proportion of sandstone + siltstone changes quite similarly to that of shale. A comparison of stratigraphic data from northern Eurasia and North America reveals some similarities, including a Lower Triassic increase in the conglomerate proportion, a Middle-Upper Triassic increase in the proportion of siliceous rocks, Upper Triassic-Lower Jurassic and Upper Jurassic-Lower Cretaceous “clastic spik.
Interactions of Indoleamine 2,3‐dioxygenase‐expressing LAMP3+ dendritic cells with CD4+ regulatory T cells and CD8+ exhausted T cells: synergistically remodeling of the immunosuppressive microenvironment in cervical cancer and therapeutic implications

Cervical cancer (CC) is the fourth most common cancer in women worldwide. Although immunotherapy has been applied in clinical practice, its therapeutic efficacy remains far from satisfactory, necessitating further investigation of the mechanism of CC immune remodeling and exploration of novel treatment targets. This study aimed to investigate the mechanism of CC immune remodeling and explore potential therapeutic targets.
Distributions and expressions of Aquaporin‐5 and 7 in the testes of developing male chicks

Aquaporins (AQPs) are integral membrane proteins that act as water channels for which a total of 13 orthologs of AQP genes in birds have been reported. Tissue expression and cellular or subcellular localization of AQPs have been poorly investigated in the male reproductive system of birds. We aimed to determine the distribution and localization of AQP5 and AQP7 proteins by immunocytochemistry in testicular tissues obtained from developing chicks (14, 21, 28, 35 and 42 days old). Totally 175 male chicks (Ross 308) were used in the study from which testicular tissue was removed, fixed in 10% formaldehyde solution, then embedded in paraffin blocks. Five μm sections were cut, mounted on poly‐L‐lysine slides, dried in an oven, then dehydrated using standard immunohistochemistry staining protocol. The sections were imaged with a Nikon Eclipse 50i trinocular light microscope. Immunohistochemical evaluation of the immune reactivity of AQP5 revealed a positive immune reaction in spermatocytes and interstitial areas of the testes in 14‐day‐old chicks. Testicular tissue AQP5 immune reactivity was observed in the tubule and the interstitial regions of 21‐, 28‐, 35‐ and 42‐day‐old chicks. AQP7 immune reactions were determined in the tubule and interstitial areas testes of developing chicks' testis tissue, with increasing positivity corresponding to older age. The expression of AQP5 and AQP7 appears to be species‐specific due to differences in localization and expression in male chicks compared with studies of other mammals, which is likely to play an important role in regulating fluid and sperm volume. This research can serve as a base for future studies that will contribute to the understanding of the male genital system of AQPs.
Diet and deprivation in pregnancy: a rat model to investigate the effects of the maternal diet on the growth of the dam and its offspring

The offspring of women in the poorest socio-economic groups in Western societies have an increased risk of developing non-communicable disease in adult life. Deprivation is closely related to the consumption of a diet with an excess of energy (sugar and fat), salt and a shortage of key vitamins. To test the hypothesis that this diet adversely affects the development and long-term health of the offspring, we have formulated two rodent diets, one with a nutrient profile corresponding to the diet of pregnant women in the poorest socio-economic group (DEP) and a second that incorporated current UK recommendations for the diet in pregnancy (REC). Female rats were fed the experimental diets for the duration of gestation and lactation and the offspring compared with those from a reference group fed the AIN-93G diet. The growth trajectory of DEP and REC offspring was reduced compared with the AIN-93G. The REC offspring diet had a transient increase in adipose reserves at weaning, but by 30 weeks of age the body composition of all three groups was similar. The maternal diet had no effect on the homoeostatic model assessment index or the insulin tolerance of the offspring. Changes in hepatic gene expression in the adult REC offspring were consistent with an increased hepatic utilisation of fatty acids and a reduction in de novo lipogenesis. These results show that despite changes in growth and adiposity maternal metabolic adaptation minimises the adverse consequences of the imbalanced maternal diet on the metabolism of the offspring.
Radiocarbon Dates from Jar and Coffin Burials of the Cardamom Mountains Reveal a Unique Mortuary Ritual in Cambodia's Late- to Post-Angkor Period (15th–17th Centuries AD)

We present the first radiocarbon dates from previously unrecorded, secondary burials in the Cardamom Mountains, Cambodia. The mortuary ritual incorporates nautical tradeware ceramic jars and log coffins fashioned from locally harvested trees as burial containers, which were set out on exposed rock ledges at 10 sites in the eastern Cardamom Massif. The suite of 28 14C ages from 4 of these sites (Khnorng Sroal, Phnom Pel, Damnak Samdech, and Khnang Tathan) provides the first estimation of the overall time depth of the practice. The most reliable calendar date ranges from the 4 sites reveals a highland burial ritual unrelated to lowland Khmer culture that was practiced from cal AD 1395 to 1650. The time period is concurrent with the 15th century decline of Angkor as the capital of the Khmer kingdom and its demise about AD 1432, and the subsequent shift of power to new Mekong trade ports such as Phnom Penh, Udong, and Lovek. We discuss the Cardamom ritual relative to known funerary rituals of the pre- to post-Angkorian periods, and to similar exposed jar and coffin burial rituals in Mainland and Island Southeast Asia.