Miracle-dz/UniFAR-FTUs huggingface dataset:
Vericiguat, a novel sGC stimulator: Mechanism of action, clinical, and translational science

Vericiguat, a novel soluble guanylate cyclase (sGC) stimulator, is approved for the treatment of heart failure (HF) with reduced ejection fraction (HFrEF). Decreased nitric oxide (NO) availability, sGC desensitization to NO, sGC deficiency, and reduced cyclic guanosine monophosphate (cGMP) signaling are potential contributing factors for HF disease progression. Vericiguat works via stimulation of sGC in the critical NO‐sGC‐cGMP pathway. Vericiguat is primarily metabolized by glucuronidation via uridine diphosphate‐glucuronosyltransferase (UGT) isoforms UGT1A1 and UGT1A9. Urinary excretion and renal clearance of vericiguat are low. No intrinsic factor had a clinically relevant effect on vericiguat exposure. Vericiguat has low drug–drug interaction potential with no clinically relevant pharmacokinetic or pharmacodynamic interactions observed with warfarin, digoxin, aspirin, or sacubitril/valsartan. The global phase III study VICTORIA included patients with HFrEF who had a recent HF hospitalization or intravenous diuretic treatment for HF. Treatment with vericiguat on top of standard of care resulted in a 10% relative reduction in the primary composite outcome of death from cardiovascular causes or first hospitalization for HF. Vericiguat was well‐tolerated with low incidence of symptomatic hypotension and syncope compared to placebo. Given its positive benefit–risk profile, vericiguat is an important option for high‐risk patients with HFrEF who are already on guideline‐directed medical therapy and had recent worsening of HF. Future efforts to develop additional effective therapies are needed to further reduce morbidity and mortality in patients with HF.
Hydration Methods for Cisplatin Containing Chemotherapy: A Systematic Review

Abstract Introduction Cisplatin-induced nephrotoxicity (CIN) can be prevented by fluid hydration, electrolyte supplementation, or forced diuresis; however, the best way to prevent CIN is still unknown. The aim of this study was to provide objective evidence on the optimal design of hydration schemes to prevent CIN based on an update of the literature. Methods A Pubmed and Embase search were conducted in December 2021 and repeated in April 2022 and March 2023. Two independent reviewers screened the articles. The included articles were categorized and reviewed per category. Results Twenty-seven articles met the inclusion criteria. The included studies varied widely. Four out of seven studies investigating diuretics found a protective effect of adding mannitol to the hydration scheme. All six studies investigating duration and amount of volume of hydration found that a short-hydration scheme resulted in less CIN than a longer hydration scheme. Seven out of nine articles evaluating the role of electrolytes found that magnesium supplementation reduced the risk of nephrotoxicity. Three studies investigated the safety of oral hydration and concluded that nephrotoxicity did not occur more frequently after oral hydration. Conclusion The hydration scheme of cisplatin should be short and consist of a relatively small amount of volume. The scheme should include mannitol and magnesium supplementation. Head-to-head studies are needed to investigate the safety of furosemide compared with mannitol and the dose of mannitol and magnesium.
Estudio epidemiológico global del síndrome de Down

Introduccion: El ECLAMC (Estudio Colaborativo Latino Americano de Malformaciones Congenitas) fue creado en 1967. Actualmente, lo integran 180 hospitales de 76 ciudades de 9 paises Latino Americanos y ha acumulado mas de 4,5 millones de nacimientos. El Hospital Clinico de la Universidad de Chile (HCUCH) ingreso en 1967 y despues otros 12 establecimientos chilenos. Objetivos: Verificar si la frecuencia de sindrome de Down (SD) esta aumentando en Chile y Latino America y como se ha visto modificada en los paises en que esta permitido el aborto electivo. Pacientes y Metodo: Se estudio 3 muestras: Todos los nacimientos del HCUCH desde 1972 a 2009; de los hospitales chilenos activos y de los 180 hospitales de 9 paises Latinoamericanos. Se comparo las frecuencias de SD de Chile y del ECLAMC con otros paises que participan en el Internacional Clearinghouse for Birth Defects Monitoring System. Resultados: La frecuencia del SD en el HCUCH aumento significativamente de 1,03 por mil nacimientos en 1972 a 2,93 por mil en 2009. Las frecuencias en los hospitales chilenos son muy homogeneas, todas mas altas que el promedio del ECLAMC: 1,88 por mil. El promedio chileno para el periodo 1998-2005 fue de 2,47 por mil. Con un rango de 1,88 por mil del HCUCH y 2,86 por mil del Hospital de Curico. En el resto del mundo se ha asistido a una disminucion significativa de las tasas de SD, siendo las mas bajas la de Iran: 0,32 por mil y Espana 0,60 por mil nacimientos vivos. Conclusion: En Chile, las tasas de SD son mayores al promedio del ECLAMC 2,47 por mil existiendo una tendencia al aumento de ellas lo mismo que en Latino America, donde el promedio para el periodo 20012005 fue de 2,89 por mil. En Europa y Asia las tasas han disminuido a cifras extremas, Iran 0,32 por mil y Espana 0,60 por mil.
Influence of Cement-Voids Ratio on Stress-Dilatancy Behavior of Artificially Cemented Sand

The addition of cement is an interesting remediation technique when the project requires improvement of the local soil for the construction of pavement base layers, in slope protection of earth dams and canal linings, as a support layer for shallow foundations and to prevent sand liquefaction. The present study was carried out to quantify the influence of the amount of cement and the porosity in a cement- voids ratio, defined as the ratio between the volume of cement and the volume of voids of a mixture, on the stress-dilatancy behavior of an artificially cemented sand. A program of triaxial compression tests considering three distinct cement-voids ratios was carried out with two combinations of volumes of voids and volumes of cement at each cement-voids ratio. Results showed that the stress-dilatancy relationship is alike for a given cement-voids ratio and that the stress-strain behavior is also similar. The cement-voids ratio is therefore an appropriate parameter to assess stress-dilatancy of the sand-cement mixture studied. DOI: 10.1061/(ASCE)GT.1943-5606.0000565. © 2012 American Society of Civil Engineers. CE Database subject headings: Stress; Dilatancy; Cement; Triaxial tests; Voids; Sand (soil type).
Pollen representation in surface samples of the Juniperus, Picea and Juglans forest belts of Kyrgyzstan, central Asia

Surface pollen deposition at five sites (Kichikol, Karakol, Nishneye and Verkhneye Ozero, and Bakaly) in four different forest types (Juniperus , Picea, Juglans and mixed forests) in Kyrgyzstan have been investigated to assess the relationship between modern vegetation and pollen composition in order to calibrate the pollen representation. Vegetation surveys with an estimation of the tree-crown cover (%) were made in 10 m × 10 m plots to relate the vegetation to surface pollen of moss polsters. Correlation calculations show a close relationship between vegetation (tree-crown cover) and pollen for the Juniperus site (eg, r 2 = 0.76 between crown cover and arboreal pollen, AP) and the Picea site (r 2 = 0.85), whereas the linkage is weaker at the Juglans site (r 2 = 0.35) and in mixed forests (r 2 = 0.32). The results of the surface samples of moss polsters are compared and discussed with surface samples of lake sediments that were taken at the same locations. We use vegetational maps from around the lakes to discuss the link between vegetation and pollen at extra-local scales (800 m around the sites). These comparisons show that AP underestimates the effective tree cover around all sites, with in extreme cases densely forested areas corresponding to AP values as low as <60; 30%. We explain this finding by the prevalent background pollen load that derives from the dry lowland and slope steppes (Artemisia, Chenopodiaceae, Poaceae). Our investigation may improve the reconstruction of Quaternary vegetation and climate history of these forest belts in Kyrgyzstan (Central Asia) on the basis of fossil pollen assemblages from mire and lake sediments. It provides new insights into the pollen reflection of forest isles (eg, on humid slopes or mountain tops) that are surrounded by continental steppes; a vegetational situation that may be used as an analogue for the conditions during the full glacial in Eurasia and Northern America.
Vaccination coverage of children with rheumatic diseases compared with healthy controls: a retrospective case-control study

ABSTRACT Objective To reveal the vaccination status of patients with pediatric rheumatic disease (PedRD) and to compare this with healthy controls. Methods The electronic health records of the Ministry of Health regarding the vaccination status of children with PedRD followed in a tertiary hospital were analyzed cross-sectionally and compared with their healthy controls. The missing vaccines were reported according to individual, age-appropriate schedule and causes of skipped vaccines in both groups were investigated with an online survey. Results The vaccination rate of patients in the last examination was 71.4% (90/126) and 95.7% (110/115) in healthy controls (p < 0.001). Measles-mumps-rubella vaccine, diphtheria, the administration rates of the second dose of tetanus-acellular pertussis-inactivated polio and Haemophilus influenzae type B, chickenpox, and hepatitis A vaccines were significantly lower in patients than in controls (p values 0.004, 0.02, 0.01, 0.013, respectively). The pre-diagnosis incomplete vaccination proportion was significantly higher in the patient group (16.6%) than in healthy controls (4.3%) (p = 0.002). In the patient group, the proportion of incomplete live-attenuated vaccines after diagnosis (25%) was more than pre-diagnosis (61.1%) (p = 0.04), while the proportion of incomplete non-live vaccines before and after diagnosis was similar (47.2% and 50%, respectively) (p = 0.73). The major reasons for missed vaccines were physicians’ recommendations (15.6%), the presence of PedRD diagnosis (12.5%), and the drugs used (12.5%). Conclusion Vaccination coverage of PedRD patients has been shown to lag behind the routine vaccination schedule (71.4%). In addition to new recommendations, electronic health system records for vaccination may be appropriate for the follow-up of these patients, and the addition of reminder alerts may be useful to reduce the rate of missed vaccinations.
Dosimetric verification of four dose calculation algorithms for spine stereotactic body radiotherapy

Abstract The applications of Type B [anisotropic analytical algorithm (AAA) and collapsed cone (CC)] and Type C [Acuros XB (AXB) and photon Monte Carlo (PMC)] dose calculation algorithms in spine stereotactic body radiotherapy (SBRT) were evaluated. Water- and bone-equivalent phantoms were combined to evaluate the percentage depth dose and dose profile. Subsequently, 48 consecutive patients with clinical spine SBRT plans were evaluated. All treatment plans were created using AXB in Eclipse. The prescription dose was 24 Gy in two fractions at a 10 MV FFF on TrueBeam. The doses were then recalculated with AAA, CC and PMC while maintaining the AXB-calculated monitor units and beam arrangement. The dose index values obtained using the four dose calculation algorithms were then compared. The AXB and PMC dose distributions agreed with the bone-equivalent phantom measurements (within ±2.0%); the AAA and CC values were higher than those in the bone-equivalent phantom region. For the spine SBRT plans, PMC, AAA and CC were overestimated compared with AXB in terms of the near minimum and maximum doses of the target and organ at risk, respectively; the mean dose difference was within 4.2%, which is equivalent with within 1 Gy. The phantom study showed that the results from AXB and PMC agreed with the measurements within ±2.0%. However, the mean dose difference ranged from 0.5 to 1 Gy in the spine SBRT planning study when the dose calculation algorithms changed. Users should incorporate a clinical introduction that includes an awareness of these differences.
The Relevance of Arterial Blood Pressure in the Management of Glaucoma Progression: A Systematic Review

Abstract BACKGROUND Glaucoma is one of the leading causes of global blindness and is expected to co-occur more frequently with vascular morbidities in the upcoming years, as both are aging-related diseases. Yet, the pathogenesis of glaucoma is not entirely elucidated and the interplay between intraocular pressure, arterial blood pressure (BP) and ocular perfusion pressure is poorly understood. OBJECTIVES This systematic review aims to provide clinicians with the latest literature regarding the management of arterial BP in glaucoma patients. METHODS A systematic search was performed in Medline, Embase, Web of Science and Cochrane Library. Articles written in English assessing the influence of arterial BP and systemic antihypertensive treatment of glaucoma and its management were eligible for inclusion. Additional studies were identified by revising references included in selected articles. RESULTS 80 Articles were included in this systemic review. A bimodal relation between BP and glaucoma progression was found. Both high and low BP increase the risk of glaucoma. Glaucoma progression was, possibly via ocular perfusion pressure variation, strongly associated with nocturnal dipping and high variability in the BP over 24 h. CONCLUSIONS We concluded that systemic BP level associates with glaucomatous damage and provided recommendations for the management and study of arterial BP in glaucoma. Prospective clinical trials are needed to further support these recommendations.
Response of Chickpea (Cicer arietinum L.) to Soil Moisture Levels in a Semiarid Environment

Chickpea ( Cicer arietinum L.) is an important food legume which is grown in most geographical regions. Chickpea can experience two types of drought: intermittent drought stress caused by breaks in winter rainfall; and terminal drought stress, resulting from receding soil moisture at the late stage of the crop growth. One way of improving the low productivity of chickpea in drought environment is to develop varieties, which can withstand moisture stress and produce high yield under such environment. A two year field experiment was carried out at the University of Jordan Research Station in the Jordan Valley. Six genotypes of chickpea; four Kabuli type and two desi type were evaluated. A line source sprinkler system was used to obtain the desired pattern of water application. Measurement on yield and yield components and other agronomic traits were made. Drought Susceptibility Index (DSI) and Water Use Efficiency (WUE) were also measured for the studied characters. Genotypes behaved differently in response to water levels for their seed yield and other characters. FLIP-98-107 gave the highest seed yield at the intermediate water level (W3) and the seed yield decreased as water level increased to W4 and W5 or decreased to W2 and W1. Results further indicated that the WUE of high yielding and/or early genotypes was better than that of the low yielding and late maturing genotypes at the lowest two water level treatments (W1 and W2). The most important traits that contribute to the ability of these genotypes to tolerate moisture stress conditions are: high harvest index, earliness, high number of pods and number of seeds per plant.
Genetic Load and Adaptive Potential of a Recovered Avian Species that Narrowly Avoided Extinction

Abstract High genetic diversity is a good predictor of long-term population viability, yet some species persevere despite having low genetic diversity. Here we study the genomic erosion of the Seychelles paradise flycatcher (Terpsiphone corvina), a species that narrowly avoided extinction after having declined to 28 individuals in the 1960s. The species recovered unassisted to over 250 individuals in the 1990s and was downlisted from Critically Endangered to Vulnerable in the International Union for the Conservation of Nature Red List in 2020. By comparing historical, prebottleneck (130+ years old) and modern genomes, we uncovered a 10-fold loss of genetic diversity. Highly deleterious mutations were partly purged during the bottleneck, but mildly deleterious mutations accumulated. The genome shows signs of historical inbreeding during the bottleneck in the 1960s, but low levels of recent inbreeding after demographic recovery. Computer simulations suggest that the species long-term small Ne reduced the masked genetic load and made the species more resilient to inbreeding and extinction. However, the reduction in genetic diversity due to the chronically small Ne and the severe bottleneck is likely to have reduced the species adaptive potential to face environmental change, which together with a higher load, compromises its long-term population viability. Thus, small ancestral Ne offers short-term bottleneck resilience but hampers long-term adaptability to environmental shifts. In light of rapid global rates of population decline, our work shows that species can continue to suffer the effect of their decline even after recovery, highlighting the importance of considering genomic erosion and computer modeling in conservation assessments.
Early calc-alkaline magmatism in the Mogollon-Data Volcanic Field, New Mexico, USA

The Mogollon-Datil Volcanic Field in southwest New Mexico was active between 40 and 20 Ma. It is situated c. 500 km from the western North American plate margin, and yet the early pre-30 Ma volcanic rocks comprise a high-K calc-alkaline suite ranging from basaltic andesites to dacites. All the samples are characterized by high and variable LILE and LREE contents, and LILE/HFSE ratios, and variable Nd and Sr isotope ratios of 0.51231–0.51250 and 0.7055–0.7065 respectively. In detail, three groups are recognized: Group 1 rocks have the lower SiO2, incompatible element abundances and 87Sr/86Sr ratios; Group 2 preserves the clearest evidence for open system differentiation, and Group 3 exhibits little variation in 87Sr/86Sr and the most coherent major and trace element arrays. The Group 2 rocks have been modelled in terms of simple binary mixing between selected Group 1 basaltic andesites and a higher silica crustal endmember, which appears to have been derived from the mid-lower crust in the presence of residual garnet. The Group 3 rocks, by contrast, are consistent with near closed system differentiation, modelled in three stages and involving Plag-Aug-O1-Mag and subsequently hornblende and K-feldspar. Published experimental data indicate that the differentiation of the parental basaltic magmas took place at elevated pressures of c. 4-5 kbar, and water contents, c. 2wt% H2O. It is argued that the parental magmas to these calc-alkaline suites were generated in a period of lithospheric extension, and that they were derived from within the continental mantle lithosphere, as inferred for mid- to Late Tertiary rocks elsewhere in the western US, with no significant contribution from contemporaneous subduction processes.
Fair Play::More Equal Laws Boost Female Labor Force Participation

This Staff Discussion Note examines the effect of gender-based legal restrictions and other policy choices and demographic characteristics on female labor force participation. Drawing on a large and novel panel data set of gender-related legal restrictions, the study finds that restrictions on women’s rights to inheritance and property, as well as legal impediments to undertaking economic activities such as opening a bank account or freely pursuing a profession, are strongly associated with larger gender gaps in labor force participation. These factors have a significant additional impact on female labor force participation over and above the effects of demographic characteristics and policies. In many cases, the gender gaps caused by these restrictions also have macro-critical effects in terms of an impact on GDP. The results from this study suggest that it would be beneficial to level the playing field by removing obstacles that prevent women from becoming economically active if they choose to do so. In recommending equal opportunities, however, this study does not intend to render a judgment of countries’ broadly accepted cultural and religious norms.
Structure guided mutagenesis of Henipavirus Receptor Binding Proteins reveals molecular determinants of receptor usage and antibody binding epitopes

Nipah virus (NiV) is a highly lethal, zoonotic henipavirus (HNV) that causes respiratory and neurological signs and symptoms in humans. Similar to other paramyxoviruses, HNVs mediate entry into host cells through the concerted actions of two surface glycoproteins: a receptor binding protein (RBP) that mediates attachment and a fusion glycoprotein (F) that triggers fusion in an RBP-dependent manner. NiV uses ephrin-B2 (EFNB2) and ephrin-B3 (EFNB3) as entry receptors. Ghana virus (GhV), a novel HNV identified in a Ghanaian bat, use EFNB2 but not EFNB3. In this study, we employ a structure-informed approach to identify receptor interfacing residues and systematically introduce GhV-RBP residues into a NiV-RBP backbone to uncover the molecular determinants of EFNB3 usage. We reveal two regions that severely impair EFNB3 binding by NiV-RBP and EFNB3-mediated entry by NiV pseudotyped viral particles. Further analyses uncovered two point mutations (NiVN557SGhV and NiVY581TGhV) pivotal for this phenotype. Moreover, we identify NiV interaction with Y120 of EFNB3 as important for usage of this receptor. Beyond these EFNB3-related findings, we reveal two domains that restrict GhV binding of EFNB2, identify the HNV-head as an immunodominant target for polyclonal and monoclonal antibodies, and describe putative epitopes for GhV and NiV-specific monoclonal antibodies. Cumulatively, the work presented here generates useful reagents and tools that shed insight to residues important for NiV usage of EFNB3, reveals regions critical for GhV binding of EFNB2, and describes putative HNV antibody binding epitopes.
VTA projections to M1 are essential for reorganization of layer 2-3 network dynamics underlying motor learning

The primary motor cortex (M1) is crucial for motor skill learning. Previous studies demonstrated that skill acquisition requires dopaminergic VTA (ventral-tegmental area) signaling in M1, however little is known regarding the effect of these inputs at the neuronal and network levels. Using dexterity task, calcium imaging, chemogenetic silencing, and geometric data analysis, we demonstrate VTA-dependent reorganization of M1 layer 2-3 during motor learning. While average activity and average functional connectivity of layer 2-3 network remain stable during learning, the activity kinetics, the correlational configuration of functional connectivity, and average connectivity strength of layer 2-3 neurons gradually transform towards an expert configuration. In addition, task success-failure outcome signaling gradually emerges. Silencing VTA dopaminergic inputs to M1 during learning, prevents all these changes. Our findings demonstrate dopaminergic VTA-dependent formation of outcome signaling and new connectivity configuration of the layer 2-3 network, supporting reorganization of the M1 network for storing new motor skills.