Miracle-dz/UniFAR-FTUs huggingface dataset:
Scavenger receptor A1 participates in uptake of Leptospira interrogans serovar Autumnalis strain 56606v and inflammation in mouse macrophages

ABSTRACT Leptospirosis, caused by pathogenic Leptospira species, has emerged as a widespread zoonotic disease worldwide. Macrophages mediate the elimination of pathogens through phagocytosis and cytokine production. Scavenger receptor A1 (SR-A1), one of the critical receptors mediating this process, plays a complicated role in innate immunity. However, the role of SR-A1 in the immune response against pathogenic Leptospira invasion is unknown. In the present study, we found that SR-A1 is an important nonopsonic phagocytic receptor on murine macrophages for Leptospira. However, intraperitoneal injection of leptospires into WT mice presented with more apparent jaundice, subcutaneous hemorrhaging, and higher bacteria burdens in blood and tissues than that of SR-A1-/- mice. Exacerbated cytokine and inflammatory mediator levels were also observed in WT mice and higher recruited macrophages in the liver than those of SR-A1-/- mice. Our findings collectively reveal that although beneficial in the uptake of Leptospira by macrophage, SR-A1 might be exploited by Leptospira to modulate inflammatory activation and increase the susceptibility of infection in the host. These results provide our new insights into the innate immune response during early infection by L. interrogans.
Embryotoxicity and Physiological Compensation in Chicken Embryos Exposed to Crude Oil

Terrestrial, marine, or aquatic oil spills can directly or indirectly contaminate bird eggs. We hypothesized that chicken embryos exposed to crude oil can physiologically compensate to mitigate the potentially toxic effect of lower doses of oil. Embryos exposed to 0, 1, 3, or 5 µL of oil on embryonic days 4 and 10 were initially analyzed for mortality. All oil doses decreased day 4 embryo survival, but only the 2 highest oil doses lowered survival when applied on day 10. Thus, day 15 embryos treated with 1, 3, and 5 µL of source oil on day 10 had arterialized blood analyzed. The hematological variables hematocrit, red blood cell concentration ([RBC]), and hemoglobin concentration increased in response to 1 µL, were unchanged by 3 µL, and decreased by 5 µL of oil treatment. No changes occurred in arterialized blood gas variables (partial pressure of O2 [PO2], pH, bicarbonate concentration) for 1 and 3 µL embryos, but 5 µL of oil decreased PO2 and caused metabolic acidosis. Increased blood lactate in embryos treated with 3 and 5 µL of oil was correlated with decreased hematocrit and [RBC] and increased body mass, the latter likely reflecting edema. We conclude that embryos in middle development physiologically compensated for negative effects of lower doses of crude oil but that higher doses of oil were harmful to the embryos at all developmental stages. Environ Toxicol Chem 2021;40:2347–2358. © 2021 SETAC
Calibration of Gypsum Blocks for Measuring Saline Soils Moisture

ABSTRACT The proper management of irrigation requires an accurate measuring of soil moisture. One of the commonly applied methods for measuring soil moisture is the use of gypsum blocks – a method that is simple and quick to apply. However, measuring moisture in saline soils using this method is prone to errors due to the effect of soil salinity on the block. In this study, the effect of different salinities (1, 2, 6, 10, and 18 deci Siemens per meter (dS m−1) on the measurements of a gypsum block type 5910 A was investigated with two repetitions in random blocks in sandy loam, loam, and clay loam soils, and corrective functions were obtained using multivariate regression for all soils with different salinity levels. The results showed different trends for measuring the soil moistures for salinities 1–6 dS m−1 compared with salinities 10–18 dS m−1, and the corrective functions in salinities 1–6 dS m−1, which had higher accuracies than those with salinities 10–18 dS m−1.
Prior SARS-CoV-2 infection rescues B and T cell responses to variants after first vaccine dose

A boost from infection During clinical trials of severe acute respiratory syndrome coronavirus 2 vaccines, no one who had survived infection with the virus was tested. A year after the pandemic was declared, vaccination of previously infected persons is a reality. Reynolds et al. address the knowledge gap in a cohort of UK health care workers given the Pfizer/BioNTech vaccine in which half of the participants had experienced natural virus infections early in the pandemic (see the Perspective by Crotty). Genotyping indicated that a genetic component underlies heterogeneity in immune responses to vaccine and to natural infection. After vaccination, naïve individuals developed antibody responses similar to those seen in naturally infected persons, but T cell responses were more limited and sometimes absent. However, antibody and memory responses in individuals vaccinated after infection were substantially boosted to the extent that a single vaccine dose is likely to protect against the more aggressive B.1. 1.7 variant. It is possible that the messenger RNA vaccine has an adjuvant effect, biasing responses toward antibody generation. Science, abh1282, this issue p. 1418; see also abj2258, p. 1392 Previous infection results in enhanced variant cross-protective T and B cell responses to a single BNT162b2 vaccine dose. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine rollout has coincided with the spread of variants of concern. We investigated whether single-dose vaccination, with or without prior infection, confers cross-protective immunity to variants. We analyzed T and B cell responses after first-dose vaccination with the Pfizer/BioNTech messenger RNA vaccine BNT162b2 in health care workers (HCW) followed longitudinally, with or without prior Wuhan-Hu-1 SARS-CoV-2 infection. After one dose, individuals with prior infection showed enhanced T cell immunity, antibody-secreting memory B cell response to the spike protein, and neutralizing antibodies effective against variants B.1. 1.7 and B.1. 351. By comparison, HCW receiving one vaccine dose without prior infection showed reduced immunity against variants. B.1. 1.7 and B.1. 351 spike mutations resulted in increased, abrogated, or unchanged T cell responses, depending on human leukocyte antigen (HLA) polymorphisms. Single-dose vaccination with BNT162b2 in the context of prior infection with a heterologous variant substantially enhances neutralizing antibody responses against variants.
Slowing Down Myopia Progression with Contact Lenses – Everyday Cases from the Clinic

Abstract Background An estimated 49.8% of the world population will be myopic by 2050. Multifocal contact lenses (MFCLs) and orthokeratology (OK) reduce peripheral retinal hyperopic defocus, which animal studies have shown to positively impact eye growth. MFCLs are expected to slow myopic progression by 20 – 50% and OK by 30 – 60%, making them valuable therapeutic tools. In view of the guidelines for myopia management published by the International Myopia Institute in 2019, the aim of this retrospective data analysis of a tertiary care center was to review past experience with OK and MFCLs for myopia control and gain information to update current practice. Patients and Methods The contact lens (CL) database of the Eye Clinic of the University Hospital of Basel was searched with the label “myopia progression” between January 2012 – 2020. Patients were included if they gave informed consent, were younger than 19 years old at baseline, and had no ocular comorbidities that could potentially compromise vision. Primary outcomes were progression of spherical equivalent refraction for MFCL patients and progression of axial length (AL) for the OK group, comparing with historical data from OK trials. Secondary outcomes were the presence of risk factors for myopia, age, refractive error at baseline, follow-up duration, and adverse effects during therapy. Results Twenty-one patients could be included, with a mean age of 12.80 ± 3.32 years (y) at baseline. The majority of patients were older than 12 years and already myopic (− 3.89 ± 2.30 diopters) when control treatment was started. Overall, follow-up ranged from 0.08 to 6.33 years (2.03 ± 1.66 y). In the patients treated with MFCLs, myopia control improved significantly when patients changed from spectacles to MFCLs. In the OK group, 14% dropped out during the first year and 2 patients had multiple AL measurements during therapy, which showed a slower growth of AL when compared to other OK trials and controls with spectacles. There were two cases of non-severe keratitis. Environmental risk factors had not been documented and only 48% of clinical records had a documented family risk assessment. Conclusion Patients showed a slower myopia progression under MFCLs or OK, which supports their role as a treatment option in myopia management. In this regard, AL measurement is an important additional parameter to be included in the assessment of myopia progression in clinical practice. Identification of children at risk of developing high/pathologic myopia (family history, environmental risk factors) needs to improve so that the first stages of myopic shift can be recognized and targeted. Changes in lifestyle should be actively encouraged, especially when the impact of decreases in outdoor time secondary to COVID-19 is yet to become clear.
Examining the predictors of use of sanitary napkins among adolescent girls: A multi-level approach

Background This paper aimed to explore various factors associated with the use of sanitary napkins among adolescent girls in Uttar Pradesh and Bihar. Methods The study uses information from the Understanding the Lives of Adolescents and Young Adults (UDAYA) project survey conducted in Uttar Pradesh and Bihar in 2016. The study sample consisted of 14,625 adolescent girls aged 10–19 years. The study sample was selected using a multi-stage systematic sampling design. Multilevel logistic regression (MLR) was used to identify the individual and community level factors associated with the use of sanitary napkins. Results The results revealed a wide variation in sanitary napkins’ use across the socio-economic and demographic factors. The use of sanitary napkins was significantly higher among girls with 8–9 (53.2%) and 10 and more (75.4%) years of schooling compared to those who had no formal education (26.4%). The use of sanitary napkins was higher among adolescent girls who were not engaged in paid work (54.7%) than those who did any paid job (40.8%). Adolescent girls reporting frequent exposure to mass media (OR = 2.10), belonging to the richest wealth quintile (OR = 3.76), and whose mothers had 10 or more years of education (OR = 2.29) had a higher propensity to use sanitary napkins than their counterparts. We did not find a significant role of community-level education of mothers on the menstrual hygiene practices of adolescents. Conclusion Ensuring that adolescent girls have access to hygienic means to manage their menses is critical from a public health perspective and in enabling them to realize their full potential. Programs to enhance menstrual hygiene are warranted. These programs should involve mothers, who are an important source of knowledge about menstrual hygiene. Facilitating girls’ access to education may also produce tangible menstrual hygiene benefits.
The stage‐specifically accelerated brain aging in never‐treated first‐episode patients with depression

Depression associated with structural brain abnormalities is hypothesized to be related with accelerated brain aging. However, there is far from a unified conclusion because of clinical variations such as medication status, cumulative illness burden. To explore whether brain age is accelerated in never‐treated first‐episode patients with depression and its association with clinical characteristics, we constructed a prediction model where gray matter volumes measured by voxel‐based morphometry derived from T1‐weighted MRI scans were treated as features. The prediction model was first validated using healthy controls (HCs) in two Chinese Han datasets (Dataset 1, N = 130 for HCs and N = 195 for patients with depression; Dataset 2, N = 270 for HCs) separately or jointly, then the trained prediction model using HCs (N = 400) was applied to never‐treated first‐episode patients with depression (N = 195). The brain‐predicted age difference (brain‐PAD) scores defined as the difference between predicted brain age and chronological age, were calculated for all participants and compared between patients with age‐, gender‐, educational level‐matched HCs in Dataset 1. Overall, patients presented higher brain‐PAD scores suggesting patients with depression having an “older” brain than expected. More specially, this difference occurred at illness onset (illness duration <3 months) and following 2 years then disappeared as the illness further advanced (>2 years) in patients. This phenomenon was verified by another data‐driven method and significant correlation between brain‐PAD scores and illness duration in patients. Our results reveal that accelerated brain aging occurs at illness onset and suggest it is a stage‐dependent phenomenon in depression.
Benzo[a]phenazine derivatives: Promising scaffolds to combat resistant Mycobacterium tuberculosis

The continuous emergence of resistant Mycobacterium tuberculosis keeps tuberculosis (TB) treatment options still insufficient, and new therapeutic alternatives are urgently needed. Considering the antimycobacterial activity of phenazine derivatives previously reported by our research group, we aimed to explore possible applications to circumvent the resistance in M. tuberculosis. Firstly, we evaluated the antimicrobial activity of seven benzo[a]phenazine derivatives against eleven M. tuberculosis strains: ten resistant and one susceptible (H37Rv). Then, we determined the cytotoxicity of benzo[a]phenazine derivatives and investigated the possible mechanism of action of the most promising compound. Among them, compound 10 was the only one active against all strains evaluated, with a minimum inhibitory concentration between 18.3 and 146.5 µM. For some resistant strains, this compound showed antimicrobial activity higher than rifampicin and it was also active against MDR strains, indicating an absence of cross‐resistance with anti‐TB drugs. Also, 10 showed a pharmacological safety for further in vivo studies and its mechanism of action seems to be related to oxidative stress. Thus, our findings indicate that benzo[a]phenazine derivatives are promising scaffolds for the development of new anti‐TB drugs, mainly focusing on the treatment of resistant TB cases.
Identification of the Core Chemical Structure in SureChEMBL Patents

The SureChEMBL database provides open access to 17 million chemical entities mentioned in 14 million patents published since 1970. However, alongside with molecules covered by patent claims, the database is full of starting materials and intermediate products of little pharmacological relevance. Herein, we introduce a new filtering protocol to automatically select the core chemical structures best representing a congeneric series of pharmacologically relevant molecules in patents. The protocol is first validated against a selection of 890 SureChEMBL patents for which a total of 51,738 manually curated molecules are deposited in ChEMBL. Our protocol was able to select 92.5% of the molecules in ChEMBL from all 270,968 molecules in SureChEMBL for those patents. Subsequently, the protocol was applied to all 240,988 US pharmacological patents for which 9,111,706 molecules are available in SureChEMBL. The unsupervised filtering process selected 5,949,214 molecules (65.3% of the total number of molecules) that form highly congeneric chemical series in 188,795 of those patents (78.3% of the total number of patents). A SureChEMBL version enriched with molecules of pharmacological relevance is available for download at https://ftp.ebi. ac.uk/pub/databases/chembl/SureChEMBLccs.
Malting studies of some selected brewing sorghum varieties

The sorghum samples studied have different protein contents but similar β-glucan levels. A maximum of 90% of the β-glucan present in sorghum was degraded during malting despite its low β-glucan content. When malted in a similar manner, the sorghum sample with the lower nitrogen content had the highest malting loss, developed higher extract yield, and produced more sugars in the wort. The sorghum samples produced different amounts of sugar in their worts. However, the ratios of glucose to maltose were similar for all worts. The combination of optimal steeping, submersion steeping, and air rest produced sorghum malt with a higher extract yield than when sorghum was steeped in water on a continuous basis. When germinated sorghum was kilned at different temperatures, a drop in extract yield, an increase in wort color, and no change in wort viscosity were observed.
Ethno-veterinary practice for the treatment of animal diseases in Neelum Valley, Kashmir Himalaya, Pakistan

Plant species are not only used as fodder or forage but also contribute substantially in the treatment of various health disorders, particularly in livestock. This study is the first quantitative ethnobotanical effort on ethnoveterinary uses of medicinal plants conducted in the Upper Neelum Valley of Azad Jammu & Kashmir, Pakistan. Information pertaining to cure different ailments of animals were collected from 126 informants through semi-structured interviews, group discussion and field walks. In order to identify the plant species used and their preferred habitats, elderly and experienced members of the tribes, locally known ’Budhair’ (aged), were interviewed and sometimes accompanied in the field. The data was further analyzed through ethnobotanical indices. In all, 39 plant species, belonging to 31 genera and 21 families were documented which were used by the indigenous communities of Kashmir Himalaya for curing 21 different diseases of 7 different types of livestock. The highest number of ethno-medicinal plants were contributed by the Polygonaceae family, followed by Crassulaceae, Asteraceae and other families. Roots were the most used part of the plant for preparing ethnoveterinary medicines, followed by the aerial parts. The highest frequency of citation (41) and relative frequency of citation (7.32) was recorded for Saussurea lappa, followed by Rumex acetosa (37/6.61), Rumex nepalensis (36/6.43), Thymus linearis (28/5.0) and Angelica cyclocarpa (28/5.0). The highest use value was recorded for Saussurea lappa (0.33), followed by Rumex acetosa (0.29), Rumex nepalensis (0.29), Thymus linearis and Angelica cyclocarpa (0.22 each). The current study has made an important contribution towards the preservation of indigenous plants-based knowledge from extinction. The phytochemical and pharmacological investigations of the plants with high use value can be a potential source of novel drugs to treat health problems of animals and humans.
An LR framework incorporating sensitivity analysis to model multiple direct and secondary transfer events on skin surface

Bayesian logistic regression is used to model the probability of DNA recovery following direct and secondary transfer and persistence over a 24 hour period between deposition and sample collection. Sub-source level likelihood ratios provided the raw data for activity-level analysis. Probabilities of secondary transfer are typically low, and there are challenges with small data-sets with low numbers of positive observations. However, the persistence of DNA over time can be modelled by a single logistic regression for both direct and secondary transfer, except that the time since deposition must be compensated by an offset value for the latter. This simplifies the analysis. Probabilities are used to inform an activity-level Bayesian Network that takes account of alternative propositions e.g. time of assault and time of social activities. The model is extended in order to take account of multiple contacts between person of interest and ‘ victim’. Variables taken into account include probabilities of direct and secondary transfer, along with background DNA from unknown individuals. The logistic regression analysis is Bayesian -for each analysis, 4000 separate simulations were carried out. Quantile assignments enable calculation of a plausible range of probabilities and sensitivity analysis is used to describe the corresponding variation of LRs that occur when modelled by the Bayesian network. It is noted that there is need for consistent experimental design, and analysis, to facilitate inter-laboratory comparisons. Appropriate recommendations are made. The open-source program written in R-code ALTRaP (Activity Level, Transfer, Recovery and Persistence) enables analysis of complex multiple transfer propositions that are commonplace in cases-work e.g. between those who cohabit. A number of case examples are provided. ALTRaP can be used to replicate the results and can easily be modified to incorporate different sets of data and variables.
Statistically optimized pentazocine loaded microsphere for the sustained delivery application: Formulation and characterization

Pentazocine (PTZ) is a narcotic analgesic used to manage moderate to severe, acute and chronic pains. In this study, PTZ loaded Ethyl cellulose microsphere has been formulated for sustained release and improved bioavailability of PTZ. These microspheres were fabricated by oil in water emulsion solvent evaporation technique. A three factorial, three levels Box-Behnken design was applied to investigate the influence of different formulation components and process variables on the formulation response using the numeric approach through the design expert® software. All the formulations were characterized for the morphology, different physicochemical properties and the results were supported with the ANOVA analysis, three dimensional contour graphs and regression equations. The maximum percentage yield was 98.67% with 98% entrapment of PTZ. The mean particle size of the formulations ranges from 50–148μm, which directly relates to the concentration of polymer and inversely proportional to the stirring speed. SEM revealed the spherical shape of PTZ microspheres with porous structures. These are physically, chemically and thermally stable as confirmed through Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD) and thermal gravimetric (TG) analysis respectively. The microspheres provided a sustained release of the PTZ for more than 12 hours, following zero order with fickian and non fickian diffusion. The results indicate that prepared microspheres can be a potential drug delivery system (DDS) for the delivery of PTZ in the management of pains.