Therapeutic targeting of TEAD transcription factors in cancer.

The Hippo signaling pathway inhibits the activity of the oncogenic YAP (Yes-associated protein)/TAZ (transcriptional co-activator with PDZ-binding motif)-TEAD (TEA/ATTS domain) transcriptional complex. In cancers, inactivating mutations in upstream Hippo components and/or enhanced activity of YAP/TAZ and TEAD have been observed. The activity of this transcriptional complex can be effectively inhibited by targeting the TEAD family of transcription factors. The development of TEAD inhibitors has been driven by the discovery that TEAD has druggable hydrophobic pockets, and is currently at the clinical development stage. Three small molecule TEAD inhibitors are currently being tested in Phase I clinical trials. In this review, we highlight the role of TEADs in cancer, discuss various avenues through which TEAD activity can be inhibited, and outline the opportunities for the administration of TEAD inhibitors.

Definitions, Etiologies, and Outcomes of Acute on Chronic Liver Failure: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a major public health concern. We aimed to assess the definitions, etiologic spectrum, organ failure (OF), and outcomes of ACLF globally. METHODS: Three databases were searched for studies on ACLF from 1990 until September 2022. Information regarding definitions, acute precipitants, underlying chronic liver disease (CLD), OF, and mortality were extracted. Meta-analyses were performed for pooled prevalence rates (95% confidence interval [CI]) using random-effects model for each definition of ACLF. RESULTS: Of the 11,451 studies identified, 114 articles (142 cohorts encompassing 210,239 patients) met the eligibility criteria. Most studies (53.2%) used the European Association for the Study of the Liver (EASL) definition, followed by Asia-Pacific Association for the Study of the Liver (APASL) (33.3%). Systemic infection was the major acute precipitant, and alcohol use was the major cause of CLD in EASL-defined studies, whereas alcohol was both the major acute precipitant and cause of CLD in APASL-defined studies. Liver failure was the major OF in APASL-based studies, whereas renal failure was predominant in EASL-based studies. Thirty-day mortality varied across definitions: APASL: 38.9%, 95% CI, 31.2%-46.9%; EASL: 47.9%, 95% CI, 42.2%-53.5%; and NACSELD: 52.2%, 95% CI, 51.9%-52.5%. Diagnostic overlap between definitions ranged from 7.7% to 80.2%. Meta-regression suggested that the World Health Organization region influenced 30-day mortality in studies using EASL definition. CONCLUSIONS: Heterogeneity in the definition of ACLF proposed by different expert societies and regional preferences in its use result in differences in clinical phenotype and outcomes. A uniform definition would enhance the comparability and interpretation of global data.

Air pollution and under-5 child mortality: linking satellite and IPUMS-DHS data across 41 countries in South Asia and Sub-Saharan Africa.

BACKGROUND: Despite progress, under-five mortality remains high, especially in Sub-Saharan Africa and South Asia, where around 13,400 children die daily. Environmental pollutants, including PM2.5 from outdoor air and household air pollution, significantly contribute to these preventable deaths. METHODS: This cross-country study combined satellite data with 113 surveys from the IPUMS-DHS dataset (1998-2019) to examine under-five child mortality in 41 developing countries. The integration of Global Annual Particulate Matter with a diameter of 2.5 micrometres or less (PM2.5) Grids from Socioeconomic Data and Applications Center (SEDAC) and geospatial data from the DHS Program enabled a focused analysis of the association between indoor and outdoor air pollution, particularly PM2.5, and child mortality rates using both logistic and multilevel logistic regression models, as well as estimating Population Attributable Fractions (PAF) to quantify the mortality burden attributable to these pollutants. RESULTS: Outdoor air pollution, measured by a one standard deviation increase in PM2.5, significantly increased the risk of child mortality (Odds Ratio [OR]: 1.14; 95% Confidence Interval [CI]: 1.10-1.18; p < 0.001). Moderate and high household air pollution exposure also heightened this risk, with increases of 37% (OR: 1.37; 95% CI: 1.24-1.53; p < 0.001) and 40% (OR: 1.40; 95% CI: 1.26-1.56; p < 0.001), respectively, compared to no exposure. Multilevel models (Models 5a and 10a) produced similar estimates to standard logistic regression, indicating robust associations. Additionally, Population Attributable Fraction analysis revealed that approximately 11.9% of under-five mortality could be prevented by reducing ambient PM2.5 exposure and 12.0% by mitigating household air pollution. The interaction between indoor and outdoor pollution revealed complex dynamics, with moderate and high household exposure associated with a reduction in mortality risk when combined with PM2.5. Geographical disparities were observed, with stronger correlations between outdoor air pollution and child mortality in Africa compared to Asia, and more pronounced impacts in low-income countries. However, household air pollution had stronger association with child mortality in Africa and lower- and middle-income countries. CONCLUSIONS: Our findings could serve as a guide for policy development aimed at reducing under-five mortality, ultimately contributing to the attainment of the Sustainable Development Goal (SDGs).

Utilizing the CFIR framework for mapping the facilitators and barriers of implementing teachers led school mental health programs - a scoping review.

BACKGROUND: Ample evidence has been generated regarding the effectiveness of school-based mental health interventions as part of the continuum of care for children and capacity building of teachers to deal with the emotional and behavioral challenges of students. The increasing trend of utilization of teachers as the natural support system of children and the huge financial impact of public health interventions highlights the need to review all available evidence regarding multilevel factors that facilitate or pose a challenge to the provision of School Mental Health Programs (SMHP) using teachers as providers. The current review aims to map extracted evidence under the Consolidated Framework for Implementation Research (CFIR) domains to support future implementation research on school-based mental health services. METHODS: The scoping review included experimental, qualitative studies, and systematic reviews involving teacher-led mental health programs conducted in the school setting to improve the socio-emotional well-being of children and adolescents irrespective of time and geographical limitations. All (published and unpublished) evidence in English from Pubmed, Cochrane database of systematic reviews and clinical trials, Scopus, and Science Direct was searched using keywords and Boolean combinations and extracted using study designs, place of study, year of publication, sample size, and target population. A qualitative analysis of implementation facilitators and barriers cited by the studies was carried out and mapped on CFIR. RESULTS: This review identified barriers and facilitators of implementation across school-based mental health Programs in 29 studies. The major emerging themes were those related to the inner setting of the organization, the process of implementation, and the characteristics of individuals involved in implementation. These included the availability of structural characteristics, positive school culture, organizational readiness, committed leadership, and beliefs of the providers. CONCLUSION: Findings highlight the need for early assessment of contextual factors acting as barriers and facilitators and careful execution following realistic planning and stakeholders' engagement to ensure the success of SMHP.

Epidemiology, genetic characterization and population structure analysis of lumpy skin disease virus from North India.

Lumpy skin disease (LSD) is a transboundary, viral disease of cattle with a significant economic impact on the livestock industry. This study describes the epidemiological investigations of outbreaks of LSD that occurred in 2022 in three Indian states viz., Haryana, Himachal Pradesh and Rajasthan and the genetic characterization of Lumpy skin disease viruses (LSDVs). Also, the population structure analysis of LSDVs was carried out. Out of 138 scab samples tested from suspected cattle for LSDV, 106 were found positive. Of these, nine representative scab samples were further genetically characterized. Phylogenetic analysis based on the P32 and EEV gene sequences depicted that the LSDV strains of the present study had nucleotide identity of 100% and 99.10-99.45%, respectively with the LSDV/2019 field strains of India. Multiple sequence alignment of the EEV glycoprotein gene sequences revealed nucleotide polymorphisms at three positions viz., G178A, G253A and A459G in circulating LSDV/2022 field strains. Based on the median joining network analysis of the EEV gene, 12 haplotypes were identified among the LSDV populations. Population structure analysis corresponding to the EEV gene revealed high haplotype (0.8486 ± 0.026) and low nucleotide diversities (0.00636 ± 0.0006) and negative values for neutrality indices, indicating a high number of closely related haplotypes and the studied population may have undergone a recent expansion. The findings will help in understanding the distribution and dynamics of LSDV populations, which will prove pivotal in designing and implementing effective management and control strategies.

Postharvest handling of ethylene with oxidative and absorptive means.

Fruit ripening is an unfolding of a series of genetically-programmed modifications and tend to be highly orchestrated irrevocable phenomenon mediated by ethylene. Phytohormone ethylene also leads to over-ripening, senescence, loss of texture, microbial attack, reduced post-harvest life and other associated problems during storage and transportation of fruits. Its harmful impacts on fresh fruits, vegetables, and ornamentals result in substantial product losses even up to 80%. Curbing of this inevitable menace is therefore need of the hour. Accrual of ethylene in packaging system should fundamentally be ducked to extend the shelf-life and uphold an adequate superiority of perishables in visual and organoleptic terms. The current review discusses about properties, factors affecting and impact of ethylene, intimidation of its impact at gene vis-à-vis activity level using gene-modification/inhibition techniques, chemical/physical in conjunction with other suitable approaches. It also entails the most commercially cultivated approaches worldwide viz. KMnO4-based oxidation together with adsorption-based scrubbing of ethylene in thorough details. Future ethylene removal strategies should focus on systematic evaluation of KMnO4-based scavenging, exploring the mechanism of adsorption, adsorbent(s) behavior in the presence of other gases and their partial pressures, volatiles, temperature, relative humidity, development of hydrophobic adsorbents to turn-up under high RH, regeneration of adsorbent by desorption, improvement in photocatalytic oxidation etc. and further improvements thereof. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05777-1.

High-throughput capillary electrophoresis analysis of biopharmaceuticals utilizing sequential injections.

The complexity of biotherapeutic products implies an ever-increasing list of product quality attributes that need to be monitored and characterized. In addition, the growing interest in implementing process analytical technology in biopharmaceutical production has further increased the testing burden, together with the need for rapid testing that can facilitate real-time or near-real-time decision-making. Capillary electrophoresis (CE) has made a place in biopharmaceutical analysis but is regarded as a low-throughput method, with the instrument dead time constituting more than 80% of the total time of analysis. In this study, the dead time of CE was utilized to analyse 3 mAb samples in a single-CE run. This approach resulted in an up to 77% reduction in the total analysis time and increased the productivity by up to 300%, compared to traditional single CE-ultraviolet runs, without compromising resolution or relative peak areas. Additionally, good method reproducibility was observed. The compatibility of the method has been demonstrated with protein A eluate and cation exchange chromatography fractions. We, thus, propose that sequential injections can be applied for fast and robust CE analysis of biopharmaceuticals.

Management of tannery waste effluents towards the reclamation of clean water using an integrated membrane system: A state-of-the-art review.

Tanning and other leather processing methods utilize a large amount of freshwater, dyes, chemicals, and salts and produce toxic waste, raising questions regarding their environmental sensitivity and eco-friendly nature. Total suspended solids, total dissolved solids, chemical oxygen demand, and ions such as chromium, sulfate, and chloride turn tannery wastewater exceedingly toxic for any living species. Therefore, it is imperative to treat tannery effluent, and existing plants must be examined and upgraded to keep up with recent technological developments. Different conventional techniques to treat tannery wastewater have been reported based on their pollutant removal efficiencies, advantages, and disadvantages. Research on photo-assisted catalyst-enhanced deterioration has inferred that both homogeneous and heterogeneous catalysis can be established as green initiatives, the latter being more efficient at degrading organic pollutants. However, the scientific community experiences significant problems developing a feasible treatment technique owing to the long degradation times and low removal efficiency. Hence, there is a chance for an improved solution to the problem of treating tannery wastewater through the development of a hybrid technology that uses flocculation as the primary treatment, a unique integrated photo-catalyst in a precision-designed reactor as the secondary method, and finally, membrane-based tertiary treatment to recover the spent catalyst and reclaimable water. This review gives an understanding of the progressive advancement of a cutting-edge membrane-based system for the management of tanning industrial waste effluents towards the reclamation of clean water. Adaptable routes toward sludge disposal and the reviews on techno-economic assessments have been shown in detail, strengthening the scale-up confidence for implementing such innovative hybrid systems.

To decipher the phytochemical agent and mechanism for Urginea indica mediated green synthesis of Ag nanoparticles and investigation of its antibacterial activity against Methicillin-resistant Staphylococcus aureus.

Globally, Methicillin-Resistant Staphylococcus aureus bacteraemia is one of the commonest bloodstream infections associated with clinical complications and high mortality. Thence, devising effective and targeted biogenic silver based strategies are in great demand. However, limited insights regarding the biosynthesis methodologies impedes the possible scale up and commercial potentials. We, hereby demonstrate the biosynthesis of Ag nanoparticles using the phytochemical agent extracted and purified from bulb extract of Urginea indica. The chemical structure of the phytochemical agent is investigated by various chromatographic and spectroscopic techniques and was found closely relatable to N-ethylacetamide. Ag nanoparticles synthesis by this agent was found to have a strong Surface Plasmon band at 402 nm. X-ray diffraction and transmission electron microscopy further validated the formation of Ag nanoparticles with face-centred cubic structure with a size range of 20-30 nm. The biogenic metal nanoparticles have shown potential antibacterial activity against S. aureus and MRSA (within a range of 10-50 µg/mL). The nanoparticles have also shown promising anti-biofim activity against the above mentioned strains. The nanoparticles were expected to induce ROS mediated bactericidal mechamism. Cell viability and in-vitro infection studies advocate noticeable biocompatibility and future clinical potential of the developed nanoparticles against Staphylococcus infections.

Compensated Advanced Chronic Liver Disease in Nonalcoholic Fatty Liver Disease: Two-Step Strategy is Better than Baveno Criteria.

BACKGROUND: Advanced fibrosis and cirrhosis (compensated advanced chronic liver disease [cACLD]) are clinically indistinguishable and increase risk of developing clinically significant portal hypertension. Baveno VII recommends using elastography to rule out and diagnose cACLD with liver stiffness measurement (LSM) cut-offs of 10/15 kPa. METHODS: In a retrospective analysis of 330 nonalcoholic fatty liver disease (NAFLD) patients, performance of the Baveno VII cut-offs for diagnosing cACLD was compared with newly suggested lower cut-offs (8/12 kPa). A model for detecting cACLD among those with LSM between 8 and 12 kPa was developed and compared with recently published models. RESULTS: Seventy (21.2%) of the 330 NAFLD patients had biopsy-proven cACLD. The Baveno VII cut-offs (10/15 kPa) had a lower sensitivity of 72.8% (60.9-82.8%) and a specificity of 93.4% (89.7-96.1%). Sensitivity and specificity of lower cut-offs (8/12 kPa) were 91.4% (82.3-96.8%) and 88.5% (83.9-92.1%), respectively. Modeling based on the presence of diabetes (odds ratio [OR] 3.625[1.161-11.320], p = 0.027) and serum aspartate aminotransferase (AST) levels (OR 1.636[1.098-2.436], p = 0.015) correctly identified 75.7% of patients with LSM between 8 and 12 kPa. Our model performed best with an area under receiver operator curve (AUROC) of 0.725 (95%CI 0.609-0.822), compared to Papatheodoridi (AUROC 0.626, CI 0.506-.736) and Zhou (AUROC 0.523, CI 0.403-0.640) models. A two-step strategy comprising application of lower LSM cut-offs followed by the predictive model correctly identified the presence of cACLD in 83% of the patients as compared to 75% by the Baveno VII cut-offs. CONCLUSION: A two-step strategy employing lower LSM cut-offs and modeling based on diabetes and AST levels outperforms Baveno VII cut-offs for identifying cACLD in NAFLD patients.

Variation in Early Pediatric Intensive Care Management Strategies and Duration of Invasive Mechanical Ventilation for Acute Viral Bronchiolitis in the United Kingdom: A Retrospective Multicenter Cohort Study.

OBJECTIVES: Management of mechanically ventilated patients with bronchiolitis is not standardized and duration of mechanical ventilation has been shown to vary widely between centers. The aim of this study was to examine practice in a large number of U.K. PICUs with a view to identify if early management choices relating to fluid prescription, sedative agent use, and endotracheal tube (ETT) placement were associated with differences in duration of invasive mechanical ventilation (IMV). DESIGN: Retrospective multicenter cohort study. Primary outcome was duration of IMV. A hierarchical gamma generalized linear model was used to test for associations between practice variables (sedative and neuromuscular blocking agents, route of endotracheal intubation at 24 hr and fluid balance at 48 hr) and duration of IMV after adjustment for known confounders. SETTING: Thirteen U.K. PICUs. Duration of 2 months between November and December 2019. PATIENTS: Three hundred fifty infants receiving IMV for bronchiolitis. Excluded were patients receiving long-term ventilation, extracorporeal life support, or who died before separation from IMV. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After adjustment for confounders, several variables were associated with an increase in the geometric mean duration of IMV (expressed as a percentage) including: nasal ETT use, 16% (95% CI, 1-32%); neuromuscular blockade use, 39% (95% CI, 21-61%); and fluid balance at 48 hr, 13% per 100 mL/kg positive fluid balance (95% CI, -1% to 28%). The association of sedative use varied with class of agent. The use of an alpha-2 agonist alone was associated with a reduction in duration of IMV by 19% in relation to no sedative agent (95% CI, -31 to -5%), whereas benzodiazepine uses alone or with alpha-2 agonist in combination were similar to using neither agent. CONCLUSIONS: Early management strategies for bronchiolitis were associated with the duration of IMV across U.K. centers after adjustment for confounders. Future work should prospectively assess the impact of fluid restriction, route of endotracheal intubation, and alpha-2 agonist use on duration of IMV in infants with bronchiolitis, with the aim of reducing seasonal bed pressure.

Body weight loss and glycemic control on the outcomes of patients with NAFLD. The role of new antidiabetic agents.

Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide affecting a third of adults and 12% of children in Western countries. In around 50-60%% of cases, NAFLD and type 2 diabetes mellitus (T2DM) coexist and act synergistically to increase the risk of adverse hepatic and extra-hepatic outcomes. T2DM is a strong risk factor for rapid progression of NAFLD to nonalcoholic steatohepatitis (NASH), cirrhosis or hepatocellular carcinoma (HCC), which have become frequent indications of liver transplantation. The pathophysiology of NAFLD is complex and its relationship with T2DM is bidirectional, where lipotoxicity and insulin resistance (IR), act as the strongest pillars. To date, no pharmacological treatment has been approved for NAFLD. However, there is an intense research with numerous drugs focused on reversing inflammation and liver fibrosis through modulation of molecular targets without good results. It has been known for some time that weight reduction >10% is associated to histological improvement of NAFLD. Recently, glycemic control has been shown to induce similar results. Diet and physical exercise for weight reduction have limitations, so alternative methods (pharmacologic, endoscopic or surgical) may be required. Currently, new antidiabetic drugs inducing weight loss, have been recently approved for the treatment of obesity. Nevertheless, their therapeutic effects on NAFLD have not been extensively studied. We will review here, recently published data on the effects of weight loss and glycemic control on the histological and metabolic parameters of NAFLD and recent published data on therapeutic studies of NAFLD with new antidiabetic drugs.

Binding of the Mycobacterium tuberculosis EccCb1 ATPase double hexameric ring to the EsxAB virulence factor is enhanced by ATP.

The EccC enzyme of Mycobacterium tuberculosis ESX-1 secretion system is involved in EsxAB virulence factor secretion and offers an attractive target for antivirulence inhibitors development against M. tuberculosis. The EccCb1 polypeptide of the EccC enzyme contains two Ftsk/SpoIIIE type ATPase domains (D2 and D3) and binds to the EsxAB factor at the C-terminal region of the D3 domain. In the current study, we have determined a low-resolution structure of EccCb1, and its mechanism involved in ATPase activity and EsxAB factor binding. Small-angle X-ray scattering data yielded a double hexameric ring structure of EccCb1 in solution and was further confirmed by SEC-MALS and dynamic light scattering. ATPase activity of wild-type, D2, and D3 mutants showed that D2-K90A and D3-K382A mutations led to a complete loss of enzyme activity. The full-length EccCb1 showed ∼3.7-fold lower catalytic efficiency than D2 domain and ∼1.7 fold lower than D3 domain. The EsxAB factor binds EccCb1 with Kd ∼ 11.3 ± 0.6 nM and its affinity is enhanced ∼2 fold in presence of ATP + Mg2+. These data indicate the involvement of ATPase activity in EsxAB factor translocation. Molecular dynamics simulation on wild-type, ATP + Mg2+, and EsxAB + ATP + Mg2+ bound EccCb1 double-ring structure showed enhanced stability of enzyme upon ATP + Mg2+ and EsxAB binding. Overall, our study showed a low-resolution structure of EccCb1, and the mechanism involved in ATPase activity and EsxAB factor recognition, which can be targeted for the development of antivirulence drugs against M. tuberculosis.

Therapeutic plasma-exchange improves short-term, but not long-term, outcomes in patients with acute-on-chronic liver failure: A propensity score-matched analysis.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is associated with a high short-term mortality rate in the absence of liver transplantation. The role of therapeutic plasma exchange (TPE) in improving the outcomes of ACLF and acute decompensation (AD) is unclear. In this retrospective analysis, we aimed to determine the impact of TPE on mortality in patients with ACLF. METHODS: ACLF patients receiving TPE with standard medical treatment (SMT) were propensity score matched (PSM) with those receiving SMT alone (1:1) for sex, grades of ACLF, CLIF C ACLF scores, and the presence of hepatic encephalopathy. The primary outcomes assessed were mortality at 30 and 90 days. Survival analysis was performed using Kaplan Meier survival curves. RESULTS: A total of 1151 patients (ACLF n = 864 [75%], AD [without organ failure] n = 287 [25%]) were included. Of the patients with ACLF (n = 864), grade 1, 2, and 3 ACLF was present in 167 (19.3%), 325 (37.6%), and 372 (43.0%) patients, respectively. Thirty-nine patients received TPE and SMT, and 1112 patients received only SMT. On PSM analysis, there were 38 patients in each group (SMT plus TPE vs SMT alone). In the matched cohort, the 30-days mortality was lower in the TPE arm compared to SMT (21% vs 50%, P = .008), however, the 90-day mortality was not significantly different between the two groups (36.8% vs 52.6%, P = .166); HR, 0.82 (0.44-1.52), P = .549. CONCLUSION: TPE improves short-term survival in patients with ACLF, but has no significant impact on long-term outcomes. Randomized control trials are needed to obtain a robust conclusion in this regard.

Barriers experienced by community midwives to provide basic emergency obstetric and newborn care in rural Pakistan.

BACKGROUND: Considering the high maternal mortality rate, the government of Pakistan has deployed Community Midwives (CMWs) in rural areas of Pakistan. This relatively new cadre of community-based skilled birth attendants has previously reported to experience several challenges in providing maternal and child healthcare. However, what barriers they experience in providing basic emergency obstetric and newborn care needs to be further studied. METHODS: This was a cross-sectional study conducted in twelve districts in Sindh province, Pakistan, with poor maternal and child health indicators. A total of 258 CMWs participated in this study and completed the questionnaire on a pretested, validated tool in their community-based stations. The trained data collectors completed the questionnaires from the respondents. The problems identified were categorized into three major issues: financial, and transport and security related; and were analyzed accordingly. Ethical approval was obtained from the institutional review board (IRB) of Health Services Academy (HSA) Islamabad, Pakistan. RESULTS: The majority (90%) of 258 CMWs had formal training in maternal and neonatal care from the recognized institutions. Financial difficulties faced by CMWs were identified as the most frequent barriers and others were transport, security, and other issues. In univariate analysis, 38.1% and 61.9% of the community midwives who faced financial difficulties had completed a graduation or intermediate level of education, respectively (p = 0.006). Round-the-clock availability for emergencies was inversely associated with having financial difficulties, i.e., 71.4%, in contrast to 28.4% who had financial difficulties were available round-the-clock for emergency calls in their community clinics (p = 0.008). Formal training (p = 0.001), work experience (p = 0.015), longer duration of work (p = 0.003), and liaison with health workers and posting district (p = 0.001) had statistically significantly higher transport related issues. Security difficulties faced by CMWs and a set of correlates such as formal training (p = 0.019), working experience (p = 0.001), longer duration of work (p = 0.023), 24 h of availability on call (p = 0.004), liaison with traditional birth attendants (TBAs) in the community (p = 0.002), and district of posting (p = 0.001) were statistically significantly different. Other issues like working experience (p = < 0.001) and Liaison with TBAs in the community (p = < 0.001) were found statistically significant. CONCLUSION: Financial, transportation and security related barriers were commonly reported by community midwives in the delivery of basic emergency obstetric and newborn care in rural Pakistan.

Effect of BsaA I genotyped intronic SNP of leptin gene on production and reproduction traits in Indian dairy cattle.

In the present study, candidate single nucleotide polymorphism (SNP) g.92450765 G > A of leptin gene was explored for Bos indicus cattle with an aim to explore its possible effect on production and reproduction traits. The genotypic and allelic frequencies of BsaA 1 genotyped SNP g.92450765 G > A indicated the predominance of AG (0.65) genotyped Sahiwal cows in our studied population. The least-squares analysis showed a significant association (p < 0.05) of identified genetic variants with total milk yield (TMY) and 305 days milk yield (MY) (p < 0.05). The GG genotyped cows were found to be associated with higher milk yields. However, for reproduction traits under study AA genotype was found to be more favorable with respect to service period and calving interval (p < 0.05). Computational analysis was also performed to predict changes if any in the transcription factor binding sites (TFBS) caused due to the identified SNP in the intronic region of the leptin gene. TFBS analysis predicted that the targeted SNP at g.92450765G > A may lead to the disappearance of TFBS such as Hypermethylated in cancer 2 protein (HIC2), Max-binding protein MNT (MNT), Cyclic AMP-dependent transcription factor -3 (ATF3), Myc-associated factor X (MAX) and Microphthalmia-associated transcription factor (MITF). It may lead to changes in transcriptional regulation.

Synthesis of green emissive terbium(III) complexes for displays: Optical, electrochemical and photoluminescent analysis.

A series of heteroleptic terbium(III) complexes with fluorinated 2-thenoyltrifluoroacetone (TTFA) and other heteroaromatic units have been synthesized. The developed heteroleptic complexes were inspected via elemental study, cyclic voltammetry, thermal analysis and spectroscopic investigations. Optical band-gap data proposed the conducting property of prepared complexes. The photoluminescence emission profiles illustrated peaks based on terbium(III) cation (Tb3+ ) positioned at ~617, 586, 546 and 491 nm, imputed to 5 D4 to 7 FJ (J = 3,4,5,6) transitions separately. Most intense peak at 546 nm corresponding to 5 D4 → 7 F5 transition is accountable for the green emissive character of developed complexes. The luminous character of complexes reveals the sensitization of Tb3+ by ligands. Color parameters further corroborates the green emanation of Tb3+ complexes. The photometric characteristics of complexes recommended their usages in designing display devices.

Genome-Wide Meta-Analysis of QTLs Associated with Root Traits and Implications for Maize Breeding.

Root system architecture (RSA), also known as root morphology, is critical in plant acquisition of soil resources, plant growth, and yield formation. Many QTLs associated with RSA or root traits in maize have been identified using several bi-parental populations, particularly in response to various environmental factors. In the present study, a meta-analysis of QTLs associated with root traits was performed in maize using 917 QTLs retrieved from 43 mapping studies published from 1998 to 2020. A total of 631 QTLs were projected onto a consensus map involving 19,714 markers, which led to the prediction of 68 meta-QTLs (MQTLs). Among these 68 MQTLs, 36 MQTLs were validated with the marker-trait associations available from previous genome-wide association studies for root traits. The use of comparative genomics approaches revealed several gene models conserved among the maize, sorghum, and rice genomes. Among the conserved genomic regions, the ortho-MQTL analysis uncovered 20 maize MQTLs syntenic to 27 rice MQTLs for root traits. Functional analysis of some high-confidence MQTL regions revealed 442 gene models, which were then subjected to in silico expression analysis, yielding 235 gene models with significant expression in various tissues. Furthermore, 16 known genes viz., DXS2, PHT, RTP1, TUA4, YUC3, YUC6, RTCS1, NSA1, EIN2, NHX1, CPPS4, BIGE1, RCP1, SKUS13, YUC5, and AW330564 associated with various root traits were present within or near the MQTL regions. These results could aid in QTL cloning and pyramiding in developing new maize varieties with specific root architecture for proper plant growth and development under optimum and abiotic stress conditions.

Modelling the impact of climate change on dengue outbreaks and future spatiotemporal shift in Pakistan.

Climate change has a significant impact on the intensity and spread of dengue outbreaks. The objective of this study is to assess the number of dengue transmission suitable days (DTSD) in Pakistan for the baseline (1976-2005) and future (2006-2035, 2041-2070, and 2071-2099) periods under Representative Concentration Pathway (RCP4.5 and RCP8.5) scenarios. Moreover, potential spatiotemporal shift and future hotspots of DTSD due to climate change were also identified. The analysis is based on fourteen CMIP5 models that have been downscaled and bias-corrected with quantile delta mapping technique, which addresses data stationarity constraints while preserving future climate signal. The results show a higher DTSD during the monsoon season in the baseline in the study area except for Sindh (SN) and South Punjab (SP). In future periods, there is a temporal shift (extension) towards pre- and post-monsoon. During the baseline period, the top ten hotspot cities with a higher frequency of DTSD are Karachi, Hyderabad, Sialkot, Jhelum, Lahore, Islamabad, Balakot, Peshawar, Kohat, and Faisalabad. However, as a result of climate change, there is an elevation-dependent shift in DTSD to high-altitude cities, e.g. in the 2020s, Kotli, Muzaffarabad, and Drosh; in the 2050s, Garhi Dopatta, Quetta, and Zhob; and in the 2080s, Chitral and Bunji. Karachi, Islamabad, and Balakot will remain highly vulnerable to dengue outbreaks for all the future periods of the twenty-first century. Our findings also indicate that DTSD would spread across Pakistan, particularly in areas where we have never seen dengue infections previously. The good news is that the DTSD in current hotspot cities is projected to decrease in the future due to climate change. There is also a temporal shift in the region during the post- and pre-monsoon season, which provides suitable breeding conditions for dengue mosquitos due to freshwater; therefore, local authorities need to take adaption and mitigation actions.

A study of the diagnostic efficacy of diffusion-weighted magnetic resonance imaging in the diagnosis of perianal fistula and its complications.

Purpose: To determine the diagnostic efficacy of diffusion-weighted magnetic resonance imaging (DWI) in the diagnosis of perianal fistula and its complications. Material and methods: This is a retrospective study based on the data of 47 patients with a clinical diagnosis of perianal fistula, who had an MRI study performed on a 1.5-T GE Signa MR scanner. DWI sequences were done using 3 different b-values. Other routine MR sequences were included. The MR images were studied to compare the diagnostic efficacy of the DW MRI sequence and other sequences in diagnosing perianal fistula and its complications. Apparent diffusion coefficient (ADC) values of abscesses and inflammatory soft tissue lesions were measured using ADC maps. The standard reference to obtain diagnostic efficacy was post-surgical data. Results: Seventy-nine perianal fistulas were diagnosed in 47 patients who had undergone an MRI study. The sensitivity and specificity of different MR sequences in diagnosing perianal fistulas are T2 FSFSE: 92% sensitivity; DWI: 96% sensitivity; combined T2+DWI: 100% sensitivity; and post-gadolinium T1 FS has 100% sensitivity in diagnosing perianal fistulas. The mean apparent diffusion coefficient for the abscess in our study was 0.990 ± 0.05 × 10-3, and the mean apparent diffusion coefficient for an inflammatory soft tissue lesion was 1.440 ± 0.05 × 10-3. The optimal ADC cut-off for the abscess was 1.098 × 10-3 mm2/s showing 100% sensitivity and 93.8% specificity. Conclusions: DW imaging is a reliable sequence to diagnose perianal fistula and its complications. Measurement of ADC values is reliable in diagnosing perianal abscess collection. DWI sequence helps patients with renal impairment in whom IV gadolinium is contraindicated.