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Background: The Lesbian, Gay, Bisexual, Transgender and additional Queer, Intersex, asexual and agender (LGBTQIAA+) community is roughly 3.8% of the population of India. However, the services in terms of availability and competence are currently limited in the Indian healthcare system.Aim: To assess self-reported competence and preparedness of primary healthcare individuals and trainees in India (primarily Delhi) and compare the findings with Western studies.Setting and design: A cross-sectional study was designed to study sexual and gender minority (SGM) healthcare issues related to the competence and preparedness among the primary healthcare individuals and trainees at a tertiary healthcare centre. The study population included: Faculty members, Residents, Postgraduate trainees, Undergraduate trainees and Nursing staff. The study was conducted using an online Google survey after ethical clearance.Method and material: A cross-sectional Web-based survey was conducted for the medical and nursing healthcare professionals and trainees at a tertiary healthcare centre to assess competence and preparedness to deal with SGM healthcare issues using a questionnaire for the assessment of self-reported competence, comfort and preparedness for sexual orientation, gender identity and sex development health issues based on competencies outlined by the AAMC (Association of American Medical Colleges). A minimum of 25 participants in each of the four equally stratified groups were recruited using purposive sampling over 3 months.Statistical analysis used: The data was analysed using Epicollect software.Results: Satisfactory comfort and competence among the study groups are in line with the available Western literature though contrary to findings of Indian studies where inadequacy of knowledge regarding homosexuality was a major finding. A majority of positive responses in comfort, competency and knowledge are reflective of the change in attitude and culture among the modern society and effectiveness of awareness and support groups in government colleges of Delhi which was comparable with the available Indian and Western literature.Conclusion: Our study is a pioneer work to assess the healthcare workers’ skills in the assessment approach for the SGM population. The findings of our study may be useful further to develop objective measures to evaluate the competency and knowledge of healthcare providers.

AbstractOwning to unique size dependent optical properties, plasmonic nanoparticles have been explored as chemical read-outs for assaying various biological and chemical analytes. We propose colorimetric sensing strategy based on tannic acid mediated silver nanoparticles (TA-AgNPs) for the detection of Coralyne (COR) and calf thymus DNA (CT-DNA). Aggregation of TA-AgNPs is observed on addition of COR molecule because of electrostatic interaction between them, which is established by change in color from yellow to brown. TA-AgNPs/COR based colorimetric probe was then employed for CT-DNA detection, utilizing anti-aggregation of nanoparticles. Formation of intercalated complex between CT-DNA and COR prevents the aggregation of nanoparticles and color of TA-AgNPs solution remains yellow. Under optimum sensing conditions, extent of aggregation and anti-aggregation of TA-AgNPs was studied. A linear correlation between absorbance value at 437 nm and COR concentration is obtained in the range of 0 to 1.2 μM with detection limit of 0.44 μM. TA-AgNPs/COR based detection probe exhibited linear response to CT-DNA in concentration range of 0 to 7.62 μM with a limit of detection down to 1.63 μM. The applicability of sensing strategy verified by analysis of COR and CT-DNA in human urine samples, which demonstrated the practical utility of method in biomedical applications.

Inverted stacking of layers or p-i-n configuration-based perovskite solar cells are gaining popularity due to their superior operational stability and lower processing temperatures over conventional stacking. Instead of potentially hazardous Pb-based perovskite solar cells, the B-γ-CsSnI3black orthorhombic solar cell is a potential alternative. We carried out a thorough investigation using drift-diffusion numerical modeling based on a p-i-n structure with four HTL layers (NiOx, CuO, PEDOT:PSS, and P3HT) and three electron transport layers (ETLs) (C60, PDINO, and PCBM). The transport layers are initially filtered based on the micro-offset between the interface layer and the energy levels of the perovskite absorber. At a valence band offset of ∼0.2 eV, for NiOx, a high-power conversion efficiency (PCE) of ∼24% is achieved. PCBM has exhibited the best ETL performance across all HTL combinations due to its efficient electron extraction characteristics. Further, PCE is optimized against concentrations of deep defects in the absorber layer, trap sites in the interfaces, and the doping of the transport layer for a better understanding of the practical devices. To combat the suboptimal electronic transitions belonging to >600 nm wavelength highlighted by density functional theory simulations in the study, we investigated the variations in absorber thickness, revealing ∼1.0 μm as a suitable absorber thickness. We also accounted for temperature and sheet resistance variance and the multiple location spectrum caused by climatic and geographical factors. The findings suggest the suitability of NiOxHTL for PCE > 24%, and it will help experimentalists better understand charge transport.

Obstructive Sleep Apnea (OSA) is a significant health concern characterized by recurrent upper airway blockages during sleep, causing various health issues. There's growing evidence of a link between air pollution and OSA, though research results have been inconsistent. This systematic review and meta-analysis aims to consolidate and examine data on the relationship between air pollution and OSA's risk and severity.

This research investigates the effect of workplace cyberbullying on innovative work behavior within Pakistan’s telecommunications sector, highlighting the mediating role of employee withdrawal and the novel moderating role of bystander behavior. Unlike existing literature that predominantly addresses cyberbullying among youth, this study extends the discourse to adult professional environments, emphasizing unique workplace dynamics. Employing structural equation modeling on data from 385 employees, the findings reveal that cyberbullying significantly increases employee withdrawal, which in turn negatively impacts innovative behavior. Critically, the study unveils the effects of bystander behavior: active bystanders can mitigate, while passive bystanders exacerbate the adverse effects of cyberbullying. These results underscore the profound influence of workplace social interactions on cyberbullying outcomes and innovative capacity. The study’s contributions are twofold: theoretically, it expands psychological strain theory by integrating bystander behavior into the framework, offering a deeper understanding of social dynamics in cyberbullying; practically, it suggests a strategic focus for organizations on fostering active bystander behavior to combat cyberbullying and support innovation. This research prompts reevaluating workplace policies and culture to enhance resilience against cyberbullying and safeguard innovation.

Ionic liquids (ILs) are poorly-coordinated ionic salts that can exist as a liquid at room temperatures (or <100 °C). ILs are also referred to as "designer solvents" because so many of them have been created to solve particular synthetic issues. ILs are regarded as "green solvents" because they have several distinctive qualities, including better ionic conduction, recyclability, improved solvation ability, low volatility, and thermal stability. These have been at the forefront of the most innovative fields of science and technology during the past few years. ILs may be employed in new drug formulation development and drug design in the field of pharmacy for various functions such as improvement of solubility, targeted drug delivery, stabilizer, permeability enhancer, or improvement of bioavailability in the development of pharmaceutical or vaccine dosage formulations. Ionic liquids have become a key component in various areas such as synthetic and catalytic chemistry, extraction, analytics, biotechnology, etc., due to their superior abilities along with highly modifiable potential. This study concentrates on the usage of ILs in various pharmaceutical applications enlisting their numerous purposes from the delivery of drugs to pharmaceutical synthesis. To better comprehend cuttingedge technologies in IL-based drug delivery systems, highly focused mechanistic studies regarding the synthesis/preparation of ILs and their biocompatibility along with the ecotoxicological and biological effects need to be studied. The use of IL techniques can address key issues regarding pharmaceutical preparations such as lower solubility and bioavailability which plays a key role in the lack of effectiveness of significant commercially available drugs.

In the pursuit of highly effective capacitive temperature sensors, a pivotal requirement lies in discovering materials that exhibit a high temperature-dependent variation in capacitance, i.e., high dC/dT value, while retaining the essential linearity within their temperature-dependent capacitive response. Relaxor ferroelectric (RFE) materials have been known for their nearly linear behavior, while antiferroelectric (AFE) materials showcase high dC/dT values. Bridging these two different classes could hold the key to unlocking high-temperature sensing capabilities. In this study, we synthesized composite materials of ( ${1}- {x}$ )Bi2MnCoO6–( ${x}$ ) NaNbO3 (with ${x}$ = 0, 0.02, 0.04, and 0.06) via the solid-state reaction method where the synergy of these materials can fulfill both requirements of linearity and sensitivity simultaneously. The dielectric response of all the synthesized composites showed almost linear behavior with high dC/dT values. The temperature-dependent capacitive response reveals that the sensitivity of Bi2MnCoO6 (RFE) is 0.42 pF $\cdot ^{\circ }\text {C}^{\text {-1}}$ within the temperature range of 35 °C–110 °C. However, the sensitivity improves significantly with the addition of NaNbO3 (AFE). The composite material with an ${x}$ value of 0.06 demonstrates the highest average sensitivity of 115 pF $\cdot ^{\circ }\text{C}^{\text {-1}}$ out of all the materials, specifically within a temperature range of 35 °C–240 °C. This study shows that the synergistic approach of utilizing RFE and AFE composites can pave the way to design a promising temperature sensor with enhanced sensitivity.

There is a significant regional variation in India's consumption patterns of electricity despite a steady rise in electrical demand. Utilizing hourly, daily, and annual data, this study analyzes electricity demand trends in Rajasthan and Maharashtra. These predictions represent a confluence of historical data analysis and advanced machine learning techniques, offering insights into future electricity demand that can inform policy-making, infrastructure development, and energy planning in the context of growing environmental and economic challenges. Despite Maharashtra's larger industrial and residential base, Rajasthan's moderate growth contrasts with its high, fluctuating demand. Detailed investigation reveals increasing annual consumption in both states, with seasonal peaks likely linked to cooling load. Moreover, the findings highlight the need for energy policies and infrastructure that are aligned with the socioeconomic composition of each state. Linkages with tourism are also explored. This comparative analysis provides valuable insight into how electricity infrastructure should be planned for future sustainable development.

AbstractThe advent in nanoscience and nanotechnology has enabled the successful synthesis and characterization of different nanomaterials with unique electrical, optical, magnetic and catalytic activities. However, with respect to sensing applications, nanomaterials intrinsically lack target recognition ability to selectively bind with the analyte. DNA, an important genetic material carrying biopolymer is polymorphic in nature and shows structural polymorphism, forming secondary/multistranded structures like hairpin, cruciform, pseudoknot, duplex, triplex, G-quadruplex and i-motif. Studies reported so far have suggested that these polymorphic structures have been targeted specifically for the treatment or diagnosis of various diseases. DNA is widely used in conjugation with nanomaterials for the development of nanoarchitectures due to its rigidity, sequence programmability and specific molecular recognition, which makes this biomolecule a treasure for designing of DNA based frameworks. These two entities (DNA and nanomaterials) can be used in association with each other, as their alliance can result into creation of novel assay platforms for different purposes, ranging from imaging, sensing and diagnostics to targeted delivery. In this review, we have discussed about the recent reports on association of various mutistranded/ polymorphic forms of DNA with nanomaterials. Furthermore, different applications using this versatile DNA-nanomaterial assembly has also been elaborated at length. This review aims to target the interests of scientists from various interdisciplinary fields, including biologists, chemists and nanotechnologists, who wish to gain an understanding of nano-fabrications using a plethora of DNA polymorphic forms.Communicated by Ramaswamy H. Sarma

In this research, we conducted a detailed granulometric analysis of 9.5 m thick palaeolake succession, exposed at Bilaspur (Bhimtal) in the Kumaun Lesser Himalaya to reconstruct the palaeoenvironmental and palaeoclimatic conditions. We carried out statistical parameters of grain-size data (i.e., standard deviation, kurtosis, and skewness, bivariate plots), and end member modelling analysis (EMMA) and our study reveal sediment’s unimodal and bimodal nature, deposited via fluvial action under low to high energy environmental conditions since the origin of the lake. Some parts of the deposit show poorly sorted and mixed character (leptokurtic to platykurtic) of sediments, indicating that the sediments were primarily transported from the proximal area of the lake basin under low-energy environmental conditions. The finely skewed and poorly sorted sediments show different modes of grain size distribution, which are attributed to fluctuations in the hydrodynamic conditions of the lake. The arid climatic conditions prevailed in the valley from ca. 42 to 40 ka BP, followed by warm and moist conditions from ca. 40 to 39 ka BP. The arid conditions under the low rainfall regime were experienced by the valley from ca. 39 to 30 ka BP, while it exercised another episode of moist and warmer conditions from ca. 30 to 24 ka BP. Further, the end-Member Modelling Analysis (EMMA) shows four end members (EM1-EM4) with different climatic conditions during the deposition, e.g., clay to fine silt-size particles reflecting higher lake levels under warm-wet climatic conditions, coarse silt fraction representing moderate energy conditions, and fine to coarse sand fractions indicating shallow lake-level conditions in the arid climatic conditions as well higher energy flow. The interpretation of energy conditions in the lake and catchment area by using various methods reveals different palaeoenvironmental conditions during the sediment deposition.

Despite the progress made in the development of new antiepileptic drugs (AEDs), poor response to them is a rising concern in epilepsy treatment. Of several hypotheses explaining AED treatment failure, the most promising theory is the overexpression of multidrug transporters belonging to ATP-binding cassette (ABC) transporter family at blood–brain barrier. Previous data show that AEDs themselves can induce these transporters, in turn affecting their own brain bioavailability. Presently, this induction and the underlying regulatory mechanism involved at human blood–brain barrier is not well elucidated. Herein, we sought to explore the effect of most prescribed first- and second-line AEDs on multidrug transporters in human cerebral microvascular endothelial cells, hCMEC/D3. Our work demonstrated that exposure of these cells to valproic acid (VPA) induced mRNA, protein, and functional activity of breast cancer resistance protein (BCRP/ABCG2). On examining the substrate interaction status of AEDs with BCRP, VPA, phenytoin, and lamotrigine were found to be potential BCRP substrates. Furthermore, we observed that siRNA-mediated knockdown of peroxisome proliferator-activated receptor alpha (PPARα) or use of PPARαantagonist, resulted in attenuation of VPA-induced BCRP expression and transporter activity. VPA was found to increase PPARαexpression and trigger its translocation from cytoplasm to nucleus. Findings from chromatin immunoprecipitation and luciferase assays showed that VPA enhances the binding of PPARαto its response element in the ABCG2promoter, resulting in elevated ABCG2transcriptional activity. Taken together, these in vitro findings highlight PPARαas the potential molecular target to prevent VPA-mediated BCRP induction, which may have important implications in VPA pharmacoresistance.SIGNIFICANCE STATEMENTInduction of multidrug transporters at blood–brain barrier can largely affect the bioavailability of the substrate antiepileptic drugs in the brains of patients with epilepsy, thus affecting their therapeutic efficacy. The present study reports a mechanistic pathway of breast cancer resistance protein (BCRP/ABCG2) upregulation by valproic acid in human brain endothelial cells via peroxisome proliferator-activated receptor alpha involvement, thereby providing a potential strategy to prevent valproic acid pharmacoresistance in epilepsy.

AbstractG-rich sequences are intrinsic parts of the genome, widespread in promoters, telomeres, or other regulatory regions. The in vivoexistence and biological significance have established the functional aspect of G-quadruplex structures and thus have developed immense interest in exploring their therapeutic aspects. Herein, using biophysical methods, we examined the structural status and comprehensive cation-dependence of a 17-bp G-rich genomic sequence (SKGT17) located in the coding region of the human TRPA1 gene, known to be associated with various neurovascular, cardiovascular, and respiratory conditions. TRPA1is primarily seen as a therapeutic target for the development of novel analgesics. Bioinformatics analysis has suggested that 17-bp quadruplex motif is a binding site for transcription factor 'Sp1'. The formation and recognition of SKGT17 G-quadruplex might impact its regulatory functioning. Biophysical studies confirmed that the presence of alkali metal ions facilitated the formation of G-quadruplex in parallel topology. Native gel further substantiated the formation of a biomolecular species. Circular dichroism (CD), UV-thermal melting (Tm), and CD melting confirmed the formation of parallel G-quadruplex with metal ion-dependent stability. The stability of the G-quadruplex formed is found to be significantly high in the presence of K+ ions than that of other ions. Intriguingly, we have also established that this segment of the TRAP1 gene favors G-quadruplex formation over its participation in the corresponding duplex formation under K+ ions conditions. This study attempts to explain the rationale for the stabilization of G-quadruplex in the presence of alkali metal ions and may add to a better understanding and insights into DNA-metal ions interactions.

Epilepsy treatment is challenging due to heterogeneous syndromes, different seizure types and higher inter-individual variability. Identification of genetic variants predicting drug efficacy, tolerability and risk of adverse-effects for anti-seizure medications (ASMs) is essential. Here, we assessed the clinical actionability of known genetic variants, based on their functional and clinical significance and estimated their diagnostic predictability. We performed a systematic PubMed search to identify articles with pharmacogenomic (PGx) information for forty known ASMs. Functional annotation of the identified genetic variants was performed using different in silico tools, and their clinical significance was assessed using the American College of Medical Genetics (ACMG) guidelines for variant pathogenicity, level of evidence (LOE) from PharmGKB and the United States-Food and drug administration (US- FDA) drug labelling with PGx information. Diagnostic predictability of the replicated genetic variants was evaluated by calculating their accuracy. A total of 270 articles were retrieved with PGx evidence associated with 19 ASMs including 178 variants across 93 genes, classifying 26 genetic variants as benign/ likely benign, fourteen as drug response markers and three as risk factors for drug response. Only seventeen of these were replicated, with accuracy (up to 95%) in predicting PGx outcomes specific to six ASMs. Eight out of seventeen variants have FDA-approved PGx drug labelling for clinical implementation. Therefore, the remaining nine variants promise for potential clinical actionability and can be improvised with additional experimental evidence for clinical utility.

Purpose: Green innovation, particularly in manufacturing firms, is one of the most advocated methods to curb the effects of climate change. This study aims to investigate the impact of the integration of green customers and suppliers on the green innovation performance of food manufacturing firms in Pakistan. The institutional and resource-based view theories determine the moderating role of regulatory pressure and the mediating role of green knowledge integration capability (GKIC). Design/methodology/approach: Data was collected from 511 middle management-level employees of food manufacturing firms in Pakistan. The questionnaire was tested for reliability and validity. Hierarchical regression is used to test the proposed hypothesis. Findings: A marginal improvement in integration with green customers can increase the green innovation performance (GIP) of a firm by 23.6%. Green supplier integration can improve the GIP by 14.2%, whereas the GKIC mediates the relationship between Green Customers Integration (GCI) and GIP but not for green suppliers integration (GSI). The moderating effect of regulatory pressure was significant for the relationship between GCI and GIP but insignificant for GSI. Originality/value: Food manufacturing accounts for approximately 16% of global green house gases (GHG) emissions. Sustainable development goals (SDGs) cannot be achieved without a significant decrease in GHG emissions by food manufacturing companies. Therefore, it is crucial to investigate firms' green innovation performance in this sector. The findings of this study can help policymakers develop policies for achieving SDGs.

Grain size analysis is an essential tool for classifying sedimentary environments. The main aim of the current research is to use granulometric analysis of the Bhikiysain palaeolake sequence along the Ramganga river to describe changes in the depositional environment within the lake during the late Quaternary. The granulometric analysis was conducted using a laser particle size analyser on 32 samples, collected at 10 cm intervals in a vertical palaeolake profile, at Bhikiyasain (Ramganga Basin). The results of the grain-size analysis indicate that the size distribution of the sediment is unimodal. The unimodal size distribution of the sediment suggests that the sediment was supplied via fluvial action. The Bhikiyasain Basin (29°43.106’ N; 79°15.682’ E) underwent tectonic activity around 44 ka, resulting in the ponding of the Ramganga river and the formation of palaeolake deposit. Based on grain size analysis, variation in the colour and lithofacies, the entire profile has been divided into 6 different zones (zones 1 to 6). The silt has the highest concentration in all the zones except for zones 1 and 3. Zones with high silt concentration are inferred to represent low energy depositional environments during the time of deposition. The higher amount of sand concentration in zones 1 and 3 represent higher energy depositional environment. For the whole profile, the sorting of the samples varies between 1.1 and 2.0, indicating poor sorting of the samples. The poorly sorted sediment in all six zones represents limited transportation of sediment from the catchment and also suggests that the sediment was deposited in a low energy environment. The ternary plots also signify the dominance of silt followed by sand and clay. The skewness values range from 0.1 to 0.5 which indicates that the samples are symmetrical to very finely skewed. Variability in the skewness values may be due to changes in the intensity of wind and hydrodynamic conditions of the lake. The kurtosis value ranges from 0.9-1.4, indicating the samples are platykurtic, leptokurtic and mesokurtic in nature. Variability in the kurtosis may be due to changes in the flow characteristics of the depositional medium.

Background: Biodegradable polymeric nanoparticles have garnered pharmaceutical industry attention throughout the past decade. PLGA [Poly(lactic-co-glycolic acid)] is an excellent biodegradable polymer explored for the preparation of nanoparticles that are administered through various routes like intravenous and transdermal. PLGA's versatility makes it a good choice for the preparation of nanoparticles.Objective: The main objective of this review paper was to summarize methods of preparation and characterization of PLGA nanoparticles along with their role in the transdermal delivery of various therapeutic agents.Methods: A literature survey for the present review paper was done using various search engines like Pubmed, Google Scholar, and Science Direct.Results: In comparison to traditional transdermal administration systems, PLGA nanoparticles have demonstrated several benefits in preclinical investigations, including fewer side effects, low dosage frequency, high skin permeability, and simplicity of application.Conclusion: PLGA nanoparticles can be considered efficient nanocarriers for the transdermal delivery of drugs. Nevertheless, the clinical investigation of PLGA nanoparticles for the transdermal administration of therapeutic agents remains a formidable obstacle.

The Choosing Wisely (CW) campaign, launched in 2012, includes oncology-specific recommendations to promote evidence-based care and deimplementation of low-value practices. However, it is unclear to what extent the campaign has prompted practice change. We systematically reviewed the literature to evaluate the uptake of cancer-specific CW recommendations focusing on the period before the declaration of the COVID-19 pandemic. We used Grimshaw's deimplementation framework to thematically group the findings and extracted information on implementation strategies, barriers, and facilitators from articles reporting on active implementation. In the 98 articles addressing 32 unique recommendations, most reported on passive changes in adherence pre-post publication of CW recommendations. Use of active surveillance for low-risk prostate cancer and reduction in staging imaging for early breast cancer were the most commonly evaluated recommendations. Most articles assessing passive changes in adherence pre-post CW publication reported improvement. All articles evaluating active implementation (10 of 98) reported improved compliance (range: 3%-73% improvement). Most common implementation strategies included provider education and/or stakeholder engagement. Preconceived views and reluctance to adopt new practices were common barriers; common facilitators included the use of technology and provider education to increase provider buy-in. Given the limited uptake of oncology-specific CW recommendations thus far, more attention toward supporting active implementation is needed. Effective adoption of CW likely requires a multipronged approach that includes building stakeholder buy-in through engagement and education, using technology-enabled forced functions to facilitate change along with policy and reimbursement models that disincentivize low-value care. Professional societies have a role to play in supporting this next phase of CW.

The present study aims to investigate the palaeoenvironmental changes around Sattal Lake, Kumaun Lesser Himalaya spanning the last 1670 years. Based on multi proxy analysis (i.e., grain size, mineral magnetism, clay mineralogy, Total Organic Carbon (TOC) and carbon isotopes), supported by a robust radiocarbon chronology, three major environmental phases were identified. Warm, wet phases occurred between 1,150–650 cal yr BP and 260 cal yr BP to the present. These phases coincide closely with the Medieval Climatic Anomaly (MCA) and modern warming, respectively. These warm/wet events were due to elevated precipitation, resulting in high lake levels and an expansion of the lake margin, which were marked by lower δ13C values, comparatively higher sand concentration, TOC values and magnetic susceptibility (χlf). The inference of a modern warm phase is supported by high resolution instrumental data. The MCA, which is marked by elevated amounts of coarse grained (sand) detrital material, is inferred to be an interval of strengthened of monsoonal intensity, which correlates with available monsoon records from various continental paleoclimate archives. Following the MCA a cold and dry phase was observed to occur between 610 and 260 cal yr BP, corresponding to the Little Ice Age (LIA). The LIA, which was characterized by high silt and clay concentration, high δ13C, low TOC and reduced magnetic susceptibility (χlf), is inferred to represent an interval of low lake levels, likely reflecting an episode of weakened monsoonal intensity.

The Government of India preferred legislative lever of public policy over economic incentives, funding support, public awareness campaigns levers by enacting the Mental Health Care Act (MHCA) in the year 2017. MHCA 2017 mandates for mental healthcare and services for persons with mental illness and to protect, promote and fulfil the rights of such persons during delivery of mental healthcare and services. MHCA 2017 is supposed to bring socio-cultural and structural changes to mental health issues in India. This article seeks to identify the various issues and challenges in the implementation of the Act at the macro level, specifically in the areas of prevention of mental morbidities, treatment gaps, reintegration and rehabilitation of the patient. It also suggests the way forward to remove the identified barriers.

Finger millet (Eleusine coracanaL.) is an important nutri-cereal crop which is sensitive to salinity and vulnerable to blast disease caused by Magnaporthe grisea.The present study was therefore aimed to explore the potential of seed biopriming with four salinity tolerant Trichodermaisolates (TRU-21, TRU-14, TRU-33 and TRU-176) on the planting value parameters, physiological and biochemical responses in finger millet grown at various salt stress levels (0, 4, 6 and 8 dSm−1) and to examine their bio-efficacy towards M. grisea. The potential of the Trichodermaisolates in inhibiting M. griseawas assessed by recording the incidence of leaf blast disease using 0–5 SES scale. The Trichodermatreatments were found effective in enhancement of germination percentage and minimizing reduction percent germination. Seedlings raised from Trichodermatreated seeds exhibited significant enhancement on plant biomass, total chlorophyll content and chlorophyll fluorescence in comparison to untreated plants at all salt stress levels. Trichodermatreatments showed lower accumulation of malondialdehyde and H2O2content revealing lower oxidative damage whereas total phenolics, proline content and superoxide dismutase content were higher in plants previously treated with Trichoderma. Current study reported resistant to moderately resistant response towards leaf blast disease in Trichodermatreated plants whereas susceptible response in untreated plants. Use of Trichodermaisolates thus, has been found to provide a sustainable approach to alleviate salt stress and leaf blast disease in finger millet by modulating growth attributes, physiological and biochemical responses, with TRU-14 (Trichoderma asperellum,ITCC-7903) showing most consistent effect for most of the traits studied.

The purpose of this paper is to examine the expectations of the students from institutions providing higher education. Students are the key stakeholder in the education system and their expectations and experience matter a lot when the question of providing satisfaction and retention of the students in higher education is concerned. For measuring satisfaction, it is essential to know the expectations of the students and the actual delivery of the service by the institutions. To know this gap the researcher undertook an extensive literature review of the previous literature by the various researchers. The gap will help us to understand the expectations of the students from the higher institutions and will also help us to know the areas of improvements where we have to work in order to remove the gap.

In this paper, we acquaint with the notion of enriched ordered contractions to prove existence and uniqueness of fixed point theorems and approximation results using Krasnoselskij iteration in a convex noncommutative Banach space. An example is also constructed to indicate the relevance of our newly obtained results in comparison to some of the existing ones in the literature.

Problems related to the environment and energy scarcity have attracted considerable interest in the development of materials that can act as photocatalysts and electrode components for energy storage applications. In this study, a nanocomposite comprising NiSe2and g-C3N4is prepared using a single-step hydrothermal method. The morphologies, structures, compositions, photocatalytic, and supercapacitor performances of the individual and composite materials are characterized. The photocatalytic degradation efficiency of composite NiSe2/g-C3N4using RhB dye is 75 % after 200 min, showing an appreciable improvement over the degradation efficiency of pure NiSe2(57 %). The addition of g-C3N4into NiSe2promotes photoinduced electron transfer and provides reaction active sites, which improves the efficiency of the composite. Furthermore, electrochemical measurements of the prepared electrode materials have been studied. The composite delivers a capacitance of 762.64 F g−1at 5 A g−1which is nearly six times that of NiSe2(127.13 F g−1at 5 A g−1). Moreover, the symmetric supercapacitor cell of the NiSe2/g-C3N4composite offers 13 Wh kg−1energy density and a power density of 0.75 kW kg−1. The cell exhibits good cyclic stability with a capacitance retention rate of 71.9 % after 2500 cycles. The synergistic effects of NiSe2and g-C3N4are responsible for the superior electrochemical behavior of the composite material. Therefore, the synthesized NiSe2/g-C3N4composite shows remarkably improved performance in both photocatalytic and supercapacitor applications.

AbstractQuasi-palindromic sequences (AT)XN12(AT)Ypresent in HS2 (hypersensitive site 2) of the human β-globin locus are known to be significantly associated with increased fetal hemoglobin (HbF) levels. High HbF levels in some adults arise due to pathological conditions such as sickle cell disease and β-thalassemia. However, elevated levels of HbF are also associated with a reducing morbidity and mortality in patients with β-thalassemia and thus ameliorate the severity of the disease. Using gel-electrophoresis, ultraviolet (UV)-thermal denaturation, and circular dichroism (CD) techniques, we demonstrated that it exhibits a hairpin-duplex equilibrium. Intramolecular species (hairpin) were observed in both low and high salt concentrations in gel assay studies displaying the unusual stability of intramolecular species even at the high counter-ion concentration. The unusual stability of hairpin secondary structures was also demonstrated by the monophasic nature of the melting profiles for the oligonucleotides which persisted at low as well as high salt and oligomer concentrations. Change in CD spectra as a function of oligomer concentration indicates that the bimolecular duplex formation is selectively favored over monomolecular hairpin formation at and above 9 µM oligomer concentration. Thus, we hypothesize that imperfect inverted repeat sequence (AT)XN12(AT)Yof HS2 of β-globin gene LCR forms the unusually stable hairpins which may result in the formation of a cruciform structure that may be recruited for binding by various nuclear proteins that could result in elevated HbF levels.Communicated by Ramaswamy H. Sarma.

Alzheimer’s disease (AD) is genetically complex with multifactorial etiology. Here, we aim to identify the potential viral pathogens leading to aberrant inflammatory and oxidative stress response in AD along with potential drug candidates using systems biology approach. We retrieved protein interactions of amyloid precursor protein (APP) and tau protein (MAPT) from NCBI and genes for oxidative stress from NetAge, for inflammation from NetAge and InnateDB databases. Genes implicated in aging were retrieved from GenAge database and two GEO expression datasets. These genes were individually used to create protein-protein interaction network using STRING database (score≥0.7). The interactions of candidate genes with known viruses were mapped using virhostnet v2.0 database. Drug molecules targeting candidate genes were retrieved using the Drug- Gene Interaction Database (DGIdb). Data mining resulted in 2095 APP, 116 MAPT, 214 oxidative stress, 1269 inflammatory genes. After STRING PPIN analysis, 404 APP, 109 MAPT, 204 oxidative stress and 1014 inflammation related high confidence proteins were identified. The overlap among all datasets yielded eight common markers (AKT1, GSK3B, APP, APOE, EGFR, PIN1, CASP8 and SNCA). These genes showed association with hepatitis C virus (HCV), Epstein– Barr virus (EBV), human herpes virus 8 and Human papillomavirus (HPV). Further, screening of drugs targeting candidate genes, and possessing anti-inflammatory property, antiviral activity along with a suggested role in AD pathophysiology yielded 12 potential drug candidates. Our study demonstrated the role of viral etiology in AD pathogenesis by elucidating interaction of oxidative stress and inflammation causing candidate genes with common viruses along with the identification of potential AD drug candidates.

Multimodal or combination therapy has been considered as a powerful approach for treatment of complex diseases like cancer. The fascinating physicochemical and optoelectronic properties of gold nanoparticles make them potential candidate for cancer therapeutic and diagnostic applications. Herein, we design a multifunctional nanosystem by conjugating a photosensitizer, Azure B (AB) with citrate reduced gold nanoparticles (CI-Au NPs) through non-covalent interactions. The conjugation of AB with CI-Au NPs was confirmed through UV–Visible absorption spectroscopy and Fourier Transform Infra-red (FT-IR) spectroscopy. The morphology, size, and charge of the prepared nano-conjugates (AB@CI-Au NPs) were determined by transmission electron microscopy (TEM), Dynamic light scattering (DLS), and zeta potential measurements. The proficiency of AB@CI-Au NPs for cancer photo-therapies was demonstrated by evaluating their potential for photothermal heating and singlet oxygen generation in solution upon Visible laser (635 nm, 500 mW/cm2) irradiation. The AB@CI-Au NPs display superior heating efficiency than CI-Au NPs alone or free AB, and offer better photostability as well as singlet oxygen generation rate compared to free photosensitizer. The interaction of AB@CI-Au NPs with Calf thymus DNA (Ct-DNA) and transport protein Bovine Serum Albumin (BSA) were studied using various biophysical techniques including Circular dichroism, UV–Visible and fluorescence spectroscopic studies. AB@CI-Au NPs show intercalative binding with Ct-DNA by inducing local perturbations in double helical structure and hence can exert chemotherapeutic action by targeting DNA. AB@CI-Au NPs also display moderate binding with BSA without any adverse effect on BSA structure, which is desirable for significant biodistribution and pharmacokinetics of AB@CI-Au NPs. Also, in vitrocytotoxicity of the AB@CI-Au NPs with and without laser irradiation (635 nm, 500 mW/cm2) was demonstrated using the hepatocellular carcinoma (HepG2) cell lines. Our findings through photophysical and biophysical studies strongly recommend the exploitation of AB@CI-Au NPs nanoconjugates as a multifunctional probe for trimodal anticancer therapy.

AbstractEukaryotic genomes contain a large number of pyrimidine-purine rich regions and such regions can assume varied DNA conformations, including triple-stranded structures. These structures have fascinated scientists because of their considerable therapeutic applications. These structures have also profound implications in the field of nanotechnology as they can be used to develop DNA-based nanostructures and materials. Therefore, for any application, it is important to understand the formation of triplex structures, both in quantitative and qualitative terms. A combination of gel electrophoresis, UV-thermal denaturation and circular dichroism (CD) spectroscopy was used to investigate the formation of inter- as well as intramolecular triplex, in pyrimidine motif at BOLF1gene of human herpesvirus 4(HH4) genome. This gene codes for inner tegument protein, which plays crucial roles in viral replication. The said oligopurine•oligopyrimidine duplex was targeted via a designed triple helix forming oligopyrimidine nucleotide (TFO) in intermolecular as well as intramolecular fashion. Our studies revealed that intramolecular triplex formation takes place at acidic as well as at neutral pH; whereas low pH is required for its intermolecular version. This comparative study between inter- and intramolecular triplex allowed us to demonstrate that intramolecular structure is more stable to its intermolecular counterpart. Numerous models for mono-, bi- and trimolecular structures adopted by these DNA sequences have been suggested. This report adds to our existing knowledge about DNA triple helical structures.

Background: Perinatal depression (PD) has important implications for maternal and infant well-being but largely goes undetected. There is a need to develop low-intensity psychosocial interventions applicable to obstetric health care facilities.Objective: To assess the effectiveness of a brief psychological intervention for mild to moderate PD delivered by a nurse as compared to treatment-as-usual (TAU).Methods: This study is a randomized, open-label, parallel-group, multicentric trial being conducted in four sites of India. A total of 816 pregnant women with mild to moderately severe depression (Patient Health Questionaire-9 score of 5–19) are being assessed for the effectiveness of the intervention. Participants are randomly allocated to two groups of trial intervention (psychological intervention given by nurse) and TAU. The primary outcome is to compare the proportion of women reporting improvement across both groups. Participants are serially followed-up in each trimester and at 6, 10, 14 weeks, and 6 months postpartum. Secondary outcomes include pregnancy outcomes, feeding practices, physical growth, and immunization status of the infants.Conclusion: It is a prospective pregnancy birth cohort with a robust design and long-term follow-up. This is one of the largest studies utilizing non-specialist health workers for the screening and management of PD. This study also holds promise to cast light on the course and outcome of depression during pregnancy in different parts of India. It is envisaged to help in developing a sound screening and referral-based protocol for obstetric settings.

There are limited data regarding the combined value of the pretransplant Deauville score (DS) from a positron emission tomography scan and clinical risk factors in patients with relapsed/refractory aggressive non-Hodgkin lymphoma (NHL). We performed a retrospective analysis to assess the prognostic role of pretransplant DS in patients with relapsed/refractory aggressive NHL who underwent salvage chemotherapy and autologous stem cell transplantation (ASCT). We identified 174 eligible patients between January 2013 and March 2019. In multivariable analysis, pretransplant DS, B symptoms, and secondary International Prognostic Index (sIPI) were independent risk factors for event-free survival (EFS). These variables were used to derive an integrated risk score that categorized 166 patients with available information for all risk factors into 3 groups: low (n = 92; 55.4%), intermediate (n = 48; 28.9%), and high (n = 26; 15.7%). The new prognostic index showed a strong association with EFS (low-risk vs intermediate-risk hazard ratio [HR], 3.94; 95% confidence interval [CI], 2.16-7.17; P < .001; low-risk vs high-risk HR, 10.83; 95% CI, 5.81-20.19; P < .001) and outperformed models based on clinical risk factors or DS alone. These results were validated in 60 patients from an independent external cohort (low-risk vs intermediate-risk HR, 4.04; 95% CI, 1.51-10.82; P = .005; low-risk vs high-risk HR, 10.49; 95% CI, 4.11-26.73; P < .001). We propose and validate a new prognostic index that risk-stratifies patients undergoing salvage chemotherapy followed by ASCT, thereby identifying patients at high risk for posttransplant treatment failure.

There are limited data regarding the combined value of the pretransplant Deauville score (DS) from a positron emission tomography scan and clinical risk factors in patients with relapsed/refractory aggressive non-Hodgkin lymphoma (NHL). We performed a retrospective analysis to assess the prognostic role of pretransplant DS in patients with relapsed/refractory aggressive NHL who underwent salvage chemotherapy and autologous stem cell transplantation (ASCT). We identified 174 eligible patients between January 2013 and March 2019. In multivariable analysis, pretransplant DS, B symptoms, and secondary International Prognostic Index (sIPI) were independent risk factors for event-free survival (EFS). These variables were used to derive an integrated risk score that categorized 166 patients with available information for all risk factors into 3 groups: low (n = 92; 55.4%), intermediate (n = 48; 28.9%), and high (n = 26; 15.7%). The new prognostic index showed a strong association with EFS (low-risk vs intermediate-risk hazard ratio [HR], 3.94; 95% confidence interval [CI], 2.16-7.17; P< .001; low-risk vs high-risk HR, 10.83; 95% CI, 5.81-20.19; P< .001) and outperformed models based on clinical risk factors or DS alone. These results were validated in 60 patients from an independent external cohort (low-risk vs intermediate-risk HR, 4.04; 95% CI, 1.51-10.82; P= .005; low-risk vs high-risk HR, 10.49; 95% CI, 4.11-26.73; P< .001). We propose and validate a new prognostic index that risk-stratifies patients undergoing salvage chemotherapy followed by ASCT, thereby identifying patients at high risk for posttransplant treatment failure.

AbstractG-quadruplex (GQ) architecture is adopted by guanine rich sequences, present throughout the eukaryotic genome including promoter locations and telomeric ends. The in vivopresence indicates their involvement and role in various biological processes. Various small ligands have been developed to interact and stabilize/destabilize G-quadruplex structures. Cationic porphyrins are among the most studied ligands, reported to bind and stabilize G-quadruplexes. Herein, we report the recognition and destabilization of a parallel G-quadruplex by porphyrins (TMPyP3 and TMPyP4). This G-quadruplex forming 23-nt G-rich sequence is in the promoter region of Human Myosin Heavy Chain β gene (MYH7β). Presence of various putative regulatory sequence elements (TATA Box, CCAAT, SP-1) located in the vicinity of this quadruplex motif, highlight its regulatory implications. Biophysical methods as Circular Dichroism Spectroscopy, UV-Absorption Spectroscopy, UV-Thermal Denaturation and Fluorescence Spectroscopy (steady as well as Time Resolved) have been used for studying the interaction and binding parameters. It is proposed that porphyrins have a destabilizing effect on the G-quadruplexes with parallel topology and a stronger binding specifically via intercalation mode is needed to cause destabilization. The study deals with better understanding and insights of DNA-Drug interactions in biological systems.Communicated by Ramaswamy H. Sarma

AbstractGuanine rich DNA sequences of regulatory genomic regions form secondary structures known as G-quadruplexes usually stabilized by tetrads of Hoogsteen hydrogen bonded guanines. The in vivoexistence of G-quadruplexes ascertains their biological roles. Human telomeric repeats are the most studied G-rich sequences. The four repeat Giardia telomeric sequence (TAGGG)4differs from its human counterpart (TTAGGG)4,by deletion of one T at the G-tract intervening site of each repeat. We show here that whilst the two repeat Giardia telomeric sequence (TAGGG)2forms parallel and antiparallel quadruplexes with tetramolecular topology exclusively, the four repeat version (TAGGG)4forms a tetramolecular (antiparallel) and unimolecular (parallel) quadruplexes in Na+. The tetramolecular (antiparallel) G-quadruplex formed by four repeats of Giardia telomeric sequence is stabilized by the additional Watson-Crick bonding between its intervening TA bases aligned in antiparallel fashion. Four stranded antiparallel quadruplex for four repeats of any telomeric sequence have not been characterized till date. We hypothesize that telomeric association in antiparallel fashion, (via G-overhangs to form tetramolecular quadruplex) could be a biologically relevant molecular event. Further, coexistence of Hoogsteen as well as Watson-Crick base pairing might give insight for recognition of conformationally diverse DNA structures by ligands. Communicated by Ramaswamy H. Sarma

Autologous stem cell transplant (ASCT) is a feasible treatment option for multiple myeloma (MM) patients with renal insufficiency; however, these patients tend to experience higher rates of drug toxicity and transplant-related mortality (TRM) during ASCT. Recent adoption of bortezomib-based induction regimens and dose reduction of melphalan during conditioning may improve outcomes in this population. In this single center retrospective study, we compared the toxicity and survival outcomes of 96 MM patients with renal insufficiency undergoing ASCT between two eras: 1998–2007 and 2008–2016. The proportion of dialysis dependent patients was similar in both groups (49 and 45%). We found no TRM in those transplanted more recently as compared with 13% in the older era of ASCT. There were significantly more high grade (grades 3–4) toxicities in the older era of ASCT including high grade electrolyte abnormalities, mucositis, delirium, and bleeding. Patients transplanted more recently had significantly higher overall response rate (ORR) as well as deeper responses to ASCT (≥VGPR in 79% vs 39%). Progression-free survival (PFS) was prolonged by 26 months in the more recent era compared with the older era. Overall, improvements in treatment regimens have resulted in reduced TRM and toxicities for patients with renal insufficiency undergoing ASCT.