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Cannabinoids, commonly used for medicinal and recreational purposes, consist of various complex hydrophobic molecules obtained from Cannabis sativa L. Acting as an inhibitory molecule; they have been investigated for their antineoplastic effect in various breast tumor models. Lately, it was found that cannabinoid treatment not only stimulates autophagy-mediated apoptotic death of tumor cells through unfolded protein response (UPRER) activated downstream effectors, but also imposes cell cycle arrest. The exploitation of UPRER tumors as such is believed to be a major molecular event and is therefore employed in understanding the development and progression of breast tumor. Simultaneously, the data on clinical trials following administration of cannabinoid is currently being explored to find its role not only in palliation but also in the treatment of breast cancer. The present study summarizes new achievements in understanding the extent of therapeutic progress and highlights recent developments in cannabinoid biology towards achieving a better cure of breast cancer through the exploitation of different cannabinoids. Keywords: Cannabinoids, Unfolded Protein Response (UPR), Endoplasmic reticulum (ER), Breast cancer

Genome analysis of individuals affected by retinitis pigmentosa (RP) identified two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream of the start codon of the ciliopathy gene TMEM216 (c.-69G>A, c.-69G>T [GenBank: NM_001173991.3]), in individuals of South Asian and African ancestry, respectively. Genotypes included 71 homozygotes and 3 mixed heterozygotes in trans with a predicted loss-of-function allele. Haplotype analysis showed single-nucleotide variants (SNVs) common across families, suggesting ancestral alleles within the two distinct ethnic populations. Clinical phenotype analysis of 62 available individuals from 49 families indicated a similar clinical presentation with night blindness in the first decade and progressive peripheral field loss thereafter. No evident systemic ciliopathy features were noted. Functional characterization of these variants by luciferase reporter gene assay showed reduced promotor activity. Nanopore sequencing confirmed the lower transcription of the TMEM216 c.-69G>T allele in blood-derived RNA from a heterozygous carrier, and reduced expression was further recapitulated by qPCR, using both leukocytes-derived RNA of c.-69G>T homozygotes and total RNA from genome-edited hTERT-RPE1 cells carrying homozygous TMEM216 c.-69G>A. In conclusion, these variants explain a significant proportion of unsolved cases, specifically in individuals of African ancestry, suggesting that reduced TMEM216 expression might lead to abnormal ciliogenesis and photoreceptor degeneration.

The etiopathologies behind autoimmune thyroid diseases (AITDs) unravel misbehavior of immune components leading to the corruption of immune homeostasis where thyroid autoantigens turn foe to the self. In AITDs lymphocytic infiltration in the thyroid shows up a deranged immune system charging the follicular cells of the thyroid gland (thyrocytes) leading to the condition of either hyperthyroidism or hypothyroidism. The inflammation in AITDs consistently associate with ER function due to which disturbances in the ER protein homeostasis leads to unfolded protein response (UPR) that promotes pathogenesis of autoimmunity. The roles of ER stress in the instantaneous downregulation of MHC class I molecules on thyrocytes and the relevance of IFN γ in the pathogenesis of AITD has been well-documented. Thyroglobulin being the major target of autoantibodies in most of the AITDs is because of its unusual processing in the ER. Autoimmune disorders display a conglomeration of ER stress-induced UPR activated molecules. Several epidemiological data highlight the preponderance of AITDs in women as well as its concurrence with breast cancer. Both being an active glandular system displaying endocrine activity, thyroid as well as breast tissue show various commonalities in the expression pattern of heterogenous molecules that not only participate in the normal functioning but at the same time share the blame during disease establishment. Studies on the development and progression of breast carcinoma display a deranged and uncontrolled immune response, which is meticulously exploited during tumor metastasis. The molecular crosstalks between AITDs and breast tumor microenvironment rely on active participation of immune cells. The induction of ER stress by Tunicamycin advocates to provide a model for cancer therapy by intervening glycosylation. Therefore, this review attempts to showcase the molecules that are involved in feeding up the relationship between breast carcinoma and AITDs.

Whole genome sequencing has been an effective tool in the discovery of variants that cause rare diseases. In this study, we determined the suitability of a novel avidity sequencing approach for rare disease applications. We built a sample to results workflow, combining this sequencing technology with standard library preparation kits, analysis workflows, and interpretation tools. We applied the workflow to ten pedigrees with inherited retinal degeneration (IRD) phenotype. Candidate variants of interest identified through whole genome sequencing were further evaluated using segregation analysis in the additional family members. Potentially causal variants in known IRD genes were detected in five of the ten cases. These high confidence variants were found in ABCA4, CERKL, MAK, PEX6 and RDH12 genes associated with retinal degeneration, that could be sufficient to cause pathology. Pending confirmatory clinical evaluation, we observed a 50% diagnostic yield, consistent with previously reported outcomes of IRD patient analysis. The study confirms that avidity sequencing is effective in detection of causal variants when used for whole genome sequencing in rare disease applications.

The influence exerted by no longer relevant intentions that have been successfully executed or cancelled is called aftereffects. The current study investigated the effect of encoding a secondary intention on the aftereffects of non-relevant prospective intentions. The study used an active phase-finished phase paradigm with participants randomly assigned to either experimental or control conditions. In the experimental condition, participants encoded a secondary intention in the finished phase of the task. In the control condition, participants did not encode any additional instructions. Commission errors and response latencies were analysed in the finished phase for fulfilled intentions or encoded but unfulfilled intentions. Independent sample t-tests found significant (p

Alzheimer’s disease (AD), a neurodegenerative disorder, is most common cause of dementia witnessed among aged people. The pathophysiology of AD develops as a consequence of neurofibrillary tangle formation which consists of hyperphosphorylated microtubule associated tau protein and senile plaques of amyloid-β (Aβ) peptide in specific brain regions that result in synaptic loss and neuronal death. The feeble buffering capacity of endoplasmic reticulum (ER) proteostasis in AD is evident through alteration in unfolded protein response (UPR), where UPR markers express invariably in AD patient’s brain samples. Aging weakens UPRER causing neuropathology and memory loss in AD. This review highlights molecular signatures of UPRER and its key molecular alliance that are affected in aging leading to the development of intriguing neuropathologies in AD. We present a summary of recent studies reporting usage of small molecules as inhibitors or activators of UPRER sensors/effectors in AD that showcase avenues for therapeutic interventions.

Background: Accessible, low-cost digital programmes are emerging as a means by which to address high rates of mental health problems. However, the development and assessment of scalable training programmes for effective use of digital interventions has lagged. This is particularly important, as coach-supported digital interventions provide benefits that substantially and consistently exceed those of programmes that are entirely self-guided.Objectives: This report describes the evaluation of a brief coach training programme consisting of a two-hour workshop and six 1-hour consultation sessions for delivery of webSTAIR, a 10-module transdiagnostic web-based programme for trauma-exposed populations.Method: The training was provided to 68 mental health counsellors at Veteran Health Administration Readjustment Counselling Services, who delivered the treatment to 99 veteran clients.Results: A total of 51% of the coaches completed the programme. Client outcomes were encouraging. Veterans enrolled in the programme demonstrated significant and clinically meaningful improvements in functioning (Cohen’s d = 0.88), emotion regulation (Cohen’s d = 0.97), posttraumatic stress disorder (PCL-5 Cohen’s d = 0.61; ITQ Cohen’s d = 0.60), and depression (Cohen’s d = 0.53).Conclusions: The study contributes much needed information regarding evidence for the effectiveness of ‘light-touch’ training strategies. The data support the integration and testing of brief training programmes in the implementation and dissemination of evidence-based digital interventions. Strategies for improving training completion rates among busy providers and resource-burdened clinical services need to be considered.

Calcium is a ubiquitous and versatile secondary messenger that enables plant growth through various processes in response to abiotic and biotic stress factors. Plants are immobile and therefore constantly exposed to various environmental stimuli (drought, waterlogging, etc.) and microorganisms such as bacteria, fungi, and viruses resulting in large crop losses. Calmodulin (CaM) is an evolutionarily conserved calcium-binding protein and sensor that occurs in all eukaryotes and performs various functions under stress. CaM-binding proteins (CBPs) such as transcription factors, enzymes and channels are involved in responses to environmental stress. Plants have evolved a sophisticated innate immune system to fight infections, commonly referred to as pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity (ETI). Soybean is an economically important legume crop that is constantly confronted with various pests and pathogens, resulting in significant yield and production losses. The article highlights the functions of calmodulin in soybean during biotic (soybean-microbe pathogenesis) and abiotic (soybean-environment) interactions in the light of currently available knowledge on the subject. It also describes the new paradigms in this field, emphasising the need for further investigation and providing up-to-date information on the most plausible approaches to combat this challenge for commercial use.

Abstract The study aims to unravel the impact of Environmental Social Governance (ESG) scores on the firm’s market performance of polluting companies. Moreover, the study also finds out moderating effect of green initiatives. The study’s population consisted of 67 companies that were chosen from the list of polluting companies given by the Central Pollution Control Board of India for the post-COVID-19 timeframe of 2020–2023. Regression analysis was conducted to analyze the relationship between the variables. The results indicate that the performance of ESG will improve the financial performance of the company. In most cases, the results suggest that firms with heightened ESG performances have better market performance. Furthermore, the results show that there is no moderating effect of green initiatives. This study’s findings have important implications for stakeholders. The examination’s findings should help managers understand the state of ESG and financial market performance after the coronavirus crisis, as well as the relationship between FP and ESG responsibility fulfilment. The study has significant practical implications that may help managers create plans and guidelines for implementing and improving ESG scores to maximize performance. Population was the major limitation of the study.

Abstract Dirac and Weyl semimetals are a central topic of contemporary condensed matter physics, and the discovery of new compounds with Dirac/Weyl electronic states is crucial to the advancement of topological materials and quantum technologies. Here we show a widely applicable strategy that uses high configuration entropy to engineer relativistic electronic states. We take the AMnSb2 (A = Ba, Sr, Ca, Eu, and Yb) Dirac material family as an example and demonstrate that mixing of Ba, Sr, Ca, Eu and Yb at the A site generates the compound (Ba0.38Sr0.14Ca0.16Eu0.16Yb0.16)MnSb2 (denoted as A 5MnSb2), giving access to a polar structure with a space group that is not present in any of the parent compounds. A 5MnSb2 is an entropy-stabilized phase that preserves its linear band dispersion despite considerable lattice disorder. Although both A 5MnSb2 and AMnSb2 have quasi-two-dimensional crystal structures, the two-dimensional Dirac states in the pristine AMnSb2 evolve into a highly anisotropic quasi-three-dimensional Dirac state triggered by local structure distortions in the high-entropy phase, which is revealed by Shubnikov–de Haas oscillations measurements.

Abstract The near-infinite compositional space of high-entropy-alloys (HEAs) is a huge resource-intensive task for developing exceptional materials. In the present study, an algorithmic framework has been developed to optimize the composition of an alloy with chosen set of elements, aiming to maximize the hardness of the former. The influence of phase on hardness prediction of HEAs was thoroughly examined. This study aims to establish generalized prediction models that aren’t confined by any specific set of elements. We trained the HEA identification model to classify HEAs from non-HEAs, the multi-labeled phase classification model to predict phases of HEAs also considering the processing route involved in the synthesis of the alloy, and the hardness prediction model for predicting hardness and optimizing the composition of the given alloy. The purposed algorithmic framework uses twenty-nine alloy descriptors to compute the composition that demonstrates maximum hardness for the given set of elements along with its phase(s) and a label stating whether it is classified as HEA or not.

Background: Worldwide healthcare systems, especially those that provide dental treatment, have been devastated by the COVID-19 epidemic. Future healthcare initiatives must take into account the pandemic’s effects on oral health and service consumption. The purpose of this retrospective study was to examine how the COVID-19 pandemic affected dental health and the use of dental services, with a particular emphasis on a tertiary care facility from 2017 to 2022. Methods: Descriptive analysis was performed on data gathered from patient records, including demographics, diagnoses, treatments, and service consumption. Prepandemic, pandemic, and postpandemic variations in oral health trends and service use were evaluated. Findings: During the pandemic, there was a notable decrease in emergency dental visits, whereas teledentistry consultations increased. Age and socioeconomic level are two demographic variables that have an impact on variations in oral health trends. Conclusion: In summary, the COVID-19 pandemic has had a significant influence on dental health and service consumption, underscoring the necessity of flexible approaches to deal with new issues and inequities in dental care access. This study adds insightful information to the conversation on healthcare resilience and pandemic preparedness.