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Prostate gland is a fibromusculoglandular structure situated at the neck of urinary bladder. So, enlargement or growth of prostate due to nodular hyperplasia (NHP) or prostatic intraepithelial neoplasia (PIN) or adenocarcinoma may give rise to bladder outlet obstruction. Malignant growth i.e., PIN or adenocarcinoma cases are associated with increased blood level of prostate-specific antigen (PSA) and increased expression of different sex-steroid receptors because the growth is dependent on the interactions of androgen, progesterone and estrogen. The aim of our study is to correlate the histopathology, PSA levels and expression of different sex-steroid receptors by immunohistochemistry in different prostatic growth lesions. Among the total 50 cases received, inclusive of transurethral resection of prostate (TURP), transrectal ultrasoundguided biopsy and radical prostatectomy, 34 cases were diagnosed as NHP, 4 cases as PIN and 12 cases as adenocarcinoma histopathologically. Serum PSA values above 10 ng/ml were seen in 2 cases of PIN and 11 cases of adenocarcinoma and none of NHP. Estrogen receptor (ER) () expressions were negative in all cases. Progesterone receptor (PR) expressions were strongly positive in 35% cases of both NHP and adenocarcinoma, whereas androgen receptor (AR) expressions were strong among all cases of adenocarcinoma and only in four cases of NHP. By observing these findings it can be suggested that antiandrogen and antiprogesterone therapy simultaneously will do better than antiandrogen alone in treating prostatic growth lesions. [ABSTRACT FROM AUTHOR]

An efficient method for per-O-acetylation of reducing sugars was developed by in situ generation of acid anhydride using acid chloride and sodium acetate. This avoids the use of pyridine and acetic anhydride. In this environment friendly methodology- the acylating agent was used in almost stoichiometric amount and per-O-acetylated glycopyranoses were obtained exclusively after simple work up. [ABSTRACT FROM AUTHOR]

Abstract: We explore methods to use thermostatically controlled loads (TCLs), such as water heaters and air conditioners, to provide ancillary services by assisting in balancing generation and load. We show that by adding simple imbedded instructions and a small amount of memory to temperature controllers of TCLs, it is possible to design open-loop control algorithms capable of creating short-term pulses of demand response without unwanted power oscillations associated with temporary synchronization of the TCL dynamics. By moving a small amount of intelligence to each of the end point TCL devices, we are able to leverage our knowledge of the time dynamics of TCLs to shape the demand response pulses for different power system applications. A significant benefit of our open-loop method is the reduction from two-way to one-way broadcast communication which also eliminates many basic consumer privacy issues. In this work, we focus on developing the algorithms to generate a set of fundamental pulse shapes that can subsequently be used to create demand response with arbitrary profiles. Demand response control methods, such as the one developed here, open the door to fast, nonperturbative control of large aggregations of TCLs. [Copyright &y& Elsevier]

Aspergilloma or mycetoma is a saprophytic fungal infection that colonizes pre-existing excavated lung lesion. However, its association with systemic sclerosis related interstitial lung disease is unusual and scarcely found in literature. We report a middle aged female with long standing systemic sclerosis, who was on immunosuppressive therapy for many years, presented with repeated haemoptysis. Although provisionally pulmonary tuberculosis was suspected, imaging investigations showed presence of bilateral masses inside bullous air spaces along with air-crescent sign suggestive of fungal ball. Subsequent Computed tomography guided needle aspiration from lung mass confirmed Aspergillus fumigatus as aetiologic agent on fungal culture. Patient was treated conservatively for haemoptysis and with oral antifungal drug as surgical removal of fungal ball was not an option due to poor pulmonary reserve. Although she had been treated with itraconazole for more than three years, she had recurrent haemoptysis during this period without any significant regression of size of the aspergilloma. Management of aspergilloma in a background of extensive interstitial lung disease remains poorly defined and complicated. Thereby, overall prognosis is unfavourable and depends on evolution of both underlying scleroderma as well as aspergilloma. [ABSTRACT FROM AUTHOR]

Complex structural variations (cxSVs) are often overlooked in genome analyses due to detection challenges. We developed ARC-SV, a probabilistic and machine-learning-based method that enables accurate detection and reconstruction of cxSVs from standard datasets. By applying ARC-SV across 4,262 genomes representing all continental populations, we identified cxSVs as a significant source of natural human genetic variation. Rare cxSVs have a propensity to occur in neural genes and loci that underwent rapid human-specific evolution, including those regulating corticogenesis. By performing single-nucleus multiomics in postmortem brains, we discovered cxSVs associated with differential gene expression and chromatin accessibility across various brain regions and cell types. Additionally, cxSVs detected in brains of psychiatric cases are enriched for linkage with psychiatric GWAS risk alleles detected in the same brains. Furthermore, our analysis revealed significantly decreased brain-region- and cell-type-specific expression of cxSV genes, specifically for psychiatric cases, implicating cxSVs in the molecular etiology of major neuropsychiatric disorders. [Display omitted] • ARC-SV uses machine learning on pangenomes to detect cxSVs with high accuracy • Rare cxSVs in the human population are enriched in neural genes • Rare cxSVs are enriched in loci that underwent rapid human-specific evolution • cxSVs contribute to the genetic architecture of major psychiatric disorders ARC-SV enables highly accurate detection and characterization of localized complex rearrangements of multiple DNA segments. Applying ARC-SV across human populations and brain cohorts uncovers connections between complex structural variantion and human-specific evolution, neural genes, and major psychiatric disorders. [ABSTRACT FROM AUTHOR]

• A patch-based, residual, asymmetric, encoder-decoder 2D CNN architecture with 11 convolutional layers and 84,217 trainable parameters is introduced. • Utilized a training strategy combining the Focal Tversky and Binary cross-entropy loss functions to overcome the class imbalance issue in CT images. • A voting mechanism is applied to the result predicted by the weight matrices to ensure stable results. • Compared the method's performance on the testing dataset with that of selected high-performing methods from the ISLES 2018 challenge and achieved the second rank. Background and objectives: This paper has introduced a patch-based, residual, asymmetric, encoder-decoder CNN that solves two major problems in acute ischemic stroke lesion segmentation from CT and CT perfusion data using deep neural networks. First, the class imbalance is encountered since the lesion core size covers less than 5% of the volume of the entire brain. Second, deeper neural networks face the drawback of vanishing gradients, and this degrades the learning ability of the network. Methods: The neural network architecture has been designed for better convergence and faster inference time without compromising performance to address these difficulties. It uses a training strategy combining Focal Tversky and Binary cross-entropy loss functions to overcome the class imbalance issue. The model comprises only four resolution steps with a total of 11 convolutional layers. A base filter of 8, used for the residual connection with two convolutional blocks at the encoder side, is doubled after each resolution step. Simultaneously, the decoder consists of residual blocks with one convolutional layer and a constant number of 8 filters in each resolution step. This proposition allows for a lighter build with fewer trainable parameters as well as aids in avoiding overfitting by allowing the decoder to decode only necessary information. Results: The presented method has been evaluated through submission on the publicly accessible platform of the Ischemic Stroke Lesion Segmentation (ISLES) 2018 medical image segmentation challenge achieving the second-highest testing dice similarity coefficient (DSC). The experimental results demonstrate that the proposed model achieves comparable performance to other submitted strategies in terms of DSC Precision, Recall, and Absolute Volume Difference (AVD). Conclusions: Through the proposed approach, the two major research gaps are coherently addressed while achieving high challenge scores by solving the mentioned problems. Our model can serve as a tool for clinicians and radiologists to hasten decision-making and detect strokes efficiently. [ABSTRACT FROM AUTHOR]

In rural areas of developing countries, solid fuels are still widely used for cooking, heating, and lighting purposes. This study investigates the effects of household air pollutants (HAPs) exposure on the occurrence of respiratory symptoms, blood pressure, and lung function. In this study, we randomly selected 123 (83 biomass and 40 clean fuel user) subjects to assess the impact of smoke generated from solid biomass fuel by assessing their health status along with the ventilation pattern of the kitchens and living rooms. HAPs (PM10, PM2.5, and CO) and different health parameters were measured along with monitoring of self-reported health symptoms for a consecutive period of eight months. Results revealed that the concentration of CO, PM2.5, and PM10 were found highest in biomass using households. Higher odds of the upper respiratory symptoms, runny nose (OR: 4.08, 95% CI: 1.22–22.14, p < 0.03), nasal congestion (OR: 9.07, 95% CI: 1.39–97.89, p < 0.01) and the odds of the lower respiratory symptoms like wheezing (OR: 1.62, 95% CI: 1.23–10.94, p < 0.01), breathlessness (OR: 4.44, 95% CI: 1.3–14.75, p < 0.01), chest tightness (OR: 4.89, 95% CI: 1.23–22.14, p < 0.03) and dry cough (OR: 3.661, 95% CI: 1.05–12.25, p < 0.04) were significantly higher in biomass fuel user. Similarly higher systolic (+11.41 mmHg), higher diastolic pressure (+3.3 mmHg), higher pulse pressure (+8.11 mmHg), and a 6 mmHg higher mean arterial pressure among biomass fuel using tribal women. The risk of hypertension was significantly (p < 0.03) higher (OR: 3.04; 95% CI: 1.18–7.89) among solid biomass fuel users. The lung abnormality was recorded 28.91% (OR: 5.02, 95% CI: 1.50 to 16.56, p < 0.01) among biomass fuel user. Finally, it is suggested that the use of efficient cookstoves, increase in cross ventilation, and cleaner fuel are urgently needed to curb the pollution load. [Display omitted] • Rural tribal women are severely exposed from indoor air pollutants. • Risk of lung disease and hypertension are predominant for heavy exposure group. • Tribal women are worst sufferer from upper and lower respiratory symptoms. • Biomass users are suffering from various morbidities/comorbidities. [ABSTRACT FROM AUTHOR]

As bisphenol A (BPA) effortlessly crosses the blood-brain barrier, its serious impacts on the neuronal microenvironment towards precocious induction of oxidative stress and neuromorphological alteration can't be ignored. Incidentally, a symmetric study establishing the possible link of transformed neurobehavior with heightened monoamine oxidase (MAO) activity and neuromorphological alteration in zebrafish brain subsequent to BPA-exposure is limiting in the literature. The study was conducted to delineate the role of BPA towards the genesis of aggressive behaviour in zebrafish and its correlation with brain MAO activity. Mirror biting test and open field test were conducted to evaluate the aggressive and explorative behaviour respectively. Biochemical studies were performed to delineate the modulation of the antioxidant defence system. Cresyl violet staining and Hoechst staining in the periventricular grey zone of the zebrafish brain were conducted to evaluate neuronal pyknosis and chromatin condensation. Our study showed that BPA exposure is associated with the genesis of aggressive neurobehavioral response. Moreover, the brain MAO activity, oxidative stress and chromatin condensation were increased with increase in exposure duration. The results of the present study gave conclusive evidence that BPA act as a potent neurotoxicant in transforming the native neurobehavioral response of zebrafish through heightened oxidative stress, MAO activity and altered neuromorphology. • Temporal bisphenol A exposure elicits aggressive behaviour in zebrafish. • Bisphenol A exposure exhibits temporal upsurge in brain MAO activity. • Bisphenol A impairs antioxidant defence system and neuromorphology in zebrafish brain. [ABSTRACT FROM AUTHOR]

To efficiently distribute blood flow to cardiac muscle, the coronary artery tree must follow a specific branching pattern over the heart. How this pattern arises in humans is unknown due to the limitations of studying human heart development. Here, we leveraged a natural variation of coronary artery anatomy, known as coronary dominance, in genetic association studies to identify the first known driver of human coronary developmental patterning. Coronary dominance refers to whether the right, left, or both coronary arteries branch over the posterior left ventricle, but whether this variability is heritable and how it would be genetically regulated was completely unknown. By conducting the first large-scale, multi-ancestry genome-wide association study (GWAS) of coronary dominance in 61,043 participants of the VA Million Veteran Program, we observed moderate heritability (27.7%) with ten loci reaching genome wide significance. An exceptionally strong association mapped DNA variants to a non-coding region near the chemokine CXCL12 in both European and African ancestries, which overlapped with variants associated with coronary artery disease. Genomic analyses predicted these variants to impact CXCL12 levels, and imaging revealed dominance to develop during fetal life coincident with CXCL12 expression. Reducing Cxcl12 in mice to model the human genetics altered septal artery dominance patterns and caused coronary branches to develop away from Cxcl12 expression domains. Cxcl12 heterozygosity did not compromise overall artery coverage as seen with full deletion, but instead changed artery patterning, reminiscent of the human scenario. Together, our data support CXCL12 as a critical determinant of human coronary artery growth and patterning and lay a foundation for the utilization of developmental pathways to guide future precision 'medical revascularization' therapeutics., Competing Interests: Competing interests: A.K. is on the scientific advisory board of SerImmune, TensorBio and OpenTargets, and a consultant with Arcadia Science and Inari Agriculture. A.K. was a scientific co-founder of RavelBio, a paid consultant with Illumina, was on the SAB of PatchBio and owns shares in DeepGenomics, Immunai, Freenome, and Illumina. All other authors declare they have no competing interests.

Type I interferon (IFN-I) response is the first line of host defense against invading viruses. In the absence of definite mouse models, the role of IFN-I in SARS-CoV-2 infection remains perplexing. Here, we develop two mouse models, one with constitutively high IFN-I response (hACE2; Irgm1 -/- ) and the other with dampened IFN-I response (hACE2; Ifnar1 -/- ), to comprehend the role of IFN-I response. We report that hACE2; Irgm1 -/- mice are resistant to lethal SARS-CoV-2 infection. In contrast, a severe SARS-CoV-2 infection along with immune cell infiltration, cytokine storm, and enhanced pathology is observed in the lungs and brain of hACE2; Ifnar1 -/- mice. The hACE2; Irgm1 -/- Ifnar1 -/- double-knockout mice display loss of the protective phenotype observed in hACE2; Irgm1 -/- mice, suggesting that heightened IFN-I response accounts for the observed immunity. Taking the results together, we demonstrate that IFN-I protects from lethal SARS-CoV-2 infection, and Irgm1 (IRGM) could be an excellent therapeutic target against SARS-CoV-2., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Many devices heavily rely on combinatorial material optimization. However, new material alloys are classically developed by studying only a fraction of giant chemical space, while many intermediate compositions remain unmade in light of the lack of methods to synthesize gapless material libraries. Here report a high-throughput all-in-one material platform to obtain and study compositionally-tunable alloys from solution is reported. This strategy is applied to make all Cs x MA y FA z PbI 3 perovskite alloys (MA and FA stand for methylammonium and formamidinium, respectively), in less than 10 min, on a single film, on which 520 unique alloys are then studied. Through stability mapping of all these alloys in air supersaturated with moisture, a range of targeted perovskites are found, which are then chosen to make efficient and stable solar cells in relaxed fabrication conditions, in ambient air. This all-in-one platform provides access to an unprecedented library of compositional space with no unmade alloys, and hence aids in a comprehensive accelerated discovery of efficient energy materials., (© 2023 The Authors. Small published by Wiley-VCH GmbH.)

Ferroelectric ceramics such as PbZr x Ti 1- x O 3 (PZT) are widely applied in many fields, from medical to aerospace, because of their dielectric, piezoelectric, and pyroelectric properties. In the past few years, hybrid organic-inorganic halide perovskites have gradually attracted attention for their optical and electronic properties, including ferroelectricity, and for their low fabrication costs. In this Review, we first describe techniques that are used to quantify ferroelectric figures of merit of a material. We then discuss ferroelectricity in hybrid perovskites, starting from controversies in methylammonium iodoplumbate perovskites and then focusing on low-dimensional perovskites that offer an unambiguous platform to obtain ferroelectricity. Finally, we provide examples of the application of perovskite ferroelectrics in solar cells, LEDs, and X-ray detectors. We conclude that the vast structure-property tunability makes low-dimensional hybrid perovskites promising, but they have yet to offer ferroelectric figures of merit (e.g., saturated polarization) and thermal stability (e.g., Curie temperature) competitive with those of conventional oxide perovskite ferroelectric materials.

The NOD1-NOD2-RIPK2-NFKB/NF-κB pro-inflammatory axis plays a significant role in regulating the immune response to bacterial infection. However, an excess of NFKB-dependent cytokine response can be detrimental and, thus, should be kept under control to maintain the innate immune balance. In our recent study, first, we showed that bacterial infection induces the biogenesis of RIPK2 oligomers (RIPosomes) that are recruited around the bacteria to enhance an NFKB-dependent pro-inflammatory response. Next, we showed that SQSTM1- and IRGM-dependent selective macroautophagy/autophagy degrades RIPosomes and their components to limit NOD1-NOD2-RIPK2-NFKB pro-inflammatory signaling. Consistently, depletion of IRGM results in an augmented RIPK2-dependent pro-inflammatory cytokine response induced by Shigella flexneri and Salmonella typhimurium . Further, bacterial infection- and DSS-induced gut inflammation in irgm1 KO mice is dampened upon therapeutic inhibition of RIPK2. Taken together, we showed that autophagy selectively degrades RIPosomes to suppress inflammation and maintain innate immune homeostasis.

Coronary artery disease (CAD) is a complex inflammatory disease involving genetic influences across cell types. Genome-wide association studies have identified over 200 loci associated with CAD, where the majority of risk variants reside in noncoding DNA sequences impacting cis-regulatory elements. Here, we applied single-nucleus assay for transposase-accessible chromatin with sequencing to profile 28,316 nuclei across coronary artery segments from 41 patients with varying stages of CAD, which revealed 14 distinct cellular clusters. We mapped ~320,000 accessible sites across all cells, identified cell-type-specific elements and transcription factors, and prioritized functional CAD risk variants. We identified elements in smooth muscle cell transition states (for example, fibromyocytes) and functional variants predicted to alter smooth muscle cell- and macrophage-specific regulation of MRAS (3q22) and LIPA (10q23), respectively. We further nominated key driver transcription factors such as PRDM16 and TBX2. Together, this single-nucleus atlas provides a critical step towards interpreting regulatory mechanisms across the continuum of CAD risk., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Renewable portfolio standards are targeting high levels of variable solar photovoltaics (PV) in electric distribution systems, which makes reliability more challenging to maintain for distribution system operators (DSOs). Distributed energy resources (DERs), including smart, connected appliances and PV inverters, represent responsive grid resources that can provide flexibility to support the DSO in actively managing their networks to facilitate reliability under extreme levels of solar PV. This flexibility can also be used to optimize system operations with respect to economic signals from wholesale energy and ancillary service markets. Here, we present a novel hierarchical scheme that actively controls behind-the-meter DERs to reliably manage each unbalanced distribution feeder and exploits the available flexibility to ensure reliable operation and economically optimizes the entire distribution network. Each layer of the scheme employs advanced optimization methods at different timescales to ensure that the system operates within both grid and device limits. The hierarchy is validated in a large-scale realistic simulation based on data from the industry. Simulation results show that coordination of flexibility improves both system reliability and economics, and enables greater penetration of solar PV. Discussion is also provided on the practical viability of the required communications and controls to implement the presented scheme within a large DSO., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.

Genome-wide association studies of neurological diseases have identified thousands of variants associated with disease phenotypes. However, most of these variants do not alter coding sequences, making it difficult to assign their function. Here, we present a multi-omic epigenetic atlas of the adult human brain through profiling of single-cell chromatin accessibility landscapes and three-dimensional chromatin interactions of diverse adult brain regions across a cohort of cognitively healthy individuals. We developed a machine-learning classifier to integrate this multi-omic framework and predict dozens of functional SNPs for Alzheimer's and Parkinson's diseases, nominating target genes and cell types for previously orphaned loci from genome-wide association studies. Moreover, we dissected the complex inverted haplotype of the MAPT (encoding tau) Parkinson's disease risk locus, identifying putative ectopic regulatory interactions in neurons that may mediate this disease association. This work expands understanding of inherited variation and provides a roadmap for the epigenomic dissection of causal regulatory variation in disease.

In recent years, 1,4-triazole rings are being widely used for the synthesis of carbohydrate derived biomimetics, due to their easy synthesis and wide range of functional group compatibility. These triazole rings lead to synthetic molecules with improved enzymatic stability, bioavailability, and structural diversity. In this present work, a benzoyl group has been introduced at the C-5 position of the triazole ring present in the synthetic glycoconjugates providing further structural diversity to the molecule. 5-Benzoyl 1,4-triazole ring containing glycoconjugates were synthesized using Cu(I) catalyzed [3 + 2] cycloaddition reaction of per-O-acetylated glycopyranosyl azide and phenyl acetylene followed by in situ electrophilic addition of benzoyl group to the Cu(I) coordinated triazole intermediate. The X-ray crystal structure of one of the 5-benzoyl 1,4-triazole linked glycoconjugate derived from d-xylose {1-N-(2,3,4-tri-O-acetyl-β-d-xylopyranosyl)-4-phenyl-5-benzoyl-1,2,3-triazole} showed unique pattern of intermolecular CH…O interactions arranging the molecules in an anti-parallel orientation. The structure and morphology of the compounds were further explored using computational calculation and scanning electron microscopic (SEM) study which firmly established the uniqueness of 5-benzoyl 1,4-triazole linked glycoconjugates compared to that of 5-H 1,4-triazole linked derivative., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Duplication-Transfer-Loss (DTL) reconciliation is a powerful and increasingly popular technique for studying the evolution of microbial gene families. DTL reconciliation requires the use of rooted gene trees to perform the reconciliation with the species tree, and the standard technique for rooting gene trees is to assign a root that results in the minimum reconciliation cost across all rootings of that gene tree. However, even though it is well understood that many gene trees have multiple optimal roots, only a single optimal root is randomly chosen to create the rooted gene tree and perform the reconciliation. This remains an important overlooked and unaddressed problem in DTL reconciliation, leading to incorrect evolutionary inferences. In this work, we perform an in-depth analysis of the impact of uncertain gene tree rooting on the computed DTL reconciliation and provide the first computational tools to quantify and negate the impact of gene tree rooting uncertainty on DTL reconciliation., Results: Our analysis of a large data set of over 4500 gene families from 100 species shows that a large fraction of gene trees have multiple optimal rootings, that these multiple roots often, but not always, appear closely clustered together in the same region of the gene tree, that many aspects of the reconciliation remain conserved across the multiple rootings, that gene tree error has a profound impact on the prevalence and structure of multiple optimal rootings, and that there are specific interesting patterns in the reconciliation of those gene trees that have multiple optimal roots., Conclusions: Our results show that unrooted gene trees can be meaningfully reconciled and high-quality evolutionary information can be obtained from them even after accounting for multiple optimal rootings. In addition, the techniques and tools introduced in this paper make it possible to systematically avoid incorrect evolutionary inferences caused by incorrect or uncertain gene tree rooting. These tools have been implemented in the phylogenetic reconciliation software package RANGER-DTL 2.0, freely available from http://compbio.engr.uconn.edu/software/RANGER-DTL/ .

Tubercular mastitis is a rare clinical entity as mammary gland tissue, like spleen and skeletal muscle, offers resistance to the survival and multiplication of the tubercle bacillus. Tuberculosis of the breast can mimic carcinoma, whereas in young patients it can be mistaken for a pyogenic breast abscess, thus labeled a "great masquerader" in recognition of its multifaceted presentation. Breast tuberculosis commonly affects women in the reproductive age group, between 21 and 30 years, and is rare in prepubescent females and elderly women. Fine needle aspiration cytology is very useful and it is a promising technique in expert hands. In tuberculosis-endemic countries, the finding of granuloma on fine needle aspiration cytology warrants empirical treatment for tuberculosis even in the absence of positive acid-fast bacilli and without culture results. We hereby report a case of tubercular mastitis in a post-menopausal seronegative female diagnosed on fine needle aspiration cytology with a positive acid-fast bacilli and a review of the recent literature.