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The global energy market is shifting toward renewable, sustainable, and low-carbon hydrogen energy due to global environmental issues, such as rising carbon dioxide emissions, climate change, and global warming. Currently, a majority of hydrogen demands are achieved by steam methane reforming and other conventional processes, which, again, are very carbon-intensive methods, and the hydrogen produced by them needs to be purified prior to their application. Hence, researchers are continuously endeavoring to develop sustainable and efficient methods for hydrogen generation and purification. Membrane-based gas-separation technologies were proven to be more efficient than conventional technologies. This review explores the transition from conventional separation techniques, such as pressure swing adsorption and cryogenic distillation, to advanced membrane-based technologies with high selectivity and efficiency for hydrogen purification. Major emphasis is placed on various membrane materials and their corresponding membrane performance. First, we discuss various metal membranes, including dense, alloyed, and amorphous metal membranes, which exhibit high hydrogen solubility and selectivity. Further, various inorganic membranes, such as zeolites, silica, and CMSMs, are also discussed. Major emphasis is placed on the development of polymeric materials and membranes for the selective separation of hydrogen from CH 4 , CO 2 , and N 2 . In addition, cutting-edge mixed-matrix membranes are also delineated, which involve the incorporation of inorganic fillers to improve performance. This review provides a comprehensive overview of advancements in gas-separation membranes and membrane materials in terms of hydrogen selectivity, permeability, and durability in practical applications. By analyzing various conventional and advanced technologies, this review provides a comprehensive material perspective on hydrogen separation membranes, thereby endorsing hydrogen energy for a sustainable future.

Sensing and quantification of gas at low concentrations is of paramount importance, especially with highly flammable and explosive gases such as hydrogen. Standard gas sensing setups have a limit of measuring ultra-low concentrations of few parts per billion unless the external gas cylinders are changed to ones with low concentrations. In this work, we describe a home-built resistance based gas sensing setup that can sense across a wide concentration range, from parts per billion to parts per million, accurately. This was achieved using two dilution chambers: a process chamber and a feedback assembly where a part of the output gas from the dilution chamber is fed back to the inlet mass flow controller, enabling enhanced dilutions without increasing the number of mass flow controllers. In addition, the gas-sensing setup can measure across a large temperature range of 77-900 K. The developed setup was then calibrated using palladium thin films and ZnO nanoparticle thin films. The setup was tested for reproducibility, concentration response, temperature response, etc. Corresponding sensitivity values were calculated and found to be in good agreement with published values, validating our setup design., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: Preeclampsia is one of the important causes of maternal and fetal mortality and morbidity. One of the important risk factors for the development of diabetes is insulin resistance (IR)., Aims: To evaluate the association of IR with pregnancy-induced hypertension (PIH) and its severity., Materials and Methods: Data from 70 pregnant females who had completed 20 weeks of gestation and developed PIH were analyzed and compared with 30 appropriate controls. All females underwent measurement of fasting glucose level, fasting insulin level, and blood pressure., Results: The mean age of the women in the control group was 26.17 years, and in the study group, it was 27.09 years. All females had completed 20 weeks of gestation. Around 86.6% of women in the control group, 54.1% with a variable degree of preeclampsia, and 48.6% of women with eclampsia were at 33-38 weeks of gestation. At the time of sampling, 13.3% of women in the control group, 45.81% of women with preeclampsia, and 51.3% of women with eclampsia were at 26-32 weeks of gestation. The mean IR among the control group was 1.37, in preeclampsia, it was 2.11, and in eclampsia, it was 3.58 with a p -value of 0.000, which is very highly significant. In this study, the severity of the disease was found to be directly proportional to IR., Conclusion: Pregnancy complicated with preeclampsia and eclampsia showed more IR in comparison to pregnant women with normal blood pressure, and this relationship is independent of the age of pregnant women., (© Journal of the Association of Physicians of India 2024.)

Background and Aims: Water exchange (WE) and cap-assisted colonoscopy (CAC) separately reduced pain during insertion in unsedated patients. We hypothesized that compared with WE, WECAC could significantly lower real-time maximum insertion pain (RTMIP)., Methods: Veterans without escort were recruited, randomized, blinded, and examined at three United States Veterans Affairs sites. The primary outcome was RTMIP, highest segmental pain (0 = no pain, 10 = most severe pain) during insertion., Results: Randomization [WECAC (n = 143) and WE (n = 137)] produced even distribution of a racially diverse group of males and females of low socioeconomic status. Intention-to-treat analysis reported results of WECAC (listed first) and WE (listed second): cecal intubation [93%, 94.2%]; mean (SD) of RTMIP [2.9 (2.5), 2.6 (2.4)]; the proportion with no pain (28.7%, 27.7%); the insertion time [18.6 (15.6), 18.8 (15.9) min]; overall ADR (55.2%, 62.8%), all P values were > 0.05. When RTMIP was binarized as "no pain" (0) vs. "some pain" (1-10), or "low pain" (0-7) vs. "high pain" (8-10), different significant predictors (see text) of RTMIP were identified., Conclusions: Unsedated colonoscopy was appropriate for unescorted Veterans. WE alone was sufficient. Adding a cap did not reduce RTMIP. Patient specific factors and application of WE with insertion suction of infused water contributed to high and low RTMIP, respectively. For unesorted patients, selecting those with low anxiety, avoiding low body mass index, history of depression or self-reported poor health and adhering to the steps of WE can minimize RTMIP to ensure success of unsedated colonoscopy., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Mosquito surveillance for vector-borne disease management relies on traditional morphological and molecular techniques, which are tedious, time-consuming, and costly. The present study describes a simple and efficient recording device that analyzes mosquito sound to estimate species composition, male-female ratio, fed-unfed status, and harmonic convergence interaction using fundamental frequency (F 0 ) bandwidth, harmonics, amplitude, and combinations of these parameters. The study examined a total of 19 mosquito species, including 3 species of Aedes, 7 species of Anopheles, 1 species of Armigeres, 5 species of Culex, 1 species of Hulecoetomyia, and 2 species of Mansonia. Among them, the F 0 ranges between 269.09 ± 2.96 Hz (Anopheles culiciformis) to 567.51 ± 3.82 Hz (Aedes vittatus) and the harmonic band (hb) number ranges from 5 (An. culiciformis) to 12 (Ae. albopictus). In terms of species identification, the success rate was 95.32 % with F 0 , 84.79 % with F 0 -bandwidth, 84.79 % with harmonic band (hb) diversity, and 49.7 % with amplitude (dB). The species identification rate has gone up to 96.50 % and 97.66 % with the ratio and multiplication of F 0 and hb, respectively. This is because of the matrices that combine multiple sound attributes. Comparatively, combinations of the amplitude of the F 0 and the higher harmonic frequency band were non-significant for species identification (60.82 %). The fed females have shown a considerable increase in F 0 in comparison to the unfed. The males of all the species possessed significantly higher frequencies with respect to the females. Interestingly, the presence of male-female of Ae. vittatus together showed harmonic convergence between the 2nd and 3rd harmonic bands. In conclusion, the sound-based technology is simple, precise, and cost-effective and provides better resolution for species, sex, and fed-unfed status detection in comparison to conventional methods. Real-time surveillance of mosquitoes could potentially utilize this technology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The foraminiferal environmental DNA (eDNA) metabarcoding based on high-throughput sequencing (HTS) is a powerful tool to unravel the hidden genetic diversity and environmental lineages. Results from the eDNA approach provided valuable insight into an unplumbed diversity of soft-bodied monothalamous foraminifers [1]. Micropaleontologists overlooked monothalamids due to their soft organic and/or finely agglutinated test, which often gets destroyed during routine morphological investigations [2]. On the other hand, some foraminifera taxonomists or studies included monothalamids (soft-shelled species) in ecological and diversity investigations ranging from deep-sea locations to coastal marine habitats [1], [3], [4]. Here, we document our metabarcoding analysis of foraminiferal diversity and abundance from the mining-affected estuaries of the Indian state of Goa. High-throughput sequencing using the Illumina platform indicated the overwhelming abundance of monothalamous foraminifers in the studied estuarine sediments. For the first time, such detailed data of the foraminiferal diversity utilizing sedimentary environmental DNA (eDNA) methods was carried out in India. The raw sequence data used for analysis is available in NCBI under the Sequence Read Archive (SRA) with the BioProjects and SRA accession number: PRJNA1040471. The presented data may be used as baseline information for eDNA-based biomonitoring and biodiversity assessment surveys from Indian marine habitats across time and space., (© 2024 The Author(s).)

Gastrointestinal (GI) cancers account for one-fourth of the global cancer incidence and are incriminated to cause one-third of cancer-related deaths. GI cancer includes esophageal, gastric, liver, pancreatic, and colorectal cancers, mostly diagnosed at advanced stages due to a lack of accurate markers for early stages. The invasiveness of diagnostic methods like colonoscopy for solid biopsy reduces patient compliance as it cannot be frequently used to screen patients. Therefore, minimally invasive approaches like liquid biopsy may be explored for screening and early identification of gastrointestinal cancers. Liquid biopsy involves the qualitative and quantitative determination of certain cancer-specific biomarkers in body fluids such as blood, serum, saliva, and urine to predict disease progression, therapeutic tolerance, toxicities, and recurrence by evaluating minimal residual disease and its correlation with other clinical features. In this review, we deliberate upon various tumor-specific cellular and molecular entities such as circulating tumor cells (CTCs), tumor-educated platelets (TEPs), circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), exosomes, and exosome-derived biomolecules and cite recent advances pertaining to their use in predicting disease progression, therapy response, or risk of relapse. We also discuss the technical challenges associated with translating liquid biopsy into clinical settings for various clinical applications in gastrointestinal cancers., Competing Interests: Author ST was employed by Trivitron Healthcare Pvt Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mondal, Shinde, Sinha, Dixit, Paul, Gupta, Thakur, Vishvakarma and Shukla.)

Large-vessel occlusion (LVO) stroke is a promising field for the use of AI, especially machine learning (ML) because optimal results are highly dependent on timely diagnosis, communication, and treatment. In order to better understand the current state of artificial intelligence (AI) in relation to LVO strokes, its efficacy, and potential future applications, we searched relevant literature to perform a comprehensive evaluation of the topic. The databases PubMed, Embase, and Scopus were extensively searched for this review. Studies were then screened using title and abstract criteria and duplicate studies were excluded. By using pre-established inclusion and exclusion criteria, it was decided whether or not to include full-text papers in the final analysis. The studies were analyzed, and the relevant information was retrieved. In recognizing LVO on computed tomography, ML approaches were very accurate. There is a shortage of AI applications for thrombectomy patient selection, despite the fact that certain research accurately evaluates individual patient eligibility for endovascular therapy. Machine learning algorithms may reasonably predict clinical and angiographic outcomes as well as associated factors. AI has shown promise in the diagnosis and treatment of people who have just suffered a stroke. However, the usefulness of AI in management and forecasting remains restricted, necessitating more studies into machine learning applications that can guide decision making in the future., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Benthic foraminifera are unicellular eukaryotic protists that construct an organic, agglutinated, or calcareous test wall. Although single-chambered (monothalamous) foraminifera are ubiquitous in marine habitats worldwide, they are poorly known compared to their multi-chambered relatives, notably from the tropical marine environments of India. In this study, we describe two new species of marine monothalamid genus Psammophaga Arnold, 1982, from the Rajapuri Creek, coastal Maharashtra, India (Arabian Sea). Psammophaga holzmannae sp. nov. is ovoid to spherical shaped, 103-246 µm in length, single aperture, translucent to orange color cytoplasm, outer surface is composed of agglutinated fine clay particles, and ingested mineral grains are concentrated near its aperture. Psammophaga sinhai sp. nov. is oblong, elliptical, or droplet-shaped, 279-448 µm in length, single aperture, yellow olive color cytoplasm, the exterior surface formed of agglutinated fine clay particles, and the ingested mineral grains are dispersed throughout the body. Phylogenetic analyses based on partial small subunit rRNA gene sequences position new species within the Clade E of monothalamids and are genetically distinct from other Psammophaga. Elemental (SEM-EDS) analysis of engulfed mineral grains revealed preferential selection and uptake of heavy opaque titaniferous minerals from the ambient environment in the cytoplasm., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Background: Vitiligo is a common depigmenting dermatosis characterized by milky-white macules or patches. Any pathological discoloration of the skin has been linked to an impact on the body image of an individual, and vitiligo has been linked to decreased self-esteem and poor socialization of the affected people. In Indian society, vitiligo is labeled as Shweta-Kushta (i.e., white-colored leprosy) and is compared to leprosy-a more stigmatizing skin condition., Aim: This study aims to study gender-related differences in the quality of life of Indian vitiligo patients., Methodology: In this hospital-based cross-sectional study, a total of 55 vitiligo patients (females 25 and males 30) were enrolled using the purposive sampling technique. The sample was assessed on Dermatology Life Quality Index (DLQI) questionnaire, Rosenberg Self-Esteem Scale (RSS), and General Health Questionnaire-12 (GHQ-12) to assess their quality of life, self-esteem, and psychological well-being, respectively. The gender differences in sociodemographic and clinical details as well as their relationship with the quality of life of the patients were sought with the help of appropriate statistical measures., Results: The patients of both genders were comparable in terms of all sociodemographic and clinical variables except the females being less educated and employed than the males. There was a statistically significant trend of higher mean DLQI total score in females than males (6.6 ± 3.55 vs 4.8 ± 2.71, Mann-Whitney U = 263.5, P =0.058). Significantly, the average DLQI score in female vitiligo patients was negatively related to family income ( r s = -.659, P <.001) and it was significantly higher for the patients from a rural background than those from an urban background (8.55 ± 3.30 vs 5.07 ± 3.03, Mann-Whitney U = 33.5, P <.05). The average DLQI score was negatively correlated to RSS score but positively correlated to GHQ-12 score in patients of both genders., Conclusion: The quality of life of female patients with vitiligo is poorer than the same in male patients. The poor financial condition of families and rural living are two factors related to the poorer quality of life of female patients. A poorer quality of life in vitiligo patients of both genders is linked with decreased self-esteem and decreased psychological well-being. Gender-related issues in the quality of life and the overall well-being of such patients are important in their management and policy-making., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Industrial Psychiatry Journal.)

Background: The Coronavirus Anxiety Scale (CAS) was developed in April 2020 as an instrument to gauge the symptoms of stress and anxiety occurring secondary to the COVID-19 pandemic. It was constructed using the English language due to which its application to a multi-linguistic country like India became a hindrance., Aim: To establish psychometric validity and reliability of the Bengali translation of CAS., Materials and Methods: Experts well-versed in the English and Bengali languages translated CAS from English to Bengali. This was followed by further correction by forward and backward translation processes until a version with high accuracy and low redundancy was procured. The original scale was applied to 91 volunteers, and the translated version was applied to the same group after 14 days., Results: The mean scores of the original version and the translated version showed a significant correlation. The Bengali version of CAS had high internal consistency, significant concurrent validity, and acceptable split-half reliability. It was hence deemed easily understandable and capable of measuring anxiety due to COVID-19 similar to the original scale., Conclusion: The Bengali translation of the CAS can be accurately used to assess symptoms of anxiety and stress with high reliability and validity in those who are able to read the Bengali language., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Industrial Psychiatry Journal.)

Cilnidipine is a calcium channel blocker that is used to treat cardiac diseases such as angina and high blood pressure. Several column and planar chromatographic methods for estimating cilnidipine in pharmaceutical dosage forms have been documented. However, these method developments have been carried out employing organic solvents such as acetonitrile, methanol, toluene, chloroform, and others as mobile phase components or as sample pretreatment diluents. These organic solvents are neurotoxic and teratogenic to humans and aquatic animals, according to International Council for Harmonization Q3C (R8) recommendations. According to the green analytical chemistry approach, such organic solvents should be reduced or removed during the development of chromatographic methods for environmental protection and the safety of human and aquatic animal life. As a result, the stability-indicating chromatographic estimation of cilnidipine was performed utilizing less toxic organic solvents. To prevent organic solvent waste during method development, mobile-phase optimization was performed using the design of experiment-based response surface modeling. Cilnidipine has been subjected to hydrolysis, oxidation, photolysis, and dry-heat decomposition to determine its stability. The greenness profiles of the suggested and published chromatographic methods were examined using the national environment method index, analytical greenness calculator, green analytical procedure index software, and eco-scale assessment tool., (© 2023 Wiley-VCH GmbH.)

Visible light communication (VLC) allows white LEDs to communicate while lighting, which improves resource consumption. Multiple relay approaches can be employed in conjunction with cooperative communications to achieve large gains in spatial diversity, expand the coverage, and possibly boost system capacity. In this paper, the nonorthogonal multiple access (NOMA) cooperative techniques for VLC systems using on-off keying (OOK) and L-pulse-position modulation (L-PPM) are proposed. The maximum ratio combining (MRC) schemes is adopted at the receiving node to combine the signals received from cooperative transmissions. Further, the decode-and-forward relaying protocol is considered for cooperation. The proposed system is analyzed for a multiuser scenario that is followed by a two- and three-user scenario for detailed analysis. This study calculates the bit error probability (BEP) of an OOK/L-PPM modulated NOMA cooperative VLC system under perfect and imperfect successive interference cancellation. Simulation results are presented to validate the produced analytical BEP results.

T-cell malignancy is a broad term used for a diverse group of disease subtypes representing dysfunctional malignant T cells transformed at various stages of their clonal evolution. Despite having similar clinical manifestations, these disease groups have different disease progressions and diagnostic parameters. The effective diagnosis and prognosis of such a diverse disease group demands testing of molecular entities that capture footprints of the disease physiology in its entirety. MicroRNAs (miRNAs) are a group of noncoding RNA molecules that regulate the expression of genes and, while doing so, leave behind specific miRNA signatures corresponding to cellular expression status in an altered stage of a disease. Using miRNAs as a diagnostic tool is justified, as they can effectively distinguish expressional diversity between various tumors and within subtypes of T-cell malignancies. As global attention for cancer diagnosis shifts toward liquid biopsy, diagnosis using miRNAs is more relevant in blood cancers than in solid tumors. We also lay forward the diagnostic significance of miRNAs that are indicative of subtype, progression, severity, therapy response, and relapse. This review discusses the potential use and the role of miRNAs, miRNA signatures, or classifiers in the diagnosis of major groups of T-cell malignancies like T-cell acute lymphoblastic lymphoma (T-ALL), peripheral T-cell lymphoma (PTCL), extranodal NK/T-cell lymphoma (ENKTCL), and cutaneous T-cell lymphoma (CTCL). The review also briefly discusses major diagnostic miRNAs having prominent metabolic roles in these malignancies to highlight their importance among other dysregulated miRNAs., Competing Interests: Authors ST and GV were employed by the company Trivitron Healthcare Pvt. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mondal, Shinde, Paul, Thakur, Velu, Tiwari, Dixit, Amit, Vishvakarma and Shukla.)

Background: Recent reports indicate that self-isolation because of coronavirus disease 2019 (COVID-19)-related lockdowns had significant influence on mental health of medical students., Aim: To understand the relationship between two different motivations for solitude - self-determined versus non-self-determined with medical students' COVID-19-related anxiety and psychological resilience during their self-isolation because of COVID-19-related lockdowns., Materials and Methods: After the approval of the Institutional Ethics Committee, this online survey was done on undergraduate Indian medical students during the COVID-19 pandemic. Expressing consent at the beginning of the online form, enabled the students to proceed to the next section comprising their sociodemographic details and clinical details. The last section of the form comprised the Motivation for Solitude Scale-Short Form, the COVID-19 Anxiety Scale, and the Connor-Davidson Resilience Scale-Abbreviated., Results: 282 out of 286 students of either sex gave their consent and completed the given form. Both self-determined and non-self-determined motivations for solitude were higher in female medical students. The self-determined motivation for solitude was directly related to all students' resilience. A past history of psychiatric illness was directly associated with the non-self-determined motivation for solitude of the students. The non-self-directed motivation for solitude of female students was indirectly related to their resilience. The COVID-19-related anxiety was not related to either type of motivation for solitude as well as the resilience of the medical students., Conclusion: Indian female medical students are more motivated for solitude, be it self-determined or non-self-determined, than their male counterparts. The student's resilience has a direct relationship with students' self-determined motivation. The COVID-19-related anxiety among the medical students is not related to their motivations for solitude or resilience., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Industrial Psychiatry Journal.)

With a population dividend of around 1.3 billion, India is the largest democracy in the world that encompasses "unity in diversity". The kaleidoscope of the socio-cultural fabric comprises the transgender population too, which has a historical context dating back millennia and also plays a vital role as described in Hindu scriptures. The Indian transgender person's community shows a variety of gender identities and sexual orientations, which is unlikely from the West, forming a culturally unique gender group. In India, transgender persons were recognised as the 'third gender' in 2014. The third gender population of India is marginalised to a great extent in every sector. Often, transgender persons have been the subjects of sociology, psychology, and health issues. There was a dearth of data regarding their major health problems including bone health, which has not been reported in India and elsewhere before this study. Through a prospective cross-sectional study design, we aimed to determine the current health status of transgender persons with a special emphasis on bone health. Descriptive statistics were used for data analysis. The preliminary results of the study show poor bone health in the transgender population of India. The majority of transgender persons have low bone mineral density (BMD) at a much young age, even before the achievement of their peak bone mass. The health status of the transgender population in India is poor overall. Transgender persons have many impediments to optimal healthcare that requires holistic care. This study presents the current health challenges of the transgender population with a special emphasis on their bone health status as 'AIIMS initiative'. This study also shows transgender persons human rights needs to be explicitly discussed. The stakeholders of social policies require an urgent attention to unfold the major concerns encompassing transgender persons., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

In recent years, visible light communication (VLC) has emerged as a potential technique for beyond 5G communication networks. In this study, an angular diversity receiver (ADR) is used to propose a multiple-input multiple-output (MIMO) VLC system employing L-pulse position modulation ( L -PPM). Repetition coding (RC) is used at the transmitter, while receiver diversity techniques such as maximum-ratio combining (MRC), selection best combining (SBC), and equal gain combining (EGC) are used at the receiver to improve performance. This study presents the exact probability of error expressions for the proposed system with and without channel estimation error (CEE). The analysis shows that the probability of error of the proposed system increases as the estimation error increases. Further, the study shows that the increase in signal-to-noise ratio is not enough to counter the impact of CEE, especially when the estimation error is large. The distribution of error probability of the proposed system using EGC, SBC, and MRC throughout the area of the room is presented. The simulation findings are compared to the analytical results.

Background: Functional gastrointestinal disorders (FGIDs), including irritable bowel syndrome (IBS), are associated with psychological abnormalities, such as anxiety and depression. Though the data on this are plenty in global literature, Indian data are sparse. We performed a systematic review and meta-analysis of Indian data on anxiety and depression among patients with IBS to estimate their pooled prevalence and to identify the shortcomings so that future areas of research can be identified., Method: A comprehensive literature search was performed for studies applying tests for psychological issues in patients with IBS. After applying prospectively decided exclusion criteria, the eligible papers were examined using a meta-analysis approach for the prevalence of anxiety and depression in IBS patients using different tests. The odds ratios (OR) of anxiety and depression among subjects with IBS were calculated compared to controls., Results: Of seven studies (590 IBS patients and 1520 controls) included in the meta-analysis, the pooled OR of anxiety was 8.060 (95% confidence interval [CI] 4.007-16.213) as compared to controls (random-effect model). The pooled OR of depression was 7.049 (95% CI 3.281-15.147) compared to controls (random-effect model). There was significant heterogeneity in the included studies., Conclusion: The current meta-analysis shows that the patients with IBS from India have eightfold greater risks of anxiety and sevenfold greater risks of depression than the controls. However, most of these data were from tertiary urban centers, and hence, there might be recruitment bias over-estimating the frequency., (© 2022. Indian Society of Gastroenterology.)

Background: Caregivers of patients with schizophrenia have a considerable burden of care and develop different coping strategies to deal with the caregiving burden., Aim: The aim of this article is to assess gender differences in the burden of care and coping strategies used among caregivers of clinically stable patients with schizophrenia., Methods: In this cross-sectional study, a total of 57 caregivers (33 males and 24 females) of the patients with schizophrenia attending a psychiatric outpatient setting were included by purposive sampling. The caregivers were assessed with the Burden Assessment Schedule 20 items (BAS-20) and Brief Approach/Avoidance Coping Questionnaire (BACQ) to assess the burden of care and coping strategies, respectively., Results: Average BAS-20 score was comparable between the male and female caregivers. If the patient was a spouse, the male caregivers had a significantly higher burden of the marital relationship than the female caregivers. On the BACQ, the socio-emotional approach subscale was significantly higher in female caregivers. The avoidance-oriented coping score and socio-emotional avoidance subscale were significantly higher in male caregivers. A significant positive correlation was found between BAS-20 score and avoidance-oriented coping scores in all caregivers except the females where a significant negative correlation was found between BAS score and socio-emotional avoidance type of coping., Conclusion: There are no gender differences in the burden of care in caregivers of clinically stable patients with schizophrenia except the male caregivers have a higher burden in the domain of marital relationship. The socio-emotional approach type of coping is higher in females while the socio-emotional avoidance type of coping is lower in male caregivers., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Industrial Psychiatry Journal.)

In the present investigation Sn 1- β Sb β Se crystals are grown using the direct vapor transport method. The crystals after growth were analyzed by EDAX and XPS to confirm the elemental composition. The surface morphological properties were studied by scanning electron microscope, confirming a flat surface and layered growth of the Sn 1- β Sb β Se crystals. The structural properties studied by X-ray diffraction and high-resolution transmission electron microscopy confirm the orthorhombic structure of the grown Sn 1- β Sb β Se crystals. The Raman spectroscopic measurements evince the presence of B2g and Ag vibration modes. The PL intensity peak at ∼400 nm to 500 nm confirms the energy band gap. The indirect energy band gap of 1.18 eV was evaluated using Tauc plot by employing UV-visible spectroscopy making it a promising candidate for optoelectronic and photonic applications. The pulse photo response of pure and doped samples was studied under a monochromatic source of wavelength 670 nm and intensity of 30 mW cm -2 at zero biasing voltage firstly on day one and then the same samples were preserved for 50 days and the stability of the photodetectors was observed. Photodetector parameters such as rise time, decay time, photocurrent, responsivity, sensitivity, and detectivity were observed, and evaluated results are presented in this article., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Bacterial contaminated water causes potential health issues. Conventional chlorine treatment has shortcomings of environmental hazards and chlorine adoptability by the bacterial cells. Ultrafiltration membrane can intercept bacterial species from feed water. Membrane having anti-biofouling/antifouling properties is needed for the removal of bacteria from feed water. Herein, interpolymer membranes with inherent antimicrobial activity and fouling release property have been prepared by the blend of poly(vinylidene fluoride) (PVDF), poly(vinyl pyrrolidone) and partially long chain alkylated (C12 chain) poly(vinyl imidazole) copolymer (PVIm-co-PVIm-C12) followed by cross-linking of the remaining VIm groups with an activated di-halide compound. The membranes obtain with copolymers of degree of alkyl substitution (DS C12 ) in the range of 0.75-0.85 and amount in the range of 0.9-3.5% w/w in the casting solutions exhibit good antimicrobial activity (>99 % of inhibition) and dynamic anti-biofouling property. The membrane prepared with 0.9% w/w of the copolymer (DS C12 =0.85) shows higher flux recovery ratio (91 % for bacterial filtration and 88 % for protein filtration) compare to a pristine membrane (57 % for bacterial filtration and 58 % for protein filtration). The membrane is able to reject the bacteria completely. Use of small amount of copolymer and facile fabrication of stable anti-biofouling/antifouling membranes show potential for the purification of bacterial contaminated water., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The low water solubility of pharmacoactive molecules limits their pharmacological potential, but the solubility parameter cannot compromise, and so different approaches are employed to enhance their bioavailability. Pharmaceutically active molecules with low solubility convey a higher risk of failure for drug innovation and development. Pharmacokinetics, pharmacodynamics, and several other parameters, such as drug distribution, protein binding and absorption, are majorly affected by their solubility. Among all pharmaceutical dosage forms, oral dosage forms cover more than 50%, and the drug molecule should be water-soluble. For good therapeutic activity by the drug molecule on the target site, solubility and bioavailability are crucial factors. The pharmaceutical industry's screening programs identified that around 40% of new chemical entities (NCEs) face various difficulties at the formulation and development stages. These pharmaceuticals demonstrate less solubility and bioavailability. Enhancement of the bioavailability and solubility of drugs is a significant challenge in the area of pharmaceutical formulations. According to the Classification of Biopharmaceutics, Class II and IV drugs (APIs) exhibit poor solubility, lower bioavailability, and less dissolution. Various technologies are discussed in this article to improve the solubility of poorly water-soluble drugs, for example, the complexation of active molecules, the utilization of emulsion formation, micelles, microemulsions, cosolvents, polymeric micelle preparation, particle size reduction technologies, pharmaceutical salts, prodrugs, the solid-state alternation technique, soft gel technology, drug nanocrystals, solid dispersion methods, crystal engineering techniques and nanomorph technology. This review mainly describes several other advanced methodologies for solubility and bioavailability enhancement, such as crystal engineering, micronization, solid dispersions, nano sizing, the use of cyclodextrins, solid lipid nanoparticles, colloidal drug delivery systems and drug conjugates, referring to a number of appropriate research reports., Competing Interests: The authors declare no conflict of interest.

Stimulator of interferon genes (STING) is an innate immune receptor activated by natural or synthetic agonists to elicit antitumoral immune response via type I IFNs and other inflammatory cytokines. Bacillus Calmette-Guerin (BCG) is the standard of care as intravesical therapy for patients with high-risk non-muscle invasive bladder cancer (NMIBC). There are limited options available for patients with NMIBC who developed BCG unresponsiveness. In this study, we characterized in vitro and in vivo antitumor effects of E7766, a macrocyle-bridged STING agonist, via intravesical instillation in two syngeneic orthotopic murine NMIBC tumor models resistant to therapeutic doses of BCG and anti-PD-1 agents. E7766 bound to recombinant STING protein with a Kd value of 40 nmol/L and induced IFNβ expression in primary human peripheral blood mononuclear cells harboring any of seven major STING genotypes with EC50 values of 0.15 to 0.79 μmol/L. Intravesical E7766 was efficacious in both NMIBC models with induction of effective immunologic memory in the treated animals. Pharmacologic activation of the STING pathway in the bladder resulted in IFN pathway activation, infiltration of T cells and natural killer (NK) cells, dendritic cell activation, and antigen presentation in bladder epithelium, leading to the antitumor activity and immunity. In addition, measurements of the pharmacodynamic markers, Ifnβ1 and CXCL10, in bladder, urine, and plasma, and of STING pathway intactness in cancer cells, supported this mode of action. Taken together, our studies reveal an antitumor immune effect of pharmacologic activation of the STING pathway in bladder epithelium and thus provide a rationale for subsequent clinical studies in patients with NMIBC., (©2022 American Association for Cancer Research.)

The extension of life span driven by 40% caloric restriction (CR) in rodents causes trade-offs in growth, reproduction, and immune defense that make it difficult to identify therapeutically relevant CR-mimetic targets. We report that about 14% CR for 2 years in healthy humans improved thymopoiesis and was correlated with mobilization of intrathymic ectopic lipid. CR-induced transcriptional reprogramming in adipose tissue implicated pathways regulating mitochondrial bioenergetics, anti-inflammatory responses, and longevity. Expression of the gene Pla2g7 encoding platelet activating factor acetyl hydrolase (PLA2G7) is inhibited in humans undergoing CR. Deletion of Pla2g7 in mice showed decreased thymic lipoatrophy, protection against age-related inflammation, lowered NLRP3 inflammasome activation, and improved metabolic health. Therefore, the reduction of PLA2G7 may mediate the immunometabolic effects of CR and could potentially be harnessed to lower inflammation and extend the health span.

By offering a wide license-free spectrum, visible light communication (VLC) has emerged as a game-changing technology for networks beyond 5G. In this study, the multiple-input multiple-output (MIMO) technology is combined with a non-orthogonal multiple access VLC (NOMA-VLC) system to provide a reliable error-free high data rate network for multi-user scenarios. A generalized L -PPM modulated MIMO based multi-user NOMA-VLC system with M × N line-of-sight connections for each user is presented. Considering a practical scenario of imperfect successive interference cancellation, a novel closed form formulation of error probability for the proposed system is obtained. This study also includes a comprehensive analysis of two-user and three-user L -PPM modulated 2×2 MIMO-NOMA-VLC systems, and exact error probability expressions are derived. With the identical set of parameters, the L -PPM modulated MIMO-NOMA-VLC system totally outperforms the on-off keying modulated MIMO-NOMA-VLC system. As the number of photodetectors per user increases, the error probability of the considered system decreases. An L -PPM modulated 2×2 MIMO based three-user NOMA-VLC system offers the best performance at a power allocation co-efficient of 0.3. The simulation results validate the derived error probability expressions.

Drive cycles in vehicle systems are important determinants for energy consumption, emissions, and safety. Estimating the frequency of the drive cycle quickly is important for control applications related to fuel efficiency, emission reduction and improving safety. Quantum computing has established the computational efficiency that can be gained. A drive cycle frequency estimation algorithm based on the quantum Fourier transform is exponentially faster than the classical Fourier transform. The algorithm is applied on real world data set. We evaluate the method using a quantum computing simulator, demonstrating remarkable consistency with the results from the classical Fourier transform. Current quantum computers are noisy, a simple method is proposed to mitigate the impact of the noise. The method is evaluated on a 15 qubit IBM-q quantum computer. The proposed method for a noisy quantum computer is still faster than the classical Fourier transform., (© 2022. The Author(s).)

Background and Aims: We aimed to determine the cause of non-secondary hyperparathyroidism (Non-SHPT) in Indian postmenopausal women., Materials & Methods: 334 apparently healthy postmenopausal women were assessed for bone mineral homeostaisis including Vitamin D, PTH and VDR polymorphism., Results: 83% of the subjects had vitamin D deficiency further associated with VDR gene polymorphism (P 0.000). A sizable number of subjects (N = 83) did evoke SHPT despite low vitamin D levels. We observe that VDR gene polymorphism was strongly associated in the sub-group of non-SHPT., Conclusion: lack of SHPT warrants researchers to study the pathophysiology of non-SHPT in detail to substantiate our findings., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Serum leptin has been considered as an important measurable diagnostic and prognostic biomarker for polycystic ovarian syndrome (PCOS), although its evidence for use in clinical practice is limited. We aim to synthesize the available evidence on the clinical use of serum leptin values in PCOS by doing a systematic review and meta-analysis of studies., Objective: To conduct a meta-analysis to determine the pooled effect size of the association of leptin levels in patients with PCOS., Methods: We searched electronic databases, i.e., PubMed, Google Scholar, Web of Science, ClinicalTrials.gov, and Medline from inception to September 2020, keeping filters for human studies and published in the English language. We used the random-effects model if heterogeneity between the studies was > 50%; otherwise, a fixed-effect model was applied to determine the standardized mean difference with 95% CI for comparison of leptin level between cases and controls. All the statistical analyses were completed using software STATA version 13., Results: The meta-analysis included a total of 35 studies involving 2015 cases and 1767 controls that suggested statistically significantly higher leptin levels in the women with PCOS as compared to controls (SMD, 1.76, 95% CI 1.28 to 2.23, P  < 0.001). In the stratified analysis when only high methodological quality studies were included, we did not observe a statistically significant difference in the leptin level between PCOS and controls (SMD 0.68, 95% CI -0.09 to 1.46). Analysis restricted to low methodological quality studies observed statistically significant high leptin levels in PCOS women as compared to controls (SMD 2.24, 95% CI 1.65 to 2.83)., Conclusion: The available evidence suggests that elevated leptin levels may be associated with risk of PCOS as compared to controls; however, failure to observe the similar association in high methodological quality studies demands further well-designed adequately powered studies to validate the findings., Competing Interests: Conflict of interestAll authors declare that they have no conflict of interest., (© Federation of Obstetric & Gynecological Societies of India 2021.)

Autonomous Vehicles (AVs) are being widely tested on public roads in several countries such as the USA, Canada, France, Germany, and Australia. For the transparent deployment of AVs in California, the California Department of Motor Vehicles (CA DMV) commissioned AV manufacturers to draft and publish reports on disengagements and crashes. These reports must be processed before any statistical analysis, which is cumbersome and time-consuming. Our dataset presents the processed disengagement data from 2014 to 2019, crash data till the 10 th of March 2020 and supplementary road network and land-use data extracted from OpenStreetMap. Primary data are manually assessed and converted into an easily processed format. Our processed data will be advantageous to the research community and enable accelerated research in this domain. For example, the data can be utilised to discern trends in disengagement, observe the distribution of disengagement causes, and investigate the contributory factors of the crashes. Such investigations can subsequently improve the reporting protocols and make policies and laws for the smooth deployment of this disruptive technology., (© 2021. The Author(s).)

We report a systematic investigation of the differences in charge transport mechanism in ultra-thin nano-island like films of palladium with thickness varying between 5 nm and 3 nm. The thicker films were found to be metallic in a large temperature range with a dominant Bloch-Grüneisen mechanism of charge transport arising due to electron-acoustic phonon scattering. These films were also found to exhibit an additional electron-magnon scattering. At temperatures below 20 K, the two films displayed a metal-insulator transition which was explained using Al'tshuler's model of increased scattering in disordered conductors. The thinner films were insulating and were found to exhibit Mott's variable range hopping mechanism of charge transport. The thinnest film showed a linear decrease of resistance with an increase in temperature in the entire temperature range. The island-like thin films were found to display very different response to hydrogenation at room temperature where the metallic films were found to display a decrease of resistance while the insulating films were found to have an increase of resistance. The decrease of resistance was ascribed to a hydrogen induced lattice expansion in the thin films that were at the percolation threshold while the resistance increase to an increase in work function of the films due to an increased adsorption of the hydrogen atoms at the surface sites of palladium., (© 2021. The Author(s).)

This paper investigates the use of a general multi-arm multi-stage (MAMS) approach for time-to-event outcomes that would streamline simultaneous comparison of a large number of promising therapies in clinical trials, thus significantly reducing the time and the number of patients needed to evaluate the treatment. Controlling type I error in this setting is different than regular clinical trials as this approach incorporates both multiple comparison between arms and multiple stages. Historically, pairwise (PWER) and familywise (FWER) type I error rates have been primarily used to regulate the type I error in such designs. This paper will focus on constructing the efficacy and futility boundaries for a MAMS clinical trial in two different scenarios. In the first, it is assumed that the same outcome is used throughout the clinical trial for both intermediate and final assessments. In this scenario, we propose using the generalized Dunnett procedure that controls FWER. In the latter scenario, where intermediate and final outcomes are different in nature, we propose modifications to the existing method that originally concentrated on controlling PWER and extend the method to include FWER in the design. We also explore the performance of the proposed MAMS design in a setting where the proportional hazard assumption is violated in the presence of a delayed treatment effect and demonstrate the loss of power because of that. An alternative test statistic that can help circumvent this problem to maintain the desired power is also suggested.

The road to computing on quantum devices has been accelerated by the promises that come from using Shor's algorithm to reduce the complexity of prime factorization. However, this promise hast not yet been realized due to noisy qubits and lack of robust error correction schemes. Here we explore a promising, alternative method for prime factorization that uses well-established techniques from variational imaginary time evolution. We create a Hamiltonian whose ground state encodes the solution to the problem and use variational techniques to evolve a state iteratively towards these prime factors. We show that the number of circuits evaluated in each iteration scales as [Formula: see text], where n is the bit-length of the number to be factorized and d is the depth of the circuit. We use a single layer of entangling gates to factorize 36 numbers represented using 7, 8, and 9-qubit Hamiltonians. We also verify the method's performance by implementing it on the IBMQ Lima hardware to factorize 55, 65, 77 and 91 which are greater than the largest number (21) to have been factorized on IBMQ hardware., (© 2021. The Author(s).)

Background: Hepatitis C is an important agent of liver damage in patients with chronic kidney disease and the advent of DAAs has dramatically changed the management of HCV positive patients, including those with advanced CKD. Sofosbuvir is the backbone of many anti-HCV regimens based on DAAs but it remains unclear whether it is appropriate for HCV-infected patients with stage 4-5 CKD., Study Aims and Design: We performed a systematic review of the literature with a meta-analysis of clinical studies in order to evaluate the efficacy and safety of SOF-based DAA regimens in patients with stage 4-5 CKD. The primary outcome was sustained viral response (as a measure of efficacy); the secondary outcomes were the frequency of SAEs and drop-outs due to AEs (as measures of tolerability). The random-effects model of DerSimonian and Laird was adopted, with heterogeneity and stratified analyses., Results: Thirty clinical studies (n=1537 unique patients) were retrieved. The pooled SVR12 and SAEs rate was 0.99 (95% confidence intervals, 0.97; 1.0, I 2 =99.8%) and 0.09 (95% CI, 0.05; 0.13, I 2 =84.3%), respectively. The pooled SVR12 rate in studies with high HCV RNA levels at baseline was lower, 0.87 (95% CI, 0.75; 1.0, I 2 =73.3%) (P<0.001). The pooled drop-out rate due to AEs was 0.02 (95% CI, -0.01; 0.04, I 2 =16.1%). Common serious adverse events were anemia (n=26, 38%) and reduced eGFR (n=14, 19%). SAEs were more common in studies adopting full-dose sofosbuvir (pooled rate of SAEs 0.15, 95% CI, 0.06; 0.25; I 2 =80.1%) and in those based on ribavirin (0.15, 95% CI, 0.07; 0.23, I 2 =95.8%). Six studies (n=69 patients) reported eGFR levels at baseline/post- antiviral therapy; no consistent changes were found., Conclusions: SOF-based regimens appear safe and effective in patients with stage 4-5 CKD. Serum creatinine should be carefully monitored during therapy with SOF in patients with CKD. Randomized controlled studies in order to expand our knowledge on this point are under way., (Copyright © 2021 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

The predictive performance of physiologically-based pharmacokinetics (PBPK) models for pharmacokinetics (PK) in renal impairment (RI) and hepatic impairment (HI) populations was evaluated using clinical data from 29 compounds with 106 organ impairment study arms were collected from 19 member companies of the International Consortium for Innovation and Quality in Pharmaceutical Development. Fifty RI and 56 HI study arms with varying degrees of organ insufficiency along with control populations were evaluated. For RI, the area under the curve (AUC) ratios of RI to healthy control were predicted within twofold of the observed ratios for > 90% (N = 47/50 arms). For HI, > 70% (N = 43/56 arms) of the hepatically impaired to healthy control AUC ratios were predicted within twofold. Inaccuracies, typically overestimation of AUC ratios, occurred more in moderate and severe HI. PBPK predictions can help determine the need and timing of organ impairment study. It may be suitable for predicting the impact of RI on PK of drugs predominantly cleared by metabolism with varying contribution of renal clearance. PBPK modeling may be used to support mild impairment study waivers or clinical study design., (© 2020 Merck Sharp & Dohme Corp. Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.)

It is well known that subtropical shallow convection transports heat and water vapor upwards from the surface. It is less clear if it also transports horizontal momentum upwards to significantly affect the trade winds in which it is embedded. We utilize unique multiday large-eddy simulations run over the tropical Atlantic with ICON-LEM to investigate the character of shallow convective momentum transport (CMT). For a typical trade-wind profile during boreal winter, CMT acts as an apparent friction to decelerate the north-easterly flow. This effect maximizes below the cloud base while in the cloud layer, friction is very small, although present over a relatively deep layer. In the cloud layer, the zonal component of the momentum flux is counter-gradient and penetrates deeper than reported in traditional shallow cumulus LES cases. The transport through conditionally sampled convective updrafts and downdrafts explains a weak friction effect, but not the counter-gradient flux near the cloud tops. The analysis of the momentum flux budget reveals that, in the cloud layer, the counter-gradient flux is driven by convectively triggered nonhydrostatic pressure-gradients and horizontal circulations surrounding the clouds. A model set-up with large domain size and realistic boundary conditions is necessary to resolve these effects., (© 2021. The Authors. Journal of Advances in Modeling Earth Systems published by Wiley Periodicals LLC on behalf of American Geophysical Union.)

An unprecedented visible light-assisted and zinc triflate-catalyzed construction of a diaryl-substituted quaternary stereocenter is reported. 2-(4-Hydroxyphenyl)-substituted aldehydes and ketones have been prepared in moderate to high yields via multicomponent reaction of acetylene, benzoquinone (BQ), and indole/aniline/thiol. The reaction is believed to proceed via in situ generation of p -quinone methide through a [2+2] cycloaddition-retroelectrocyclization of BQ and acetylene in blue light followed by a zinc triflate-catalyzed vinylogous Michael addition reaction with nucleophiles.

Impaired interleukin-2 (IL-2) production and regulatory T-cell dysfunction have been implicated as immunological mechanisms central to the pathogenesis of multiple autoimmune and inflammatory diseases. NKTR-358, a novel regulatory T-cell stimulator, is an investigational therapeutic that selectively restores regulatory T-cell homeostasis in these diseases. We investigated NKTR-358's selectivity for regulatory T-cells, receptor-binding properties, ex vi vo and in vivo pharmacodynamics, ability to suppress conventional T-cell proliferation in mice and non-human primates, and functional activity in a murine model of systemic lupus erythematosus. In vitro, NKTR-358 demonstrated decreased affinity for IL-2Rα, IL-2Rβ, and IL-2Rαβ compared with recombinant human IL-2 (rhIL-2). A single dose of NKTR-358 in cynomolgus monkeys produced a greater than 15-fold increase in regulatory T-cells, and the increase lasted until day 14, while daily rhIL-2 administration for 5 days only elicited a 3-fold increase, which lasted until day 7. Repeated dosing of NKTR-358 over 6 months in cynomolgus monkeys elicited cyclical, robust increases in regulatory T-cells with no loss in drug activity over the course of treatment. Regulatory T-cells isolated from NKTR-358-treated mice displayed a sustained, higher suppression of conventional T-cell proliferation than regulatory T-cells isolated from vehicle-treated mice. NKTR-358 treatment in a mouse model (MRL/MpJ-Fas lpr ) of systemic lupus erythematosus for 12 weeks maintained elevated regulatory T-cells for the treatment duration and ameliorated disease progression. Together, these results suggest that NKTR-358 has the ability to elicit sustained and preferential proliferation and activation of regulatory T-cells without corresponding effects on conventional T-cells, with improved pharmacokinetics compared with rhIL-2., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. All authors, except JR and YK, were employees and shareholders of Nektar Therapeutics during this study. JR reports research funding from Amgen, Equillium, and Kite Pharma and consulting income from Aleta Biotherapeutics, Avrobio, Celgene, Falcon Therapeutics, LifeVault Bio, Rheos Medicines, Tal, and TScan Therapeutics. YK has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Background: While often grouped with other noise aversions, fearful behaviour during storms is considered more complex than noise aversion alone. The objective here was to assess the effect of imepitoin for the treatment of storm anxiety in dogs., Methods: In this double-blind, placebo-controlled randomised study, eligible dogs completed a baseline then were randomised to receive either imepitoin (n = 30; 30 mg/kg BID) or placebo (n = 15) for 28 days. During storms, owners rated their dog's intensity for 16 behaviours using a Likert scale. Weekly, owners rated intensity and frequency of these behaviours. Summary scores were compared to baseline and between groups., Results and Conclusions: Imepitoin was significantly superior to placebo in storm logs and weekly surveys for weeks 2 and 4, and in the end-of-study survey. Mild/moderate adverse events were reported in 26 patients (24 active: two placebo); the most frequent adverse event was ataxia. Owners of dogs in the imepitoin group, compared to placebo, were significantly more likely to report that treatment reduced their dogs fear and anxiety during storms (p < 0.001) and other noise events (p < 0.001). Twice daily administration of imepitoin decreased anxiety scores in dogs with storm anxiety. Future work may evaluate optimal dosage regimens., (© 2021 The Authors. Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

E7766 represents a novel class of macrocycle-bridged dinucleotides and is under clinical development for immuno-oncology. In this report, we identified mechanism of systemic clearance E7766 and investigated the hepatobiliary transporters involved in the disposition of E7766 and potential drug interactions of E7766 as a victim of organic anion-transporting polypeptide (OATP) inhibitors. In bile-duct cannulated rats and dogs, E7766 was mainly excreted unchanged in bile (>80%) and to a lesser extent in urine (<20%). Sandwich-cultured human hepatocytes (SCHHs), transfected cells, and vesicles were used to phenotype the hepatobiliary transporters involved in the clearance of E7766. SCHH data showed temperature-dependent uptake of E7766 followed by active biliary secretion. In vitro transport assays using transfected cells and membrane vesicles confirmed that E7766 was a substrate of OATP1B1, OATP1B3, and multidrug resistance-associated protein 2. Phenotyping studies suggested predominant contribution of OATP1B3 over OATP1B1 in the hepatic uptake of E7766. Studies in OATP1B1/1B3 humanized mice showed that plasma exposure of E7766 increased 4.5-fold when coadministered with Rifampicin. Physiologically based pharmacokinetic models built upon two independent bottom-up approaches predicted elevation of E7766 plasma exposure when administered with Rifampicin, a clinical OATP inhibitor. In conclusion, we demonstrate that OATP-mediated hepatic uptake is the major contributor to the clearance of E7766, and inhibition of OATP1B may increase its systemic exposure. Predominant contribution of OATP1B3 in the hepatic uptake of E7766 was observed, suggesting polymorphisms in OATP1B1 would be unlikely to cause variability in the exposure of E7766. SIGNIFICANCE STATEMENT: Understanding the clearance mechanisms of new chemical entities is critical to predicting human pharmacokinetics and drug interactions. A physiologically based pharmacokinetic model that incorporated parameters from mechanistic in vitro and in vivo experiments was used to predict pharmacokinetics and drug interactions of E7766, a novel dinucleotide drug. The findings highlighted here may shed a light on the pharmacokinetic profile and transporter-mediated drug interaction propensity of other dinucleotide drugs., (Copyright © 2021 by The Author(s).)

Background: Hepatitis B is an important agent of liver disease in patients with chronic kidney disease and chronic HBV infection promotes the development of CKD in the adult general population. Patients with CKD have a suboptimal response to various vaccines, and it remains unclear how we boost the immune response of CKD patients to HB vaccine., Study Aims and Design: We performed a narrative review to assess the mechanisms of lower immunogenicity of HBV vaccine in CKD population; multiple approaches to improve the response rate of CKD patients to HBV vaccine have been reported. This is a very important topic for nephrologists who often serve as primary case providers for patients with CKD., Results: The recommended vaccine schedule for CKD patients including those on maintenance dialysis is based on recombinant vaccine, four doses (month 0,1,2, and 6; 40mcg each) by intramuscular route (deltoid muscle). According to RCTs or observational studies, some recombinant vaccines with adjuvants (i.e., HBV-AS02 and HBV-AS04) look promising. HBV-AS04 showed to give better seroprotection rates and durable immune response over extended follow-ups compared with licensed HBV vaccine in CKD patients. The seroprotection rate was 95% (97/102) and 82% (202/248) in pre-dialysis and dialysis patients, respectively, one month after completing vaccine schedule with HBV-AS04. HBV-AS02 was superior to licensed vaccine in terms of seroprotection rate, 76.9% vs. 37.6%., Conclusions: We suggest adjuvanted recombinant (HBV-AS04) vaccine (0,1,2 and 3 months; 20 mcg each dose) and post vaccination testing of anti-HBs antibody after vaccination. Booster doses to patients whose anti-HBs titers fall below the seroprotection level (<10IU/mL) during the follow-up are appropriate. The patho-physiologic mechanisms responsible for the poor immunogenicity of HBV vaccine in CKD patients are under active investigation., (Copyright © 2020 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Hepatitis B is an important agent of liver disease in patients with chronic kidney disease and chronic HBV infection promotes the development of CKD in the adult general population. Patients with CKD have a suboptimal response to various vaccines, and it remains unclear how we boost the immune response of CKD patients to HB vaccine., Study Aims and Design: We performed a narrative review to assess the mechanisms of lower immunogenicity of HBV vaccine in CKD population; multiple approaches to improve the response rate of CKD patients to HBV vaccine have been reported. This is a very important topic for nephrologists who often serve as primary case providers for patients with CKD., Results: The recommended vaccine schedule for CKD patients including those on maintenance dialysis is based on recombinant vaccine, four doses (month 0,1,2, and 6; 40mcg each) by intramuscular route (deltoid muscle). According to RCTs or observational studies, some recombinant vaccines with adjuvants (i.e., HBV-AS02 and HBV-AS04) look promising. HBV-AS04 showed to give better seroprotection rates and durable immune response over extended follow-ups compared with licensed HBV vaccine in CKD patients. The seroprotection rate was 95% (97/102) and 82% (202/248) in pre-dialysis and dialysis patients, respectively, one month after completing vaccine schedule with HBV-AS04. HBV-AS02 was superior to licensed vaccine in terms of seroprotection rate, 76.9% vs. 37.6%., Conclusions: We suggest adjuvanted recombinant (HBV-AS04) vaccine (0,1,2 and 3 months; 20 mcg each dose) and post vaccination testing of anti-HBs antibody after vaccination. Booster doses to patients whose anti-HBs titers fall below the seroprotection level (<10IU/mL) during the follow-up are appropriate. The patho-physiologic mechanisms responsible for the poor immunogenicity of HBV vaccine in CKD patients are under active investigation., (Copyright © 2020 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

The germanium auto-diffusion effects on the inter-atomic distance between the nearest neighbors of the Ga atom in GaP epilayers are investigated using high-resolution X-ray diffraction (HRXRD) and X-ray absorption spectroscopy. The GaP layers grown on Ge (111) are structurally coherent and relaxed but they show the presence of residual strain which is attributed to the auto-diffusion of Ge from the results of secondary ion mass spectrometry and electrochemical capacitance voltage measurements. Subsequently, the inter-atomic distances between the nearest neighbors of Ga atom in GaP are determined from X-ray absorption fine-structure spectra performed at the Ga K-edge. The estimated local bond lengths of Ga with its first and second nearest neighbors show asymmetric variation for the in-plane and out-of-plane direction of GaP/Ge(111). The magnitude and direction of in-plane and out-of-plane microscopic residual strain present in the GaP/Ge are calculated from the difference in bond lengths which explains the presence of macroscopic residual tensile strain estimated from HRXRD. Modified nearest neighbor configurations of Ga in the auto-diffused GaP epilayer are proposed for new possibilities within the GaP/Ge hetero-structure, such as the conversion from indirect to direct band structures and engineering the tensile strain quantum dot structures on (111) surfaces.

Introduction: Within a short period, the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) spread all over the globe and became the first pandemic of the present century. Early diagnostic tools and effective drugs are urgently needed to effectively manage the COVID-19 pandemic. Based on current literature, we provide recent updates on SARS-CoV-2 biology, available diagnostic methods, and therapeutic options for the management of COVID-19 pandemic., Methods: A literature survey was done using Google and PubMed and Web of Science to summarize the current updates on this topic., Results: Current coronavirus diagnostic tests are reverse transcription polymerase chain reaction (RT-PCR), real-time RT-PCR (qRT-PCR), and reverse transcription loop-mediated isothermal amplification (RT-LAMP) which detects the presence of specific genome sequence of virus. Existing antiviral drugs or new therapeutic options such as neutralizing antibody or plasma therapy are mostly used to restrict the virus growth with a limited success., Conclusion: As there is no specific treatment or vaccine available to limit the infection of SARS-CoV-2, we need to rely on the existing way to limit the disease. The first priority to fight COVID-19 is development of early diagnostic tools so that infected persons can be identified and further viral transmission can be blocked. Evaluation of existing drugs or identification of new therapeutic entities becomes the major challenge to deal with the present pandemic., (© 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Background: The aryl hydrocarbon receptor repressor (AHRR), a member of the growing superfamily, is a basic helix-loop-helix/PerAHR nuclear translocator (ARNT)-Sim (bHLH-PAS) protein. AHRR has been proposed to function as a putative new tumor suppressor gene based on studies in multiple types of human cancers. This current study aims to investigate AHHR expression and its prognostic significance in gallbladder cancer., Methods: The study includes 48 gallbladder cancer and 34 chronic cholecystitis cases as controls. The expression level of AHRR was analyzed by using semi-quantitative PCR and immunohistochemical staining. The results were correlated with different clinical parameters., Results: We demonstrate that the expression of AHRR is significantly down-regulated in gallbladder cancer tissue samples as compared to that in chronic cholecystitis tissue samples by reverse transcriptase PCR (RT-PCR) (P = 0.017) and immunohistochemistry analysis (P = 0.002). Interestingly, our RT-PCR data revealed that AHRR mRNA expression is frequently down-regulated (45.8%; 22/48) in cases as compared to 14.7% (5/34) in controls. Similarly, immunohistochemical analysis data show significant down-regulation of AHRR expression in 77.1% (37/48) of gallbladder cancer cases than 44.1% (15/34) in controls (P < 0.017). Reduced mRNA and protein expression is significantly associated with advanced T-stage (P = 0.001), histological differentiation (P = 0.001), and tumors with nodal metastasis (P = 0.001). Decreased expression of AHRR is significantly associated with poor prognosis in gallbladder cancer patients., Conclusion: In conclusion, the present study suggests that low AHRR expression may be critical in gallbladder cancer development. Our data suggests that AHRR may act as a tumor suppressor gene and its expression profile may be useful as a diagnostic marker in gallbladder cancer., Competing Interests: None

Background and Aims: The entire globe is undergoing an unprecedented challenge of COVID-19 which has affected the lifestyle behaviour of individuals. The present review is an attempt to summarize the effect of pandemic COVID-19 on lifestyle behaviour among the Indian population., Methods: A review was carried out to summarize the effect of pandemic COVID-19 on lifestyle behaviour focusing on changes in dietary or eating behaviour, stress, sleep pattern, and level of physical activity among the Indian population. Literature searches were conducted in PubMed and Google Scholar from inception till October 2020 to identify all relevant studies., Results: A total of 11 studies (n = 5957, age group 18-70 years, comprising both genders) consisting of 1 hospital and 10 community based, were included in the present review. A change in lifestyle behaviour was observed due to COVID-19. Psychosocial or any kind of mental stress among the participants was found to be prevalent. Weight gain and decline in physical activity were also observed. Not only sleep quantity but sleep quality was also found to be affected due to COVID-19., Conclusion: The present review indicates the need for lifestyle behaviour programmes via using the platform of E-media and also for the dissemination of health education., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Study Design: Cross-sectional, observational., Objectives: (i) To develop a cross-culturally adapted Hindi translation of the Scoliosis Research Society (SRS)-22r (refined) questionnaire and (ii) validate it in Hindi-speaking Indian patients with adolescent idiopathic scoliosis (AIS)., Background Data: Health-related quality of life (HRQoL)-based questionnaires have superseded objective clinical and radiological measurements as tools to assess the outcome of health-related interventions. The SRS-22r is an extensively validated HRQoL-based questionnaire for AIS patients and has been adapted and translated in other languages., Methodology: A Hindi version of SRS-22r was developed in accordance with standard guidelines for cross-cultural adaptation. The final Hindi version was administered to 108 AIS patients. Subsequently, 58/108 patients answered the Hindi version again after 10-14 days. Another 50/108 bilingual patients answered the original English version after 10-14 days. In addition, 52/108 patients answered a previously validated Hindi version of Short Form (SF)-36 health survey. Content analysis, floor/ceiling effects, internal consistency, test/retest reproducibility and concurrent validity with the English version and the SF-36 questionnaire were determined for the Hindi version of SRS-22r., Results: High ceiling effect was noted for the pain and satisfaction with management domains of Hindi version of SRS-22r. Overall internal consistency was good (Cronbach α = 0.77)-all domains, except the function domain (α = 0.61) had good or excellent internal consistency. The test/retest reliability for all domains was excellent (intraclass coefficient/ICC > 0.80). The concurrent validity with the English version showed an excellent correlation for all domains (ICC > 0.80). Concurrent validity with SF-36 showed good correlation between relevant domains of SRS-22r and SF-36, except for the self-image and satisfaction with management domains of SRS-22r., Conclusion: Based on the results proving its reliability and validity, the adapted Hindi version of SRS-22r can be effectively used in Hindi-speaking, Indian AIS patients., Level of Evidence: 3.

Background: This phase 1 study examined the safety, maximum-tolerated dose (MTD) and antitumour activity of E7449, a novel PARP 1/2 and tankyrase 1/2 inhibitor., Methods: E7449 was orally administered once daily in 28-day cycles to patients with advanced solid tumours (50-800-mg doses). Archival tumour samples from consenting patients were evaluated for the expression of 414 genes in a biomarker panel (2X-121 drug-response predictor [DRP]) found to be predictive of the response to E7449 in cell lines., Results: Forty-one patients were enrolled (13 pancreatic, 5 ovarian, 4 each with breast, lung or colorectal cancer and 11 with other tumour types). The most common grade ≥3 treatment-related adverse event was fatigue (n = 7, 17.1%). Five patients experienced a dose-limiting toxicity (fatigue, n = 4, 800 mg; anaphylaxis, n = 1, 600 mg) for an MTD of 600 mg. E7449 exhibited antitumour activity in solid tumours, including 2 partial responses (PRs), and stable disease (SD) in 13 patients, which was durable (>23 weeks) for 8 patients. In 13 patients, the 2X-121 DRP identified those achieving PR and durable SD. E7449 showed good tolerability, promising antitumour activity and significant concentration-dependent PARP inhibition following 50-800-mg oral dosing., Conclusion: The results support further clinical investigation of E7449 and its associated biomarker 2X-121 DRP., Clinical Trial Registration: www.ClinicalTrials.gov code: NCT01618136.

Connected and Automated Vehicle (CAV) technology, although in the development stage, is quickly expanding throughout the vehicle market. However, full market penetration will most likely require considerable planning as key stakeholders, manufacturers, consumers and governing agencies work together to determine optimal deployment strategies. Specifically, road safety is a critical challenge to the widespread deployment and adoption of this disruptive technology. During the transition period fleets will be composed of a combination of CAVs and conventional vehicles, and therefore it is imperative to investigate the repercussions of CAVs on traffic safety at different penetration rates. Since crash severity and frequency in conjunction reflect traffic safety, this study attempts to investigate the effect of CAVs on both crash severity and frequency through a microsimulation modelling exercise. VISSM microsimulation platform is used to simulate a case study of the M1 Geelong Ring Road network (Princes Freeway) in Victoria, Australia. Network performance is evaluated using performance metrics (Total System Travel Time, Delay) and kinematic variables (Speed, acceleration, jerk rate). Surrogate safety measures (time to collision, post encroachment time, etc.) are examined to inspect the safety in the network. The results indicate that the introduction of CAVs does not achieve the expected decrease in crash severity and rates involving manual vehicles, despite the improvement in network performance, given the demand and the set of parameters used in our operational CAV algorithm are intact. Additionally, the study identifies that the safety benefits of CAVs are not proportional to CAV penetration, and full-scale benefits of CAVs can only be achieved at 100 % CAV penetration. Further, considering network efficiency as a performance metric and total crash rate involving conventional vehicles as a safety metric, a Pareto frontier is extracted, for varying CAV operational behaviour. The results presented in this study provide insights into the impacts of CAVs on traffic safety valuable for insurance companies and other industry participants, enabling safety-related services and more enterprising business models., (Copyright © 2020 Elsevier Ltd. All rights reserved.)