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The ubiquitin-proteasome pathway (UPP) regulates protein stability and normal cellular functions with the help of autocatalytic proteasome complex. Studies have linked aberrant proteasome activity to malignant cells and found that proteasome inhibitors play a significant role as therapeutic drugs for various types of cancer, specifically multiple myeloma and mantle cell lymphoma. Bortezomib, the first FDA-approved proteasome inhibitor for treating different stages of multiple myeloma, acts on cancer cells by inhibiting the 26S proteasome, modulating NF-κB, phosphorylating Bcl-2, upregulating of NOXA, blocking p53 degradation, activating caspase, generating reactive oxygen species (ROS), and inhibiting angiogenesis. However, its efficacy is limited due to side effects such as peripheral neuropathy (PN), thrombotic microangiopathy (TMA), and acute interstitial nephritis (AIN). Therefore, a better understanding of its precise mechanism of action may help mitigate these side effects. In this review, we have discussed the proposed mechanisms of action and off target effects of Bortezomib, along with the prospects of next generation potential proteasome inhibitor drugs in the treatment of cancer., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Triple-negative breast cancer (TNBC) presents a significant challenge for treatment due to its aggressive nature and the lack of effective therapies. This study developed dual inhibitors against cell division cycle 25 (CDC25) and histone deacetylases (HDACs) for TNBC treatment. CDC25 phosphatases are crucial for activating cyclin-dependent kinases (CDKs), the master regulators of cell cycle progression. HDACs regulate various biological processes by deacetylating histone and non-histone proteins, affecting gene expression, chromatin structure, cell differentiation, and proliferation. Dysregulations of HDAC and CDC25 are associated with several human malignancies. We generated a group of dual inhibitors for CDC25 and HDAC by combining the molecular structures of CDC25 (quinoline-5,8-dione) and HDAC (hydroxamic acid or benzamide) pharmacophores. The newly developed compounds were evaluated against various solid-tumor, leukemia, and non-malignant breast epithelial cells. Among the synthesized compounds, 18A emerged as a potent inhibitor, demonstrating significant cytotoxicity against TNBC cells, superior to its effects on other cancer types while sparing non-malignant cells. 18A possessed similar HDAC inhibitory activity as MS-275 and potently suppressed CDC25 activity in vitro and the CDK1 dephosphorylation in cells. Additionally, 18A hindered the progression of S and G 2 /M phases, triggered DNA damage, and induced apoptosis. These findings underscore the potential of 18A as a targeted therapy for TNBC and warrants further preclinical development., (© 2024. The Author(s).)

Disruptor of telomeric silencing 1-like (DOT1L) is a key hub in histone lysine methyltransferase and an attractive therapeutic target for treating hematological malignancies including acute myeloid leukemia (AML). In this study, we report the design and synthesis of a new series of adenosine derivatives as DOT1L inhibitors by accommodating a basic linker piperidine-4-ylmethyl motif to respective aryl-urea/benzimidazole scaffolds. The anti-DOT1L enzyme activity analysis demonstrated that compounds 8, 12, and 13 strongly suppressed DOT1L activity with IC 50 values ranging from 0.125 to 0.408 µM among all the synthetics, and the structure-activity relationships were summarized. Moreover, compound 12 possessed relatively potent DOT1L inhibitory activity by significantly reduced histone H3 di-methylation at lysine 79 (H3K79me2) level in cells. Subsequently, all the synthetics were screened against various leukemia cell lines, indicating the DOT1L active adenosine derivatives exhibited low to moderate while compound 15 showed strong cellular inhibition despite its unsuccessful DOT1L inhibition. Therefore, acknowledging the distinctive potency of compound 15 against five different leukemia cell lines, including MLL-r (MV4-11) and non-MLL-r cell lines (HL-60, HH, K562, and KG-1), with IC 50 values in the 0.45 ∼ 1.66 μM range and its mode of action was explored. Furthermore, compound 15 hindered histone acetylation, induced remarkable DNA damage, and triggered apoptosis. Importantly, normal T lymphocytes only showed moderate response to compound 15. These findings provide a basis for future studies on its potential application against AML., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jing-Ping Liou reports financial support was provided by the National Science and Technology Council of Taiwan. If there are other authors, they 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 Inc. All rights reserved.)

Hepatic edema is caused by decreased hepatic protein synthesis, a consequence of decompensated liver cirrhosis. Fluid accumulation occurs when there is an increase in hydrostatic pressure in the hepatic sinusoids and splanchnic capillaries, as well as low albumin. The first-line treatment for cirrhosis-related ascites is an aldosterone antagonist (spironolactone); however, in severe and recurring ascites, a combination of aldosterone antagonists and loop diuretics (torsemide, furosemide, and bumetanide) is preferable. Torsemide outperformed furosemide in terms of natriuretic and diuretic effects at an equivalent dose. Pharmacological features of torsemide, such as lesser hypokalemia effect, longer duration of action, higher bioavailability, and extended half-life, make it a better alternative than furosemide. In clinical studies, it is considered a safer and more acceptable choice with fewer complications., (© Journal of the Association of Physicians of India 2024.)

Ruminococcus gnavus is a mucolytic commensal bacterium whose increased gut colonization has been associated with chronic inflammatory and metabolic diseases in humans. Whether R. gnavus metabolites can modulate host intestinal physiology remains largely understudied. We performed untargeted metabolomic and bulk RNA-seq analyses using R. gnavus monocolonization in germ-free mice. Based on transcriptome-metabolome correlations, we tested the impact of specific arginine metabolites on intestinal epithelial production of nitric oxide (NO) and examined the effect of NO on the growth of various strains of R. gnavus in vitro and in nitric oxide synthase 2 (Nos2)-deficient mice. R. gnavus produces specific arginine, tryptophan, and tyrosine metabolites, some of which are regulated by the environmental richness of sialic acid and mucin. R. gnavus colonization promotes expression of amino acid transporters and enzymes involved in metabolic flux of arginine and associated metabolites into NO. R. gnavus induced elevated levels of NOS2, while Nos2 ablation resulted in R. gnavus expansion in vivo. The growth of various R. gnavus strains can be inhibited by NO. Specific R. gnavus metabolites modulate intestinal epithelial cell NOS2 abundance and reduce epithelial barrier function at higher concentrations. Intestinal colonization and interaction with R. gnavus are partially regulated by an arginine-NO metabolic pathway, whereby a balanced control by the gut epithelium may restrain R. gnavus growth in healthy individuals. Disruption in this arginine metabolic regulation will contribute to the expansion and blooming of R. gnavus., Competing Interests: Conflict of interests The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There are limited studies examining local control (LC) and overall survival (OS) following stereotactic ablative radiation therapy (SABR) for adolescent and young adult (AYA) populations/histologies with local recurrences or metastatic disease., Methods: The RSSearch® Patient Registry, an international SABR registry, was evaluated for AYA patients treated with SABR. AYA patients with adult histologies/primaries were excluded. Kaplan-Meier analyses were employed to characterize LC and OS following SABR. Potential prognostic factors were assessed with log-rank tests for initial univariate analysis (UVA). For multivariate analyses (MVA), a Cox proportional hazards multivariate model was utilized., Results: A total of 19 AYA patients with 39 lesions treated with SABR were identified and included in the analysis. Four lesions (10.3%) were treated with SABR for primary tumor recurrence and 35 lesions were treated for metastatic disease. The median patient age was 34 years (range: 16-39 years). Common lesion locations included lung (11 lesions; 28.2%), non-spinal bone (nine lesions; 23.1%), and spine (six lesions; 15.4%). The median biological effective dose (BED 10 ) was 61.5 Gy (range: 26.4-180). One-year LC and OS following SABR were 77.7% (95% CI: 58.5-88.7) and 72.7% (95% CI: 46.3-87.6), respectively. On UVA, BED 10 ≥ 60 Gy was associated with superior one-year LC (94.4% vs. 47.6%; p<0.0001) as were sarcoma primaries (two-year LC: 92.3% vs. 42.2%;p = 0.0002). Central nervous system (CNS) primaries had significantly poorer one-year LC (20% vs 87.5%; p<0.0001) as well as spinal metastases (33.3% vs. 87.0%; p<0.0001). On MVA, BED 10 < 60 Gy was associated with inferior LC (hazard ratio (HR) = 5.51;p = 0.01) with sarcoma primaries associated with superior LC (HR = 0.04;p = 0.008)., Conclusion: SABR with BED 10 ≥ 60 Gy resulted in durable LC for AYA patients, particularly those with sarcoma primaries, though poor outcomes were noted in metastatic CNS malignancies., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. IRB at St. Mary's Medical Center issued approval 117716. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Singh et al.)

Head and Neck Squamous Cell Carcinoma (HNSCC) comprises a diverse group of tumors with variable treatment response and prognosis. The tumor microenvironment (TME), which includes microbiome and immune cells, can impact outcomes. Here, we sought to relate the presence of specific microbes, gene expression, and tumor immune infiltration using tumor transcriptomics from The Cancer Genome Atlas (TCGA) and associate these with overall survival (OS). RNA sequencing (RNAseq) from HNSCC tumors in TCGA was processed through the exogenous sequences in tumors and immune cells (exotic) pipeline to identify and quantify low-abundance microbes. The detection of the Papillomaviridae family of viruses assessed HPV status. All statistical analyses were performed using R. A total of 499 RNAseq samples from TCGA were analyzed. HPV was detected in 111 samples (22%), most commonly Alphapapillomavirus 9 (90.1%). The presence of Alphapapillomavirus 9 was associated with improved OS [HR = 0.60 (95%CI: 0.40-0.89, p  = .01)]. Among other microbes, Yersinia pseudotuberculosis was associated with the worst survival (HR = 3.88; p  = .008), while Pseudomonas viridiflava had the best survival (HR = 0.05; p  = .036). Microbial species found more abundant in HPV- tumors included several gram-negative anaerobes. HPV- tumors had a significantly higher abundance of M0 ( p  < .001) and M2 macrophages ( p  = .035), while HPV+ tumors had more T regulatory cells ( p  < .001) and CD8+ T-cells ( p  < .001). We identified microbes in HNSCC tumor samples significantly associated with survival. A greater abundance of certain anaerobic microbes was seen in HPV tumors and pro-tumorigenic macrophages. These findings suggest that TME can be used to predict patient outcomes and may help identify mechanisms of resistance to systemic therapies.

Purpose: Theranostic approaches combining prostate-specific membrane antigen (PSMA)-PET/CT or PET/MRI with PSMA-targeted radionuclide therapy have improved clinical outcomes in patients with prostate cancer (PCa) especially metastatic castrate resistant prostate cancer. Dural metastases in PCa are rare but can pose a diagnostic challenge, as meningiomas, a more common dural based lesions have been shown to express PSMA. The aim of this study is to compare PSMA PET parameters between brain lesions classified as dural metastases and meningiomas in prostate cancer patients., Methods: A retrospective analysis of PSMA PET/CT scans in patients with PCa and intracranial lesions was conducted. Brain lesions were categorized as dural metastases or meningiomas based on MRI characteristics, longitudinal follow-up, and histopathological characteristics. Standardized uptake values (SUVmax) of each brain lesion were measured, along with SUV ratio referencing parotid gland (SUVR). SUVs between lesions classified as metastases and meningiomas, respectively, were compared using Mann-Whitney-test. Diagnostic accuracy was evaluated using ROC analysis., Results: 26 male patients (median age: 76.5 years, range: 59-96 years) met inclusion criteria. A total of 44 lesions (7 meningiomas and 37 metastases) were analyzed. Median SUVmax and SUVR were significantly lower in meningiomas compared to metastases (SUVmax: 2.7 vs. 11.5, p = 0.001; SUVR: 0.26 vs. 1.05, p < 0.001). ROC analysis demonstrated AUC 0.903; the optimal cut-off value for SUVR was 0.81 with 81.1 % sensitivity and 100 % specificity., Conclusion: PSMA PET has the potential to differentiate meningiomas from dural-based metastases in patients with PCa, which can optimize clinical management and thus improve patient outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: 1. Investigator initiated trial grant, funding paid to institution (Weill Cornell Medicine) from Novartis Pharmaceuticals. 2. Investigator initiated trial grant, funding paid to institution (Weill Cornell Medicine) from GE Healthcare. 3. Investigator initiated trial grant, funding paid to institution (Weill Cornell Medicine) from Curium Pharma. Other authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The gastrointestinal tract is continuously exposed to foreign antigens in food and commensal microbes with potential to induce adaptive immune responses. Peripherally induced T regulatory (pTreg) cells are essential for mitigating inflammatory responses to these agents 1-4 . While RORγt + antigen-presenting cells (RORγt-APCs) were shown to program gut microbiota-specific pTregs 5-7 , understanding of their characteristics remains incomplete, and the APC subset responsible for food tolerance has remained elusive. Here, we demonstrate that RORγt-APCs are similarly required for differentiation of food antigen-specific pTregs and establishment of oral tolerance. The ability of these cells to direct both food and microbiota-specific pTreg cell differentiation is contingent on expression of RORγt and on a unique cis-regulatory element within the Rorc gene locus ( Rorc(t) +7kb). Absent this +7kb element, there was a notable increase in food antigen-specific T helper 2 (Th2) cells in lieu of pTregs, leading to compromised tolerance in a mouse asthma model. By employing single-cell analyses across these models, as well as freshly resected mesenteric lymph nodes from a human organ donor, we identified a rare subset of evolutionarily conserved APCs that are dependent on RORγt, uniquely express the Prdm16 transcription factor, and are endowed with essential mediators for inducing pTreg cell differentiation. Our findings suggest that a better understanding of how RORγt-APCs develop and how they regulate T cell responses to food and microbial antigens could offer new insights into developing therapeutic strategies for autoimmune and allergic diseases as well as organ transplant tolerance.

There are limited data available on clinical outcomes after stereotactic body radiation therapy (SBRT) for nonspinal bone metastases. We performed a systematic review and meta-analysis to characterize local control (LC), overall survival (OS), pain response rates, and toxicity after SBRT. The primary outcomes were 1-year LC, incidence of acute and late grade 3 to 5 toxicities, and overall pain response rate at 3 months. The secondary outcome was 1-year OS. The Newcastle-Ottawa scale was used for assessment of study bias, with a median score of 5 for included studies (range, 4-8). Weighted random-effects meta-analyses were conducted to estimate effect sizes. We identified 528 patients with 597 nonspinal bone lesions in 9 studies (1 prospective study and 8 retrospective observational studies) treated with SBRT. The estimated 1-year LC rate was 94.6% (95% CI, 87.0%-99.0%). The estimated 3-month combined partial and complete pain response rate after SBRT was 87.7% (95% CI, 55.1%-100.0%). The estimated combined acute and late grade 3 to 5 toxicity rate was 0.5% (95% CI, 0%-5.0%), with an estimated pathologic fracture rate of 3.1% (95% CI, 0.2%-9.1%). The estimated 1-year OS rate was 71.0% (95% CI, 51.7%-87.0%). SBRT results in excellent LC and palliation of symptoms with minimal related toxicity. Prospective investigations are warranted to further characterize long-term outcomes of SBRT for patients with nonspinal bone metastases., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Traditionally, renal cell carcinoma (RCC) was considered a radioresistant tumor, thereby limiting definitive radiation therapy management options. However, several recent studies have demonstrated that stereotactic body radiation therapy (SBRT) can achieve high rates of local control for the treatment of primary RCC. In the setting of expanding use of SBRT for primary RCC, it is crucial to provide guidance on practical considerations such as patient selection, fractionation, target delineation, and response assessment. This is particularly important in challenging scenarios where a paucity of evidence exists, such as in patients with a solitary kidney, bulky tumors, or tumor thrombus. The Radiosurgery Society endorses this case-based guide to provide a practical framework for delivering SBRT to primary RCC, exemplified by 3 cases. This article explores topics of tumor size and dose fractionation, impact on renal function and treatment in the setting of a solitary kidney, and radiation's role in the management of inferior vena cava tumor thrombus. Additionally, we review existing evidence and expert opinion on target delineation, advanced techniques such as magnetic resonance imaging guided SBRT, and SBRT response assessment., Competing Interests: Disclosures Rohann J. M. Correa reports research funding from Droplet Biosciences. Alan Dal Pra reports research support from Veracyte. Tugce Kutuk reports a travel stipend from GammaTile. Simon S. Lo reports research support from Elekta AB and the Kuni Foundation, travel support from the Japanese Society for Radiation Oncology, and leadership roles as a member of the ICON Gamma Knife Expert Group, American College of Radiology, and the Radiosurgery Society. Alexander Louie reports honoraria from AstraZeneca and serves on an AstraZeneca advisory board. Sarah P. Psutka reports grants from the National Institutes on Aging, Bladder Cancer Advisory Network, and PRIME Education, as well as serving on advisory or data safety monitoring boards for Janssen, Merck, Immunity Bio, and CG Oncology, and leadership roles for European Urology journal, Bladder Cancer journal, and American Urological Association. Shankar Siva reports research funding from Merck-Sharp-Dohme, Bayer Pharmaceuticals, and Varian Medical Systems. Karin A. Skalina reports a leadership role with the Radiosurgical Society. Anand Swaminath reports honoraria from AstraZeneca and Bristol Myers Squibb, as well as serving on an AstraZeneca advisory board. Chad Tang reports consulting fees from Telix Pharmaceutical, as well as advisory board service for Siemens Healthineer, Lantheus Pharmaceutical, and Bayer, as well as clinical trial research support from Merck and Myriad. Rituraj Upadhyay reports payment or honoraria and travel support from Varian Medical Systems. Nicholas G. Zaorsky reports support from the American Cancer Society – Tri State CEOs Against Cancer Clinician Scientist Development Grant, CSDG-20-013-01-CCE and the Department of Defense, as well as remuneration from the American College of Radiation Oncology for chart review and accreditation of radiation oncology facilities nationally and remuneration from Spring Nature for the textbook Absolute Clinical Radiation Oncology Review; he was supported by the National Institutes of Health Grant LRP 1 L30 CA231572-01. All other authors report no disclosures., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Handwritten signatures in biometric authentication leverage unique individual characteristics for identification, offering high specificity through dynamic and static properties. However, this modality faces significant challenges from sophisticated forgery attempts, underscoring the need for enhanced security measures in common applications. To address forgery in signature-based biometric systems, integrating a forgery-resistant modality, namely, noninvasive electroencephalography (EEG), which captures unique brain activity patterns, can significantly enhance system robustness by leveraging multimodality's strengths. By combining EEG, a physiological modality, with handwritten signatures, a behavioral modality, our approach capitalizes on the strengths of both, significantly fortifying the robustness of biometric systems through this multimodal integration. In addition, EEG's resistance to replication offers a high-security level, making it a robust addition to user identification and verification. This study presents a new multimodal SignEEG v1.0 dataset based on EEG and hand-drawn signatures from 70 subjects. EEG signals and hand-drawn signatures have been collected with Emotiv Insight and Wacom One sensors, respectively. The multimodal data consists of three paradigms based on mental, & motor imagery, and physical execution: i) thinking of the signature's image, (ii) drawing the signature mentally, and (iii) drawing a signature physically. Extensive experiments have been conducted to establish a baseline with machine learning classifiers. The results demonstrate that multimodality in biometric systems significantly enhances robustness, achieving high reliability even with limited sample sizes. We release the raw, pre-processed data and easy-to-follow implementation details., (© 2024. The Author(s).)

The management of edema requires a systematic approach to screening, diagnosis, and treatment, with an essential initial assessment to differentiate between generalized and localized edema. The Association of Physicians of India (API) aimed to develop the first Indian Edema Consensus (Edema India), offering tailored recommendations for screening, diagnosing, and managing edema based on the insights from the expert panel. The panel suggested when evaluating edema symptoms, important factors to consider include the patient's current illness, medical history, risk factors, family history, and medications. Key diagnostic investigations for edema include complete blood count, cardiovascular imaging and markers, deep vein thrombosis (DVT) assessment, along with renal, hepatic, and thyroid function tests. Edema management involves a combination of pharmacologic and nonpharmacologic interventions, including limb elevation, physiotherapy, compression therapy, fluid removal, diuretics (loop diuretics: first-line therapy), and a sodium-restricted diet. The panel believed that educating patients could foster a preventive mindset, helping to prevent the worsening of edema., (© Journal of the Association of Physicians of India 2024.)

Background and Objectives: Pleomorphic xanthoastrocytoma (PXA) is a rare low-grade glial tumor primarily affecting young individuals. Surgery is the primary treatment option; however, managing residual/recurrent tumors remains uncertain. This international multi-institutional study retrospectively assessed the use of stereotactic radiosurgery (SRS) for PXA., Methods: A total of 36 PXA patients (53 tumors) treated at 11 institutions between 1996 and 2023 were analyzed. Data included demographics, clinical variables, SRS parameters, tumor control, and clinical outcomes. Kaplan-Meier estimates summarized the local control (LC), progression-free survival, and overall survival (OS). Secondary end points addressed adverse radiation effects and the risk of malignant transformation. Cox regression analysis was used., Results: A total of 38 tumors were grade 2, and 15 tumors were grade 3. Nine patients underwent initial gross total resection, and 10 received adjuvant therapy. The main reason for SRS was residual tumors (41.5%). The median follow-up was 34 months (range, 2-324 months). LC was achieved in 77.4% of tumors, with 6-month, 1-year, and 2-year LC estimates at 86.7%, 82.3%, and 77.8%, respectively. Younger age at SRS (hazard ratios [HR] 3.164), absence of peritumoral edema (HR 4.685), and higher marginal dose (HR 6.190) were significantly associated with better LC. OS estimates at 1, 2, and 5 years were 86%, 74%, and 49.3%, respectively, with a median OS of 44 months. Four patients died due to disease progression. Radiological adverse radiation effects included edema (n = 8) and hemorrhagic change (n = 1). One grade 3 PXA transformed into glioblastoma 13 months after SRS., Conclusion: SRS offers promising outcomes for PXA management, providing effective LC, reasonable progression-free survival, and minimal adverse events., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Metastatic renal cell carcinoma (mRCC) is a heterogenous disease with a variable clinical course. While therapies for treatment of this condition have progressed, they are not without toxicity. In some patients, active surveillance (AS) of this disease is increasingly considered to delay its toxicity. This article seeks to review the literature and discuss management of metastatic renal cell carcinoma, specifically regarding upfront AS, the role of radiation therapy in delaying systemic therapy, and surveillance after initial treatment with systemic therapy. Median time on AS prior to initiation of systemic therapy ranged from 14 to 60 months across studies. AS is appropriate to offer in favorable or intermediate risk, asymptomatic, and systemic treatment naïve patients with mRCC., (Copyright: Dason S., et al.)

This paper investigates the dynamics of a tritrophic food chain model incorporating an Allee effect, sexually reproductive generalist top predators, and Holling type IV and Beddington-DeAngelis functional responses for interactions across different trophic levels. Analytically, we explore the feasible equilibria, their local stability, and various bifurcations, including Hopf, saddle-node, transcritical, and Bogdanov-Takens bifurcations. Numerical findings suggest that higher Allee intensity in prey growth leads to the inability of species coexistence, resulting in a decline in species density. Likewise, a lower reproduction rate and a higher strength of intraspecific competition among top predators also prevent the coexistence of species. Conversely, a rapid increase in the reproduction rate and a decrease in the strength of intraspecific competition among top predators enhance the densities of prey and top predators while decreasing intermediate predator density. We also reveal the presence of bistability and tristability phenomena within the system. Furthermore, we extend our autonomous model to its nonautonomous counterpart by introducing seasonally perturbed parameters. Numerical analysis of the nonautonomous model reveals that higher seasonal strength in the reproduction rate and intraspecific competition of top predators induce chaotic behavior, which is also confirmed by the maximum Lyapunov exponent. Additionally, we observe that seasonality may lead to the extinction of species from the ecosystem. Factors such as the Allee effect and growth rate of prey can cause periodicity in population densities. Understanding these trends is critical for controlling changes in population density within the ecosystem. Ecologists, environmentalists, and policymakers stand to benefit significantly from the invaluable insights garnered from this study. Specifically, our findings offer pivotal guidance for shaping future strategies aimed at safeguarding biodiversity and maintaining ecological stability amidst changing environmental conditions. By contributing to the existing body of knowledge, our study advances the field of ecological science, enhancing the comprehension of predator-prey dynamics across diverse ecological conditions., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Around the world, the market for plant-derived beverages is one of the fastest-expanding segments in the functional and specialty beverage areas of newer food product development. Consumers are increasingly likely to choose alternatives to bovine beverages due to factors including lactose intolerance, hypercholesterolemia prevalence, allergies to bovine beverages, and preference for vegan diets that contain functionally active ingredients with health-promoting characteristics. Due to health, ecological, and ethical concerns, many customers are interested in reducing their usage of animal products like bovine milk. A variety of plant-based beverage substitutes are being created by the food sector as a result. To create viable alternatives, it is first necessary to provide an overview of the chemical composition, structure, features, and nutritional attributes of ordinary bovine milk. Sensory acceptability in the case of substitutes for beverages made from legumes is a significant barrier to their widespread acceptance, and thus saliva acts as a sophisticated fluid that serves a variety of purposes in the cavity of the mouth. Designing and producing next-generation plant-based beverages that mimic the physicochemical and functional qualities of conventional bovine-based beverages is gaining popularity, and many of these products can be thought of as colloidal materials that contain the particles or polymers that give them their unique qualities NG-PB foods can have a wide range of rheological qualities, such as fluids with low viscosity (such as plant-based beverages), high-viscosity liquids (like creams), soft liquids (like yogurt), as well as hard solids (such as some cheeses)., (© 2024 Wiley Periodicals LLC.)

Background: Pediatric patients with metastatic and/or recurrent solid tumors have poor survival outcomes despite standard-of-care systemic therapy. Stereotactic ablative radiation therapy (SABR) may improve tumor control. We report the outcomes with the use of SABR in our pediatric solid tumor population., Methods: This was a single-institutional study in patients < 30 years treated with SABR. The primary endpoint was local control (LC), while the secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. The survival analysis was performed using Kaplan-Meier estimates in R v4.2.3., Results: In total, 48 patients receiving 135 SABR courses were included. The median age was 15.6 years (interquartile range, IQR 14-23 y) and the median follow-up was 18.1 months (IQR: 7.7-29.1). The median SABR dose was 30 Gy (IQR 25-35 Gy). The most common primary histologies were Ewing sarcoma (25%), rhabdomyosarcoma (17%), osteosarcoma (13%), and central nervous system (CNS) gliomas (13%). Furthermore, 57% of patients had oligometastatic disease (≤5 lesions) at the time of SABR. The one-year LC, PFS, and OS rates were 94%, 22%, and 70%, respectively. No grade 4 or higher toxicities were observed, while the rates of any grade 1, 2, and 3 toxicities were 11.8%, 3.7%, and 4.4%, respectively. Patients with oligometastatic disease, lung, or brain metastases and those who underwent surgery for a metastatic site had a significantly longer PFS. LC at 1-year was significantly higher for patients with a sarcoma histology (95.7% vs. 86.5%, p = 0.01) and for those who received a biological equivalent dose (BED10) > 48 Gy (100% vs. 91.2%, p = 0.001)., Conclusions: SABR is well tolerated in pediatric patients with 1-year local failure and OS rates of <10% and 70%, respectively. Future studies evaluating SABR in combination with systemic therapy are needed to address progression outside of the irradiated field.

Food antigens elicit immune tolerance through the action of regulatory T cells (Tregs) in the intestine. Although antigens that trigger common food allergies are known, the epitopes that mediate tolerance to most foods have not been described. Here, we identified murine T cell receptors specific for maize, wheat, and soy, and used expression cloning to de-orphan their cognate epitopes. All of the epitopes derive from seed storage proteins that are resistant to degradation and abundant in the edible portion of the plant. Multiple unrelated T cell clones were specific for an epitope at the C-terminus of 19 kDa alpha-zein, a protein from maize kernel. An MHC tetramer loaded with this antigen revealed that zein-specific T cells are predominantly Tregs localized to the intestine. These cells, which develop concurrently with weaning, constitute up to 2% of the peripheral Treg pool. Bulk and single-cell RNA sequencing revealed that these cells express higher levels of immunosuppressive markers and chemokines compared to other Tregs. These data suggest that immune tolerance to plant-derived foods is focused on a specific class of antigens with common features, and they reveal the functional properties of naturally occurring food-specific Tregs., Competing Interests: Competing interests: D.R.L. consults and has equity interest in Vedanta, Immunai, Imidomics, Sonoma Biotherapeutics and Pfizer Pharmaceuticals. M.A.F. is a co-founder of Kelonia and Revolution Medicines, a member of the scientific advisory boards of the Chan Zuckerberg Initiative, Stand Up to Cancer, NGM Biopharmaceuticals, and TCG Labs/Soleil Labs, and an innovation partner at The Column Group. The remaining authors have no conflict of interest.

Background: Depression is a prevalent mental health condition worldwide but there is limited data on its presentation and associated symptoms in primary care settings in low- and middle-income countries like Nepal. This study aims to assess the prevalence of depression, its hallmark and other associated symptoms that meet the Diagnostic and Statistical Manual (DSM-5) criteria in primary healthcare facilities in Nepal. The collected information will be used to determine the content of a mobile app-based clinical guidelines for better detection and management of depression in primary care., Methods: A total of 1,897 adult patients aged 18-91 (63.1% women) attending ten primary healthcare facilities in Jhapa, a district in eastern Nepal, were recruited for the study between August 2, 2021, and March 25, 2022. Trained research assistants conducted face-to-face interviews in private spaces before the consultation with healthcare providers. Depression symptoms, including hallmark symptoms, was assessed using the validated Nepali version of the Patient Health Questionnaire (PHQ-9)., Results: One in seven (14.5%) individuals attending primary health care facilities in Jhapa met the threshold for depression based on a validated cut-off score ( > = 10) on the PHQ-9. The most commonly reported depressive symptoms were loss of energy and sleep difficulties. Approximately 25.4% of women and 18.9% of men endorsed at least one of the two hallmark symptoms on the PHQ-9. Using a DSM-5 algorithm (at least one hallmark symptom and five or more total symptoms) to score the PHQ-9, 6.3% of women and 4.3% of men met the criteria for depression. The intra-class correlation coefficient for PHQ-9 total scores by health facility as the unit of clustering was 0.01 (95% confidence interval, 0.00-0.04)., Conclusion: Depression symptoms are common among people attending primary healthcare facilities in Nepal. However, the most common symptoms are not the two hallmark criteria. Use of total scores on a screening tool such as the PHQ-9 risks overestimating the prevalence and generating false positive diagnoses. Compared to using cut off scores on screening tools, training health workers to first screen for hallmark criteria may increase the accuracy of identification and lead to better allocation of treatment resources., (© 2024. The Author(s).)

Hydrated shale formations often lead to severe drilling problems and may lead to wellbore instability. These instabilities can result in issues such as bit balling, borehole collapse, formation damage, stuck pipe, and low drilling rates. Keeping these fundamental issues with drilling in shale formation in mind, this study is aimed at designing a water-based drilling fluid system for effective shale inhibition, ensuring enhanced wellbore stability and drilling efficiency. The designed mud system comprises a typical base fluid along with newly synthesized chitosan derivative chitosan- N -(2-hydroxyl)-propyl trimethylammonium chloride (HACC) as an additive. This additive was found to be soluble in water and conducive for shale inhibition. The derived product was characterized by field emission scanning electron microscopy, thermogravimetric analysis, and Fourier-transform infrared spectroscopy (FTIR). Various drilling fluid tests, including filtration and rheological experiments, were conducted to evaluate its proficiency as a drilling mud additive. The results showed improvement in rheological and filtration properties after hot rolling at 100 °C in comparison to a conventional shale inhibitor, polyethylenimine. As we increase the concentration of synthesized chitosan derivative from 0.3 to 1.5 w/v%, the filtration loss is reduced from 40% to 65% as compared to the base fluids. Shale recovery tests were also conducted using shale samples from an Indian field to assess its viability for field application. The addition of 0.3 to 1.5 w/v% chitosan derivative resulted in high shale recovery above 88% to 96% at 100 °C compared to polyethylenimine, which showed a change in recovery from 62% to 73%. HACC intercalates into clay platelets, reducing the interlayer spacing between particles and preventing clay from hydrating and swelling. This mechanism of inhibition is evaluated by X-ray diffraction, FTIR, and zeta potential analysis. This bolsters the hypothesis of using the synthesized chitosan derivative as a shale inhibitor., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Purpose: A dedicated magnetic resonance imaging simulation (MRsim) for radiation treatment (RT) planning in patients with high-grade glioma (HGG) can detect early radiologic changes, including tumor progression after surgery and before standard of care chemoradiation. This study aimed to determine the effect of using postoperative magnetic resonance imaging (MRI) versus MRsim as the baseline for response assessment and reporting pseudoprogression on follow-up imaging at 1 month (FU1) after chemoradiation., Methods and Materials: Histologically confirmed patients with HGG were planned for 6 weeks of RT in a prospective study for adaptive RT planning. All patients underwent postoperative MRI, MRsim, and follow-up MRI scans every 2 to 3 months. Tumor response was assessed by 3 independent blinded reviewers using Response Assessment in Neuro-Oncology criteria when baseline was either postoperative MRI or MRsim. Interobserver agreement was calculated using Light's kappa., Results: Thirty patients (median age, 60.5 years; IQR, 54.5-66.3) were included. Median interval between surgery and RT was 34 days (IQR, 27-41). Response assessment at FU1 differed in 17 patients (57%) when the baseline was postoperative MRI versus MRsim, including true progression versus partial response or stable disease in 11 (37%) and stable disease versus partial response in 6 (20%) patients. True progression was reported in 19 patients (63.3%) on FU1 when the baseline was postoperative MRI versus 8 patients (26.7%) when the baseline was MRsim (P = .004). Pseudoprogression was observed at FU1 in 12 (40%) versus 4 (13%) patients, when the baseline was postoperative MRI versus MRsim (P = .019). Interobserver agreement between observers was moderate (κ = 0.579; P < .001)., Conclusions: Our study demonstrates the value of acquiring an updated MR closer to RT in patients with HGG to improve response assessment, and accuracy in evaluation of pseudoprogression even at the early time point of first follow-up after RT. Earlier identification of patients with true progression would enable more timely salvage treatments including potential clinical trial enrollment to improve patient outcomes., (Copyright © 2024. Published by Elsevier Inc.)

Background: Current standard of care treatment for patients with ≥15 brain metastases (BM) is whole brain radiation therapy (WBRT), despite poor neurocognitive outcomes. We analyzed our institutional experience of treating these patients with stereotactic radiosurgery (SRS), with the aim of evaluating safety, cognitive outcomes, and survival metrics., Methods: Patients who received SRS for ≥15 BMs in 1 to 5 fractions from 2014 to 2022 were included. Cognitive outcomes were objectively evaluated using serial Patient-Reported Outcome Measurement Information System (PROMIS) scores. The Kaplan-Meier method was used for survival analysis and log-rank test for intergroup comparisons., Results: Overall, 118 patients underwent 124 courses of LINAC-based SRS. The median number of lesions treated per course was 20 (range, 15-94). Most patients received fractionated SRS to a dose of 24 Gy in 3 fractions (81.5%). At the time of SRS, 19.4% patients had received prior WBRT, and 24.2% had received prior SRS. The rate of any grade radiation necrosis (RN) and grade ≥3 RN were 15.3% and 3.2%, respectively. When evaluating longitudinal PROMIS score trends, 25 of 31 patients had a stable/improved PROMIS score. Patients who did not receive prior brain RT had a longer median survival (7.4 months vs 4.6 months, P = .034). The 12m local control was 97.6%, and the cumulative incidence of distant intracranial failure, with death as a competing event, was 46% (95% CI, 36%, 55%). One year freedom from neurologic death, leptomeningeal disease, and salvage WBRT were 89%, 94.6%, and 84%, respectively., Conclusion: We present here one of the largest studies evaluating SRS for patients with ≥15 BMs. SRS was safe, had favorable cognitive outcomes, and had comparable survival outcomes to contemporary studies evaluating WBRT in this population. Treatment-naïve patients had a median survival of >6 months, long enough to benefit from cognitive sparing with SRS. Our study supports randomized studies comparing SRS and hippocampal avoidance WBRT approaches for these patients., (© 2024 Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.)

Background and Objectives: End-stage renal disease (ESRD) rates are on the rise globally, including in India. However, the affordability of dialysis treatment remains a significant challenge for many, with costs varying across different regions. Although cost-effective, kidney transplantation faces challenges like a surgeon shortage, lack of infrastructure, and lack of logistic support. The study examines Indian laparoscopic nephrectomy outcomes and their benefits for donor recovery. It covers kidney donor procedural details, demographics, preoperative health evaluations, complications, and one-month follow-up., Methods: Ethical approval was obtained, and the study involved 102 cases at the Indira Gandhi Institute of Medical Science, Patna, Bihar, India, from 2019 to 2023. Detailed preoperative assessments, postoperative complications, and one-month follow-up analyses were conducted. Statistical analysis employed SPSS version 17 (IBM Corp., Armonk, NY)., Results: The results revealed an average surgery time of 152.3 min, blood loss of 205 ± 42 ml, and a hospital stay of 4.6 ± 2.2 days. The study found a female predominance (80.39%), with a mean donor age of 35.9 ± 5.2 years. Preoperative assessments showed robust patient health, with glomerular filtration rate (GFR) exceeding the expected threshold and normal urea levels, creatinine, electrolytes, liver enzymes, bilirubin, albumin, and total protein. Post-nephrectomy complications were reported, with females experiencing more difficulties than males., Conclusion: This study underscores the efficiency and safety of laparoscopic nephrectomy in the Indian context, providing valuable insights into donor demographics, preoperative health assessments, complications, and postoperative outcomes. The findings contribute to understanding laparoscopic nephrectomy outcomes and associated risk factors despite certain limitations., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Mahmood et al.)

Background: Urethroplasty using a buccal mucosa graft (BMG) and a preputial skin flap (PSF) are two common techniques used for the treatment of anterior urethral stricture. The present study compared the efficacy of these two techniques on the basis of success rate, preservation of sexual function, and complications., Materials and Methods: This prospective, randomized, interventional study was conducted on adult male patients diagnosed with non-obliterative anterior urethral strictures of length >2 cm from August 2021 to December 2022. Pre-operative and post-operative work-up done included assessment of the International Prostate Symptom Score (IPSS), Quality of Life (QOL), International Index of Erectile Function (IIEF) Score, Male Sexual Health Questionnaire for Ejaculatory Dysfunction (MSHQ-EJD), Bother score, Urethral Stricture Surgery-Patient-Related Outcome Measure (USS-PROM), and peak urinary flow rate (Qmax) for each patient. Post-operative values for each score were compared with pre-operative values., Results: Out of 31 patients, 16 underwent BMG urethroplasty, and 15 underwent PSF urethroplasty. The most common cause of stricture in both groups was idiopathic (35.5% and 53.3%). A statistically significant increase in IIEF score was observed in the BMG group in comparison to the PSF group (P<0.0001). The mean IPPS score in USS-PROM has shown a significant drop in BMG (19.6 vs. 17.3; P = 0.020). Hemoglobin drop was significantly higher in PSF than in BMG (2.6 vs. 1.9; P = 0.011). A higher incidence of surgical site infection was reported in the PSF group than in the BMG group (46.7% vs. 12.5%). The average operative time for surgery was higher in PSF than in BMG (154.8 min vs. 145.0 min), respectively. Each group had one patient with a recurrence., Conclusion: Both techniques are equally good for urethral reconstruction (UR); however, improvement of sexual function is more in favor of the BMG urethroplasty group., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Kumar et al.)

Objectives: Patients with recurrent and metastatic head and neck cancer (HNC) have limited treatment options. 'QuadShot' (QS), a hypofractionated palliative radiotherapy regimen, can provide symptomatic relief and local control and may potentiate the effects of immune checkpoint inhibitors (ICIs). We compared outcomes of QS ± concurrent ICIs in the palliative treatment of HNC., Materials and Methods: We identified patients who received ≥three cycles of QS from 2017 to 2022 and excluded patients without post-treatment clinical evaluation or imaging. Outcomes for patients who received QS alone were compared to those treated with ICI concurrent with QS, defined as receipt of ICI within 4 weeks of QS., Results: Seventy patients were included, of whom 57% received concurrent ICI. Median age was 65.5 years (interquartile range [IQR]: 57.9-77.8), and 50% patients had received prior radiation to a median dose of 66 Gy (IQR: 60-70). Median follow-up was 8.8 months. Local control was significantly higher with concurrent ICIs (12-month: 85% vs. 63%, p = 0.038). Distant control (12-month: 56% vs. 63%, p = 0.629) and median overall survival (9.0 vs. 10.0 months, p = 0.850) were similar between the two groups. On multivariable analysis, concurrent ICI was a significant predictor of local control (HR for local failure: 0.238; 95% CI: 0.073-0.778; p = 0.018). Overall, 23% patients experienced grade 3 toxicities, which was similar between the two groups., Conclusions: The combination of QS with concurrent ICIs was well tolerated and significantly improved local control compared to QS alone. The median OS of 9.4 months compares favorably to historical controls for patients with HNC treated with QS. This approach represents a promising treatment option for patients with HNC unsuited for curative-intent treatment and warrants prospective evaluation.

Objectives. Studies related to a systematic approach for intervention design to reduce whole-body vibration (WBV) exposure are scarce. This study presents a systematic approach to identifying, selecting and prioritizing safety interventions to fulfill that research gap. Methods. A total of 130 vibration readings for dumper operators were taken from two surface iron ore mines to identify significant determinants of WBV exposure. Initially, age, weight, seat design, awkward posture, machine's age, load tonnage, dumper speed and haul road condition were hypothesized as determinants. Data were collected through standardized questionnaires and field-based observation. A multivariate statistical approach was applied for the practical use of the intervention program. Results. As some of the hypothesized factors were correlated, exploratory factor analysis (EFA) followed by multiple linear regression (MLR) was used to investigate their association with WBV exposure. As per EFA results, hypothesized factors were clubbed under individual, ergonomics and occupational factors. Occupational and ergonomics factors were found to be significantly associated with WBV exposure through MLR and used to form safety interventions to reduce WBV exposure. Conclusions. Our methodological approach is original in the occupational health research area and can be helpful to tailor the safety interventions for the unit level with minimum effort.

The recent pandemic has highlighted the need to understand how we resist infections and their causes, which may differ from the ways we often think about treating epidemic diseases. The current study presents an improved version of the susceptible-infected-recovered (SIR) epidemic model, to better comprehend the community's overall dynamics of diseases, involving numerous infectious agents. The model deals with a non-monotone incidence rate that exhibits psychological or inhibitory influence and a saturation treatment rate. It has been identified that depending on the measure of medical resources and the effectiveness of their supply, the model exposes both forward and backward bifurcations where two endemic equilibria coexist with infection-free equilibrium. The model also experiences local and global bifurcations of codimension two, including saddle-node, Hopf, and Bogdanov-Takens bifurcations. Additionally, the stability of equilibrium points is investigated. For a spatially extended SIR model system, we have shown that cross-diffusion allows S and I populations to coexist in a habitat. Also, the Turing instability requirements and Turing bifurcation regime are derived. The relationship between distinct role-playing model parameters and various pattern formations like spot and stripe patterns is validated by carrying out in-depth numerical simulations. The findings in the vicinity of the endemic equilibrium solution demonstrate the significance of positive and negative valued cross-diffusion coefficients in regulating the genesis of spatial patterns in susceptible as well as diseased individuals. The discussion of the findings of epidemiological ramifications concludes the manuscript., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Coalbed methane (CBM) reservoirs are naturally fractured formations with cleats surrounding the coal matrix. Analyzing and predicting CBM production performance is challenging because of the complex fracture networks and gas-water two-phase flow, along with the permeability and porosity variation and time-dependent desorption. During depletion, pressure decreases and consequently stress increases, thereby decreasing cleat aperture and permeability, while the matrix shrinkage effect increases cleat width and permeability. The two effects compete with one another, and dominance depends on coal's geomechanical properties and the change in reservoir properties. In addition, though the gas composition from CBM wells predominantly consists of methane, it contains traces of other gases like ethane, carbon dioxide, nitrogen, etc. The combined effects of pressure-dependent diffusivity, time-dependent desorption, and multicomponent sorption in a two-phase flowing CBM well make the flow dynamics in CBM reservoirs complex. A modified semi-analytical mathematical model is developed to characterize the time-dependent desorption and pressure-dependent diffusivity phenomena, also considering the dynamic variation of composition and multicomponent desorption for two-phase flow of CBM wells producing under semi-steady state conditions. The novelty of the model presented in this study lies in manifesting multicomponent sorption effects in the form of an equivalent single-component sorption phenomenon by establishing new transforms. A fully coupled mathematical model is developed that integrates multicomponent sorption effects in CBM reservoirs with pressure-dependent diffusivity and time-dependent desorption effects. The Article presents a new method to intertwine the desorption material balance of individual components with fully coupled flow equations and gives a workflow to predict and evaluate the production performance of a producing CBM well. The study reveals that a multicomponent, two-phase coalbed methane system can be represented in the form of an equivalent single-component single-phase system, thus paving the way for application of CBM flow equations valid for a single phase and single component. The results of the model have been verified using a CMG-GEM numerical simulator as well as in-field production data. This study brings out a novel computational approach for the compositional simulation of the CBM wells, which is unconditionally stable and involves less complexity than commercial simulators, without compromising the accuracy of the results. The findings of this study can help improve the understanding of the complex flow behavior of CBM reservoirs, where multiple phenomena occur simultaneously, like multicomponent sorption, two-phase flow, pressure-dependent diffusion, and time-dependent desorption., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Objective: The aim of the study was to find the estimate of the prevalence of urinary tract infections following invasive urodynamic studies (UDS) in a hospital setup and to identify the risk factors related to it., Method: A total of 100 patients were enrolled in this prospective observational study after standard preoperative work, which included both urine analysis and culture procedure. The study was carried out from April 2022 to April 2023 at the Department of Urology, Indira Gandhi Institute of Medical Sciences, India. Three days following the UDS test, all the patients underwent repeat urine analysis and culture, besides screening for any lower urinary tract symptoms, abdominal pain, and fever., Result: Among all, 14 patients (i.e., 6.1% of 85 individuals) had significant bacteriuria, and six patients (4.7%) developed symptoms of UTI. However, a strong association was observed between the maximal detrusor pressure during voiding (Pdet at Q max) and post-void residue (PVR), which were >20 mL before UDS, along with positive urine cultures after UDS, which was significant at <0.05., Conclusion: The study demonstrated that the risk of UTIs with this diagnostic technique is minimal and that prophylactic antibiotic medication is not necessary prior to UDS in all patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Upadhyay et al.)

The fragile nature of quantum circuits is a major bottleneck to scalable quantum applications. Operating at cryogenic temperatures, quantum circuits are highly vulnerable to amplifier backaction and external noise. Non-reciprocal microwave devices such as circulators and isolators are used for this purpose. These devices have a considerable footprint in cryostats, limiting the scalability of quantum circuits. As a proof-of-concept, here we report a compact microwave diode architecture, which exploits the non-linearity of a superconducting flux qubit. At the qubit degeneracy point we experimentally demonstrate a significant difference between the power levels transmitted in opposite directions. The observations align with the proposed theoretical model. At - 99 dBm input power, and near the qubit-resonator avoided crossing region, we report the transmission rectification ratio exceeding 90% for a 50 MHz wide frequency range from 6.81 GHz to 6.86 GHz, and over 60% for the 250 MHz range from 6.67 GHz to 6.91 GHz. The presented architecture is compact, and easily scalable towards multiple readout channels, potentially opening up diverse opportunities in quantum information, microwave read-out and optomechanics., (© 2024. The Author(s).)

Background & Aims: Lacticaseibacillus rhamnosus GG (LGG) is the world's most consumed probiotic but its mechanism of action on intestinal permeability and differentiation along with its interactions with an essential source of signaling metabolites, dietary tryptophan (trp), are unclear., Methods: Untargeted metabolomic and transcriptomic analyses were performed in LGG monocolonized germ-free mice fed trp-free or -sufficient diets. LGG-derived metabolites were profiled in vitro under anaerobic and aerobic conditions. Multiomic correlations using a newly developed algorithm discovered novel metabolites tightly linked to tight junction and cell differentiation genes whose abundances were regulated by LGG and dietary trp. Barrier-modulation by these metabolites were functionally tested in Caco2 cells, mouse enteroids, and dextran sulfate sodium experimental colitis. The contribution of these metabolites to barrier protection is delineated at specific tight junction proteins and enterocyte-promoting factors with gain and loss of function approaches., Results: LGG, strictly with dietary trp, promotes the enterocyte program and expression of tight junction genes, particularly Ocln. Functional evaluations of fecal and serum metabolites synergistically stimulated by LGG and trp revealed a novel vitamin B 3 metabolism pathway, with methylnicotinamide (MNA) unexpectedly being the most robust barrier-protective metabolite in vitro and in vivo. Reduced serum MNA is significantly associated with increased disease activity in patients with inflammatory bowel disease. Exogenous MNA enhances gut barrier in homeostasis and robustly promotes colonic healing in dextran sulfate sodium colitis. MNA is sufficient to promote intestinal epithelial Ocln and RNF43, a master inhibitor of Wnt. Blocking trp or vitamin B 3 absorption abolishes barrier recovery in vivo., Conclusions: Our study uncovers a novel LGG-regulated dietary trp-dependent production of MNA that protects the gut barrier against colitis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This study focuses on evaluating the exposure to whole-body vibration (WBV) and association of musculoskeletal disorders (MSDs) with various risk factors among dumper operators in the mining industry. Despite the issue's significance, prior research has been limited., Objective: The study introduces a novel fuzzy-based approach for identifying, selecting, and prioritizing safety measures to mitigate MSD risks., Methods: Data collection comprised face-to-face interviews, anthropometric measurements, Rapid Upper Limb Assessment (RULA) scoring for posture assessment, and the Nordic Musculoskeletal questionnaire for assessment of MSD prevalence. Multiple linear and logistic regression models were used to analyse the contributing risk factors to MSDs and WBV exposure. These risk factors formed the basis for a practical approach to select appropriate safety measures based on fuzzy based aggregation method of expert's judgment aimed at mitigating the risk of MSDs., Results: The results revealed that the risk factors such as poor work posture, WBV exposure and poor seat design were significantly associated with neck (adjusted odds ratio aOR = 4.81), upper limb and shoulder (aOR = 3.28), upper back (aOR = 5.09), and lower back pain (aOR = 3.67) at p < 0.05. Using these factors to formulate safety measures to reduce MSD risk, the minimization of sharp turns and abrupt changes in elevation in designing the haul roads, scheduled maintenance practices, and ergonomic seat design were found as important safety measures in this study., Conclusion: Our unique methodological approach in occupational health research could be highly beneficial for tailoring safety measures at the unit level with minimal effort.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has a direct impact on the dopaminergic neurons in the substantia nigra pars compacta (SNpc), dopamine in the striatum (ST), homovanillic acid (HVA), neurotrophic factors of the SNpc, and ST regions leading to Parkinson's disease (PD). Dopaminergic neuron atrophy in the SNpc and dopamine degradation in the ST have an explicit link to disrupted homeostasis of the neurotrophic factor brain-derived neurotrophic factor (BDNF) of the SNpc and ST regions. Chrysin is a flavonoid with a pharmacological potential that directly influences neurotrophic levels as well as neurotransmitters. As a result, analysis of the altering levels of neurotransmitters such as dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), are observed via high-performance liquid chromatography (HPLC) and the confirmation of the influential role of BDNF and glial-derived neurotrophic factor (GDNF) in the homeostasis of dopamine, DOPAC, and HAV via examination of gene expression. The observation confirmed that chrysin balances the altering levels of neurotransmitters as well as neurotrophic factors. The protocols for reverse transcription-polymerase chain reaction (RT-PCR) and HPLC analysis for neurotransmitter levels from the SNpc and ST regions of acute PD mice brain-induced MPTP are described in this chapter., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Gastroesophageal reflux disease (GERD) has a pooled prevalence of 15.2% in India with varying presentation in different subset of patients. The approach towards the management of GERD includes use of monotherapy or a combination of OTCs like antacids and/or prescription drugs like H2 receptor antagonists and proton pump inhibitors (PPI). Better efficacy and safety profile of PPIs have contributed to its wide spread use as compared with other drugs for the same indication. Among PPIs, most of the healthcare professionals prefer to prescribe pantoprazole in India. Standard dose of Pantoprazole (40 mg) is unable to meet the needs in case of extraesophageal symptoms, partial responders, patients with concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs), or severe presentation in cases of overweight/obese patients. Multiple guidelines recommend doubling the dose of PPI in such cases. Twice daily dosing of PPI may reduce compliance. Thus, there is a need for a higher dose of Pantoprazole (80 mg) to be prescribed once daily in these cases so that improved compliance leads to better outcomes. The use of dual release Pantoprazole 80 mg may help to improve compliance and also enhance the time for which acid suppression takes place. In this review, we discuss the use of higher dose PPI based on scientific evidence and experience of clinicians for the same., How to Cite This Article: Upadhyay R, Soni NK, Kotamkar AA, et al . High Dose Pantoprazole for Gastroesophageal Reflux Disease: Need, Evidence, Guidelines and Our Experience. Euroasian J Hepato-Gastroenterol 2024;14(1):86-91., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2024; The Author(s).)

Purpose: Stereotactic radiosurgery (SRS) is the current standard of care in patients with brain metastases and controlled extracranial disease. Radiation necrosis (RN) is the dose-limiting side effect of SRS, but the dose constraints especially for fractionated SRS remain poorly defined. We assessed the risk of RN after 3-fraction SRS with a goal to identify specific dose-volume constraints associated with grade 3 or higher RN (G3RN)., Methods and Materials: A single-institutional retrospective review of patients treated with 3-fraction SRS was performed. The primary endpoint was G3RN, which was defined as severe symptoms with evidence of necrosis on magnetic resonance imaging with perfusion and/or biopsy confirmation. Tissue volume around each target lesion was contoured, and volumetric doses per lesion were recorded. Logistic regression models were used to estimate the relationship between RN and each volumetric dose, and normal tissue complication probability modeling was performed using a modified Lyman-Kutcher-Burman model., Results: From 2015 to 2021, 434 patients underwent 539 courses of linear accelerator-based SRS; 2518 lesions were treated. Median SRS dose was 24 Gy. Median follow-up after SRS was 7.9 months, and the median overall survival was 9 months. A total of 93 patients (17.2%) and 123 lesions (4.9%) developed any RN. Forty-two patients (7.8%) and 57 lesions (2.3%) developed G3RN. On logistic regression, V20 and V23 were best predictors of any grade RN and G3RN, respectively, with cutoff values of 4 cc, 10 cc, and 20 cc associated with <5%, <7.5%, and <10% risk of any RN, respectively, and V23 < 15 cc associated with <5% risk of G3RN. With constrained optimization of the normal tissue complication probability Lyman-Kutcher-Burman model for G3RN, we obtained a TD50 (uniform dose resulting in a 50% complication risk) of 31.4 Gy (95% CI, 27.8-35.1 Gy)., Conclusions: In patients receiving 3-fraction SRS, G3RN was seen in 7.8% of patients, and 2.3% of the lesions were treated. V20 and V23 were the most robust dosimetric parameters associated with RN. Further studies evaluating the outcomes and RN in patients treated with fractionated SRS compared with single-fraction SRS are warranted., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Breast cancer is the second most common cause of brain metastases (BM). Despite increasing incidence of BM in older women, there are limited data on the optimal management of BM in this age group. In this study, we assessed the survival outcomes and treatment patterns of older breast cancer patients ≥65 years old with BM compared to younger patients at our institution., Methods: An IRB-approved single-institutional retrospective review of biopsy-proven breast cancer patients with BM treated with 1- to 5-fraction stereotactic radiation therapy (SRS) from 2015 to 2020 was performed. Primary endpoint was intracranial progression-free survival (PFS) defined as the time interval between the end of SRS to the date of the first CNS progression. Secondary endpoints were overall survival (OS) from the end of SRS and radiation treatment patterns. Kaplan-Meier estimates and Cox proportional hazard regression method were used for survival analyses., Results: A total of 112 metastatic breast cancer patients with BMs were included of which 24 were ≥65 years old and 88 were <65 years old. Median age at RT was 72 years (range 65-84) compared to 52 years (31-64) in younger patients. There were significantly higher number of older women with ER/PR positive disease (75% vs. 49%, p = 0.036), while younger patients were more frequently triple negative (32% vs. 12%, p = 0.074) and HER2 positive (42% vs. 29%, p = 0.3). Treatment-related adverse events were similar in both groups. Overall, 14.3% patients had any grade radiation necrosis (RN) (older vs. young: 8.3% vs. 16%, p = 0.5) while 5.4% had grade 3 or higher RN (0% vs. 6.8%, p = 0.7). Median OS after RT was poorer in older patients compared to younger patients (9.5 months vs. 14.5 months, p = 0.037), while intracranial PFS from RT was similar between the two groups (9.7 months vs. 7.1 months, p = 0.580). On univariate analysis, significant predictors of OS were age ≥65 years old (hazard risk, HR = 1.70, p = 0.048), KPS ≤ 80 (HR = 2.24, p < 0.001), HER2 positive disease (HR = 0.46, p < 0.001), isolated CNS metastatic disease (HR = 0.29, p < 0.001), number of brain metastases treated with RT (HR = 1.06, p = 0.028), and fractionated SRS (HR = 0.53, p = 0.013). On multivariable analysis, KPS ≤ 80, HER2 negativity and higher number of brain metastases predicted for poorer survival, while age was not a significant factor for OS after adjusting for other variables. Patients who received systemic therapy after SRS had a significantly improved OS on univariate and multivariable analysis (HR = 0.32, p < 0.001). Number of brain metastases treated was the only factor predictive of worse PFS (HR = 1.06, p = 0.041), which implies a 6% additive risk of progression for every additional metastasis treated., Conclusions: Although older women had poorer OS than younger women, OS was similar after adjusting for KPS, extracranial progression, and systemic therapy; and there was no difference in rates of intracranial PFS, neurological deaths, and LMD in the different age groups. This study suggests that age alone may not play an independent role in treatment-selection and that outcomes for breast cancer patients with BMs and personalized decision-making including other clinical factors should be considered. Future studies are warranted to assess neurocognitive outcomes and other radiation treatment toxicities in older patients.

Objective: Patients with deep-seated arteriovenous malformations (AVMs) have a higher rate of unfavorable outcome and lower rate of nidus obliteration after primary stereotactic radiosurgery (SRS). The aim of this study was to evaluate and quantify the effect of AVM location on repeat SRS outcomes., Methods: This retrospective, multicenter study involved 505 AVM patients managed with repeat, single-session SRS. The endpoints were nidus obliteration, hemorrhage in the latency period, radiation-induced changes (RICs), and favorable outcome. Patients were split on the basis of AVM location into the deep (brainstem, basal ganglia, thalamus, deep cerebellum, and corpus callosum) and superficial cohorts. The cohorts were matched 1:1 on the basis of the covariate balancing score for volume, eloquence of location, and prescription dose., Results: After matching, 149 patients remained in each cohort. The 5-year cumulative probability rates for favorable outcome (probability difference -18%, 95% CI -30.9 to -5.8%, p = 0.004) and AVM obliteration (probability difference -18%, 95% CI -30.1% to -6.4%, p = 0.007) were significantly lower in the deep AVM cohort. No significant differences were observed in the 5-year cumulative probability rates for hemorrhage (probability difference 3%, 95% CI -2.4% to 8.5%, p = 0.28) or RICs (probability difference 1%, 95% CI -10.6% to 11.7%, p = 0.92). The median time to delayed cyst formation was longer with deep-seated AVMs (deep 62 months vs superficial 12 months, p = 0.047)., Conclusions: AVMs located in deep regions had significantly lower favorable outcomes and obliteration rates compared with superficial lesions after repeat SRS. Although the rates of hemorrhage in the latency period and RICs in the two cohorts were comparable, delayed cyst formation occurred later in patients with deep-seated AVMs.

The N -alkylation of amines with alcohols using earth-abundant and nonprecious metal catalysts has gained considerable attention in the pharmaceutical industry. We described titanium-catalyzed synthetic protocol for N -alkylation of amines with alcohols via borrowing hydrogen or hydrogen autotransfer reactions. The methodology enables the selective monoalkylation of various substituted (hetero)aromatic amines in good to excellent yields (up to 97% yield). The importance of the protocol was further demonstrated by the applicability of earth-abundant metal catalysis and the synthesis of 32 N -alkylated amines. The work allows the utilization of titanium-based catalysts for various reactions to expand the nature blueprint in catalysis.

Introduction: Craniospinal irradiation (CSI) is indicated for adult patients diagnosed with leptomeningeal disease (LMD). Proton-based vertebral body sparing (VBS) CSI has been explored with pediatric patients to minimize hematologic toxicity; however, utilization of VBS in an adult population is limited. A recent phase II trial has shown efficacy of proton-based CSI to treat non-small cell lung and breast cancer with LMD. We hypothesize that VBS CSI using volumetric modulated arc therapy (VMAT) could also effectively reduce dose to vertebral bodies and surrounding organs at risk, minimizing toxicity for adult patients with LMD and comparing favorably to proton-based CSI., Methods and Materials: Consecutive patients with LMD received VMAT VBS CSI, 30 Gy in 10 fractions, as a part of a prospective registry. Full VMAT arcs for the brain fields matched to 2 spine isocenters for the upper and lower spine were created using limited posterior arcs. To further decrease the vertebral body dose, an avoid entry and exit contour was created. Acute toxicity data were collected using Common Terminology Criteria for Adverse Events v5., Results: Ten adult patients were treated in this cohort. One patient experienced grade 2 neutropenia with the remaining 9 experiencing grade 1 hematologic toxicity. Three patients experienced grade 2 gastrointestinal toxicity with the remaining 7 experiencing grade 1 nausea. No patient experienced grade 3+ toxicities in this cohort. One patient experienced a 5-day delay in systemic therapy initiation due to neutropenia; otherwise, all patients planned for systemic therapy started without delay., Conclusions: In this study, VMAT VBS CSI led to acceptable toxicity compared with patients treated with proton CSI on a phase 2 clinical trial. Given its promising early results, future prospective evaluation of the technique is warranted., (© 2023 The Author(s).)

Stereotactic ablative radiotherapy (SABR) has challenged the conventional wisdom surrounding the radioresistance of renal cell carcinoma (RCC). In the past decade, there has been a significant accumulation of clinical data to support the safety and efficacy of SABR in RCC. Herein, we review the use of SABR across the spectrum of RCC. We performed an online search of the Pubmed database from January 1990 through April 2023. Studies of SABR/stereotactic radiosurgery targeting primary, extracranial, and intracranial metastatic RCC were included. For SABR in non-metastatic RCC, this includes its use in small renal masses, larger renal masses, and inferior vena cava tumor thrombi. In the metastatic setting, SABR can be used at diagnosis, for oligometastatic and oligoprogressive disease, and for symptomatic reasons. Notably, SABR can be used for both the primary renal tumor and metastasis-directed therapy. Management of RCC is evolving rapidly, and the role that SABR will have in this landscape is being assessed in a number of ongoing prospective clinical trials. The objective of this narrative review is to summarize the evidence corroborating the use of SABR in RCC.

Antibiotic resistance associated with various microorganisms such as Gram-positive, Gram-negative, fungal strains, and multidrug-resistant tuberculosis increases the risk of healthcare survival. Preliminary therapeutics becoming ineffective that might lead to noteworthy mortality presents a crucial challenge for the scientific community. Hence, there is an urgent need to develop hybrid compounds as antimicrobial agents by combining two or more bioactive heterocyclic moieties into a single molecular framework with fewer side effects and a unique mode of action. This review highlights the recent advances (2013-2023) in the pharmacology of rhodanine-linked quinoline hybrids as more effective antimicrobial agents. In the drug development process, linker hybrids acquire the top position due to their excellent π-stacking and Van der Waals interaction with the DNA active sites of pathogens. A molecular hybridization strategy has been optimized, indicating that combining these two bioactive moieties with an arylidene and an amino spacer linker increases the antimicrobial potential and reduces drug resistance. Moreover, the structure-activity relationship study is discussed to express the role of various functional groups in improving and decrementing antimicrobial activities for rational drug design. Also, a linker approach may accelerate the development of dynamic antimicrobial agents through molecular hybridization., (© 2023 John Wiley & Sons Ltd.)

Because of their adaptability and user-friendliness, internal combustion engines are widely used for a variety of purposes, including the generation of consistent power as well as transportation. As a result, the question of whether or not these engines can make use of bio-oils is an important one today. Bio-oils derived from biomass pyrolysis differ significantly from those derived from petroleum-based fuels and biodiesel. They could, however, be valuable alternatives to fossil fuels in order to attain a carbon-neutral future. Bio-oil obtained from catalytic pyrolysis of Argemone Mexicana seed using titanium oxide (TiO 2 ) nanoparticles was employed in IC engine to check its suitability as an alternative fuel. Engine performance analysis was conducted at B5, B10, B15, B20, B25, and B30 blend for different parameters such as brake thermal efficiency, exhaust gas temperature, and brake-specific fuel consumption with change in engine load. Emission analysis was also carried out for carbon monoxide, hydrocarbon, nitrogen oxides, and carbon dioxide emissions. It was found that B30 blend resembled best performance and the bio-oil produced from catalytic pyrolysis of Argemone mexicana seed can be utilised as a substitute of fossil fuels in IC engine., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Three-dimensional (3D) printing, one of the forms of additive manufacturing, has become a popular trend worldwide with a wide range of applications including food. The technology is adaptable and meets foods nutritional and sensory needs allowing meat processing to reach a sustainable level, technology addressing the food requirement of the ever-increasing population and the fast-paced lifestyle by reducing food preparation time. By minimizing food waste and the strain on animal resources, technology can help to create a more sustainable economy and environment. This review article discusses the 3D printing process and various 3D printing techniques used for food printing, such as laser powder bed fusion, inkjet food printing, and binder jetting, a suitable 3D technique used for meat printing, such as extrusion-based bioprinting. Moreover, we discuss properties that affect the printability of meat and its products with their applications in the meat industry, 3D printing market potential challenges, and future trends., (© 2023 Wiley Periodicals LLC.)

Carbon-fiber reinforced (CFR) polyetheretherketone hardware is an alternative to traditional metal hardware used for spinal fixation surgeries before postoperative radiation therapy for patients with spinal metastases. CFR hardware's radiolucency decreases metal artifact, improving visualization and accuracy of treatment planning. We present the first clinical use and proof of principle of CFR spinal hardware with tantalum markers used for successful tracking of intrafraction motion (IM) using Varian TrueBeam IMR (Intrafraction Motion Review) software module during postoperative spine stereotactic radiation. A 63-year-old woman with history of endometrial cancer presented with acute back pain. Imaging demonstrated pathologic T12 vertebral fracture with cord compression. She underwent T12 vertebrectomy with circumferential decompression and posterior instrumented T10-L2 fusion at our facility using CFR-polyetheretherketone hardware with tantalum screw markers followed by postoperative stereotactic body radiation therapy to 3000 cGy in 5 fractions delivered to T11-T12. Tantalum screw markers were used for IMR tracking. During irradiation, 260 kV images were acquired, and IMR software was able to identify and track markers. During the entire treatment, the IM motions were less than 3 mm. This is the first presented case of CFR spinal hardware with tantalum markers used for successful IMR tracking of IM during daily spine stereotactic treatment. Future work will be needed to improve workflow and create a spine-specific IMR protocol., Competing Interests: Disclosures JDP reports research and speaking fees from Icotec, outside submitted work: Varian speeking fees, Novocure advisory board, Kroger trial funding, NIH R01CA269948, NIH R702 award, Biocept clinical trial funding, genentech clinical trial funding, (Copyright © 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Introduction: Tuberculosis (TB) is a major public health problem in the developing world. Depression affects medicine adherence in TB patients. There is a scarcity of data regarding the prevalence of depression among TB patients from any city in central India. Therefore, the aim of this research was to study the prevalence of depression and associated factors in TB patients in the Vidisha district of Madhya Pradesh, India., Methods: This was a cross-sectional study conducted on 106 TB patients visiting the TB and chest outpatient department of Atal Bihari Vajpayee Government Medical College (ABVGMC). It is a tertiary health care facility located in the district of Vidisha in Madhya Pradesh, India. Data collection was done from September 2020 to January 2021. Depression was measured using the Patient Health Questionnaire-9 (PHQ-9). We used a semi-structured questionnaire to collect data regarding relevant demographic and behavioral factors. Analyses were done in IBM SPSS software, version 25 (IBM Corp., Armonk, NY)., Results: The prevalence of depression among TB patients was 55.7% (n = 59). Depression in the mild category was most common (n = 44, 41.5%), followed by moderate (n = 10, 9.4%), and the moderately severe (n = 5, 4.7%) category. Depression prevalence was found to be slightly more common in females (58.5% vs. 52.8% in males), married participants (58.2% vs. 51.3% in unmarried), educated more than high school (56.8% vs. 54.8% in less than high school), socioeconomically Above Poverty Line (APL) (60.5% vs. 52.4% in Below Poverty Line (BPL)), living in urban areas (60.9% vs. 47.6% in rural areas), and in the continuation phase of anti-TB treatment (58.6% vs. 52.1% in intensive phase), but differences were statistically non-significant. Depression was significantly associated with the medicine non-adherence group (vs. the medicine adherence group; p-value: 0.022) and the previously treated TB patient category (vs. the new case group; p-value: 0.031)., Conclusion: The prevalence of depression among TB patients was very high (55.7%). The prevalence of depression was significantly higher in the medicine non-adherent group (p-value: 0.022) and the previously treated TB patient group (p-value: 0.031). In this study, we have not found any significant association between the prevalence of depression among TB patients and sex, marital status, education attainment, poverty status, or living in an urban or rural areas., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Solanki et al.)

Background Adolescents are highly vulnerable to different types of behavioural problems that can affect their academic and social lives. If left untreated, serious mental illness can develop. Objective The objective of this study was to find out emotional and behavioural problems among adolescents. Method A descriptive cross-sectional study was conducted among 275 adolescents studying in grades 7-11 at five private schools in Kathmandu. A non-probability convenience sampling technique was used to select required sample. The self-reported Strengths and Difficulties Questionnaire was used to collect data. Ethical approval was obtained from the Institutional Review Committee at the Institute of Medicine, Tribhuvan University. Descriptive statistics were used to analyse the data. The chi-square test was used to measure the association between behavioural problems and selected variables at a 95.0% confidence level. Result The mean age of the adolescents was 13.66 (SD ± 1.13) years, and 53.1% were female. In total, 7.3% and 13.8% of adolescents had abnormal and borderline levels of behavioural problems (total difficulties), respectively. Across different domains of difficulty levels, 5.0%, 12.0%, 3.3%, 5.5%, and 1.5% of adolescents had abnormal levels of emotional problems, conduct problems, hyperactivity/ inattention problems, peer relationship problems, and pro-social behaviours, respectively. Fathers' occupation was significantly associated with behavioural problems among adolescents (p=0.020), and 15.3% of adolescents had a significant impact on their daily life, such as at home, with friends, in the classroom, or during leisure activities, due to emotional and behavioural difficulties. Conclusion Emotional and behavioural problems are quite prevalent among adolescents and have a significant adverse impact on their daily lives.

The immune response to SARS-CoV-2 antigen after infection or vaccination is defined by the durable production of antibodies and T cells. Population-based monitoring typically focuses on antibody titer, but there is a need for improved characterization and quantification of T cell responses. Here, we used multimodal sequencing technologies to perform a longitudinal analysis of circulating human leukocytes collected before and after immunization with the mRNA vaccine BNT162b2. Our data indicated distinct subpopulations of CD8 + T cells, which reliably appeared 28 days after prime vaccination. Using a suite of cross-modality integration tools, we defined their transcriptome, accessible chromatin landscape and immunophenotype, and we identified unique biomarkers within each modality. We further showed that this vaccine-induced population was SARS-CoV-2 antigen-specific and capable of rapid clonal expansion. Moreover, we identified these CD8 + T cell populations in scRNA-seq datasets from COVID-19 patients and found that their relative frequency and differentiation outcomes were predictive of subsequent clinical outcomes., (© 2023. The Author(s).)

The lead-free perovskite halides emerge as the great alternative for highly efficient and environment friendly photovoltaics due to the inherent optoelectronic properties. In this paper, the numerical study of all-inorganic regular n-i-p structured perovskite photovoltaics using solar cells capacitance simulator (SCAPS-1D) has been performed. The optimised device structure using rGO provided best performance compared to the other hole transport layers (HTLs) like CuI, CuSCN, Cu 2 O, NiO, WSe 2 , MoO 3 with CsSnI 3 as an active material and TiO 2 as electron transport layer (ETL). Furthermore, WS 2 as an ETL compared to TiO 2 , Li-TiO 2 , ZnO, Al-ZnO, etc. provided the best performance with rGO as HTL and CsSnI 3 as active material. Therefore, the optimized solar cell structure (FTO/WS 2 /CsSnI 3 /rGO/Pt) showed best photovoltaic performance with power conversion efficiency (PCE) of 31%, fill factor (FF) of 88.48%, open circuit voltage (V OC ) of 1.15 V, and short circuit current density (J SC ) of 30.47 mA/cm 2 , respectively. Consequently, the effect of variation of temperature, thickness, defect density, doping density of active layer and variation of illumination intensity on the photovoltaic performance of the optimised device are also analysed. Furthermore, this study is also focused on the analysis of photovoltaic parameters for the optimized structure using concept of ideality factor associated with the illumination intensity. Therefore, this analysis suggests a route for further development of all-inorganic, lead-free perovskite photovoltaics experimentally with improved photovoltaic performance., (© 2023. Springer Nature Limited.)