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Abstract Extensive research is currently underway to determine the security of existing ciphers in light of the advancements in quantum computing. Against symmetric key cryptography, Grover’s search algorithm is a prominent attack, capable of reducing search costs to the square root. For using Grover’s algorithm, it is imperative to embed the target cipher into a quantum circuit. Even so, this area of research is relatively new; it has garnered significant attention from the research community. In this study, we provide the first estimation of the cost of Grover’s key search attack against the AES-based AEAD schemes Rocca-S, AEGIS-128, and Tiaoxin-346. Our analysis considers circuit depth restrictions specified in NIST’s PQC standardization process. Considering NIST’s maximum depth constraints, We present the overall cost of these attacks using gate count and depth-times-width metrics. We observed that for $$\textsf{MAXDEPTH} = 2^{40}$$ MAXDEPTH = 2 40 , Rocca-S, AEGIS-128, and Tiaoxin-346 can be retrieved using Grover’s search algorithm with gate count of 1.09 × 2253, 1.14 × 2124, and 1.22 × 2124 respectively. Concerning the current updated values by NIST, these ciphers are secure in terms of the cost of implementing Grover’s attack for key recovery. The quantum circuits of these ciphers are implemented using QISKIT, an open-source software development kit (SDK) designed for working with quantum computers running on the IBM Quantum Experience platform.

The interventional cardiac catheterization for treating congenital heart disease has evolved. Complications following interventional procedures might need emergency surgery as a bailout. Here, we report a case of cardiac perforations in three different sites following device closure of atrial septal defect (ASD). In literature, the major sites of ASD device erosion are at the roof of the right atrium (RA), left atrium (LA), or at the atrial junction with the aorta. In our patient, the device eroded at all three sites: the roof of the LA, RA, and the aorta, causing hemopericardium.

Radiation therapy is often utilised for the treatment of pelvic malignancies. Radiation-induced haemorrhagic cystitis can occur in such patients and may sometimes lead to uncontrolled haematuria. Various treatment modalities for managing this condition include urinary bladder irrigation, cystoscopy-guided procedures, hyperbaric oxygen therapy, fulguration, and other surgical techniques. Transarterial super-selective vesical artery embolisation has emerged as a modern management technique for patients with refractory radiation-induced haemorrhagic cystitis. Hereby, the authors present a case report of a 62-year-old elderly female patient diagnosed with radiation-induced haemorrhagic cystitis, which was refractory to continuous urinary bladder irrigation and medical management. She was successfully treated with super-selective vesical artery embolisation, resulting in complete resolution of haematuria, even on follow-up. This minimally invasive and effective modality can be utilised as a first-line therapy as well as in cases where other treatment options have failed.

Abstract Anthropogenic and climatic changes affect the water and energy cycles in High Mountain Asia (HMA), home to over two billion people and the largest reservoirs of freshwater outside the polar zone. Despite their significant importance for water management, consistent and reliable estimates of water storage and fluxes over the region are lacking because of the high uncertainties associated with the estimates of atmospheric conditions and human management. Here, we relied on multivariate data assimilation (MVDA) to provide estimates of energy and water storage and fluxes that reflect the processes occurring in the region such as greening and irrigation-driven groundwater depletion. We developed and employed an ensemble precipitation estimate by blending different precipitation products thereby reducing the uncertainties and inconsistencies associated with precipitation in HMA. Then, we assimilated five variables that capture the changes in hydrology in response to climate change and anthropogenic activities. Overall, our results have shown that MVDA has allowed a better representation of the land surface processes including greening and irrigation-driven groundwater depletion in HMA.

Objective: To determine the optimal letrozole regimen for ovulation induction (OI) in women with polycystic ovary syndrome (PCOS) Design: Retrospective cohort study. Setting: Single academic fertility clinic from 2015–2022. Patient(s): A total of 189 OI cycles in 52 patients with PCOS Intervention(s): Patients were prescribed 1 of 4 letrozole regimens (group 1: 2.5 mg for 5 days, group 2: 2.5 mg for 10 days, group 3: 5 mg for 5 days, and group 4: 5 mg for 10 days). Main outcome measure(s): The primary outcome was ovulation, and secondary outcomes included multifollicular development, and clinical pregnancy rate, which were analyzed with binary logistic regression. Kaplan-Meier cumulative response curves and a Cox proportional hazard regression model were used for time-dependent analyses. Results: Mean age was 30.9 years (standard deviation [SD], 3.6) and body mass index was 32.1 kg/m2 (SD, 4.0). Group 2 (odds ratio [OR], 9.12; 95% confidence interval [CI], 1.92–43.25), group 3 (OR, 3.40; 95% CI, 1.57-7.37), and group 4 (OR, 5.94; 95% CI, 2.48–14.23) had improved ovulation rates after the starting regimen as compared with group 1. Cumulative ovulation rates exceeded 84% in all groups, yet those who received 5 mg and/or 10 days achieved ovulation significantly sooner. Multifollicular development was not increased in groups 2–4 as compared with group 1. Groups 2–4 also demonstrated improved time to pregnancy. Conclusions: Ovulation rates are improved when starting with letrozole at 5 mg and/or a 10-day extended course as compared with the frequently-used 2.5 mg for 5 days. This may shorten time to ovulation and pregnancy.

Precision medicine, which among other aspects includes an individual's genomic data in diagnosis and management, has become the standard‐of‐care for Mendelian cardiovascular disease (CVD). However, early identification and management of asymptomatic patients with potentially lethal and manageable Mendelian CVD through screening, which is the promise of precision health, remains an unsolved challenge. The reduced costs of genomic sequencing have enabled the creation of biobanks containing in‐depth genetic and health information, which have facilitated the understanding of genetic variation, penetrance, and expressivity, moving us closer to the genotype‐first screening of asymptomatic individuals for Mendelian CVD. This approach could transform health care by diagnostic refinement and facilitating prevention or therapeutic interventions. Yet, potential benefits must be weighed against the potential risks, which include evolving variant pathogenicity assertion or identification of variants with low disease penetrance; costly, stressful, and inappropriate diagnostic evaluations; negative psychological impact; disqualification for employment or of competitive sports; and denial of insurance. Furthermore, the natural history of Mendelian CVD is often unpredictable, making identification of those who will benefit from preventive measures a priority. Currently, there is insufficient evidence that population‐based genetic screening for Mendelian CVD can reduce adverse outcomes at a reasonable cost to an extent that outweighs the harms of true‐positive and false‐positive results. Besides technical, clinical, and financial burdens, ethical and legal aspects pose unprecedented challenges. This review highlights key developments in the field of genotype‐first approaches to Mendelian CVD and summarizes challenges with potential solutions that can pave the way for implementing this approach for clinical care.

Abstract Solid-state spin qubits within silicon crystals at mK temperatures show great promise in the realisation of a fully scalable quantum computation platform. Qubit coherence times are limited in natural silicon owing to coupling to the 29Si isotope which has a non-zero nuclear spin. This work presents a method for the depletion of 29Si in localised volumes of natural silicon wafers by irradiation using a 45 keV 28Si focused ion beam with fluences above 1 × 1019 ions cm−2. Nanoscale secondary ion mass spectrometry analysis of the irradiated volumes shows residual 29Si concentration down to 2.3 ± 0.7 ppm and with residual C and O comparable to the background concentration in the unimplanted wafer. After annealing, transmission electron microscopy lattice images confirm the solid phase epitaxial re-crystallization of the as-implanted amorphous enriched volume extending over 200 nm in depth.

Abstract Ganges and Brahmaputra, two of Asia’s most prominent rivers, have a crucial role in Southeast Asia’s geopolitics and economy and are home to one of the world’s biggest marine ecosystems. Irrigation-driven groundwater depletion and climate change affect the Ganges-Brahmaputra’s hydrology, threatening the stability of the Bay of Bengal. Here, we quantify, using results from a land reanalysis, the impacts of a changing climate and intensive irrigation on the surface water flowing into the Bay of Bengal. The effects of such activities mostly occurring in the Ganges basin, either intensified or lessened depending on the area by the climatic conditions, decrease freshwater flow into the bay by up to 1200 m3/s/year. While the increase in precipitation in the Ganges basin reduces the effects of groundwater depletion on the streamflow, the decrease in precipitation and the snowmelt decline in the Brahmaputra basin exacerbate streamflow reduction due to groundwater depletion at the delta.

Objective: This study examines the effects of surface-level, deep-level, and functional-level diversity on team innovation. This study also examines the moderation effect of the collaborative capability toward diversity and team innovation. Design/methodology/approach – The sample for this research was 175 creative team members who were then integrated into 38 creative teams of radio and television broadcasting institutions. Data collection was done using a survey method. Findings – This study indicates that surface-level and deep-level diversity negatively impact team innovation, while functional-level diversity has a positive. In addition, the study found that collaborative capability has been moderated on surface-level diversity and team innovation. However, collaborative capability does not moderate the effect of deep- and functional-level diversity on the innovation team. Originality/value – This research contributes to the team innovation literature by examining the influence of three characteristics of team diversity consisting of surface level, deep level, and functional comprehensively on team innovation, as well as the moderating role of collaboration capability as a contextual factor. Practical/Policy implication: From a practical perspective, this study has important implications for how practitioners in creative teams overcome surface and deep-level diversity challenges and take advantage of the functional-level diversity of members in creative teams. This research also increases understanding of the value of diversity in the context of team innovation.

Abstract A significant amount of study is being done to review the security promises made for the various ciphers now in use as a result of the development of quantum computing technology. A general attack against symmetric key cryptography primitives that can reduce search costs to the square root is Grover's search algorithm. To implement Grover's algorithm, it is necessary that the target cipher be implemented as a quantum circuit. Despite being relatively new, this area of study has received significant attention from the research community. The authors have estimated the cost of Grover's key search attack against the stream cipher Atom, for the first time, under circuit depth restrictions defined in National Institute of Standards and Technology (NIST) PQC standardisation process. The authors implement the quantum circuit of Atom in QISKIT, (open‐source software development kit for working with quantum computers running on IBM Quantum Experience). The results are also compared with other existing literature on LFSR‐based stream ciphers, such as Grain‐v1, Grain‐128‐AEAD, and Lizard. The authors also find that, to the best of their knowledge, in the existing literature on estimating the cost of Grover's attack on symmetric ciphers, Atom is the only 128‐bit key cipher that meets the threshold of ≈2170 set by NIST for quantum security of 128‐bit key ciphers. The authors also analyse the security of Atom against quantum TMDTO attacks.

Abstract Background Emergency laparotomy is a commonly performed surgical procedure that has higher post-operative morbidity and mortality than elective surgery. Previous research has identified that patients valued postoperative quality of life (QoL) more than the risk of mortality when deciding to undergo emergency surgery. Current pre-operative scoring and risk stratification systems for emergency laparotomy do not account for or provide prediction tools for post-operative QoL. This study aims to systematically review previous literature to determine post-operative QoL in patients who undergo emergency laparotomy. Methods A literature search was undertaken in Medline, EMBASE and the Cochrane Library to identify studies measuring post-operative QoL in patients who have had emergency laparotomy up to 29th April 2023. Mean QoL scores from the studies included were combined to calculate the average effect of emergency laparotomy on QoL. The primary outcome of the review was postoperative QoL after emergency laparotomy when compared with a comparator group. Secondary outcomes included the quality of included studies. Results Ten studies in the literature assessing the QoL of patients after emergency laparotomy were identified. Three studies showed that patients had improved QoL and seven showed worse QoL following emergency laparotomy. Length of time for QoL to return to baseline varied ranged from 3 to 12 months post-operatively. Length of hospital stay was identified as an independent risk factor for poorer QoL post-surgery. Conclusions Outcome reporting for patients who undergo emergency laparotomy should be expanded further to include QoL. Further work is required to investigate this and elicit factors that can improve QoL post-operatively.

This paper aims to forecast the stock price and analyze the return volatility of India’s top three socially responsible companies. This study used ARIMA and GARCH models to forecast the stock price and analyze return volatility. For the analysis, the required time series data are collected from Yahoo Finance from 01-08-2012 to 29-07-2022 of the companies’ Monthly and daily closing stock prices. The socially responsible companies are selected based on India’s sustainability indices. The findings of the study show that the ARIMA (9,1,9) model for HDFC Ltd, ARIMA (10,1,7) for Reliance Industries Ltd, and ARIMA (2,1,2) are suitable models to forecast the stock price. Also, the study’s findings forecasted stock prices from August 2022 to July 2023. The forecasted stock price for July 2023 of HDFC Ltd is INR 2,613.78, Reliance industries Ltd is INR 3,073.75, and ICICI Bank Ltd is INR 857.73. Reliance Industries Ltd (σ2t = 0.9270586) is less volatile, and HDFC Ltd (σ2t = 0.9665041) is more volatile among the three companies, ICICI Bank Ltd (σ2t = 0.9507527) is the second high volatile company. The present study is limited to the top three companies that were selected from the three sustainability indices of BSE. The study is also limited to analysis of past volatility of stock price returns.

Background: Keeping in view the role of tobacco consumption as a modifiable risk factor in various diseases and gaps in scientific knowledge among the apparently healthy adult male population in India, the researchers chose to undertake this study. Materials and Methods: A cross-sectional study was conducted among apparently healthy adult males employed in various government offices to determine the prevalence of tobacco consumption. The minimum sample size to estimate a 95% confidence interval for the prevalence of tobacco consumption with 5% absolute precision was calculated to be 340. However, 500 subjects were included in the study. The tool used for data collection was the “personal interview technique.” Standard statistical methods were utilized for data analysis. Results: The overall mean age (standard deviation (SD)) of the study subjects was 30.96 yrs (4.32). Overall, the mean (SD) of number of years of tobacco use was 5.64 years (1.98). The mean (SD) of number of cigarettes smoked per day was 6.36 (3.09). The prevalence of current smokers showed a statistically significant increase from the age groups of 20–29 yrs to 50–59 yrs (P < 0.001). All subjects in the study were able to name at least three harmful effects of tobacco consumption. The overall mean amount spent on tobacco consumption per month was Rs 536.97 (1.44% of basic salary). Overall, the most common reason for smoking was peer pressure, where 40 (93.02%) gave this reason. Of forty-three tobacco users, 27 (62.79%) expressed a desire to quit tobacco consumption. The most common reason for expressing a desire to quit tobacco was the ill effects of tobacco consumption, where 23 (85.18%) tobacco users gave this reason. Conclusion: Our study on the prevalence of tobacco consumption among government employees provides an adequately clear picture of this public health epidemic in India. There is an immediate need for target group-specific policies for tobacco control, which should be integrated with the relevant national health programs at all levels.

Objective: To compare the consistency of endometrial receptivity array (ERA) and histologic dating among 3 spatially distinct endometrial samples obtained during a cycle of exogenous estrogen and progesterone. Design: Prospective blinded study. Setting: University practice. Patients: Twelve patients undergoing a mock frozen embryo transfer cycle. Intervention: Endometrial biopsy was performed in a manner that provided a spatially organized endometrial specimen, corresponding to the fundus, middle, and lower segment. Each of these 3 sections was further divided into immediately adjacent specimens for ERA and histology. Main Outcome Measure: Consistency of the ERA and histology results among fundal, mid, and lower endometrial biopsy specimens. Results: The ERA showed variability in outcome among different patients but dated all specimens originating from the same patient identically. Histologic dating showed variability between patients as well as between different locations within the uterus. When comparing average dating results for each patient, we saw a positive correlation between histologic and ERA dating (Spearman Rho = 0.45); however, this did not reach statistical significance. The ERA results from upper, mid, and lower uterine biopsy specimens were identical for each autologous biopsy, whereas histologic dating showed variability with an average standard deviation of 0.71 days. Conclusions: The increased heterogeneity of histologic dating is likely to be attributed to the subjectivity of the test. Furthermore, we did not observe a consistent lag or advancement in histologic or ERA dating between the fundal or lower uterine biopsies. Overall, clinicians should be reassured that endometrial tissue will return consistent ERA results independent of the location within the uterus in which it was obtained.

The Cohen–Grossberg neural network is studied in the case when the dynamics of the neurons is modeled by a Riemann–Liouville fractional derivative with respect to another function and an appropriate initial condition is set up. Some inequalities about both the quadratic function and the absolute values functions and their fractional derivatives with respect to another function are proved and they are based on an appropriate modification of the Razumikhin method. These inequalities are applied to obtain the bounds of the norms of any solution of the model. In particular, we apply the squared norm and the absolute values norms. These bounds depend significantly on the function applied in the fractional derivative. We study the asymptotic behavior of the solutions of the model. In the case when the function applied in the fractional derivative is increasing without any bound, the norms of the solution of the model approach zero. In the case when the applied function in the fractional derivative is equal to the current time, the studied problem reduces to the model with the classical Riemann–Liouville fractional derivative and the obtained results gives us sufficient conditions for asymptotic behavior of the solutions for the corresponding model. In the case when the function applied in the fractional derivative is bounded, we obtain a finite bound for the solutions of the model. This bound depends on the initial function and the solution does not approach zero. An example is given illustrating the theoretical results.

Abstract Solute diffusion in partially saturated porous media is an important fundamental process in many natural and environmental systems. At low water saturation, the solute transport is governed by the diffusion in thin water films on the surfaces of solids. In this study, we established an improved pore‐scale simulation framework successfully describing the solute diffusion in variably saturated porous media (e.g., soils), which considers the contribution of the diffusion within the thin water film on the surface of the solid matrix. The model takes into account the liquid–gas distribution in the underlying porous media by the Shan‐Chen lattice Boltzmann Method (LBM) and simulates the solute diffusion in the bulk liquid phase and the water film. Based on the numerical results, an easy‐to‐use theoretical formula was also developed to predict the effective diffusivity in microporous materials at low saturation levels. The average relative error of its prediction with respect to the experimental data from the literature is about 30%, while that of the classical power law exceeds 70%. A simple phase diagram was defined, which allows us to identify the situations under which it is necessary to take the influence of surface water films on the effective diffusivity in unsaturated microporous media into account. The present study improves the pore‐scale model to address solute diffusion in the water films at low water saturation and elucidates the contribution of thin water films on solute transport.

BackgroundImplementation of remote monitoring solutions and digital alerting tools in health care has historically been challenging, despite the impetus provided by the COVID-19 pandemic. To date, a health systems–based approach to systematically describe barriers and facilitators across multiple domains has not been undertaken. ObjectiveWe aimed to undertake a comprehensive mixed methods analysis of barriers and facilitators for successful implementation of remote monitoring and digital alerting tools in complex health organizations. MethodsA mixed methods approach using a modified Technology Acceptance Model questionnaire and semistructured interviews mapped to the validated fit among humans, organizations, and technology (HOT-fit) framework was undertaken. Likert frequency responses and deductive thematic analyses were performed. ResultsA total of 11 participants responded to the questionnaire and 18 participants to the interviews. Key barriers and facilitators could be mapped onto 6 dimensions, which incorporated aspects of digitization: system use (human), user satisfaction (human), environment (organization), structure (organization), information and service quality (technology), and system quality (technology). ConclusionsThe recommendations proposed can enhance the potential for future remote sensing solutions to be more successfully integrated in health care practice, resulting in more successful use of “virtual wards.” Trial RegistrationClinicalTrials.gov NCT05321004; https://www.clinicaltrials.gov/study/NCT05321004

The circadian clock is an evolutionarily-conserved molecular oscillator that enables species to anticipate rhythmic changes in their environment. At a molecular level, the core clock genes induce circadian oscillations in thousands of genes in a tissue-specific manner, orchestrating myriad biological processes. While previous studies have investigated how the core clock circuit responds to environmental perturbations such as temperature, the downstream effects of such perturbations on circadian regulation remain poorly understood. By analyzing bulk-RNA sequencing of Drosophila fat bodies harvested from flies subjected to different environmental conditions, we demonstrate a highly condition-specific circadian transcriptome: genes are cycling in a temperature-specific manner, and the distributions of their phases also differ between the two conditions. Further employing a reference-based gene regulatory network (Reactome), we find evidence of increased gene-gene coordination at low temperatures and synchronization of rhythmic genes that are network neighbors. We report that the phase differences between cycling genes increase as a function of geodesic distance in the low temperature condition, suggesting increased coordination of cycling on the gene regulatory network. Our results suggest a potential mechanism whereby the circadian clock mediates the fly's response to seasonal changes in temperature.

In this paper, we propose a new family of low-latency pseudorandom functions (PRFs), dubbed Gleeok. Gleeok utilizes three 128-bit branches to achieve a 256-bit key size while maintaining low latency. The first two branches are specifically designed to defend against statistical attacks, especially for differential attacks, while the third branch provides resilience against algebraic attacks. This unique design enables Gleeok to offer ultralow latency while supporting 256-bit keys, setting it apart from existing ciphers dedicated to low-latency requirements. In addition, we propose wide-block variants having three 256-bit branches. We also present an application of Gleeok to short-input authenticated encryption which is crucial for memory encryption and various realtime communication applications. Furthermore, we present comprehensive hardware implementation results that establish the capabilities of Gleeok and demonstrate its competitiveness against related schemes in the literature. In particular, Gleeok achieves a minimum latency of roughly 360 ps with the NanGate 15 nm cell library and is thus on par with related low-latency schemes that only feature 128-bit keys while maintaining minimal overhead when equipped in an authenticated mode of operation.

Background:. Fracture-related infection is one of the most challenging complications in orthopaedic trauma surgery. However, the effect of infection on functional and pain-related outcomes has not been well established. The aims of this study were to evaluate functional recovery for patients with fracture and a deep surgical site infection compared with patients with fracture without infection and to evaluate whether pain severity, social support, and preinjury mental health have a moderating effect on the magnitude and direction of the relationship between deep surgical site infection and functional recovery. Methods:. This is a secondary retrospective cohort study using prospectively collected data from the VANCO trial (Local Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection) and the OXYGEN (Supplemental Perioperative Oxygen to Reduce Surgical Site Infection After High Energy Fracture Surgery) trial. In this study, 2,116 patients with tibial plateau, pilon, or calcaneal fractures at high risk for infection were included. Patients were divided into cohorts of patients who experienced a deep surgical site infection and those who did not. The primary outcome measure was the functional outcome using the Veterans RAND 12-Item Health Survey (VR-12). Results:. After controlling for covariates, deep surgical site infection was independently associated with functional outcome, with a 3.3-point reduction in the VR-12 Physical Component Score, and pain severity was independently associated with functional outcome, with a 2.5-point reduction in the VR-12 Physical Component Score. Furthermore, the Brief Pain Inventory pain severity demonstrated an important moderating effect on the relationship between infection and functional outcome. In patients with lower pain scores, infection had a large negative impact on functional outcome, whereas, in patients with higher pain scores, infection had no significant impact on functional outcome. Furthermore, the functional outcome in the entire cohort remains at only 61% of baseline. Conclusions:. This study documents the negative impact of postoperative infection on functional recovery after injury, as well as the novel finding of pain severity as an important moderating factor. This study emphasizes not only the importance of developing effective interventions designed to reduce postoperative infection, but also the role that factors that moderate pain severity plays in limiting recovery of physical function. Level of evidence:. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

With the advancement of technology in the field of medicine, minimally invasive vascular procedures are widely utilised for therapeutic effects. Embolisation is a minimally invasive approach to occlude a vessel for therapeutic benefit. However, these procedures are associated with a small percentage of complications, one of which is the migration of the embolising agent. Migration refers to the movement of the embolisation agent (mostly a coil) from the original placement site to an unwanted location. A 59-year-old male presented with complaints of abdominal pain lasting 2-3 months. A Contrast-enhanced Computed Tomography (CECT) scan of the abdomen revealed an ill-defined infiltrative lesion arising from the neck and body of the gallbladder. Curative surgery was planned in the form of an extended right hepatectomy; however, the Future Liver Remnant (FLR) calculated was not optimal (19%). The patient was therefore referred for preoperative Portal Vein Embolisation (PVE). During the procedure, there was an accidental microcoil migration to the right heart post-PVE, which was managed by minimally invasive techniques. The importance of multimodality imaging techniques used to identify the location and multidisciplinary approaches to aid management has also been highlighted.

The soft tissue lesions around the knee range from congenital, traumatic, and vascular to neoplastic in aetiology. The various imaging modalities employed for diagnostic work-up include plain radiographs, ultrasonography, Computed Tomography (CT) scan, and Magnetic Resonance Imaging (MRI). Based on the peculiar imaging findings, the differential diagnosis can be narrowed down; however, the final diagnosis relies on histopathological findings. Some of the highly vascular lesions are arteriovenous malformation, malignant fibrous histiocytoma, haemangiopericytoma, and synovial sarcoma. The abundant neovascularity within these lesions poses a major problem during surgery due to potential blood loss. Presurgical interventional management in the form of endovascular embolisation significantly reduces intraoperative blood loss. Here, four different cases, one of each type, presenting as highly vascular lesions around the knee joint, were successfully managed with endovascular embolisation.

Introduction: Hepatitis B virus (HBV) is a life-threatening infection that is amenable to prevention by a safe and efficacious vaccine. Healthcare workers including medical students are among the high-risk group for HBV infection. This study is carried out to estimate HBV vaccination coverage and assess the knowledge, attitude, and practice (KAP) of HBV infection among healthcare workers in a tertiary care teaching hospital, in Tamil N?du, India Methods: A cross-sectional study was conducted using a structured questionnaire to collect data on socio-demographic characteristics, vaccination status, a set of knowledge, attitude and practice questions on preventive measures for hepatitis B infection. Results: The prevalence of complete hepatitis B vaccination 195 (44.2.%) among Health Care Workers (HCWs) was very low. The remaining 256 (56.8%) of HCWs were either partially vaccinated 128 (28.4%) or nonvaccinated 128 (28.4%). Merely, 8.4% of vaccinated persons were aware of testing of antibody titer after hepatitis B vaccination. Only 97 (30%) knew the protective values of anti-hepatitis B antibodies. Study participants had adequate knowledge attitude and practice (KAP) on preventive measures for Hepatitis B infection (overall KAP score of 100.8 out of 125). Vaccination status was found to be an independent predictor of the KAP score in the final model predicted using multiple linear regression. Conclusion: The government and institutions should take proactive measures to vaccinate the unvaccinated HCWs including the medical students against vaccine-preventable diseases. Also, it is prudent to perform HBV testing among those already vaccinated or partially vaccinated to determine their level of protective antibodies.

In this paper, we consider an integro-differential model of nerve conduction which presents the propagation of impulses in the nerve’s membranes. First, we approximate the original problem via cellular nonlinear networks (CNNs). The dynamics of the CNN model is investigated by means of local activity theory. The edge of chaos domain of the parameter set is determined in the low-dimensional case. Computer simulations show the bifurcation diagram of the model and the dynamic behavior in the edge of chaos region. Moreover, stabilizing control is applied in order to stabilize the chaotic behavior of the model under consideration to the solutions related to the original behavior of the system.

The reduction of carbon emissions in the transportation sector will be aided by the electrification of transportation in RES-based energy systems. However, the inactive addition of electric vehicles is expected to hinder sustainability efforts owing to the rise in power consumption and the significant peak impacts of charging. The three main charging methods for Electric Vehicles (EVs) in Europe are: Smart Charging (SC), Power Charging (PC), and Vehicle-To-Grid (V2G) that give varying degrees of flexibility are examined in this research. This flexibility is compared to the flexibility provided by interconnections. We depict immediate action and future planning in the power organization using the Balmorel optimization tool, and we advance the state of the art by creating new approaches to stand for battery deterioration & at-home charging. Our results show that, up to the year 2050, any rise in charging flexibility reduces system costs, modifies the energy mix, affects spot prices, and reduces CO2emissions.We quantify the reciprocal benefits of flexible charging and variable generation, which limits the economics of permanently installed batteries and causes solar energy to take the place of wind energy in passive charging. The framework that includes and lacks connection development highlights the interplay between European countries in terms of the power price framework of electric mobility. The condition of the nations with the cheapest and most decarbonizes power mix is harmed beneath the most bendable situation at the EU level, even if the best result is achieved. This necessitates an adjusted coordinating strategy at the EU level.

Abstract Poly-ADP Ribose Polymerase (PARP) targeted therapy is clinically approved for the treatment of homologous recombination (HR) repair deficient tumors. The remarkable success of this therapy in the treatment of HR repair deficient cancers has not translated to HR-proficient cancers. Our studies identify the novel role of non-receptor lymphocyte-specific protein tyrosine kinase (LCK) in the regulation of HR repair in endometrioid epithelial ovarian cancer (eEOC) model. We show that DNA damage leads to direct interaction of LCK with the HR repair proteins RAD51 and BRCA1 in a kinase dependent manner RAD51 and BRCA1 stabilization. LCK expression is induced and activated in the nucleus in response to DNA damage insult. Disruption of LCK expression attenuates RAD51, BRCA1, and BRCA2 protein expression by hampering there stability and results in inhibition of HR-mediated DNA repair including suppression of RAD51 foci formation, and augmentation of γH2AX foci formation. In contrast LCK overexpression leads to increased RAD51 and BRCA1 expression with a concomitant increase in HR DNA damage repair. Importantly, attenuation of LCK sensitizes HR-proficient eEOC cells to PARP inhibitor in cells and pre-clinical mouse studies. Collectively, our findings identify a novel therapeutic strategy to expand the utility of PARP targeted therapy in HR proficient ovarian cancer. Graphical Abstract

The combination of ninhydrin and o-phenylenediamine, followed by their reaction with a phenylhydrazine derivative produces quinoxaline-based ligands (L1 – L6). These ligands react with K2PtCl4 to form Pt(II) complexes (I – VI). The ligands and Pt(II) chelate were characterized through various spectroscopic and analytical techniques, like 1H NMR, 13C NMR, C, H, N-elemental analysis, IR spectroscopy, and mass spectrometry. DFT calculations were used to optimize the structures of metal complexes. To investigate the binding mode of complexes to CT-DNA/BSA, absorption titration, viscosity measurements, and molecular docking analysis were employed. The results indicated that the DNA binding mechanism involved intercalation. The antibacterial efficacy of the compounds was evaluated against five strains of bacteria. The lower minimum inhibitory concentration (MIC) of complexes suggests that they are more potent than quinoxaline-based ligands. The synthesized compounds were evaluated for cytotoxicity using brine shrimp. The LC50 values of ligands and complexes ranged from 7.64 to 11.45 μg/mL and 5.27 to 7.02 μg/mL, respectively. The capacity of the molecule to suppress cell proliferation using the MCF-7 cancer cell was tested, and the IC50 value was discovered to be comparable to that of a standard drug. Thus in this work, complexes demonstrated intercalation as the binding mode with CT-DNA/BSA and exhibited enhanced antibacterial efficacy compared to the ligands. The compounds also showed promising cytotoxicity against brine shrimp and MCF-7 cancer cells, with comparable IC50 values to a standard drug, indicating their potential as therapeutic agents.

A field experiment was conducted at Biratnagar-4, Morang of Nepal during April – July, 2019 to evaluate the effects of organic manures and their combinations on soil properties and yield of okra var parvati. The experiment was conducted in randomized complete block design with seven treatments and three replications. The treatments consisted of human urine, poultry manure, FYM, goat manure, FYM + human urine, goat manure + human urine and recommended fertilizer. All the treatments were based on fulfillment of required nitrogen by the crop. The result showed that the highest pod yield (24.303 Mg ha-1) was obtained from the application of poultry manure. After okra harvest, the highest soil organic matter (0.4760 %), total soil nitrogen (0.243%), and available phosphorus (26.17 kg/ha) were determined from the soil of poultry manure treatments but the highest available potassium (109.2 kg/ha) was from FYM + human urine treatments. The highest N concentration in straw (5.280 %) and pod (2.253 %), P2O5 concentration in straw (0.2607 %) and pod (0.3447 %) was obtained from poultry manure treatment and the highest K2O concentration in straw (1.320 %) and pod (2.757 %) was determined from FYM + human urine application. Uptake of N (286.7 kg/ha) and P (25.60 kg/ha) was significantly higher in poultry manure application followed by the application of FYM + human urine. Higher uptake of K (163.1 kg/ha) was obtained under FYM + human urine application followed by goat manure + human urine (148.1 kg/ha). The highest benefit cost ratio (2.99) was obtained from the application of poultry manure application and the lowest benefit cost ratio (2.22) was found under human urine application. This result suggest that poultry manure was important for increasing soil properties and performance of okra and can be used as an alternative to the chemical fertilizer.

The reaction of 2-acetyl pyrazine with phenyl hydrazine gives Schiff base ligands. The Schiff base further reacted with K2PtCl4 to provide Pt(II) complexes. Ligands and Pt(II) complexes were characterized using 1H NMR, IR, mass spectrometry, elemental analysis, electronic spectra, and conductivity measurement. DFT studies were performed to optimize the structure of Pt(II) complexes. ADMET profile of the synthesized molecule was predicted using admetSAR. The antibacterial, DNA-binding, and molecular docking capabilities highlighted the influence of the various functional groups in the Schiff base ligands and platinum(II) complexes. For example, when the electron-withdrawing (nitro or methoxy) group is added to the Schiff base ligands, absorption maxima shifted to a higher wavelength, and antibacterial potency increases. Anticancer properties on the MCF-7 cancer cell line were tested to evaluate the potency of the compounds toward the cancer cell line. The IC50 value of the ligands and metal complexes ranged from 183 to 146 μg/mL and 120 to 88 μg/mL, respectively.

This research article focuses on the development of an in-situ nasal gel formulation for the antimigraine agent, Rizatriptan (RZT), to enhance its bioavailability and efficacy in treating migraine. The aim of the study was to overcome the challenges of rapid mucociliary clearance. Carbopol 934P (1–2 %w/v) was added to the primary solution, followed by HPMC K4M (0.4–1.2 %w/v). Different copolymers were tested, and HPMC K4M was chosen due to its compatibility with the other ingredients. The pH of all formulations was in the nasal pH range, and the drug content was above 97% in all batches. Gelling time varied from 1.3 to 8.6 sec, with low gelling time observed when viscosity and mucoadhesive strength were high. The results were analyzed using a statistical model with interactive and polynomial terms. The statistical analysis showed a good correlation between dependent and independent variables, with R2 values of 0.97758 and 0.948931 for viscosity and mucoadhesive strength, respectively. The Cmax of RZT in the brain was significantly higher (p

The present paper is devoted to the solvability of various two-point boundary value problems for the equation y(4)=f(t,y,y′,y″,y‴), where the nonlinearity f may be defined on a bounded set and is needed to be continuous on a suitable subset of its domain. The established existence results guarantee not just a solution to the considered boundary value problems but also guarantee the existence of monotone solutions with suitable signs and curvature. The obtained results rely on a basic existence theorem, which is a variant of a theorem due to A. Granas, R. Guenther and J. Lee. The a priori bounds necessary for the application of the basic theorem are provided by the barrier strip technique. The existence results are illustrated with examples.

Dengue is a mosquito-borne disease caused by the dengue virus belonging to family flaviviridae and has grown to be a major global public health issue. Despite decades of effort, the global comeback of dengue is evidence of the inadequacy of present management techniques. Due to the loss of healthy lives and the depletion of scarce medical resources, dengue has a significant negative economic impact in underdeveloped countries. In recent years, research for tackling the incidences of dengue infection has increased. The structure of the viral genome has been deciphered with the non-structural protein, known as NS5 serving as a potential target. NS5 consisting of an MTase domain involved in RNA capping and an RdRp domain involved in viral replication. In the presented work, a series of new Oxindoline Carboxamide derivatives were designed and synthesized for inhibiting the viral RNA dependent RNA-polymerase (RdRp) activity of DENV. The novel compounds were put through tests including molecular docking and surface plasmon resonance (SPR) binding analysis to evaluate their affinity for the viral protein and their potential as novel inhibitors of the virus. From a total of 12 derivative compounds, four compounds OCA-10c, OCA-10f, OCA-10j & OCA-10i, were found to exhibit high affinity for NS5 RdRp, the KD values being 1.376 μM, 1.63 μM, 7.08 μM & 9.32 μM respectively. Overall, we report novel inhibitors of DENV RdRp activity with potential to be utilized against DENV for treating humans after further optimization.

Summary: By sorting receptor tyrosine kinases into endolysosomes, the endosomal sorting complexes required for transport (ESCRTs) are thought to attenuate oncogenic signaling in tumor cells. Paradoxically, ESCRT members are upregulated in tumors. Here, we show that disruption of hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), a pivotal ESCRT component, inhibited tumor growth by promoting CD8+ T cell infiltration in melanoma and colon cancer mouse models. HRS ablation led to misfolded protein accumulation and triggered endoplasmic reticulum (ER) stress, resulting in the activation of the type I interferon pathway in an inositol-requiring enzyme-1α (IRE1α)/X-box binding protein 1 (XBP1)-dependent manner. HRS was upregulated in tumor cells with high tumor mutational burden (TMB). HRS expression associates with the response to PD-L1/PD-1 blockade therapy in melanoma patients with high TMB tumors. HRS ablation sensitized anti-PD-1 treatment in mouse melanoma models. Our study shows a mechanism by which tumor cells with high TMB evade immune surveillance and suggests HRS as a promising target to improve immunotherapy.

A frequently occurring genetic disorder, 22q11.2 deletion syndrome can manifest with various abnormalities. The range of cardiac anomalies associated with this syndrome is extensive, with conotruncal defects being the most prevalent. In this study, we report the case of a patient with a unique combination of anatomical abnormalities such as crisscross pulmonary arteries, a cervical aortic arch with coarctation of the aorta, and a ventricular septal defect. The patient underwent initial surgical intervention, which resulted in significant clinical improvement.

This study investigates the resistance against alkali-silica reaction (ASR) of two alternative binder systems, alkali-activated slag (AAS) and Celitement (Celite). Experimental studies on expansion and mechanical strength are carried out. Coupled kinetic and equilibrium thermodynamic modeling is used to clarify the role of binder chemistry on ASR. It was observed that under accelerated conditions OPC based mortars were more susceptible to ASR compared to AAS and Celite-based mortars. Based on experimental and modeling results, a correlation is shown between the dissolution of silica and the degree of expansion, but no correlation was found between the predicted amount of ASR products and the measured degree of expansion. Finally, the expansion degree could only be correlated with the reduction in compressive and flexural tensile strength for ASR-exposed samples.

Introduction: The successful restoration of damaged tissue requires a complicated, dynamic process called wound healing, which is supported by a wide range of cellular activities. Natural materials generated from medicinal plants have been identified, and their therapeutic potential evaluation has resulted in the development of novel, affordable medicines that can be used to treat a variety of illnesses, including chronic wounds, with limited side effects. Aims and Objectives: This study aimed to assess the wound-healing property of Glycyrrhiza Glabra (Athimathuram) plant extracts by using an in vitro scratch assay test, as well as to evaluate their cellular toxicity. Materials and Methods: Using the Soxhlet device, ethanolic extraction of the plant material was done, and the cytotoxicity of the extract on the Vero cell line was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. One of the most often utilized mammalian in vitro cell lines in research was Vero cells. To assess the wound healing properties of G. glabra plant extract, an in vitro scratch assay was used, and their potential mechanisms of action were examined. Results: Even at higher concentrations, the MTT assay showed that G. Glabra plant extracts had no cytotoxic effects on the cells. In vitro scratch assay showed that the healing process of the cell line was increased by 23.33% when compared with the controlled cell lines. Conclusion: Our research demonstrated that G. glabra has in vitro wound healing capabilities. As a result, G. glabra can be suggested as a possible source of compounds that treat wounds.

Background : Junctional ectopic tachycardia (JET) is the most common arrhythmia after pediatric open-heart surgeries (OHS), causing high morbidity and mortality. As diagnosis is often missed in patients with minimal hemodynamic instability, its incidence depends on active surveillance. A prospective randomized trial evaluated the efficacy and safety of prophylactic amiodarone and dexmedetomidine to prevent and control postoperative JET. Methods : Consecutive patients aged under 12 years were randomized into amiodarone, dexmedetomidine (initiated during anesthetic induction) and control groups. Outcome measures included incidence of JET, inotropic score, ventilation, and intensive care unit (ICU) duration and hospital stay, as well as adverse drug effects. Results : Two hundred and twenty-five consecutive patients with a median age of 9 months (range 2 days–144 months) and a median weight of 6.3 kg (range 1.8 kg–38 kg) were randomized with 70 patients each to amiodarone and dexmedetomidine groups, and the rest were controls. Ventricular septal defect and Fallot's tetralogy were the common defects. The overall incidence of JET was 16.4%. Syndromic patients, hypokalemia, hypomagnesemia, longer bypass, and cross-clamp duration were the risk factors for JET. Patients with JET had significantly prolonged ventilation (P = 0.043), longer ICU (P = 0.004), and hospital stay (P = 0.034) than those without JET. JET was less frequent in amiodarone (8.5%) and dexmedetomidine (14.2%) groups compared to controls (24.7%) (P = 0.022). Patients receiving amiodarone and dexmedetomidine had significantly lower inotropic requirements, lower ventilation duration (P = 0.008), ICU (P = 0.006), and hospital stay (P = 0.05). Adverse effects such as bradycardia and hypotension after amiodarone and ventricular dysfunction after dexmedetomidine were not significantly different from controls. Conclusion : Prophylactic amiodarone or dexmedetomidine started before OHS is effective and safe for the prevention of postoperative JET.

Abstract As IoT has increasingly evolved in recent years, it has become more important to ensure security on IoT devices. Many of such devices are under the threat of attacks in the beyond black‐box model. To protect from the threat, the cryptographic implementation that can offer secure execution in the grey‐/white‐box model is important. However, such cryptographic implementations require a large number of clock cycles to execute and cannot fully cover resistance against various types of side‐channel attacks. In this paper, a new family of table‐based cipher dubbed Cubicle is proposed, which can offer efficient execution and sufficient security against side‐channel attacks on IoT devices powered by ARM Cortex‐M processors, which are widely deployed in IoT applications. To evaluate the security of Cubicle in the grey‐box model, the authors derive the bound of table leakage in the grey‐box model by applying space hardness, which is the notion to evaluate the security against code lifting attacks in the white‐box. The security of Cubicle in the grey‐box model is shown by using this bound. In addition, the security of Cubicle is also shown in the black‐box and white‐box models. Finally, the performance of Cubicle and other ciphers in some devices powered by ARM Cortex‐M3, ‐M4, and ‐M7 processors is evaluated. The authors show that Cubicle is significantly efficient compared to other grey‐/white‐box‐ model‐secure ciphers in target experiments for IoT applications.

Pieta C Wijsman,1,&ast; Annika WM Goorsenberg,1,&ast; Abilash Ravi,1,2,&ast; Julia NS d’Hooghe,1 Barbara S Dierdorp,2 Tamara Dekker,2 Charlotte CLM van Schaik,1 Nick HT ten Hacken,3 Pallav L Shah,4– 6 Els JM Weersink,1 Elisabeth H Bel,1 Jouke T Annema,1 René Lutter,1,2 Peter I Bonta1 1Department of Pulmonary Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; 2Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; 3Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 4Department of Pulmonology, Royal Brompton Hospital, London, UK; 5National Heart & Lung Institute, Imperial College, London, UK; 6Department of Pulmonology, Chelsea & Westminster Hospital, London, UK&ast;These authors contributed equally to this workCorrespondence: Peter I Bonta, Email p.i.bonta@amsterdamumc.nlBackground: Bronchial thermoplasty (BT) is a bronchoscopic treatment for severe asthma, of which the working mechanism and responder profile are partly unknown. The aim of this study is to analyse whether BT alters airway inflammation by epithelial gene expression, inflammatory cell counts and cytokines, and whether this relates to treatment response.Methods: In this clinical trial, 28 severe asthma patients underwent bronchoscopy before and after treatment to obtain bronchial brushes and bronchoalveolar lavage fluid (BALF) from treated and untreated airways. RNA was extracted from bronchial brushes for transcriptome analysis, and BALF cells and cytokines were analysed. Asthma quality of life questionnaires were used to distinguish responders from non-responders. We compared results before and after treatment, between treated and untreated airways, and between responders and non-responders.Results: Gene expression of airway epithelium related to airway inflammation gene set was significantly downregulated in treated airways compared to untreated airways, although this did not differ for patients before and after treatment. No differences were observed in cell counts and cytokines, neither from the untreated compared to treated airways, nor before and after treatment. At baseline, compared to non-responders, the expression of genes related to glycolysis in bronchial epithelium was downregulated and both BALF and blood eosinophil counts were higher in responders.Conclusion: Local differences in gene sets pertaining to epithelial inflammatory status were identified between treated and untreated airways after treatment, not resulting in changes in differential cell counts and cytokine analyses in BALF. Secondly, baseline epithelial glycolysis genes and eosinophil counts in BALF and blood were different between responders and non-responders. The observations from this study demonstrate the potential impact of BT on epithelial gene expression related to airway inflammation while also identifying a possible responder profile.Keywords: airway inflammation, bronchial thermoplasty, bronchoalveolar lavage fluid cells, cytokines, epithelial transcriptome

Objective We studied the safety and efficacy of hydroxychloroquine (HCQ) as pre-exposure prophylaxis for COVID-19 in healthcare workers (HCWs), using a meta-analysis of randomised controlled trials (RCTs).Data sources PubMed and EMBASE databases were searched to identify randomised trials studying HCQ.Study selection Ten RCTs were identified (n=5079 participants).Data extraction and synthesis The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review and meta-analysis between HCQ and placebo using a Bayesian random-effects model. A pre-hoc statistical analysis plan was written.Main outcomes The primary efficacy outcome was PCR-confirmed SARS-CoV-2 infection and the primary safety outcome was incidence of adverse events. The secondary outcome included clinically suspected SARS-CoV-2 infection.Results Compared with placebo, HCWs randomised to HCQ had no significant difference in PCR-confirmed SARS-CoV-2 infection (OR 0.92, 95% credible interval (CI): 0.58, 1.37) or clinically suspected SARS-CoV-2 infection (OR 0.78, 95% CI: 0.57, 1.10), but significant difference in adverse events (OR 1.35, 95% CI: 1.03, 1.73).Conclusions and relevance Our meta-analysis of 10 RCTs investigating the safety and efficacy of HCQ as pre-exposure prophylaxis in HCWs found that compared with placebo, HCQ does not significantly reduce the risk of confirmed or clinically suspected SARS-CoV-2 infection, while HCQ significantly increases adverse events.PROSPERO registration number CRD42021285093.

Summary: Background: Only a minority of melanoma patients experience durable responses to immunotherapies due to inter- and intra-tumoral heterogeneity in melanoma. As a result, there is a pressing need for suitable preclinical models to investigate resistance mechanisms and enhance treatment efficacy. Methods: Here, we report two different methods for generating melanoma patient-derived organoids (MPDOs), one is embedded in collagen gel, and the other is inlaid in Matrigel. MPDOs in Matrigel are used for assessing the therapeutic effects of anti-PD-1 antibodies (αPD-1), autochthonous tumor infiltrating lymphocytes (TILs), and small molecule compounds. MPDOs in collagen gel are used for evaluating the chemotaxis and migratory capacity of TILs. Finding: The MPDOs in collagen gel and Matrigel have similar morphology and immune cell composition to their parental melanoma tissues. MPDOs show inter- and intra-tumoral heterogeneity and contain diverse immune cells such as CD4+, CD8+ T, Treg, CD14+ monocytic, CD15+, and CD11b+ myeloid cells. The tumor microenvironment (TME) in MPDOs is highly immunosuppressive, and the lymphoid and myeloid lineages express similar levels of PD-1, PD-L1, and CTLA-4 as their parental melanoma tissues. Anti-PD-1 antibodies (αPD-1) reinvigorate CD8+ T cells and induce melanoma cell death in the MPDOs. TILs expanded by IL-2 and αPD-1 show significantly lower expression of TIM-3, better migratory capacity and infiltration of autochthonous MPDOs, and more effective killing of melanoma cells than TILs expanded by IL-2 alone or IL-2 with αCD3. A small molecule screen discovers that Navitoclax increases the cytotoxicity of TIL therapy. Interpretation: MPDOs may be used to test immune checkpoint inhibitors and cellular and targeted therapies. Funding: This work was supported by the NIH grants CA114046, CA261608, CA258113, and the Tara Miller Melanoma Foundation.

This case describes the first example of a double-barreled aorta in the setting of a common arterial trunk. Our use of annotated and segmented 3-dimensional models greatly enhanced our ability to elucidate the complex anatomy. (Level of Difficulty: Advanced.)

Background This phase 1 study evaluated PF-06753512, a vaccine-based immunotherapy regimen (PrCa VBIR), in two clinical states of prostate cancer (PC), metastatic castration-resistant PC (mCRPC) and biochemical recurrence (BCR).Methods For dose escalation, patients with mCRPC received intramuscular PrCa VBIR (adenovirus vector and plasmid DNA expressing prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA), and prostate stem cell antigen (PSCA)) with or without immune checkpoint inhibitors (ICIs, tremelimumab 40 or 80 mg with or without sasanlimab 130 or 300 mg, both subcutaneous). For dose expansion, patients with mCRPC received recommended phase 2 dose (RP2D) of PrCa VBIR plus tremelimumab 80 mg and sasanlimab 300 mg; patients with BCR received PrCa VBIR plus tremelimumab 80 mg (Cohort 1B-BCR) or tremelimumab 80 mg plus sasanlimab 130 mg (Cohort 5B-BCR) without androgen deprivation therapy (ADT). The primary endpoint was safety.Results Ninety-one patients were treated in dose escalation (mCRPC=38) and expansion (BCR=35, mCRPC=18). Overall, treatment-related and immune-related adverse events occurred in 64 (70.3%) and 39 (42.9%) patients, with fatigue (40.7%), influenza-like illness (30.8%), diarrhea (23.1%), and immune-related thyroid dysfunction (19.8%) and rash (15.4%), as the most common. In patients with mCRPC, the objective response rate (ORR, 95% CI) was 5.6% (1.2% to 15.4%) and the median radiographic progression-free survival (rPFS) was 5.6 (3.5 to not estimable) months for all; the ORR was 16.7% (3.6% to 41.4%) and 6-month rPFS rate was 45.5% (24.9% to 64.1%) for those who received RP2D with measurable disease (n=18). 7.4% of patients with mCRPC achieved a ≥50% decline in baseline PSA (PSA-50), with a median duration of 4.6 (1.2–45.2) months. In patients with BCR, 9 (25.7%) achieved PSA-50; the median duration of PSA response was 3.9 (1.9–4.2) and 10.1 (6.9–28.8) months for Cohorts 5B-BCR and 1B-BCR. Overall, antigen specific T-cell response was 88.0% to PSMA, 84.0% to PSA, and 80.0% to PSCA.Conclusions PrCa VBIR overall demonstrated safety signals similar to other ICI combination trials; significant side effects were seen in some patients with BCR. It stimulated antigen-specific immunity across all cohorts and resulted in modest antitumor activity in patients with BCR without using ADT.Trial registration number NCT02616185.

The risks of development of colorectal and endometrial cancers in individuals with Lynch syndrome (LS) are well known and have been widely studied. In recent years, the potential association of other malignancies, including prostate cancer, with LS has been considered. Decision-making regarding screening for prostate cancer in the generalized population can be complicated; accounting for the possibility of a higher risk of cancer conferred by a potential genetic predisposition confounds the creation of salient guidelines even further. Although tissue-agnostic treatment approvals have been granted to several immune checkpoint inhibitors (ICIs) for their use in the treatment of subsets of patients whose tumors exhibit high levels of microsatellite instability or high tumor mutational burden, a paucity of data exists regarding the use of ICIs in the first line treatment of patients with locally advanced prostate cancer harboring these features. A significant reduction in tumor volume in response to the combination of immune checkpoint inhibition and androgen deprivation therapy is described in this report of a male with Muir-Torre syndrome who was found to have locally advanced adenocarcinoma of the prostate. While anecdotal, the anti-tumor activity of this combination of therapy is notable and calls attention to the importance of considering further investigation of the use of immune checkpoint blockade as a primary therapeutic option in patients with localized prostate cancer.

Traditionally, atherosclerotic risk factors for cardiovascular disease and cancer are assessed using coronary artery calcium scoring. However, this neglects the impact of atherosclerotic disease more proximal to the cancer site. This study assesses whether aortoiliac atherosclerotic plaque is associated with prostate cancer. The dataset consisted of abdominopelvic CT of 93 patients with prostate cancer and 186 asymptomatic patients who underwent CT colonography as an age- and gender-matched control group. Agatston scores were measured in the abdominal aorta, common iliac, and internal iliac arteries. The scores were evaluated for associations with age, Framingham risk score, and prostate cancer-related biomarkers, including prostate-specific antigen, Gleason score, tumor location, prostatectomy, androgen deprivation therapy, mortality, and bone metastasis. The atherosclerotic plaque of prostate cancer patients did not differ from the control group (p = 0.22) and was not correlated with any of the prostate cancer-related biomarkers (p > 0.05). However, Agatston scores of abdominal plaques correlated well with age (p < 0.001) and Framingham risk scores (p = 0.002).

Cracks in reinforced concrete structures can accelerate the local depassivation of reinforcement due to carbonation. Different approaches have been proposed to account for pre-existing cracks within engineering models to predict the carbonation depth. In this study, we provide a detailed comparative analysis of different extensions available for the fib carbonation model to account for cracks, viz., crack influence factor (CIF) approaches, a diffusion-based model and the crack depth adaption. The model extensions are first validated against a dataset of lab data collected from the literature and additional experiments performed as the part of this study. The CIF approaches achieved the highest accuracy for the carbonation depth prediction when compared against lab data. The diffusion-based model was inaccurate for low CO2 concentrations. The crack depth adaption provides overly conservative results. No model was found to be best performing, and large scatter was observed between predicted and experimental values. This emphasizes the need for more detailed multi-physics-based models to achieve accurate predictions. For further comparison, service life predictions were conducted for two structural scales, viz., the whole structure and the cracked area. It is concluded that the choice of model extension and the structural scale of analysis have a large influence on predicted probability of failure.

In this work, a novel, high boost, DC-to-DC converter topology is proposed and validated. The proposed topology is an extension of the existing two leg bridge type Watkins Johnson DC to DC converter. In the proposed system, an additional leg is included along with an additional inductor and an additional capacitor. The inclusion of the third leg to the existing, two-leg version of Watkins Johnson DC–to-DC bridge type converter helps to boost further the voltage gain. This paper presents the proposed topology and a detailed analysis of the topology using the circuit model in the MATLAB SIMULINK simulation environment. An experimental prototype was also developed to validate the proposed idea. The results obtained from the simulations and the experimental prototype are also presented herein. The studies were carried out with open loop configuration.

Purpose: Comparative study of intraoperative and postoperative complications, visual outcomes, and cost-effectiveness between conventional and 4-mm manual small-incision cataract surgery with MVR blade. Methods: In total, 600 patients having nuclear sclerosis grade I–IV were operated under peribulbar anesthesia and were divided into two groups of 300 each. In group A (300), conventional small-incision cataract surgery was done, whereas in group B (300), 4-mm manual small-incision cataract surgery was performed through a 4-mm sclerocorneal tunnel. A wire vectis was passed through the 4-mm incision below the nucleus to stabilize it, and a 20-G MVR blade was introduced from 11o'clock limbus and nucleus was bisected into two halves, which were removed through main incision. Cortical wash was given, and foldable IOL was implanted. Intraoperative and postoperative complications between the two groups were compared. Postoperative visual outcome and surgically induced astigmatism between the two groups was studied. Results: The most common intraoperative complication was hyphema (11.33%) and irido-dialysis (8.00%), whereas postoperatively, striate keratopathy (36.33%) and hyphema (19.33%) were common. Short-term complications such as striate keratopathy, hyphema, and irido-dialysis were significantly more in group B, and long-term results in terms of visual outcome and surgically induced astigmatism were significantly less in group B. Conclusion: Although intraoperative and short-term postoperative complications were observed more in 4-mm manual small-incision cataract surgery, it was found to be more effective in terms of surgically induced astigmatism and final visual outcome. In addition, it is cost-effective as compared to phacoemulsification.