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Key Clinical Message Foreign body ingestion is common in pediatric age group however can be found in any age group with intellectual disability and neurodevelopmental delay. There is usually a delay in presentation and interventions following foreign body ingestion in patients with neurodevelopmental delay, leading to increased morbidity, mortality, and complications owing to inability of such patients giving relevant history. Most ingested foreign bodies naturally pass through the digestive tract without untoward effects. Only a few patients may require surgical interventions. Principle of management should be to reduce anxiety among patients and their visitors. Speedy recovery is enhanced so that they can return to their familiar environment soon. Abstract Foreign body ingestion is common in pediatric populations and may be found in any age group with intellectual disability and neurodevelopmental delay. As the patient cannot give a clear and relevant history, there is usually a delay in presentation and interventions following foreign body ingestion in patients with neurodevelopmental delay, leading to increased morbidity, mortality, and complications. Most foreign bodies pass through the digestive system without any complications, and very few require surgical intervention. The goal should be to reduce anxiety among patients and their visitors and to enhance speedy recovery so that they can return to their familiar environment soon. Here we report a case of Acute intestinal obstruction secondary to ingestion of the head portion of a doll which was managed with emergency laparotomy with enterotomy and removal of foreign body in a 16 years female with Autism Spectrum Disorder.

IntroductionDry eye disease (DED) is multifactorial and characterized by a loss of tear film homeostasis that causes a cycle of tear film instability, tear hyperosmolarity, and inflammation. While artificial tears are the traditional mainstay of treatment, addressing the underlying pathophysiology could relieve symptoms and prevent progression. Increasing evidence indicates a role for oral nutritional supplementation in multiple ophthalmic diseases, including DED. Lutein, zeaxanthin, curcumin, and vitamin D3 have demonstrated protective and anti-inflammatory properties in ocular models. This prospective, randomized, double-blind, parallel, placebo-controlled study evaluated the efficacy and safety of a proprietary blend of lutein, zeaxanthin isomers, curcumin, and vitamin D3 (LCD) as a daily supplement in adult participants with DED.MethodsParticipants were randomized to receive one LCD supplement capsule (lutein 20 mg, zeaxanthin isomers 4 mg, curcumin 200 mg curcuminoids, and vitamin D3 600 IU) or placebo per day for 8 weeks (LCD, n=77; placebo, n=78). Primary outcomes were changes in tear volume (Schirmer’s test) and ocular symptoms (Ocular Surface Disease Index [OSDI]).ResultsThe study met its primary endpoints: the LCD group demonstrated significantly better Schirmer’s test scores and improvement in overall OSDI score, versus placebo, at Day 56 (p

Rationale & Objective: The incidence of arrhythmia varies by time of day. How this affects individuals on maintenance dialysis is uncertain. Our objective was to quantify the relationship of arrhythmia with the time of day and timing of dialysis. Study Design: Secondary analysis of the Monitoring in Dialysis study, a multicenter prospective cohort study. Settings & Participants: Loop recorders were implanted for continuous cardiac monitoring in 66 participants on maintenance dialysis with a follow up of 6 months. Exposure: Time of day based on 6-hour intervals. Outcomes: Event rates of clinically significant arrhythmia. Analytical Approach: Negative binomial mixed effects regression models for repeated measures were used to evaluate data from the Monitoring in Dialysis study for differences in diurnal patterns of clinically significant arrhythmia among those with end-stage kidney disease with heart failure and end-stage kidney disease alone. We additionally analyzed rates according to presence of heart failure, time of dialysis shift, and dialysis versus nondialysis day. Results: Rates of clinically significant arrhythmia peaked between 12:00 AM and 5:59 AM and were more than 1.5-fold as frequent during this interval than the rest of the day. In contrast, variations in atrial fibrillation peaked between 6:00 AM and 11:59 AM, but variations across the day were qualitatively small. Clinically significant arrhythmia occurred at numerically higher rate in individuals with end-stage kidney disease and heart failure (5.9 events/mo; 95% CI, 1.3-26.8) than those without heart failure (4.0 events/mo; 95% CI, 0.9-17.9). Although differences in overall rate were not significant, their periodicity was significantly different (P

Urinary biomarkers are a promising diagnostic modality whose role was explored in nephrotic syndrome (NS). We estimated urinary apolipoprotein A1 (Apo A1) and neutrophil gelatinase-associated lipocalin (NGAL) in children with first-episode NS (FENS) and controls with a longitudinal follow-up to see the serial changes during remission. The study groups comprised 35 children with FENS and an equal number of age- and sex-matched controls. Patients were followed up at regular intervals, and 32 patients were classified as having steroid-sensitive NS (SSNS) and 3 as having steroid-resistant NS (SRNS). The mean follow-up period was 8.7 ± 4.2 months. Three patients in the SSNS group were labeled as having frequent relapses or steroid-dependent disease during follow-up. Of the three children with SRNS, two had minimal changes in the disease and one had idiopathic membranous nephropathy. The levels of Apo A1:creatinine, NGAL:creatinine, and spot urinary protein:urinary creatinine ratios were significantly higher in children with FENS compared with controls. The levels of the urine biomarkers decreased significantly at subsequent follow-up with remission. The Apo A1 and NGAL levels in SSNS patients were significantly high compared with both the controls and FENS patients. Urinary Apo A1 levels in SRNS patients were lower at initial presentation. This longitudinal study revealed changes in the urinary Apo A1 and NGAL in NS over the course of the disease.

While machine learning (ML) has been quite successful in the field of structural health monitoring (SHM), its practical implementation has been limited. This is because ML model training requires data containing a variety of distinct instances of damage captured from a real structure and the experimental generation of such data is challenging. One way to tackle this issue is by generating training data through numerical simulations. However, simulated data cannot capture the bias and variance of experimental uncertainty. To overcome this problem, this work proposes a deep-learning-based domain transformation method for transforming simulated data to the experimental domain. Use of this technique has been demonstrated for debonding location and size predictions of stiffened panels using a vibration-based method. The results are satisfactory for both debonding location and size prediction. This domain transformation method can be used in any field in which experimental data for training machine-learning models is scarce.

Abstract Background Osteopathia is a benign entity characterized by linear densities along the diaphysis and metaphysis of the longitudinal axes of the long bone. Parathyroid adenoma is a non-malignant parathyroid gland tumor characterized by increased parathormone levels, causing defecting calcium levels leading to multiple brown tumors, renal calculi, bone pains, polyuria, and arrhythmias in the patient. The coexistence of parathyroid adenoma with osteopathia striata has not been reported yet in the literature. To our knowledge, this is the first case of its kind. Case presentation An 18-year-old male patient presented to our institution with the complaint of genu valgum deformity in his right knee and was admitted for corrective surgery. While undergoing a preoperative evaluation, we came across multiple focal, lytic lesions in his radiographs and an atypical finding of osteopathia striata in his long bones. Further examination led us to the findings of cranial sclerosis and acro-osteolysis of distal phalanges. The tumor, whose catalyst was unclear, directed us toward an ultrasonographic analysis of the patient’s neck, leading us to a solitary parathyroid adenoma. Conclusions Radiological examinations played a very crucial role in the diagnosis of this condition. Though the reason behind osteopathia and the parathyroid lesion in this patient remains unknown, this presentation remains an exceptional and never-reported case of parathyroid adenoma and associated brown tumors in a patient with osteopathia striata.

ABSTRACTRhizopus delemar, an opportunistic fungal pathogen, causes a highly fatal disease, mucormycosis. Spore germination is a crucial mechanism for disease pathogenesis. Thus, exploring the molecular mechanisms of fungal germination would underpin our knowledge of such transformation and, in turn, help control mucormycosis. To gain insight into the developmental process particularly associated with cell wall modification and synthesis, weighted gene co-expression network analysis (WGCNA) was performed including both coding and non-coding transcripts identified in the current study, to find out the module of interest in the germination stages. The module-trait relationship identified a particular module to have a high correlation only at the resting phase and further analysis revealed the module to be enriched for protein phosphorylation, carbohydrate metabolic process, and cellular response to stimulus. Moreover, co-expression network analysis of highly connected nodes revealed cell wall modifying enzymes, especially those involved in mannosylation, chitin-glucan crosslinking, and polygalacturonase activities co-expressing and interacting with the novel lncRNAs among which some of them predicted to be endogenous target mimic (eTM) lncRNAs. Hence, the present study provides an insight into the onset of spore germination and the information on the novel non-coding transcripts with key cell wall–related enzymes as potential targets against mucormycosis.

Abstract P2Y12 inhibitors (i.e., clopidogrel, prasugrel, or ticagrelor) are effective at reducing adverse cardiovascular outcomes post‐revascularization in coronary artery disease (CAD). However, the choice of a specific P2Y12 inhibitor may vary according to the patient's characteristics, and trends in the use of different P2Y12 inhibitors are not well studied in real‐world settings. The objective of this study is to determine trends in the prescription patterns of P2Y12 inhibitors in patients with CAD. We studied 137,073 patients with CAD cross‐sectionally using the IBM MarketScan database (2013–2018). Patients with CAD prescribed P2Y12 inhibitors within 14 days of index revascularization were included to compare the utilization of P2Y12 inhibitors based on age and clinical characteristics. There were differences in prescription patterns by age. Among patients aged less than or equal to 65 years (N = 92,734), a continuously increased utilization of ticagrelor was observed from 13.7% to 45.6% replacing clopidogrel as the most prescribed medication by 2018. Similarly, ticagrelor was the choice of drug among patients undergoing percutaneous coronary intervention. Among the patients at high bleeding risk, clopidogrel remained the most prescribed medication with use in 50.6% of patients in 2018 in patients aged less than or equal to 65 years. Contrarily, among the older adults with age 65 or above (N = 44,339), although ticagrelor use increased with time, clopidogrel remained the most utilized drug and was used by 66.2% of patients in 2018. Additionally, clopidogrel was the preferred medication among patients with stroke history. With the increasing use of ticagrelor in real‐world practice, further research is needed to observe its impact on cardiovascular outcomes.

Abstract Due to waning immunity following primary immunization with COVID-19 vaccines, booster doses may be required. The present study assessed a heterologous booster of SII-NVX-CoV2373 (spike protein vaccine) in adults primed with viral vector and inactivated vaccines. In this Phase 3, observer-blind, randomized, active controlled study, a total of 372 adults primed with two doses of ChAdOx1 nCoV-19 (n = 186) or BBV152 (n = 186) at least six months ago, were randomized to receive a booster of SII-NVX-CoV2373 or control vaccine (homologous booster of ChAdOx1 nCoV-19 or BBV152). Anti-S IgG and neutralizing antibodies (nAbs) were assessed at days 1, 29, and 181. Non-inferiority (NI) of SII-NVX-CoV2373 to the control vaccine was assessed based on the ratio of geometric mean ELISA units (GMEU) of anti-S IgG and geometric mean titers (GMT) of nAbs (NI margin > 0.67) as well as seroresponse (≥ 2 fold-rise in titers) (NI margin −10%) at day 29. Safety was assessed throughout the study period. In both the ChAdOx1 nCoV-19 prime and BBV152 prime cohorts, 186 participants each received the study vaccines. In the ChAdOx1 nCoV-19 prime cohort, the GMEU ratio was 2.05 (95% CI 1.73, 2.43) and the GMT ratio was 1.89 (95% CI 1.55, 2.32) whereas the difference in the proportion of seroresponse was 49.32% (95% CI 36.49, 60.45) for anti-S IgG and 15% (95% CI 5.65, 25.05) for nAbs on day 29. In the BBV152 prime cohort, the GMEU ratio was 5.12 (95% CI 4.20, 6.24) and the GMT ratio was 4.80 (95% CI 3.76, 6.12) whereas the difference in the proportion of seroresponse was 74.08% (95% CI 63.24, 82.17) for anti-S IgG and 24.71% (95% CI 16.26, 34.62) for nAbs on day 29. The non-inferiority of SII-NVX-CoV2373 booster to the control vaccine for each prime cohort was met. SII-NVX-CoV2373 booster showed significantly higher immune responses than BBV152 homologous booster. On day 181, seroresponse rates were ≥ 70% in all the groups for both nAbs and anti-S IgG. Solicited adverse events reported were transient and mostly mild in severity in all the groups. No causally related SAE was reported. SII-NVX-CoV2373 as a heterologous booster induced non-inferior immune responses as compared to homologous boosters in adults primed with ChAdOx1 nCoV-19 and BBV152. SII-NVX-CoV2373 showed a numerically higher boosting effect than homologous boosters. The vaccine was also safe and well tolerated.

Abstract Mucopolysaccharidosis type IIIB (MPS IIIB) is a rare and devastating childhood-onset lysosomal storage disease caused by complete loss of function of the lysosomal hydrolase α-N-acetylglucosaminidase. The lack of functional enzyme in MPS IIIB patients leads to the progressive accumulation of heparan sulfate throughout the body and triggers a cascade of neuroinflammatory and other biochemical processes ultimately resulting in severe mental impairment and early death in adolescence or young adulthood. The low prevalence and severity of the disease has necessitated the use of animal models to improve our knowledge of the pathophysiology and for the development of therapeutic treatments. In this study, we took a systematic approach to characterizing a classical mouse model of MPS IIIB. Using a series of histological, biochemical, proteomic and behavioral assays, we tested MPS IIIB mice at two stages: during the pre-symptomatic and early symptomatic phases of disease development, in order to validate previously described phenotypes, explore new mechanisms of disease pathology and uncover biomarkers for MPS IIIB. Along with previous findings, this study helps provide a deeper understanding of the pathology landscape of this rare disease with high unmet medical need and serves as an important resource to the scientific community.

Zika virus (ZIKV; family, Flaviviridae), which causes congenital Zika syndrome, Guillain-Barré Syndrome, and other severe diseases, is transmitted mainly by mosquitoes; however, the virus can be transmitted through other routes. Among the three structural and seven nonstructural proteins, the surface envelope (E) protein of ZIKV plays a critical role in viral entry and pathogenesis, making it a key target for the development of effective entry inhibitors. This review article describes the life cycle, genome, and encoded proteins of ZIKV, illustrates the structure and function of the ZIKV E protein, summarizes E protein-targeting entry inhibitors (with a focus on those based on natural products and small molecules), and highlights challenges that may potentially hinder the development of effective inhibitors of ZIKV infection. Overall, the article will provide useful guidance for further development of safe and potent ZIKV entry inhibitors targeting the viral E protein.

We report a transformative epoxy system with a microalgae-derived bio-binder from hydrothermal liquefaction processing (HTL). The obtained bio-binder not only served as a curing agent for conventional epoxy resin (e.g., EPON 862), but also acted as a modifying agent to enhance the thermal and mechanical properties of the conventional epoxy resin. This game-changing epoxy/bio-binder system outperformed the conventional epoxy/hardener system in thermal stability and mechanical properties. Compared to the commercial EPON 862/EPIKURE W epoxy product, our epoxy/bio-binder system (35 wt.% bio-binder addition with respect to the epoxy) increased the temperature of 60% weight loss from 394 °C to 428 °C and the temperature of maximum decomposition rate from 382 °C to 413 °C, while the tensile, flexural, and impact performance of the cured epoxy improved in all cases by up to 64%. Our research could significantly impact the USD 38.2 billion global market of the epoxy-related industry by not only providing better thermal and mechanical performance of epoxy-based composite materials, but also simultaneously reducing the carbon footprint from the epoxy industry and relieving waste epoxy pollution.

The integration of nanocomposite thin films with combined multifunctionalities on flexible substrates is desired for flexible device design and applications. For example, combined plasmonic and magnetic properties could lead to unique optical switchable magnetic devices and sensors. In this work, a multiphase TiN-Au-Ni nanocomposite system with core–shell-like Au-Ni nanopillars embedded in a TiN matrix has been demonstrated on flexible mica substrates. The three-phase nanocomposite film has been compared with its single metal nanocomposite counterparts, i.e., TiN-Au and TiN-Ni. Magnetic measurement results suggest that both TiN-Au-Ni/mica and TiN-Ni/mica present room-temperature ferromagnetic property. Tunable plasmonic property has been achieved by varying the metallic component of the nanocomposite films. The cyclic bending test was performed to verify the property reliability of the flexible nanocomposite thin films upon bending. This work opens a new path for integrating complex nitride-based nanocomposite designs on mica towards multifunctional flexible nanodevice applications.

In this investigation, a three-dimensional (3D) axisymmetric potential well-based nonlinear piezoelectric energy harvester is proposed to increase the broadband frequency response under low-strength planar external excitation. Here, a two-dimensional (2D) planar bi-stable Duffing potential is generalized into three dimensions by utilizing axial symmetry. The resulting axisymmetric potential well has infinitely many stable equilibria and one unstable equilibria at the highest point of the potential barrier for this cantilevered oscillator. Dynamics of such a 3D piezoelectric harvester with axisymmetric multi-stability are studied under planar circular excitation motion. Bifurcations of average power harvested from the two pairs of piezoelectric patches are presented against the frequency variation. The results show the presence of several branches of large-amplitude cross-well type period-1 and subharmonic solutions. Subharmonics involved in such responses are verified from the Fourier spectra of the solutions. The identified subharmonic solutions perform interesting patterns of curvilinear oscillations, which do not cross the potential barrier through its highest point. These solutions can completely or partially avoid the climbing of the potential barrier, thereby requiring low input excitation energy for barrier crossing. The influence of excitation amplitude on the bifurcations of normalized power is also investigated. Through multiple solution branches of subharmonic solutions, producing comparable power to the period-1 branch, broadband frequency response characteristics of such a 3D axisymmetically multi-stable harvester are highlighted.

This case report discusses the management of multiple myeloma in a 59-year-old male patient through an integrative approach of Ayurvedic and conventional medical care. The patient presented with symptoms of pain in ribs, fatigue, nausea, weight loss, and mental stress. After undergoing chemotherapy and steroid therapy, the patient opted for Ayurvedic treatment instead of a recommended bone marrow transplant. Ayurvedic examination revealed imbalances in Vata and Pitta doshas, affecting various body tissues and mental state. The Ayurvedic regimen led to the recovery of the patient without adverse effects. This case highlights the role of Ayurvedic medication in managing multiple myeloma, warranting further research and clinical trials for broader validation.

Globalization of Ayurveda is a continuous process. It happens due to committed collaboration of expert vaidyas from India and abroad, professionals from different countries, pharmaceutical suppliers, and patients. The obstacles to practise, regulate and educate Ayurveda, differ from country to country; however there are some common threads. The International Delegates Assembly through the platform of World Ayurveda Congress strives to bring the stakeholders together biannually to discuss the issues and find solutions. The present narrative sheds light on the objectives, status and expectations of the stakeholders and provides insights into the process.

A series of Eu3+-doped of CaAlSiO4F red-emitting phosphors for different concentrations were successfully synthesized by using high temperature solid state diffusion method. The phase identification of the prepared phosphor was recorded using x-ray diffraction (XRD). In PL study, the emission peak of prepared phosphor was located at 595 nm and 618 nm due to 5D0 → 7F1 and 5D0 → 7F2 transitions at excitation of 257 nm, 395 nm and 465 nm. Morphological behaviour of prepared sample was analyzed by using scanning electron microscope (SEM). Commission de l'Eclairage chromaticity (CIE) coordinates were analyzed based on the PL emission spectra of the series CaAlSiO4F: Eu3+ activated phosphor. Therefore, these possible outcomes indicate that the CaAlSiO4F: Eu3+ products have great potential applications in solid state lighting industry.

Providing food for the growing population is a challenging task, however, with historical agricultural practices, we can’t meet the food requirement of the world population. We are in the need to adopt modern technology to overcome adverse climatic and cultural challenges, which are faced by current generation, that is Artificial Intelligence (AI). AI is the booming technology in the agriculture, which uses different sensors and neural networks and uses resources minimally based on need and predict the coming obstacles, which causes huge loss to crop. This review explain is, various applications of AI in the sustainable agriculture for crop managemen by overcoming realtime challenges and importance of AI in agriculture by comparing with traditional methods.

Background The rapid evolution of artificial intelligence (AI) in conjunction with recent updates in dual antiplatelet therapy (DAPT) management guidelines emphasizes the necessity for innovative models to predict ischemic or bleeding events after drug‐eluting stent implantation. Leveraging AI for dynamic prediction has the potential to revolutionize risk stratification and provide personalized decision support for DAPT management. Methods and Results We developed and validated a new AI‐based pipeline using retrospective data of drug‐eluting stent‐treated patients, sourced from the Cerner Health Facts data set (n=98 236) and Optum's de‐identified Clinformatics Data Mart Database (n=9978). The 36 months following drug‐eluting stent implantation were designated as our primary forecasting interval, further segmented into 6 sequential prediction windows. We evaluated 5 distinct AI algorithms for their precision in predicting ischemic and bleeding risks. Model discriminative accuracy was assessed using the area under the receiver operating characteristic curve, among other metrics. The weighted light gradient boosting machine stood out as the preeminent model, thus earning its place as our AI‐DAPT model. The AI‐DAPT demonstrated peak accuracy in the 30 to 36 months window, charting an area under the receiver operating characteristic curve of 90% [95% CI, 88%–92%] for ischemia and 84% [95% CI, 82%–87%] for bleeding predictions. Conclusions Our AI‐DAPT excels in formulating iterative, refined dynamic predictions by assimilating ongoing updates from patients' clinical profiles, holding value as a novel smart clinical tool to facilitate optimal DAPT duration management with high accuracy and adaptability.

ObjectivePatients living with rheumatologic diseases on disease-modifying antirheumatic drugs (DMARD) are at an increased risk of developing tuberculosis (TB). Current guidelines recommend screening for latent tuberculosis infection (LTBI) before initiating DMARD. However, data is lacking on the value of yearly screening for LTBI.MethodsA retrospective chart review was conducted on adult patients (≥ 18 years) with rheumatologic disease on DMARD followed longitudinally in the outpatient rheumatology clinics between 2017-2021. Collected data included patient demographics, rheumatologic diagnosis, medications, TB-related risk factors, interferon gamma release assay (IGRA) results, LTBI diagnosis and treatment. Descriptive statistics were performed.ResultsAmong 339 patients, 81 (23.9%) were male, 259 (76.4%) were white, and 93 (27.5%) were Latinx. Inflammatory arthritis (84.1%) was the most common rheumatic diagnosis. Common DMARD were JAK inhibitors (19.2%), TNF-alpha inhibitors (18.9%), and IL-17 A inhibitors (18.0%). Only 2 patients at baseline had positive IGRA, and both had a history of treated LTBI. Positive IGRA tests were recorded in 1 (0.7%), 3 (1.8%), 3 (1.3%), and 3 (1.1%) in the years 2018, 2019, 2020, and 2021, respectively. Four patients converted from negative to positive during serial yearly IGRA testing. After reviewing the IGRA test and TB risk factors, only one patient was considered newly diagnosed with LTBI, requiring 4 months of rifampin.ConclusionIn a non-endemic area, serial IGRA testing of low-risk patients on DMARD yielded very low rate of newly diagnosed LTBI. A targeted LTBI screening based on TB-related risk factors should be performed prior to IGRA testing rather than universal yearly screening in a non-endemic setting.

Abstract Large, open‐gate transistors made from metal nanoparticle arrays offer possibilities to build new electronic devices, such as sensors. A nanoparticle necklace network (N3) of Au particles from 300 K to cryogenic temperatures exhibit a nonohmic I–Vd behavior, I ≈ (Vd–VT)ζ, where VT is a conduction gap and ζ is a constant critical exponent. The conduction gap in N3, made from disordered networks of 1D chains of 10 nm diameter Au particles exhibits room temperature (RT) gating. Although the I–Vd behavior at RT is identical to Coulomb blockade, the conduction is modulated by field‐assisted tunneling exhibiting classical critical behavior. In this study, based on three results, invariance of VT on gating, invariance of VT on temperature, and zero–bias conductance, a sharp transition temperature at ≈140 K is discovered where the conduction mechanism switches from Coulomb blockade to classical critical percolation behavior. The N3 architecture allows the reconciliation of the Coulomb blockade versus activation process as a sharp thermal transition to serve as a model system to study the exotic behavior in nanogranular‐metallic materials. The novel global critical behavior to local Coulomb blockade governed transition in these N3 architectures may potentially lead to novel sensors and biosensors.

Continuous evolution in bacterial strains confines utility of frontline antibacterial agents due to development of multiple resistance mechanisms. Especially gram-negative multidrug bacterial resistance is foremost important topic of concern. The current manuscript details the development of different synthetic strategies for stereo-controlled synthesis of WCK 5153, a specific and high-affinity PBP2 binding, novel β-lactam enhancer (BLE) discovered through systematic structure activity (SAR) relationship. Earlier the synthesis of parent i.e. diastereomeric mixture WCK 5133 achieved from benzyl amine and chloromethyl trimethyl silane. Subsequently preparative HPLC helped to separate the diastereomers as WCK 5153 and WCK 5154 from parent WCK 5133. Based on potency differences synthesis of side chain for chiral isomer WCK 5153 accomplished through reaction of methyl itaconate and (R)-phenyl ethylamine to get optically pure methyl 5-oxo-1-((R)-1-phenylethyl) pyrrolidine-3-carboxylate. For removing the hurdle of chromatographic separation, crystallization of diastereomeric side chain; at acid intermediate, 5-oxo-1-((R)-1-phenylethyl)-R,S)-pyrrolidine-3-carboxylic acid was achieved. Reaction of Itaconic acid and (R)-phenyl ethylamine in methanol at 80 °C created an opportunity for separation through crystallization. This methodology completes the stereoselective synthesis of requisite hydrazide side chain in 11-steps.

Neurodegenerative Alzheimer's disease (AD) leads to cognitive and behavioral decline. The current crop of FDA-approved treatments for AD can only reduce symptoms and postpone the disease's progression by facilitating communication between neurons in brain of AD patient. Any potential treatment for Alzheimer's should reduce inflammation, prevent acetylcholine hydrolysis, and act as an antioxidant. Traditional treatments, such as acetylcholinesterase inhibitors, frequently fall short of their intended effects due to solubility, bioavailability, and blood–brain barrier (BBB) bridging. Therapy failure is frequently caused due to inadequate pharmacokinetics and pharmacodynamics of commonly used medications. Systemic delivery to the central nervous system using cationic nanosized carriers is a promising area of research. Adsorption-mediated translocation refers to their ability to interrelate electrostatically with cell membranes that are negatively charged and cross the BBB through endocytosis or adsorption-mediated transcytosis. Cationic nanopharmaceuticals (CNPs) showed potential for treating AD in-vivo following systemic administration. Adsorption-mediated transcytosis across the BBB can be easily facilitated by cationic lipids, increasing mucoadhesion in the nasal cavity by enhancing electrostatic interactions with mucus. Nano-cationic formulations' dimensions, elasticity, hydrophobicity, surface charge, chemistry, and morphology significantly impact their in-vivo journey. In this review the current state of cationic nanoformulation for targeting AD and promising future directions for this approach have been briefly discussed with dricption that fill the gap in knowledge.

The unique thermokinetics of laser-powder bed fusion additive manufacturing (L-PBFAM) has been exploited for development of a novel high-strength Al-Ni-Ti-Zr-Mn alloy. The addition of 0.5 wt% Mn leads to extraordinary improvement in ultimate tensile strength (502 MPa) and work hardening due to the activation of two Mn-induced strengthening mechanisms. First, by a bimodal particle strengthening effect due to Al31Mn6Ni12 nano-quasi-crystal particles rejected in inter-dendritic spaces and fibrous Al3Ni eutectic dendritic channels, which predominately contributes to the strength improvement, and second by solid solution strengthening from remaining Mn entrapped in Al. These mechanisms supplement the particle strengthening effect imparted by coherent and incoherent Al3(Ti,Zr) co-precipitates present at melt pool boundaries, dislocation strengthening due to solidification induced strain, and Hall-Petch and backstress strengthening effect due to heterogenous grain size distribution occurring at various length scales. The solidification dynamics and hierarchical heat distribution that are associated with L-PBFAM resulted in complex spatial variations in these strengthening phenomena and were investigated via a high-throughput multiscale structure–property correlation that involved thermokinetic simulation, X-ray diffraction, high-resolution nanoindentation mapping, and site-specific transmission electron microscopy of the alloy.

As we navigate the modern era, the intersection of time-honoured natural remedies and contemporary scientific approaches forms a burgeoning frontier in global healthcare. For generations, natural products have been foundational to health solutions, serving as the primary healthcare choice for 80% to 85% of the world's population. These herbal-based, nature-derived substances, significant across diverse geographies, necessitate a renewed emphasis on enhancing their quality, efficacy, and safety. In the current century, the advent of biogenic phytonanoparticles has emerged as an innovative therapeutic conduit, perfectly aligning with principles of environmental safety and scientific ingenuity. Utilizing green chemistry techniques, a spectrum of metallic nanoparticles including elements such as copper, silver, iron, zinc, and titanium oxide can be produced with attributes of non-toxicity, sustainability, and economic efficiency. Sophisticated herb-mediated processes yield an array of plant-originated nanomaterials, each demonstrating unique physical, chemical, and biological characteristics. These attributes herald new therapeutic potentials, encompassing antioxidants, anti-aging applications, and more. Modern technology further accelerates the synthesis of natural products within laboratory settings, providing an efficient alternative to conventional isolation methods. The collaboration between traditional wisdom and advanced methodologies now signals a new epoch in healthcare. Here, the augmentation of traditional medicine is realized through rigorous scientific examination. By intertwining ethical considerations, cutting-edge technology, and natural philosophy, the realms of biogenic phytonanoparticles and traditional medicine forge promising pathways for research, development, and healing. The narrative of this seamless integration marks an exciting evolution in healthcare, where the fusion of sustainability and innovation crafts a future filled with endless possibilities for human well-being. The research in the development of metallic nanoparticles is crucial for unlocking their potential in revolutionizing fields such as medicine, catalysis, and electronics, promising groundbreaking applications with enhanced efficiency and tailored functionalities in future technologies. This exploration is essential for harnessing the unique properties of metallic nanoparticles to address pressing challenges and advance innovations across diverse scientific and industrial domains.

Abstract Molybdenum supported on zeolites has been extensively studied as a catalyst for methane dehydroaromatization. Despite significant progress, the actual intermediates and particularly the first C-C bond formation have not yet been elucidated. Herein we report evolution of methyl radicals during non-oxidative methane activation over molybdenum single sites, which leads selectively to value-added chemicals. Operando X-ray absorption spectroscopy and online synchrotron vacuum ultraviolet photoionization mass spectroscopy in combination with electron microscopy and density functional theory calculations reveal the essential role of molybdenum single sites in the generation of methyl radicals and that the formation rate of methyl radicals is linearly correlated with the number of molybdenum single sites. Methyl radicals transform to ethane in the gas phase, which readily dehydrogenates to ethylene in the absence of zeolites. This is essentially similar to the reaction pathway over the previously reported SiO2 lattice-confined single site iron catalyst. However, the availability of a zeolite, either in a physical mixture or as a support, directs the subsequent reaction pathway towards aromatization within the zeolite confined pores, resulting in benzene as the dominant hydrocarbon product. The findings reveal that methyl radical chemistry could be a general feature for metal single site catalysis regardless of the support (either zeolites MCM-22 and ZSM-5 or SiO2) whereas the reaction over aggregated molybdenum carbide nanoparticles likely facilitates carbon deposition through surface C-C coupling. These findings allow furthering the fundamental insights into non-oxidative methane conversion to value-added chemicals.

Abstract Hypercholesterolemia is often correlated with obesity which is considered a risk factor for various cancers. With the growing population of hypercholesterolemic individuals, there is a need to understand the role of increased circulatory cholesterol or dietary cholesterol intake towards cancer etiology and pathology. Recently, abnormality in the blood cholesterol level of colon cancer patients has been reported. In the present study, we demonstrate that alteration in cholesterol levels (through a high-cholesterol or high-fat diet) increases the incidence of chemical carcinogen-induced colon polyp occurrence and tumor progression in mice. At the cellular level, low-density lipoprotein cholesterol (LDLc) and high-density lipoprotein cholesterol (HDLc) promote colon cancer cell proliferation by tuning the cellular glucose and lipid metabolism. Mechanistically, supplementation of LDLc or HDLc promotes cellular glucose uptake, and utilization, thereby, causing an increase in lactate production by colon cancer cells. Moreover, LDLc or HDLc upregulates aerobic glycolysis, causing an increase in total ATP production through glycolysis, and a decrease in ATP generation by OXPHOS. Interestingly, the shift in the metabolic status towards a more glycolytic phenotype upon the availability of cholesterol supports rapid cell proliferation. Additionally, an alteration in the expression of the molecules involved in cholesterol uptake along with the increase in lipid and cholesterol accumulation was observed in cells supplemented with LDLc or HDLc. These results indicate that colon cancer cells directly utilize the cholesterol associated with LDLc or HDLc. Moreover, targeting glucose metabolism through LDH inhibitor (oxamate) drastically abrogates the cellular proliferation induced by LDLc or HDLc. Collectively, we illustrate the vital role of cholesterol in regulating the cellular glucose and lipid metabolism of cancer cells and its direct effect on the colon tumorigenesis. Graphical Abstract

This article highlights the significance of measuring plateau pressure in spontaneously breathing patients as it provides valuable information about PMI (Pmusc Index), which serves as a surrogate for the patient's efforts during mechanical ventilation. The PMI value obtained from the difference between the end-inspiratory occlusion plateau pressure and the airway pressure before the occlusion (PEEP + PS) enables clinicians to estimate the patient's inspiratory effort accurately. The accurate measurement of patient efforts is crucial in optimizing pressure support during lung protective weaning strategies. By titrating pressure support based on PMI values, clinicians can provide personalized care to patients, reducing the risk of ventilator-induced lung injury and enhancing the likelihood of successful weaning.

Abstract This study collected evidence on the use of early sown wheat varieties and complementary zero tillage technologies in Northwest India. Detailed information on farmers’ knowledge, adoption decisions, personal experience, and perceptions of early sown wheat and zero tillage technologies were collected at the household level using different survey tools. Additional information on agricultural practices during the Rabi Season 2021/22 were collected at the plot level and geocoded. Overall, the dataset comprises responses from 1206 wheat farmers in 70 villages across 7 districts in Punjab and Haryana that were collected between September and October 2022. The villages were selected using stratified random sampling based on a sampling frame of 1722 communities that had been identified as predominantly wheat growing areas based on remote-sensing data from satellite images. The dataset provides rich information that may be used for assessing the diffusion and impact of recently developed wheat varieties designed for early sowing, identifying barriers to the wider adoption of these technologies, and informing policy making aimed at improving adoption and usage decisions of agricultural innovations.

Background: Otomycosis is a superficial mycotic infection of the external auditory canal. Clinical presentation, along with otoscopic findings, is sufficient to make the diagnosis in most of the cases. Treatment includes aural cleaning followed by the instillation of anti-fungal ear drops. In the recent years, there has been an increasing trend of antifungal resistance for the commonly used antifungals such as fluconazole and clotrimazole. Drug sensitivity patterns have also shown variability from one region to another. Aims and Objectives: To evaluate the clinico-mycological profile along with antifungal susceptibility pattern and treatment outcome of primary otomycosis. Materials and Methods: A total of 230 clinically diagnosed patients of primary otomycosis were included in this prospective study. Microbiological causes were evaluated by KOH wet mount and culture of samples collected from external auditory meatus using sterile swabs. Fungal culture was done on Sabouraud dextrose agar with chloramphenicol at 25°C and 37°C. Anti-fungal susceptibility test was done by disk diffusion method using medium Muller-Hilton agar with glucose and methylene blue. All the patients were treated with the removal of fungal debris with topical clotrimazole instillation and were followed up after 7 days. Non-responders were treated with topical itraconazole. Results: Male-to-female ratio in study participants was 1:1.3. The most frequently observed risk factor was the instillation of oil in the ear (20%). Ear itching was the commonest symptom (70.9%). Positive fungal growth was seen in 203 (88.3%) cases. Aspergillus was present in 185 (91.1%) cases, followed by Candida in 18 (8.9%) cases. Voriconazole had the highest sensitivity followed by itraconazole. 167 (83.3%) patients responded to primary treatment (topical Clotrimazole), 36 (16.7%) patients were non-responders. Conclusion: All the clinically suspected patients should be evaluated for fungal positivity, which may further guide in the selection of appropriate anti-fungal agents. Awareness regarding the predisposing factors for otomycosis in the general population may result in a significant drop in the incidence of otomycosis.

Background Local wound care in perianal burn wounds is difficult owing to the risk of contamination from fecal soiling. The problem is aggravated in small children and bedridden critical patients who are unable to convey passage of stools. We used diaper-based wound care to reduce contamination.

Abstract Background Neurofibromatosis type 1 is an autosomal dominant disorder with an incidence of 1 in 3000 births. Neurofibromas can occur anywhere in the body. Of all the head and neck tumours parapharyngeal space tumours constitute 0.5%. Neurofibromas can constitute about 9% of all the neurogenic tumours (41%) of the parapharyngeal space. Prevalence of nasal obstruction and obstructive sleep-disordered breathing symptoms due to Plexiform neurofibroma in Neurofibromatosis type 1 is rare amounting to less than 0.5% of cases of parapharyngeal space tumours. Case presentation We present a case report of a 24-year-old female patient of Neurofibromatosis type 1 who presented with obstructive sleep-disordered breathing symptoms due to Plexiform neurofibroma in the parapharyngeal space. She had complaints of progressive nasal obstruction with associated snoring, disturbed sleep, and daytime somnolence without any significantly large external neck swelling. She underwent excision of the right parapharyngeal tumor by combined trans parotid and transcervical approach. After histopathological examination, a diagnosis of Plexiform neurofibroma was made. On 1-year follow-up, she is doing well without any recurrence and her presenting symptoms of obstructive sleep-disordered breathing symptoms had improved. Conclusion The symptoms of obstructive sleep-disordered breathing symptoms need to be kept in mind while evaluating such patients and careful attention needs to be given to the patients who report disturbed sleep. Neurofibromatosis type 1 is a multi-system disease which needs holistic care and approach. Such patients should be offered symptomatic treatment and leading questions on the quality of sleep should be asked. Any treatable cause of disturbed sleep like organic sleep disorder should be treated promptly in such patients.

With the worldwide awareness of sustainability, biomass-derived carbon electrode materials for supercapacitors have attracted growing attention. In this research, for the first time, we explored the feasibility of making use of the carbon byproduct from hydrothermal liquefaction (HTL) of microalgae, termed herein as algae-derived carbon (ADC), to prepare sustainable carbon electrode materials for high-performance supercapacitor development. Specifically, we investigated carbon activation with a variety of activating reagents as well as N- and Fe-doping of the obtained ADC with the intention to enhance its electrochemical performance. We characterized the structure of the activated and doped ADCs using scanning electron microscope (SEM), Raman spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and BET surface area and pore analysis, and correlated the ADCs’ structure with their electrochemical performance as evaluated using cyclic voltammetry (CV), galvanostatic charge/discharge (GCD), impedance, and cycle stability through an assembled symmetric two-electrode cell with 1 M H2SO4 as electrolyte. It was found that the ADC that is activated using KOH (KOH-ADC) showed the best electrochemical performance, and its specific capacitance was 14.1-fold larger with respect to that of the raw ADC and reached 234.5 F/g in the GCD test at a current density of 0.5 A/g. The KOH-ADC also demonstrated excellent capacitance retention (97% after 10,000 cycles at a high current density of 10 A/g) for stable long-term operations. This research pointed out a promising direction to develop sustainable electrode materials for supercapacitors from the carbon byproduct produced after HTL processing of algae.

The highly pathogenic coronaviruses SARS-CoV-2 and SARS-CoV have led to the COVID-19 pandemic and SARS outbreak, respectively. The receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2, particularly the Omicron variant, has frequent mutations, resulting in the reduced efficiency of current COVID-19 vaccines against new variants. Here, we designed two lipid nanoparticle-encapsulated mRNA vaccines by deleting the mutant RBD of the SARS-CoV-2 Omicron variant (SARS2-S (RBD-del)) or by replacing this mutant RBD with the conserved and potent RBD of SARS-CoV (SARS2-S (SARS-RBD)). Both mRNA vaccines were stable at various temperatures for different time periods. Unlike SARS2-S (RBD-del) mRNA, SARS2-S (SARS-RBD) mRNA elicited effective T-cell responses and potent antibodies specific to both SARS-CoV-2 S and SARS-CoV RBD proteins. It induced strong neutralizing antibodies against pseudotyped SARS-CoV-2 and SARS-CoV infections and protected immunized mice from the challenge of the SARS-CoV-2 Omicron variant and SARS-CoV by significantly reducing the viral titers in the lungs after Omicron challenge and by completely preventing SARS-CoV-induced weight loss and death. SARS2-S (SARS-RBD)-immunized serum antibodies protected naïve mice from the SARS-CoV challenge, with its protective efficacy positively correlating with the neutralizing antibody titers. These findings indicate that this mRNA vaccine has the potential for development as an effective vaccine against current and future SARS-CoV-2 variants and SARS-CoV.

Background: Traboulsi syndrome is a sporadic autosomal recessive disorder. Very few cases reported and no surgical treatment has been described. Purpose: The purpose of the study was to describe the surgical treatment of a case of Traboulsi syndrome with intercalary staphyloma. Synopsis: Traboulsi syndrome[1-3] is a type of spontaneous filtering bleb. The case was of a 31-year-old lady with a flat anterior chamber and large intercalary staphyloma, with a subluxated clear lens. Liberal peritomy was done. The staphyloma was cut and the displaced lens was delivered through it. It was closed with 7-0 vicryl continuous suture. A cross-linked cornea was used after removing the Descemet membrane. It was modified to match the crescentic shape of the limbus by using 11 and 6 mm trephine. Two wedge-shaped defects were created and tissue was excised between them, which were then sutured to increase the arc radius. A peripheral flange at the corneal edge was created. A pocket was created in the host cornea to accommodate the donor corneal flange. The donor cornea was tucked in and the graft was sutured. The sclera was used to suture another side prophylactically, making a 360-degree encirclage. The patient got ambulatory vision postsurgery. The use of the cornea as biological encirclage has not been described previously. Highlights: Using a cross-linked cornea. Creating wedge-shaped defects in crescentic corneal graft to increase arc radius. Use of cornea as encirclage. Link of video: https://youtu.be/T3b5rkvFmlc

Insomnia is a major global health issue, highlighting the need for treatments that are both effective and safe. Valerian extract, a traditional remedy for sleep problems, offers potential therapeutic options. This research examined the potential sleep-enhancing effects of VA (Valerian Pdr%2) in mice. The study evaluated sleep quality by comparing the impact of the VA extract against melatonin on brain activity, using electrocorticography (ECoG) to assess changes in brain waves. For this purpose, the study utilized two experimental models on BALB/c mice to explore the effects of caffeine-induced insomnia and pentobarbital-induced sleep. In the first model, 25 mice were assigned to five groups to test the effects of caffeine (caffeine, 7.5 mg/kg i.p) alone, caffeine with melatonin (2 mg/kg), or caffeine with different doses of valerian extract (100 or 300 mg/kg) given orally on brain activity, assessed via electrocorticography (ECoG) and further analyses on the receptor proteins and neurotransmitters. In the second model, a different set of 25 mice were divided into five groups to examine the impact of pentobarbital (42 mg/kg) alone, with melatonin, or with the valerian extract on sleep induction, observing the effects 45 min after administration. The study found that ECoG frequencies were lower in groups treated with melatonin and two doses of valerian extract (100 and 300 mg/kg), with 300 mg/kg showing the most significant effect in reducing frequencies compared to the caffeine control group, indicating enhanced sleep quality (p < 0.05). This was supported by increased levels of serotonin, melatonin, and dopamine and higher levels of certain brain receptors in the melatonin and valerian extract groups (p < 0.05). Modulatory efficacy for the apoptotic markers in the brain was also noted (p < 0.05). Additionally, melatonin and both doses of VA increased sleep duration and reduced sleep onset time compared to the pentobarbital control, which was particularly notable with high doses. In conclusion, the findings suggest that high doses (300 mg/kg) of valerian extract enhance both the quantity and quality of sleep through the GABAergic pathway and effectively increase sleep duration while reducing the time to fall asleep in a pentobarbital-induced sleep model in mice.

The proposed energy harvesting system is based on a rotational pendulum-like electromagnetic device. Pendulum energy harvesting systems can be used to generate power for wearable devices such as smart watches and fitness trackers, by harnessing the energy from the human body motion. These systems can also be used to power low-energy-consuming sensors and monitoring devices in industrial settings where consistent ambient vibrations are present, enabling continuous operation without any need for frequent battery replacements. The pendulum-based energy harvester presented in this work was equipped with additional adjustable permanent magnets placed inside the induction coils, governing the movement of the pendulum. This research pioneers a novel electromagnetic energy harvester design that offers customizable potential configurations. Such a design was realized using the 3D printing method for enhanced precision, and analyzed using the finite element method (FEM). The reduced dynamic model was derived for a real-size device and FEM-based simulations were carried out to estimate the distribution and interaction of the magnetic field. Dynamic simulations were performed for the selected magnet configurations of the system. Power output analyses are presented for systems with and without the additional magnets inside the coils. The primary outcome of this research demonstrates the importance of optimization of geometric configuration. Such an optimization was exercised here by strategically choosing the size and positioning of the magnets, which significantly enhanced energy harvesting performance by facilitating easier passage of the pendulum through magnetic barriers.

Aim: Our study aimed to audit prescriptions for the prescription indicators given by WHO and to analyze prescription errors, evaluating the frequency and types of prescription errors. Methodology: Prospective study was done in Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pimpri, Pune, under Pharmacology Department in October 2020. The prescriptions from all the OPD (outpatient departments) were collected from the pharmacy store. Prescriptions for the follow-up medication and devoid of medicine were excluded from the study. Results: Total of 1451 errors were found from 400 collected prescriptions, out of which 324 (22.3%) were errors of omission and 145 (10.0%) were errors of commission related to drugs whereas 982 (67.7%) were the error of omission other than drug details. A total of 1257 drugs were prescribed making an average of 3.14 drugs per prescription, out of which 28.72% drugs were prescribed by generic name. About 34.0% of patients were prescribed antibiotics and 2.25% of patients were prescribed injectable drugs. All the drugs were prescribed from the National Essential Drug List (NEDL). Conclusion: The prescription audit showed that there is a need to train prescribing doctors as per the standard MMC and NMC guidelines for rational prescription writing to minimize the chance of major errors like not writing the dose of the drug, not writing it in capital letters, drug-related instructions, diagnosis and so on. The prescription audit should be carried out at regular intervals to improve prescription writing skills to establish a better healthcare system.

This paper deals with study of the plane elasticity of thermoelastic problems for inhomogenous strip. Here, the original problems are reduced to set the governing equations in the volterra integral equations by making the use of direct integration method. Further using the iteration technique the numerical calculations has been performed. The stress distribution obtained and calculated numerically and shown graphically.

We present the case of a 22-year-old male patient who developed “double” pseudoaneurysm of the superficial palmar arch of the left hand after trivial trauma with a kitchen knife. Following an unsuccessful embolization attempt, surgical excision of the pseudoaneurysm was performed during which the pseudoaneurysm was found to arise from the anterior wall of the palmar arch. Intraoperatively, a second pseudoaneurysm arising from the deeper surface of the superficial palmar arch was found and excised. This is probably the only reported case of double pseudoaneurysm of the palmar arch in literature. The possible mechanism of arterial injury, diagnosis, and management is discussed.

Abstract Highly connected smart power systems are subject to increasing vulnerabilities and adversarial threats. Defenders need to proactively identify and defend new high‐risk access paths of cyber intruders that target grid resilience. However, cyber‐physical risk analysis and defense in power systems often requires making assumptions on adversary behaviour, and these assumptions can be wrong. Thus, this work examines the problem of inferring adversary behaviour in power systems to improve risk‐based defense and detection. To achieve this, a Bayesian approach for inference of the Cyber‐Adversarial Power System (Bayes‐CAPS) is proposed that uses Bayesian networks (BNs) to define and solve the inference problem of adversarial movement in the grid infrastructure towards targets of physical impact. Specifically, BNs are used to compute conditional probabilities to queries, such as the probability of observing an event given a set of alerts. Bayes‐CAPS builds initial Bayesian attack graphs for realistic power system cyber‐physical models. These models are adaptable using collected data from the system under study. Then, Bayes‐CAPS computes the posterior probabilities of the occurrence of a security breach event in power systems. Experiments are conducted that evaluate algorithms based on time complexity, accuracy and impact of evidence for different scales and densities of network. The performance is evaluated and compared for five realistic cyber‐physical power system models of increasing size and complexities ranging from 8 to 300 substations based on computation and accuracy impacts.

Abstract Background Cancer immunotherapy is implemented by identifying antigens that are presented on the cell surface of cancer cells and illicit T-cell response (Schumacher and Schreiber, Science 348:69–74, 2015; Waldman et al., Nat Rev Immunol 20:651–668, 2020; Zhang et al., Front Immunol 12:672,356, 2021b). Classical candidates of such antigens are the peptides resulting from genetic alterations and are named “neoantigen" (Schumacher and Schreiber, Science 348:69–74, 2015). Neoantigens have been widely catalogued across several human cancer types (Tan et al., Database (Oxford) 2020;2020b; Vigneron et al., Cancer Immun 13:15, 2013; Yi et al., iScience 24:103,107, 2021; Zhang et al., BMC Bioinformatics 22:40, 2021a). Recently, a new class of inducible antigens has been identified, namely Substitutants, that are produced as a result of aberrant protein translation (Pataskar et al., Nature 603:721–727, 2022). Main Catalogues of Substitutant expression across human cancer types, their specificity and association to gene expression signatures remain elusive for the scientific community's access. As a solution, we present ABPEPserver, an online database and analytical platform that can visualize a large-scale tumour proteomics analysis of Substitutant expression across eight tumour types sourced from the CPTAC database (Edwards et al., J Proteome Res 14:2707–2713, 2015). Functionally, ABPEPserver offers the analysis of gene-association signatures of Substitutant peptides, a comparison of enrichment between tumour and tumour-adjacent normal tissues, and a list of peptides that serve as candidates for immunotherapy design. ABPEPserver will significantly enhance the exploration of aberrant protein production in human cancer, as exemplified in a case study. Conclusion ABPEPserver is designed on an R SHINY platform to catalogue Substitutant peptides in human cancer. The application is available at https://rhpc.nki.nl/sites/shiny/ABPEP/ . The code is available under GNU General public license from GitHub ( https://github.com/jasminesmn/ABPEPserver ).

Purpose – Block chain technology (BCT) has apparent capability of handling information in digital format, which has dragged attention of the practitioners for its utility in industrial and manufacturing practices. Conversely, the managerial adoption of BCT is relatively limited, which motivated the authors to identify crucial dimensions that can persuade the acceptance of BCT from an executive perspective. Thus, the present study is aimed to conduct to understand crucial barriers under BCT for managerial implementation in supply chain management (SCM) of small and medium enterprises (SMEs). Design/methodology/approach – The present study investigated evident barriers to understand implementation of BCT. A questionnaire based survey is performed to collect primary data from service and manufacturing based companies in India. Survey responses are received online and the data is analyzed in a scorecard. The scorecard embedded the scribed entries of Likert scale to determine the relative score. Findings – In present study, sixteen barriers from three categories named as technological, organizational and environmental are evaluated, where, five sub-barriers from technological domain, seven sub-barriers from organizational domain and four sub-barriers from environmental domain are evaluated. The findings of the study determined that the three factors, i.e. “complexity in setup/use”, “Security and privacy concern” and “Technological awareness” mostly affect the adaptation of BCT in SCM. Conversely, “Market dynamics”, “Scalability” and “Cost” do not influence the intention to adopt the technology. Originality/value – Only few studies have endeavored to ascertain the BCT adoption in SCM of SMEs in developing country like India. Thus, the study is filling a momentous gap of mapping BCT dimensions in the scholastic literature. The findings are expected to enable SMEs to understand important factors to be considered for adopting BCT in their curriculum. Furthermore, the study may benefit the BCT developers and suppliers to endure customized solutions based on the findings.

How morphogenetic movements are robustly coordinated in space and time is a fundamental open question in biology. We study this question using the wing of Drosophila melanogaster, an epithelial tissue that undergoes large-scale tissue flows during pupal stages. Previously, we showed that pupal wing morphogenesis involves both cellular behaviors that allow relaxation of mechanical tissue stress, as well as cellular behaviors that appear to be actively patterned (Etournay et al., 2015). Here, we show that these active cellular behaviors are not guided by the core planar cell polarity (PCP) pathway, a conserved signaling system that guides tissue development in many other contexts. We find no significant phenotype on the cellular dynamics underlying pupal morphogenesis in mutants of core PCP. Furthermore, using laser ablation experiments, coupled with a rheological model to describe the dynamics of the response to laser ablation, we conclude that while core PCP mutations affect the fast timescale response to laser ablation they do not significantly affect overall tissue mechanics. In conclusion, our work shows that cellular dynamics and tissue shape changes during Drosophila pupal wing morphogenesis do not require core PCP as an orientational guiding cue.

Sulphate based phosphors shows great impact in the field of luminescence in recent times. In the present investigation, Dy3+, Eu3+ activated/co-activated LiNaSO4 phosphor prepared by simple combustion method using urea as a fuel. Phase identification and crystal structure of prepared phosphor is investigated by XRD and Reitveld refinement. Vibrational features of proposed phosphors were confirmed by Fourier Transform Infrared Spectroscopy (FTIR). Morphological study of the proposed phosphor with elemental analysis of the sample is investigated by SEM analysis. Photoluminescence study of the proposed phosphor shows three simultaneous emission peaks in the visible range gives white light emission. These all results confirm that the proposed phosphor is potential candidate for WLEDs and solid state lighting applications.

Background: ROTASIIL, an oral live attenuated bovine-human reassortant pentavalent rotavirus vaccine, was approved in 2017. This post-marketing surveillance (PMS) was conducted to collect real-world data on the safety of ROTASIIL in India. Methods: Observational, active PMS was conducted in approximately 10,000 infants aged ≥ 6 weeks. ROTASIIL was administered as a 3-dose regimen, at least 4 weeks apart, beginning at ≥ 6 weeks of age concomitantly with other Expanded Programme on Immunization (EPI) vaccines. Participants were followed for one month after the last dose. The adverse events (AEs) and serious adverse events (SAEs), including intussusception (IS) reported during the follow up period were collected. Findings: A total of 9940 infants were enrolled and were considered for safety analysis. Around 9913 (99.7 %) infants received 2 doses, while 9893 (99.5 %) infants completed all three doses. Total 3693 AEs were reported in 2516 (25.3 %) participants. Most of these AEs were pyrexia (78.01 % of events) and injection-site reactions (19.14 % of events). Nearly all AEs were causally unrelated to orally administered ROTASIIL and could be caused by the concomitant injectable vaccines. Only 4 AEs (2 events of vomiting and 1 event each of discomfort and pyrexia) in 4 (

In 2023, approximately 288,300 new diagnoses of prostate cancer will occur, with 34,700 disease-related deaths. Death from prostate cancer is associated with metastasis, enabled by progression of tumor phenotypes and successful extracapsular extension to reach Batson’s venous plexus, a specific route to the spine and brain. Using a mouse-human tumor xenograft model, we isolated an aggressive muscle invasive cell population of prostate cancer, called DU145J7 with a distinct biophysical phenotype, elevated histone H3K27, and increased matrix metalloproteinase 14 expression as compared to the non-aggressive parent cell population called DU145WT. Our goal was to determine the sensitivities to known chemotherapeutic agents of the aggressive cells as compared to the parent population. High-throughput screening was performed with 5,578 compounds, comprising of approved and investigational drugs for oncology. Eleven compounds were selected for additional testing, which revealed that vorinostat, 5-azacitidine, and fimepinostat (epigenetic inhibitors) showed 2.6-to-7.5-fold increases in lethality for the aggressive prostate cancer cell population as compared to the parent, as judged by the concentration of drug to inhibit 50% cell growth (IC50). On the other hand, the DU145J7 cells were 2.2-to-4.0-fold resistant to mitoxantrone, daunorubicin, and gimatecan (topoisomerase inhibitors) as compared to DU145WT. No differences in sensitivities between cell populations were found for docetaxel or pirarubicin. The increased sensitivity of DU145J7 prostate cancer cells to chromatin modifying agents suggests a therapeutic vulnerability occurs after tumor cells invade into and through muscle. Future work will determine which epigenetic modifiers and what combinations will be most effective to eradicate early aggressive tumor populations.