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Abstract Personal and family history of suicidal thoughts and behaviors (PSH and FSH, respectively) are significant risk factors associated with suicides. Research is limited in automatic identification of such data from clinical notes in Electronic Health Records. This study developed deep learning (DL) tools utilizing transformer models (Bio_ClinicalBERT and GatorTron) to detect PSH and FSH in clinical notes derived from three academic medical centers, and compared their performance with a rule-based natural language processing tool. For detecting PSH, the rule-based approach obtained an F1-score of 0.75 ± 0.07, while the Bio_ClinicalBERT and GatorTron DL tools scored 0.83 ± 0.09 and 0.84 ± 0.07, respectively. For detecting FSH, the rule-based approach achieved an F1-score of 0.69 ± 0.11, compared to 0.89 ± 0.10 for Bio_ClinicalBERT and 0.92 ± 0.07 for GatorTron. Across sites, the DL tools identified more than 80% of patients at elevated risk for suicide who remain undiagnosed and untreated.

This study analyzed the water quality of the Yamuna river in Prayagraj across nine locations where the sampling was done upstream, downstream and middle stream from May 2019 to April 2020 using fourteen water quality parameters. Quarterly samples showed good Water Quality Index (WQI) values for summer (95.19), monsoon (77.28), and winter (90.77), but a decline in spring (102.11) due to religious activities was observed. Inductively coupled plasma mass spectroscopy suggested high concentration of Ca2+, Mg2+, K, and P in the river. Principal Component Analysis revealed 9 significant factors (eigen value >0.5) covering 25.13 – 93.89 % variance. Strong correlations included TDS-EC (0.853) and Ca2+ – Mg2+ (1.00) was observed. The correlation between water quality parameters generated by principal component analysis showed that the main parameters affecting the water quality vary in all the seasons. Based on the water quality indicators, anthropogenic activities are accountable to deteriorate the quality of river water. Therefore, the pollution status of the river need to be made publicly.

Reduced Type-I heavy-tailed Weibull (RTI-HTW) distribution is a particular case of the Type-I heavy-tailed family of distributions. This article has studied the properties, inference and real-life applications of RTI-HTW distribution. Firstly, properties such as quantile function, moment-generating function, stress–strength reliability, measure of uncertainty, and mean residual life have been discussed. Further, the inference of RTI-HTW distribution has been discussed under classical and Bayesian frameworks. We have studied the point and interval estimations of model parameters under the progressive Type-II censoring scheme. Four point estimation methods have been used to find the point estimates, such as maximum likelihood estimate (MLE), improved MLE, and Bayesian estimates under informative and kernel priors. Additionally, the approximate confidence interval has been calculated using MLEs, whereas the credible interval has been derived using the Bayesian estimates under informative prior. A Monte Carlo simulation study has been discussed to compare the results of all methods. To illustrate the practical applicability of the proposed model and methodologies, we have analyzed two real-world data sets: the mortality rate of COVID-19 patients in Canada and the infant mortality rate in China. Numerical results demonstrate that the proposed model provides a good fit for both data sets, and the estimation methods discussed are effective and satisfactory.

Background: India is a vast and diverse country with existing variations in the frequency and distribution of cancers across its various parts. In regions lacking population-based cancer registries (PBCRs) in a vast country like India, hospital-based cancer registry (HBCR) data become an important source of information on the trends and patterns of a region. To determine the numerical trends of cases of the top ten cancer sites reporting to HBCR of a tertiary care cancer center in Bihar from 2014 to 2021. Materials and Methods: The details of all histopathologically confirmed cancer cases registered in the HBCR department of radiation oncology, State Cancer Institute, Indira Gandhi Institute of Medical Sciences, Patna, India between January 2014 and December 2021 were included in this retrospective observational study. All these cases were grouped site-wise and listed in descending order of the total number of cases reported in each group. Cross-tabulation with age and sex distribution was done. The frequency distribution of the top ten leading cancers for every consecutive calendar year was plotted in line diagrams for time trend analysis. Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.). was used for analysis. Annual percent change (APC) was determined for the number of cases of all ten cancer sites using joinpoint regression analysis (Joinpoint Regression Software, Version 4.0.4—May 2013; Statistical Methodology and Applications Branch, Surveillance Research Program of the US National Cancer Institute; Bethesda, MD, USA). Results: Out of 32,057 total cancer cases registered between Jan 2014 and Dec 2021, 21,848 patients (68.2%) cases constituted the top ten cancers. The top ten cancers among both sexes were cancer gallbladder (n = 4204, 13.1%), head and neck (n = 3395, 10.6%), breast (n = 3392, 10.6%), lung (n = 2069, 6.5%), cervix (n = 2039, 6.4%), hematolymphoid (n = 1930, 6.0%), liver (n = 1572, 4.9%), stomach (n = 1116, 3.5%), ovary (n = 1103, 3.4%), and colon-rectum (n = 1028, 3.2%). Except for cervical and hematolymphoid cancers, the rest all showed a rising trend over consecutive years. Conclusion: Cancer of the gallbladder continues to be among the most common cancers in the region. Focused research in all aspects of this deadly disease is needed. Strengthening of prevention and screening programs for common cancers and upliftment of the existing infrastructure for diagnosis and treatment of cancer in the region are necessitated.

Introduction: Thyroidectomy is considered a relatively safe procedure with a low risk of postoperative complications, making it challenging to identify predictors of complications to improve shared decision making. Recent advancements in clinical bioinformatics and surgical decision-making tools have the potential to improve patient outcomes. This systematic review aimed to assess the current understanding of factors predicting such complications following thyroidectomy. Methods: We searched PubMed/MEDLINE, Web of Science, and EMBASE for studies published between 2010 and October 2023, investigating predictors of postoperative complications after thyroidectomy. Studies were included if they investigated predictors of hypocalcemia, hypoparathyroidism, vocal cord paresis (VCP), hematoma, or other postoperative complications. Studies solely reliant on univariate and ROC analyses were excluded. Independent predictors of each postoperative complication were evaluated and categorized as biochemical, surgical, and patient/disease specific. Results: Forty-five studies were included. Biochemical hypocalcemia and transient hypoparathyroidism were the most investigated complications, with reported rates ranging from 15.7 % to 76.7 % and 12.9 % to 53.8 %, respectively. The majority of studies (n = 35, 77 %) focused on these complications. Biochemical markers (e.g., serum calcium, parathyroid hormone) were the most frequent predictors identified for these complications. Surgical factors (inadvertent parathyroidectomy) were frequently studied for all complications. Age, gender, and thyroid pathology were common patient/disease-specific predictors. Conclusion: This review highlights the disparity in research on complication predictors. Most studies focused on hypocalcemia and hypoparathyroidism, with fewer examining VCP, hematoma, and mortality. Notably, a lack of high-quality evidence exists due to the scarcity of prospective and randomized controlled trials. Future research should explore incorporating a wider range of independent predictors, especially surgical factors, into comprehensive predictive models. This review can serve as a foundation for developing such models to improve risk prediction for a broader spectrum of thyroidectomy complications.

In this report, we have investigated the CsMgCl3 compound with the help of the WIEN2K software package. The structural and electronic properties are performed using the full potential augmented plane wave (FP-LAPW) method with the generalised gradient approximation (GGA) approximation as exchange correlation potentials. We used the Birch-Murnaghan equation (BME) to find the structural properties of the material. These include the lattice parameter, the bulk modulus, the first derivative of the bulk modulus, the minimum energy, and the volume. The structural properties match up with the experimental data. Electronic properties in terms of the band structure (BS) and total and partial density of state (T-DOS and P-DOS) profiles of CsMgCl3 using GGA potentials exhibit an indirect wide energy band gap of 5.35 eV. All these properties show that the CsMgCl3 compound is used as a perovskite in solar cells.

IntroductionImmunogenicity refers to the ability of a substance, such as a therapeutic drug, to elicit an immune response. While beneficial in vaccine development, undesirable immunogenicity can compromise the safety and efficacy of therapeutic proteins by inducing anti-drug antibodies (ADAs). These ADAs can reduce drug bioavailability and alter pharmacokinetics, necessitating comprehensive immunogenicity risk assessments starting at early stages of drug development. Given the complexity of immunogenicity, an integrated approach is essential, as no single assay can universally recapitulate the immune response leading to the formation of anti-drug antibodies.MethodsTo better understand the Dendritic Cell (DC) contribution to immunogenicity, we developed two flow cytometry-based assays: the DC internalization assay and the DC activation assay. Monocyte-derived dendritic cells (moDCs) were generated from peripheral blood mononuclear cells (PBMCs) and differentiated over a five-day period. The internalization assay measured the accumulation rate of therapeutic antibodies within moDCs, while the activation assay assessed the expression of DC activation markers such as CD40, CD80, CD86, CD83, and DC-SIGN (CD209). To characterize these two assays further, we used a set of marketed therapeutic antibodies.ResultsThe study highlights that moDCs differentiated for 5 days from freshly isolated monocytes were more prone to respond to external stimuli. The internalization assay has been shown to be highly sensitive to the molecule tested, allowing the use of only 4 donors to detect small but significant differences. We also demonstrated that therapeutic antibodies were efficiently taken up by moDCs, with a strong correlation with their peptide presentation on MHC-II. On the other hand, by monitoring DC activation through a limited set of activation markers including CD40, CD83, and DC-SIGN, the DC activation assay has the potential to compare a series of compounds. These two assays provide a more comprehensive understanding of DC function in the context of immunogenicity, highlighting the importance of both internalization and activation processes in ADA development.DiscussionThe DC internalization and activation assays described here address key gaps in existing immunogenicity assessment methods by providing specific and reliable measures of DC function. The assays enhance our ability to pre-clinically evaluate the immunogenic potential of biotherapeutics, thereby improving their safety and efficacy. Future work should focus on further validating these assays and integrating them into a holistic immunogenicity risk assessment framework.

This study compared the regeneration status, vegetation diversity, stand structure, and carbon stock of two community-managed forests located in different ecological regions of Nepal. A total of 61 concentric sample plots were investigated by using systematic random sampling with 1 % sampling intensity. The phytosociological parameters of trees and regeneration density were calculated using standard techniques. The aboveground tree carbon was estimated using a non-destructive method. Correlation analysis was performed to assess the variation of carbon stock with biomass, stand density, tree diameter at breast height (DBH), tree height, basal area, and seedling density. Janata community forest had higher regeneration than the Hazare community forest, with a bell-shaped distribution of DBH in Janata and an interrupted curve in Hazare community forest. Both forests were dominated by Shorea robusta. Hazare had higher Shannon diversity index, Simpson's index, and evenness index, while Janata community forest had higher carbon stock. The observed differences in the studied parameters between the two community forests can be attributed to the difference in ecological factors such as temperature, rainfall, soil nutrient availability, and management practices. Future studies focusing on investigating the underlying factors driving the observed patterns and relationships, such as the effects of disturbance, climate, and management practices on forest structure and function are also needed. These findings have important implications for forest management and conservation policies, especially in the context of climate change mitigation and biodiversity conservation.

IntroductionNuclear medicine infection imaging is routinely performed with the use of leukocytes radiolabelled with technetium-99m hexamethylpropyleneamine oxime ([99mTc]Tc-HMPAO) and single-photon emission computed tomography (SPECT). Positron emission tomography (PET) is more sensitive than SPECT and results in higher-quality images. Zirconium-89 (89Zr) is a positron emitter with a half-life of 78.4 h, which translates to the biological half-life and slow biodistribution of intact cells and allows delayed PET imaging for more accurate biodistribution of the labelled leukocytes to infection foci. A first-in-human study with [89Zr]Zr-oxine-leukocytes in four healthy volunteers was reported in 2022. Our first-in-human study utilising the cell surface labelling approach aimed to image infection in patients with the use of 89Zr-labelled leukocytes, using p-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) as a bifunctional chelating agent, and to compare the scan quality and biodistribution of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes on PET images to SPECT images obtained with [99mTc]Tc-HMPAO-labelled leukocytes.MethodsLeukocytes were isolated from whole-blood samples of eight patients with clinically and/or radiologically confirmed infection. Isolated leukocytes were labelled with [99mTc]Tc-HMPAO according to standardised methods, and [89Zr]Zr-Df-Bz-NCS according to our previously published radiolabelling method. Whole-body SPECT imaging was performed 2 and 18 h post injection of [99mTc]Tc-HMPAO-labelled leukocytes, and whole-body PET/CT was performed 3 and 24 h post injection of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes in seven patients.ResultsSuccessful [89Zr]Zr-Df-Bz-NCS-leukocyte labelling was achieved. High labelling efficiencies were obtained (81.7% ± 3.6%; n = 8). A mean high viability of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes was observed (88.98% ± 12.51%). The [89Zr]Zr-Df-Bz-NCS-leukocyte labelling efficiency was not significantly affected by the white blood cell count of the patient. The performance of [99mTc]Tc-HMPAO- and [89Zr]Zr-Df-Bz-NCS-labelled leukocytes, in terms of the ability to accurately detect infection, were similar in two out of seven patients, and [99mTc]Tc-HMPAO-labelled leukocytes outperformed [89Zr]Zr-Df-Bz-NCS-labelled leukocytes in one patient with femoral osteomyelitis. However, in two cases of pulmonary pathology, [89Zr]Zr-Df-Bz-NCS-labelled leukocytes demonstrated improved pathological uptake. No skeletal activity was observed in any of the patients imaged with [89Zr]Zr-Df-Bz-NCS-labelled leukocytes, illustrating the in vivo stability of the radiolabel.DiscussionAlthough the [89Zr]Zr-Df-Bz-NCS-leukocyte labelling aspect of this study was noteworthy, infection imaging did not yield convincingly positive results due to the pulmonary trapping of intravenously administered [89Zr]Zr-Df-Bz-NCS-labelled leukocytes.

The proliferation of online social networking websites has resulted in the growth of online communities and increased communication among users. However, sharing personal information can pose a privacy threat to users, leaving them vulnerable to attacks like blackmail and fraud. Also, with the rise in scandals such as Geofeedia and Cambridge Analytica, as well as Facebook’s admission of sharing user data with top mobile phone manufacturers, worries about privacy on social networking platforms have become increasingly palpable. This paper discusses the privacy risks of sharing personal information on social networking websites. The proposed approaches offer a comprehensive protection of user privacy and prevents unauthorized access to user’s data and information by social network providers and unauthorized users. The study employs a preferential selective encryption approach that encompasses not only tweets but also other personally identifiable components, including images, memes, and metadata. This approach serves as a comprehensive solution to encrypt all elements within a social network, making it a one-stop destination for privacy protection in online social networks (OSN). When compared to other investigated schemes, the proposed approach significantly reduces privacy leakage to 0.48 units while achieving a high utility score of 0.8116 units for non-sensitive attributes in tweets. Moreover, it demonstrates remarkable performance in maintaining sensitive information coverage with notably minimal information loss: 0.4 units for images, 0.3 units for memes, and 12.7 units for metadata. Thus, in essence these findings, backed by quantifiable measures of privacy and utility, strongly validate the effectiveness of the proposed methods in achieving a superior balance between privacy preservation and utility when compared to its contemporaries, particularly in applications like online social networks (OSNs). Furthermore, the suggested method’s architecture makes it platform-neutral; it can be customized for any social networking website, such as Facebook, Instagram, and LinkedIn, and it may include any attribute that the user chooses to keep private.

Abstract Objectives The use of topical corticosteroids to manage postoperative sinonasal symptoms after endoscopic skull base surgery (ESBS) has not been well studied. We quantified long‐term impact of postoperative steroid irrigations (SIs) on quality of life of patients after ESBS. Methods Retrospective review of patients at the University of Pennsylvania undergoing ESBS from 2010 to 2019. Data on patient demographics and postoperative treatment with nasal saline irrigation twice daily with and without dissolved steroids (mometasone or budesonide) was collected. Preoperative, and 1‐, 3‐, 6‐, 12‐, 18‐, and 24‐month postoperative Sino‐Nasal Outcome Test (SNOT‐22) scores were assessed. Results A total of 727 patients were assessed (53.4% males), with 479 patients in the no SI group and 248 patients in the SI group. Preoperative SNOT‐22 scores did not differ significantly (P = 0.19). 1‐, 3‐, 6‐, 12‐, 18‐, and 24‐month post‐op SNOT‐22 scores did not significantly differ between groups. However, mometasone irrigations resulted in significantly lower postoperative 2‐year SNOT‐22 scores compared to budesonide (P

IntroductionImpaired cognition is a core feature of schizophrenia that is evident early in the first episode and is frequently accompanied by compromised physical health. Although physical health confers benefits to cognition, it remains unclear whether physical activity, body mass index (BMI) and cardiorespiratory fitness are associated with neurocognition in first episode schizophrenia patients. The purpose of this study was to examine differences in stimulus categorization and motor response selection processes between first-episode schizophrenia patients compared to age-matched controls and explore associations between physical health and these stages of information processing.MethodsFourteen young adult patients receiving care following a first episode of psychosis and a matched sample of nonpsychiatric controls completed a visual oddball task from which the P3 and LRP (lateralized readiness potential) event-related potential (ERP) components were extracted to assess stimulus categorization and response selection processes, respectively. Physical activity, aerobic fitness, and BMI were correlated with ERP measures.ResultsCompared with controls, patients had lower physical activity levels and longer P3 and LRP latencies. Regardless of stimulus probability, patients had reduced accuracy and slower reaction times relative to controls. In patients, marginal associations were found between physical activity and P3 difference waveform amplitude, and BMI was negatively associated with parent P3 waveform amplitude.DiscussionThe present findings suggest that cognitive impairment in first-episode schizophrenia spans both stimulus- and response-related stages of information processing, and may be targeted through physical activity interventions.

Abstract Chimeric antigen receptor (CAR) T‐cell subsets and immunophenotypic composition of the pre‐infusion product, as well as their longitudinal changes following infusion, are expected to affect CAR T‐cell expansion, persistence, and clinical outcomes. Herein, we sequentially evolved our previously described cellular kinetic‐pharmacodynamic (CK‐PD) model to incorporate CAR T‐cell product‐associated attributes by utilizing published preclinical and clinical datasets from two affinity variants (FMC63 and CAT19 scFv) anti‐CD19 CAR T‐cells. In step 1, a unified cell‐level PD model was used to simultaneously characterize the in vitro killing datasets of two CAR T‐cells against CD19+ cell lines at varying effector:target ratios. In step 2, an augmented CK‐PD model for anti‐CD19 CAR T‐cells was developed, by integrating CK dataset(s) from two bioanalytical measurements (quantitative polymerase chain reaction and flow cytometry) in patients with cancer. The model described the differential in vivo expansion properties of CAR T‐cell subsets. The estimated expansion rate constant was ~1.12‐fold higher for CAR+CD8+ cells in comparison to CAR+CD4+ T‐cells. In step 3, the model was extended to characterize the disposition of four immunophenotypic populations of CAR T‐cells, including stem‐cell memory, central memory, effector memory, and effector cells. The model adequately characterized the longitudinal changes in immunophenotypes post anti‐CD19 CAR T‐cell infusion in pediatric patients with acute lymphocytic leukemia. Polyclonality in the pre‐infusion product was identified as a categorical covariate influencing differentiation of immunophenotypes. In the future, this model could be leveraged a priori toward optimizing the composition of CAR T‐cell infusion product, and further understand the CK‐PD relationship in patients.

Abstract The microvasculature plays a key role in tissue perfusion and exchange of gases and metabolites. In this study we use human blood vessel organoids (BVOs) as a model of the microvasculature. BVOs fully recapitulate key features of the human microvasculature, including the reliance of mature endothelial cells on glycolytic metabolism, as concluded from metabolic flux assays and mass spectrometry-based metabolomics using stable tracing of 13C-glucose. Pharmacological targeting of PFKFB3, an activator of glycolysis, using two chemical inhibitors results in rapid BVO restructuring, vessel regression with reduced pericyte coverage. PFKFB3 mutant BVOs also display similar structural remodelling. Proteomic analysis of the BVO secretome reveal remodelling of the extracellular matrix and differential expression of paracrine mediators such as CTGF. Treatment with recombinant CTGF recovers microvessel structure. In this work we demonstrate that BVOs rapidly undergo restructuring in response to metabolic changes and identify CTGF as a critical paracrine regulator of microvascular integrity.

This case describes an atypical cutaneous presentation of metastatic gastric carcinoma in a patient initially presenting with dysphagia and a sclerotic red plaque overlying the anterior neck and chest. Skin biopsy revealed metastatic adenocarcinoma from the upper gastrointestinal tract. Esophagogastroduodenoscopy revealed stage IV metastatic gastric adenocarcinoma. Treatment with chemotherapy was initiated.

Abstract West Nile virus (WNV) is the most significant arbovirus in the United States in terms of both morbidity and mortality. West Nile exists in a complex transmission cycle between avian hosts and the arthropod vector, Culex spp. mosquitoes. Human spillover events occur when humans are bitten by an infected mosquito and predicting these rates of infection and therefore the risk to humans may be associated with fluctuations in environmental conditions. In this study, we evaluate the hydrological and meteorological drivers associated with mosquito biology and viral development to determine if these associations can be used to forecast seasonal mosquito infection rates with WNV in the Coachella Valley of California. We developed and tested a spatially resolved ensemble forecast model of the WNV mosquito infection rate in the Coachella Valley using 17 years of mosquito surveillance data and North American Land Data Assimilation System‐2 environmental data. Our multi‐model inference system indicated that the combination of a cooler and dryer winter, followed by a wetter and warmer spring, and a cooler than normal summer was most predictive of the prevalence of West Nile positive mosquitoes in the Coachella Valley. The ability to make accurate early season predictions of West Nile risk has the potential to allow local abatement districts and public health entities to implement early season interventions such as targeted adulticiding and public health messaging before human transmission occurs. Such early and targeted interventions could better mitigate the risk of WNV to humans.

This research introduces an approach to visible spectroscopy leveraging image processing techniques and machine learning (ML) algorithms. The methodology involves calculating the hue value of an image and deriving the corresponding dominant wavelength. Initially, a six-degree polynomial regression supervised machine learning model is trained to establish a relationship between the hue values and dominant wavelengths. Subsequently, the ML model is employed to analyse the visible wavelengths emitted by various sources, including sodium vapour, neon lamps, mercury vapour, copper vapour lasers, and helium vapour. The performance of the proposed method is evaluated through error analysis, revealing remarkably low error percentages of 0.04%, 0.01%, 3.7%, 1%, and 0.07% for sodium vapour, neon lamp, copper vapour laser, and helium vapour, respectively. This approach offers a promising avenue for accurate and efficient visible spectroscopy, with potential applications in diverse fields such as material science, environmental monitoring, and biomedical research. This research presents a visible spectroscopy method harnessing image processing and machine learning algorithms. By calculating hue values and identifying dominant wavelengths, the approach demonstrates consistently low error rates across diverse light sources.

Introduction Dual antiplatelet therapy (DAPT) is necessary to minimize the risk of periprocedural thromboembolic complications associated with aneurysm embolization using Pipeline embolization device (PED). We sought to assess the impact of platelet function testing (PFT) on reducing periprocedural thromboembolic complications associated with PED flow diversion in patients receiving aspirin and clopidogrel. Methods Patients with unruptured intracranial aneurysms requiring PED flow diversion were identified from 13 centers for retrospective evaluation. Clinical variables including the results of PFT prior to treatment, periprocedural DAPT regimen, and intracranial complications occurring within 72‐hours of embolization were identified from the medical record. Complication rates were compared between PFT and non‐PFT groups. Differences between groups were tested for statistical significance using the Wilcoxon rank sum, Fisher exact, or Chi‐square tests. A p‐value 0.9). Conclusion Pre‐procedural PFT prior to PED treatment of intracranial aneurysms in patients pre‐medicated with an aspirin and clopidogrel DAPT regimen may not be necessary to significantly reduce the risk of procedure‐related intracranial complications.

Introduction 18‐36% of all intracranial aneurysms are middle cerebral artery(MCA) bifurcation aneurysms. While some are much higher risk than others, they have an overall low estimated annual rupture rate of 0.36%.(1) MCA bifurcation aneurysms have been historically challenging to treat endovascularly given they often have complex morphology and wide necks. The Woven EndoBridge (WEB) is an ellipsoid embolization device designed to provide intrasaccular flow disruption along the aneurysm neck, which has been proven to be an effective method in treating a wide spectrum of wide‐necked bifurcation aneurysms. Thromboembolism and recanalization are the main concerns in treatment with the WEB device, like any aneurysm treatment approach .(2),(3) Occasionally, irregularities and secondary lobules at the base of the primary aneurysm can have persistent filling despite treatment. Methods We present a case of a right MCA bifurcation aneurysm treated by a WEB device and coil embolization. Results 48‐year‐old female with a medical history significant only for active smoking who presented with sudden onset of the worst headache of her life followed by brief loss of consciousness. No neurological evaluation was sought initially, until 2 weeks later as she continued to experience a moderate‐intensity headache associated with nausea and vomiting with frequent falls. On exam, she was alert and oriented, moving all extremities with full strength. CT head revealed an evolving acute to subacute right MCA infarction with adjacent small volume subarachnoid hemorrhage. CTA head revealed a right MCA bifurcation aneurysm measuring 6 x 6 x 7 mm with irregularity of the wall. Multifocal severe stenosis was noted in the right distal right M1 and right M2 divisions. She underwent a diagnostic subtraction angiography which confirmed an irregular right MCA bifurcation aneurysm measuring 4.3 x 4.5 x 5.7 mm (Figure 1 ‐A,B). While it was believed that the subarachnoid hemorrhage was more likely related to the recent infarct, a decision was made to treat the aneurysm given its relatively large size and irregular shape. Embolization was performed with a WEB SL 6 x 4 mm device (Figure 1: C,D ‐blue arrow). Post‐deployment angiograph showed occlusion of the aneurysm dome but persistent filling of the secondary lobule near the base of the aneurysm. Given this residual lobule filling, a decision was made to continue additional embolization with a hyper soft 3D 2 mm X 2 cm coil(Figure 1: C,D ‐ yellow arrow). Final angiography revealed complete occlusion of the aneurysm. Vasospasm of the distal M2 divisions and multiple M3 branches in the right MCA vascular territory was also noted. Therefore, she was treated with 20 mg of intra‐arterial Verapamil with improvement. She was started on Aspirin 325 mg daily. Daily transcranial dopplers were negative for vasospasm. She remained neurologically stable and was discharged home 5 days after admission ambulating independently. Conclusion With modern advances in endovascular devices, many MCA bifurcation aneurysms can be treated minimally invasively. However, there are some limitations to the WEB since every aneurysm is different and there are a finite number of sizes and shapes available for WEB. This case illustrates that adjunctive coil embolization can successfully occlude a residual secondary base lobule after WEB embolization.

This case describes a patient with known mantle cell lymphoma without cutaneous involvement presenting with a diffuse morbilliform rash during an inpatient admission for bacterial pneumonia. The patient was thought to have a hypersensitivity to antibiotics but failed to improve after the offending agents were stopped. A skin biopsy revealed metastatic cutaneous mantle cell lymphoma. Treatment with high-dose corticosteroids and chemotherapy was initiated resulting in the resolution of the rash.

Most of the periodic pattern mining algorithms extract fully periodic patterns by strictly monitoring the cyclic behaviour of patterns in transactional as well as temporal databases. The most recent and preferred method for discarding non-periodic uninteresting patterns is partial periodic pattern mining, which has control over the strictness measure on cyclic repetitions of patterns. Recently, a variety of industries, including fraud detection, telecommunications, retail marketing, research, and medical have found applications for rare association rule mining, which uncovers unusual or unexpected combinations. A limited amount of literature demonstrated how periodicity is essential in mining low-support rare patterns. However, time of occurrence is also a vital phrase that is ignored which further aids in significant information retrieval. With this inspiration, a novel depth-first search framework named 3P-BitVectorMiner, is proposed to extract entire partial periodic patterns from a temporal database. Experiments are carried out by varying support and periodicity thresholds for a variety of datasets. It is found that 3P-BitVectorMiner consistently displays greater performance over the state-of-the-art algorithm 3P-Growth. Further, the scalability of the 3P-BitVectorMiner algorithm is also presented to demonstrate the efficiency over the 3P-Growth algorithm on large temporal databases. In addition, two variations named RFPP-BitVectorMiner and R3P-BitVectorMiner are proposed to mine rare fully periodic patterns and rare partial periodic patterns from temporal databases respectively. Different experiments carried out show that these proposed frameworks successfully capture periodic rare patterns in temporal databases.

The rise and growing prevalence of juvenile delinquency is a matter of concern for many parties. This study aims to establish a research instrument in the form of a questionnaire that can be deployed to assess the learning environment perceived by high school students. This research endeavor constitutes a developmental study, wherein the outcomes are a single survey instrument encompassing six variables, nineteen indicators, and forty questions. The data-collecting process involved the utilization of a Google Form across five schools in five districts, containing a total of 1615 participants. The analysis of expert data was conducted utilizing V. Aiken and field trials employing confirmatory factor analysis (CFA) Second Order. The findings of this study indicate that the diagnostic survey instrument used to assess the learning environment's impact on the mental health of high school students demonstrated validity, as evidenced by loading factor values exceeding the established minimal threshold. The reliability of the instrument remains insufficient. This survey can be utilized to detect adolescent persistent tendencies carried out by students or other school members that interfere with mental health: the emergence and significant raising of juvenile delinquency.

Civil Engineering structures are constantly subjected to environmental forces and changes around the surroundings hence a strong need for assessment of the interaction and predictive measures that lead to pro-active actions towards the structural safety and health monitoring. Significant damage is caused to buildings and port infrastructure when soil is subjected to dynamic loadings and high-frequency vibrations as in earthquakes and events that involve the interaction of soil structures. Dynamic loadings, cause significant displacements and tilting in soil-supported structures. Sands, gravels, and other granular materials that support buildings, bridges, port infrastructure, and retaining structures have to withstand the impact of dynamic loadings, with the requirement of serious considerations, to account for liquefaction risk in the soil. Hence there is a need for careful assessments of soil under dynamic loadings. Data from the laboratory for cyclic triaxial experiments and cyclic direct shear experiments from LEAP-2020 (Liquefaction Experiment and Analysis Project) have been used to assess soil fatigue by comparing cyclic triaxial and direct shear strength data. CSR (Cyclic Stress ratio) had correlations with cycle count, axial strain, axial stress, load in KPa, void ratio. In this paper, machine learning (decision tree, extra tree, knn, random forest) and deep learning (artificial neural networks) techniques are applied to the laboratory dataset and results include prediction of the cyclic stress ratio of soil corresponding to the standard input parameters as per ASTM D 3999–91 and ASTM D 6528–07. This study predicts the CSR of soil that can be used for the predictive assessment of the soil. Additionally, CSR (cyclic stress ratio) is a crucial element in determining soil liquefaction

Abstract Background and aims Many patients with intracerebral hemorrhage (ICH) develop intraventricular hemorrhage (IVH), which is associated with higher mortality and worse clinical outcome. External ventricular drains (EVDs) are often placed, but there is little data on how much patients benefit from this intervention. We explored the use, timing, and location of EVD in ICH patients and any association with clinical outcome. Results During the study period, 2870 patients presented with primary ICH, and 2486 were included in analyses. Overall, patients were 73 (± 13) years old; 54% were male, and 46% had associated IVH. An EVD was placed in 29% of patients with IVH and 4% of those without. IVH patients with EVD were younger (67 ± 13 vs 74 ± 13, p

Twenty-four scientists met for the annual Auxological conference held at Krobielowice castle, Poland, to discuss the diverse influences of the environment and of social behavior on growth following last year’s focus on growth and public health concerns (Hermanussen et al., 2022b). Growth and final body size exhibit marked plastic responses to ecological conditions. Among the shortest are the pygmoid people of Rampasasa, Flores, Indonesia, who still live under most secluded insular conditions. Genetics and nutrition are usually considered responsible for the poor growth in many parts of this world, but evidence is accumulating on the prominent impact of social embedding on child growth. Secular trends not only in the growth of height, but also in body proportions, accompany the secular changes in the social, economic and political conditions, with major influences on the emotional and educational circumstances under which the children grow up (Bogin, 2021). Aspects of developmental tempo and aspects of sports were discussed, and the impact of migration by the example of women from Bangladesh who grew up in the UK. Child growth was considered in particular from the point of view of strategic adjustments of individual size within the network of its social group. Theoretical considerations on network characteristics were presented and related to the evolutionary conservation of growth regulating hypothalamic neuropeptides that have been shown to link behavior and physical growth in the vertebrate species. New statistical approaches were presented for the evaluation of short term growth measurements that permit monitoring child growth at intervals of a few days and weeks.

Objective: Several clinical practice guidelines have been produced and disseminated for the evaluation of a neck mass. However, to date, the quality and methodologic rigor of these clinical practice guidelines have not been appraised. Therefore, this study set out to identify and assess the methodologic quality of national and international guidelines for the evaluation and management of neck masses in adults. Methods: We conducted a comprehensive search of EMBASE, MEDLINE/PubMed, SCOPUS and grey literature sources until September 2020. The quality of these guidelines was assessed by four reviewers using the Appraisal of Guidelines for Research and Evaluation, 2nd edition (AGREE II). Domain scores were considered acceptable quality if they scored >60%, and Intraclass Correlation Coefficients (ICC) were calculated to assess agreement among the appraisers. Results: Seven guidelines were assessed for evaluation. Among these, only the American Academy of Otolaryngology (AAO), Cancer Care Manitoba (CCMB), and the American Society of Clinical Oncology (ASCO) achieved an overall rating of “high”. The remaining four guidelines achieved ratings of either “average” or “low”. The “Scope and Purpose” domain achieved the highest mean score (94.4% ± 5.0%), and lowest was “Applicability” (51.5% ± 29.2%). ICC analysis showed substantial to very good agreement across all domains (0.75–0.98). Conclusion: These findings highlight the variability in methodologic quality of guidelines for the evaluation and management of adult neck mass. The results from this analysis highlight the need to improve guidelines development process for this topic and may guide the selection and use of these guidelines in clinical practice.

Abstract Enhanced recovery after surgery (ERAS) protocols have been developed in numerous surgical specialties as a means of systematically improving patient recovery, functional outcomes, cost savings, and resource utilization. Such multidisciplinary initiatives seek to minimize variability in several aspects of perioperative patient care, helping to reduce inpatient length of hospital stay, complications, and the overall resource and financial burden of surgical care. Head and neck oncology patients stand to benefit from the implementation of comprehensive ERAS protocols, as these patients have complex medical needs that may dramatically impact multiple aspects of their recovery, including breathing, eating, nutrition, pain, speech, swallowing, and communication. Implementing ERAS protocols for head and neck cancer patients may present unique challenges, and require significant interdisciplinary coordination and collaboration. We therefore sought to provide a comprehensive guide to the planning and institution of such ERAS systems at institutions undertaking care of head and neck cancer patients. Key elements to consider in the implementation of successful ERAS protocols for this population include organizing a team consisting of frontline leaders such as nursing staff, medical specialists, and associated health professionals; designing interventions based on systematically evaluated, high‐quality literature; and instituting a clear methodology for regularly updating protocols and auditing the success or potential limitations of a given intervention. Potential obstacles to the success of ERAS interventions for head and neck cancer patients include challenges in systematically tracking progress of the protocol, as well as resource limitations in a given health system.

Abstract Rationale Transbronchial cryobiopsy has been increasingly used to diagnose interstitial lung diseases. However, there is uncertainty regarding its accuracy and risks, mainly due to a paucity of prospective or randomized trials comparing cryobiopsy to surgical biopsy. Objectives To evaluate the diagnostic yield and complications of cryobiopsy in patients selected by multidisciplinary discussion. Methods This was a prospective cohort from 2017 to 2019. We included consecutive patients with suspected interstitial lung diseases being considered for lung biopsy presented at our multidisciplinary meeting. Measurements and main results Of 112 patients, we recommended no biopsy in 31, transbronchial forceps biopsy in 16, cryobiopsy in 54 and surgical biopsy in 11. By the end of the study, 34 patients had had cryobiopsy and 24 patients, surgical biopsy. Overall pathologic and multidisciplinary diagnostic yield of cryobiopsy was 47.1% and 61.8%, respectively. The yield increased over time for both pathologic (year 1: 28.6%, year 2: 54.5%, year 3: 66.7%, p = 0.161) and multidisciplinary (year 1: 50%, year 2: 63.6%, year 3: 77.8%, p = 0.412) diagnosis. Overall rate of grade 4 bleeding after cryobiopsy was 11.8%. Cryobiopsy required less chest tube placement (11.8% vs 100%, p

Summary: Background: Early childhood is a vital period for development and growth. Promoting beneficial lifestyle behaviours in early childhood can help optimise children's health, development and learning, shape their behaviours in adulthood and offer the best protection against future non-communicable diseases (NCDs). In the Asia–Pacific region, NCDs are significant causes of healthcare burden and mortality. Furthermore, there is also a high prevalence of adverse metabolic risk factors and unhealthy lifestyle behaviours among these children. Method: Representatives from 19 Asia–Pacific nations and/or jurisdictions developed a consensus statement on integrated 24-hour activity guidelines for the early years using the GRADE-ADOLOPMENT framework. Findings: These guidelines apply to all infants, toddlers and pre-schoolers below 5 years of age. The guidelines aim to provide a holistic and practical approach to lifestyle activities by framing physical activity, sedentary behaviour and sleep within a 24-hour period. Dietary patterns were included as they play an integral role in metabolic health and energy balance. Interpretation: Aligned with the World Health Organization's Global Action Plan for the Prevention and Control of NCDs through health promotion interventions in early life, through cultivating healthy lifestyle behaviours in the children's early years, we aim to provide children with the best start in life and reduce the burden of future NCDs in the Asia–Pacific region. Funding: Funded by Integrated platform for research in advancing metabolic health outcomes of women and children

Spatial transcriptomics experiments profile genome-wide gene expression at localized spots across a tissue. Here, the authors identify spot swapping, an artifact where RNA expressed at one tissue spot binds probes at another, and they propose SpotClean to adjust for it.

Description of the subject. Prunella vulgaris L. (Lamiaceae) is an edible herb used in Europe and Asia as herbal tea, food, dietary supplement or medicinal plant since several centuries. Although the composition and properties of the aerial parts are well documented in the literature, Prunella vulgaris seeds have never been investigated. Objectives. The aim of this work was to characterize the composition of these seeds to assess not only their nutritional potential (protein, lipid and minerals content), but also their antioxidant and anti-inflammatory potential as well as their specialized metabolites composition. Method. The protein, lipids and mineral content were determined. The phenolic compounds were isolated; elucidation of their structures was done by means of HR-MS and one- and two-dimensional NMR analysis. They were then evaluated for their biological activity, together with seed extracts. Results. Omega-3 rich oil and an interesting amino acids profile were detected in the seeds as well as the presence of a high content of polyphenolic compounds, including two structurally new compounds (phenylpropane derivatives) which were isolated and structurally characterized. The two compounds described here for the first time, were named amolsamic acids A&B. The seeds and amolsamic acids showed an interesting antioxidant potential, and a strong anti-inflammatory activity on neutrophils, MPO and HRP models. Conclusions. These findings highlight the real health promoting potential of P. vulgaris seeds and make them a good candidate as super-food or food supplement.

Abstract Background Anatomy education in US medical schools has seen numerous changes since the call for medical education reform in 2010. The purpose of this study was to survey US medical schools to assess recent trends in anatomy education, the impact of the COVID-19 pandemic on anatomy teaching, and future directions of medical school anatomy curricula. Methods We sent a 29-item survey to anatomy course directors of 145 AAMC-associated allopathic medical schools inquiring about their schools’ anatomy curricula. The survey contained objective discrete questions concerning the curricula changes preceding COVID-19 and those directly related to COVID-19. We also asked subjective and open-ended questions about the impact of COVID-19 and future directions of anatomy education. Results A total of 117/143 course directors (82%) completed the survey. Most schools (60%) reported a major change to their anatomy course within the past five years, including a decrease in total course time (20%), integration of anatomy into other courses (19%), and implementation of a “flipped classroom” (15%) teaching style. Due to COVID-19, there was a decrease in the fraction of course time dedicated to “hands-on” learning (p

Summary: Ion and analyte changes in the tumor microenvironment (TME) alter the metabolic activity of cancer cells, promote tumor cell growth, and impair anti-tumor immunity. Consequently, accurate determination and visualization of extracellular changes of analytes in real time is desired. In this study, we genetically combined FRET-based biosensors with nanobodies (Nbs) to specifically visualize and monitor extracellular changes in K+, pH, and glucose on cell surfaces. We demonstrated that these Nb-fused biosensors quantitatively visualized K+ alterations on cancer and non-cancer cell lines and primary neurons. By implementing a HER2-specific Nb, we generated functional K+ and pH sensors, which specifically stained HER2-positive breast cancer cells. Based on the successful development of several Nb-fused biosensor combinations, we anticipate that this approach can be readily extended to other biosensors and will open new opportunities for the study of extracellular analytes in advanced experimental settings.

Purpose The prevalence of rickets is increasing worldwide in association with an increase in vitamin D deficiency. This study aimed to investigate the vitamin D profile of healthy school-aged children in a sun-rich country and its contributing factors. Methods This cross-sectional study was conducted in 120 healthy children from 7–12 years of age who live in Jakarta, Indonesia. Their demographic status, sun exposure duration time, and lifestyle were recorded using a structured questionnaire. Serum calcium, phosphate, bone-alkaline phosphatase (B-ALP), and 25-hydroxy vitamin D (25(OH)2D3) levels were measured. The participants were categorized into vitamin D sufficient and non-vitamin D sufficient groups, and we analyzed variables that contributed to the 25(OH)2D3 level. Results Of the participants, 73 (60.8%) were vitamin D sufficient, 45 (37.5%) were vitamin D insufficient, and 2 (1.7%) were vitamin D deficient. Sex, age, body mass index, Fitzpatrick skin type, daily milk intake, and clothing type were not different between the vitamin D sufficient and non-vitamin D sufficient groups. There were no differences in serum calcium, phosphate, and B-ALP between the 2 groups. Sun exposure time was significantly longer in the vitamin D sufficient group compared with that in the non-vitamin D sufficient group (511.4 min/wk vs. 318.7 min/wk, P=0.004), and this effect remained consistent on multivariate analysis after adjustment for covariates (adjusted odds ratio, 1.002; 95% confidence interval, 1.000–1.003). More participants in the vitamin D sufficient group did not use sunscreen (59 vs. 27, P=0.02), but this finding was inconsistent with our multivariate analysis. Conclusions Despite year-round sun exposure, approximately 1 in 3 primary school-aged children had insufficient vitamin D level. Sun exposure duration was a major contributing factor.

Purpose: To determine medical student ability to accurately obtain and interpret POCUS exams of varying difficulty in the pediatric population after a short didactic and hands-on POCUS course. Methods: Five medical students were trained in four POCUS applications (bladder volume, long bone for fracture, limited cardiac for left ventricular function, & inferior vena cava collapsibility) and enrolled pediatric ED patients. Ultrasound-fellowship-trained emergency medicine physicians reviewed each scan for image quality and interpretation accuracy using the American College of Emergency Physicians’ quality assessment scale. We report acceptable scan frequency and medical student vs. Ultrasound-fellowship-trained emergency medicine physician interpretation agreement with 95% confidence intervals (CI). Results: Ultrasound-fellowship-trained emergency medicine physicians graded 51/53 bladder volume scans as acceptable (96.2%; 95% CI 87.3-99.0%) and agreed with 50/53 bladder volume calculations (94.3%; 95% CI 88.1-100%). Ultrasound-fellowship-trained emergency medicine physicians graded 35/37 long bone scans as acceptable (94.6%; 95% CI 82.3-98.5%) and agreed with 32/37 medical student long bone scan interpretations (86.5%; 95% CI 72.0-94.1%). Ultrasound-fellowship-trained emergency medicine physicians graded 116/120 cardiac scans as acceptable (96.7%; 95% CI 91.7-98.7%) and agreed with 111/120 medical student left ventricular function interpretations (92.5%; 95% CI 86.4-96.0%). Ultrasound-fellowship-trained emergency medicine physicians graded 99/117 inferior vena cava scans as acceptable (84.6%; 95% CI 77.0-90.0%) and agreed with 101/117 medical student interpretations of inferior vena cava collapsibility (86.3%; 95% CI 78.9-91.4%). Conclusions: Medical students demonstrated satisfactory ability within a short period of time in a range of POCUS scans on pediatric patients after a novel curriculum. This supports the incorporation of a formal POCUS education into medical school curricula and suggests that novice POCUS learners can attain a measure of competency in multiple applications after a short training course.

In the genome of various Leptospira interrogans serovars, the subtype I-B locus of CRISPR-Cas possesses either one or multiple CRISPR arrays. In silico database (CRISPRCasdb) for predicting CRISPR-Cas reveals seven CRISPR arrays in L. interrogans serovar Lai positioned between the two independent cas-operons. Here, we present the redefined repeat-spacer boundaries of the CRISPR subtype I-B locus of serovar Lai. Such refinement of boundaries of arrays in serovar Lai was done after comparison with the characterized array of another serovar Copenhageni and the manual analysis of CRISPR flanking sequences. Using the reverse transcription-PCR (RT-PCR), we account that the seven CRISPR are transcriptionally active in serovar Lai. Our RT-PCR and quantitative real-time PCR analysis of transcripts in serovar Lai indicated that seven CRISPR of subtype I-B transcribe together as a single precursor unit. Moreover, the cleavage of the two miniature pre-crRNA of the subtype I-B by Cas6 demonstrates the biogenesis of the expected size of mature crRNA essential for the guided interference of foreign DNA. This study features insight into transcription direction and the crRNA biogenesis in serovar Lai essential for RNA-mediated interference of invading nucleic acids.

Abstract Despite tremendous success of chimeric antigen receptor (CAR) T cell therapy in clinical oncology, the dose‐exposure‐response relationship of CAR‐T cells in patients is poorly understood. Moreover, the key drug‐specific and system‐specific determinants leading to favorable clinical outcomes are also unknown. Here we have developed a multiscale mechanistic pharmacokinetic (PK)‐pharmacodynamic (PD) model for anti‐B‐cell maturation antigen (BCMA) CAR‐T cell therapy (bb2121) to characterize (i) in vitro target cell killing in multiple BCMA expressing tumor cell lines at varying effector to target cell ratios, (ii) preclinical in vivo tumor growth inhibition and blood CAR‐T cell expansion in xenograft mice, and (iii) clinical PK and PD biomarkers in patients with multiple myeloma. Our translational PK‐PD relationship was able to effectively describe the commonly observed multiphasic CAR‐T cell PK profile in the clinic, consisting of the rapid distribution, expansion, contraction, and persistent phases, and accounted for the categorical individual responses in multiple myeloma to effectively calculate progression‐free survival rates. Preclinical and clinical data analysis revealed comparable parameter estimates pertaining to CAR‐T cell functionality and suggested that patient baseline tumor burden could be more sensitive than dose levels toward overall extent of exposure after CAR‐T cell infusion. Virtual patient simulations also suggested a very steep dose‐exposure‐response relationship with CAR‐T cell therapy and indicated the presence of a “threshold” dose, beyond which a flat dose‐response curve could be observed. Our simulations were concordant with multiple clinical observations discussed in this article. Moving forward, this framework could be leveraged a priori to explore multiple infusions and support the preclinical/clinical development of future CAR‐T cell therapies.

Adeno-associated virus (AAV) is one of the most important gene delivery vehicles for in vivo gene therapy. Intramuscular (i.m.) and intravascular (i.v.) injection are commonly used for AAV gene transfer. Unfortunately, the fate of AAV vectors following administration remains unclear at the histological level. Taking advantage of RNAscope, a recently developed in situ hybridization technique that can reveal high-resolution viral DNA localization information, in this study, we evaluated body-wide distribution of an AAV9 vector in the context of the cell and tissue microenvironments. We observed distinctive kinetics of cell and nuclear entry of the AAV DNA in striated muscle and liver following i.m. and i.v. injection. We also found characteristic distribution patterns of the AAV DNA in various histological structures in internal organs, including gonads and lymph nodes, following i.v. injection. Finally, we showed significantly body-wide spreading of the AAV DNA following i.m. injection. These results add a new dimension to our understanding of AAV transduction biology and provide a basis for assessing the full impact of AAV gene therapy.

Abstract Background Prednisone has been shown to reverse lung function declines in hypersensitivity pneumonitis patients without established fibrosis. Second line immunosuppressants like azathioprine and mycophenolate mofetil have a steroid sparing effect and improve DLCO. There is no published literature on the use of leflunomide in such patients. Methods We reviewed our experience with leflunomide for treatment of chronic hypersensitivity pneumonitis in 40 patients. We stratified patients according to the presence or absence of significant (> 20%) fibrosis. We studied the effect of leflunomide on FVC and DLCO trajectory and reported the changes at 12 months. Results Treatment with leflunomide tended to improve the estimated FVC slope from 0.18 ± 1.90% (SEM) of predicted per year to 4.62 ± 1.65% of predicted (NS, p = 0.118). It significantly improved the FVC at 12 months of treatment by 4.4% of predicted (p = 0.02). DLCO continued to increase at 1.45 ± 1.44% (SEM) of predicted per year. Non-fibrotic cHP patients had the largest gain in pulmonary function. Their FVC increased by 8.3% (p = 0.001) and DLCO by 4.8% (p = 0.011). Patients with fibrotic cHP did not improve. Leflunomide treatment was associated with significant gastrointestinal and other adverse effects leading 40% of patients to discontinue therapy. It had a significant steroid sparing effect with half the patients weaned off prednisone entirely. Conclusions Leflunomide appears to be a fairly well tolerated steroid sparing immunosuppressant that improves pulmonary function in cHP patients. It is most effective in patients without significant fibrosis.

Vaccines are one of the most successful health interventions in history. Yet, vaccine-preventable diseases still claim the lives of 2.5 million individuals globally every year. Approximately 60% of the 19.4 million infants that did not have access to routine immunization services in 2018 live in 10 countries, one of which is Indonesia. In order to reach global targets, it is critical for countries such as Indonesia to prioritize, tailor, and operationalize vaccination strategies to address immunization gaps. Pediatricians and national pediatric societies (NPS) are trusted stakeholders in their countries and are uniquely qualified to promote vaccination programs. The American Academy of Pediatrics (AAP) partnered with the Indonesian Pediatric Society (IPS), with support from the US Centers for Disease Control and Prevention (CDC), to initiate a multiyear project to build the capacity of IPS, individual members, and other child health clinicians to strategically advocate for improved immunization services across both public and private sectors.

INTRODUCTION: Laparoscopic ventral hernia repair (LVHR) was first described in 1992 by Karl Leblanc and has increasingly gained popularity in this current era of minimal access surgery, hereby establishing itself as a well-accepted option for the treatment of these hernias. OBJECTIVE: To assess; if the repair of Symptomatic Ventral hernia using Laparoscopic IPOM-PLUS is an effective modality in the treatment of such hernias or not. AIM: The study reviews our experience in Laparoscopic Intraperitoneal Onlay Mesh repair (IPOM- PLUS) of symptomatic ventral hernia in a single surgical unit at Artemis Hospital, Gurgaon. METHODS: A Prospective observational study was conducted where in we analysed the electronic medical records of 429 patients who underwent Laparoscopic Ventral Hernia Repair between July 2012 to January 2020 at Artemis Hospital, Gurgaon, Haryana. A Follow up period of 24 months was undertaken . RESULTS: Four hundred and twenty nine patients underwent Laparoscopic IPOM in a span of 8 years. All patient's with a defect size of more than 2 cm were included in the study. Average BMI of the cohort was between 28.42 ± 4.8 kg/m2. Primary closure of all hernias greater than 2 cm was done (Trans-fascial sutures taken using Prolene No.1). Dual mesh was used as prosthesis and it was fixed using non absorbable tacking device. Hernia recurrence was found to occur in 2 of the 429 patient's (0.4%) where in one had chronic cough on account of COPD and the other showed excessive weight gain of 12 kg during the follow up period of 24 Months. CONCLUSION: Laparoscopic IPOM- PLUS is a safe, highly efficacious and accepted method for ventral hernia repair with a very low recurrence rate.

Postoperative pseudomeningocele is a common complication of craniotomies for tumor resection. Intracranial hypertension can hinder dural repair and potentially lead to refractory or severe cases of pseudomeningocele. We present an unconventional use of venous sinus stenosis stenting to treat postcraniotomy pseudomeningocele driven by intracranial hypertension.

Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counterintuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfvén waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, α = 2 as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed >600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: preflare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that α = 1.63 ± 0.03. This is below the critical threshold, suggesting that Alfvén waves are an important driver of coronal heating.

Isolated growth hormone (GH) deficiency (IGHD) type 2 is a rare autosomal dominant disorder characterized by severe short stature with low GH level. Timely diagnosis is important for optimal results of recombinant human GH (rhGH) treatment and detection of additional pituitary deficiencies in affected relatives. A male child presented at the age of one year with severe, proportionate short stature [-4.9 standard deviation score (SDS)] and with a normal body mass index (-1.1 SDS). Physical examination revealed frontal bossing, midfacial hypoplasia, normal external genitalia and no dysmorphic features. Paternal and maternal heights were -6.1 and -1.9 SDS. Serum insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 were undetectable and the peak GH concentration by clonidine stimulation test was extremely low (0.18 ng/mL). Brain magnetic resonance imaging showed anterior pituitary hypoplasia. Genetic analysis identified a novel heterozygous mutation (c.291+2T>G) expected to lead to splicing out exon 3 of GH1. rhGH from age 2.4 years led to appropriate catch-up. In conclusion, we identified a novel GH1 gene mutation in an infant with classical IGHD type 2 presentation.

Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130 is the causative agent of leptospirosis in animals and humans. This organism carries a functional cas1 gene classified under CRISPR-Cas I-B. In this study, using various nuclease assays and bioinformatics analysis, we report that the recombinant Cas1 (LinCas1) possesses metal-ion dependent DNase activity, which is inhibited upon substitution or chelation of metal-ion and/or interaction with recombinant Cas2 (LinCas2) of L. interrogans. Model of LinCas1 structure shows a shorter N-terminal domain unlike other Cas1 orthologs reported to date. The C-terminal domain of LinCas1 contains conserved divalent-metal binding residues (Glu108, His176, and Glu191) and the mutation of these residues leads to abolition in DNase activity. Immunoassay using anti-LinCas2 demonstrates that LinCas1 interacts with LinCas2 and attains a saturation point. Moreover, the nuclease activity of the LinCas1-Cas2 mixture on ds-DNA displayed a reduction in activity compared to the pure core LinCas proteins under in vitro condition. The DNase activity for LinCas1 is consistent with a role for this protein in the recognition/cleavage of foreign DNA and integration of foreign DNA as spacer into the CRISPR array.

BackgroundFrequency, dimensions, management, and outcomes of the COVID-19 pandemic in children with endocrine disorders and diabetes were assessed.MethodsA cross-sectional electronic survey was distributed to the global network of endocrine societies. Respondents’ professional and practice profiles, clinic sizes, their country of practice, and the impact of COVID-19 on endocrine diseases were investigated.ResultsRespondents from 131 pediatric endocrine centers in 51 countries across all continents completed the survey. Routine check-ups and education were altered in most pediatric endocrine clinics. Over 20% of clinics experienced a shortage of critical medications or essential supplies. ICU treatment was required for patients with diabetes and COVID-19 in 21.2% of centers. In diabetes, 44% of respondents reported increased diabetic ketoacidosis episodes in newly diagnosed cases and 30% in established cases. Biopsychosocial and behavioral changes were explicitly reported to be occurring among pediatric patients with endocrine disorders.ConclusionsThis large global survey conducted during the COVID-19 pandemic highlights that diabetes is more challenging to manage than any other pediatric endocrine disorder, with an increased risk of morbidity. Psychological distress due to COVID-19 needs to be recognized and addressed. The importance of close contact with healthcare professionals should be emphasized, and medical supplies should be readily available to all patients.

Since the outbreak of the COVID-19 pandemic, there has been a rapid expansion in vaccine research focusing on exploiting the novel discoveries on the pathophysiology, genomics, and molecular biology of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although the current preventive measures are primarily socially distancing by maintaining a 1 m distance, it is supplemented using facial masks and other personal hygiene measures. However, the induction of vaccines as primary prevention is crucial to eradicating the disease to attempt restoration to normalcy. This literature review aims to describe the physiology of the vaccines and how the spike protein is used as a target to elicit an antibody-dependent immune response in humans. Furthermore, the overview, dosing strategies, efficacy, and side effects will be discussed for the notable vaccines: BioNTech/Pfizer, Moderna, AstraZeneca, Janssen, Gamaleya, and SinoVac. In addition, the development of other prominent COVID-19 vaccines will be highlighted alongside the sustainability of the vaccine-mediated immune response and current contraindications. As the research is rapidly expanding, we have looked at the association between pregnancy and COVID-19 vaccinations, in addition to the current reviews on the mixing of vaccines. Finally, the prominent emerging variants of concern are described, and the efficacy of the notable vaccines toward these variants has been summarized.

In the profession of education, predicting students' academic success is an essential responsibility. This study introduces a novel methodology for predicting students' pass or fail outcome in certain courses. The system utilises academic, demographic, emotional, and VLE sequence information of students. Traditional prediction methods often struggle to capture the temporal dynamics inherent in student data, such as learning trajectories, study habits, and evolving performance patterns. In response, this research leverages Recurrent Neural Network (RNNs) and Long Short Term Memory (LSTM) network (LSTMs), which are specifically designed to model sequences and long-term dependencies from OULAD and self-generated Emotional dataset. By incorporating these architectures, the proposed methodology excels in capturing the intricate relationships between various factors over time. Further, various ML models such as Random Forest (RF), Support Vector Machine (SVM), Naive Bayes (NB) and Decision Tree (DT) are integrated with RNN + LSTM to enhance the predictive power of model. The proposed system with RNN + LSTM + RF techniques gained approximately 97% accuracy that is comparatively higher than RNN + LSTM + SVM, RNN + LSTM + NB and RNN + LSTM + DT i.e., 90.67%, 86.45% & 84.42% respectively.

In the United States, culturally responsive computing is a framework that aims to support broadening the participation of racially and linguistically diverse children in computing and technology education through bottom-up interventions that are community-oriented, technology rich, and culturally dynamic. Despite the important role that youth sports play in many local neighborhoods and communities across demographic groups there is only a small amount of research on developing culturally responsive computing education that incorporates these activities. We report findings from a culturally responsive computing collaboration between computing education researchers and coaches, mentors, and academic staff who ran a youth boxing program that predominantly served African American children. The purpose of the collaboration was to learn about and represent the adults' expertise and knowledge in the co-development of culturally responsive computing activities. Using an emergent mixed methods research design, we collected qualitative data (i.e., interviews and group discussions) and quantitative data (i.e., pre- and post-surveys) throughout the collaboration. We analyzed these data to study how coaches, mentors, and staff members brought their knowledge and expertise to bear on the co-development of culturally responsive computing activities for the youth boxing program. Our findings show how the coaches, mentors, and academic staff used their expertise and knowledge in ways that leveraged boxing culture to go beyond boxing itself in the co-development of the activities. In addition, even when connections between computing and boxing did not appear authentically motivated this did not negate the adults' engagement with the culturally responsive computing project. These findings have implications for anti-deficit theorizing about authenticity and inauthenticity in the co-development of culturally responsive computing in youth sports contexts. The construction of authenticity in culturally responsive computing might be less understood as a direct translation from community into education and more so as a negotiation between locally defined demarcations of what is considered authentic and inauthentic.