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Vitamin D deficiency in infants is widely prevalent. Most paediatric professional associations recommend routine vitamin D prophylaxis for infants. However, the optimal dose and duration of supplementation are still debated. We aimed to compare the efficacy and safety of different vitamin D supplementation regimens in term and late preterm neonates. For this systematic review and network meta-analysis, we searched MEDLINE, the Cochrane Central Register of Controlled Trials and Embase. Randomised and quasi-randomised clinical trials that evaluated any enteral vitamin D supplementation regimen initiated within 6 weeks of life were included. Two researchers independently extracted data on study characteristics and outcomes and assessed quality of included studies. A network meta-analysis with a Bayesian random-effects model was used for data synthesis. Certainty of evidence (CoE) was assessed using GRADE. Primary outcomes were mean serum vitamin D concentrations and the proportion of infants with vitamin D insufficiency (VDI). We included twenty-nine trials that evaluated fourteen different regimens of vitamin D supplementation. While all dosage regimens of ≥400 IU/d increased the mean 25(OH)D levels compared with no treatment, supplementation of ≤250 IU/d and 1400 IU/week did not. The CoE varied from very low to high. Low CoE indicated that 1600 IU/d, compared with lower dosages, reduced the proportion of infants with VDI. However, our results indicated that any dosage of ≥800 IU/d increased the risk of hypervitaminosis D and hypercalcaemia. Data on major clinical outcomes were sparse. Vitamin D supplementation of 400-600 IU/d may be the most effective and safest in infants.

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Multiple myeloma (MM) treatment guidelines recommend waiting for formal progression criteria (FPC) to be met before proceeding to the next line of therapy. As predicting progression may allow early switching to next-line therapy while the disease burden is relatively low, we evaluated the predictive accuracy of a mathematical model to anticipate relapse 180 days before the FPC is met. A subset of 470/1143 patients from the IA16 dataset who were initially treated with VRd (Velcade (bortezomib), Revlimid (lenalidomide), and dexamethasone) in the CoMMpass study (NCT01454297) were randomly split 2:1 into training and testing sets. A model of M-protein dynamics was developed using the training set and used to predict relapse probability in patients in the testing set given their response histories up to 12 or more months of treatment. The predictive accuracy of this model and M-protein "velocity" were assessed via receiver operating characteristics (ROC) analysis. The final model was a two-population tumor growth inhibition model with additive drug effect and transit delay compartments for cell killing. The ROC area under the curve value of relapse prediction 180 days ahead of observed relapse by FPC was 0.828 using at least 360 days of response data, which was superior to the M-protein velocity ROC score of 0.706 under the same conditions. The model can predict future relapse from early M-protein responses and can be used in a future clinical trial to test whether early switching to second-line therapy results in better outcomes in MM.

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OBJECTIVES: In this study, we have reviewed the association between esophageal pressure-guided positive end-expiratory pressure (PEEP) setting and oxygenation and lung mechanics with a conventional mechanical ventilation (MV) strategy in patient with moderate to severe pediatric acute respiratory distress syndrome (PARDS). DESIGN: Retrospective cohort, 2018-2021. SETTING: Tertiary PICU. PATIENTS: Moderate to severe PARDS patients who required MV with PEEP of greater than or equal to 8 cm H2O. INTERVENTIONS: Esophageal pressure (i.e., transpulmonary pressure [PTP]) guided MV vs. not. MEASUREMENTS AND MAIN RESULTS: We identified 26 PARDS cases who were divided into those who had been managed with PTP-guided MV (PTP group) and those managed with conventional ventilation strategy (non-PTP). Oxygenation and lung mechanics were compared between groups at baseline (0 hr) and 24, 48, and 72 hours of MV. There were 13 patients in each group in the first 24 hours. At 48 and 72 hours, there were 11 in PTP group and 12 in non-PTP group. On comparing these groups, first, use of PTP monitoring was associated with higher median (interquartile range) mean airway pressure at 24 hours (18 hr [18-20 hr] vs. 15 hr [13-18 hr]; p = 0.01) and 48 hours (19 hr [17-19 hr] vs. 15 hr [13-17 hr]; p = 0.01). Second, use of PTP was associated with higher PEEP at 24, 48, and 72 hours (all p < 0.05). Third, use of PTP was associated with lower Fio2 and greater Pao2 to Fio2 ratio at 72 hours. Last, there were 18 of 26 survivors, and we failed to identify an association between use of PTP monitoring and survival. CONCLUSIONS: In this cohort of moderate to severe PARDS cases undergoing MV with PEEP greater than or equal to 8 cm H2O, we have identified some favorable associations of oxygenation status when PTP-guided MV was used vs. not. Larger studies are required.

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With technological advancement, neonatal intensive care units (NICUs) have become noisier than ever. Studies have shown the detrimental effects of increasing noise in NICU on growing pre-term and sick neonates. The present study aimed primarily to compare the amount of noise in NICUs of private and government hospitals. The secondary aim was to compare the strategies adopted by these hospitals to control the detrimental effects of noise on newborns. A detailed noise survey was conducted in the NICUs of two private and two government hospitals in the Jodhpur district, India. The noise survey was performed for a duration of 48 h using "Sound Ear 3-300" noise meters. The analyses were measured in Leq (equivalent continuous sound level) A-weighted decibels (dBA). The extracted data analysis revealed that the noise measured was in the range of 61.62-82.32 dBA in four NICUs of the district. The results also revealed a statistically significant difference between the NICU noise of private and government hospitals. The levels of alarming sounds differed between the hospitals with a general trend of lesser alarming sounds in private hospitals. The major differences in strategies adopted were that both private hospitals had a protocol to purposely reduce levels of alarming sounds when heard, and purposely limited the number of staff present in certain areas of the NICU, which were correlated with reduced sound compared to the government hospitals. Strategies like these require no additional cost to make drastic changes in the average noise measured.

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CONTEXT: Heel prick is one among the common painful procedures in neonates. We performed a systematic review and network meta-analysis (NMA) to compare the efficacy of different interventions for analgesia during heel prick in neonates. EVIDENCE ACQUISITION: Medline, Cochrane, Embase and CINAHL databases were searched from inception until February 2023. Randomized and quasi-randomized trials that evaluated different pharmacological and non-pharmacological interventions for analgesia during heel prick for neonates were included. Data from the included trials were extracted in duplicate. A NMA with a frequentist random-effects model was used for data synthesis. Certainty of evidence (CoE) was assessed using GRADE. We adhered to the PRISMA-NMA guidelines. RESULTS: One-hundred-and-three trials comparing 51 different analgesic measures were included. Among the 38 interventions, for pain "during" heel prick, non-nutritive suckling (NNS) plus sucrose [SMD -3.15 (-2.62, -3.69)], followed by breastfeeding, glucose, expressed breast milk (EBM), sucrose, NNS and touch massage, had a high certainty of evidence (CoE) to reduce pain scores when compared to no intervention. Among the 23 interventions for pain at 30 seconds after heel-prick, moderate CoE was noted for facilitated tucking plus NNS plus music, glucose, NNS plus sucrose, sucrose plus swaddling, mother holding, EBM, sucrose and NNS. CONCLUSIONS: Oral sucrose 2 minutes before combined with NNS during the procedure, was the best intervention for reducing pain during heel prick. It also effectively reduced pain scores 30 seconds and 1 minute after the procedure. Other interventions with moderate to high CoE for a significant reduction in pain during and at 30 seconds after heel prick are oral sucrose, oral glucose, EBM and NNS. All these are low-cost and feasible interventions for most of the settings.

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The presence of lead(II) ion poses a significant threat to water systems due to their toxicity and potential health hazards. The detection of Pb2+ ions in contaminated water is very crucial. The ionic liquid functionalized multiwalled carbon nanotubes (IL@MWCNT) nanocomposite was fabricated using ionic liquid (IL) 1-methyl-3-(4-sulfobutyl)-imidazolium chloride and multiwalled carbon nanotubes (MWCNTs) for detection of lead(II) ions. It is a novel method to heterogenize the layer of IL on the surface of MWCNTs. The XPS and FTIR analyses confirm that the ionic liquid is not decomposed during annealing process. Moreover, the XRD analysis shows the presence of MWCNTs and carbon quantum dots (CQDs). The HRTEM results exhibit the aggregation of MWCNTs with IL, and formation of small distorted round shaped flakes of CQDs. Further, the successful heterogenization of IL on the surface of MWCNTs is also confirmed by TGA-DSC analysis. The quenching phenomenon of nanocomposite was observed by UV-Visible spectroscopy. The nanocomposite exhibits high performance for the selective detection of lead(II) ions in comparison to other metal ions. The presence of lead(II) ions eventually reduced the intensity of absorption. A limit of detection (LOD) of 9.16 nM was attained for Pb2+ ions in a concentration range of 0-20 nM.

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Background: There is paucity of reliable epidemiological data regarding the burden of food allergy in most developing countries, including India. Objective: To provide current estimates of the prevalence and distribution of food allergy among urban and rural school children aged 6-14 years in Delhi and the National Capital Region (NCR) of Khekra in India. Methods: A cross-sectional study was conducted from January 2022 to February 2023 to enroll school children, 6-14 years, from select urban and rural schools in Delhi and NCR. A questionnaire consisting of questions focused on household environment, early life factors, and pediatric food allergy characteristics was administered by a trained medical researcher to collect parent-proxy data. Univariate statistics were used to describe frequencies, percentages, and 95% confidence intervals for survey items. Results: The estimated prevalence of parent-reported food allergy was 0.8% (95% CI: 0.4-1.5; urban: 0.4%, 95% CI: 0.1-1.1; rural: 1.7%, 95% CI: 0.7-3.5). Fruits such as mango (0.3%, 95% CI: 0.1-0.9), strawberry (0.1%, 95% CI: 0.0-0.7), orange (0.1%, 95% CI: 0.0-0.7), and custard apple (0.1%, 95% CI: 0.0-0.7) were reported only by urban children, while rural children reported yogurt (0.6%, 95% CI: 0.1-1.8) and wheat (0.3%, 95% CI: 0.0-1.3). Both groups reported brinjal (also known as eggplant) and banana, 0.1% (95% CI: 0.0-0.7) of urban and 0.3% (95% CI: 0.0-1.3) of rural, respectively. Overall, commonly reported clinical symptoms were diarrhea and/or vomiting (100%, 95% CI: 76.2-100), abdominal pain (88.9%, 95% CI: 58.6-98.8), and rash/itchy skin (66.7%, 95% CI: 34.8-89.6). Among children with parent reported food allergy, 66.7% (95% CI: 34.8-89.6) of food allergies were physician diagnosed, of which 33.3% were diagnosed via history alone (95% CI:7.7-71.4) while 66.7% (95% CI: 28.6-92.3) were confirmed via skin prick test and/or blood test. Conclusion: The overall prevalence of food allergy is very low in Delhi and Khekra, India. Future work should focus on elucidating the complex interplay of early-life, environmental, genetic, and lifestyle factors to understand the reasons for India's low food allergy burden and improve epidemiological clues to prevention for the nations with higher disease burden.

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Multiple myeloma management requires a balance between maximizing survival, minimizing adverse events to therapy, and monitoring disease progression. While previous work has proposed data-driven models for individual tasks, these approaches fail to provide a holistic view of a patient's disease state, limiting their utility to assist physician decision-making. To address this limitation, we developed a transformer-based machine learning model that jointly (1) predicts progression-free survival (PFS), overall survival (OS), and adverse events (AE), (2) forecasts key disease biomarkers, and (3) assesses the effect of different treatment strategies, e.g., ixazomib, lenalidomide, dexamethasone (IRd) vs lenalidomide, dexamethasone (Rd). Using TOURMALINE trial data, we trained and internally validated our model on newly diagnosed myeloma patients (N = 703) and externally validated it on relapsed and refractory myeloma patients (N = 720). Our model achieved superior performance to a risk model based on the multiple myeloma international staging system (ISS) (p < 0.001, Bonferroni corrected) and comparable performance to survival models trained separately on each task, but unable to forecast biomarkers. Our approach outperformed state-of-the-art deep learning models, tailored towards forecasting, on predicting key disease biomarkers (p < 0.001, Bonferroni corrected). Finally, leveraging our model's capacity to estimate individual-level treatment effects, we found that patients with IgA kappa myeloma appear to benefit the most from IRd. Our study suggests that a holistic assessment of a patient's myeloma course is possible, potentially serving as the foundation for a personalized decision support system.

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Objective: To determine the effectiveness of the telemedicine-based pulmonary rehabilitation programme in COVID-19 pneumonitis. Design: Prospective intervention study. Setting: Rehabilitation outpatient department, Tertiary-Care institute. Participants: Consecutive sample of patients (N = 50) in recovered COVID-19 infection. Intervention: Six weeks of telemedicine-based pulmonary rehabilitation in recovered patients of COVID-19 infection. Outcome Measures: All patients were clinically assessed by six minutes walk test (6MWT), Modified Medical Research Council Scale (mMRC), 30s-STS and SF 36 at zero week and six weeks post-intervention. Statistical Analysis: Difference in means of pre- and post-intervention was compared using paired t-test. A P value <0.05 was considered statistically significant. Results: The 6MWT, mMRC Scale, 30 seconds sit-to-stand test, and WHO QoL scale-SF 36 were assessed and post-rehabilitation sessions, all the patients' showed improvement in the prescribed parameters. After six weeks of respiratory rehabilitation, the distance covered in the 6MWT was significantly longer than that of before the intervention. There was a significant difference between zero and six weeks during the PR intervention. mMRC and 30s-STS results showed a significant difference between zero and six weeks (2.36 ± 0.598, 4.54 ± 1.94. Quality of life improved significantly after six weeks of pulmonary rehabilitation in eight domains of the SF-36. Conclusion: Six-week pulmonary rehabilitation programme delivered through telemedicine platform improves respiratory function, QoL and anxiety in patients with post-COVID-19 pneumonia during a recovery phase.

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This work reports the preparation of a metal-free nitrogen and sulphur functionalized graphitic carbon sheets from a unique and less expensive precursor Lantana camara, which is a common hazardous weed in India. The synthesized material NS-CN-180 was successfully tested for the adsorption and removal of fluoroquinolone antibiotics ciprofloxacin. The surface morphology and elemental composition of NS-CN-180 were investigated through FESEM and XPS analyses. The SEM data reveals the graphitic sheets stacked onto each other with cavities in between them. The presence of various functional groups was identified through FT-IR spectroscopy and the degree of graphitization was calculated from XRD pattern. The probable mechanism of interaction for ciprofloxacin molecule with NS-CN-180 was also investigated with the help of FT-IR and zeta potential analyses. The fabricated material was found to be excellent for ciprofloxacin detection with a limit of detection value 16.08 nM. Also, the prepared material efficiently removes the 66.2% ciprofloxacin drug in 1 h. Adsorption and desorption experiments were performed to demonstrate the reusability of the material.

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Crop diseases pose significant threats to agriculture, impacting crop production. Biotic factors contribute to various diseases, including fungal, bacterial, and viral infections. Recent advancements in deep learning present a novel approach to the detection and recognition of these crop diseases. While considerable research has focused on identifying and recognizing crop diseases, fungal disease-affected crops have received relatively less attention and also detecting disease on different region datasets. This paper is about spotting fungal diseases in crops across different regions with diverse climates. It emphasizes the need for tailored detection methods, addressing the risk of mycotoxin production by fungi, which can harm both humans and animals. Detecting fungal diseases in apple, guava, and custard apple crops such as spot, scab, rust, rot, leaf spot, and insect ate. In the proposed work, the modified ResNeXt variant of the convolution neural network (CNN) technique was employed to predict 3 major crop classes of fungal disease. Initially, using Inception-v7 and ResNet for fungal disease in crops did not yield satisfactory results. A modified ResNeXt CNN model was proposed, showing improved fungal disease prediction. The novel model underwent a comparison with established methodologies. The suggested model draws upon a benchmark dataset consisting of 14,408 images capturing fungal diseases, categorized into three distinct classes: apple, custard apple, and guava. Experimental outcomes show that the proposed mutated ResNeXt model outperformed the state-of-the-art approaches. The model achieved 98.92% accuracy and high performance across recall, precision, and F1-score (above 99%) for the benchmark dataset, which gained encouragement and was comparable with the state-of-the-art approach.

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Mobocertinib (TAK-788) is a first-in-class oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that received accelerated approval for the treatment of patients with non-small cell lung cancer with EGFR exon 20 insertion mutations previously treated with platinum-based chemotherapy. This phase 1, 2-period, study was conducted to assess the absolute bioavailability of mobocertinib (Period 1), as well as mass balance, pharmacokinetics, metabolism, and excretion of [14C]-mobocertinib (Period 2) in healthy adult males. In Period 1, participants received a single oral capsule dose of 160 mg mobocertinib, followed by a 15-minute intravenous infusion of 50 µg (~ 2 µCi) [14C]-mobocertinib administered from 3.75 to 4 h after the capsule dose. In Period 2, a single oral dose of 160 mg (~ 100 µCi) [14C]-mobocertinib was administered as an oral solution. The geometric mean absolute bioavailability of mobocertinib was determined to be 36.7%. After oral administration of [14C]-mobocertinib, mobocertinib and its active metabolites, AP32960 and AP32914, were minor components in plasma, accounting for only 0.275% of total plasma radioactivity as the majority of mobocertinib-related material was covalently bound to plasma proteins. The geometric mean percentage of the administered radioactive dose recovered in the urine and feces was 3.57% and 76.0%, respectively. Only 0.39% of the oral dose of [14C]-mobocertinib was recovered in the urine as mobocertinib; thus, indicating that renal excretion of unchanged drug was a very minor pathway of elimination. In both treatment periods, mobocertinib was generally safe and well-tolerated as all adverse events were Grade 1 in severity. (Trial registration number ClinicalTrials.gov NCT03811834. Registration date January 22, 2019).

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The landscape of oncology drug development has witnessed remarkable advancements over the last few decades, significantly improving clinical outcomes and quality of life for patients with cancer. Project Optimus, introduced by the U.S. Food and Drug Administration, stands as a groundbreaking endeavor to reform dose selection of oncology drugs, presenting both opportunities and challenges for the field. To address complex dose optimization challenges, an Oncology Dose Optimization IQ Working Group was created to characterize current practices, provide recommendations for improvement, develop a clinical toolkit, and engage Health Authorities. Historically, dose selection for cytotoxic chemotherapeutics has focused on the maximum tolerated dose, a paradigm that is less relevant for targeted therapies and new treatment modalities. A survey conducted by this group gathered insights from member companies regarding industry practices in oncology dose optimization. Given oncology drug development is a complex effort with multidimensional optimization and high failure rates due to lack of clinically relevant efficacy, this Working Group advocates for a case-by-case approach to inform the timing, specific quantitative targets, and strategies for dose optimization, depending on factors such as disease characteristics, patient population, mechanism of action, including associated resistance mechanisms, and therapeutic index. This white paper highlights the evolving nature of oncology dose optimization, the impact of Project Optimus, and the need for a tailored and evidence-based approach to optimize oncology drug dosing regimens effectively.

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This study was conducted to isolate and identify the chemical compounds from the roots of Aloe debrana (L.) and evaluate their antioxidant and antibacterial activities. From the acetone (99.5%) extract of the roots of this plant, four anthraquinones, such as chrysophanol (1), asphodeline (2), aloesaponarin I (5), and laccaic acid D-methyl ester (6), and a new catechol derivative, 5-allyl-3-methoxybenzene-1,2-diol (3), were isolated and elucidated by different chromatographic and spectroscopic methods together with linoleic acid (4), respectively. Compounds 2, 3, and 4 were reported here for the first time from this plant and compound 3 from the genus Aloe. The compounds were evaluated for their antioxidant activity using H2O2 and DPPH assays and bactericidal activity against S. aureus and E. coli. Compounds 3 and 6 showed highest antioxidant activities with IC50 values of 19.38 ± 0.64 and 32.81 ± 0.78 µg/mL in DPPH, and 28.52 ± 1.08 and 27.31 ± 1.46 µg/mL in H2O2, respectively. The isolated compounds also demonstrated considerable activity towards S. aureus. Among these compounds, compound 3 exhibited the highest activity (91.20 ± 0.12% and 9.14 ± 0.93 mm at 1.0 mg/mL) against this bacterium. The overall results suggest that the isolated compounds may be considered as potential sources of the bioactive agents to be used in the pharmacological, food, and other industries. Moreover, their high sensitivity against S. aureus may also support the use of A. debrana plant in the traditional medicine to treat wounds. Therefore, the isolated compounds are responsible for medicinal properties of this plant.

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This mini-review on doping and heterojunctions for catalysis applications provides a comprehensive overview of key aspects. Doping, when carried out adequately with a uniform distribution, creates a new energy level that significantly enhances charge transfer and light absorption. This new level alters the material's morphology and enhances intrinsic defects. For instance, ZnO, despite its exceptional band edge concerning oxygen reduction and water oxidation redox potentials, faces the issue of electron-hole recombination. However, forming a heterojunction can effectively aid charge transfer and prolong electron-hole relaxation without recombination. This is where the role of doping and heterojunctions becomes crucial. Additionally, incorporating noble metals with S- and Z-scheme heterojunctions offers a promising mechanism for charge transfer and visible light harvesting, further amplifying the catalytic properties.

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