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Abstract This study aimed to classifying wheat genotypes using support vector machines (SVMs) improved with ensemble algorithms and optimization techniques. Utilizing data from 302 wheat genotypes and 14 morphological attributes to evaluate six SVM kernels: linear, radial basis function (RBF), sigmoid, and polynomial degrees 1–3. Various optimization methods, including grid search, random search, genetic algorithms, differential evolution, and particle swarm optimization, were used. The radial basis function kernel achieves the highest accuracy at 93.2%, and the weighted accuracy ensemble further improves it to 94.9%. This study shows the effectiveness of these methods in agricultural research and crop improvement. Notably, optimization-based SVM classification, particularly with particle swarm optimization, saw a significant 1.7% accuracy gain in the test set, reaching 94.9% accuracy. These findings underscore the efficacy of RBF kernels and optimization techniques in improving wheat genotype classification accuracy and highlight the potential of SVMs in agricultural research and crop improvement endeavors.

Introduction: Surgical treatment for Benign Prostatic Hyperplasia (BPH) has advanced significantly in recent years. Transurethral Resection of the Prostate (TURP) is a minimally invasive procedure associated with a low risk of complications and clinical limitations, including life-threatening Transurethral Resection (TUR) syndrome, as, well as higher costs due to longer hospital stays and challenges in managing large glands. Aim: To compare the safety and effectiveness of prostate enucleation using Holmium Laser Enucleation of the Prostate (HoLEP) with bipolar resection of the prostate in cases of BPH. Materials and Methods: A hospital-based prospective interventional study was conducted in the Department of Urology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India, from January 2020 to July 2022. The study included 60 patients, divided into two groups of 30 each. Males aged ≥45 years with recurrent Lower Urinary Tract Symptoms (LUTS) secondary to BPH, with or without Acute Urinary Retention (AUR) (drug-refractory) or with failed medical therapy (alpha-blockers, 5-alpha reductase inhibitors), were included in the study. In the first group, HoLEP was performed (Group I), while in the second group (Group II), patients underwent bipolar resection. Data were analysed and statistically evaluated using Statistical Package for the Social Sciences (SPSS) software version 21.0. A p-value of less than 0.05 was considered statistically significant. Results: The mean age of patients in the HoLEP group was 60.25 years, while in the Bipolar TURP (B-TURP) group, it was 59.67 years. Both groups had similar proportions of patients with moderate urinary symptoms {International Prostate Symptom Score (IPSS)} and large prostates (>80 grams). The mean amount of irrigation fluid used (40.83±9 litres vs. 21.2±5.9 litres) and the duration of surgery (106.33±14.24 min vs. 67.4±9.73 minutes) were significantly higher in the HoLEP group compared to the B-TURP group (p-value

Abstract Multiple studies have demonstrated that cancer cells with microsatellite instability (MSI) are intolerant to loss of the Werner syndrome helicase (WRN), whereas microsatellite-stable (MSS) cancer cells are not. Therefore, WRN represents a promising new synthetic lethal target for developing drugs to treat cancers with MSI. Given the uncertainty of how effective inhibitors of WRN activity will prove in clinical trials, and the likelihood of tumours developing resistance to WRN inhibitors, alternative strategies for impeding WRN function are needed. Proteolysis-targeting chimeras (PROTACs) are heterobifunctional small molecules that target specific proteins for degradation. Here, we engineered the WRN locus so that the gene product is fused to a bromodomain (Bd)-tag, enabling conditional WRN degradation with the AGB-1 PROTAC specific for the Bd-tag. Our data revealed that WRN degradation is highly toxic in MSI but not MSS cell lines. In MSI cells, WRN degradation caused G2/M arrest, chromosome breakage and ATM kinase activation. We also describe a multi-colour cell-based platform for facile testing of selective toxicity in MSI versus MSS cell lines. Together, our data show that a degrader approach is a potentially powerful way of targeting WRN in MSI cancers and paves the way for the development of WRN-specific PROTAC compounds.

We present a case of a young male from a low socioeconomic background who presented with mucosal ulceration, hematemesis episodes, and pancytopenia following treatment with trimethoprim-sulfamethoxazole (TMP-SMX) for a urinary tract infection. On examination, the patient exhibited signs of severe anemia and hemodynamic instability. After stabilization and a thorough workup a diagnosis of idiosyncratic drug reaction secondary to TMP-SMX was established, believed to be exacerbated by the patient’s immune-hyperactive state due to a recent HIV diagnosis. Initiation of methylprednisolone therapy resulted in rapid improvement in blood parameters. This case highlights the complexity of TMP-SMX-induced pancytopenia in the context of HIV infection and emphasizes the prompt recognition and management of such life-threatening adverse reactions in immunocompromised individuals.

Abstract Oscillatory flow in confined spaces is central to understanding physiological flows and rational design of synthetic periodic-actuation based micromachines. Using theory and experiments on oscillating flows generated through a laser-induced cavitation bubble, we associate the dynamic bubble size (fluid velocity) and bubble lifetime to the laser energy supplied—a control parameter in experiments. Employing different channel cross-section shapes, sizes and lengths, we demonstrate the characteristic scales for velocity, time and energy to depend solely on the channel geometry. Contrary to the generally assumed absence of instability in low Reynolds number flows ( $$

Background: Germ cell tumours (GCT) are tumours arising from primordial germ cells. Gonadal and extragonadal GCT are infrequent in childhood occurring at a rate of 2.4 cases per million children accounting for 2-3 % of paediatric malignancies with most common subtype being a matured Teratoma. Case presentation: We present a case of a 10-year-old female child who presented to the emergency department of a tertiary care centre with complaints of cough with massive expectoration of blood of approximately 200 ml in quantity which on imaging revealed a left anterior mediastinal mass which was managed by left lateral thoracotomy with a non-anatomical left sided pulmonary lobectomy which on histopathology was diagnosed to be a case of mature teratoma. Conclusion: This case report describes a unique presentation of extra-gonadal mediastinal teratoma which presented as a rare complication with rupture into the left bronchus. It emphasizes caution and a high clinical suspicion is required in managing cases of varied presentations of teratomas.

Introduction: Orthodontic treatment of severe Bi-maxillary protrusion cases involves extractions of all four premolars to provide space for anterior teeth retraction. Over the years different methods of retraction have been developed for individual tooth retraction and en-masse anterior teeth retraction utilising different types of mechanics for retraction purposes. Anchorage consideration has been a problem because of anchor loss, but it has been overcome by utilising absolute anchorage with Temporary Anchorage Devices (TAD). Need for the study: The TAD devices mini plates and mini-screw have been Known for providing absolute anchorage for retraction purposes but there has been limited evidence to prove which TAD device is better in terms of time taken for retraction and external root resorption. Therefore, the present clinical study aims to determine the superior treatment method using the two devices based on duration in terms of time taken and amount of retraction achieved in the specified time. Aim: Evaluation and comparison of the effectiveness of mini-plate and mini-screw for retraction of anterior teeth in severe bimaxillary protrusion cases with extraction of Ist bicuspids. Materials and Methods: A split-mouth randomised controlled trial will be carried out in the Department of Orthodontics and Dentofacial Orthopedics, Sharad Pawar Dental College and Hospital, Sawangi, Wardha, from October 2024 to March 2026 with a total of 11 subjects. The sample will be selected from the Outpatient Department based on the study’s inclusion and exclusion criteria. Informed written consent will be gathered from all participants. The patient sample will be divided into two groups: Group-A: will receive a mini screw (control group) and Group-B: will receive a mini-plate (experimental group). The statistical analysis for comparing the en-mass rate of retraction of anterior teeth (mm) in the allocated groups will be done using the Mann-Whitney test, and student’s t-test, with the significance level set at 5%.

One in seven neonates on antenatal scan detected hydronephrosis has Pelviureteric Junction Obstruction (PUJO), making PUJO one of the most common cause of congenital urinary tract obstruction, with an incidence of one in 1000 to one in 2000 live births. Hereby, the authors present a case report of 19-year-old female who presented with pain in abdomen since, two weeks. There was no history of dysuria, haematuria. No history of lower urinary tract symptoms. No history of fever. There was no history of co-morbidity. No similar episodes of pain in past. All blood investigations were within normal limits with serum creatinine of 0.78 mg/dL. Computed Tomography (CT) Intravenous Urography (IVU) showed right ectopic kidney with Pelviureteric junction obstruction with left small atrophic kidney. Diethylenetriaminepentaacetic Acid (DTPA) reported crossed fused kidneys. Two investigations gave two different diagnoses. It made diagnosis and treatment challenging. Cystoscopy showed two ureteric orifices are normal position. Retrograde pyelogram showed left blind ureter. Right pelvic kidney was seen. Delayed drainage of contrast made diagnosis of pelvi ureteric junction obstruction. So it ruled out diagnosis of crossed fused kidneys with help of cystoscopy and retrograde pyelogram. Such anomalous kidneys are rare to find in day to day life. As anomalous kidneys usually have abnormal blood supply it makes surgery challenging. Abnormal position of kidney, malrotation makes surgery difficult. So decision was made to do open surgery for present patient. Open pyeloplasty was performed for right pelvi ureteric obstruction. Also, DTPA interpretation as anatomical investigation should be used with pinch of salt.

Background and Aims: Anemia impairs glucose homeostasis, affects glycemic control, and predisposes to complications in diabetics. It correlates with oxidative stress and increases the risk of developing microvascular and macrovascular complications. However, it is an underrecognized comorbidity in diabetics. This study was conducted to assess the prevalence of anemia in diabetic patients and compare the metabolic profiles of anemic and non-anemic diabetics. Methods: This is a cross-sectional study, conducted among type 2 diabetes (T2DM) patients, at the outpatient clinic. Patients with chronic kidney disease (CKD), known hematological disorders, and chronic inflammatory disorders were excluded. Results: Of the 97 patients, 37 (38.14%) were found to be anemic (hemoglobin (Hb): male

Abstract This work experimentally addresses damage calibration of an unmanned aerial vehicle in operational condition. A wide range of damage level and types are simulated and controlled by an electric motor via pulse width modulation in this regard. The measurement is carried out via established protocols of using a piezo-patch on one of the 8 arms, utilising the vibration sensitivity and flexibility of the arms, demonstrating repeatability of such protocol. Subsequently, recurrence analysis on the voltage time series data is performed for detection of damage. Quantifiers of damage extent are then created for the full range of damage conditions, including the extreme case of complete loss of power. Experimental baseline condition for no damage condition is also established in this regard. Both diagonal-line and vertical-line based indicators from recurrence analysis are sensitive to the quantitative estimates of damage levels and a statistical test of significance analysis confirms that it is possible to automate distinguishing the levels of damage. The damage quantifiers proposed in this paper are useful for rapid monitoring of unmanned aerial vehicle operations of connection.

Abstract One of the most vital parameters to achieve sustainability in any field is encompassing the Occupational Health and Safety (OHS) of the workers. In mining industry where heavy earth moving machineries are largely employed, ergonomic hazards turn out to be significant OHS hazards causing Musculoskeletal Disorders (MSDs) in the operators. Nevertheless, the Indian mining industry lacks a comprehensive technique of OHS risk assessment, especially for ergonomic hazards that cause MSDs. This research appraises ergonomic hazards and develops Fuzzy Musculoskeletal-disorders Index (FMI) model to evaluate ergonomic-related MSDs. Work process and work tool ergonomic risk factors were identified through literature review and directives recommended by experts. Work posture was evaluated using RULA. The data-collecting approach was implemented using participatory ergonomic and design science principles. The FMI results show average MSDs score of 3.69, indicating high to extremely high risk. Surface plots show that combined work tool and work process was the most sensitive factors to MSDs risk compared to other two combinations. A two-sample t-test validated the FMI. The findings should help safety experts and managers develop effective OHS management plans and programmes for the sustainability of Indian mining industry.

Abstract Urinary bladder dysfunction can be caused by environmental, genetic, and developmental insults. Depending upon insult severity, the bladder may lose its ability to maintain volumetric capacity and intravesical pressure resulting in renal deterioration. Bladder augmentation enterocystoplasty (BAE) is utilized to increase bladder capacity to preserve renal function using autologous bowel tissue as a “patch.” To avoid the clinical complications associated with this procedure, we have engineered composite grafts comprised of autologous bone marrow mesenchymal stem cells (MSCs) co-seeded with CD34+ hematopoietic stem/progenitor cells (HSPCs) onto a pliable synthetic scaffold [poly(1,8-octamethylene-citrate-co-octanol)(POCO)] or a biological scaffold (SIS; small intestinal submucosa) to regenerate bladder tissue in our baboon bladder augmentation model. We set out to determine the global protein expression profile of bladder tissue that has undergone regeneration with the aforementioned stem cell seeded scaffolds along with baboons that underwent BAE. Data demonstrate that POCO and SIS grafted animals share high protein homogeneity between native and regenerated tissues while BAE animals displayed heterogeneous protein expression between the tissues following long-term engraftment. We posit that stem cell-seeded scaffolds can recapitulate tissue that is nearly indistinguishable from native tissue at the protein level and may be used in lieu of procedures such as BAE.

Synovial sarcomas constitute 5-10% of all soft-tissue sarcomas and tend to occur in the extremities, particularly the lower extremity. Renal sarcoma is a rare entity, constituting approximately 1-5% of all malignant renal tumours. Metastatic large renal synovial sarcoma with Inferior Vena Cava (IVC) thrombus is a rare surgical challenge that demands thorough preoperative evaluation and planning for its management. A 31-year-old young male presented with symptoms of left flank pain for 10 days, with a past history of similar complaints two years prior. On examination, a massively large renal mass was palpable. A Computed Tomography (CT) scan showed an IVC thrombus and metastatic deposits. The patient underwent a radical nephrectomy with ileal segment resection, followed by chemotherapy, which showed near-complete resolution of the metastatic deposits. Renal synovial sarcoma should be considered as a differential diagnosis in young patients presenting with a metastatic, exceptionally large renal mass complicated by an IVC thrombus, necessitating thorough preoperative evaluation for effective management.

Background: The aim of this study was to evaluate the feasibility of ultrasound-guided pectoral nerve block combined with interpleural block for surgical anesthesia during the modified radical mastectomy (MRM). Methods: Thirty-six female patients scheduled to undergo MRM were included in this study. After taking all aseptic precautions, an ultrasound-guided pectoral nerve block and interpleural block were performed with 20 ml of 0.25% bupivacaine for each block. We started all patients on dexmedetomidine infusion to achieve conscious sedation and used injection ketamine as rescue analgesia. We recorded hemodynamic parameters throughout the surgery and visual analog scale scores of pain at baseline and after providing rescue analgesia. Postoperatively, we assessed surgeon and patient satisfaction scores. Results: MRM was completed in 31 (86%) out of the 36 recruited patients. Among these 31 patients, 5 (16%) did not require a rescue dose of ketamine, 14 (45%) required one rescue dose, and 12 (39%) patients required two rescue doses of ketamine. Postoperatively, the median patient and surgeon satisfaction scores were 85 (75–90) and 85 (80–90), respectively. The mean dose of dexmedetomidine was 175 (±27) μg, and the mean dose of ketamine was 32.8 (±6) mg. No serious adverse events were reported. Conclusion: MRM can be feasibly performed under ultrasound-guided pectoral nerve block and interpleural block, along with conscious sedation, without any significant adverse events.

Background: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide. It causes alteration in the cardiac performance that can be recorded by electrocardiogram (ECG) and echocardiography noninvasively. Methods: In this observational study, we studied ECG changes and their relation with the disease severity and disease duration amongst 100 COPD patients. Results: Their mean age was 58.1 ± 12.0 years, and the mean disease duration was 7.9 ± 4.1 years. ECG was found normal in 31% and abnormal in 69% of subjects. Right axis deviation (RAD), right ventricular hypertrophy, right bundle branch block and P-pulmonale were noted in 38%, 28%, 20% and 17% of study subjects, respectively. Left bundle branch block, ventricular premature contractions (VPC) and second and third-degree block were seen in none of the subjects. ECG was found abnormal in 78% of patients with Stage 4 COPD, whereas only 17% of patients with Stage 1 COPD had their ECGs abnormal (P < 0.01). ECG was abnormal in 91% of patients with a disease duration of more than 10 years and 39% of patients with a disease duration of

Introduction: The standard approaches to ultrasound-guided central line insertion by Short Axis (SAX) and Long Axis (LAX) have limitations. The Medial Oblique Axis (M-OAX) approach allows visualisation of the length of the needle in real-time along with both the artery and vein. Aim: To compare the three approaches for ultrasound-guided right Internal Jugular Vein (IJV) cannulation with respect to ease of access and complications. Materials and Methods: A total of 171 patients scheduled to undergo right IJV cannulation were divided equally into three groups-SAX (Group-1), LAX (Group-2), and M-OAX (Group-3). They were compared with respect to first pass success, Venous Access Time (VAT), guide wire insertion time, catheterisation time, and complications. Continuous variables were compared with Analysis of Variance (ANOVA) test. Categorical variables were analysed using the Chi-square test. The p-value 0.05). Conclusion: The medial oblique approach to IJV cannulation combines the advantages of both LAX and SAX and is a safer alternative with easier and faster venous access.

Background: An increased chance of developing chronic kidney disease (CKD), which has higher morbidity and mortality, exists among patients with Type 2 diabetes (T2D). Aims and Objectives: Our goal was to determine and classify the anthropometric, physiological, and demographic risk factors for CKD in individuals with T2D. Materials and Methods: A cross-sectional research study was conducted at a tertiary care hospital involving 218 participants. Data were collected on various parameters including age, gender, education level, employment status, height, weight, blood pressure, hemoglobin levels, and estimated glomerular filtration rates (eGFRs). Participants were selected based on specific inclusion and exclusion criteria, and rigorous statistical analyses were applied to the collected data. Using the SPSS program, we analyzed the data, and when the P

Background: The internet, computers, smartphones, and other electronic device’s use has increased suddenly over recent decades. Although this increase has benefits to the users, but also excessive use often leads negative health consequences. Aims and Objectives: The objective of this study was to measure the prevalence of internet addiction (IA) and stress among undergraduate medical students. Materials and Methods: A descriptive cross-sectional study was conducted among 299 undergraduate medical students enrolled in the government medical college, Almora. A 20-item Young’s IA test which is a Likert scale-based interview schedule was used to measure the prevalence of IA and the perceived stress scale 14 scale is used to assess stress among them. Results: Among the 299 study subjects, 49.5% were males and 50.5% were females. Males were more addicted to the internet than females. The prevalence of IA among the study subjects in the present study was 45.4% mild, 13.8% moderate, while 40.8% of students reported normal internet usage. Conclusion: IA is a growing health problem among medical students these days, thus necessary preventive and therapeutic interventions are very important to promote healthy and safe usage of the internet.

Atherosclerosis is a primary cause of illness and death globally and its mechanism is still unclear. Different animal models have been created to evaluate the progression of atherosclerosis, allowing researchers to carefully control the circumstances of the experiment as well as the nutrition and environmental risk factors. To investigate the negative effects of various interventions, pathophysiological alterations might be generated utilizing genetic or pharmacological methods. These models’ molecular and pathophysiological mechanisms have been clarified through experiments, and they have served as platforms for the creation of new drugs. Different models can be employed to address various research problems, each with its own benefits and drawbacks. In the current review study, various species of atherosclerosis models are discussed, along with the viability of using them in experiments.

Background: Lichen planus is a chronic inflammatory disease of the skin and mucous membrane with higher predilection seen in the female population. Oral lichen planus (OLP) has been associated with various etiological factors, such as stress, hormonal imbalance, and immunological variation. The purpose of this study was to assess serum and salivary estrogen (E2) levels in OLP patients and correlate them with stress levels. Objectives: This study aimed to evaluate serum and salivary estrogen levels in female patients with OLP, along with the assessment of stress and its correlation with estrogen levels. Methods: A total of 78 females, 39 clinically diagnosed with OLP and 39 healthy females, were included in the study as the case and control groups, respectively. 2 ml each of salivary and serum samples was obtained from each participant to measure the estrogen levels. Stress levels in the study group patients were assessed using the Depression Anxiety Stress Scale (DASS-21) and the Perceived Stress Scale (PSS). The nonparametric Mann–Whitney test was used for intergroup comparisons. Results: Significantly higher serum estrogen levels with higher DASS-21 and PSS scores were noted in patients with OLP. Overall, significant positive correlations were observed between salivary E2 and serum E2 (r = 0.361, P = 0.001). There was a positive correlation between salivary and serum E2 and DASS score (r = 0.410, P < 0.001, and r = 0.768, P < 0.001, respectively), serum/salivary E2 and PSS score (r = 0.745, P < 0.001, and r = 0.410, P < 0.001, respectively), and DASS score and PSS score (r = 0.878, P < 0.001). Conclusion: Estrogen can be used as a useful biomarker for OLP in the future. Salivary samples can prove to be an accurate and feasible alternative to serum estrogen level determination. We also suggest that OLP patients must be given supportive psychological treatment for improved life quality and disease management.

Introduction: The Coronavirus disease 2019 (COVID-19) pandemic has been the biggest threat to humankind during the last 3 years. It has caused the loss of more than 6.9 million precious lives across the world. The only method by which the massacre could be stopped was by mass vaccination or mass immunization. The patients suffering from autoimmune rheumatic disorders (AIRDs) and treated with immunosuppressants were the high-priority candidates for vaccination. However, the data regarding the efficacy of COVID-19 vaccines in this group of patients are very less. Hence, this study was planned to study the immunogenicity of Covishield in patients with AIRDs attending the rheumatology OPD at DMCH, Ludhiana. Materials and Methods: It was a prospective cohort study and was planned by the Department of Biochemistry and Department of Clinical Immunology and Rheumatology at Dayanand Medical College and Hospital, Ludhiana. Fifty patients with AIRDs attending the DMCH rheumatology OPD and 52 age and sex-matched healthy controls who had received two doses of Covishield vaccine were included in this study. Patients having any other immunosuppressive conditions like uncontrolled diabetes, hepatitis, malignancy or HIV were excluded. Patients who had suffered from previous laboratory-confirmed COVID-19 infection (by RT-PCR) were also excluded. Blood samples were collected following all aseptic precautions from patients and controls on the 28th day after administration of a second dose of Covishield vaccine and total antibodies to the severe acute respiratory syndrome coronavirus 2 spike (S) protein receptor binding domain was measured using Elecsys Anti-SARS-CoV-2 S kit from Roche. Results: It was observed that no significant difference was there in antibody titre between cases and controls (6213 ± 4418 vs. 8331 ± 7979, P = 0.1022). It was also observed that no statistically significant difference in antibody titre in cases without prednisolone and those taking treatment with prednisolone was found (P = 0.7058). A similar observation was found in terms of methotrexate also (P = 0.457). No significant difference in antibody titres was there when compared with controls (for prednisolone, P = 0.169, for methotrexate, P = 0.078). We found that only the patients receiving mycophenolate mofetil showed a statistically significant decrease in antibody titre in comparison to healthy controls (P = 0.03). Our study showed no statistically significant difference in antibody titres between patients suffering from different AIRDs. Conclusion: Our study supplements the fact that patients with AIRDs in India can receive Covishield as the primary vaccine against COVID-19 without concerns regarding decreased immunogenicity or increased adverse effects.

Abstract In the era of social media, the use of emojis and code-mixed language has become essential in online communication. However, selecting the appropriate emoji that matches a particular sentiment or emotion in the code-mixed text can be difficult. This paper presents a novel task of predicting multiple emojis in English-Hindi code-mixed sentences and proposes a new dataset called SENTIMOJI, which extends the SemEval 2020 Task 9 SentiMix dataset. Our approach is based on exploiting the relationship between emotion, sentiment, and emojis to build an end-to-end framework. We replace the self-attention sublayers in the transformer encoder with simple linear transformations and use the RMS-layer norm instead of the normal layer norm. Moreover, we employ Gated Linear Unit and Fully Connected layers to predict emojis and identify the emotion and sentiment of a tweet. Our experimental results on the SENTIMOJI dataset demonstrate that the proposed multi-task framework outperforms the single-task framework. We also show that emojis are strongly linked to sentiment and emotion and that identifying sentiment and emotion can aid in accurately predicting the most suitable emoji. Our work contributes to the field of natural language processing and can help in the development of more effective tools for sentiment analysis and emotion recognition in code-mixed languages. The codes and data will be available at https://www.iitp.ac.in/~ai-nlp-ml/resources.html#SENTIMOJI to facilitate research.

Abstract 5q-spinal muscular atrophy (SMA) is a neuromuscular disorder (NMD) that has become one of the first 5% treatable rare diseases. The efficacy of new SMA therapies is creating a dynamic SMA patient landscape, where disease progression and scoliosis development play a central role, however, remain difficult to anticipate. New approaches to anticipate disease progression and associated sequelae will be needed to continuously provide these patients the best standard of care. Here we developed an interpretable machine learning (ML) model that can function as an assistive tool in the anticipation of SMA-associated scoliosis based on disease progression markers. We collected longitudinal data from 86 genetically confirmed SMA patients. We selected six features routinely assessed over time to train a random forest classifier. The model achieved a mean accuracy of 0.77 (SD 0.2) and an average ROC AUC of 0.85 (SD 0.17). For class 1 ‘scoliosis’ the average precision was 0.84 (SD 0.11), recall 0.89 (SD 0.22), F1-score of 0.85 (SD 0.17), respectively. Our trained model could predict scoliosis using selected disease progression markers and was consistent with the radiological measurements. During post validation, the model could predict scoliosis in patients who were unseen during training. We also demonstrate that rare disease data sets can be wrangled to build predictive ML models. Interpretable ML models can function as assistive tools in a changing disease landscape and have the potential to democratize expertise that is otherwise clustered at specialized centers.

Background: Subarachnoid block is the most commonly used anesthetic technique for lower limb surgeries. Fentanyl is very often combined with hyperbaric bupivacaine as an adjuvant. This study was conducted to compare the block characteristics by administrating bupivacaine and fentanyl in a sequential and premixed manner. Aims and Objectives: The primary objective was to compare the effects of hyperbaric bupivacaine and fentanyl administered either as a premixed solution or sequentially on block characteristics-onset of sensory and motor blockade, regression of block and duration of analgesia. The secondary objective was to study the hemodynamic changes and adverse effects. Materials and Methods: A total of 72 patients scheduled to undergo lower limb surgery were allocated to three groups. Patients in Group A received 15 mg of 0.5 % bupivacaine heavy (H), followed by 25 mcg of fentanyl intrathecally using different syringes. Group B received 25 mcg of fentanyl, followed by 15 mg of 0.5% bupivacaine H in a separate syringe. Group C received premixed 0.5 % bupivacaine H 15 mg and fentanyl 25 mcg in single syringe. The block characteristics-onset and regression of sensory and motor blockade, duration of analgesia, and adverse effects were studied. Results: The mean time (minutes) taken for onset of sensory block was 2.40±0.51 in group A, 4.80±0.53 in Group B and 6.70±0.50 in Group C. Mean time (minutes) taken for onset of motor block was 4.35±0.43 in Group A, while it was 5.64±0.65 and 7.32±0.64 in Groups B and C, respectively. Two segment regression and duration of motor blockade were found to be longer in Group A. Conclusion: Sequential intrathecal administration of bupivacaine followed by fentanyl has a faster onset and prolonged duration of block when compared to the premixed group.

Background: The use of menopausal hormone therapy (MHT) was significantly reduced following the publication of the Women’s Health Initiative study results and has remained low ever since. However, from 2015 onwards, the UK has seen a substantial increase in MHT prescribing compared to other European countries. Objectives: To evaluate the factors contributing to the shift in women’s and healthcare professionals’ (HCPs) perception of MHT in the United Kingdom and to provide learning points for other European countries. Design: An exploratory, descriptive and qualitative study Methods: An interactive virtual panel discussion in which seven UK-based HCPs with a special interest in the menopause discussed the evolution of its management in the United Kingdom. Results: In the last 8 years, there has been a substantial increase in MHT prescriptions in the United Kingdom due to improved menopause awareness and acceptance of MHT. Accessibility to accurate, scientific, information and guidance from respected institutions is one of the main drivers of this change. Social media has increased that reach with ‘influencers’ empowering women to seek help. Women are demanding access to menopause health care so that they can receive holistic and individualized treatment based on their clinical conditions and needs. Standardized education of HCPs is an essential pillar to provide appropriate and equitable care to menopausal women and to guarantee safe prescribing of MHT. Furthermore, up to date and factually correct menopausal education would benefit all the population. Conclusions: Publication of new scientific data reporting a more favourable benefit/risk ratio with MHT, production of national guidance and an increased awareness via social media have led to the significant rise in MHT prescribing and improvement of menopause care in the United Kingdom. The lessons learned may benefit other European countries.

BackgroundUpwards of ninety percent of individuals living with depression in India do not have access to evidence-based treatments, especially in rural areas. Integrating these treatments into primary care is essential for bridging this care gap. This trial aims to evaluate whether a remote coaching implementation support strategy, referred to as Enhanced Implementation Support, is superior to routine support, referred to as Routine Implementation Support, in supporting the delivery of collaborative depression care in rural primary care centers.MethodsEmploying a cluster-randomized hybrid type-III implementation trial design, 14 primary care facilities in Sehore district, Madhya Pradesh, will implement a collaborative depression care package based on the WHO's mhGAP program. Facilities will be randomized to either Enhanced Implementation Support or the Routine Implementation Support control condition. Enhanced Implementation Support consists of remote coaching and technical assistance, supplemented with in-person visits, and guided by the Plan-Do-Study-Act implementation cycles. The primary implementation outcome is the proportion of outpatients screened for depression by facility staff, with secondary outcomes including the proportions of outpatients who screen positive for depression, are referred to the medical officer, and initiate treatment. Secondary patient outcomes include proportion of patients who achieve reduction in depression symptom severity at 3-month follow up. Acceptability, feasibility, and fidelity of the depression care package will be assessed through routine observations collected during field visits, facility audits, and qualitative exit interviews with facility staff. Costs of delivering the Enhanced Implementation Support strategy will also be estimated.DiscussionThis trial can inform efforts to integrate depression care in rural primary care facilities in a low-resource setting, and illuminate whether external coaching support is superior relative to existing implementation support for achieving these goals. Trial RegistrationNCT05264792.

Background Sudden and unexpected deaths are increasing drastically. The main cause of sudden death is cardiovascular disease, out of which coronary artery disease predominates forming 80% of the cases. Most of the time, detecting early changes in myocardial infarction during the autopsy is challenging since gross infarct changes do not appear until after 24 to 48 hours of myocardial ischemia injury. So, the aim of this study was to compare two test to detect early changes of Myocardial Infarction one by using Triphenyl Tetrazolium Chloride (TTC) staining of the myocardial tissue, during autopsy and other by histopathological examination. Methods The sample size of 60 hearts taken from all the sudden deaths cases brought to Mortuary with suspected cause of death due to cardiac origin. The heart was obtained from the deceased by standard post-mortem technique. Serial full-thickness transverse sections of the heart were taken at 2 cm intervals from the apex to the atrioventricular groove. All the serial slices of heart are taken for histochemical staining and TTC staining. Results In histopathological examination 34 hearts were diagnosed with myocardial infarction and 26 hearts reported non myocardial infarction. With TTC 40 hearts remained unstained suggestive of myocardial infarction and 20 hearts were stained suggestive of non-infarcted hearts. TTC staining in our study shows an accuracy of 88.33%. Conclusion The result of this study shows that the Triphenyl Tetrazolium Chloride test, a histochemical staining technique of heart, is reliable approach for forensic pathologists to diagnose early myocardial infarction during the post-mortem examination.

Introduction Tuberculosis (TB) continues to be one of the deadliest infectious diseases over the centuries, killing more people worldwide than any other single infectious disease. There is an urgent need for additional strategies which can expedite efforts to combat TB including a preventive vaccine. In this endeavour, we have developed a protocol for a multisite, double-blind, placebo-controlled clinical trial in India that aims to evaluate the efficacy and safety of two TB vaccines; namely, VPM1002 and Immuvac (M.w) (Mycobacterium Indicus Pranii) (MIP) among healthy household contacts (HHCs) of sputum smear-positive pulmonary TB (PTB) patients.Methods and analysis In the three-arm randomised double-blind placebo-controlled trial study protocol, a total of 12 000 HHCs (aged 6−99 years) of sputum smear-positive PTB patients will be randomised to receive either of the two vaccine candidates VPM1002 and MIP or placebo. The primary efficacy endpoint is the prevention of microbiologically confirmed TB. Secondary endpoints will include (1) prevention against Latent TB infection, (2) incidence of adverse events and serious adverse events in study participants, (3) efficacy of vaccine in prevention of PTB/extra PTB in different age groups (6–18 years, 19–35 years, 36–60 years and above 60 years) and (4) immunogenicity of VPM1002 and MIP at month 2 and month 6 after first vaccination in terms of flow cytometric analysis of M.Tb specific CD4+ and CD8+ T cells secreting cytokines and Luminex assays for the presence of different cytokines in the sera and supernatants of peripheral blood mononuclear cells cultures stimulated with whole cell lysates of M.Tb and subsequently similar analysis for the cases who develop TB postvaccination during the follow-up period.Ethics and dissemination Ethics committees’ approvals have been granted by the Institutional Human Ethics Committees of all participating centres in this study and the names of the ethics committees and approvals are as follows: (1) National Institute for Research in Tuberculosis (NIRT)-Chennai (including subsites): ECR/135/Inst/TN/2013/RR-19, Approval No. 390/NIRT-Institutional Ethics Committee (IEC)/2018 dated 5 December 2018 (NIRT-Madurai-ECR/1365/Inst/TN/2020; approval dated 8 June 2020; NIRT, Vellore: ECR/1215/Inst/TN/2019; approval dated 26 September 2020); (2) All India Institute of Medical Sciences (AIIMS), Delhi (including subsites)-Institute Ethics Committee, ECR/547/Inst/DL/2014/RR-17 ECR/538/Inst/DL/2014/RR-20; approval No.IEC-385/06-07-2018, approval OP-28/05.04.2019 and SFH- ECR/593/Inst/DL/2014/RR-20 IEC/VMMC/SJH/project/2019-05/25 ; 23 May 2019; (3) National Institute of Tuberculosis and Respiratory Diseases (NITRD), Delhi: ECR/315/Inst/DL/2013/RR-19; approval IEC-No-NITRD/EC/2019/9004; 8 January 2019; (4) Pune-National AIDS Research Institute (NARI) and subsite-ECR/23/Inst/MH/2013/RR-19; IEC-NARI/EC/approval/2018/196; 29 May 2018; (5) Regional Medical Research Centre-Bhubaneshwar-ECR/911/Inst/OR-2017/RR-21; approval, dated 25 April 2018; Subsites- AIIMS, Bhubaneshwar ECR/534/Inst/OD/2014/RR-17 and 20 approval No. T/EMF/Pulm. Med/19/01 dated 13 May 2019; SCB, Cuttack No. No.ECR/84/Inst/OR/2013/RR-20; approval no.186 dated 7 February 2020; (6) NTI-Bengaluru: Ethics Committee-No-ECR/1819/Inst/KA/2019; approval No NTI-IEC/1.2019/principal investigator, dated 31 January 2019; (7) BMMRC, Hyderabad- ECR/450/Inst/AP/2013/RR-16 approval No. 779/BMMRC/2018/IEC, dated 11 June 2018 (Subsite Share India- Mediciti Ethics Committee-ECR/283/Inst/AP/2013/RR-20; Approval no. EC/11/VII/2K20(1) dated 11 July 2020) and (8) SJMC-Bengaluru: ECR/238/Inst/KA/2013/RR-19; approval IEC/1/491/2020; 7 August 2020.The trial findings will be published in accordance with the Consolidated Standards of Reporting Trials guidance. The results of this clinical trial will be presented at scientific conferences and disseminated through publications in peer-reviewed journals, conference presentations and shared with Ministry of Health and Family Welfare, policy-makers and other stakeholders.Trial registration number CTRI/2019/01/017026.

Agenesis of the Dorsal Pancreas (ADP) is a rare anatomical manifestation of the pancreas, characterised by the total or partial absence of the dorsal pancreatic regions, body, and tail. The anatomy of the pancreas missing the pancreatic tail is considered partial agenesis, while the absence of the body and tail, with the presence of only the pancreatic head, is considered to be complete dorsal agenesis of the pancreas. Here the authors present the case of 20 years old male patient with uncontrolled blood sugars and recent onset of blurred vision. Diagnostic imaging, including Ultrasonography (USG) and Computed Tomography (CT), revealed the pancreatic head, but the body and tail were not seen. Using CT, the patient’s condition was identified as complete ADP. Treatment involved initiating basal bolus insulin therapy, leading to glycaemic control. The patient also underwent cataract surgery for diabetic-related complications. This case underscores the importance of considering congenital pancreatic anomalies in young adults and highlights the utility of advanced imaging techniques in confirming the diagnosis of agenesis of the dorsal pancreas. Early recognition and intervention are crucial for optimising patient outcomes. Further research is needed to enhance understanding of ADP pathophysiology and develop effective management strategies.

Abstract Quinoa (Chenopodium quinoa Willd.), an Andean crop, is a facultative halophyte food crop recognized globally for its high nutritional value and plasticity to adapt to harsh conditions. We conducted a genome-wide association study on a diverse set of quinoa germplasm accessions. These accessions were evaluated for the following agronomic and biochemical traits: days to 50% flowering (DTF), plant height (PH), panicle length (PL), stem diameter (SD), seed yield (SY), grain diameter (GD), and thousand-grain weight (TGW). These accessions underwent genotyping-by-sequencing using the DNBSeq-G400R platform. Among all evaluated traits, TGW represented maximum broad-sense heritability. Our study revealed average SNP density of ≈ 3.11 SNPs/10 kb for the whole genome, with the lowest and highest on chromosomes Cq1B and Cq9A, respectively. Principal component analysis clustered the quinoa population in three main clusters, one clearly representing lowland Chilean accessions, whereas the other two groups corresponded to germplasm from the highlands of Peru and Bolivia. In our germplasm set, we estimated linkage disequilibrium decay to be ≈ 118.5 kb. Marker-trait analyses revealed major and consistent effect associations for DTF on chromosomes 3A, 4B, 5B, 6A, 7A, 7B and 8B, with phenotypic variance explained (PVE) as high as 19.15%. Nine associations across eight chromosomes were also found for saponin content with 20% PVE by qSPN5A.1. More QTLs were identified for PL and TGW on multiple chromosomal locations. We identified putative candidate genes in the genomic regions associated with DTF and saponin content. The consistent and major-effect genomic associations can be used in fast-tracking quinoa breeding for wider adaptation across marginal environments.

Abstract Background Varicose vein is a chronic condition that affects the lower extremities of the human body. Several factors have been implicated in the development of this disease, viz age, gender, weight, height and prolonged standing. Recently, genome-wide studies have identified genetic biomarkers that are associated with varicose veins in different ethnic groups. Such genetic studies are lacking in South Asians specifically in Indians where the prevalence of varicose veins is high, and it is important to replicate these variants in the stated population. The study aimed to replicate the association of genetic variants associated with varicose veins in this target population, which were found to be associated with the other ethnic groups. Methodology The studied cohort is of the Indian population comprising unrelated 104 varicose veins cases and 448 non-varicose vein controls. The samples were genotyped using the Illumina Global Screening Array. Using the genomic data from UK BioBank and 23andMe studied cohorts; eight genetic variants were selected to replicate in our dataset. The allelic association was performed to identify the effective allele and risk was estimated using odds ratio and p-value as level of significance. Multifactor Dimensionality Reduction was used to estimate the cumulative effect of variants in Indians. Result Variant rs3791679 of EFEMP1 was found to be associated with varicose veins in Indians. After observing the association of the EFEMP1 with varicose veins, we further ensued to identify all genetic variants within EFEMP1 to uncover the additional variants associated with this trait. Interestingly, we identified six new variants of EFEMP1 gene that have shown association. Moreover, the cumulative effect of all associated variations was estimated and the risk was 2.7 times higher in cases than controls whereas independently their effect ranges from 0.37–1.58. Conclusion This study identifies EFEMP1 as a potential gene related to the risk of varicose veins in Indians. It also highlights that evaluating the maximum number of variants of a gene rather than focusing solely on replicating single variations offers a more comprehensive and nuanced understanding of the genetic factors contributing to a complex trait like varicose veins.

Abstract The survival of leukemic cells is significantly influenced by the bone marrow microenvironment, where stromal cells play a crucial role. While there has been substantial progress in understanding the mechanisms and pathways involved in this crosstalk, limited data exist regarding the impact of leukemic cells on bone marrow stromal cells and their potential role in drug resistance. In this study, we identify that leukemic cells prime bone marrow stromal cells towards osteoblast lineage and promote drug resistance. This biased differentiation of stroma is accompanied by dysregulation of the canonical Wnt signaling pathway. Inhibition of Wnt signaling in stroma reversed the drug resistance in leukemic cells, which was further validated in leukemic mice models. This study evaluates the critical role of leukemic cells in establishing a drug-resistant niche by influencing the bone marrow stromal cells. Additionally, it highlights the potential of targeting Wnt signaling in the stroma by repurposing an anthelmintic drug to overcome the microenvironment-mediated drug resistance.

Background: Bone marrow edema (BME) refers to the accumulation of excess fluid in the bone marrow, often indicative of injury or inflammation. Some studies suggest that incorporating plant-based therapies, rich in anti-inflammatory compounds and nutrients, may contribute to alleviating BME and promoting overall bone health. Aims and Objective: The study aims to evaluate the effect of Cissus quadrangularis and Dalbergia sissoo therapy on BME and knee pain associated with degenerative medial compartment knee osteoarthritis (OA). Materials and Methods: This retrospective study examined seven individuals with medial tibial condyle BME associated with medial compartment OA. These patients were treated with initial 10 days of non-steroidal anti-inflammatory drugs along with once-a-day tablet containing C. quadrangularis (500 mg) and D. sissoo (400 mg). Visual analogue scores (VAS) and Oxford knee score (OKS) were noted at the beginning of the therapy and at 12 weeks of completion of therapy. Before treatment, BME (percentage of the medial tibial condyle) and presence/absence of subtle subchondral fracture were diagnosed with T2-weighted magnetic resonance imaging (MRI) images, and subsequently, its resolution was confirmed with a repeat MRI scan at 12 weeks. Results: At the end of 12 weeks of therapy, there was a statistically significant improvement in the mean VAS score (baseline 8.14±0.90 improved to 2.00±0.58 at 12 weeks, [P

Neurofibromatosis 2 (NF2) is characterised by numerous tumours in the central and peripheral nervous systems due to NF2 gene abnormalities that cause the tumour suppressor protein, Merlin, to disappear. Often referred to as Multiple Inherited Schwannomas, Meningiomas, and Ependymomas (MISME), a distinctive characteristic of NF2 is bilateral vestibular schwannomas manifesting in late adolescence with symptoms such as sensorineural hearing loss, tinnitus, and balance issues. Two distinct phenotypes, Wishart and Feiling-Gardner, characterise NF2. This case report discusses the case of a paediatric patient who presented with bilateral hearing loss, giddiness, and blurring of vision and sought a Magnetic Resonance Imaging (MRI) examination which revealed bilateral vestibular schwannomas, non vestibular schwannomas, left sphenoid wing meningiomas, multidirectional spinal schwannomas, spinal nerve sheath tumours, and lesions in the retroperitoneal region. Despite an absent family history, significant involvement of cranial nerves strongly indicates classical NF2. Management focuses on preserving function, and surgery is contemplated for symptomatic lesions and tumours causing cord compression. Gamma Knife radiosurgery and targeted therapies have been investigated.

Objectives: To study epidemiological characteristics, clinical features, laboratory findings, and clinical outcomes in cases of scrub typhus. Additionally, the study aims to identify the predictors of disease severity. Methods: This cross-sectional study was conducted in the Department of General Medicine at Dr PDM Medical College in Amaravati, India. The study duration was 6 months, from July 2023 to December 2023. All clinically confirmed patients with scrub typhus were evaluated through history, clinical examination, and appropriate laboratory investigations. The clinical and laboratory profiles, hospital course, and outcomes were analyzed. Organ dysfunction upon admission was assessed using the sequential organ failure assessment (SOFA) score. Results: A total of 200 cases were included in the study. The majority of the cases were in the age range of 31-40 years, and most of them were males. The highest number of scrub typhus cases occurred in September. The most common presenting symptoms were fever (81%), followed by nausea (37.5%), generalized weakness (34%), abdominal pain, eschar (21.5%), breathlessness, and cough (21% each), headache (19%), vomiting (15%), and altered sensorium (4.5%). The majority of patients (72.5%) did not experience any complications, while 55 patients (27.5%) developed multi-organ dysfunction syndrome (MODS) as a complication. The mortality rate was 1%. Conclusion: Scrub typhus is a significant cause of acute febrile illness in the Vidarbha region of Maharashtra. It can present with various clinical manifestations, with or without an eschar. Early diagnosis and appropriate treatment of these cases can lead to minimal complications.

Background: Maxillofacial surgery patients frequently pose challenges to airway management due to anatomical and functional constraints. While fiber-optic-aided nasotracheal intubation is considered the gold standard, not all medical facilities have access to fiber-optic bronchoscopes, particularly in low-resource settings. In such situations, awake nasal tracheal intubation is often the safest approach for managing patients with known or suspected difficult airways. Aims and Objectives: (1) To assess the technique of capnography-assisted airway management by awake blind nasal intubation (ABNI) in maxillofacial surgeries. (2) To find out any complications encountered by the technique of capnography-assisted airway management by ABNI in maxillofacial surgeries. Materials and Methods: 40 patients undergoing various maxillofacial surgeries and in whom blind nasotracheal intubation was attempted were included in this study. The institutional ethical committee approved the study, and informed consent was obtained from all the patients. The number of attempts for ABNI, successful versus failed ABNI, and complications encountered were studied. SSPS 21.0 software was used for statistical analysis. Results: There were 23 (57.50%) males and 17 (42.50%) females. There was a male preponderance, with the M: F ratio being 1:0.73. The mean age of the patients was 40.97±8.92 years. In 36 (90%) of the patients, the intubation could be successfully done. In 19 (47.50%) patients, blind nasal intubation was successfully done in the first attempt; 2 attempts were required in 15 (37.50%) patients, and 3 attempts were required in 2 (5%) patients. Epistaxis (10%) and sore throats (7.5%) were the most common complications in the studied cases. Conclusion: Capnography-assisted ABNI is an effective technique for airway control in patients undergoing maxillofacial surgeries with an acceptable complication rate.

Introduction: Renal mesenchymal tumours are a subset of primary renal tumours arising from the mesenchymal tissue in the kidney. They are a heterogeneous group of mostly benign tumours that exhibit varied behaviours and molecular characteristics. Aim: To analyse the wide spectrum of histological subtypes, their unique clinical presentation, and pathological features of primary renal mesenchymal neoplasms. Materials and Methods: This was a retrospective cross- sectional observational clinicopathological study conducted in Department of General Pathology, Christian Medical College, tertiary care hospital, Vellore, Tamil Nadu, India, looking at data of adult Primary Renal Mesenchymal Tumours (PRMT) for a 15-year period between January 2006 and March 2021. Clinical details such as age, presenting symptoms, and tumour size were obtained from the hospital information system. Histopathology and immunohistochemical slides were reviewed for all the cases. Additional Immunohistochemistry (IHC) and molecular studies were performed for the undifferentiated sarcomas. The tumours were categorised into three groups as recommended by the World Health Organisation (WHO) 2020 classification of soft-tissue tumours based on biological behaviour: benign, intermediate, and malignant. Continuous variables are expressed as mean and Standard Deviation (SD). Comparison of categorical variables between groups was performed using the Chi-squared test. Continuous variables between groups were compared using the Student’s t-test for significance. A p-value of less than 0.05 was considered statistically significant. Results: Of the 2164 nephrectomies performed for neoplastic conditions, 97 (4.5%) were diagnosed as renal mesenchymal tumours. There were 59 (60.8%) benign, 10 (10.3%) with intermediate biologic behaviour and 28 (28.9%) malignant tumours. The mean ages at presentation were 40.5 years for benign, 43.4 years for intermediate, and 41 years for malignant tumours, respectively. Haematuria was seen in 11 of 38 (29%) intermediate grade and malignant tumours and in only 6 of 59 (10%) benign tumours, a difference that was statistically significant (p-value=0.017). Malignant tumours 24 of 28 (86%) were more likely to be larger (>7 cm) when compared to benign tumours 28 of 59 (47%) at the time of presentation (p-value=0.027). Classical angiomyolipomas constituted 53/59 (90%) of the benign tumours. Of the 10 intermediate grade tumours, epithelioid angiomyolipomas and solitary fibrous tumours were the most common, accounting for 50% and 30% of the intermediate group, respectively. Undifferentiated small round cell sarcoma was the most common malignant neoplasm, making up 12/28 (43%) of the malignant tumours. Conclusion: The present study found that renal mesenchymal tumours constitute a small but unique group of renal tumours. They are predominantly benign, but up to a quarter are malignant. Malignant tumours tend to be larger and more often present with haematuria. The present study highlights the importance of IHC in the diagnosis of intermediate and malignant mesenchymal tumours and the requirement of exhaustive molecular studies individually tailored to the immuno-profile of malignant tumours.

Abstract Scaling up the synthesis of fluorescent silica nanoparticles to meet the current demand in diverse applications involves technological limitations. The present study relates to the hydrothermal synthesis of water-soluble, crystalline, blue-emitting amine-functionalized silica nanoparticles from coal fly ash sustainably and economically. This study used tertiary amine (trimethylamine) to prepare amine-functionalized fluorescent silica nanoparticles, enhancing fluorescence quantum yield and nitrogen content for nanofertilizer application. The TEM and FESEM studies show that the silica nanoparticles have a spherical morphology with an average diameter of 4.0 nm. The x-ray photoelectron and Fourier transform infrared spectroscopy studies reveal the presence of the amine group at the surface of silica nanoparticles. The silica nanoparticles exhibit blue fluorescence with an emission maximum of 454 nm at 370 nm excitation and show excitation-dependent emission properties in the aqueous medium. With the perfect spectral overlap between silica nanoparticle emission (donor) and chlorophyll absorption (acceptor), fluorescent silica nanoparticles enhance plant photosynthesis rate by resonance energy transfer. This process accelerates the photosynthesis rate to improve the individual plant’s quality and growth. These findings suggested that the fly ash-derived functionalized silica nanoparticles could be employed as nanofertilizers and novel delivery agents.

Abstract Background TBL1XR1 encodes a F-box-like/WD40 repeat-containing protein that plays a role in transcription mediated by nuclear receptors and is a known genetic cause of neurodevelopmental disease of childhood (OMIM# 608628). Yet the developmental trajectory and progression of neurologic symptoms over time remains poorly understood. Methods We developed and distributed a survey to two closed Facebook groups devoted to families of patients with TBL1XR1-related disorder. The survey consisted of 14 subsections focused upon the developmental trajectories of cognitive, behavioral, motor, and other neurological abnormalities. Data were collected and managed using REDCap electronic data capture tools. Results Caregivers of 41 patients with a TBL1XR1-related disorder completed the cross-sectional survey. All reported variants affecting a single amino acid, including missense mutations and in-frame deletions, were found in the WD40 repeat regions of Tbl1xr1. These are domains considered important for protein–protein interactions that may plausibly underlie disease pathology. The majority of patients were diagnosed with a neurologic condition before they received their genetic diagnosis. Language appeared most significantly affected with only a minority of the cohort achieving more advanced milestones in this domain. Conclusion TBL1XR1-related disorder encompasses a spectrum of clinical presentations, marked by early developmental delay ranging in severity, with a subset of patients experiencing developmental regression in later childhood.

Introduction: Central Nervous System (CNS) tumours are a common cause of cancer-related deaths in adolescents and young adults. The challenges in diagnosing and treating CNS tumours in this age group are unique and require special attention. Aim: To study the histopathological spectrum of CNS tumours in Adolescents and Young Adults (AYA). Materials and Methods: Present five-year cross-sectional study was conducted on CNS biopsies received in the Department of Pathology at Dayanand Medical College and Hospital, Ludhiana, Punjab, India, from July 1, 2016, to June 30, 2021, to analyse the histopathological spectrum of CNS tumours in the AYA group based on the site of the lesion, age, gender, and Isocitrate Dehydrogenase (IDH) status. Results: During the study period, a total of 215 cases of CNS tumours were identified, of which 52 (24.2%) belonged to the AYA group. Of these, 35 (67.3%) were males and 17 (32.7%) were females. The majority of the patients presented with complaints of headache (50/52, 96.1%), with the frontal lobe being the most common site of involvement (21/52, 40.4%). Diffuse astrocytic and oligodendroglial tumours were the most commonly observed (23/52, 44.2%). Conclusion: CNS tumours are one of the most common cancer diagnosis among the AYA group, and awareness should be enhanced among histopathologists and oncologists regarding these tumours based on the updated classification.

Lesbian, Gay, Bisexual, Transgender, Queer, Intersex and Asexual (LGBTQIA+) people struggle to identify a healthcare service that understands their problems and needs. Additionally, healthcare professionals also find it difficult to care for LGBTQIA+ as very little is studied or heard about management. The article presents a protocol for a pilot study aimed at the development of an LGBTQIA+ care curriculum for health science professionals. The study includes Phase I: The development of a curriculum based on a literature review and focus group discussion among LGBTQIA+ individuals, and Phase II: Pilot testing of LGBTQIA+ care curriculum. The study outcome will reflect the improvement in the knowledge of healthcare professionals on LGBTQIA+ care.

Background: Esomeprazole (ESO) gastro-resistant tablets (40 mg) are sold under the brand name, Zosa, which effectively manages conditions associated with the overproduction of gastric acid, including peptic ulcer disease and Zollinger-Ellison syndrome. The present study quantifies impurities in esomeprazole using advanced analytical techniques known as analytical quality by design with high-performance liquid chromatography. Methods: Buffer selection (pH 7.6) and mobile phase composition (75:25 v/v) were optimized utilizing a YMC C18 column (150 mm × 4.6 mm; particle size, 3 μm) with a flow rate of 1.0 mL/min. The analyte was monitored with a UV/PDA detector at a wavelength of 280 nm. The stability-indicating nature of the method was confirmed based on forced degradation studies. The method validation was performed per ICH guidelines. Linearity, specificity, limit of detection, limit of quantification, precision, accuracy, solution stability, and robustness parameters were validated. Results: All validation parameters were within an acceptable range. Excellent linearity with correlation coefficient values > 0.99 was achieved across the quantification limit. The solution stability study demonstrated no significant increase in percent impurity over a 24-h period. Analytical quality by design was instrumental in defining the design range for buffer pH and mobile phase composition, ensuring robust method performance. It was confirmed that 75% buffer solution, 25% acetonitrile, and pH 7.6 were the ideal conditions for determination of ESO impurities. Conclusion: The validated method provides a reliable tool for accurately quantifying impurities in ESO tablet formulations.

Objective This study aimed to systematically review the psychometric properties of outcome measures that assess dysfunctional breathing (DB) in adults.Methods Studies on developing and evaluating measurement properties to assess DB were included. The study investigated the empirical research published between 1990 and February 2022, with an updated search in May 2023 in the Cochrane Library database of systematic reviews and the Cochrane Central Register of Controlled Trials, the Ovid Medline (full), the Ovid Excerta Medica Database, the Ovid allied and complementary medicines database, the Ebscohost Cumulative Index to Nursing and Allied Health Literature and the Physiotherapy Evidence Database. The included studies’ methodological quality was assessed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) risk of bias checklist. Data analysis and synthesis followed the COSMIN methodology for reviews of outcome measurement instruments.Results Sixteen studies met the inclusion criteria, and 10 outcome measures were identified. The psychometric properties of these outcome measures were evaluated using COSMIN. The Nijmegen Questionnaire (NQ) is the only outcome measure with ‘sufficient’ ratings for content validity, internal consistency, reliability and construct validity. All other outcome measures did not report characteristics of content validity in the patients’ group.Discussion The NQ showed high-quality evidence for validity and reliability in assessing DB. Our review suggests that using NQ to evaluate DB in people with bronchial asthma and hyperventilation syndrome is helpful. Further evaluation of the psychometric properties is needed for the remaining outcome measures before considering them for clinical use.PROSPERO registration number CRD42021274960.

Introduction Early childhood development forms the foundations for functioning later in life. Thus, accurate monitoring of developmental trajectories is critical. However, such monitoring often relies on time-intensive assessments which necessitate administration by skilled professionals. This difficulty is exacerbated in low-resource settings where such professionals are predominantly concentrated in urban and often private clinics, making them inaccessible to many. This geographic and economic inaccessibility contributes to a significant ‘detection gap’ where many children who might benefit from support remain undetected. The Scalable Transdiagnostic Early Assessment of Mental Health (STREAM) project aims to bridge this gap by developing an open-source, scalable, tablet-based platform administered by non-specialist workers to assess motor, social and cognitive developmental status. The goal is to deploy STREAM through public health initiatives, maximising opportunities for effective early interventions.Methods and analysis The STREAM project will enrol and assess 4000 children aged 0–6 years from Malawi (n=2000) and India (n=2000). It integrates three established developmental assessment tools measuring motor, social and cognitive functioning using gamified tasks, observation checklists, parent-report and audio-video recordings. Domain scores for motor, social and cognitive functioning will be developed and assessed for their validity and reliability. These domain scores will then be used to construct age-adjusted developmental reference curves.Ethics and dissemination Ethical approval has been obtained from local review boards at each site (India: Sangath Institutional Review Board; All India Institute of Medical Science (AIIMS) Ethics Committee; Indian Council of Medical Research—Health Ministry Screening Committee; Malawi: College of Medicine Research and Ethics Committee; Malawi Ministry of Health—Blantyre District Health Office). The study adheres to Good Clinical Practice standards and the ethical guidelines of the 6th (2008) Declaration of Helsinki. Findings from STREAM will be disseminated to participating families, healthcare professionals, policymakers, educators and researchers, at local, national and international levels through meetings, academic journals and conferences.

Crossed fused ectopic kidney is a rare congenital anomaly wherein the kidneys are present on the same side due to fusion. It is a rare disease that may remain undiagnosed throughout life. Its rarity and anatomical abnormality make any intervention challenging. A 32-year-old male patient presented with symptoms of pain in the abdomen and burning micturition for a year. Serum creatinine, along with other blood tests, was normal. X-ray KUB showed renal calculi in the region of the right kidney. However, a Computed Tomography (CT) scan showed that the left kidney was malrotated and fused with the lower pole of the right kidney, suggestive of crossed fused renal ectopia. A cystoscopy and retrograde pyelography were performed, followed by open pyelolithotomy, wherein calculi were removed, and a stent was placed. Through this case report, it is suggested that adequate presurgery evaluation is necessary for patients with such malformations.

Abstract Background While antibiotics remain our primary tools against microbial infection, increasing antibiotic resistance (inherent and acquired) is a major detriment to their efficacy. A practical approach to maintaining or reversing the efficacy of antibiotics is the use of other commonly used therapeutics, which show synergistic antibacterial action with antibiotics. Here, we investigated the extent of antibacterial synergy between the antibiotic gentamicin and the anti-inflammatory ketorolac regarding the dynamics of biofilm growth, the rate of acquired resistance, and the possible mechanism of synergy. Methods Control (ATCC 12600, ATCC 35984) and clinical strains (L1101, L1116) of Staphylococcus aureus and Staphylococcus epidermidis with varying antibiotic susceptibility profiles were used in this study to simulate implant-material associated low-risk and high-risk biofilms in vitro. The synergistic action of gentamicin sulfate (GS) and ketorolac tromethamine (KT), against planktonic staphylococcal strains were determined using the fractional inhibitory concentration measurement assay. Nascent (6 h) and established (24 h) biofilms were grown on 316L stainless steel plates and the synergistic biofilm eradication activity was determined and characterized using adherent bacteria count, minimum biofilm eradication concentration (MBEC) measurement for GS, visualization by live/dead imaging, scanning electron microscopy, gene expression of biofilm-associated genes, and bacterial membrane fluidity assessment. Results Gentamicin-ketorolac (GS-KT) combination demonstrated synergistic antibacterial action against planktonic Staphylococci. Control and clinical strains showed distinct biofilm growth dynamics and an increase in biofilm maturity was shown to confer further resistance to gentamicin for both ‘low-risk’ and ‘high-risk’ biofilms. The addition of ketorolac enhanced the antibiofilm activity of gentamicin against acquired resistance in staphylococcal biofilms. Mechanistic studies revealed that the synergistic action of gentamicin–ketorolac interferes with biofilm morphology and subverts bacterial stress response altering bacterial physiology, membrane dynamics, and biofilm properties. Conclusion The results of this study have a significant impact on the local administration of antibiotics and other therapeutic agents commonly used in the prevention and treatment of orthopaedic infections. Further, these results warrant the study of synergy for the concurrent or sequential administration of non-antibiotic drugs for antimicrobial effect.

Abstract Even though many varieties have been recommended across agro-climate zones of Himachal Pradesh, yet the information on stability is lacking in this State. Hence, the present investigation was carried out to identify high yielding stable genotypes among various pre-adapted landraces. The material consists of 20 chilli landraces including check i.e. DKC-8. The experiment was laid out in a RCBD. The data were recorded and analyzed to work out mean performances and the inferences were drawn for parameters of variability, correlation coefficients, path coefficients and stability analysis. As per mean performances, CS7 and CS9 were earliest in flowering, CS13 is earliest in days to ripe maturity, CS10 had highest plant height and CS9 had highest average fruit weight and ripe fruit yield plant−1. High PCV and GCV were recorded for ripe fruit yield plant−1. Heritability and genetic advance were recorded maximum for plant height in summer seasons and were recorded maximum for number of ripe fruits plant−1 in winter season. Correlation coefficients showed that number of ripe fruits plant−1 and average ripe fruit weight were positively and significantly correlated with ripe fruit yield plant−1. Path coefficient analysis in summer and winter seasons showed that average ripe fruit weight had the highest positive direct effect on ripe fruit yield plant−1. The pooled data over environments were analyzed to estimate the interaction effects between genotypes × environment. The mean sum of squares due to genotypes, environments and genotypes × environment interaction were significant for all the characteristics. CS1, CS3, CS6, CS10, CS13, CS15 were adapted to all environments, CS7 and CS9 were specifically adapted to favourable environment and CS2 was specifically adapted to unfavorable environment for 50% flowering, landraces CS1, CS2 and CS3were well adapted to all environments for ripe maturity whereas landraces CS6, CS10 and CS19 were well adapted to all environment for number of ripe fruit and ripe fruit yield.

Pseudohypoparathyroidism (PHP) is a rare metabolic disorder, characterized by target organ resistance to parathyroid hormone (PTH), affecting PTH mediated calcium homeostasis in the body. This PTH resistance biochemically manifests with hypocalcaemia and hyperphosphataemia in spite of normal or elevated serum PTH level. Here we present a case scenario of PHP type 1a in a young male patient who manifested with painful muscle spasm, numbness and tingling sensations in all four limbs; and had features of Albright’s hereditary osteodystrophy such as round face, short neck, short stature, heterotopic calcifications and skeletal abnormalities (short 4th and 5th fingers). He was emergently managed with intravenous calcium gluconate therapy for hypocalcemic tetany. Later, he was put on high dose oral calcium salt with vitamin D therapy and discharged on stable condition. Keywords: Pseudohypoparathyroidism, PTH Resistance, Albright's Hereditary Osteodystrophy, Hypocalcemic Tetany