bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study of platelet activation, hypercoagulable state, and pulmonary hypertension in patients with transfusion-dependent beta-thalassemia
Authors: Haji Lanja Othman , Polus Ranan Kardagh , Mohammed Nawsherwan Sadiq 
Published: September 2024

Abstract

BACKGROUND:
Thalassemic patients require lifelong blood transfusions, which can lead to complications such as pulmonary arterial hypertension. The pathogenesis involves hypercoagulability, in which researches on coagulation abnormalities in this regard are limited.

OBJECTIVES:
The aims of the study was to investigate the mechanism of hypercoagulability and pulmonary hypertension in transfusion-dependent thalassemic patients and compare it with healthy controls.

PATIENTS, MATERIALS AND METHODS:
This case–control analysis enrolled 50 transfusion-dependent thalassemia patients and 50 healthy controls. Complete blood counts, liver function tests, coagulation markers (P-selectin, protein C, antithrombin III, and fibrinogen), serum ferritin, and transthoracic echocardiography were performed, and blood transfusion/chelation history and splenectomy status were recorded.

RESULTS:
Thalassemia patients revealed severe anemia, leukocytosis, thrombocytosis, significantly elevated serum ferritin (1957.50 ± 2455.05 g/L), elevated liver enzymes serum glutamic oxaloacetic transaminase (22.01 ± 9.89 U/L), serum glutamic pyruvic transaminase (22.70 ± 9.78 U/L) in comparison to controls, and mean serum P-selectin was significantly higher in thalassemic patients (100.48 ± 53.29 ng/mL). Mean serum antithrombin-III and protein C were significantly lower in thalassemic patients (89.27 ± 16.08 units/h, 86.04 ± 25.21 μg/mL) in comparison to controls.

CONCLUSIONS:
Transfusion-dependent thalassemia is characterized by severe anemia and splenomegaly, leading to complex hemodynamic changes with evidence of platelet activation, hypercoagulable state, liver injury, and increased atherosclerosis. It induces pulmonary artery thrombosis contributing to the development of pulmonary artery hypertension.
Pharmacological benefits of durva swaras (Cynodon dactylon L. Pers.) administration in APAP-induced liver injury model of mice – Assessment by metabolic and inflammatory markers
Authors: Sindhoora B. , Singh Vandana , Mungamuri Sathish Kumar , Bharatraj Dinesh Kumar 
Published: September 2024

Abstract

OBJECTIVE:
Liver derangement underlies the development of metabolic syndrome in perimenopause. Previously, we have observed that durva swaras (DS) improved metabolic-associated fatty liver disease (MAFLD) and abnormal liver enzymes (aspartate aminotransferase and alanine aminotransferase) along with other complications of menopause in ovariectomized rats. We aimed to decipher the hepatoprotective mechanisms of DS in acetaminophen (APAP)-induced liver injury model, which is analogous to the pathophysiology of MAFLD.

MATERIALS AND METHODS:
Male Swiss albino mice were distributed into three groups at random. Group I (Control) was administered with vehicle (distilled water) for 7 days. Group II (APAP) received vehicle for the first 6 days and APAP (350 mg/kg - single dose) on the 7th day. Group III (APAP + D) received test compound DS (quality complied) at a dose of 133 mg/kg for 6 days and APAP (350 mg/kg - single dose) on the 7th day. Subsequently, blood and liver tissues were subjected to biochemical, ultrastructural, and gene expression analysis.

RESULTS:
DS pretreatment protected the liver from APAP-induced disruption of sinusoids and necrosis. DS prevented the elevation of liver enzymes – AST and ALT induced by APAP. Importantly, DS inhibited the APAP-elicited increase in messenger ribonucleic acid levels of hepatic nuclear factor-kappa beta (NF-κB) and pro-inflammatory cytokines, namely interleukin-1 beta, interleukin 6, and tumor necrosis factor-alpha. Moreover, DS activated gene expression of nuclear factor erythroid 2-related factor 2 and liver-X-receptor-alpha (LXR-α) to combat the liver damage.

CONCLUSION:
DS hinders APAP-induced liver damage by activating LXR-α and inhibiting the NF-κB-associated pro-inflammatory cytokine gene expression. These observations confirm the protective role of DS in metabolic dysfunction-associated liver conditions.
Implementing pharmacogenetic testing to optimize proton-pump inhibitors use among Indian population based on CPIC-CYP2C19-PPI dosing guidelines: The need of the hour
Authors: Chenchula Santenna , Atal Shubham , Jhaj Ratinder , Uppugunduri Chakradhara Rao S. 
Published: September 2024

Abstract
Proton-pump inhibitors (PPIs) are widely prescribed to decrease stomach acid and treat various acid-related Gastrointestinal tract (GIT) diseases. However, genetic variations, particularly in the CYP2C19 gene, affect PPIs metabolism and efficacy. Variants in CYP2C19 can result in different rates of PPI metabolism, influencing their effectiveness. Personalized medicine strategies, such as genotyping for CYP2C19, have the potential to enhance the effectiveness of PPI therapy and patient safety. This review aims to describe the relevance of CYP2C19 genetic profiling in the indian population, including normal function (e.g. CYP2C19*1, *11, *13, *15, *18, *28, and 38), decreased function (e.g., CYP2C19*9, *10, *16, *19, *25, and 26), loss of function (e.g., CYP2C19*2, *3, *4, *5, *6, *7, *8, *22, *24, *35, *36, and *37), and increased function (e.g., CYP2C19*17) variants. This review also examines the clinical pharmacogenomics implementation consortium (CPIC)-CYP2C19-PPI guidelines to highlight the importance of pharmacogenomics (PGx)-informed personalized PPI therapy for gastroesophageal reflux disease and peptic ulcer disease treatment. On average, each person in India possesses eight pharmacogenetic (PGx) variants that can be clinically significant, underscoring the need for preemptive testing. Implementing CYP2C19 genetic testing in India requires expanding laboratory capacity, increasing accessibility in primary care, increasing public awareness, collaboration between pharmacovigilance and PGx programs, investing in advanced sequencing technologies, data management systems, and integration with electronic health records and clinical decision support systems. Addressing challenges such as genetic diversity, socioeconomic factors, health-care access issues, and shortage of trained professionals is essential for implementation. Due to the lack of definitive country-specific policies and PGx guidelines from Indian drug regulatory agencies, guidelines from international consortia such as the Clinical Pharmacogenetics Implementation Consortium and drug labeling offer crucial foundational evidence. This evidence can be used to enhance patient outcomes and ensure the safe and effective use of PPIs in India.
Applying quantitative and systems pharmacology to drug development and beyond: An introduction to clinical pharmacologists
Authors: Ramasubbu Mathan Kumar , Paleja Bhairav , Srinivasann Anand , Maiti Rituparna , Kumar Rukmini 
Published: September 2024

Abstract
Quantitative and systems pharmacology (QSP) is an innovative and integrative approach combining physiology and pharmacology to accelerate medical research. This review focuses on QSP’s pivotal role in drug development and its broader applications, introducing clinical pharmacologists/researchers to QSP’s quantitative approach and the potential to enhance their practice and decision-making. The history of QSP adoption reveals its impact in diverse areas, including glucose regulation, oncology, autoimmune disease, and HIV treatment. By considering receptor–ligand interactions of various cell types, metabolic pathways, signaling networks, and disease biomarkers simultaneously, QSP provides a holistic understanding of interactions between the human body, diseases, and drugs. Integrating knowledge across multiple time and space scales enhances versatility, enabling insights into personalized responses and general trends. QSP consolidates vast data into robust mathematical models, predicting clinical trial outcomes and optimizing dosing based on preclinical data. QSP operates under a “learn and confirm paradigm,” integrating experimental findings to generate testable hypotheses and refine them through precise experimental designs. An interdisciplinary collaboration involving expertise in pharmacology, biochemistry, genetics, mathematics, and medicine is vital. QSP’s utility in drug development is demonstrated through integration in various stages, predicting drug responses, optimizing dosing, and evaluating combination therapies. Challenges exist in model complexity, communication, and peer review. Standardized workflows and evaluation methods ensure reliability and transparency.
Demographic profile of ophthalmic injuries following road traffic accidents at a tertiary care hospital in Western India
Authors: Tamboli Nikhat Iqbal , Jakkal Tapan P , Joshi Rajesh S , Husain Bilal 
Published: September 2024

Context:
Road traffic accidents (RTAs) are one of the leading and most common causes of ocular injuries, especially in developing countries like India.

Aims:
The aim of the study was to study the incidence and clinical presentation of ophthalmic injuries in RTAs.

Settings and Design:
This was a prospective hospital-based study observational study.

Subjects and Methods:
A prospective cross-sectional study was conducted among 300 patients in the department of ophthalmology of a tertiary hospital in Western India from October 2021 to October 2023. Detailed ocular examination and investigations were done. Various parameters, including demographics, type of vehicle, type and severity of the injury, and visual acuity at presentation, were studied. The data obtained from the results were expressed in frequency and percentages.

Statistical Analysis Used:
Not applicable.

Results:
A total of 300 patients were included in the study. The right eye was affected in 177 out of 320 cases. Male preponderance was noted. The most common ocular finding was ecchymosis 168 (56%) followed by lid lacerations 81 (27%). Majority of the cases were in the age group of 31–40 years (31.67%). The incidence of injuries in two-wheeler riders was 283 (94.33%), of which people who were driving without a helmet were 256 (90.5%).

Conclusion:
We concluded from our study that the most common age group, 31–40 years, was involved in ocular injuries due to RTAs with male preponderance. Most of those who sustained injuries were riding two-wheeler vehicles without helmets. The involvement of the right eye was more common in unilateral cases. The most common injury found was blunt trauma presenting as preorbital edema and ecchymosis.
Ethambutol-induced optic neuropathy: Another conundrum
Authors: Kharkande Pinank Chetan , Chandran Avani B. , Kumar Karthik , Shah Virna 
Published: September 2024

Purpose:
The purpose was to study the effect of ethambutol (EMB) and cause for optic neuropathy in the hope that better understanding of the condition will help us to reduce the burden of visual loss.

Materials and Methods:
A retrospective analysis of patients with EMB-induced optic neuropathy was done, which included 30 patients attending our outpatient department from January 2022 to March 2022.

Results:
The mean age was 53.73 with male (70%) preponderance. Visual fields showed bitemporal hemianopia in 43% (13), temporal field defects in 26% (8), centrocecal scotoma in 17% (5), and low reliability in 10% (3). Visual evoked potential amplitude was reduced in 87% (26). Magnetic resonance imaging showed enhancement of optic chiasma in 40% (12). After discontinuing and replacing EMB, with Vitamin B complex and zinc supplements, 53% (16) had visual improvement on 1-month follow-up.

Conclusion:
India has launched the Pradhan Mantri TB Mukt Bharat Abhiyan “Ni-kshay 2.0” portal to eradicate tuberculosis by 2025. Hence, aggressive treatment protocols are underway. The increased duration of EMB in new directly observed therapy short-course regimen has caused increased incidence of EMB optic neuropathy. Regular screening is needed to diagnose and prevent further visual deterioration in these patients. Timely replacement of the drug with another drug is a key in visual recovery of these patients. Further studies are needed to assess if the genetic predisposition is responsible for optic nerve damage.
Janus kinase 2 mutation-negative polycythemia-associated retinal changes in otherwise asymptomatic patients
Authors: Singh Alok Pratap , Gala Deep A. , Husain Ahmad , Yadav Sanjeev , Maroof Lubna , Kanaujia Vikas 
Published: September 2024

Purpose:
The purpose of this study was to document secondary polycythemia (SP)-associated retinal changes and the favorable role of phlebotomy in the treatment of SP-induced retinal complications.

Design:
This was a retrospective, observational, noncomparative case series.

Participants:
A total of 8 eyes of 4 male patients with an age range of 28–78 years were studied.

Materials and Methods:
A total of 04 consecutive patients were received over a year on an outpatient basis at a single tertiary care center, with only vision-related complaints. After documentation of ocular findings, all the patients were subjected to meticulous clinical and laboratory evaluation to determine the cause of ocular conditions. Patients were subjected to the treatment for underlying pathological conditions based on the outcomes of their clinical and laboratory evaluation.

Main Outcome Measures:
Determination of Janus kinase 2 (JAK2) mutation-negative SP as a cause of associated retinal complications and favorable role of phlebotomy as a treatment measure.

Results:
All the patients were adult, nonsmoker, and nonalcoholic males. A total of 05 eyes were diagnosed with proliferative vitreoretinopathy while 2 eyes had retinal venous occlusion. One eye was normal. Except SP, no other cause for retinal lesions could be ascertained in all patients. Three patients underwent phlebotomy as decided by the hematologists. Each patient was followed monthly for 6 months. All the patients showed resolution of retinal lesions at the end of follow-up.

Conclusion:
Nonpolycythemia vera (PV) erythrocytosis or unmutated JAK2 SP is still a very poorly studied entity. Almost no information is available regarding ocular involvement and its treatment in SP. Our observations suggest that SP may run a chronic course causing serious retinal damage such as other myeloproliferative disorders or PV and that phlebotomy has an important role in the management of such cases.
A study of nonglaucomatous optic neuropathies in a teaching hospital in Western Maharashtra
Authors: Kakulavaram Manasa Reddy , Joshi Ajit Kamalakar 
Published: September 2024

Background:
Nonglaucomatous optic neuropathy (NGON) is defined as clinical evidence of optic nerve impairment without glaucomatous field/disc changes. Etiology is diverse and elusive in many patients. Causes of NGON include traumatic, compressive, inflammatory, demyelinating, toxic, nutritional, hereditary, vascular, infiltrative, and idiopathic. NGON disorders can be misdiagnosed as glaucoma and can be preventable or life-threatening. In some, fellow eye involvement is common. This can lead to inadequate management and influence prognosis which can be prevented by multispecialty approach. Physicians and ophthalmologists must be vigilant against threatening NGON forms. It is essential to track burden as most literature focused on particular NGON subtype.

Aim:
The aim was to study the clinical presentation of NGON in a teaching hospital.

Setting and Design:
This was a prospective, hospital-based, cross-sectional, observational study.

Materials and Methods:
A total of 86 eyes of 61 NGON patients were studied from January 2021 to June 2022 in a tertiary care hospital. Detailed history and comprehensive ophthalmic examination were performed in ambulatory patients. Nonambulatory patients were examined using torchlight. Ancillary investigations were performed, to confirm the clinical diagnosis wherever applicable.

Statistical Analysis:
Microsoft Excel was used for statistical analysis.

Results:
The mean age of study patients was 44.87 ± 16.05 years with a male: female ratio of 2.8:1. Unilateral eye involvement was seen in 36 (59.02%). Best-corrected visual acuity = 3/60–1/60 was noted in 41 (47.67%) patients. Red-green defect and contrast sensitivity were reduced by 59.30% and 66.28%, respectively. Relative afferent pupillary defect (RAPD) was noted in 52.46% of patients with Grade 5 RAPD in 40.63%. The most common visually evoked potential type and visual field defect noted were axonal and central scotoma (n = 31 [36.05%] and n = 26 [30.23%]), respectively. Traumatic optic neuropathy was diagnosed in 15 (24.59%) followed by inflammatory optic neuritis in 11 (18.04%) patients.

Conclusion:
Diagnosing cause of NGON in clinical practice is challenging, but emerging burden cannot be neglected. Knowledge of various NGON types helps narrow differential diagnoses and execute efficient, targeted workup. Timely recognition alters visual, neurological prognosis and saves the lives of patients sometimes.
The 2023 outbreak of viral conjunctivitis: Clinical features and treatment patterns from five states in India
Authors: Chatterjee Samrat , Kapur Neha , Chanda Sanjay , Bhavatharini M. , Sawant Sanil , Sangwan Virender Singh , Majumdar Atanu 
Published: September 2024

Background:
In July 2023, an outbreak of viral conjunctivitis swept across India. A knowledge of clinical features and outcome of treatment helps in the management of future outbreaks.

Aim:
The aim of this study was to report the clinical presentation, treatment, and outcome in patients affected during the outbreak of viral conjunctivitis.

Setting and Design:
This was a multicentric retrospective case series.

Materials and Methods:
This study reviewed the medical records of all consecutive patients diagnosed with viral conjunctivitis between July 1, 2023, and August 10, 2023, in five centers across India.

Results:
Of the 793 patients, 525 (66.2%) were male and 268 (33.8%) were female, with a mean age of 34.1 ± 19.0 years. The mean symptom duration was 2.6 ± 2.1 days with bilateral disease in 591 (74.5%) patients. The common ocular signs were conjunctival congestion (793, 100%), lid edema (479, 60.4%), follicles (607, 76.5%), and conjunctival hemorrhages (339, 42.7%). Artificial tears were used in 730 (92.1%) patients, antibiotic eye drops in 661 (83.4%) patients, and steroid eye drops in 428 (54.0%). The time to resolution was the least in patients who had been treated with only artificial tears (4.61 ± 2.24 days) and was maximum in patients who had been treated with topical steroids (6.5 ± 2.51 days), and the difference was significant (P < 0.001).

Conclusion:
The presence of conjunctival hemorrhages indicated acute hemorrhagic conjunctivitis. Although many patients were treated with topical antibiotics, it was unnecessary, as the shortest resolution time was found in patients who had been received supportive therapy with artificial tear eye drops and not topical antibiotics or steroids.
Advancing Precision in Penile Length Measurement: Evidence-based Synthesis of Stretched Penile Length INdicator Technique (SPLINT)
Authors: Goel Prabudh , Choudhury Prativa , Saroya Komal Kaur , Jain Vishesh , Dhua Anjan Kumar , Yadav Devendra Kumar , Anand Sachit , Agarwala Sandeep , Sharma Kanika , Agrawal Vikesh , Saha Subhasis , Singh Harpreet , Sharma Naveen , Singh V. P. 
Published: September 2024

ABSTRACT

Purpose:
The purpose of this study was to synthesize evidence and propose a technique for estimation of stretched penile length (SPL) applicable to children.

Materials and Methods:
This review has been conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, Embase, and Scopus databases were queried on penile length (PL) measurement techniques in humans published from 1990 onward. The devices and the techniques used for PL measurement, state of the penis, the habitus of the participants, proximal and distal landmarks for measurement, handling the foreskin and pubic pad of fat, optimal stretching of the penis, and other factors (including the environment) which should be accounted for in the technique were identified from the study cohort (90895 participants across 145 included studies).

Results:
PL has been represented through flaccid (33.79%), stretched (81.3%), and erect (12.41%) PLs as well as the greatest corporeal length (1.4%). Following devices have been used to measure the PL in the study cohort: rulers [54.68%], calipers [9.7%], measuring tapes [14.5%], coloured measuring strips [2.06%], spatulas/tongue depressors [11.03%], FitKit, syringe [1.4%], cotton swab (and ruler), titan cylinders, slide gauge and ultrasonography [1.37%]. The factors relevant to SPL measurement have been incorporated into the proposed SPL INdicator Technique (SPLINT) which is essentially a holistic extension of the “Conventional PL Measurement” technique.

Conclusions:
There is a wide range of heterogeneity in the technique for estimation of PL across the study cohort; the underlying factors have been identified along with the respective variables, and the SPLINT for SPL has been described.
Correlation of Hand Digit Length Ratio, Anogenital Distance, and Severity of Hypospadias among Prepubertal Boys
Authors: Prasad Gaurav , Dhua Anjan Kumar , Goel Prabudh , Yadav Devendra Kumar , Agarwala Sandeep , Pandey Shivam 
Published: September 2024

ABSTRACT

Aims:
Antenatal androgen exposure has been suggested as a contributing factor in hypospadias etiology. This study aimed to investigate the correlation between anogenital distance (AGD), index finger-to-ring finger ratio (2D:4D ratio), and hypospadias severity in prepubertal boys, with the goal of exploring these parameters as potential markers of genital anomalies in utero.

Materials and Methods:
A cross-sectional observational study was conducted on boys under 8 years old presenting to our outpatient department (April 2020–December 2022). Those with hypospadias were included in the study group, whereas those without hypospadias formed the comparator group. Confounding factors (age, weight, and height) were accounted for using multivariate linear regression analysis. AGD, 2D:4D ratio, and hypospadias severity were measured during clinical visits, with still images taken for precise measurements. Statistical analysis was performed using the Mann–Whitney U and student’s t-tests (software: STATA Version 14).

Results:
Data were collected for 100 cases of hypospadias (26 proximal and 74 distal) and 50 controls. There was no significant difference in mean age between groups (P = 0.90). AGD was slightly lower in cases (3.44 ± 1.13 cm) compared to controls (3.70 ± 1.43) (P = 0.88). 2D:4D ratios were marginally higher in cases compared to controls (P = 0.12 for both hands).

Conclusions:
Although our study did not find significant associations between AGD and 2D:4D ratios with hypospadias severity, it offers insights into the role of prenatal androgen in genital development. The lack of significance underscores the need for region-specific research, suggesting AGD and 2D:4D ratio may not universally apply as hypospadias markers.