bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virtual screening and molecular dynamics simulation study of approved drugs as a binder to the linoleic acid binding site on spike protein of SARS-CoV-2 and double mutant (E484Q and L452R)
Authors: Prajapat Manisha , Sarma Phulen , Shekhar Nishant , Chauhan Arushi , Kaur Gurjeet , Bhattacharyya Anusuya , Avti Pramod , Choudhary Gajendra , Bansal Seema , Sharma Saurabh , Kaur Hardeep , Kumar Subodh , Mann Harvinder , Raja Anupam , Singh Ashutosh , Singh Rahul , Sharma Amit Raj , Prakash Ajay , Medhi Bikash 
Published: May 2024

INTRODUCTION:
Binding of linoleic acid (LA) to the spike trimer stabilizes it in closed conformation hindering its binding to angiotensin-converting enzyme-2, thus decreasing infectivity. In the current study, we tend to repurpose Food and Drug Administration-approved drugs as binder to the LA binding pocket in wild and double mutant spike protein.

MATERIALS AND METHODS:
Approved drugs from DrugBank database (n = 2456) were prepared using Ligprep module of Schrodinger. Crystal structure of LA bound to spike trimer was retrieved (PDB: 6ZB4) and prepared using protein preparation wizard and grid was generated. A virtual screening was performed. With the help of molecular dynamics (MD) studies interaction profile of screened drugs were further evaluated. The selected hits were further evaluated for binding to the double mutant form of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

RESULTS AND DISCUSSION:
Following virtual screening, a total of 26 molecules were shortlisted, which were further evaluated using 1ns MD simulation study. Four ligands showing better root mean square deviation (RMSD), RMSD to LA with interaction profile similar to LA were further evaluated using 100 ns MD simulation studies. A total of 2 hits were identified, which performed better than LA (selexipag and pralatrexate). Both these ligands were also found to bind to LA binding site of the double mutant form (E484Q and L452R); however, the binding affinity of pralatrexate was found to be better.

CONCLUSION:
We have identified 2 ligands (selexipag and pralatrexate) as possible stable binders to the LA binding site in spike trimer (wild and mutant form). Among them, pralatrexate has shown in vitro activity against SARS-CoV-2, validating our study results.
Investigation of the Asyogh’s rectangular device for learning and memory testing in Wistar rats
Authors: Yadav Yogesh Chand 
Published: May 2024

Abstract:
This study aimed to design Asyogh’s rectangular device that is used for memory testing in rodents. It was found that scopolamine (3 mg/kg i.p.) and diazepam (1 mg/kg i.p.) caused significant memory deficits in rats, as evidenced by increased transfer latency times. However, these memory deficits were significantly reversed when the rats were pretreated with Donepezil. It further demonstrates that pretreated donepezil is able to effectively restore the memory deficits induced by scopolamine and diazepam, as indicated by the significant recovery in TLT. The present study showed that the device used to measure transfer latency time that was a valuable tool for assessing memory and cognitive function in rodents.
The clinical effect of ossotide for injection in the treatment of condylar fracture
Authors: Jiang Qian , Chen Yifei , Zhu Fangyong , Xie Yujia , Zhu Zhidan , Sun Xiaojing 
Published: May 2024

Abstract:

OBJECTIVES:
Patients with condylar fractures were treated with osteopeptide injections as an adjuvant therapy to assess pain control and changes in interleukin-1b (IL-1β) and bone G-gla protein (BGP) levels.

MATERIALS AND METHODS:
Eighty-two patients with a condylar neck fracture were randomly assigned to two groups. The control group received conventional surgical treatment, while the experimental group received osteopeptide injections in addition to surgery. Pain level, IL-1β, and BGP levels were evaluated at 1, 2, and 4 weeks postsurgery.

RESULTS:
One and two weeks postsurgery, the experimental group had lower Numeric Rating Scale scores compared to the control group. In addition, the IL-1β level in patients receiving osteopeptide injections was lower than the control group at all three evaluation points (1, 2, and 4 weeks postsurgery) and the BGP level was higher with statistically significant differences (P < 0.05).

CONCLUSIONS:
The administration of osteopeptide injections as an adjuvant therapy for patients with condylar fractures can effectively reduce pain and facilitate faster initiation of muscle function training. In addition, the reduction of inflammatory factors and promotion of active osteogenesis leads to quicker wound healing.
Raptinal ameliorates 1,2-dimethylhydrazine-induced colon cancer through p53/Bcl2/Bax/caspase-3-mediated apoptotic events in vitro and in vivo
Authors: Lan Yongting , Yang Yang , Das Abhijit , Bhattacharya Barshana , Roy Souvik 
Published: May 2024

OBJECTIVES:
Colon carcinoma stands as the most familiar malignancy throughout across the globe. Raptinal induce apoptosis through the alteration of cellular events. Thus, in the present investigation, the anticancer activity of raptinal counter to 1,2-dimethylhydrazine (DMH) persuaded colon carcinoma has been evaluated through both in vivo and in vitro systems.

MATERIALS AND METHODS:
The pharmacophore analysis demonstrated the binding efficacy of raptinal with the apoptotic proteins. The chemotherapeutic activity of raptinal was examined through HT-29 human colorectal cancer (CRC) cell line as well as DMH persuaded CRC in the rat model. The cytotoxicity analysis, flow cytometry, and DAPI analysis have been carried out on HT-29 cell line through in vitro assessment. The colon carcinoma has been induced through DMH administration and subsequently Dextran sulfate sodium treatment in male Wistar rats. After 18 weeks of raptinal treatment, the colon tissues have been investigated for aberrant crypt foci (ACF) count, antioxidant status, histology, immunohistochemical assessment, and apoptotic analysis.

RESULTS:
The raptinal therapy on HT-29 cells demonstrated a substantial % of early apoptosis followed by G0 and G1 phase arrest, which subsequently led to apoptosis. Furthermore, it inhibits ACF development with improved colonic abrasions and structural integrity of colonic mucosa with increased levels of antioxidants, proapoptotic biomarkers including p53, caspase-3, Bax and downstream effects of Bcl-2, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 mutation.

CONCLUSIONS:
These findings indicate the raptinal effectively reduces colon cancer by inducing apoptosis through p53/Bcl2/Bax/caspase-3 pathway and suppressing IL-6, TNF-mediated chronic inflammation in the colon cancer microenvironment.
Treatment of hydatid cyst with albendazole desensitization: A pediatric case report
Authors: Çalişkan Nilay , Coskun Raif , Bologur Hamit , Yildırım Güler , Güngör Hilal , Bosnali Oktav , Özçeker Deniz 
Published: May 2024

Abstract:
Albendazole is a benzimidazole group drug used alone or in combination with surgery in the treatment of many helminthiasis, especially hydatid cysts. Type 1 hypersensitivity reaction has been reported rarely. Treatment with desensitization has been successfully applied in a few adult patients, however literature information on pediatric patients was not available. Here, we present a pediatric case in which Type 1 reaction occurred due to the use of albendazole during hydatid cyst treatment and undergone desensitization.
Influence of trazodone on the pharmacodynamics and pharmacokinetics of pioglitazone
Authors: Pradeepkumar Bhupalam , Goruntla Narayana , Chinthaginjala Haranath , Reddy K. Somasekhar , Ahad Abdul , Sudheer A. , Raghavendra M. 
Published: May 2024

BACKGROUND:
These days, poly pharmacy is very common for the treatment of multiple diseases and majority of drugs were metabolized with CYP 450 enzymes. Diabetes mellitus is such a disorder, which requires continuous therapy for the control of blood glucose concentration. Depression was quite common in diabetic patients. Therefore, multiple drugs required to treat diabetes mellitus and depression. Simultaneous administration of these drugs leads to drug interaction. Pioglitazone and trazodone metabolized by CYP3A4 enzymes which may lead to potential drug interaction.

OBJECTIVES:
This study aimed to find the influence of trazodone on the pharmacokinetics & pharmacodynamics of pioglitazone in normal & diabetic rats, also on rabbits and subsequently effectiveness and safety of the combination was evaluated.

METHODS AND MATERIAL:
Blood glucose concentration was determined by Glucose oxidase/peroxidase method in normal and diabetic rats. Diabetes was induced with Streptozotocin at a dose of 55 mg/kg body weight. Serum pioglitazone concentration was estimated by high performance liquid chromatography method for pharmacokinetic data. The values were expressed as Mean ± Standard Error Mean (SEM), GraphPad Prism 3.0 (San Diego, California, USA) software was used to express the data. Student's paired 't' test was used to determine the significance.

RESULTS:
Pioglitazone produces hypoglycaemia in normal rats with a maximum decrease of 36.78 % ± 0.81 at 3 hours interval and anti-hyperglycaemic activity in diabetic rats with maximum reduction of 45.13 % ± 1.52 at 2 hours interval. Trazodone altered the pharmacokinetics of pioglitazone and improved the pioglitazone hypoglycaemic effect.

CONCLUSION:
Trazodone apparently produced pharmacokinetic interaction with pioglitazone which might be by attenuating the metabolism of pioglitazone. Therefore, care should be taken in simultaneous therapy with pioglitazone and trazodone.
Efficacy and safety analysis of prucalopride in refractory chronic constipation cases in a tertiary care hospital in Eastern India
Authors: Dehury Suhasini , Mohapatra Sourya , Das Haribhakti Seba , Goutam Siddhartha , Kaushik Chetna 
Published: May 2024

OBJECTIVES:
Chronic constipation (CC), a common functional gastrointestinal disorder, has laxatives as its mainstay of treatment. Refractoriness to laxatives calls for better treatment options. Prucalopride is a novel, well-tolerated enterokinetic with high 5-hydroxytryptamine 4 receptor selectivity. This study was undertaken with the intention to establish the efficacy and safety of prucalopride with placebo in adults with refractory CC.

MATERIALS AND METHODS:
Patients were screened and 180 patients fulfilling the inclusion criteria were simply randomized into 2 groups either to receive prucalopride 2 mg (n = 90) or placebo (n = 90) once daily for a duration of 12 weeks. The efficacy endpoints (primary) were intended to measure the proportion of patients with three or more spontaneous complete bowel movements (SCBMs) per week over 12 weeks. Secondary endpoints were assessed via the validated questionnaires. Adverse events, electrocardiogram, and other laboratory parameters were monitored at different time intervals.

RESULTS:
Efficacy and safety were analyzed in 180 patients simply randomized (1:1) into group A (prucalopride arm, n = 90) and group B (placebo arm, n = 90). Patients having three or more SCBMs per week in the prucalopride arm (2 mg) were 41% as against to 12% in the placebo arm (P < 0.001). A significant increase (P < 0.001) in the number of spontaneous bowel movements per week plus an increase of average bowel movement by 1 point per week was seen in the prucalopride arm. Secondary efficacy endpoints which included patients' treatment satisfaction, improvement in the perception of constipation symptoms using the patient assessment of constipation -symptoms and stool consistency score changes were more pronounced in the prucalopride arm than the placebo. The most common adverse events reported from both the groups were headache, nausea, bloating, and diarrhea. No significant cardiovascular changes or laboratory abnormality was detected throughout the study period.

CONCLUSION:
Prucalopride is effective in laxative refractory CC cases with a good safety profile.
Analysis of adverse drug reactions of imatinib in chronic myeloid leukemia patients
Authors: Swain Trupti Rekha , Goutam Siddhartha , Jena Rabindra Kumar , Rout Niranjan 
Published: May 2024

BACKGROUND:
Imatinib mesylate is the cornerstone therapy in the management of chronic myeloid leukemia (CML). Monitoring of adverse drug reactions (ADRs) of imatinib in our patients is very important to ensure their safety. Aims and Objectives: The current study aims to monitor ADRs encountered in CML patients in the chronic phase with imatinib (400 mg/day).

MATERIALS AND METHODS:
This prospective, observational study was conducted from November 2011 to May 2015 on 310 patients presented to the Departments of Clinical Hematology and Pharmacology of SCB MCH, Cuttack, diagnosed with CML at chronic phase. Collected ADRs were entered in the ADR reporting form (PvPI) and were analyzed for causality and severity.

RESULTS:
Anemia was the most common hematological ADR, whereas hyperpigmentation and nausea were the most common nonhematological ADRs reported. Maximum ADRs were mild to moderate and required no change in the treatment course.

CONCLUSION:
The study revealed that imatinib mesylate, a well tolerated drug, has very few cases of severe ADRs in Indian patients at the chronic stable phase of CML.
Comparison of patients using lamivudine, entecavir, and tenofovir according to liver fibrosis markers fibrosis-4 and aspartate aminotransferase-to-platelet ratio index scores
Authors: Okan Huseyin Dogus , Karabay Oguz , Guclu Ertugrul , Inci Mustafa Baran , Ogutlu Aziz 
Published: May 2024

OBJECTIVES:
It was intended to assess the efficacy of lamivudine, entecavir, and tenofovir regimens in the management of chronic hepatitis B (CHB) guided by Fibrosis-4 (FIB-4) and aspartate aminotransferase-to-platelet ratio index (APRI) scores.

MATERIALS AND METHODS:
Our study was conducted on patients who applied to the hepatitis outpatient clinic between 2008 and 2015 retrospectively. Lamivudine, entecavir, and tenofovir regimens used in the practice of CHB cases were compared by measuring noninvasive FIB tests.

RESULTS:
Entirely 199 patients involved in the research were evaluated in three treatment arms; 48 used lamivudine, 46 used entecavir, and 105 used tenofovir. Similar statistical characteristics were observed between research arms regarding age, gender, and alanine aminotransferase normalization by years (P > 0.05). Totally 5 (13.5%) of patients developed Hepatitis B e antigen (HBeAg) seroconversion among 36 HBeAg positivity, and similar statistical features were seen by comparing the groups (P > 0.05). In the entecavir and tenofovir arms, a significant decrease was seen in FIB-4, and APRI index values in the 1st year of treatment (P < 0.001). At the graph curve, a plateau was observed in the APRI test after the 1st year, and a plateau was observed in the FIB-4 test after the 2nd year.

CONCLUSION:
Consistent with the study outcome, when we consider FIB regression, tenofovir and entecavir regimens were found more effective than lamivudine. In addition, entecavir was more effective than the other two drugs after the 1st year.
Efficacy, safety, and dose-response effects of calcifediol supplementation on 25-hydroxyvitamin D, parathyroid hormone, and 1,25-dihydroxyvitamin D levels in healthy adults
Authors: Das Liza , Holick Michael F. , Sachdeva Naresh , Bhadada Sanjay Kumar , Singhmar Shallu , Thakur Neetika , Dutta Pinaki , Marwaha Raman Kumar 
Published: May 2024

BACKGROUND:
Vitamin D deficiency (VDD) is highly prevalent across the globe. Cholecalciferol (Vitamin D3) fails to attain sufficient serum concentrations of 25-hydroxyvitamin D (25(OH)D) in a significant proportion of supplemented individuals. Calcifediol (25-hydroxyvitamin D3) is less studied in healthy adults and its effects on 25(OH)D, parathyroid hormone (PTH), and 1,25-dihydroxyvitamin D (1,25(OH)2D) at higher doses are not well known.

MATERIALS AND METHODS:
The study was an open-label, interventional trial recruiting consecutive participants with VDD who were allocated to receive either 2 capsules (50 μg-group) or 1 capsule (25 μg-group) daily doses of calcifediol. Baseline assessment included clinicodemographic parameters, dietary calcium, calcemic (calcium, inorganic phosphate, albumin, alkaline phosphatase, urine spot calcium/creatinine), and hormonal parameters (25(OH)D, PTH, and 1,25(OH)2D). Participants were followed up at 4 and 8 weeks with repeat assessments of calcemic and hormonal parameters.

RESULTS:
There were 64 participants, 35 (50 μg-group) and 29 (25 μg-group), without any significant difference in any of the baseline parameters. 97.1% participants in the 50 μg-group (at 4 and 8 weeks) and 93.1% (at 4 weeks) and 96.5% (at 8 weeks) in the 25 μg-group attained 25(OH)D sufficiency (≥30 ng/ml) with calcifediol. The mean serum 25(OH)D was 84.0 ± 27.7 ng/ml in the 50 μg-group and 58.0 ± 23.6 ng/ml in the 25 μg-group group at 4 weeks, which later rose to 94.3 ± 21.8 ng/ml and 76.0 ± 16.4 ng/ml, respectively, at 8 weeks. PTH levels decreased in both groups at both time points. 1,25(OH)2D rose significantly in both groups at 4 and 8 weeks but was not significantly different between both groups. There was no case of incident hypercalcemia or symptomatic nephrolithiasis.

CONCLUSION:
Calcifediol is a safe and efficacious alternative for oral Vitamin D supplementation in young adults. Increment in 25(OH)D levels is rapid and dose-dependent.
Use of drugs not listed in the National List of Essential Medicines
Authors: Jhaj Ratinder , Banerjee Aditya , Kshirsagar Nilima Arun , Sadasivam Balakrishnan , Chandy Sujith J , Bright Heber Rew , Chugh Preetha Kaur , Tripathi C D , Badyal Dinesh Kumar , Samuel Madhulika Peter , Medhi Bikash , Prakash Ajay , Joshi Rupa , Kamat Sandhya , Tripathi Raakhi , Parmar Urwashi Indrakumar , Dikshit Harihar , Mishra Hitesh , Roy Sukalyan Saha , Trivedi Niyati , Chauhan Janki , Chatterjee Suparna , Bhattacharya Manjari , Desai Chetna K , Sheth Shamil , Gupta Pooja , Roy Atanu , Raveendran Ramasamy , Mathaiyan Jayanthi , Jeevitha G , Kaushal Sandeep , Gupta Kanchan , Jain Samriti , Kaul Rajni 
Published: May 2024

BACKGROUND:
The concept of listing essential medicines can lead to improved supply and access, more rational prescribing, and lower costs of drugs. However, these benefits hinge on the prescription of drugs from an Essential Medicines List (EML). Several studies have highlighted the problem of underutilization of EMLs by prescribers. Therefore, as part of prescription research by the Indian Council of Medical Research-Rational Use of Medicines Centres Network, we evaluated the extent of prescription of drugs not listed in the National List of Essential Medicines (NLEM).

MATERIALS AND METHODS:
Prescriptions of outpatients from participating centers were included after obtaining verbal/written informed consent as approved by the Ethics Committee, and evaluated for prescription of drugs from the NLEM 2015.

RESULTS:
Analysis of 4838 prescriptions from 13 tertiary health-care institutes revealed that 2677 (55.33%) prescriptions had at least one non-NLEM drug prescribed. In all, 5215 (31.12%) of the total 16,758 drugs prescribed were not in NLEM. Of these, 2722 (16.24%) were single drugs and 2493 (14.88%) were fixed-dose combinations (FDCs). These comprised 700 different drug products – 346 single drugs and 354 FDCs. The average number of non-NLEM drugs prescribed per prescription was 1.08, while the average number of all drugs prescribed was 3.35 per prescription. It was also found that some of the non-NLEM drugs prescribed had the potential to result in increased cost (for example, levocetirizine), increased adverse effects (dextromethorphan), and less effectiveness (losartan) when compared to their NLEM counterparts. Nonavailability of an essential drug (oral hydroxocobalamin) was another important finding of our study.

CONCLUSION:
This study highlights the extent and pattern of drugs prescribed from outside the NLEM at the tertiary health-care level and the need for training and enhanced awareness among prescribers for greater utilization of the NLEM.
Lasmiditan abortive therapy for episodic migraine in Phase II/III randomized clinical trials
Authors: Ahsan Marya , Mallick Ayaz Khurram 
Published: May 2024

OBJECTIVE:
Although migraine is common, there are very few treatment options. Recently, lasmiditan, a specific 5-HT1F agonist, has gained approval as abortive therapy for migraine. This meta-analysis and trial sequential analysis (TSA) was performed to analyze efficacy and tolerability of lasmiditan therapy for episodic migraine.

MATERIALS AND METHODS:
Phase II and Phase III double-blinded placebo-controlled randomized controlled trials (RCTs) evaluating lasmiditan for episodic migraine were searched for from electronic databases. The risk of bias was estimated, data were extracted, and relative risk (RR) were calculated for efficacy and safety outcomes with a fixed/random effect model. Forest plots and funnel plots were created. TSA graph was plotted. Therapeutic gain with lasmiditan was calculated.

RESULTS:
Six high-quality RCTs were included with 7122 patients. Compared to placebo, lasmiditan demonstrated a significant proportion of migraineurs reporting freedom from headache, most bothersome symptom, headache response, no disability, global impression “very much/much better” 2 h posttreatment and sustained pain freedom at 24 and 48 h with 50, 100, 200, and 400 mg doses (RR range = 1.26–2.50). 39.3% of patients in the lasmiditan group (RR = 2.43) reported one or more treatment-emergent adverse event (TEAE). Dizziness, somnolence, paresthesia, fatigue, nausea, vertigo, hypoesthesia, asthenia, muscular weakness, lethargy, and malaise had a high incidence (RR range = 3.16–12.77). Most TEAEs were mild to moderate. No vasoconstriction-related TEAE was reported.

CONCLUSION:
Lasmiditan demonstrated efficacy as abortive therapy for episodic migraine with central nervous system-related side effects.
Two-Arm Observational Study to Assess the Efficacy of Cooled versus Conventional Radiofrequency Ablation of Medial Branch Nerves in Patients with Lumbar Facet Joint Arthropathy
Authors: Saroha Swati , Bhattacharya Dipasri , Arya Prashant , Choudhury Arpita , Biswas Rajasree 
Published: May 2024

Background:
Pain originating in the facet joint accounts for an estimated 15%–45% of cases of low back pain. Radiofrequency ablation (RFA) of the medial branch nerves (MBN) is used in refractory cases. However, very few studies have compared the clinical outcomes of cooled versus conventional/traditional RFA (T-RFA) for the treatment of lumbar facet joint pain.

Objective:
To determine the clinical outcomes of MBN cooled RFA (C-RFA) compared with T-RFA, as measured by improvements in pain and physical function.

Methodology:
Forty patients with positive diagnostic MBN blocks were allocated to C-RFA or T-RFA group. Reduction in pain (NRS “Numerical Rating Scale” score), improvement in quality of life (Oswestry Disability Index [ODI]), proportion of responders/successful treatment (≥50% NRS reduction, and or ≥30% or ≥15 point reduction in ODI at 6 months follow up) in the two groups were recorded.

Results:
Total 34 patients were analysed, C-RFA (n = 18) and T-RFA (n = 16). There was significant reduction in pain scores as well as improvement in quality of life in both the groups, but the difference between the two groups was not significant. NRS reduction of ≥50% was observed in 72.22% and 68.5% of participants in the C-RFA and T-RFA groups, respectively (P = 0.824). A ≥15-point or ≥30% reduction in ODI score was observed in 77.77% and 75% of participants in the C-RFA and T-RFA groups, respectively (P = 0.849).

Conclusions:
Both the groups showed significant improvement in pain scores and quality of life. C-RFA resulted in greater treatment success rate than conventional RFA, but the difference was not significant.