The 100 most influential papers in medical artificial intelligence; a bibliometric analysis.

Objective: To assess the current trends in the field of artificial intelligence in medicine by analysing 100 most cited original articles relevant to the field. METHODS: The bibliometric analysis was conducted in September 2022, and comprised literature search on Scopus database for original articles only. Google and Medical Subject Headings databases were used as resources to extract key words. In order to cover a broad range of articles, original studies comprising human as well as non-human subjects, studies without abstract and studies in languages other than English were part of the inclusion criteria. There was no specific time period applied to the search and no specific selection was done regarding the journals in the database. The screening was done using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to extract the top 100 most cited articles in the field of artificial intelligence usage in medicine. Data was analysed using SPSS 23. RESULTS: Of the 11,571 studies identified, 100(0.86%) were analysed in detail. The studies were published between 1986 and 2021, with a median of 43 citations (IQR 53) per article. The journal 'Artificial Intelligence in Medicine' accounted for the highest number 9(9%)) of articles, and the United States was the country of origin for most of the articles 36(36%). Conclusion: The trends, development and shortcomings in field of artificial intelligence usage in medicine need to be understood to conduct an effective research in areas that still need attention, and to guide the authorities to direct their funding accordingly.

Immunoinformatics-driven In silico vaccine design for Nipah virus (NPV): Integrating machine learning and computational epitope prediction.

The Nipah virus (NPV) is a highly lethal virus, known for its significant fatality rate. The virus initially originated in Malaysia in 1998 and later led to outbreaks in nearby countries such as Bangladesh, Singapore, and India. Currently, there are no specific vaccines available for this virus. The current work employed the reverse vaccinology method to conduct a comprehensive analysis of the entire proteome of the NPV virus. The aim was to identify and choose the most promising antigenic proteins that could serve as potential candidates for vaccine development. We have also designed B and T cell epitopes-based vaccine candidate using immunoinformatics approach. We have identified a total of 5 novel Cytotoxic T Lymphocytes (CTL), 5 Helper T Lymphocytes (HTL), and 6 linear B-cell potential antigenic epitopes which are novel and can be used for further vaccine development against Nipah virus. Then we performed the physicochemical properties, antigenic, immunogenic and allergenicity prediction of the designed vaccine candidate against NPV. Further, Computational analysis indicated that these epitopes possessed highly antigenic properties and were capable of interacting with immune receptors. The designed vaccine were then docked with the human immune receptors, namely TLR-2 and TLR-4 showed robust interaction with the immune receptor. Molecular dynamics simulations demonstrated robust binding and good dynamics. After numerous dosages at varied intervals, computational immune response modeling showed that the immunogenic construct might elicit a significant immune response. In conclusion, the immunogenic construct shows promise in providing protection against NPV, However, further experimental validation is required before moving to clinical trials.

Carbon trade-off and energy budgeting under conventional and conservation tillage in a rice-wheat double cropping system.

Amid rising energy crises and greenhouse gas (GHG) emissions, designing energy efficient, GHG mitigation and profitable conservation farming strategies are pertinent for global food security. Therefore, we tested a hypothesis that no-till with residue retaining could improve energy productivity (EP) and energy use efficiency (EUE) while mitigating the carbon footprint (CF), water footprint (WF) and GHG emissions in rice-wheat double cropping system. We studied two tillage viz., conventional and conservation, with/without residue retaining, resulting as CT0 (puddled-transplanted rice, conventional wheat -residue), CTR (puddled-transplanted rice, conventional wheat + residue), NT0 (direct seeded rice, zero-till wheat -residue), and NTR (direct seeded rice, zero-till wheat + residue). The overall results showed that the NTR/NT0 had 34% less energy consumption and 1.2-time higher EP as compared to CTR/CT0. In addition, NTR increased 19.8% EUE than that of CT0. The grain yield ranged from 8.7 to 9.3 and 7.8-8.5 Mg ha-1 under CT and NT system, respectively. In NTR, CF and WF were 56.6% and 17.9% lower than that of CT0, respectively. The net GHG emissions were the highest (7261.4 kg CO2 ha-1 yr-1) under CT0 and lowest (4580.9 kg CO2 ha-1 yr-1) under NTR. Notably, the carbon sequestration under NTR could mitigate half of the system's CO2-eq emissions. The study results suggest that NTR could be a viable option to offset carbon emissions and water footprint by promoting soil organic carbon sequestration, and enhancing energy productivity and energy use efficiency in the South Asian Indo-Gangetic Plains.

The Use of Telemedicine in Providing Mental Health Support for the Flood Victims of Pakistan.

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A rare case report of recurrent primary intra-abdominal synovial sarcoma: An unusual manifestation.

Synovial sarcomas are a rare and aggressive subtype of soft tissue sarcomas that typically affects young adults and involves the extremities. Synovial sarcoma of the kidney is a rare and aggressive tumor with a poor prognosis, accounting for only 1% of all renal tumors. The imaging features of this tumor often overlap with those of other renal tumors, and a definitive diagnosis can only be made through immunohistochemical analysis. In this case report, we present the case of a 55-year-old female with left flank pain, who was diagnosed with primary renal synovial sarcoma following a left-sided radical nephrectomy. Despite initial successful surgical intervention, restaging scans showed local recurrence and metastatic disease, which was subsequently managed with 6 cycles of chemotherapy followed by radiation therapy with palliative intent. This case underscores the importance of early detection and aggressive management of rare renal tumors to improve patient outcomes.

Diagnostic Dilemma: Infective Endocarditis in the Setting of an Esophageal Abscess.

Transesophageal echocardiography (TEE) is the preferred imaging modality to diagnose infective endocarditis (IE). However, esophageal disease can preclude performing a TEE. We present such a scenario. A patient with an esophageal abscess, methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia, and septic pulmonary emboli with suspicion for IE based on the modified Duke criteria. However, due to the patient's esophageal abscess, TEE could not be performed safely. We present this case to demonstrate a rare scenario in which a patient with an esophageal abscess also had presumed IE.

Predictive ability of physiochemical properties of benzene derivatives using Ve-degree of end vertices-based entropy.

Topological indices relate chemical structure to chemical reactivity, physical properties, and biological activity. Quantitative structure-activity relationships (QSPR) are mathematical models proposed for the correlation of various types of chemical reactivity, biological activity, and physical properties with topological indices/entropies. In this article, we have proposed the QSPR between the ve-degree of end vertices of edge based entropies and the physiochemical properties of benzene derivatives. We have designed a Maple-based algorithm for the computation of entropies. The relationship was analyzed using SPSS. We have shown that the physiochemical properties such as critical pressure, Henry's law, critical temperature, Gibb's energy, logP, critical volume, and molar refractivity can be predicted by entropies. All the results were highly positive and significant. The Randic, Balaban, and redefined third Zagreb entropies showed the best relations with physiochemical properties.Communicated by Ramaswamy H. Sarma.

Catastrophic Antiphospholipid Syndrome: A Rare Cause of Acute Heart Failure.

Catastrophic antiphospholipid syndrome (CAPS) is a rare variant of antiphospholipid syndrome (APLS). CAPS is a syndrome characterized by microvascular thrombosis leading to multi-organ failure, including acute heart failure. Diagnosis is challenging, and disease progression is rapid. Treatment includes triple therapy with anticoagulation, glucocorticoids, and plasma exchange. We present a case of a patient with CAPS who developed de novo acute heart failure. With treatment, the patient's multi-organ failure improved, including cardiac function. It is our goal to present this case in order to facilitate greater diagnostic suspicion and the early treatment of CAPS to reduce morbidity and mortality.

Temporomandibular Disorders among Dental Students in Pakistan: Assessment of Prevalence, Severity, and Associated Factors Based on Questionnaire.

Objective: To evaluate the prevalence, severity, and associated factors of temporomandibular disorder (TMD) among dental students. Methods: This cross-sectional study was performed on undergraduate dental students from four dental colleges in Punjab, Pakistan. Fonseca's questionnaire was used to measure the prevalence and severity of the TMD among the study participants. Bivariate and multiple logistic regression analyses were performed. Results: Of 364 dental students, 323 returned the completed questionnaires and the response rate of the study was 88.7%. The study included 52.6% males and 47.4% females. The prevalence of TMD was 66.9% with mild TMD in 40.90%, moderate TMD in 14.6%, and severe TMD in 11.50% of the participants. Psychological stress (29.6%), malocclusion (20%), and hypersensitivity (19.5%) were common among participants. The mean TMD score of the sample was 31.54 ± 24.86 which was significantly higher among participants with no/school-educated mothers (P=0.021) and fathers (P=0.002). The participants with arthritis (72.81 ± 32.19) and malocclusion (59.46 ± 31.09) and those who received orthodontic treatment (53.21 ± 34.21) demonstrated higher TMD. After controlling for other study variables, the participants with arthritis were 4.71 times more likely to have moderate/severe TMD (P=0.042) than those without arthritis. Similarly, the participants with malocclusion had significantly higher odds (OR = 3.57, P=0.029) of having moderate/severe TMD than those without malocclusion. Conclusion: This sample of dental students demonstrated a high prevalence and severity of TMD. The participants with arthritis and malocclusion demonstrated higher TMD. The study findings underscore the importance of prevention, early diagnosis, and management of TMD among the dental students.

Thymus linearis Extracts Ameliorate Indices of Metabolic Syndrome in Sprague Dawley Rats.

Materials and Methods: The extract library (n-hexane (NH), ethyl acetate (EA), methanol (M), distilled water (DW), and combined extract (CE)) was standardized using in vitro phytochemical, antioxidant, and α-amylase inhibition assays, after which the protective effect of selected "hit," i.e., CE against metabolic syndrome, was determined in vivo, using rats fed a high-fat diet supplemented with additional cholesterol administration. CE was administered to Sprague Dawley rats in high dose as 100 mg/kg in carboxymethyl cellulose (CMC) (1 ml; 0.75% in DW) and low-dose group as 50 mg/kg in CMC (0.5 ml; 0.75% in DW). After 10 weeks, the effects of CE on insulin resistance, lipid metabolism, nonalcoholic fatty liver disease (NAFLD), oxidative stress, and genotoxicity were assessed through histological, biochemical, and hematological investigations. Results: Phytochemical analysis including RP-HPLC analysis of the extracts showed that flavonoids and phenolics (myricetin, kaempferol, and apigenin), previously known to be effective against obesity and diabetes, are present in the extracts. Antioxidant studies revealed that the plant possesses a highly significant (p < 0.05) concentration of antioxidants. Satisfactory α-amylase inhibitory activity was also observed in in vitro experiments. In vivo studies showed that CE-administered animals had significantly (p < 0.05) lower weight gain and smaller adipocytes than the control group. Moreover, CE resisted any significant (p < 0.05) change in the organ weights. Analogous to findings from its traditional use, the plant extract had a positive modulatory effect on insulin resistance and hyperglycemia. The study also indicated that CE resisted high-fat diet-induced disturbance in lipid profile and countered any pathological changes in liver enzymes caused by fat-infused diet. Furthermore, a study on endogenous antioxidant levels indicated that CE was effective in maintaining catalase and peroxidase levels within the normal range and resisted the effects of lipid peroxidation of thiobarbituric acid reactive substances. Conclusion: In principle, the current study's findings scientifically validate the implication of T. linearis in metabolic syndrome and recommend further studies on molecular insights of the observed therapeutic activity.

Acute Liver Failure Secondary to Pyogenic Hepatic Abscess.

Hepatic abscesses are rare and can be pyogenic or amebic. Pyogenic hepatic abscesses are treated with antibiotics, percutaneous drainage when larger than 5 cm, and rarely requires surgical treatment. Clinical and laboratory manifestations of pyogenic hepatic abscesses include fever, abdominal pain, and elevations in liver enzymes. There is little documentation that a pyogenic hepatic abscess can cause acute liver failure. We present a case of a patient who developed acute liver failure secondary to a 14 cm pyogenic liver abscess. The patient's hepatic function normalized with percutaneous drain placement and antibiotics.

Different Translocations of Multiple Myeloma on Fluorescent In Situ Hybridization (FISH) with Clinical Correlation.

OBJECTIVE: To evaluate the association of chromosomal translocations in multiple myeloma (MM) detected by Fluorescent In Situ Hybridization (FISH) and its clinical characteristics. STUDY DESIGN: Cross-sectional study. Place and Duration of the Study: Department of Haematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan, from February to August 2022. METHODOLOGY: A total of 40 cases of MM were included. All cases were diagnosed using international myeloma working group (IMWG) criteria. Clinical presentations like bone pain, backache, fatigue, pallor, and weight loss were noted. The workup for myeloma-defining events was done. FISH analysis was done for t (4;14), t (11,14), t (14;16), t (14;20), and del 17p. Data were analysed using the chi-square test. A p-value ≤0.05 was considered statistically significant. RESULTS: Out of 40 patients, 8 (20%) were females and 32 (80%) were males. The highest frequency of cases were noted among males in the age group >60 years and females in the age group 40-60 years. FISH for t (4;14) was positive in 22 (55%) patients, for t (11;14) was positive in 4 (10%) patients, for t (14;16) was positive in 3 (7.5%) patients, and for t (14;20) was positive in 3 (7.5%) patients, while for del17p was positive in 8 (20%) patients. Cases with t (4;14), t (11;14), and t (14;20) had bone pain, fatigue, and backache as the most common presentations. Among the various parameters studied, lytic lesions, beta-2 microglobulin, spike protein, deranged haemoglobin, TLC, ESR, albumin, and creatinine were significant risk factors in patients who were tested positive for various mutations. CONCLUSION: The FISH technique has brought an immense uprising in the genetic analysis of MM. Among translocations, t (4;14) and del17p are associated with poor clinical outcomes and prognosis. If the diagnosis of MM is delayed, then an increase in morbidity and mortality can occur. KEY WORDS: Multiple myeloma, FISH, Translocations.

Withametelin, a steroidal lactone, isolated from datura innoxa attenuates STZ-induced diabetic neuropathic pain in rats through inhibition of NF-kB/MAPK signaling.

Diabetic neuropathic pain is one of the microvascular complications of diabetes mellitus characterized by symmetrical pain and sensory abnormalities. A steroidal lactone isolated from the datura innoxa plant, withametelin (WMT), exhibited significant neuroprotective, anti-inflammatory, antioxidant, and anticancer properties. The current study aimed to investigate anti-neuropathic pain activity and the molecular mechanism of WMT against streptozotocin (STZ)-induced diabetic neuropathy. Rats were given a single injection of STZ (60 mg/kg, intraperitoneally (i.p.)) for induction of diabetes on the first day of the study. After the onset of diabetic neuropathy, pregabalin (10 mg/kg, i.p.) and WMT (0.1 and 1 mg/kg, i.p.) treatments were started from day 14 up to day 42. It was found that STZ-induced neuropathic pain behaviors were markedly reduced by WMT. It inhibited the STZ-associated histopathological changes and genotoxicity in the sciatic nerve and spinal cord. Additionally, Fourier transforms infrared (FTIR) spectroscopy results revealed that STZ-induced alterations in the biochemical components of the sciatic nerve's myelin sheath were inhibited by WMT. In the spinal cord, it markedly reduced the immunoreactivity of mitogen-activated protein kinases (MAPKs) signaling components such as p38-MAPK, c-Jun N-terminal kinase (JNK), extracellular-signal-regulated-kinase (ERK), and activator-protein 1 (AP-1). It also reduced the expression levels of nuclear factor-kappa-B (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). The production of inflammatory cytokines was considerably reduced by WMT. This study provides convincing evidence that WMT treatment attenuated STZ-induced diabetic neuropathic pain by inhibition of MAPK/NF-κB signaling.

Efficacy and Safety of COVID-19 Vaccines-An Update.

A few centuries ago, the first vaccine vial was formulated, and since then, they have resulted in an eminent reduction in infectious diseases associated morbidity and mortality. The discovery of the novel SARS-CoV-2 virus and the COVID-19 disease and its steady progression to a global pandemic with 603,711,760 confirmed cases and 6,484,136 reported deaths according to the World Health Organization (WHO) on 7 September 2022 was exceedingly catastrophic. This brought about an unexpected need for preventative and cost-effective measures to curb the devastating impact of the virus, followed by accelerated competition within the pharma giants to manufacture and dispense vaccines at an exponential rate. Non-pharmaceutical medications such as mandated face mask policies, the imposition of travel limitations and generalized disinfectant use were somewhat successful in mitigating the catastrophic effect, but the onus fell upon vaccination strategies and other medical interventions to counteract and subdue this international health threat. The need to ensure current and future pandemic preparedness, however, presents multiple hurdles, among which are equitable vaccine access and the rising trend of vaccine hesitancy at an individual and international level, which are beyond the scope of this discussion. With this review article, we seek to draw perspective on current COVID-19 virus variants, in-hand vaccine types with their mechanism of action along with their effectiveness and safety profile. We also aim to discuss substantial side effects while adding a segment on the booster dose controversy.

Toxicity evaluation induced by single and 28-days repeated exposure of withametelin and daturaolone in Sprague Dawley rats.

Safe preclinical dose determination is predictive of human toxicity and can have a profound impact on the overall progress of the compound in early drug discovery process. In this respect, current study sought to investigate for the first time the acute and subacute oral toxicity of two pharmacologically active natural compounds i.e., withametelin and daturaolone in Sprague Dawley rats following OECD guideline 420 and 407, respectively. As per acute toxicity studies, withametelin and daturaolone were characterized as Globally Harmonized System (GHS) category 4 and 5 compounds, respectively. Sub-acute daily dose of withametelin was 5, 2.5, and 1.25 mg/kg but, for daturaolone, it was 10, 5, and 2.5 mg/kg. High dose (5 and 2.5 mg/kg) withametelin groups showed dose dependent changes in the general, hematological, biochemical and histopathological parameters in both sexes, the most prominent being hyperthyroidism while no toxicity was observed at lower doses (1.25 and 0.75 mg/kg), No Observable Adverse Effect Level (NOAEL) being 1.25 mg/kg. Daturaolone was comparatively safer and showed dose dependent significant changes in hepatic enzyme (Alanine Transaminase), bilirubin, creatinine, and glucose levels while histological changes in testes were also observed. Lower doses (5, 2.5, and 1.25 mg/kg) of daturaolone showed no significant toxic effects and 5 mg/kg was declared as its NOAEL. Depending upon our findings, starting effective oral dose levels of 1.25 mg/kg/day for withametelin and 5 mg/kg/day for daturaolone are proposed for repeated dose (up to 28 days) preclinical pharmacological evaluation models. Long term studies with more behavioral, biochemical, histopathological and hormonal parameters are proposed to strengthen the findings.

Datura stramonium Leaf Extract Exhibits Anti-inflammatory Activity in CCL4-Induced Hepatic Injury Model by Modulating Oxidative Stress Markers and iNOS/Nrf2 Expression.

Background: Inflammation is a frequent phenomenon in the pathogenesis of hepatic disorders leading to fibrosis and cirrhosis. Phytopharmaceuticals developed from traditional medicine can provide effective therapeutic alternatives to conventional medications. Datura stramonium (DS) has reported traditional uses in inflammatory diseases. In this study, we have tried to validate its potential as a source of anti-inflammatory agents. Methods: Powdered leaf part of DS was extracted using ethyl acetate (EA) to provide the extract (DSL-EA). Lymphocyte and macrophage viability and acute toxicity assays established the safety profile, while nitric oxide (NO) scavenging assay estimated the in vitro anti-inflammatory potential. Noninvasive anti-inflammatory, antidepressant, and antinociceptive activities were monitored using BALB/c mice using low and high doses (150 and 250 mg/kg). Major inflammatory studies were performed on Sprague-Dawley male rats using CCl4-induced liver injury model. Disease induction was initiated by intraperitoneal injections of CCl4 (1 mL/kg of 30% CCl4 in olive oil). The rats were divided into six groups. The anti-inflammatory potential of DSL-EA in low and high doses (150 and 300 mg/kg, respectively) was assessed through hematological, biochemical, liver antioxidant defense, oxidative stress markers, and histological studies as well as the expression of Nrf2 and iNOS. Results: DSL-EA exhibited prominent in vitro NO scavenging (IC50: 7.625 ± 0.51 µg/mL) and in vivo anti-inflammatory activity in paw and anal edema models. In CCl4 model, hematological investigations revealed vasotonic effects. Liver functionality was significantly (P < 0.001 - 0.05) improved in DSL-EA-treated rats. The activity level of endogenous antioxidant enzymes in liver tissues was improved in a manner identical to silymarin. The extract reduced the percent concentration of oxidative stress markers in liver tissues. Furthermore, DSL-EA displayed restorative effects on histological parameters (H and E and Masson's trichrome staining). Immunohistochemistry studies showed marked decline in Nrf2 expression, while overexpression of iNOS was also observed in disease control rats. The damage was distinctly reversed by the extract.

The effect of ivermectin on non-severe and severe COVID-19 disease and gender-based difference of its effectiveness.

The COVID-19 pandemic has led to mortality and morbidity since December 2019. Many possible treatment options have been advised till date. The role of ivermectin in the treatment of COVID-19 disease remains controversial. The aim of our study was to evaluate the effect of ivermectin in hospitalized patients with non-severe and severe COVID-19 disease. We conducted a retrospective cohort study that compared outcomes in 2 groups of COVID-19 patients hospitalized at the largest tertiary care center of Pakistan. The study group was given ivermectin along with standard treatment of covid-19 disease; the comparison group was not. Data on mortality, inflammatory markers such as C-reactive protein (CRP) and ferritin, length of hospital stay and baseline characteristics were collected from Aga Khan University's database from October 2020 till February 2021. Statistical analysis was done to determine the effectiveness of ivermectin in non-severe and severe COVID-19. Comparison of effectiveness of Ivermectin in both the genders was also conducted. The cohort included 188 patients out of which 90 were treated with ivermectin. Mortality and length of hospitalization was not found to be significantly different in the study group compared with the control group (5.6% vs 5.1%; p=0.87 and 5 days vs 4 days; p=0.27). Analysis of secondary outcomes did not yield statistically significant results, apart from ferritin levels which were significantly less in patients treated with ivermectin (547.1 vs 756.7; p=0.03). The ferritin and CRP levels in affected males were higher than in females on admission and discharge. Our findings suggest ivermectin does not significantly affect all-cause mortality, length of hospitalization and CRP levels in hospitalized COVID-19 patients. Large scale randomized controlled trials (RCTs) are required to further evaluate the role of ivermectin in covid-19 disease.