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The accurate staging of breast cancer is fundamental for guiding treatment decisions and predicting patient outcomes. However, there can be considerable variation in routine clinical practice based on individual interpretation of guidelines and depending on the healthcare provider initially involved in working up patients newly diagnosed with breast cancer, ranging from primary care providers, triage nurses, surgeons, and/or oncologists. The optimal approach for clinical staging, particularly in asymptomatic patients presenting with intermediate-risk disease, remains a topic of dialogue among clinicians. Given this area of uncertainty, the Research Excellence, Active Leadership (REAL) Canadian Breast Cancer Alliance conducted a modified Delphi process to assess the level of agreement among Canadian expert clinicians on various staging recommendations. In total, 20 items were drafted covering staging based on biological status, the utilization of localization clips, both for the axilla during diagnosis and primary surgical site for margins and radiation therapy planning, and the use of advanced imaging for the investigation of distant metastases. Overall, the consensus threshold among all participants (i.e., ≥75% agreement) was reached in 20/20 items. Differences in clinical practice and recent findings from the literature are provided in the discussion. These consensus recommendations are meant to help standardize breast cancer staging practices in Canada, ensuring accurate diagnosis and optimal treatment planning.

Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is an aggressive subtype of breast cancer associated with a poor prognosis when sub-optimally treated. Recent advances include new and effective targeted therapies that have significantly improved outcomes for patients. Despite these advances, there are significant gaps across Canada, underscoring the need for evidence-based consensus guidance to inform treatment decisions. Addressing these gaps is crucial to ensuring that effective therapies are integrated into clinical practice, so as to improve the lives of patients affected by this aggressive form of breast cancer. The Research Excellence, Active Leadership (REAL) Canadian Breast Cancer Alliance is a standing nucleus committee of clinical-academic oncologists across Canada and Breast Cancer Canada, a patient organization. The mandate of this group is to provide evidence-based guidance on best practices in the management of patients with breast cancer. These consensus recommendations were developed using a modified Delphi process with up to three rounds of anonymous voting. Consensus was defined a priori as ≥75% of voters agreeing with the recommendation as written. There are 9 recommendations in the early setting; 7 recommendations in the metastatic setting; and 10 recommendations for patients with brain metastases.

Sacituzumab Govitecan (SG) is an antibody-drug conjugate (ADC) comprised of an anti-Trop-2 IgG1 molecule conjugated to SN-38, the active metabolite of irinotecan, via a pH-sensitive hydrolysable linker. As a result of recent Canadian funding for SG in advanced hormone receptor (HR)-positive breast cancer and triple-negative breast cancer (TNBC), experience with using SG and managing adverse events (AEs) has grown. This review presents a summary of evidence and adverse event recommendations derived from Canadian experience, with SG use in metastatic TNBC for extrapolation and guidance in all indicated settings. SG is dosed at 10 mg/kg on day 1 and day 8 of a 21-day cycle. Compared to treatment of physicians’ choice (TPC) the phase III ASCENT and TROPiCS-02 studies demonstrated favorable survival data in unresectable locally advanced or metastatic TNBC and HR-positive HER2 negative metastatic breast cancer, respectively. The most common AEs were neutropenia, diarrhea, nausea, fatigue, alopecia, and anemia. This review outlines AE management recommendations for SG based on clinical trial protocols and Canadian guidelines, incorporating treatment delay, dose reductions, and the use of prophylactic and supportive medications.

Managing breast cancer in premenopausal women poses unique challenges due to its considerable effect on both morbidity and mortality. Goserelin, a gonadotropin-releasing hormone agonist, has emerged among the various modalities as a preferred option for ovarian function suppression, owing to its efficacy in reducing ovarian estrogen production in premenopausal women with hormone receptor-positive breast cancer. Recent studies have affirmed the efficacy and safety of long-acting (LA) goserelin 10.8 mg every 12 weeks, offering comparable outcomes to monthly injections. This flexibility enables personalized treatment approaches, potentially enhancing patient satisfaction. Off-label utilization of goserelin LA surged during the coronavirus disease pandemic, prompting initiatives to broaden its use for breast cancer treatment. Switching to goserelin LA can streamline treatment, boost adherence, and optimize resource utilization. With the recent approval of goserelin 10.8 mg LA by Health Canada on 6 May 2024, for use in breast cancer, Canada is the latest to join over 60 countries worldwide to expand the accepted indications for goserelin LA and ensure its availability to potentially enhance healthcare delivery, patient care, and breast cancer outcomes. Goserelin LA offers premenopausal patients a means to more effectively manage the constraints imposed by breast cancer treatment and its impact on survivorship.

This article explores the impact of Tasawuf (Islamic mysticism) practices on entrepreneurial success, focusing specifically on jeans entrepreneurs in Wonopringgo, Pekalongan District. This study adopts a qualitative approach with a Tasawuf Akhlaki framework to understand how spiritual values influence business behaviors. The subjects of the research include three entrepreneurs, with data collected through observation, in-depth interviews, and documentation. Descriptive analysis reveals that the continuity of worship practices, particularly prayer, significantly contributes to developing entrepreneurs who are resilient and have integrity. The findings affirm that entrepreneurs who are consistent in their worship practices tend to experience better business stability and growth. This study confirms that integrating Tasawuf in entrepreneurship not only enriches the personal dimensions of entrepreneurs but also yields a competitive advantage. These conclusions suggest the importance of considering spiritual factors in modern business development strategies. Abstrak: engan fokus khusus pada pengusaha celana jeans di Wonopringgo, Kabupaten Pekalongan. Penelitian ini menggunakan pendekatan kualitatif dengan kerangka tasawuf akhlaki untuk memahami bagaimana nilai-nilai spiritual mempengaruhi perilaku bisnis. Subjek penelitian meliputi tiga pengusaha, dengan data dikumpulkan melalui observasi, wawancara mendalam, dan dokumentasi. Analisis deskriptif menunjukkan bahwa keberlanjutan praktik ibadah, khususnya shalat, secara signifikan berkontribusi pada pembentukan karakter pengusaha yang resilien dan berintegritas. Hasil ini menegaskan bahwa pengusaha yang konsisten dalam praktik ibadahnya cenderung mengalami stabilitas dan pertumbuhan bisnis yang lebih baik. Studi ini mengkonfirmasi bahwa integrasi tasawuf dalam kewirausahaan tidak hanya memperkaya dimensi pribadi pengusaha tetapi juga menghasilkan keuntungan kompetitif. Kesimpulan ini menyarankan pentingnya mempertimbangkan faktor spiritual dalam strategi pengembangan bisnis modern.

Patient access to new oncology drugs in Canada is only possible after navigating multiple sequential systemic checkpoints for national regulatory approval, health technology assessment (HTA) and collective government price negotiation. These steps delay access and prevent health care providers from being able to prescribe optimal therapy. Eighteen Canadian oncology clinicians from the medicine, nursing and pharmacy professions met to develop consensus recommendations for defining reasonable government performance standards around process and timeliness to improve Canadian cancer patients’ access to best care. A modified Delphi methodology was used to identify consensus on 30 questions involving five themes: accountability, disparities, endpoints, timeliness, and cost-effectiveness. It was agreed that greater transparency is required across regulatory and HTA processes. Health professionals in oncology are frustrated for their patients because they are unable to deliver the modern guideline-supported therapies they want to provide due to delays in approval or funding. Canadian health care providers request improvements in timely access to life-saving therapeutics in line with other comparator countries. Clinicians expect urgent improvements in Canadian health systems to give our patients their best chance of survival.

ABSTRACTThe revolution in the organization of work, induced by the COVID-19 pandemic, has had, and will have, some long-lasting consequences on how jobs will be performed, affecting adult life well-being. What we know so far about the determinant of satisfaction for work–life balance may not be valid anymore considering this sudden revolution in work organization. This paper presents an empirical analysis based on a cross-sectional survey of 803 workers in October 2020. Results suggest that the profile that benefits the most from the revolution in work organization is represented by a male, married, public sector worker working remotely and not living in the southern part of Italy.

Islamic Religious and Character Education (hereafter PAI) textbooks are part of an important means of teaching character values, including tolerance. Some cases of intolerance are still common in Indonesia and are even associated with Islamic religious education in schools. Therefore, there is a need to review Islamic religious education in schools. This study examines the PAI materials that include tolerance learning in Islamic religious education textbooks at the 7th, 8th, and 9th grade junior high school levels. This research is important so that in the future, tolerance learning materials can be provided to students in accordance with the portions. This study uses a literature review with a qualitative approach that analyzes the content of Islamic Religious and Character Education textbooks published by the Ministry of Education and Culture of the Independent Curriculum (7th and 8th grade books) and the Revised 2013 Curriculum (9th grade books). The data obtained are then collected and analyzed using the content analysis method. The data analysis techniques in this study used 3 data analysis steps, namely: data reduction, data display, and data verification. This study shows whether there is tolerance learning in Islamic Religious Education and Character Education textbooks or not. The results of the study show that the Islamic Religious Education and Character Education textbooks at the junior high school level strongly promote tolerance.

Indonesia is the country with the most active volcanoes, several of which are renowned for climate-changing eruptions. Here the authors show a rather moderate sulfur emissions budget and reinforce the idea that sulfur-rich eruptions reflect long-term accumulation of volatiles in the reservoirs.

Abstract Bromo is among the very active volcanoes in Indonesia and is known for its recurrent and long-lasting eruptive manifestations. Past volcanic gas studies have revealed Bromo as one of the principal sources of volcanic degassing in Indonesia. This high degassing from Bromo volcano is further characterized in this work, based on more than 10 years of intermittent ground-based gas measurements, combined with daily SO2 mass, captured by the OMI sensor. Over the past decade, Bromo has released 0.7 Tg of SO2 into the atmosphere, representing 3% of the volcanic degassing budget of Indonesia and 0.3% of the global volcanic SO2 emission budget outside eruptive periods. Results also reveal that 18.8 Tg of H2O, 2.0 Tg of CO2, 0.1 Tg of H2S, and 0.005 Tg of H2 were released from the Bromo volcano in one decade. About 81% of these gases are released passively between eruptive events. The chemistry of the eruptive products, sampled between 2001 and 2019, indicate that Bromo volcanic activity is sustained by a basaltic-andesite to basalt trachy-andesite magma source with a transition from medium-K to high-K composition. Such an evolution associated to a C-rich gas likely resulted from a low partial melting and sediment contribution to the genesis of the source magma. New magma injections into the reservoir and fractional crystallization have further amplified the changes of magma composition. Finally, we speculate that the shallow reservoir replenishment, in response to the continuous strong degassing is the driving mechanism behind the Bromo frequent eruptive events.

Pandemi ini membawa perubahan yang signifikan terhadap sektor pendidikan, hal ini membuat tenaga kependidikan harus mengelola dan membuat berbagai rancangan atau program untuk berlangsungnya kegiatan belajar. Tujuan penelitian ini yaitu untuk menganalisis permasalahan mengenai penyesuaian tenaga kependidikan dalam masa pandemi dan tetap memberikan pelayanan yang terbaik. Metode penelitian yang digunakan yaitu studi literatur atau kepustakaan dengan menggunakan sumber bacaan berupa jurnal ilmiah, buku teks, e-book serta bacaan lainnya. Hasil penelitian ini dapat menunjukan bahwa pada masa pandemi ini harus memiliki beberapa keterampilan bagi tenaga kependidikan dalam menghadapi permasalahan baik media, waktu serta sarana dan prasarana pada masa pandemi ini. Dengan adanya penelitian ini terdapat beberapa kesulitan para tenaga kependidikan dalam melakukan perbaikan permasalahan yang ada pada lembaga pendidikan untuk mempersiapkan segala kebutuhan yang diperlukan untuk masa ini dan masa yang akan datang. Situasi ini harus dapat memanajemen diri dalam mengelola pendidikan serta lebih meningkatkan kemampuan diri dalam teknologi dan memberikan motivasi belajar yang baik

Abstract Background Anaemia is a worldwide problem and iron deficiency is the most common cause. In pregnancy, anaemia increases the risk of adverse maternal, foetal and neonatal outcomes. India’s anaemia rate is among the highest in the world with India’s National Family Health Survey indicating over 50% of pregnant women were affected by anaemia. India’s Anaemia Mukt Bharat-Intensified National Iron Plus Initiative aims to reduce the prevalence of anaemia among reproductive-age women, adolescents and children by 3% per year and facilitate the achievement of a Global World Health Assembly 2025 objective to achieve a 50% reduction of anaemia among women of reproductive age. However, preliminary results of the NFHS-5 survey completed in 2020 indicate that anaemia rates are increasing in some states and these targets are unlikely to be achieved. With oral iron being the first-line treatment for iron deficiency anaemia (IDA) in pregnancy, these results are likely to be impacted by the side effects, poor adherence to tablet ingestion and low therapeutic impact of oral iron. These reports suggest a new approach to treating IDA, specifically the importance of single-dose intravenous iron infusions, may be the key to India effectively reaching its targets for anaemia reduction. Methods This 3-arm, randomized controlled trial is powered to report two primary outcomes. The first is to assess whether a single dose of two different intravenous formulations administered early in the second trimester of pregnancy to women with moderate IDA will result in a higher percentage of participants achieving a normal for pregnancy Hb concentration at 30–34 weeks’ gestation or just prior to delivery when compared to participants taking standard doses of oral iron. The second is a clinical outcome of low birth weight (LBW) (< 2500 g), with a hypothesis that the risk of LBW delivery will be lower in the intravenous iron arms when compared to the oral iron arm. Discussion The RAPIDIRON trial will provide evidence to determine if a single-dose intravenous iron infusion is more effective and economically feasible in reducing IDA in pregnancy than the current standard of care. Trial registration Clinical Trials Registry – India CTRI/2020/09/027730. Registered on 10 September 2020, http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=46801&EncHid=&userName=anemia%20in%20pregnancy

Background: Social distancing is important preventive strategy to prevent spreading of SARSCOV-2. The medical faculties are continuing the teaching-learning session using different online platform. Aims and Objective: This online survey aims at exploring the different aspect of online teaching effects among medical students. Materials and Methods: Forty-four validated questions in the Google survey form were distributed among the MBBS students of different medical colleges of West Bengal in this cross-sectional study, and analysed. Results: The responses from 416 participants show that internet-based teaching has been adopted by 96.4% of colleges. Practical class and classes regarding clinical exposure are the two most neglected section of the MBBS curriculum during this pandemic. Total teaching hours per day also drastically reduced from mean of 5.56 h/ day in pre-pandemic time to 1.95 h/ day during this pandemic. Out of 69.7% of the participants who faced difficulty in following online classes, majority (56.25%) was due to technical problems including issues related to internet connectivity and software. Participants were of opinion that current session should be extended on an average of 3 months as the practical and clinical classes are way behind in syllabus completion. According to 72.35% of participants, online classes are less effective than the offline classes. Conclusions: In nutshell, online teaching activities cannot replace the classical classroom teaching, though it is a cost-effective and viable method during this pandemic period.

Background: Hormone receptor-positive and HER2-negative breast cancer (HR + BC) is the most prevalent breast cancer. Endocrine therapy is the mainstay of treatment, however, due to the heterogeneous nature of the disease, resistance to endocrine therapy is not uncommon. Over the past decades, the emergence of novel targeted therapy in combination with endocrine therapy has shown improvement in outcomes of HR + BC. This paper reviews available data of targeted therapy and the results of pivotal clinical trials in the management of HR + BC. Methods: A literature search in PubMed and Google Scholar was performed using keywords related to HR + BC and targeted therapy. Major relevant studies that were presented in international cancer research conferences were also included. Results: Endocrine therapy with tamoxifen and aromatase inhibitors are backbone treatments for women with early-stage HR + BC leading to a significant reduction in mortality. They can also be used for primary prevention in women with a high risk of breast cancer. Preliminary data has shown the efficacy of adjuvant cyclin-dependent kinase (CDK) 4/6 inhibitor, abemaciclib, in high-risk disease in combination with aromatase inhibitors. For most women with advanced HR + BC, endocrine therapy is the primary treatment. Recent evidence has shown that the use of CKD 4/6 inhibitors, mTOR inhibitors, and PI3K inhibitors in combination with endocrine therapy has been associated with better outcomes and delays initiation of chemotherapy. Several novel agents are under study for HR + BC. Discussion: Targeted treatment options for HR + BC have evolved. The future of overcoming resistance to targeted therapy, novel compounds, and predictive markers are key to improving HR + BC outcomes.

Penelitian ini bertujuan untuk menciptakan dan menerapkan nilai pancasila terhadap negara seiring dengan perkembangan teknologi yang berkembang pesat. Metode penelitian ini menggunakan metode kualitatif dengan metode literatur. Informasi penelitian ini yaitu dengan membaca beberapa jurnal dan buku serta mencari tahu mengenai penerapan antara nilai pancasila dengan era disrupsi ini. Hasil penelitian menunjukkan bahwa dalam era disrupsi ini nilai pancasila perlu di implementasikan dengan perkembangan teknologi terhadap anak sekolah dasar di Indonesia tetap mentaati dan menjalankan kehidupan sesuai dengan aturan-aturan yang berlaku serta tidak merubah maknanya. Dalam penerapan nilai pancasila ini mengharapkan anak sekolah dasar tetap mencintai bangsa dan negara, memiliki akhlak yang baik, berbudi pekerti yang luhur dan memiliki sopan santun.

Background: Pregnancy loss is a distressing problem and retention of dead fetus in utero has its own ill effects on physical, psychological, and social aspects, and hence, it is better to recommend medical induction, provided this can be safely undertaken. Aims: The aim of this study is to compare the efficacy, tolerability, induction-delivery interval, and perceived stress scores between induction methods in late intrauterine fetal death (IUFD) with misoprostol alone and mifepristone with misoprostol combination in a rural population of Eastern India. Materials and Methods: This pilot study was conducted on 125 patients after taking institutional ethical clearance and informed consent of the patients in a time span of 1 year. Group 2 patients received 200 mg of mifepristone per orally and observed for 48 h, followed by 50 μg misoprostol administered in the posterior vaginal fornix, and repeated 6th hourly up to a maximum of four doses. Group 1 received 50 μg misoprostol per vaginally 6 hourly for four doses. Induction-delivery interval was calculated. Perceived stress level was calculated on admission and before discharge. Results: Significantly lower induction-delivery interval was observed in Group 2 as compared to Group 1 with P < 0.001. There was no significant difference of Cohen's perceived stress scores on admission, but the difference was significantly lower in Group 2 on discharge with the value of P = 0.03. Group 1 had significantly lower hospital stay in days as compared to Group 2 of patients with P < 0.001. Conclusions: Patients with IUFD administered misoprostol per vaginally only may require shorter hospital stay as compared to patients administered with oral mifepristone followed by misoprostol vaginally but the delivery induction time increases significantly and may increase perceived stress levels which may have short- and long-term negative psychological impact.

Previously, we demonstrated that the zinnia plant was effective for the phytoremediation of oil-contaminated soils and that it had a higher remediation effect during the initial growth period. Therefore, repeated planting of zinnia for the initial growth period might enhance the remediation of contaminated soils, so we performed the following study. Seeds were sown in soils containing 4% (w/w) diesel oil and grown for 100 days. We carried out two treatments: replanted plots where above-ground parts of plants were cut after 50 days, and new seeds were sown; or non-replanted plots where plants were allowed to grow for 100 days. The soil dehydrogenase activity and soil total petroleum hydrocarbon concentrations were analyzed. At the end of the study, no significant differences were found between replanted and non-replanted plots for either measurement. Therefore, replanting did not affect remediation. Degradable oil components in the soils may have been degraded in the initial growth period of the first planting, but by the time of replanting there may have been few degradable oil components left in the soil, so there was no beneficial effect of replanting. We concluded that replanting is unsuitable for phytoremediation of oil-contaminated soils.

Diabetes mellitus (DM) can be treated with various medications. However, individuals in underdeveloped countries may face challenges in using these treatments due to side effects and high costs. Anti-diabetic medications can inhibit enzymes, such as α-amylase, which is responsible for breaking down carbohydrates. In this investigation, 16 phytoconstituents were identified from Pterocarpus santalinus leaf extract through GC-MS analysis, and their significant antioxidant activities were noted. Among these, the pure compound lupeol demonstrated α-amylase inhibition activity of 86.13 ± 1.27 % (IC 50  = 58.50 ± 0.83 μg/mL) in vitro. Additionally, lupeol showed the highest binding affinity in silico using PyRx and CB-Dock, with values of -9.5 and -9.3 kcal/mol, respectively. The in silico analysis also indicated that lupeol possesses acceptable ADMET properties, suggesting its potential as an anti-diabetic drug. A molecular dynamics simulation lasting 500 ns was conducted to evaluate hydrogen bonds, RMSF, RMSD, Rg, and SASA, confirming the stability and integrity of the docking scenarios. In STZ-induced diabetic mice, lupeol significantly reduced blood glucose levels by 70.82 % from day 0 to day 28. Furthermore, lupeol markedly decreased total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), while improving high-density lipoprotein cholesterol (HDL-C) levels in these mice. The antidiabetic effect of lupeol was further validated through histological examinations of the pancreas, heart, kidney, and liver of treated mice, alongside correlation analysis, CAP, and ANOSIM tests. Based on the findings from the in vitro, in silico, and in vivo investigations, this study concludes that lupeol may have potential anti-diabetic effects through the inhibition of the α-amylase enzyme., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

The pancreas is involved in digestion and glucose regulation in the human body. Given the recognized link between chronic pancreatitis and pancreatic cancer, addressing pancreatic disorders and pancreatic cancer is particularly challenging. This review aims to highlight the limitations of traditional methods in diagnosing pancreatic disorders and cancer and explore several next-generation sequencing (NGS) approaches as a promising alternative. There are distinct clinical symptoms that are shared by a number of clinical phenotypes of pancreatic illness induced by particular genetic mutations. Traditional diagnostic methods encompass computed tomography, magnetic resonance imaging, contrast-enhanced Doppler ultrasound, endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, transabdominal ultrasound, laparoscopy, and positron emission tomography have a prognostic ability of only 5% or less and a 5-year survival rate. Genetic sequencing can be employed as an alternative to conventional diagnostic techniques. Sanger sequencing and NGS are currently largely operated genome analysis, with no exception for pancreatic disease diagnosis. The NGS methods can sequence millions to billions of short DNA fragments, enabling enormous sample screening in a short amount of time with low-abundance detection, like in 0.1%-1% mutation prevalence declining approximate cost. Whole-genome sequencing, whole-exome sequencing, RNA sequencing, and single-cell NGS are a few NGS methods utilized to diagnose pancreatic disease. For both research and clinical applications, the NGS techniques can provide a precise diagnosis of pancreatic disorders in a short amount of time at a reasonable expenditure., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

A deadly respiratory disease Middle East Respiratory Syndrome (MERS) is caused by a perilous virus known as MERS-CoV, which has a severe impact on human health. Currently, there is no approved vaccine, prophylaxis, or antiviral therapeutics for preventing MERS-CoV infection. Due to its inexorable and integral role in the maturation and replication of the MERS-CoV virus, the 3C-like protease is unavoidly a viable therapeutic target. In this study, 2369 phytoconstituents were enlisted from Japanese medicinal plants, and these compounds were screened against 3C-like protease to identify feasible inhibitors. The best three compounds were identified as Kihadanin B, Robustaflavone, and 3-beta-O- ( trans -p-Coumaroyl) maslinic acid, with binding energies of -9.8, -9.4, and -9.2 kcal/mol, respectively. The top three potential candidates interacted with several active site residues in the targeted protein, including Cys145, Met168, Glu169, Ala171, and Gln192. The best three compounds were assessed by in silico technique to determine their drug-likeness properties, and they exhibited the least harmful features and the greatest drug-like qualities. Various descriptors, such as solvent-accessible surface area, root-mean-square fluctuation, root-mean-square deviation, hydrogen bond, and radius of gyration, validated the stability and firmness of the protein-ligand complexes throughout the 100ns molecular dynamics simulation. Moreover, the top three compounds exhibited better binding energy along with better stability and firmness than the inhibitor (Nafamostat), which was further confirmed by the binding free energy calculation. Therefore, this computational investigation could aid in the development of efficient therapeutics for life-threatening MERS-CoV infections., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Male infertility is significantly influenced by the plasma-protein sex hormone-binding globulin (SHBG). Male infertility, erectile dysfunction, prostate cancer, and several other male reproductive system diseases are all caused by reduced testosterone bioavailability due to its binding to SHBG. In this study, we have identified 345 phytochemicals from 200 literature reviews that potentially inhibit severe acute respiratory syndrome coronavirus 2. Only a few studies have been done using the SARS-CoV-2 inhibitors to identify the SHBG inhibitor, which is thought to be the main protein responsible for male infertility. In virtual-screening and molecular-docking experiments, cryptomisrine, dorsilurin E, and isoiguesterin were identified as potential SHBG inhibitors with binding affinities of -9.2, -9.0, and -8.8 kcal/mol, respectively. They were also found to have higher binding affinities than the control drug anastrozole (-7.0 kcal/mol). In addition to favorable pharmacological properties, these top three phytochemicals showed no adverse effects in pharmacokinetic evaluations. Several molecular dynamics simulation profiles' root-mean-square deviation, radius of gyration, root-mean-square fluctuation, hydrogen bonds, and solvent-accessible surface area supported the top three protein-ligand complexes' better firmness and stability than the control drug throughout the 100 ns simulation period. These combinatorial drug-design approaches indicate that these three phytochemicals could be developed as potential drugs to treat male infertility.

The current coronavirus disease 2019 (COVID-19) pandemic, caused by the coronavirus 2 (SARS-CoV-2), involves severe acute respiratory syndrome and poses unprecedented challenges to global health. Structure-based drug design techniques have been developed targeting the main protease of the SARS-CoV-2, responsible for viral replication and transcription, to rapidly identify effective inhibitors and therapeutic targets. Herein, we constructed a phytochemical dataset of 1154 compounds using deep literature mining and explored their potential to bind with and inhibit the main protease of SARS-CoV-2. The three most effective phytochemicals Cosmosiine, Pelargonidin-3-O-glucoside, and Cleomiscosin A had binding energies of -8.4, -8.4, and -8.2 kcal/mol, respectively, in the docking analysis. These molecules could bind to Gln189, Glu166, Cys145, His41, and Met165 residues on the active site of the targeted protein, leading to specific inhibition. The pharmacological characteristics and toxicity of these compounds, examined using absorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses, revealed no carcinogenicity or toxicity. Furthermore, the complexes were simulated with molecular dynamics for 100 ns to calculate the root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), and hydrogen profiles from the simulation trajectories. Our analysis validated the rigidity of the docked protein-ligand. Taken together, our computational study findings might help develop potential drugs to combat the main protease of the SARS-CoV-2 and help alleviate the severity of the pandemic., Competing Interests: The authors have declared that no competing interests exist.

The emergence of several novel SARS-CoV-2 variants regarded as variants of concern (VOCs) has exacerbated pathogenic and immunologic prominences, as well as reduced diagnostic sensitivity due to phenotype modification-capable mutations. Furthermore, latent and more virulent strains that have arisen as a result of unique mutations with increased evolutionary potential represent a threat to vaccine effectiveness in terms of incoming and existing variants. As a result, resisting natural immunity, which leads to higher reinfection rates, and avoiding vaccination-induced immunization, which leads to a lack of vaccine effectiveness, has become a crucial problem for public health around the world. This study attempts to review the genomic variation and pandemic impact of emerging variations of concern based on clinical characteristics management and immunization effectiveness. The goal of this study is to gain a better understanding of the link between genome level polymorphism, clinical symptom manifestation, and current vaccination in the instance of VOCs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Biswas, Mahmud, Mita, Afrose, Hasan, Paul, Shimu, Uddin, Zaman, Park, Siyadatpanah, Obaidullah, Saleh, Simal-Gandara and Kim.)

Mitochondria are major contributors to ATP synthesis, generating more than 90% of the total cellular energy production through oxidative phosphorylation (OXPHOS): metabolite oxidation, such as the β-oxidation of fatty acids, and the Krebs's cycle. OXPHOS inadequacy due to large genetic lesions in mitochondrial as well as nuclear genes and homo- or heteroplasmic point mutations in mitochondrially encoded genes is a characteristic of heterogeneous, maternally inherited genetic disorders known as mitochondrial disorders that affect multisystemic tissues and organs with high energy requirements, resulting in various signs and symptoms. Several traditional diagnostic approaches, including magnetic resonance imaging of the brain, cardiac testing, biochemical screening, variable heteroplasmy genetic testing, identifying clinical features, and skeletal muscle biopsies, are associated with increased risks, high costs, a high degree of false-positive or false-negative results, or a lack of precision, which limits their diagnostic abilities for mitochondrial disorders. Variable heteroplasmy levels, mtDNA depletion, and the identification of pathogenic variants can be detected through genetic sequencing, including the gold standard Sanger sequencing. However, sequencing can be time consuming, and Sanger sequencing can result in the missed recognition of larger structural variations such as CNVs or copy-number variations. Although each sequencing method has its own limitations, genetic sequencing can be an alternative to traditional diagnostic methods. The ever-growing roster of possible mutations has led to the development of next-generation sequencing (NGS). The enhancement of NGS methods can offer a precise diagnosis of the mitochondrial disorder within a short period at a reasonable expense for both research and clinical applications.

The phytochemicals of medicinal plants are regarded as a rich source of diverse chemical spaces that have been used as supplements and alternative medicines in the millennium. Even in this era of combinatorial chemical drugs, phytomedicines account for a large share of the statistics of newly approved drugs. In the field of computational aided and rational drug design, there is an urgent need to develop and build a useful phytochemical database management system with a user-friendly interface that allows proper data storage, retrieval and management. We showed 'phytochemdb', a manually managed database that compiles 525 plants and their corresponding 8093 phytochemicals, aiming to incorporate the activities of phytochemicals from medicinal plants. The database collects molecular formula, three-dimensional/two-dimensional structure, canonical SMILES, molecular weight, no. of heavy atoms, no. of aromatic heavy atoms, fraction Csp3, no. of rotatable bonds, no. of H-bond acceptors, no. of H-bond donors, molar refractivity, topological polar surface area, gastrointestinal absorption, Blood-Brain Barrier (BBB) permeant, P-gp substrate, CYP1A2 inhibitor, CYP2C19 inhibitor, CYP2C9 inhibitor, CYP2D6 inhibitor, CYP3A4 inhibitor, Log Kp, Ghose, Veber, Egan, Muegge, bioavailability scores, pan-assay interference compounds, Brenk, Leadlikeness, synthetic accessibility, iLOGP and Lipinski rule of five with the number of violations for each compound. It provides open contribution functions for the researchers who screen phytochemicals in the laboratory and have released their data. 'phytochemdb' is a comprehensive database that gathers most of the information about medicinal plants in one platform, which is considered to be very beneficial to the work of researchers on medicinal plants. 'phytochemdb' is available for free at https://phytochemdb.com/., (© The Author(s) 2022. Published by Oxford University Press.)

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic due to the high transmission and mortality rate of this virus. The world health and economic sectors have been severely affected by this deadly virus, exacerbated by the lack of sufficient efficient vaccines. The design of effective drug candidates and their rapid development is necessary to combat this virus. In this study, we selected 23 antimicrobial peptides from the literature and predicted their structure using PEP-FOLD 3.5. In addition, we docked them to the SARS-CoV-2 spike protein receptor-binding domain (RBD) to study their capability to inhibit the RBD, which plays a significant role in virus binding, fusion and entry into the host cell. We used several docking programs including HDOCK, HPEPDOCK, ClusPro, and HawkDock to calculate the binding energy of the protein-peptide complexes. We identified four peptides with high binding free energy and docking scores. The docking results were further verified by molecular dynamics (MD) simulations to characterize the protein-peptide complexes in terms of their root-mean-square fluctuation (RMSF), root-mean-square deviation (RMSD), radius of gyration (Rg), solvent-accessible surface area (SASA), and hydrogen bond formation. Allergenicity and toxicity predictions suggested that the peptides we identified were non-allergenic and non-toxic. This study suggests that these four antimicrobial peptides could inhibit the RBD of SARS-CoV-2. Future in vitro and in vivo studies are necessary to confirm this., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Biswas, Mahmud, Mita, Afrose, Hasan, Sultana Shimu, Saleh, Mostafa-Hedeab, Alqarni, Obaidullah and Batiha.)

Coronavirus disease 2019 (COVID-19) is a potentially lethal and devastating disease that has quickly become a public health threat worldwide. Due to its high transmission rate, many countries were forced to implement lockdown protocols, wreaking havoc on the global economy and the medical crisis. The main protease (M pro ) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus for COVID-19, represent an effective target for the development of a new drug/vaccine because it is well-conserved and plays a vital role in viral replication. M pro inhibition can stop the replication, transcription as well as recombination of SARS-CoV-2 after the infection and thus can halt the formation of virus particles, making M pro a viable therapeutic target. Here, we constructed a phytochemical dataset based on a rigorous literature review and explored the probability that various phytochemicals will bind with the main protease using a molecular docking approach. The top three hit compounds, medicagol, faradiol, and flavanthrin, had binding scores of -8.3, -8.6, and -8.8 kcal/mol, respectively, in the docking analysis. These three compounds bind to the active groove, consisting of His41, Cys45, Met165, Met49, Gln189, Thr24, and Thr190, resulting in main protease inhibition. Moreover, the multiple descriptors from the molecular dynamics simulation, including the root-mean-square deviation, root-mean-square fluctuation, solvent-accessible surface area, radius of gyration, and hydrogen bond analysis, confirmed the stable nature of the docked complexes. In addition, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis confirmed a lack of toxicity or carcinogenicity for the screened compounds. Our computational analysis may contribute toward the design of an effective drug against the main protease of SARS-CoV-2., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mahmud, Hasan, Biswas, Paul, Afrose, Mita, Sultana Shimu, Promi, Hani, Rahamathulla, Khan, Zaman, Uddin, Rahmatullah, Jahan, Alqahtani, Saleh and Emran.)

Background: The high transmission and pathogenicity of SARS-CoV-2 has led to a pandemic that has halted the world's economy and health. The newly evolved strains and scarcity of vaccines has worsened the situation. The main protease (M pro ) of SARS-CoV-2 can act as a potential target due to its role in viral replication and conservation level., Methods: In this study, we have enlisted more than 1100 phytochemicals from Asian plants based on deep literature mining. The compounds library was screened against the M pro of SARS-CoV-2., Results: The selected three ligands, Flemichin, Delta-Oleanolic acid, and Emodin 1-O-beta-D-glucoside had a binding energy of -8.9, -8.9, -8.7 KJ/mol respectively. The compounds bind to the active groove of the main protease at; Cys145, Glu166, His41, Met49, Pro168, Met165, Gln189. The multiple descriptors from the simulation study; root mean square deviation, root mean square fluctuation, radius of gyration, hydrogen bond, solvent accessible surface area confirms the stable nature of the protein-ligand complexes. Furthermore, post-md analysis confirms the rigidness in the docked poses over the simulation trajectories., Conclusions: Our combinatorial drug design approaches may help researchers to identify suitable drug candidates against SARS-CoV-2.

The recent coronavirus outbreak has changed the world's economy and health sectors due to the high mortality and transmission rates. Because the development of new effective vaccines or treatments against the virus can take time, an urgent need exists for the rapid development and design of new drug candidates to combat this pathogen. Here, we obtained antiviral peptides obtained from the data repository of antimicrobial peptides (DRAMP) and screened their predicted tertiary structures for the ability to inhibit the main protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using multiple combinatorial docking programs, including PatchDock, FireDock, and ClusPro. The four best peptides, DRAMP00877, DRAMP02333, DRAMP02669, and DRAMP03804, had binding energies of -1125.3, -1084.5, -1005.2, and -924.2 Kcal/mol, respectively, as determined using ClusPro, and binding energies of -55.37, -50.96, -49.25, -54.81 Kcal/mol, respectively, as determined using FireDock, which were better binding energy values than observed for other peptide molecules. These peptides were found to bind with the active cavity of the SARS-CoV-2 main protease; at Glu166, Cys145, Asn142, Phe140, and Met165, in addition to the substrate-binding sites, Domain 2 and Domain 3, whereas fewer interactions were observed with Domain 1. The docking studies were further confirmed by a molecular dynamics simulation study, in which several descriptors, including the root-mean-square difference (RMSD), root-mean-square fluctuation (RMSF), solvent-accessible surface area (SASA), radius of gyration (Rg), and hydrogen bond formation, confirmed the stable nature of the peptide-main protease complexes. Toxicity and allergenicity studies confirmed the non-allergenic nature of the peptides. This present study suggests that these identified antiviral peptide molecules might inhibit the main protease of SARS-CoV-2, although further wet-lab experiments remain necessary to verify these findings., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Currently, a worldwide pandemic has been declared in response to the spread of coronavirus disease 2019 (COVID-19), a fatal and fast-spreading viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The low availability of efficient vaccines and treatment options has resulted in a high mortality rate, bringing the world economy to its knees. Thus, mechanistic investigations of drugs capable of counteracting this disease are in high demand. The main protease (M pro ) expressed by SARS-CoV-2 has been targeted for the development of potential drug candidates due to the crucial role played by M pro in viral replication and transcription. We generated a phytochemical library containing 1672 phytochemicals derived from 56 plants, which have been reported as having antiviral, antibacterial, and antifungal activity. A molecular docking program was used to screen the top three candidate compounds: epicatechin-3-O-gallate, psi-taraxasterol, and catechin gallate, which had respective binding affinities of -8.4, -8.5, and -8.8 kcal/mol. Several active sites in the targeted protein, including Cys145, His41, Met49, Glu66, and Met165, were found to interact with the top three candidate compounds. The multiple simulation profile, root-mean-square deviation, root-mean-square fluctuation, radius of gyration, and solvent-accessible surface area values supported the inflexible nature of the docked protein-compound complexes. The toxicity and carcinogenicity profiles were assessed, which showed that epicatechin-3-O-gallate, psi-taraxasterol, and catechin gallate had favorable pharmacological properties with no adverse effects. These findings suggest that these compounds could be developed as part of an effective drug development pathway to treat COVID-19.

The recently emerged coronavirus (SARS-CoV-2) has created a crisis in world health, and economic sectors as an effective treatment or vaccine candidates are still developing. Besides, negative results in clinical trials and effective cheap solution against this deadly virus have brought new challenges. The viral protein, the main protease from SARS-CoV-2, can be effectively targeted due to its viral replication and pathogenesis role. In this study, we have enlisted 88 peptides from the AVPdb database. The peptide molecules were modeled to carry out the docking interactions. The four peptides molecules, P14, P39, P41, and P74, had more binding energy than the rest of the peptides in multiple docking programs. Interestingly, the active points of the main protease from SARS-CoV-2, Cys145, Leu141, Ser139, Phe140, Leu167, and Gln189, showed nonbonded interaction with the peptide molecules. The molecular dynamics simulation study was carried out for 200 ns to find out the docked complex's stability where their stability index was proved to be positive compared to the apo and control complex. Our computational works based on peptide molecules may aid the future development of therapeutic options against SARS-CoV-2., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mahmud, Paul, Biswas, Afrose, Mita, Hasan, Shimu, Hossain, Promi, Ema, Chidambaram, Chandrasekaran, Alqahtani, Emran and Saleh.)