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[This corrects the article DOI: 10.1371/journal.pmed.1003818.].

Abstract Background Pakistan has one of the highest burdens of Hepatitis C virus (HCV) infection globally. To achieve the World Health Organization’s goals for HCV elimination, there is a need for substantial scale-up in testing, treatment, and a reduction in new infections. Data on the population impact of scaling up treatment is not available in Pakistan, nor is there reliable data on the incidence of infection/reinfection. This project will fill this gap by providing important empirical data on the incidence of infection (primary and reinfection) in Pakistan. Then, by using this data in epidemic models, the study will determine whether response rates achieved with affordable therapies (sofosbuvir plus daclatasvir) will be sufficient to eliminate HCV in Pakistan. Methods This prospective multi-centre cohort study will screen 25,000 individuals for HCV antibody (Ab) and RNA (if Ab-positive) at various centers in Pakistan- Karachi (Sindh) and Punjab, providing estimates of the disease prevalence. HCV positive patients will be treated with sofosbuvir and daclatasvir for 12-weeks, (extended to 24-weeks in those with cirrhosis) and the proportion responding to this first-line treatment estimated. Patients who test HCV Ab negative will be recalled 12 months later to test for new HCV infections, providing estimates of the incidence rate. Patients diagnosed with HCV (~ 4,000) will be treated and tested for Sustained Virological Response (SVR). Questionnaires to assess risk factors, productivity, health care usage and quality of life will be completed at both the initial screening and at 12-month follow-up, allowing mathematical modelling and economic analysis to assess the current treatment strategies. Viral resistance will be analysed and patients who have successfully completed treatment will be retested 12 months later to estimate the rate of re-infection. Conclusion The HepFREEPak study will provide evidence on the efficacy of available and widely used treatment options in Pakistan. It will also provide data on the incidence rate of primary infections and re-infections. Data on incidence risk factors will allow us to model and incorporate heterogeneity of risk and how that affects screening and treatment strategies. These data will identify any gaps in current test-and-treat programs to achieve HCV elimination in Pakistan. Study registration This study was registered on clinicaltrials.gov (NCT04943588) on June 29, 2021.

Abstract Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile.

Summary: Chronic infection with hepatitis delta virus (HDV) affects between 12-20 million people worldwide and represents the most severe form of viral hepatitis, leading to accelerated liver disease progression, cirrhosis and its complications, such as end-stage-liver disease and hepatocellular carcinoma. From the discovery of HDV in 1977 by Prof. Mario Rizzetto, knowledge on the HDV life cycle and mechanisms of viral spread has expanded. However, little is still known about the natural history of the disease, host-viral interactions, and the role of the immune system in HDV persistence. Diagnosis of HDV is still challenging due to a lack of standardised assays, while accurate viral load quantification is needed to assess response and endpoints of antiviral treatment. Until recently, interferon has represented the only treatment option in patients with chronic hepatitis delta; however, it is associated with low efficacy and a high burden of side effects. The discovery of the entry inhibitor bulevirtide has represented a breakthrough in HDV treatment, by demonstrating high rates of viral suppression in phase II and III trials, results which have been confirmed in real-world settings and in patients with compensated advanced liver disease. In the meantime, other compounds (i.e. lonafarnib, new anti-hepatitis B virus drugs) are under development to provide alternative or combined strategies for HDV cure. The first international Delta Cure meeting was organised in Milan in October 2022 with the aim of sharing and disseminating the latest data; this review summarises key takeaway messages from state-of-the-art lectures and research data on HDV.

Summary: Prevention of mother-to-child transmission of hepatitis B virus (HBV) infection is a cornerstone of efforts to support progress towards elimination of viral hepatitis. Current guidelines recommend maternal screening, antiviral therapy during the third trimester of high-risk pregnancies, universal and timely HBV birth dose vaccination, and post-exposure prophylaxis with hepatitis B immunoglobulin for selected neonates. However, serological and molecular diagnostic testing, treatment and HBV vaccination are not consistently deployed, particularly in many high endemicity settings, and models predict that global targets for reduction in paediatric incidence will not be met by 2030. In this article, we briefly summarise the evidence for current practice and use this as a basis to discuss areas in which prevention of mother-to-child transmission can potentially be enhanced. By reducing health inequities, enhancing pragmatic use of resources, filling data gaps, developing advocacy and education, and seeking consistent investment from multilateral agencies, significant advances can be made to further reduce vertical transmission events, with wide health, societal and economic benefits.

Cement kiln dust (CKD) is released as an accidental product in large quantities and is classified as solid waste and has negative effects on the environment to benefit from these wastes and achieve an environmental and economic return, this research was carried out to study the effect of cement dust produced from Kufa Cement Factory on the properties of concrete by preparing four concrete mixtures by adding cement dust as a partial substitute for cement in proportions: 5%, 10%, 15%, and 20% and comparing it with the reference mixture and conduct the ripening process for ages 7, 28, and 90 days, a set of tests were carried out: (compressive strength, slump, hardening time, density, absorption, porosity, The results of the tests showed, in general, a decrease in the compressive strength, slump and density of concrete, an increase in the water percentage, the initial hardening time, porosity and absorption with an increasing the percentage of addition of cement dust, but by a small amount to 10%, and the percentage of increase or decrease becomes more clear when the percentage of adding cement dust is increased by more than 10%. , on the level of laboratory application, a hollow block was produced by pressing method with an added percentage of cement dust (5%, 10%, 15%, and 20%) of the weight of the cement, a compression and absorption resistance test was conducted, and the results were in accordance with the approved specification and for all percentages of addition.

Abstract Patients with preexisting chronic liver disease (CLD) may experience a substantial burden from both coronavirus 2019 (COVID‐19) infection and pandemic‐related life disruption. We assessed the impact of the COVID‐19 pandemic on patients with CLD. Patients enrolled in our Global Liver Registry were invited to complete a COVID‐19 survey. As of June 2021, 2500 patients (mean age ± SD, 49 ± 13 years; 53% men) from seven countries completed the survey. Of all survey completers, 9.3% had COVID‐19. Of these patients, 19% were hospitalized, 13% needed oxygen support, but none required mechanical ventilation. Of all patients including those not infected with COVID‐19, 11.3% reported that the pandemic had an impact on their liver disease, with 73% of those reporting delays in follow‐up care. The Life Disruption Event Perception questionnaire confirmed worsening in at least one area (food/nutrition, exercise, social life, vocation/education, financial situation, housing, or health care) in 81% and 69% of patients with and without a history of COVID‐19, respectively (p = 0.0001). On a self‐assessed Likert health score scale (range, 1–10; 10 indicates perfect health), patients with a COVID‐19 history scored lower (mean ± SD, 6.7 ± 2.2 vs. 7.4 ± 2.2, respectively; p

A Sorghum flour (SF) is a leading and prominent food source for humans in African countries. Recently extensive studies have been conducted on Sorghum bread (SB) or sorghum composite bread (SCB), covering various aspects. However, there are many technical challenges in the formation of SF and sorghum composite flour (SCF) that impact the quality of the bread and fail to meet the consumer’s desires and expectations. This review primarily focuses on the characteristics of SF, SCF, SB, and SCB, with discussions encompassing the rheological and morphological properties of the dough, improvement strategies, and bread quality. Moreover, a comprehensive analysis has been conducted to investigate the behavior of SF and SCF along with a discussion of the challenges affecting bread quality and the strategies applied for improvement. The significant demand for nutrients-rich and gluten-free bread indicates that sorghum will become one of the most vital crops worldwide. However, further comprehensive research is highly demanded and necessary for an in-depth understanding of the key features of SF and the resulting bread quality. Such understanding is vital to optimize the utilization of sorghum grain in large-scale bread production.

Abstract Background Globally, just 21% of the estimated 58 million people living with hepatitis C virus (HCV) know their status. Thus, there is considerable need to scale-up HCV testing if the World Health Organization (WHO) 2030 hepatitis elimination goals are to be achieved. HCV self-testing may assist with this; however, there are currently no data on the real-world impact of HCV self-testing. With an estimated 5% of the general population living with HCV, Pakistan has the second highest HCV burden in the world. This study aims to evaluate the acceptability and impact of home delivery of HCV self-testing for secondary distribution in the context of a house-to-house HCV micro-elimination programme in Pakistan. Methods This is a parallel group, non-blinded, cluster randomised trial comparing secondary distribution of HCV self-testing with secondary distribution of information pamphlets encouraging individuals to visit a testing facility for HCV screening. The cluster allocation ratio is 1:1. Clusters will be randomised either to HCV self-testing distributed via study staff or control clusters where information on HCV will be given and the participant will be requested to attend their local hospital for HCV screening. In both clusters, only households with a member who has not yet been screened as part of the larger micro-elimination project will be included. The primary outcome is the number and proportion of participants who report completion of testing. Secondary outcomes include the number and proportion of participants who a) receive a positive result and are made aware of their status, b) are referred to and complete HCV RNA confirmatory testing, and c) start treatment. Acceptability, feasibility, attitudes towards HCV testing, and cost will also be evaluated. The target sample size is 2,000 participants. Discussion This study will provide the first ever evidence regarding secondary distribution of HCV self-testing. By comparing HCV self-testing with facility-based testing, we will assess whether HCV self-testing increases the uptake of HCV testing. The findings will inform micro-elimination programmes and determine whether HCV self-testing can enable individuals to be reached who may otherwise be missed. Trial Registration This study and was registered on clinicaltrials.gov ( NCT04971538 ) 21 July 2021.

Physiologically based pharmacokinetic (PBPK) modeling is of great importance in the field of medicine. This study aims to construct a PBPK model, which can provide reliable drug pharmacokinetic (PK) predictions in both healthy and chronic kidney disease (CKD) subjects. To do so, firstly a review of the literature was thoroughly conducted and the PK information of vildagliptin was collected. PBPK modeling software, PK-Sim®, was then used to build and assess the IV, oral, and drug-specific models. Next, the average fold error, visual predictive checks, and predicted/observed ratios were used for the assessment of the robustness of the model for all the essential PK parameters. This evaluation demonstrated that all PK parameters were within an acceptable limit of error, i.e., 2 fold. Also to display the influence of CKD on the total and unbound AUC (the area under the plasma concentration–time curve) and to make modifications in dose, the analysis results of the model on this aspect were further examined. This PBPK model has successfully depicted the variations of PK of vildagliptin in healthy subjects and patients with CKD, which can be useful for medical practitioners in dosage optimization in renal disease patients. [ABSTRACT FROM AUTHOR]

Cefaclor is a bactericidal antibiotic recommended for treating diverse types of infections. This review aims to comprehensively assess the pharmacokinetic (PK) data on cefaclor in humans. Google Scholar, PubMed, Cochrane Library, and EBSCO databases were systematically performed to identify all the relevant studies containing at least one reported PK parameter of cefaclor. Cefaclor shows the linear PK profile as the area under the plasma concentration-time curve from 0 to t (AUC0-t) and maximum plasma concentration (Cmax) increase in a dose-dependent manner. The AUC0-t of cefaclor in the rice diet was found to be higher than that of bread food, i.e. 19.9 ± 2.6 ug/ml.hr vs 15.4 ± 4 ug/ml.hr. The AUC in paediatrics during the fed state was significantly higher compared to that in adults. Patients with renal impairments showed a Cmax 2.2 times higher than that of normal subjects. A significant increase in Cmax was depicted among individuals following a vegetarian diet in comparison with the non-vegetarian diet. Moreover, cefaclor exhibits time-dependent killing above the minimum inhibitory concentration (MIC < 2 ug), favouring its use in treating infections caused by specific pathogens. This systematic review summarises all the reported PK parameters of cefaclor in healthy and diseased subjects in the literature. This data can help practitioners in adjusting cefaclor doses among different diseases and populations to avoid drug interactions and adverse effects. [ABSTRACT FROM AUTHOR]

Field training is a link between architectural education and professional practice. Is it also true from the point of views of students of the Architecture and Planning Faculty at King Saud University in Riyadh? This is the main question that this study seeks to answer. King Saud University was chosen because of the history of the College of Architecture and Planning as the oldest school at GCC and Arabian Peninsula. The College is also keen to provide summer training programs for students in many government bodies, offices, and local and foreign companies. In order to achieve the objective of the study, a questionnaire was distributed to 85 students who were trained between 2015 and 2016. The first question was about students’ evaluation for the training supervisor and the second question related to students’ evaluation for the training institute and the third question related to students’ evaluation for the content of the training program. The questionnaire aimed to identify the most important problems facing field training and its role in improving the professional practice of the students at the College of Architecture and Planning at KSU. The questionnaire also aimed to investigate the students’ views about the field training program offered to them in terms of training content and Its compatibility with the theoretical study. The results of the questionnaire analysis showed students' overall satisfaction with the field training they received, which was generally intended to relate the practical part to theoretical. The research indicated that training may not achieve the desired goal due to some problems. One of the most important problems affecting the achievement of the objectives of the field training is the lack of a clear plan for training, or the existence of an organized plan but not being committed by the implementing agencies. Failure to adhere to the timetable for training is one of the major problems that hinder the achievement of the objectives of field training. The study recommended that students must complete the training period to achieve the benefit. It recommended that the supervisor of the training should follow up trainees in continuous method and with strong cooperation with the provider of the training. التدريب الميداني حلقة وصل بين التعليم المعماري والممارسة المهنية، إذ أنه يمثل الخبرة العملية الأولى لطالب العمارة في التعايش مع بيئة مهنية واقعية يتلمس من خلالها تطبيق علوم ومعارف تلقاها على مقاعد الدراسة. تهدف هذه الدراسة إلى استطلاع وجهة نظر طلبة كلية العمارة والتخطيط في جامعة الملك سعود بالرياض عن دور برنامج التدريب الميداني الذي تلقوه في تحسين الممارسة المهنية لديهم، وقد وقع الاختيار على جامعة الملك سعود بوصف كلية العمارة والتخطيط بها من أقدم كليات العمارة بمنطقة الخليج العربي وشبه الجزيرة وتوفر لطلابها مقاعد تدريبية في الكثير من الهيئات الحكومية والمكاتب والشركات المحلية والأجنبية. ومن أجل تحقيق هدف الدراسة، تم توزيع استبانة على جميع الطلاب الذين تلقوا تدريبهم ما بين عامي (2015 و2016) وتم استجابة(85) 85 طالبا يمثلون (42.5%) من مجتمع الدراسة وكانت الاستبانة موزعة على ثلاثة محاور؛ المحور الأول يستقصي وجهة نظر الطالب بمشرف التدريب من قبل الكلية والثاني يستقصي وجهة نظر الطالب بالجهة التي يتدرب بها والمحتوى التدريبي الذي تلقاه والثالث يتعلق بالدور الذي يقوم به الطالب لإنهاء متطلبات التدريب. تهدف الاستبانة إلى تحديد أهم المشكلات التي تواجه التدريب الميداني وتحديد دوره في تحسين الممارسة المهنية لدى طلاب كلية العمارة والتخطيط بجامعة الملك سعود، ومعرفة آرائهم حول برنامج التدريب الميداني المقدم لهم من حيث المحتوى التدريبي ومدى توافقه مع الدراسة النظرية. أظهرت نتائج تحليل الاستبانة رضا الطلاب بشكل عام عن التدريب الميداني الذي تلقوه، لكنها أظهرت وجود بعض المشاكل التي تؤثر على تحقيق أهداف التدريب الميداني ومنها عدم وجود خطة واضحة للتدريب، أو وجود خطة منظمة ولكن لا يتم الالتزام بها من قبل الجهات المنفذة. كما أن عدم الالتزام بالجدول الزمنى المخصص للتدريب يعد من المشاكل التي تعوق تحقيق الأهداف المرجوة من التدريب الميداني. أوصت الدراسة بالاهتمام بمرحلة ما قبل التدريب والمراجعة الدورية لمحتوى التدريب الميداني والتنسيق المستمر مع الجهة المدربة مع ربط التدريب بمتطلبات واستراتيجيات رؤية (2030) وضرورة تقديم شرح واضح للطلاب عن برنامج التدريب وماهيته ومساعدتهم على فهم محتوى البرنامج والمتوقع منهم من قبل الجهة المدربة. كما أوصت الدراسة بضرورة متابعة الطلبة المتدربين بصورة مكثفة أثناء فترة التدريب والوقوف على ما قد يعترضهم من اشكاليات ووضع الحلول لها أولا بأول. وأوصت الدراسة – أخيرا- بالاهتمام بمرحلة ما بعد التدريب وذلك بالتقويم المستمر لبرنامج التدريب وحصر الايجابيات وتلافي السلبيات.