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Abstract Background Little is known about HIV in South Sudan and even less about HIV among female sex workers (FSW). We characterized progress towards UNAIDS 90–90-90 targets among female sex workers (FSW) and sexually exploited female adolescents in Juba and Nimule, South Sudan. Methods We conducted a biobehavioral survey of FSW and sexually exploited female adolescents using respondent-driven sampling (RDS) in Juba (November 2015–March 2016) and in Nimule (January–March 2017) to estimate achievements toward the UNAIDS 90–90-90 targets (90% of HIV-positive individuals know their status; of these, 90% are receiving antiretroviral therapy [ART]; and of these, 90% are virally suppressed). Eligibility criteria were girls and women who were aged ≥15 years; spoke English, Juba Arabic, or Kiswahili; received money, goods, or services in exchange for sex in the past 6 months; and resided, worked, or socialized in the survey city for ≥1 month. Data were weighted for RDS methods. Results We sampled 838 FSW and sexually exploited female adolescents in Juba (HIV-positive, 333) and 409 in Nimule (HIV-positive, 108). Among HIV-positive FSW and sexually exploited female adolescents living in Juba, 74.8% self-reported being aware of their HIV status; of these, 73.3% self-reported being on ART; and of these, 62.2% were virally suppressed. In Nimule, 79.5% of FSW and sexually exploited female adolescents living with HIV self-reported being aware of their HIV status; of these, 62.9% self-reported being on ART; and of these, 75.7% were virally suppressed. Conclusions Although awareness of HIV status is the lowest of the 90–90-90 indicators in many countries, treatment uptake and viral suppression were lowest among FSW and sexually exploited female adolescents in South Sudan. Differentiated service delivery facilitate linkage to and retention on treatment in support of attainment of viral suppression.

There is no regulation in emerging markets, i.e. Indonesia imposing the gender diversity quota. Therefore, based on the different characteristics and attributes between developed and emerging markets, this study aims to analyze the impact of the boardroom’s gender diversity on the quality of accruals, i.e. earnings in big Indonesian firms. This study used a sample of 100 big manufacturing firms in Indonesia. Moreover, this paper utilized a widely used proxy for the quality of earnings and the boardroom’s gender diversity. Data panel with fixed effect method was used to compute the quality of accruals while path analysis was utilized for hypotheses testing. Furthermore, the results showed evidence that the boardroom’s gender diversity indirectly influenced the quality of accruals through cash flow variability. However, the presence of female directors is not a significant inducement for managers to report better quality of earnings. The managerial implication of this study is that the boardroom’s gender diversity is good for the emerging markets since it supports better accounting accruals indirectly. Future studies should incorporate many industries and consider the potential of endogeneity, which has not been tackled in this paper.

This study assesses the environmental impact of integrated water supply and sanitation management with a focus on wastewater and rainwater treatment. The study uses an integrated methodology including comparative data analysis, evaluation of water treatment technologies and environmental modeling. The results show that the integration of different treatment technologies such as physico-chemical and biological processes significantly improves water quality, making it suitable for reuse or safe discharge into ecosystems. The study emphasizes the effectiveness of these technologies in reducing environmental pollution, especially in urban areas. In addition, the analysis demonstrates the cost-effectiveness of integrated water management approaches that reduce water consumption and treatment costs, while emphasizing the importance of complying with water quality and environmental regulations. The study also identifies the need for further technological and infrastructural innovations to improve the efficiency of water supply and sanitation systems in response to climate change and urbanization. These findings contribute to the development of sustainable water management strategies that minimize environmental impacts and promote long-term sustainability in urban and rural settings. [ABSTRACT FROM AUTHOR]

In this work, the implications of AAV9 capsid design and column reuse on AAV9 vector product quality were assessed with POROS CaptureSelect (PCS) AAVX and AAV9 resins using sf9 insect cell‐derived model AAV9 vectors with varying viral protein (VP) ratios. Chromatographic experiments with purified drug substance AAV9 model feeds indicated consistent vector elution profiles, independent of adeno‐associated virus (AAV) VP ratio, or cycle number. In contrast, the presence of process impurities in the clarified lysate feeds resulted in clear changes in the elution patterns. This included increased aggregate content in the vector eluates over multiple cycles as well as clear differences in the performance of these affinity resin systems. The AAV9‐serotype specific PCS AAV9 column, with lower vector elution pH, resulted in higher aggregate content over multiple cycles as compared to the serotype‐independent PCS AAVX column. Further, the results with vectors of varying VP ratio indicated that while one vector type eluate displayed higher aggregation in both affinity columns over column reuse, the eluate with the other vector type did not exhibit changes in the aggregation profile. Interestingly, vector aggregates in the affinity eluates also contained double‐stranded DNA impurities and histone proteins, with similar trends to the aggregate levels. This behavior upon column reuse indicates that these host cell impurities are likely carried over to subsequent runs due to incomplete clean‐in‐place (CIP). These results indicate that feed impurities, affinity resin characteristics, elution pH, column CIP, and vector stability can impact the reusability of AAV affinity columns and product quality. [ABSTRACT FROM AUTHOR]

As of August 2021, coronavirus disease (COVID-19) had caused >199 million cases and >4.2 million deaths worldwide (1). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, [...]

As the coronavirus pandemic continues, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequence data are required to inform vaccine efforts. We provide SARS-CoV-2 sequence data from South Sudan and document the dominance of SARS-CoV-2 lineage B.1.525 (Eta variant) during the country's second wave of infection.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) first emerged in December 2019 and spread quickly causing the coronavirus disease 2019 (COVID‐19) pandemic. Recent single cell RNA‐Seq analyses have shown the presence of SARS‐CoV‐2 entry factors in the human corneal, limbal, and conjunctival superficial epithelium, leading to suggestions that the human ocular surface may serve as an additional entry gateway and infection hub for SARS‐CoV‐2. In this article, we review the ocular clinical presentations of COVID‐19 and the features of the ocular surface that may underline the overall low ocular SARS‐CoV‐2 infection. We critically evaluate the studies performed in nonhuman primates, ex vivo organ culture ocular models, stem cell derived eye organoids and the differences in infection efficiency observed in different parts of human ocular surface epithelium. Finally, we highlight the additional work that needs to be carried out to understand the immune response of the ocular surface to SARS‐CoV‐2 infection, which can be translated into prophylactic treatments that may be applied to other organ systems.

BackgroundPatients with breast cancer are assumed to be susceptible to anxiety and depression, while there is a lack of evidence about the epidemiology and underlying factors in Ethiopia. Hence, we aimed to assess the prevalence and predictors of anxiety and depression among patients with breast cancer in Ethiopia.MethodAn institutional-based cross-sectional study was conducted among patients with breast cancer who were attending treatment at the Oncology Center of the Tikur Anbessa Specialized Hospital, the largest referral teaching hospital in Ethiopia. The Hospital Anxiety and Depression Scale (HDAS) was used to evaluate the anxiety and depression status of the participants, and a structured questionnaire was used to collect sociodemographic, socioeconomic, and clinical data from the participants. Medical records of the participants were reviewed to collect and correlate information about the grade and stage of cancer. An analysis was done using STATA 15.1.ResultsThe study included 333 randomly selected participants, of which 35.4% were on stage III and 33% on stage II, and 67.9% were on chemotherapy and surgery. The prevalence of anxiety and depression were 60.7 and 58.6%, respectively. Poor patient-provider interaction (adjusted odds ratio [AOR] = 4.5, 95% CI: 2.49, 8.12) and having no financial support (AOR = 2.83, 95% CI: 1.63, 4.91) were the significant predictors of anxiety. Age >49 years (AOR = 0.48, 95% CI: 0.25, 0.90), poor patient-provider interactions (AOR = 3.36, 95% CI: 1.87, 6.02), and having no financial support (AOR = 3.36, 95% CI: 1.95, 5.79) were the significant predictors of depression.ConclusionIn this study, the prevalence of anxiety and depression was high among patients with breast cancer, and the lack of financial support and poor patient-provider interactions were significant predictors of anxiety and depression among these groups of patients. Patients with cancer need regular screening for mental health and better emotional support from their healthcare providers and families to prevent and treat anxiety and depression.

Globally, >100 million cases and >2.6 million deaths had been attributed to coronavirus disease (COVID-19) as of March 14, 2021 (2). Most cases have been reported in Europe and the [...]

Relatively few coronavirus disease cases and deaths have been reported from sub-Saharan Africa, although the extent of its spread remains unclear. During August 10–September 11, 2020, we recruited 2,214 participants for a representative household-based cross-sectional serosurvey in Juba, South Sudan. We found 22.3% of participants had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain IgG titers above prepandemic levels. After accounting for waning antibody levels, age, and sex, we estimated that 38.3% (95% credible interval 31.8%–46.5%) of the population had been infected with SARS-CoV-2. At this rate, for each PCR–confirmed SARS-CoV-2 infection reported by the Ministry of Health, 103 (95% credible interval 86–126) infections would have been unreported, meaning SARS-CoV-2 has likely spread extensively within Juba. We also found differences in background reactivity in Juba compared with Boston, Massachusetts, USA, where the immunoassay was validated. Our findings underscore the need to validate serologic tests in sub-Saharan Africa populations.

Abstract A single dose of bevacizumab reduced the density of angiopoietin-2-positive vessels while improving the infiltration of CD4+ T and CD8+ T cells, and mature dendritic cells in patients with primary triple-negative breast cancer. Our findings provide a rationale for including bevacizumab during neoadjuvant treatment to enhance the efficacy of immune checkpoint blockers in this disease.

Solomon Tsegaye,1 Mohammed Mehdi,2 Wajana L Labisso,3 Daniel Seifu Melka2 1Department of Biochemistry, College of Health Sciences, Assela University, Addis Ababa, Ethiopia; 2Department of Biochemistry, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; 3Department of Pathology, College of Health Sciences, Addis Ababa University, Addis Ababa, EthiopiaCorrespondence: Mohammed MehdiDepartment of Biochemistry, College of Health Sciences, Addis Ababa University, P.o.box: 9086, Addis Ababa, EthiopiaTel +251910066838Email mohammed.mehdi@aau.edu.etBackground: Cellular proteases are thought to increase the likelihood of cancer cell infiltration and metastasis by degrading constituents of the extracellular matrix (ECM). Measuring activities of these proteases may be used as tumor markers for early diagnosis, prognosis, and as a possible target for treatment plan.Objective: The aim of the current study is to evaluate cysteine cathepsins (CTSK and CTSL) and matrix metalloproteases-2 (MMP-2) and 9 (MMP-9) activities in human breast tumor tissue.Methods: A comparative cross-sectional study plan was devised to study the enzymatic activities ofCTSK and CTSL andMMP-2 and MMP-9 via zymographic detection method. Sites of tissue sample collection were St Paul’s Millennium Medical College, Menelik II Hospital and Zewditu Memorial Hospital, Addis Ababa, Ethiopia. A total of 36 breast cancer patients were recruited and tissue samples were collected for the study.Results: Activities of CTSK and CTSL were significantly elevated in cancerous tissue than the adjacent normal non-cancerous breast tissue of the same patients (n = 36, p ≤ 0.05). Also, activities ofMMP-2 and MMP-9 were increased significantly in tumor tissues than normal tissues (n = 36, P ≤ 0.05).Conclusion: It is found that there are different patterns of protease enzymatic activity expression between normal and tumor tissue using zymography. Compared with normal tissue samples, the protease enzymatic activity in cancerous tissue is higher. Thus, tissue proteases can be used in conjunction with histological techniques to identify patients in the same clinical group.Keywords: breast cancer, cathepsin K; CTSK, cathepsin L; CTSL, matrix metalloprotinease-9; MMP-9, matrix metalloprotinease-2; MMP-2

Abstract Background The world’s second largest Ebola outbreak occurred in the Democratic Republic of Congo from 2018 to 2020. At the time, risk of cross-border spread into South Sudan was very high. Thus, the South Sudan Ministry of Health scaled up Ebola preparedness activities in August 2018, including implementation of a 24-h, toll-free Ebola virus disease (EVD) hotline. The primary purpose was the hotline was to receive EVD alerts and the secondary goal was to provide evidence-based EVD messages to the public. Methods To assess whether the hotline augmented Ebola preparedness activities in a protracted humanitarian emergency context, we reviewed 22 weeks of call logs from January to June 2019. Counts and percentages were calculated for all available data. Results The hotline received 2114 calls during the analysis period, and an additional 1835 missed calls were documented. Callers used the hotline throughout 24-h of the day and were most often men and individuals living in Jubek state, where the national capital is located. The leading reasons for calling were to learn more about EVD (68%) or to report clinical signs or symptoms (16%). Common EVD-related questions included EVD signs and symptoms, transmission, and prevention. Only one call was documented as an EVD alert, and there was no documentation of reported symptoms or whether the person met the EVD case definition. Conclusions Basic surveillance information was not collected from callers. To trigger effective outbreak investigation from hotline calls, the hotline should capture who is reporting and from where, symptoms and travel history, and whether this information should be further investigated. Electronic data capture will enhance data quality and availability of information for review. Additionally, the magnitude of missed calls presents a major challenge. When calls are answered, there is potential to provide health communication, so risk communication needs should be considered. However, prior to hotline implementation, governments should critically assess whether their hotline would yield actionable data and if other data sources for surveillance or community concerns are available.

Background: Malaria remains a public health concern and the leading cause of mortality in children aged under five years in South Sudan. Understanding the burden of malaria in children may assist in developing a strategy for mitigating and eliminating malaria. This would contribute to attaining the Sustainable Development Goals. We planned to determine the prevalence and outcome of malaria among hospitalized children in Al Sabah Children Hospital, South Sudan. Methods: We carried out a retrospective analysis of hospitalized children in Al Sabah Children Hospital between January to June 2020. The data for this study were analysed using Stata version 11 to calculate the prevalence and outcome of malaria among these children during the study period. Results: A total 781 children were recruited, of whom 777 contributed to the analysis (the others were excluded because of missing data). Overall prevalence of malaria was 78% among hospitalized children. Severe malaria alone affected 28%, while 50% had severe malaria in combination with other diseases. The highest death rate was amongst children from Munuki Block (11%, p= 0.001). Severe malaria alone and in combination was the diagnosis for 58% of the children who died. Severe malaria alone contributed to 14% of deaths. Conclusion: Malaria remains the number one cause of mortality in hospitalized children in this paediatric hospital. It predominantly affects young children, who are also at the highest risk of dying. Measures envisaged to protect children during their first five years of life are likely to have the greatest impact.

Every five minutes, somebody dies from a snakebite. According to the World Health Organization (WHO), an estimated 5.4 million people get bitten worldwide every year and around 81,000 to 138,000 people die each year because of snake bites.[1] In Africa alone, 435,000 to 580,000 victims[2] suffer snakebite envenoming and South Sudan could be one of the countries with the highest incidence. However, snakebite still receives less attention globally than other Neglected Tropical Diseases (NTDs) and comprehensive programmes and efforts to provide care to snakebite patients are limited.

Abstract Introduction Mutations in pre‐mRNA processing factor 31 (PRPF31), a core protein of the spliceosomal tri‐snRNP complex, cause autosomal‐dominant retinitis pigmentosa (adRP). It has remained an enigma why mutations in ubiquitously expressed tri‐snRNP proteins result in retina‐specific disorders, and so far, the underlying mechanism of splicing factors‐related RP is poorly understood. Methods We used the induced pluripotent stem cell (iPSC) technology to generate retinal organoids and RPE models from four patients with severe and very severe PRPF31‐adRP, unaffected individuals and a CRISPR/Cas9 isogenic control. Results To fully assess the impacts of PRPF31 mutations, quantitative proteomics analyses of retinal organoids and RPE cells were carried out showing RNA splicing, autophagy and lysosome, unfolded protein response (UPR) and visual cycle‐related pathways to be significantly affected. Strikingly, the patient‐derived RPE and retinal cells were characterised by the presence of large amounts of cytoplasmic aggregates containing the mutant PRPF31 and misfolded, ubiquitin‐conjugated proteins including key visual cycle and other RP‐linked tri‐snRNP proteins, which accumulated progressively with time. The mutant PRPF31 variant was not incorporated into splicing complexes, but reduction of PRPF31 wild‐type levels led to tri‐snRNP assembly defects in Cajal bodies of PRPF31 patient retinal cells, altered morphology of nuclear speckles and reduced formation of active spliceosomes giving rise to global splicing dysregulation. Moreover, the impaired waste disposal mechanisms further exacerbated aggregate formation, and targeting these by activating the autophagy pathway using Rapamycin reduced cytoplasmic aggregates, leading to improved cell survival. Conclusions Our data demonstrate that it is the progressive aggregate accumulation that overburdens the waste disposal machinery rather than direct PRPF31‐initiated mis‐splicing, and thus relieving the RPE cells from insoluble cytoplasmic aggregates presents a novel therapeutic strategy that can be combined with gene therapy studies to fully restore RPE and retinal cell function in PRPF31‐adRP patients.

Abstract Destruction of the limbus and depletion of limbal stem cells (LSCs), the adult progenitors of the corneal epithelium, leads to limbal stem cell deficiency (LSCD). LSCD is a rare, progressive ocular surface disorder which results in conjunctivalisation and neovascularisation of the corneal surface. Many strategies have been used in the treatment of LSCD, the common goal of which is to regenerate a self-renewing, transparent, and uniform epithelium on the corneal surface. The development of these techniques has frequently resulted from collaboration between stem cell translational scientists and ophthalmologists. Direct transplantation of autologous or allogeneic limbal tissue from a healthy donor eye is regarded by many as the technique of choice. Expansion of harvested LSCs in vitro allows smaller biopsies to be taken from the donor eye and is considered safer and more acceptable to patients. This technique may be utilised in unilateral cases (autologous) or bilateral cases (living related donor). Recently developed, simple limbal epithelial transplant (SLET) can be performed with equally small biopsies but does not require in vitro cell culture facilities. In the case of bilateral LSCD, where autologous limbal tissue is not available, autologous oral mucosa epithelium can be expanded in vitro and transplanted to the diseased eye. Data on long-term outcomes (over 5 years of follow-up) for many of these procedures is needed, and it remains unclear how they produce a self-renewing epithelium without recreating the vital stem cell niche. Bioengineering techniques offer the ability to re-create the physical characteristics of the stem cell niche, while induced pluripotent stem cells offer an unlimited supply of autologous LSCs. In vivo confocal microscopy and anterior segment OCT will complement impression cytology in the diagnosis, staging, and follow-up of LSCD. In this review we analyse recent advances in the pathology, diagnosis, and treatment of LSCD.

Abstract Background Following the West Africa Ebola virus disease (EVD) outbreak (2013–2016), WHO developed a preparedness checklist for its member states. This checklist is currently being applied for the first time on a large and systematic scale to prepare for the cross border importation of the ongoing EVD outbreak in the Democratic Republic of Congo hence the need to document the lessons learnt from this experience. This is more pertinent considering the complex humanitarian context and weak health system under which some of the countries such as the Republic of South Sudan are implementing their EVD preparedness interventions. Main text We identified four main lessons from the ongoing EVD preparedness efforts in the Republic South Sudan. First, EVD preparedness is possible in complex humanitarian settings such as the Republic of South Sudan by using a longer-term health system strengthening approach. Second, the Republic of South Sudan is at risk of both domestic and cross border transmission of EVD and several other infectious disease outbreaks hence the need for an integrated and sustainable approach to outbreak preparedness in the country. Third, a phased and well-prioritized approach is required for EVD preparedness in complex humanitarian settings given the costs associated with preparedness and the difficulties in the accurate prediction of outbreaks in such settings. Fourth, EVD preparedness in complex humanitarian settings is a massive undertaking that requires effective and decentralized coordination. Conclusion Despite a very challenging context, the Republic of South Sudan made significant progress in its EVD preparedness drive demonstrating that it is possible to rapidly scale up preparedness efforts in complex humanitarian contexts if appropriate and context-specific approaches are used. Further research, systematic reviews and evaluation of the ongoing preparedness efforts are required to ensure comprehensive documentation and application of the lessons learnt for future EVD outbreak preparedness and response efforts.

Abstract Calcium pyrophosphate dehydrate deposition (CPDD) disease very rarely affects the temporomandibular joint (TMJ). It may resemble synovial chondromatosis, chondrosarcoma, chondroblastoma, or a parotid tumor. Clinical examination, CT, and MRI are important in making the correct diagnosis. Surgical removal of CPDD is necessary with or without excision of the TMJ.

A Phase I/II trial previously revealed variable anti-tumor efficacy of the PARP inhibitor niraparib in combination with the PD-1 inhibitor pembrolizumab in platinum-resistant ovarian cancer patients. Here, the authors perform an integrated genomic and immunomics analysis of tumor samples from the same patients and find potential predictive biomarkers of response to such combination therapy.

Abstract Coffee is one of the most commonly consumed beverages in the worldwide and is assumed to have protective effects against metabolic syndrome. The present study was aimed at investigating the effect of coffee on body weight, serum glucose, uric acid and lipid profile levels in male albino Wistar rats feeding on high fructose diet. A post-test experimental study was conducted on a total of 30 (9–10 weeks old) male albino Wistar rats. The rats were divided into 6 groups: group I (normal control)-fed on standard chow and plain tap water only; group II (fructose control)-fed on standard chow and 20% of fructose solution; group III–VI (treatment groups)-fed on standard chow, 20% of fructose solution and treated with 71, 142, 213 and 284 mg/kg body weight/day of coffee respectively for six weeks. At the end, body weight, serum glucose, uric acid and lipid profile levels were investigated. Data was entered and cleared by epi-data software version 3.1 and analyzed by one way ANOVA followed by Tukey post hoc multiple comparison tests using SPSS V. 23.00. Statistical significance was considered at p