bluuebunny/crossref_metadata_2025 huggingface dataset:
A randomized controlled trial to evaluate the acceptability and effectiveness of two eating disorders prevention interventions: the HEIDI BP-HW project
Authors: Carrard Isabelle , Cekic Sezen , Bucher Della Torre Sophie
Published: August 2023

Background

Eating disorders (ED) are common in Switzerland, as in other Western countries, with a prevalence of any ED of 3.5%. However, no specific prevention intervention has been evaluated in the French-speaking part of the country. In this study, we assessed the acceptability and effectiveness of two well-validated eating disorders prevention interventions: the Body Project intervention (BP), based on cognitive dissonance techniques, and the Healthy Weight intervention (HW), based on the implementation of a healthy lifestyle.

Methods

Forty female students, aged 18–28, with body dissatisfaction, were randomized into three arms: a BP group, an HW group, and a waiting-list control group (WLCG). The primary outcome measure was body dissatisfaction. Secondary outcomes were thin-ideal internalization, dietary restraint, negative affect, and ED psychopathology. Thirty-three participants completed the assessments before and after the one-month interventions or waiting period. A follow-up measurement was conducted one month after the interventions to assess the stability of the results.

Results

Both interventions, delivered via a virtual web platform, were considered acceptable. The reduction in body dissatisfaction was greater in the BP group (r = 0.7; p < 0.01) or the HW group (r = 0.6; p < 0.01) than in the WLCG, with large effect sizes. Dietary restraint and shape concern were also significantly reduced in the BP group (r = 0.6 and r = 0.7, respectively; p < 0.01) and HW group (r = 0.5 and r = 0.5, respectively; p < 0.05) compared to the WLCG, with moderate to large effect sizes. The results obtained in each intervention group were stable at the one-month follow-up.

Conclusions

This study showed encouraging results in young women with body dissatisfaction, arguing in favor of the French adaptations of the BP and HW interventions. However, the feasibility of recruitment was difficult, partly due to the pandemic situation at the time of the study, and should be further considered to improve dissemination.

Trial registration

ClinicalTrials.gov Identifier: NCT04558073, 22/09/2020 and Swiss National Clinical Trial Portal (SNCTP000003978).
The SENTINEL study of differentiated service delivery models for HIV treatment in Malawi, South Africa, and Zambia: research protocol for a prospective cohort study
Authors: Pascoe Sophie , Huber Amy , Mokhele Idah , Lekodeba Nkgomeleng , Ntjikelane Vinolia , Sande Linda , Tchereni Timothy , Haimbe Prudence ,   AMBIT SENTINEL study team, Phiri Bevis , Hasweeka Pamfred , Gunda Andrews , Hendrickson Cheryl , Scott Nancy , Kaiser Jeanette , Ncgobo Nkosinathi , Mutanda Nyasha , Mokgethi Oratile , Birhanu Frehiwot , Phiri Wyness , Kamanga Aniset , Makwalu Taurai , Shakewelele Hilda , Lumano-Mulenga Priscilla , Nyandera Rose , Mukumbwa-Mwenechanya Mpande , Rosen Sydney
Published: August 2023

Background

Many countries in sub-Saharan Africa are rapidly scaling up “differentiated service delivery” (DSD) models for HIV treatment to improve the quality of care, increase access, reduce costs, and support the continued expansion and sustainability of antiretroviral therapy (ART) programs. Although there is some published evidence about the health outcomes of patients in DSD models, little is known about their impacts on healthcare providers’ job satisfaction, patients’ quality of life, costs to providers or patients, or how DSD models affect resource allocation at the facility level.

Methods

SENTINEL is a multi-year observational study that will collect detailed data about DSD models for ART delivery and related services from 12 healthcare facilities in Malawi, 24 in South Africa, and 12 in Zambia. The first round of SENTINEL included a patient survey, provider survey, provider time-and-motion observations, and facility resource use inventory. A survey of clients testing for HIV and a supplement to the facility resource use component to describe service delivery integration will be added for the second round. The patient survey will ask up to 10 patients enrolled in each DSD model at each study site about their experiences in HIV care and in DSD models, costs incurred seeking treatment, and preferences for HIV service delivery. The provider survey will ask up to 10 providers per site about the impact of DSD models on their positions and clinics. The time-and-motion component will directly observe the time use of a sample of providers implementing DSD models. Finally, the resource utilization component will collect facility-level data about DSD model availability and enrollment and the human and other resources needed to implement them. SENTINEL is planned to include four or more approximately annual rounds of data collection between 2021 and 2026.

Discussion

As national DSD programs for HIV treatment mature, it is important to understand how individual healthcare facilities are interpreting and implementing national guidelines and how healthcare workers and clients are adapting to new models of service delivery. SENTINEL will help policy makers and program managers understand the benefits and costs of differentiated service delivery and improve resource allocation going forward.
An unexplored equity factor: differential beliefs and attitudes toward contingency management by providers’ ethnicity
Authors: Oluwoye Oladunni , Weeks Douglas L. , McDonell Michael G.
Published: August 2023

Background

Although considered one of the most effective interventions for substance use disorders (SUD), the widespread implementation of contingency management (CM) has remained limited. In more recent years there has been surge in the implementation of CM to address increasing rates of substance use. Prior studies at the provider-level have explored beliefs about CM among SUD treatment providers and have tailored implementation strategies based on identified barriers and training needs, to promote implementation of CM. However, there have been no implementation strategies that have actively sought to identify or address potential differences in the beliefs about CM that could be influenced by the cultural background (e.g., ethnicity) of treatment providers. To address this knowledge gap, we examined beliefs about CM among a sample of inpatient and outpatient SUD treatment providers.

Methods

A cross-sectional survey of SUD treatment providers was completed by 143 respondents. The survey asked respondents about their attitudes toward CM using the Contingency Management Beliefs Questionnaire (CMBQ). Linear mixed models examined the effect of ethnicity (non-Hispanic White and Hispanic) on CMBQ subscale (general barriers, training-related barriers, CM positive-statements) scores.

Results

Fifty-nine percent of respondents to the CMBQ self-identified as non-Hispanic White and 41% as Hispanic. Findings revealed that treatment providers who identified as Hispanic had significantly higher scores on the general barriers (p < .001) and training-related barriers (p = .020) subscales compared to the non-Hispanic White treatment providers. Post-hoc analyses identified differences in the endorsement of specific individual scale items on the general barriers (e.g., CM interventions create extra work for me) and training-related (e.g., I want more training before implementing CM) subscales.

Conclusions

Dissemination and implementation strategies for CM need to consider equity-related factors at the provider-level that may be associated with the adoption and uptake of CM.
Why do consumers choose private over public health services? Reflective accounts of health providers in Vietnam
Authors: Nguyen Mai P. , Tariq Amina , Hinchcliff Reece , Dunne Michael P.
Published: August 2023

Background

In Vietnam and many developing countries, private healthcare is increasingly being leveraged by governments to complement public services and increase health service access and utilisation. Extensive understanding of patterns of utilisation of private over public health services, and the rationale for such consumer decisions, is important to ensure and promote safe, affordable and patient-centred care in the two sectors. Few studies within the Southeast Asian Region have explored how private and public providers interact (via social networks, marketing, and direct contact) with consumers to affect their service choices. This study investigates providers’ views on social factors associated with the use of private over public health services in Vietnam.

Method

A thematic analysis was undertaken of 30 semi-structured interviews with experienced health system stakeholders from the Vietnam national assembly, government ministries, private health associations, health economic association, as well as public and private hospitals and clinics.

Results

Multiple social factors were found to influence the choice of private over public services, including word-of-mouth, the patient-doctor relationship and relationships between healthcare providers, healthcare staff attitudes and behaviour, and marketing. While private providers maximise their use of these social factors, most public providers seem to ignore or show only limited interest in using marketing and other forms of social interaction to improve services to meet patients’ needs, especially those needs beyond strictly medical intervention. However, private providers faced their own particular challenges related to over-advertisement, over-servicing, excessive focus on patients’ demands rather than medical needs, as well as the significant technical requirements for quality and safety.

Conclusions

This study has important implications for policy and practice in Vietnam. First, public providers must embrace social interaction with consumers as an effective strategy to improve their service quality. Second, appropriate regulations of private providers are required to protect patients from unnecessary treatments, costs and potential harm. Finally, the insights from this study have direct relevance to many developing countries facing a similar challenge of appropriately managing the growth of the private health sector.
Factors related to the internal social capital of elderly-caring social organizations: a cross-sectional study in Chongqing, China
Authors: Xu Fuqin , Ding Shuo , Liu Guoqing , Wang Zhengsheng , Otsen Benjamin , Ji Kai , Zheng Xin , Chen Ren
Published: August 2023

Background

Aging has given birth to the demand for high-quality elderly care service and social organizations (ESOs) are gradually taking on a supportive role in the field of elderly care services.. In view of this, our study is designed to examine influencing factors of social capital within the elderly-caring social organizations.

Method

The study was conducted in four districts of Chongqing Province and a multi-stage random sampling method was used to sample 80 ESOs as subjects for the research. Through a meticulously crafted questionnaire, we gathered valuable data on internal social capital, basic information about the organization, and other variables. Univariate and Binary Logistic Regression analysis were performed on the data to explore the factors associated with social capital within the elderly-caring social organizations using IBM SPSS version 26.0.

Result

The results showed that 67(83.8%) OF ESOs surveyed were A-type institutions and 13(16.3%) B-type institutions. Among them, 49(61.3%) institutions covered an area of more than 50m2.The institutions of ≤ 2 years were 33(41.3%), 21(26.3%) were established for ≤ 3 ≤ 8 years, and residual 26(32.5%) were institutions ˃ 8 years old. ESOs that possessed 4–6 management employees were 52.422 times more likely to score high for social support (p<0.05, OR = 52.422). Accommodating special care objects and hiring 16–30 employees were significantly linked to the shared language and shared vision dimension (p<0.001, OR = 0.8) and (p<0.05, OR = 8.672), respectively. and the overall social capital dimension (p<0.01, OR = 0.221) (p<0.05, OR = 5.730).

Conclusion

ESOs with different basic conditions have different amounts of social capital. Factors such as the presence of special care and volunteer staff, a certain number of full-time staff as well as types of services rendered are accompanied with the higher internal social capital of ESOs.
Successes and challenges towards improving quality of primary health care services: a scoping review
Authors: Endalamaw Aklilu , Khatri Resham B , Erku Daniel , Nigatu Frehiwot , Zewdie Anteneh , Wolka Eskinder , Assefa Yibeltal
Published: August 2023

Background

Quality health services build communities’ and patients’ trust in health care. It enhances the acceptability of services and increases health service coverage. Quality primary health care is imperative for universal health coverage through expanding health institutions and increasing skilled health professionals to deliver services near to people. Evidence on the quality of health system inputs, interactions between health personnel and clients, and outcomes of health care interventions is necessary. This review summarised indicators, successes, and challenges of the quality of primary health care services.

Methods

We used the preferred reporting items for systematic reviews and meta-analysis extensions for scoping reviews to guide the article selection process. A systematic search of literature from PubMed, Web of Science, Excerpta Medica dataBASE (EMBASE), Scopus, and Google Scholar was conducted on August 23, 2022, but the preliminary search was begun on July 5, 2022. The Donabedian’s quality of care framework, consisting of structure, process and outcomes, was used to operationalise and synthesise the findings on the quality of primary health care.

Results

Human resources for health, law and policy, infrastructure and facilities, and resources were the common structure indicators. Diagnosis (health assessment and/or laboratory tests) and management (health information, education, and treatment) procedures were the process indicators. Clinical outcomes (cure, mortality, treatment completion), behaviour change, and satisfaction were the common indicators of outcome. Lower cause-specific mortality and a lower rate of hospitalisation in high-income countries were successes, while high mortality due to tuberculosis and the geographical disparity in quality care were challenges in developing countries. There also exist challenges in developed countries (e.g., poor quality mental health care due to a high admission rate). Shortage of health workers was a challenge both in developed and developing countries.

Conclusions

Quality of care indicators varied according to the health care problems, which resulted in a disparity in the successes and challenges across countries around the world. Initiatives to improve the quality of primary health care services should ensure the availability of adequate health care providers, equipped health care facilities, appropriate financing mechanisms, enhance compliance with health policy and laws, as well as community and client participation. Additionally, each country should be proactive in monitoring and evaluation of performance indicators in each dimension (structure, process, and outcome) of quality of primary health care services.
Learning tools used to translate resilience in healthcare into practice: a rapid scoping review
Authors: Haraldseid-Driftland Cecilie , Dombestein Heidi , Le Anh Hai , Billett Stephen , Wiig Siri
Published: August 2023

Background

Historically, efforts to improved healthcare provisions have focussed on learning from and understanding what went wrong during adverse events. More recently, however, there has been a growing interest in seeking to improve healthcare quality through promoting and strengthening resilience in healthcare, in light of the range of changes and challenges to which healthcare providers are subjected. So far, several approaches for strengthening resilience performance have been suggested, such as reflection and simulation. However, there is a lack of studies that appraise the range of existing learning tools, the purposes for which they are designed, and the types of learning activities they comprise. The aim of this rapid scoping review is to identify the characteristics of currently available learning tools designed to translate organizational resilience into healthcare practice.

Methods

A rapid scoping review approach was used to identify, collect, and synthesise information describing the characteristics of currently available learning tools designed to translate organizational resilience into healthcare practice. EMBASE and Medline Ovid were searched in May 2022 for articles published between 2012 and 2022.

Results

The review identified six different learning tools such as serious games and checklists to guide reflection, targeting different stakeholders, in various healthcare settings. The tools, typically, promoted self-reflection either individually or collaboratively in groups. Evaluations of these tools found them to be useful and supportive of resilience; however, what constitutes resilience was often difficult to discern, particularly the organizational aspect. It became evident from these studies that careful planning and support were needed for their successful implementation.

Conclusions

The tools that are available for review are based on guidelines, checklists, or serious games, all of which offer to prompt either self-reflection or group reflections related to different forms of adaptations that are being performed. In this paper, we propose that more guided reflections mirroring the complexity of resilience in healthcare, along with an interprofessional collaborative and guided approach, are needed for these tools to be enacted effectively to realise change in practice. Future studies also need to explore how tools are perceived, used, and understood in multi-site, multi-level studies with a range of different participants.
Insight into de-regulation of amino acid feedback inhibition: a focus on structure analysis method
Authors: Naz Sadia , Liu Pi , Farooq Umar , Ma Hongwu
Published: August 2023

Regulation of amino acid’s biosynthetic pathway is of significant importance to maintain homeostasis and cell functions. Amino acids regulate their biosynthetic pathway by end-product feedback inhibition of enzymes catalyzing committed steps of a pathway. Discovery of new feedback resistant enzyme variants to enhance industrial production of amino acids is a key objective in industrial biotechnology. Deregulation of feedback inhibition has been achieved for various enzymes using in vitro and in silico mutagenesis techniques. As enzyme’s function, its substrate binding capacity, catalysis activity, regulation and stability are dependent on its structural characteristics, here, we provide detailed structural analysis of all feedback sensitive enzyme targets in amino acid biosynthetic pathways. Current review summarizes information regarding structural characteristics of various enzyme targets and effect of mutations on their structures and functions especially in terms of deregulation of feedback inhibition. Furthermore, applicability of various experimental as well as computational mutagenesis techniques to accomplish feedback resistance has also been discussed in detail to have an insight into various aspects of research work reported in this particular field of study.
Women’s empowerment and uptake of sulfadoxine–pyrimethamine for intermittent preventive treatment of malaria during pregnancy: results from a cross-sectional baseline survey in the Lake endemic region, Kenya
Authors: Odwe George , Matanda Dennis Juma , Zulu Tchaiwe , Kizito Stephen , Okoth Oscar , Kangwana Beth
Published: August 2023

Background

Malaria in pregnancy remains a major public health problem in endemic areas of the sub-Saharan African (SSA) region. However, there is limited understanding of the association between women’s empowerment and the uptake of sulfadoxine–pyrimethamine for intermittent preventive treatment of malaria during pregnancy (IPTp-SP) in Kenya. This study examines the association between women’s empowerment indicators (decision-making power, control of assets, education, and employment status) and the uptake of three or more doses of IPTp-SP in the Lake endemic region of Kenya.

Methods

The analysis utilized a dataset from a cross-sectional baseline survey of 3129 women aged 15–49 years in Kisumu and Migori Counties who had a live birth within the last 2 years preceding the study. Data were collected between June to August 2021. A descriptive analysis was conducted to show the distribution of respondents by key background characteristics, and bivariate and multivariate logistic regression to examine statistically significant associations between women’s empowerment measures and the uptake of 3+ doses of IPTp-SP.

Results

Among the 3129 women surveyed, 1978 (65.7%) received 3+ doses of IPTp-SP during their most recent pregnancy. Controlling for individual characteristics and the number of ANC visits, the odds of taking 3+ doses of IPTp-SP increased among women who had high decision-making autonomy (AOR = 2.33; CI = 1.81–3.01; P < 0.001); and tertiary level of educational attainment (AOR = 1.51; CI = 1.10–2.06). However, the association between control of assets and uptake of IPTp-SP was positive but not statistically significant.

Conclusion

Women’s decision-making autonomy and educational attainment were positively associated with the uptake of IPTp-SP. As a result, maternal health interventions should focus on less empowered women, specifically those with less decision-making autonomy and no/low formal education, as they are less likely to achieve optimal uptake of IPTp-SP during pregnancy.
Exploring the diverse biomedical applications of programmable and multifunctional DNA nanomaterials
Authors: Fang Liuru , Shi Chen , Wang Yuhua , Xiong Zuzhao , Wang Yumei
Published: August 2023

DNA nanoparticles hold great promise for a range of biological applications, including the development of cutting-edge treatments and diagnostic tests. Their subnanometer-level addressability enables precise, specific modifications with a variety of chemical and biological entities, making them ideal as diagnostic instruments and carriers for targeted delivery. This paper focuses on the potential of DNA nanomaterials, which offer scalability, programmability, and functionality. For example, they can be engineered to provide highly specific biosensing and bioimaging capabilities and show promise as a platform for disease diagnosis and treatment. Successful operation of various biomedical nanomaterials has been demonstrated both in vitro and in vivo. However, there are still significant challenges to overcome, including the need to improve the scalability and reliability of the technology, and to ensure safety in clinical applications. We discuss these challenges and opportunities in detail and highlight the progress and prospects of DNA nanotechnology for biomedical applications.
Liposomal delivery of gene therapy for ovarian cancer: a systematic review
Authors: Son Jin Sung , Chow Ryan , Kim Helena , Lieu Toney , Xiao Maria , Kim Sunny , Matuszewska Kathy , Pereira Madison , Nguyen David Le , Petrik Jim
Published: August 2023

Objective

To systematically identify and narratively synthesize the evidence surrounding liposomal delivery of gene therapy and the outcome for ovarian cancer.

Methods

An electronic database search of the Embase, MEDLINE and Web of Science from inception until July 7, 2023, was conducted to identify primary studies that investigated the effect of liposomal delivery of gene therapy on ovarian cancer outcomes. Retrieved studies were assessed against the eligibility criteria for inclusion.

Results

The search yielded 564 studies, of which 75 met the inclusion criteria. Four major types of liposomes were identified: cationic, neutral, polymer-coated, and ligand-targeted liposomes. The liposome with the most evidence involved cationic liposomes which are characterized by their positively charged phospholipids (n = 37, 49.3%). Similarly, those with neutrally charged phospholipids, such as 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine, were highly researched as well (n = 25, 33.3%). Eight areas of gene therapy research were identified, evaluating either target proteins/transcripts or molecular pathways: microRNAs, ephrin type-A receptor 2 (EphA2), interleukins, mitogen-activated protein kinase (MAPK), human-telomerase reverse transcriptase/E1A (hTERT/EA1), suicide gene, p53, and multidrug resistance mutation 1 (MDR1).

Conclusion

Liposomal delivery of gene therapy for ovarian cancer shows promise in many in vivo studies. Emerging polymer-coated and ligand-targeted liposomes have been gaining interest as they have been shown to have more stability and specificity. We found that gene therapy involving microRNAs was the most frequently studied. Overall, liposomal genetic therapy has been shown to reduce tumor size and weight and improve survivability. More research involving the delivery and targets of gene therapy for ovarian cancer may be a promising avenue to improve patient outcomes.
Acetylglutamine facilitates motor recovery and alleviates neuropathic pain after brachial plexus root avulsion in rats
Authors: Wu Lin , Chen Shuangxi , He Bing , Zhou Guijuan , Xu Yan , Zhu Guanghua , Xie Juan , Deng Limin , Wen Xuanwei , Li Sijing , Xiao Zijian
Published: August 2023

Background

Brachial plexus root avulsion (BPRA), a disabling peripheral nerve injury, induces substantial motoneuron death, motor axon degeneration and denervation of biceps muscles, leading to the loss of upper limb motor function. Acetylglutamine (N-acetyl-L-glutamine, NAG) has been proven to exert neuroprotective and anti-inflammatory effects on various disorders of the nervous system. Thus, the present study mainly focused on the influence of NAG on motor and sensory recovery after BPRA in rats and the underlying mechanisms.

Methods

Male adult Sprague Dawley (SD) rats were subjected to BPRA and reimplantation surgery and subsequently treated with NAG or saline. Behavioral tests were conducted to evaluate motor function recovery and the mechanical pain threshold of the affected forelimb. The morphological appearance of the spinal cord, musculocutaneous nerve, and biceps brachii was assessed by histological staining. Quantitative real-time PCR (qRT‒PCR) was used to measure the mRNA levels of remyelination and regeneration indicators in myocutaneous nerves. The protein levels of inflammatory and pyroptotic indicators in the spinal cord anterior horn were measured using Western blotting.

Results

NAG significantly accelerated the recovery of motor function in the injured forelimbs, enhanced motoneuronal survival in the anterior horn of the spinal cord, inhibited the expression of proinflammatory cytokines and pyroptosis pathway factors, facilitated axonal remyelination in the myocutaneous nerve and alleviated atrophy of the biceps brachii. Additionally, NAG attenuated neuropathic pain following BPRA.

Conclusion

NAG promotes functional motor recovery and alleviates neuropathic pain by enhancing motoneuronal survival and axonal remyelination and inhibiting the pyroptosis pathway after BPRA in rats, laying the foundation for the use of NAG as a novel treatment for BPRA.
Partial gene suppression improves identification of cancer vulnerabilities when CRISPR-Cas9 knockout is pan-lethal
Authors: Krill-Burger J. Michael , Dempster Joshua M. , Borah Ashir A. , Paolella Brenton R. , Root David E. , Golub Todd R. , Boehm Jesse S. , Hahn William C. , McFarland James M. , Vazquez Francisca , Tsherniak Aviad
Published: August 2023

Background

Hundreds of functional genomic screens have been performed across a diverse set of cancer contexts, as part of efforts such as the Cancer Dependency Map, to identify gene dependencies—genes whose loss of function reduces cell viability or fitness. Recently, large-scale screening efforts have shifted from RNAi to CRISPR-Cas9, due to superior efficacy and specificity. However, many effective oncology drugs only partially inhibit their protein targets, leading us to question whether partial suppression of genes using RNAi could reveal cancer vulnerabilities that are missed by complete knockout using CRISPR-Cas9. Here, we compare CRISPR-Cas9 and RNAi dependency profiles of genes across approximately 400 matched cancer cell lines.

Results

We find that CRISPR screens accurately identify more gene dependencies per cell line, but the majority of each cell line’s dependencies are part of a set of 1867 genes that are shared dependencies across the entire collection (pan-lethals). While RNAi knockdown of about 30% of these genes is also pan-lethal, approximately 50% have selective dependency patterns across cell lines, suggesting they could still be cancer vulnerabilities. The accuracy of the unique RNAi selectivity is supported by associations to multi-omics profiles, drug sensitivity, and other expected co-dependencies.

Conclusions

Incorporating RNAi data for genes that are pan-lethal knockouts facilitates the discovery of a wider range of gene targets than could be detected using the CRISPR dataset alone. This can aid in the interpretation of contrasting results obtained from CRISPR and RNAi screens and reinforce the importance of partial gene suppression methods in building a cancer dependency map.
Long-read sequencing identifies a common transposition haplotype predisposing for CLCNKB deletions
Authors: Tschernoster Nikolai , Erger Florian , Kohl Stefan , Reusch Björn , Wenzel Andrea , Walsh Stephen , Thiele Holger , Becker Christian , Franitza Marek , Bartram Malte P. , Kömhoff Martin , Schumacher Lena , Kukat Christian , Borodina Tatiana , Quedenau Claudia , Nürnberg Peter , Rinschen Markus M , Driller Jan H. , Pedersen Bjørn P. , Schlingmann Karl P. , Hüttel Bruno , Bockenhauer Detlef , Beck Bodo , Altmüller Janine
Published: August 2023

Background

Long-read sequencing is increasingly used to uncover structural variants in the human genome, both functionally neutral and deleterious. Structural variants occur more frequently in regions with a high homology or repetitive segments, and one rearrangement may predispose to additional events. Bartter syndrome type 3 (BS 3) is a monogenic tubulopathy caused by deleterious variants in the chloride channel gene CLCNKB, a high proportion of these being large gene deletions. Multiplex ligation-dependent probe amplification, the current diagnostic gold standard for this type of mutation, will indicate a simple homozygous gene deletion in biallelic deletion carriers. However, since the phenotypic spectrum of BS 3 is broad even among biallelic deletion carriers, we undertook a more detailed analysis of precise breakpoint regions and genomic structure.

Methods

Structural variants in 32 BS 3 patients from 29 families and one BS4b patient with CLCNKB deletions were investigated using long-read and synthetic long-read sequencing, as well as targeted long-read sequencing approaches.

Results

We report a ~3 kb duplication of 3′-UTR CLCNKB material transposed to the corresponding locus of the neighbouring CLCNKA gene, also found on ~50 % of alleles in healthy control individuals. This previously unknown common haplotype is significantly enriched in our cohort of patients with CLCNKB deletions (45 of 51 alleles with haplotype information, 2.2 kb and 3.0 kb transposition taken together, p=9.16×10−9). Breakpoint coordinates for the CLCNKB deletion were identifiable in 28 patients, with three being compound heterozygous. In total, eight different alleles were found, one of them a complex rearrangement with three breakpoint regions. Two patients had different CLCNKA/CLCNKB hybrid genes encoding a predicted CLCNKA/CLCNKB hybrid protein with likely residual function.

Conclusions

The presence of multiple different deletion alleles in our cohort suggests that large CLCNKB gene deletions originated from many independently recurring genomic events clustered in a few hot spots. The uncovered associated sequence transposition haplotype apparently predisposes to these additional events.

The spectrum of CLCNKB deletion alleles is broader than expected and likely still incomplete, but represents an obvious candidate for future genotype/phenotype association studies.

We suggest a sensitive and cost-efficient approach, consisting of indirect sequence capture and long-read sequencing, to analyse disease-relevant structural variant hotspots in general.
Cellular characterisation of advanced osteoarthritis knee synovium
Authors: Mimpen Jolet Y. , Hedley Robert , Ridley Anna , Baldwin Mathew J. , Windell Dylan , Bhalla Ananya , Ramos-Mucci Lorenzo , Buckley Christopher D. , Coles Mark C. , Alvand Abtin , Price Andrew J. , Carr Andrew J. , Dakin Stephanie G. , Snelling Sarah J. B.
Published: August 2023

Objectives

Osteoarthritis (OA) is increasingly recognised as a whole joint disease, with an important role for synovium. However, the repertoire of immune cells and fibroblasts that constitute OA synovium remains understudied. This study aims to characterise the cellular composition of advanced OA synovium and to explore potential correlations between different cell types and patient demographics or clinical scores.

Methods

Synovium, collected from 10 patients with advanced OA during total knee replacement surgery, was collagenase-digested, and cells were stained for flow cytometry analysis. Formalin-fixed paraffin-embedded synovium was sectioned, stained with immunofluorescence, and imaged using the multiplex Cell DIVE platform. Patient demographics and clinical scores were also collected.

Results

The proportion of immune cells in OA synovium varied between patients (8–38% of all cells). Macrophages and T cells were the dominant immune cell populations, together representing 76% of immune cells. Age positively correlated with the proportion of macrophages, and negatively correlated with T cells. CCR6+ T cells were found in 6/10 patients; these patients had a higher mean Kellgren-Lawrence grade across the three knee compartments. Immunofluorescence staining showed that macrophages were present in the lining as well as distributed throughout the sublining, while T and B cells were mainly localised near vessels in the sublining. Fibroblast subsets (CD45−PDPN+) based on the expression of CD34/CD90 or FAP/CD90 were identified in all patient samples, and some populations correlate with the percentage of immune cells or clinical scores. Immunofluorescence staining showed that FAP expression was particularly strong in the lining layer, but also present throughout the sublining layer. CD90 expression was exclusively found around vessels in the sublining, while CD34 was mostly found in the sublining but also occasionally in the lining layer.

Conclusions

There are significant differences in the relative proportions and subsets of immune cells in OA synovium; exploratory correlative analyses suggest that these differences might be correlated with age, clinical scores, or fibroblast subsets. Additional studies are required to understand how different cell types affect OA pathobiology, and if the presence or proportion of cell subsets relates to disease phenotypes.
Isolation and characterization of multidrug resistant Gallibacterium anatis biovar haemolytica strains from Polish geese and hens
Authors: Karwańska Magdalena , Wieliczko Alina , Bojesen Anders Miki , Villumsen Kasper Rømer , Krzyżewska-Dudek Eva , Woźniak-Biel Anna
Published: August 2023

Gallibacterium anatis biovar haemolytica is a bacterium that is frequently associated with infections of the reproductive tract and respiratory system in poultry. To assess the current prevalence and resistance profile of these bacteria in Poland, we collected and investigated 63 strains of Gallibacterium from diseased domestic poultry flocks including geese, laying hens, breeding hens and an ornamental hen. Detailed characterization of the isolates included the analysis of phenotypic antimicrobial resistance profiles and biofilm formation ability. Furthermore, the genetic background of 40 selected isolates regarding the presence of virulence and antimicrobial resistance genes and mobile genetic elements was determined. All investigated isolates were multidrug resistant, most prominently to β-lactams, fluoroquinolones, sulfonamides and macrolides. A total of 48 different resistance profiles were detected. Of all isolates, 50.8% formed a strong biofilm, where strains isolated from geese appeared to be better at biofilm formation than strains isolated from laying and breeding hens. Single-nucleotide polymorphism genotyping revealed that G. anatis bv. haemolytica strains are restricted in host and geographical distribution, and the geese isolates showed greater phylogenetic similarity. Whole genome sequencing enabled identification of 25 different antimicrobial resistance determinants. The most common resistance genes were tetB, blaROB-1, and blaTEM-1 which may be located on mobile genetic elements. All isolates possessed the toxin gene gtxA, and the fimbrial gene flfA was identified in 95% of strains. Our results indicated that all G. anatis bv. haemolytica isolates showed multidrug resistant phenotypes. Strains isolated from geese were characterized by the highest percentage of isolates resistant to selected antimicrobials, probably reflecting host-related adaptations.
ClpP protease modulates bacterial growth, stress response, and bacterial virulence in Brucella abortus
Authors: Sun Dongjie , Liu Yufu , Peng Xiaowei , Dong Hao , Jiang Hui , Fan Xuezheng , Feng Yu , Sun Jiali , Han Kun , Gao Qiang , Niu Jianrui , Ding Jiabo
Published: August 2023

The process of intracellular proteolysis through ATP-dependent proteases is a biologically conserved phenomenon. The stress responses and bacterial virulence of various pathogenic bacteria are associated with the ATP-dependent Clp protease. In this study, a Brucella abortus 2308 strain, ΔclpP, was constructed to characterize the function of ClpP peptidase. The growth of the ΔclpP mutant strain was significantly impaired in the TSB medium. The results showed that the ΔclpP mutant was sensitive to acidic pH stress, oxidative stress, high temperature, detergents, high osmotic environment, and iron deficient environment. Additionally, the deletion of clpP significantly affected Brucella virulence in macrophage and mouse infection models. Integrated transcriptomic and proteomic analyses of the ΔclpP strain showed that 1965 genes were significantly affected at the mRNA and/or protein levels. The RNA-seq analysis indicated that the ΔclpP strain exhibited distinct gene expression patterns related to energy production and conversion, cell wall/membrane/envelope biogenesis, carbohydrate transport, and metabolism. The iTRAQ analysis revealed that the differentially expressed proteins primarily participated in amino acid transport and metabolism, energy production and conversion, and secondary metabolites biosynthesis, transport and catabolism. This study provided insights into the preliminary molecular mechanism between Clp protease to bacterial growth, stress response, and bacterial virulence in Brucella strains.
Multimodal environmental cleaning strategies to prevent healthcare-associated infections
Authors: Browne Katrina , Mitchell Brett G
Published: August 2023

Infection transmission in healthcare is multifaceted and by in large involves the complex interplay between a pathogen, a host and their environment. To prevent transmission, infection prevention strategies must also consider these complexities and incorporate targeted interventions aimed at all possible transmission pathways. One strategy to prevent and control infection is environmental cleaning. There are many aspects to an environmental cleaning strategy. We believe the key to successfully reducing the risk of healthcare-associated infections through the environment, is to design and implement a multimodal intervention. This paper aims to provide an overview of important considerations for designing a meaningful and sustainable environmental program for healthcare facilities.
Mechanism-based biomarkers for the quality control of Dangkwisoo-san: a scoping review
Authors: Lee Ji Hwan , Jin Shihui , Lee Myong Jin , Tran Nguyen Khoi Song , Kim Young-Joo , Lee Sanghyun , Kim Song-Yi , Kang Ki Sung
Published: August 2023

Dangkwisoo-san (DS) is a traditional Korean herbal medicine used to treat traumatic diseases, including pulmonary contusions, traumatic pneumothorax, bruising, and ankle sprain. Quality control (QC) biomarkers for DS can help ensure its safety and efficacy. Although chemical quality assessments are performed to ensure consistent efficacy of DS, the identity and quantity of the compounds contained within a given natural product is a frequent complication. We conducted a literature review to identify biological assays that support the chemical QC of DS. The results of our investigation confirmed that in vitro experiments with aqueous and alcoholic extracts of DS exhibited positive effects on many aspects of treatment. With 80% EtOH extraction, a low concentration of DS (1 μg/ml) significantly diminished the expression of inflammatory factors, such as nitric oxide (NO), TNF-α, IL-1β, and IL-6, in the Raw264.7 cell line. MeOH extracts activated NRF2 and antioxidant activities in response to the inflammatory inducer LPS, and water extracts of DS remarkably reduced proinflammatory cytokine levels compared to dexamethasone and cyclosporin treatments. Aqueous extracts of DS at a moderate dose of 125 μg/ml supported bone regeneration, recovered ischemic injury in an eNOS-dependent manner, and prevented metabolic disorders (TRPM7 channel inhibition). Cytokines, NO, and immunoglobulins are potential biological QC biomarkers to assess the anti-inflammation and immune response to DS. Future quality evaluation studies of herbal medicines (herbal prescriptions) should aim to select the mechanism-based in vitro efficacy evaluation methods that can estimate consistent clinical effects.
Recent trends in agri-food Made in Italy exports
Authors: Carbone Anna , Henke Roberto
Published: August 2023

The agri-food sector is a key component of the Italian economy and the Made in Italy products are altogether the core of it with a strong export propensity. This paper analyses the recent export performance of the Made in Italy as a whole and at product level. The analysis is based on the conjoint measure of export specialization (RCA) and sophistication (Prody). Results show that the Made in Italy aggregate is performing well but, at the same time, which single products face significant difficulties. On the one hand, this is the case for those items for which Italy is improving its specialization, but international competition is increasingly based on price, thus reducing profitability (e. g. prepared vegetables, chocolate products, blue cheeses). On the other hand, there are products whose sophistication is growing, and remuneration perspectives rise with it, but for which Italy is eroding its comparative advantage (e. g. ice creams, pasta, grape and wine > 2lt).
Long-read assembled metagenomic approaches improve our understanding on metabolic potentials of microbial community in mangrove sediments
Authors: Zhang Zhi-Feng , Liu Li-Rui , Pan Yue-Ping , Pan Jie , Li Meng
Published: August 2023

Background

Mangrove wetlands are coastal ecosystems with important ecological features and provide habitats for diverse microorganisms with key roles in nutrient and biogeochemical cycling. However, the overall metabolic potentials and ecological roles of microbial community in mangrove sediment are remained unanswered. In current study, the microbial and metabolic profiles of prokaryotic and fungal communities in mangrove sediments were investigated using metagenomic analysis based on PacBio single-molecule real time (SMRT) and Illumina sequencing techniques.

Results

Comparing to Illumina short reads, the incorporation of PacBio long reads significantly contributed to more contiguous assemblies, yielded more than doubled high-quality metagenome-assembled genomes (MAGs), and improved the novelty of the MAGs. Further metabolic reconstruction for recovered MAGs showed that prokaryotes potentially played an essential role in carbon cycling in mangrove sediment, displaying versatile metabolic potential for degrading organic carbons, fermentation, autotrophy, and carbon fixation. Mangrove fungi also functioned as a player in carbon cycling, potentially involved in the degradation of various carbohydrate and peptide substrates. Notably, a new candidate bacterial phylum named as Candidatus Cosmopoliota with a ubiquitous distribution is proposed. Genomic analysis revealed that this new phylum is capable of utilizing various types of organic substrates, anaerobic fermentation, and carbon fixation with the Wood-Ljungdahl (WL) pathway and the reverse tricarboxylic acid (rTCA) cycle.

Conclusions

The study not only highlights the advantages of HiSeq-PacBio Hybrid assembly for a more complete profiling of environmental microbiomes but also expands our understanding of the microbial diversity and potential roles of distinct microbial groups in biogeochemical cycling in mangrove sediment.
Extracting chain lines and laid lines from digital images of medieval paper using spectral total variation decomposition
Authors: Grossmann Tamara G. , Schönlieb Carola-Bibiane , Da Rold Orietta
Published: August 2023

Medieval paper, a handmade product, is made with a mould which leaves an indelible imprint on the sheet of paper. This imprint includes chain lines, laid lines and watermarks which are often visible on the sheet. Extracting these features allows the identification of the paper stock and gives information about the chronology, localisation and movement of manuscripts and people. Most computational work for feature extraction of paper analysis has so far focused on radiography or transmitted light images. While these imaging methods provide clear visualisation of the features of interest, they are expensive and time consuming in their acquisition and not feasible for smaller institutions. However, reflected light images of medieval paper manuscripts are abundant and possibly cheaper in their acquisition. In this paper, we propose algorithms to detect and extract the laid and chain lines from reflected light images. We tackle the main drawback of reflected light images, that is, the low contrast attenuation of chain and laid lines and intensity jumps due to noise and degradation, by employing the spectral total variation decomposition and develop methods for subsequent chain and laid line extraction. Our results clearly demonstrate the feasibility of using reflected light images in paper analysis. This work enables feature extraction for paper manuscripts that have otherwise not been analysed due to a lack of appropriate images. We also open the door for paper stock identification at scale.