bluuebunny/crossref_metadata_2025 huggingface dataset:
Country-of-Origin or Host-Country Effects? Code-of-Conduct Effect and Labor-Standards Compliance in Chinese Overseas Garment Factories: The Cases of Cambodia and Myanmar
Authors: Hu Xiaoli , Li Min , Huang Yan , Jia Hailong
Published: November 2024

Focusing on the global garment supply chain, this article explores a third effect, apart from the country-of-origin and the host-country effects, that impact the employment relations of overseas Chinese companies. This paper is based on field research and interviews of 42 stakeholders in the Cambodia and Burmese garment industries, and employs thematic qualitative text analysis to examine the data, revealing three main findings: First, the compliance of Chinese overseas factories to labor standards is significantly affected by codes of conduct if these factories supply lead firms in the global garment supply chain. Second, if Chinese overseas factories do not supply lead firms in the global garment supply chain, their compliance to labor standards is significantly influenced by the country-of-origin effect. Third, the strength of regulations in the host country is an important factor that moderates the relationship between code-of-conduct effect and labor-standards compliance as well as the relationship between country-of-origin effect and labor-standards compliance by Chinese overseas factories.
The Tyres of Change: Remittances as a Wheel of Development in Pirot, Serbia
Authors: Ðulovic´ Sara Žeric´
Published: November 2024

This article explores the agency of Yugoslav migrant workers ( Gastarbeiter) and their visions of development, focusing on the establishment of a so-called remittance factory (a manufacturing facility founded primarily using the earnings of citizens working abroad, known as remittances) in the town of Pirot in today’s Serbia. The factory, ‘Tigar’, a major producer of radial Tyres since 1972, became the ‘wheel of development’ in Pirot during the socialist era. The social effects of Gastarbeiter remittances, including changes in gender roles and community cohesion, will also be explored. While Yugoslav migration theorists have primarily critiqued the irrational expenditure of Gastarbeiter savings, my research reveals that, when examined at the micro-level, Gastarbeiter demonstrated prudent investment behaviour, utilising their savings purposefully to contribute to local development upon their return. Through the use of different historical sources (documentary evidence, newspapers and oral history), this article will contribute to a deeper understanding of the complex dynamics of migration, remittance behaviour and development in socialist Yugoslavia. It will underscore the importance of recognising the agency of Gastarbeiter as one of the key contributors to the development of ‘Tigar’ factory, which still operates today, now as part of the French-owned Michelin group. Despite the article’s focus on a single case study, the same research approach can be applied to similar cases, not only in Southeast Europe but also in other emigration regions.
Absentee Landowners and their Impact: A Village-Level Study in Andhra Pradesh and Telangana
Authors: Sreenivasulu Y.
Published: November 2024

This study investigates the implications of the rise of non-cultivating absentee landowning households within the agrarian economy. A primary survey was conducted across eight villages—four in Telangana and four in Andhra Pradesh—selected based on their irrigation sources, including canals, tube wells or tanks, while dry/rainfed villages were chosen based on rainfall, particularly in drought-affected areas. These selected villages represent a diverse range of agrarian structures seen in broader regions of Andhra Pradesh and Telangana. Absentee landowning households have become increasingly significant within the agrarian landscape of the study area. Their proportion is notable, particularly in regions with public irrigation provisions (canals and tanks). In contrast, in drought-affected and tube-well-irrigated regions, a smaller percentage of absentee landowning households reside in urban areas. The study underscores the adverse effects of absentee landowning households on agriculture. These households are often reluctant to sell their land due to expectations of future value appreciation, fixed rental income and benefits from government policies. Consequently, this reluctance leads to a lack of agricultural investment, adversely impacting the agrarian economy.
Monitoring Patient Adherence and Follow-up in Option B+ Program: Understanding Healthcare Workers’ Practices, Challenges, and Facilitators in Lilongwe, Malawi
Authors: Kumwenda Wiza , Bengtson Angela M. , Wallie Shaphil , Bula Agatha K. , Villiera Jimmy Ba , Ngoma Edith , Hosseinipour Mina C. , Mwapasa Victor
Published: November 2024

Background

Option B+ aims to prevent mother-to-child transmission of HIV by providing lifelong antiretroviral therapy (ART) to pregnant and breastfeeding women living with HIV (PBWHIV). Identifying and reengaging PBWHIV who disengage or fail to initiate ART is essential for the success of Option B+. However, the process is often suboptimal, leading to challenges such as misclassification of patients as lost to follow-up. Healthcare workers (HCWs) are pivotal for monitoring engagement, but little is known about their monitoring practices. This study aimed to explore how HCWs monitor women's engagement in Option B+ services.

Methods

A qualitative study was conducted in five high-volume health facilities in Lilongwe, Malawi. Thirty HCWs responsible for monitoring women in Option B+ were purposively selected as key informants. Semistructured interviews were conducted between March and June 2021. Thematic analysis employing deductive and inductive coding methods was utilized. The Consolidated Framework for Implementation Research was used to map gaps, strategies, barriers, and facilitators of monitoring.

Results

Monitoring was described as tracking a PBWHIV from HIV diagnosis to initiation of ART to subsequent ART visits for up to 2 years postpartum. The gaps included timing variations in tracing. No procedures to follow up formal transfer-outs or management of silent transfers during emergency ART refills were identified. Strategies identified included interfacility collaboration, record review, tracing, escorting women during initial visits, and self-reports. Technological innovations, such as WhatsApp groups, were highlighted as game changers in interfacility collaboration when tracking women's movements. Barriers included resource constraints (human and operational), poor work attitudes, and challenges faced by women (partner support, stigma, and HCW rapport). The facilitators included implementing partner support, leadership, and strategies such as education and tracing.

Conclusion

Addressing resource constraints, women's relationship dynamics for self-management, HCWs’ attitudes, and standardizing tracing protocols are crucial for effective monitoring. Leveraging instant messaging for clinic coordination may enhance tracing. Further research and interventions should target identified gaps to promote effective monitoring in similar settings.
Effect of Acetabular Labral Tear Orientation on Hip Joint Kinematics: A Comparison of Radial Tears, Chondrolabral Junction Tears and Complex Tears in Cadaveric Hips
Authors: Fithian Andrew T. , Storaci Hunter W. , Chan Calvin K. , Finlay Andrea K. , Safran Marc R.
Published: November 2024

Background:

Acetabular labral tear morphology or orientation may influence hip stability.

Hypothesis:

A radial tear of the acetabular labrum would result in greater rotational and translational motion compared with a chondrolabral separation.

Study Design:

Controlled laboratory study.

Methods:

Included were 12 unpaired nonarthritic hip specimens, none of which had capsular laxity (8 male; mean age, 34.5 years). The specimens were stripped of all soft tissue except the hip capsule and labrum and, then potted using a custom jig. In 6 specimens, a 1-cm anterosuperior separation of the labrum from the acetabular rim (chondrolabral junction tear; CLJT) was created. In the other 6 specimens, a radial tear was created at the anterosuperior acetabulum. Subsequently, a complex labral tear was created in all specimens by adding a radial tear to the CLJT specimens and vice versa. The specimens were mounted on a load frame, and the femoral head displacement in the neutral and hyperextended positions was recorded at 5 N·m of internal/external rotation (IR/ER) torque and at 50 N of superior-inferior (S-I), anterior-posterior (A-P), and medial-lateral (M-L) force. Testing occurred at 0° extension and at maximal extension both before and after initial labral tear creation and again after creation of the complex labral tear. Before testing (intact state), the joint was vented to remove the effect of intra-articular pressure difference between the intact capsule and after capsulotomy for labral tear creation. The t test was used to calculate group differences by each range of motion measure (IR/ER and S-I, A-P, and M-L translations) for neutral and hyperextension.

Results:

Neither the radial labral injury nor the CLJT produced differences from the vented state in any combination of hip position or plane of motion. The complex labral tear showed increased IR/ER rotation at maximal hip extension. There was no difference between CLJT and radial labral tear in any combination of hip position or plane of motion.

Conclusion:

A simple labral tear did not affect hip joint stability when the capsule was intact, and no capsular laxity was present. A complex labral tear caused increased rotational laxity at maximal extension. Capsular laxity or a complex labral tear may be a prerequisite for labral injury to cause increased hip joint motion and/or translation.

Clinical Relevance:

Study findings suggest that labral tears in the absence of capsular laxity may not play a role in producing microinstability by increasing motion or translation.
Suboptimal Oral Health, Multimorbidity, and Access to Dental Care
Authors: Limo L. , Nicholson K. , Stranges S. , Gomaa N.
Published: November 2024

Introduction:

Emerging studies on the links between suboptimal oral health and multimorbidity (MM), or the co-existence of multiple chronic conditions, have raised controversy as to whether enhancing access to dental care may mitigate MM in those with suboptimal oral health. In this study, we aim to assess the extent of the association between suboptimal oral health and MM and whether access to dental care can modify this association.

Methods:

We conducted a cross-sectional analysis using data from the Canadian Longitudinal Study on Aging (CLSA) (N = 44,815, 45 to 84 y old). Edentulism, self-reported oral health (SROH), and other oral health problems (e.g., toothache, bleeding gums) were used as indicators of suboptimal oral health. MM was defined according to the Public Health Agency of Canada as having 2 or more of the following chronic conditions: cancer, cardiovascular diseases, chronic respiratory diseases, diabetes, and mental illnesses. For robustness, we also used a cutoff of having 3 or more of these chronic conditions. Variables for access to dental care included (1) dental visits within the past year, (2) availability of dental insurance, and (3) cost barriers to dental care. We constructed robust Poisson regression models to estimate the association between suboptimal oral health and MM and then assessed the effect measure modification by indicators of access to dental care on a multiplicative scale. We also calculated the relative excess risk due to interaction for prevalence ratio (PR) on an additive scale.

Results:

Indicators of suboptimal oral health were significantly associated with MM (edentulism PR 1.17, 95% confidence interval [CI] 1.08, 1.27; poor SROH PR 1.44, 95% CI 1.33, 1.54; other oral health problems PR 1.52, 95% CI 1.44, 1.78). The magnitude of this association was higher in individuals who reported fewer dental visits within the past year, lacked dental insurance, and avoided dental care due to costs.

Conclusion:

The association between suboptimal oral health and MM may be exacerbated by barriers to accessing dental care. Policies aiming to enhance access to dental care may help mitigate MM in middle-aged and older Canadians with suboptimal oral health.

Knowledge Transfer Statement:

This study offers insights into the connection among suboptimal oral health, multimorbidity, and access to dental care factors in middle-aged and older Canadians. The findings can be of value for clinicians and policy makers aiming to enhance medical-dental integration and improve accessibility to dental care and to patients seeking information about the connections between oral health and chronic conditions. Implementation has the potential to enhance individual well-being and drive systemic improvements in health care.
A Review: Novel Therapies for Advanced Clear Cell Renal Cell Carcinoma
Authors: Mar Nataliya , Dwabe Sami , Kaakour Dalia , Seyedin Steven N. , Rezazadeh Arash , Daneshvar Michael
Published: November 2024

The therapeutic landscape of clear cell renal cell carcinoma (ccRCC) has dramatically evolved in the last decade. Immuno-oncology (IO) and/or tyrosine kinase inhibitor (TKI) based doublet therapies have become standard in the frontline setting for most patients with advanced ccRCC. For previously-treated advanced ccRCC, multiple agents are available including belzutifan, a hypoxia inducible factor 2 alpha (HIF2-α) inhibitor. However, the challenging goal of developing therapies with a unique mechanism of action remains. Many such promising agents are currently in development such as novel TKIs, inhibitors targeting alternative checkpoints, cellular therapies, radioligands, antibody-drug conjugates, and agents targeting fatty acid metabolism. Further, the role of microbiome is being actively investigated in advanced ccRCC, with ongoing studies evaluating its effect when combined with standard therapies. Mature data from trials with these agents is eagerly awaited.
Rivers across worlds: A conceptual framework for ontological inclusion & exclusion in participatory water governance
Authors: Rickard Thomas , Ludwig David
Published: November 2024

Water-related crises and disasters are increasing in frequency and severity. Integrated Water Resources Management (IWRM) has been established over the last few decades aiming to achieve sustainable and participatory water governance. However, this article argues that IWRM is often based on ontological exclusion in the sense that participation is conditional on adopting a dominant ontology of water as a natural resource. Drawing on the Ontological Turn, we present a conceptual framework of ontological inclusion to support the analysis of established water governance. This is engaged in a case study of a participatory process for water-body classification in the Doce River basin. The ontologies of river-as-Watú, of the Indigenous Krenak, and river-as-home, of riverine communities, are shown to be excluded from the participatory process; furthermore, the ontologies of river-as-contested and river-as-state-failure are excluded from the policy instrument. The ontologies of river-as-resource and river-as-state-responsibility are enacted in the participatory process and the policy instrument. While state managers expressed concern for participation and plurality, the process and policy instrument remained ontologically exclusive. The nuances of ontological overlap and partial exclusion are explored alongside reflections on the challenges of plurality in state governance. The conceptual framework provides a normative resource for evaluating ontological inclusion and exclusion in established environmental governance.
The magnitude of short interpregnancy intervals and associated factors among women who delivered in North Wollo Zone public hospitals, northeastern Ethiopia, 2023: A facility-based cross-sectional study
Authors: Arage Mulugeta Wodaje , Shimels Samrawit , Kassaw Abebe Tarekegn , Yilak Gizachew
Published: November 2024

Background:

Maternal and child mortality rates remain a serious public health challenge in Ethiopia. Short interpregnancy intervals are known to negatively impact perinatal and child health; therefore, improving this practice is a key strategy to reduce mortality and adverse outcomes.

Objective:

This study aimed to evaluate the extent of short intervals between pregnancies and the factors associated with them among women who gave birth at public hospitals in the North Wollo Zone of northeastern Ethiopia in 2023.

Design:

A facility-based cross-sectional study was conducted in the North Wollo Zone of northeastern Ethiopia in 2023.

Methods:

This study was conducted on mothers who delivered at public hospitals in the North Wollo Zone of northeastern Ethiopia. The study participants were selected using a systematic random sampling technique between February 1, 2023, and April 1, 2023. Data were collected through an interviewer-administered questionnaire using the Kobo Collect tool and analyzed using SPSS version 27.0. Bivariable and multivariable analyses were performed to determine the relationship between the outcome and predictor variables. A p value of less than 0.05 was considered significant in the multivariable analysis.

Results:

The study found that 51.5% of participants had short interpregnancy intervals. Several independent factors were associated with a short birth interval, including the status of the last pregnancy (adjusted odds ratio (AOR): 9.51; 95% CI: 3.932–23.0028), educational status of the woman (AOR: 4.545; 95% CI: 1.208–17.108), and use of modern contraceptives in previous pregnancies (AOR: 6.460, 95% CI: 3.882–23.008).

Conclusion:

Despite the efforts made through public health interventions in Ethiopia, the prevalence of short interpregnancy intervals in this study was high. Therefore, increasing the utilization of modern contraceptives and promoting health education at both health facilities and community levels could contribute to addressing this issue.
Medication-Taking Trajectory and Its Correlates in Patients With Diabetes: Based on the Information–Motivation–Behavioral Skills Model
Authors: Seo Shinae , Kim Chun-Ja , Kang Hee Sun , Kim Dae Jung , Schlenk Elizabeth A.
Published: November 2024

Purpose

The purpose was to identify trajectories of medication taking among patients with diabetes and investigate correlates of these trajectories using the information–motivation–behavioral skills (IMB) model.

Methods

This study employed a descriptive correlational, longitudinal design using convenience sampling. The participants were 96 adults with diabetes from an outpatient diabetes clinic at a university-affiliated hospital. Medication taking was assessed at 3 time points: baseline, 6 months, and 12 months. At baseline, study variables based on the IMB model were measured: medication knowledge (information), motivational readiness and social support (motivation), and medication self-efficacy (behavioral skills). Group-based trajectory modeling was used to identify medication-taking trajectories, and multinomial logistic regression was used to assess factors associated with medication-taking trajectories.

Results

Three distinct medication-taking trajectory groups were identified: “high medication taking,” “increasing medication taking,” and “low medication taking.” Higher medication knowledge was associated with the high and increasing medication-taking trajectory groups. Motivational readiness was associated with the high and increasing medication-taking groups. In contrast, higher medication self-efficacy was associated only with the high medication-taking group, not with the increasing and low medication-taking groups.

Conclusions

The findings suggest that knowledge, motivational readiness, and self-efficacy are essential in IMB model-based intervention strategies across dynamic medication-taking patterns to enhance medication taking. Health care providers can help patients with diabetes improve medication taking by understanding their medication-taking trajectories and their correlates. Strategies that enhance medication self-efficacy are essential for patients in the increasing and low medication-taking groups.
Endophthalmitis patients in Makassar City: molecular identification of pathogenic fungal profile
Authors: Guslianto Willy Wirawan , Pertiwi Yunialthy Dwia , Hatta Mochammad , Tenriesa Lisa , Nislawati Ririn , Syamsuri Fadhilah , Massi Muhammad Nasrum , Hamid Firdaus
Published: November 2024

Background

Endophthalmitis is a severe inflammation of the internal ocular structures, usually caused by bacterial or fungal infections, and can lead to rapid, irreversible blindness. Fungal endophthalmitis (FE), primarily due to Candida albicans and Aspergillus, is less common than bacterial endophthalmitis but has shown an increase in prevalence over the past two decades. Diagnosing FE is challenging and often delayed due to the time-consuming nature of traditional culture methods. The timely initiation of targeted antifungal therapy based on the specific fungal pathogen identified by molecular method can improve patient outcomes and reduce the risk of vision loss. This study aims to determine the presence of pathogenic fungal infections in patients with endophthalmitis using molecular methods at Hasanuddin University Hospital Makassar.

Methods

This cross-sectional observational study analyzed 83 intraocular fluid samples from patients with endophthalmitis at Hasanuddin University Hospital, Makassar, Indonesia. Samples were examined using microscopy, culture, and molecular methods, including polymerase chain reaction (PCR) and deoxyribonucleic acid (DNA) sequencing.

Results

The study population comprised 49 males (59%) and 34 females (41%), with an average age of 45.85 years. The distribution of affected eyes was nearly equal, with 50.6% involving the right eye and 49.4% involving the left eye. Exogenous transmission, primarily related to external risk factors such as ocular trauma or surgical procedures, was identified as the most common mode of fungal transmission in this population (97.6%). No fungal elements were detected through microscopy or culture; however, PCR could identify 5 positive samples (6%); 3 were males and 2 were females; all have exogenous transmission, predominantly showing Candida species. Sequencing revealed Candida parapsilosis, Lodderomyces beijingensis, and Trichophyton rubrum among the findings.

Conclusion

Cases of fungal endophthalmitis are rare but increasing, posing diagnostic challenges. Our study concludes that PCR is more effective than traditional culture methods in identifying fungal pathogens, with a predominance of Candida species identified in endophthalmitis. Molecular techniques like PCR offer rapid and accurate diagnosis, improving patient treatment outcomes by enabling earlier initiation of targeted antifungal therapy.
Trends in medications for autoimmune disorders during pregnancy and factors for their discontinuation: a population-based study
Authors: Mainbourg Sabine , Sheehy Odile , Gorgui Jessica , Vinet Evelyne , Bérard Anick
Published: November 2024

Objectives

The medications used for autoimmune diseases have significantly evolved in recent years, but there is limited knowledge about how treatment practices changed during pregnancy. This study aimed to describe the temporal trends of immunosuppressants, immunomodulators and biologics use during pregnancy among women with autoimmune diseases, compare their use before, during, and after pregnancy, and identify factors predicting the discontinuation of these medications during pregnancy.

Methods

Using data from the Quebec Pregnancy Cohort (1998–2015), which included women under the RAMQ prescription drug plan for at least 12 months before and after pregnancy, the analysis focused on those with at least one International Classification of Diseases Ninth or Tenth Revision code in the year before pregnancy for inflammatory bowel disease, rheumatoid arthritis, spondylarthropathies, connective tissue diseases, systemic lupus erythematosus, or vasculitis. Exposure to immunosuppressants, immunomodulators and biologics were evaluated before and during the pregnancy. Discontinuation during pregnancy was defined as having no prescriptions filled during pregnancy or overlapping with the first day of gestation (1DG), given that at least one prescription was filled in the year prior to pregnancy. Generalized estimating equations were applied to estimate adjusted odds ratios (aOR) for predicting medication discontinuation during pregnancy.

Results

Among 441,570 pregnant women, 3,285 had autoimmune diseases. From 1998 to 2014, the use of immunomodulators increased from 3.7% to 11.9%, immunosuppressants from 4.1% to 13.7%, and biologics from 0% to 15.6%. During pregnancy, compared to before, there was a significant decrease in exposure to immunomodulators (8.6% to 5.4%), immunosuppressants (14.2% to 8.7%), and biologics (5.1% to 4.7%). Factors influencing discontinuation varied by medication type; for immunosuppressants, prior biologics use (aOR = 2.12, 95%CI 1.16–3.85) and the year of pregnancy (aOR = 0.93, 95%CI 0.89–0.98) were key factors, while for biologics, it was only the year of pregnancy (aOR = 0.68, 95%CI 0.54–0.86).

Conclusions

The use of immunomodulators, immunosuppressants, and biologics has increased over time. However, exposure during pregnancy decreased, with recent years showing a lower rate of discontinuation. Understanding the factors influencing medication discontinuation during pregnancy can improve management strategies for women with autoimmune diseases.
Survey in ruminants from Rwanda revealed high diversity and prevalence of extended-spectrum cephalosporin-resistant Enterobacterales
Authors: Irimaso Emmanuel , Keinprecht Helga , Szostak Michael P. , Rosel Adriana Cabal , Stessl Beatrix , Desvars-Larrive Amelie , Ntakirutimana Christophe , Fischer Otto W. , Wittek Thomas , Müller Elke , Feßler Andrea T. , Braun Sascha D. , Schwarz Stefan , Monecke Stefan , Ehricht Ralf , Spergser Joachim , Ruppitsch Werner , Loncaric Igor
Published: November 2024

Background

Antimicrobial resistance (AMR) in Enterobacterales constitutes a significant threat to the health of both humans and animals and a socioeconomic problem. Enterobacterales, mainly Escherichia coli, carrying β-lactamases has become one of the main indicators to estimate the burden of AMR in animals within “One Health” approach.

Objectives

To assess the presence of extended-spectrum cephalosporin-resistant Enterobacterales associated with ruminants (cattle, sheep, goats) habituated in all five provinces of Rwanda and to perform in depth characterization of isolates.

Methods

We screened 454 rectal swabs from 203 cows, 170 goats, and 81 sheep and selective isolation of extended-spectrum cephalosporin-resistant Enterobacterales was conducted. Isolates were identified as a members of the order Enterobacterales by MALDI-TOF MS and further characterized by susceptibility testing and by whole-genome sequencing.

Results

Out of the 454 samples, 64 extended-spectrum cephalosporin-resistant Enterobacterales were isolated from 58 animals. Isolates belonged to seven bacterial species and were identified as Escherichia coli (n = 54), Enterobacter bugandensis (n = 4), Enterobacter mori (n = 2), Klebsiella pneumoniae (n = 2), Enterobacter dykesii (n = 1), and Citrobacter freundii (n = 1). All isolates displayed an Extended-spectrum β-lactamases (ESBL) phenotype, with exception of Citrobacter freundii isolate displayed both an ESBL and AmpC phenotype. In addition, all Enterobacter isolates were identified as stably de-repressed AmpC-producers. ESBLs genes, blaCTX−M−15 was predominant. Resistance to tetracycline and tet(A) was most frequently observed among non-β-lactam resistance. Forty-eight isolates displayed multidrug-resistance phenotypes. A shiga toxin-producing E. coli and an enterotoxigenic E. coli isolate were observed. Genome comparisons revealed thirty-five E. coli sequence types (ST) (ST10, ST307 being predominate).

Conclusions

Considering the high proximity between ruminants and humans in Rwanda, the dissemination of antimicrobial drug resistance highlights the public health threats and requires the joint and multisectoral action of human and veterinary medicine, at human-animal-environment interfaces. Therefore, it is important to establish national and global “One Health” surveillance programs of AMR to tackle the antibiotic-resistant crisis in human and veterinary medicine.
Engineering an Escherichia coli strain for enhanced production of flavonoids derived from pinocembrin
Authors: Hanko Erik K. R. , Robinson Christopher J. , Bhanot Sahara , Jervis Adrian J. , Scrutton Nigel S.
Published: November 2024

Background

Flavonoids are a structurally diverse group of secondary metabolites, predominantly produced by plants, which include a range of compounds with pharmacological importance. Pinocembrin is a key branch point intermediate in the biosynthesis of a wide range of flavonoid subclasses. However, replicating the biosynthesis of these structurally diverse molecules in heterologous microbial cell factories has encountered challenges, in particular the modest pinocembrin titres achieved to date. In this study, we combined genome engineering and enzyme candidate screening to significantly enhance the production of pinocembrin and its derivatives, including chrysin, pinostrobin, pinobanksin, and galangin, in Escherichia coli.

Results

By implementing a combination of established strain engineering strategies aimed at enhancing the supply of the building blocks phenylalanine and malonyl-CoA, we constructed an E. coli chassis capable of accumulating 353 ± 19 mg/L pinocembrin from glycerol, without the need for precursor supplementation or the fatty acid biosynthesis inhibitor cerulenin. This chassis was subsequently employed for the production of chrysin, pinostrobin, pinobanksin, and galangin. Through an enzyme candidate screening process involving eight type-1 and five type-2 flavone synthases (FNS), we identified Petroselinum crispum FNSI as the top candidate, producing 82 ± 5 mg/L chrysin. Similarly, from a panel of five flavonoid 7-O-methyltransferases (7-OMT), we found pinocembrin 7-OMT from Eucalyptus nitida to yield 153 ± 10 mg/L pinostrobin. To produce pinobanksin, we screened seven enzyme candidates exhibiting flavanone 3-hydroxylase (F3H) or F3H/flavonol synthase (FLS) activity, with the bifunctional F3H/FLS enzyme from Glycine max being the top performer, achieving a pinobanksin titre of 12.6 ± 1.8 mg/L. Lastly, by utilising a combinatorial library of plasmids encoding G. max F3H and Citrus unshiu FLS, we obtained a maximum galangin titre of 18.2 ± 5.3 mg/L.

Conclusion

Through the integration of microbial chassis engineering and screening of enzyme candidates, we considerably increased the production levels of microbially synthesised pinocembrin, chrysin, pinostrobin, pinobanksin, and galangin. With the introduction of additional chassis modifications geared towards improving cofactor supply and regeneration, as well as alleviating potential toxic effects of intermediates and end products, we anticipate further enhancements in the yields of these pinocembrin derivatives, potentially enabling greater diversification in microbial hosts.
Phylogenetic reconstruction of Tuberolachnini and Lachninae (Insecta, Hemiptera): Morphological and molecular analyses revealed a new tribe
Authors: Kanturski Mariusz , Lee Yerim , Kim Hyojoong
Published: November 2024

Background

Lachninae (Insecta: Aphididae) represent a fascinating group of aphids that are traditionally divided into five tribes. Among these, members of the tribe Tuberolachnini exhibit remarkable morphological and biological diversity. One genus of this group, Miyalachnus, known from Japan, is characterized by unique features. Our study aimed to re-examine the tribal classification within Lachninae, with a focus on the diverse Tuberolachnini and the previously understudied genera Miyalachnus and Sinolachnus.

Results

We conducted a comprehensive phylogenetic analysis using four genes (COI, COII, CytB, and EF1α), employing both maximum likelihood (ML) and Bayesian inference (BI) methods on a combined dataset. Our findings challenge the monophyly of Tuberolachnini. The analyses revealed that Miyalachnus and Sinolachnus are phylogenetically distinct from the core Tuberolachnini genera (Nippolachnus, Pyrolachnus, and Tuberolachnus), instead showing a closer relationship with Tramini. Specifically, the Miyalachnus clade forms a sister clade to the clade containing Sinolachnus and Tramini.

Conclusions

On the basis of these molecular results, corroborated by morphological evidence, we propose to erect a new tribe within the Lachninae-Miyalachnini trib. nov. with Miyalachnus as the type genus. We also provide updated taxonomic diagnoses for the remaining tribes and discuss their relationships as well as distinguishing features.
Recurrent BMP4 variants in exon 4 cause non-HFE-associated hemochromatosis via the BMP/SMAD signaling pathway
Authors: Ouyang Qin , Li Yanmeng , Xu Anjian , Zhang Ning , Chen Sisi , Zhou Donghu , Zhang Bei , Ou Xiaojuan , Jia Jidong , Huang Jian , Zhang Wei
Published: November 2024

Background

Hereditary hemochromatosis (HH) is an iron overload disorder and can be caused by variants in non-HFE genes in Chinese patients. However, there is still a considerable proportion of patients suffering from unexplained iron overload. In our previous study, we had identified the p.R269Q variant in exon 4 of the Bone morphogenetic protein 4 (BMP4) gene in Chinese patients with unexplained primary iron overload by Whole Exome sequencing, and then the BMP4 p.H251Y variant was identified by Sanger sequencing in a Chinese patient with secondary iron overload. Our study aimed to explore the pathogenicity and underlying mechanism of BMP4 p.H251Y and BMP4 p.R269Q variants in patients with iron overload.

Methods

Sanger sequencing was conducted to identify the novel variants in the BMP4 gene of patients with unexplained iron overload. MRI and liver biopsy were used to display iron overload in the liver of the patient harboring the BMP4 p.H251Y variant. The BMP4 and hepcidin levels in BMP4 knockdown and BMP4 variant cells were examined by enzyme-linked immunosorbent assay. The effects of BMP4 p.H251Y and BMP4 p.R269Q variants on the hepcidin-regulation pathway were studied.

Results

One of 54 HH patients (1.85%) harbored the BMP4 p.R269Q variant. One of 148 patients (0.68%) with secondary hemochromatosis harbored the BMP4 p.H251Y variant, and these two variants were not found in 100 Chinese general population. For the patient harboring the BMP4 p.H251Y variant, abdominal MRI and Perl's staining of liver tissue displayed iron overload in the liver. Cells transfected with the BMP4 p.H251Y and p.R269Q variants showed down-regulation of hepcidin level and BMP/SMAD pathway compared with cells transfected with the wild-type BMP4 vector.

Conclusion

The BMP4 p.H251Y and p.R269Q variants can downregulate hepcidin levels by inhibiting the BMP/SMAD axis, suggesting they may play pathogenic roles in iron overload.
Associations of epigenetic age acceleration at birth and age 12 years with adolescent cardiometabolic risk: the HOME study
Authors: Arzu Jennifer L. , Kelsey Karl T. , Papandonatos George D. , Cecil Kim M. , Chen Aimin , Langevin Scott M. , Lanphear Bruce P. , Yolton Kimberly , Buckley Jessie P. , Braun Joseph M.
Published: November 2024

Background

Cardiometabolic risk factors among youth are rising. Epigenetic age acceleration, a biomarker for aging and disease-risk, has been associated with adiposity in children, but its association with other cardiometabolic risk markers remains understudied. We employed data from the Health Outcomes and Measures of the Environment (HOME) study, a prospective pregnancy and birth cohort in the greater Cincinnati metropolitan area, to examine whether accelerated epigenetic age at birth as well as accelerated epigenetic age and faster pace of biological aging at age 12 years were associated with higher cardiometabolic risk in adolescents.

Results

After adjusting for potential confounders, including estimated cell type proportions, epigenetic gestational age acceleration at birth, derived from the Bohlin, Knight, and Haftorn clocks using cord blood DNA methylation data, was not associated with cardiometabolic risk z-scores or individual cardiometabolic risk score components (visceral fat, leptin to adiponectin ratio, HOMA-IR, triglycerides to HDL-C ratio, HbA1c, or systolic blood pressure) at age 12 years. We also did not observe any associations of epigenetic age acceleration, calculated with Horvath’s skin and blood, Hannum’s, and Wu’s epigenetic clocks using peripheral blood at age 12 years, with these same cardiometabolic risk markers. In contrast, faster pace of biological aging was associated with higher cardiometabolic risk [βs (95% CIs)] cardiometabolic risk score 0.25 (0.07, 0.42); visceral fat 0.21 (0.05, 0.38); and hemoglobin A1c 0.23 (0.05, 0.41) per standard deviation increase in pace of biological aging. Faster pace of biological aging was also positively associated with systolic blood pressure, triglycerides to HDL-C ratio, HOMA-IR, and leptin to adiponectin ratio, although these associations were not statistically significant.

Conclusions

Our findings provide evidence that faster pace of biological aging was associated with higher cardiometabolic risk score, visceral fat, and HbA1c at age 12 years. Further research is needed to determine whether these associations persist from adolescence through adulthood.
A comparative study on bone density before and after implant placement using osseodensification technique: a clinical evaluation
Authors: Vaddamanu Sunil Kumar , Saini Ravinder S. , Vyas Rajesh , Kanji Masroor Ahmed , Alshadidi Abdulkhaliq Ali F. , Hafedh Salah , Cicciù Marco , Minervini Giuseppe
Published: November 2024

Background

Dental implant success critically depends on the primary stability of the implant, which is significantly influenced by the bone density at the osteotomy site. Traditional drilling techniques for osteotomy preparation often compromise bone volume and quality. This study aimed to evaluate the impact of osseodensification, a novel osteotomy preparation technique, on bone density and implant stability. The technique utilizes specialized drills that operate in a counter-clockwise direction to compact autografted bone laterally and apically, preserving and enhancing bone density.

Methods

A total of 32 patients undergoing dental implant surgery were included in this study. Pre-operative and post-operative bone densities at the apical, mesial, and distal regions of the osteotomy sites were measured using Dentascan (CT) and analyzed with Radiant DICOM software. The study utilized osseodensification drills for osteotomy preparation, comparing pre-operative and post-operative bone densities to assess the technique’s efficacy.

Results

The study found a statistically significant increase in bone density post-operatively (p < 0.001), with the greatest improvement observed in the distal region, followed by the mesial and apical regions. The findings underscore osseodensification’s effectiveness in enhancing bone density and primary stability, with the distal region exhibiting the highest bone density.

Conclusion

Osseodensification represents a significant advancement in implant dentistry for osteotomy preparation. By preserving and increasing bone density through compact autografting, this technique not only improves primary stability but also offers potential benefits in indirect sinus lifting and alveolar ridge expansion. The study advocates for the broader adoption of osseodensification drills in clinical practice to achieve better outcomes in dental implantology.

Trial Registration

This study received ethical approval from The Research Ethics Committee at King Khalid University’s under Approval no. ECM#2024 − 216. Additionally, it was registered with ClinicalTrials.gov, identifier no: NCT06268639.

Graphical Abstract
Computational analysis of variability and uncertainty in the clinical reference on magnetic resonance imaging radiomics: modelling and performance
Authors: Xue Cindy , Yuan Jing , Lo Gladys G. , Poon Darren M.C. , Chu Winnie CW
Published: November 2024

To conduct a computational investigation to explore the influence of clinical reference uncertainty on magnetic resonance imaging (MRI) radiomics feature selection, modelling, and performance. This study used two sets of publicly available prostate cancer MRI = radiomics data (Dataset 1: n = 260; Dataset 2: n = 100) with Gleason score clinical references. Each dataset was divided into training and holdout testing datasets at a ratio of 7:3 and analysed independently. The clinical references of the training set were permuted at different levels (increments of 5%) and repeated 20 times. Four feature selection algorithms and two classifiers were used to construct the models. Cross-validation was employed for training, while a separate hold-out testing set was used for evaluation. The Jaccard similarity coefficient was used to evaluate feature selection, while the area under the curve (AUC) and accuracy were used to assess model performance. An analysis of variance test with Bonferroni correction was conducted to compare the metrics of each model. The consistency of the feature selection performance decreased substantially with the clinical reference permutation. AUCs of the trained models with permutation particularly after 20% were significantly lower (Dataset 1 (with ≥ 20% permutation): 0.67, and Dataset 2 (≥ 20% permutation): 0.74), compared to the AUC of models without permutation (Dataset 1: 0.94, Dataset 2: 0.97). The performances of the models were also associated with larger uncertainties and an increasing number of permuted clinical references. Clinical reference uncertainty can substantially influence MRI radiomic feature selection and modelling. The high accuracy of clinical references should be helpful in building reliable and robust radiomic models. Careful interpretation of the model performance is necessary, particularly for high-dimensional data.
Comparative analysis of primary versus secondary paranasal sinus mucoceles: a case control study
Authors: Minh Le Tran Quang , Tuan Nguyen Thanh , Hon Nguyen Minh Hao
Published: November 2024

Background

Paranasal sinus mucoceles are benign cystic lesions characterized by mucous accumulation that can lead to significant complications due to erosion of sinus walls and compression of adjacent structures. This retrospective study aims to compare the clinical characteristics and treatment outcomes of primary and secondary mucoceles.

Methods

We reviewed medical records of 68 patients treated for mucoceles at the Ear, Nose, and Throat Hospital in Ho Chi Minh City, Vietnam, from June 2022 to June 2024. Advanced diagnostic imaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI), were utilized in the management of these lesions. Statistical analysis was conducted using chi-square and t-tests to compare the characteristics and outcomes between the two groups.

Results

The study found that primary mucoceles often presented with less severe symptoms compared to secondary mucoceles, which occur post-surgery or post-trauma and are associated with more severe symptoms and complications. Primary mucoceles were most frequently located in the frontal-ethmoid region (47.4%), while secondary mucoceles had a similar distribution but were more prevalent following previous surgical interventions. Endoscopic sinus surgery was the primary treatment for both groups, with secondary mucoceles frequently requiring more complex surgical interventions. Postoperative improvement was significant in both groups, though secondary mucoceles exhibited slower recovery and higher rates of residual minor visual impairments.

Conclusion

The comparison between primary and secondary paranasal sinus mucoceles reveals critical differences in clinical profiles and treatment outcomes. Understanding these differences is essential for optimizing management strategies and improving prognosis for patients with these challenging conditions. Further research is needed to explore long-term treatment effects and the efficacy of different surgical approaches.
Characterization of desi cotton (
Gossypium arboreum
) germplasm through morpho-biochemical and fiber traits and exploring molecular marker based diversity along with allied (un)cultivated Gossypium species
Authors: Vadodaria Hrushik , Patidar Dhramendra , Kumar Sushil , Patel Dipak A. , Patel Hardik
Published: November 2024

Desi
cotton (
Gossypium arboreum
) or the Asian tree cotton occupies the least area amongst all the cultivated
Gossypium
species, but it is of paramount importance as a vital source of high-quality lint and stress resistance for commercially cultivated cotton species. Hence, it is essential to analyze the genetic diversity of this crop for future advancements in cotton breeding. An study comprising of 30
G. arboreum
accessions was undertaken to estimate the genetic variability using morphological traits, fibre quality parameters and oil quality. Likewise, molecular diversity analysis using 24 SSR markers was carried out for the 30
G. arboreum
genotypes and 11 additional cotton species. Presence of substantial genetic variability was revealed by analysis of variance (ANOVA) amongst all genotypes for all the traits. Morphological studies indicated that genotype PA 255 had higher seed cotton yield (80.07 g/plant). Examination of fibre and oil quality suggested that genotype Cernuum had the highest fibre fineness (7.27 µg/inch) and oil (17.68%), while genotypes 824 (29.57 mm) and PA 812 (29.30 g/tex) had the maximum UHML and fibre strength, respectively. 30 genotypes were classified into 3 classes based on the seed cotton yield, which is considered a very important trait. Manhattan dissimilarity co-efficient based phenotypic diversity divided the 30 genotypes into four main clusters, with an average dissimilarity value of 0.17, indicating low phenotypic variability. The dendrogram generated using SSR marker data based on Nei’s genetic distance grouped 41 genotypes into three clusters, with average distance of 0.47. Based upon the placement of the number of genotypes in same clusters in both matrices, it can be inferred that there is considerable correlation between morphological and molecular analysis as the value for Mantel statistic R was 0.42 (
p
value 0.0003). Fatty acid profiles of 30
desi
cotton genotypes revealed the presence of nine different fatty acids of which linoleic, palmitic and oleic acid were found to be in highest amount, with an average of 43.22%, 25.13% and 24.97%, respectively. Overall, the study suggested that the variability available in diploid cotton can be exploited through hybridization, mapping population development and polyploidization based pre-breeding.