bluuebunny/crossref_metadata_2025 huggingface dataset:
Intimate partner violence among reproductive-age women in central Gondar zone, Northwest, Ethiopia: a population-based study
Authors: Getinet Wondale , Azale Telake , Getie Eskedar , Salelaw Endalamaw , Amare Tadele , Demilew Demeke , Lemma Alemu , Kibret Destaw , Aklilu Abayneh , Tensae Techalo , Srahbzu Mengesha , Shumet Shegaye
Published: April 2022

Background

Violence against women is the most widespread kind of human rights violation, and it has been linked to a wide range of consequences. The most prominent psychosocial and mental health concern that has serious effects for women's physical and mental well-being. This study assessed the prevalence and associated factors of women’s violence by intimate partner among women in the reproductive age group (15–49).

Methods

Multistage community-based cross-sectional study was conducted among reproductive age group women in the central Gondar zone. We recruited 845 participants and interviewed by health extension workers using face-to-face interviews. We used a Women's Abuse Screening test to outcome variable; it has a total score ranges 0–16, a score > 1 indicates positive for the presence of intimate partner violence within a year. Variables were coded and entered to Epi data version 3.1 and exported to SPSS version 21 for analysis. Descriptive statistics and multivariate logistic regression analysis was run for data analysis. Adjusted odds ratios (AOR) with a 95% confidence level (CI) were declared significant.

Result

Among a total of 845 participants 804 responded to the interviews with a response rate of 95%. The prevalence rate of intimate partner violence is 391(48.6%). From multivariate logistic regression analysis women being married [AOR:3.85; 95% CI (2.38, 6.22)], high school and above educational status [(AOR: 0.43; 95% CI (0.30, 0.61), women’s having > 3children [(AOR: 1.82, 95% CI (1.0, 3.1)], having a household food insecurity[(AOR: 2.09, 95% CI (1.51, 2.91)], having life threatening events [(AOR: 2.09; 95% CI (1.51, 2.91)], moderate social support [(AOR: 0.60; 95% CI (0.41, 0.83)], depression [(AOR: 3.12; 95% CI (1.60, 6.07) were significantly associated with violence by intimate partner at 95% CI .

Conclusion

Intimate partner violence is common among reproductive-age women. Married, women with several children, food insecurity, life-threatening events, and depression were all found to be significant predictors of violence. Measures should be taken to raise community awareness, particularly among intimate partners, their families, and government officials.
Perceptions of pelvic floor dysfunction and rehabilitation care amongst women in southeast China after radical hysterectomy: a qualitative study
Authors: Lai Yu-ting , Lin Ai-wu , Zheng Zhi-hui , Wang Ya-li , Yu Hong-hong , Jiang Xin-yong , Ge Li
Published: April 2022

Objective

To investigate the perceptions of pelvic floor dysfunction (PFD) and rehabilitation care amongst women after radical hysterectomy and to explore ways to improve quality of care.

Methods

Thirty-six women who underwent radical hysterectomy at a hospital in southeast China were enrolled via purposive sampling. Semi-structured in-depth interviews were conducted. The texts were analysed via qualitative content analysis.

Results

Four themes were obtained: serious lack of knowledge, heavy psychological burden, different coping strategies and great eagerness to receive multiparty support on PFD rehabilitation care.

Conclusion

The society and professional staff should strengthen health education on PFD. Professionals should offer education before and after surgery and actively provide rehabilitation consultation to promote the availability of rehabilitation to support women with PFD rehabilitation care. In addition, family-centred care is an important way to support women to return to normal life, and women's need for family support should be more actively expressed. Moreover, knowledge of medical insurance should be popularised, especially in rural areas in China.
HPV knowledge, screening barriers and facilitators, and sources of health information among women living with HIV: perspectives from the DC community during the COVID-19 pandemic
Authors: Ciceron Annie Coriolan , Jeon Min Jeong , Monroe Anne Kress , Clausen Michelle Elise , Magnus Manya , Le Daisy
Published: April 2022

Background

High-risk human papillomavirus (HPV) causes 99% of cervical cancer cases. Despite available prevention methods through the HPV vaccine and two screening modalities, women continue to die from cervical cancer worldwide. Cervical cancer is preventable, yet affects a great number of women living with HIV (WLH). Low screening rates among WLH further exacerbate their already high risk of developing cervical cancer due to immunosuppression. This study explores WLH’s current cervical cancer knowledge, screening barriers and facilitators, and sources of health information.

Methods

Focus group discussions were conducted with 39 WLH aged 21 years old or older, who resided in the Washington-Baltimore Metropolitan Area. Emergent themes were classified and organized into overarching domains and assembled with representative quotations.

Results

The women had limited knowledge of HPV and the cervical cancer screening guidelines for WLH. Coronavirus 2019 (COVID-19) pandemic has amplified screening barriers due to decreased accessibility to usual medical appointment and cervical cancer screenings. Screening facilitators included knowing someone diagnosed with cervical cancer and provider recommendations. WLH indicated that they obtained health information through in-person education (providers, peer groups) and written literature. Due to the pandemic, they also had to increasingly rely on remote and technology-based communication channels such as the internet, social media, television, radio, email, and short message service (SMS) text messaging.

Conclusions

Future health interventions need to explore the possibility of sharing messages and increasing cervical cancer and HPV knowledge of WLH through the use of SMS and other technology-based channels.
Correction to: Alleviation of 4-nitroquinoline 1-oxide induced oxidative stress by Oroxylum indicum (L.) leaf extract in albino Wistar rats
Authors: Mohan Shalini , Thiagarajan Kalaivani , Sundaramoorthy Balaji , Gurung Vivek , Barpande Manas , Agrawal Shilpi , Chandrasekaran Rajasekaran
Published: April 2022

An amendment to this paper has been published and can be accessed via the original article.
Core procedural skills competencies and the maintenance of procedural skills for medical students: a Delphi study
Authors: Green Patricia , Edwards Elizabeth J. , Tower Marion
Published: April 2022

Background

It is well recognised that medical students need to acquire certain procedural skills during their medical training, however, agreement on the level and acquisition of competency to be achieved in these skills is under debate. Further, the maintenance of competency of procedural skills across medical curricula is often not considered. The purpose of this study was to identify core procedural skills competencies for Australian medical students and to establish the importance of the maintenance of such skills.

Methods

A three-round, online Delphi method was used to identify consensus on competencies of procedural skills for graduating medical students in Australia. In Round 1, an initial structured questionnaire was developed using content identified from the literature. Respondents were thirty-six experts representing medical education and multidisciplinary clinicians involved with medical students undertaking procedural skills, invited to rate their agreement on the inclusion of teaching 74 procedural skills and 11 suggested additional procedures. In Round 2, experts re-appraised the importance of 85 skills and rated the importance of maintenance of competency (i.e., Not at all important to Extremely important). In Round 3, experts rated the level of maintenance of competence (i.e., Observer, Novice, Competent, Proficient) in 46 procedures achieving consensus.

Results

Consensus, defined as > 80% agreement, was established with 46 procedural skills across ten categories: cardiovascular, diagnostic/measurement, gastrointestinal, injections/intravenous, ophthalmic/ENT, respiratory, surgical, trauma, women’s health and urogenital procedures. The procedural skills that established consensus with the highest level of agreement included cardiopulmonary resuscitation, airway management, asepsis and surgical scrub, gown and gloving. The importance for medical students to demonstrate maintenance of competency in all procedural skills was assessed on the 6-point Likert scale with a mean of 5.03.

Conclusions

The findings from the Delphi study provide critical information about procedural skills for the Clinical Practice domain of Australian medical curricula. The inclusion of experts from medical faculty and clinicians enabled opportunities to capture a range of experience independent of medical speciality. These findings demonstrate the importance of maintenance of competency of procedural skills and provides the groundwork for further investigations into monitoring medical students’ skills prior to graduation.
Ethical and practical considerations for cell and gene therapy toward an HIV cure: findings from a qualitative in-depth interview study in the United States
Authors: Dubé Karine , Kanazawa John , Patel Hursch , Louella Michael , Sylla Laurie , Sheehy Jeff , Dee Lynda , Taylor Jeff , Adair Jen , Anthony-Gonda Kim , Dropulić Boro , Sauceda John A. , Peluso Michael J. , Deeks Steven G. , Simoni Jane
Published: April 2022

Background

HIV cure research involving cell and gene therapy has intensified in recent years. There is a growing need to identify ethical standards and safeguards to ensure cell and gene therapy (CGT) HIV cure research remains valued and acceptable to as many stakeholders as possible as it advances on a global scale.

Methods

To elicit preliminary ethical and practical considerations to guide CGT HIV cure research, we implemented a qualitative, in-depth interview study with three key stakeholder groups in the United States: (1) biomedical HIV cure researchers, (2) bioethicists, and (3) community stakeholders. Interviews permitted evaluation of informants’ perspectives on how CGT HIV cure research should ethically occur, and were transcribed verbatim. We applied conventional content analysis focused on inductive reasoning to analyze the rich qualitative data and derive key ethical and practical considerations related to CGT towards an HIV cure.

Results

We interviewed 13 biomedical researchers, 5 community members, and 1 bioethicist. Informants generated considerations related to: perceived benefits of CGT towards an HIV cure, perceived risks, considerations necessary to ensure an acceptable benefit/risk balance, CGT strategies considered unacceptable, additional ethical considerations, and considerations for first-in-human CGT HIV cure trials. Informants also proposed important safeguards to developing CGT approaches towards an HIV cure, such as the importance of mitigating off-target effects, mitigating risks associated with long-term duration of CGT interventions, and mitigating risks of immune overreactions.

Conclusion

Our study identified preliminary considerations for CGT-based HIV cure across three key stakeholder groups. Respondents identified an ideal cure strategy as one which would durably control HIV infection, protect the individual from re-acquisition, and eliminate transmission to others. Known and unknown risks should be anticipated and perceived as learning opportunities to preserve and honor the altruism of participants. Preclinical studies should support these considerations and be transparently reviewed by regulatory experts and peers prior to first-in-human studies. To protect the public trust in CGT HIV cure research, ethical and practical considerations should be periodically revisited and updated as the science continues to evolve. Additional ethics studies are required to expand stakeholder participation to include traditionally marginalized groups and clinical care providers.
The “better data, better planning” census: a cross-sectional, multi-centre study investigating the factors influencing patient attendance at the emergency department in Ireland
Authors: Cummins Niamh M. , Barry Louise A. , Garavan Carrie , Devlin Collette , Corey Gillian , Cummins Fergal , Ryan Damien , Cronin Sinead , Wallace Emma , McCarthy Gerard , Galvin Rose
Published: April 2022

Background

Internationally Emergency Department (ED) crowding is a significant health services delivery issue posing a major risk to population health. ED crowding affects both the quality and access of health services and is associated with poorer patient outcomes and increased mortality rates. In Ireland the practising of “Corridor Medicine” and “Trolley Crises” have become prevalent. The objectives of this study are to describe the demographic and clinical profile of patients attending regional EDs and to investigate the factors influencing ED utilisation in Ireland.

Methods

This was a multi-centre, cross-sectional study and recruitment occurred at a selection of urban and rural EDs (n = 5) in Ireland throughout 2020. At each site all adults presenting over a 24 h census period were eligible for inclusion. Clinical data were collected via electronic records and a questionnaire provided information on demographics, healthcare utilisation, service awareness and factors influencing the decision to attend the ED.

Results

Demographics differed significantly between ED sites in terms of age (p ≤ 0.05), socioeconomic status (p ≤ 0.001), and proximity of health services (p ≤ 0.001). Prior to ED attendance 64% of participants accessed community health services. Most participants (70%) believed the ED was the “best place” for emergency care or attended due to lack of awareness of other services (30%). Musculoskeletal injuries were the most common reason for presentation to the ED in this study (24%) and almost a third of patients (31%) reported presenting to the ED for an x-ray or scan.

Conclusions

This study has identified regional and socioeconomic differences in the drivers of ED presentations and factors influencing ED attendance in Ireland from the patient perspective. Improved awareness of, and provision of alternative care pathways could potentially decrease ED attendances, which would be important in the context of reducing ED crowding during the COVID-19 pandemic. New strategies for integration of acute care in the community must acknowledge and plan for these issues as a universal approach is unlikely to be implemented successfully due to regional factors.
The importance of chronic conditions for potentially avoidable hospitalizations among non-Hispanic Black and non-Hispanic White older adults in the US: a cross-sectional observational study
Authors: Jørgensen Terese Sara Høj , Allore Heather , Elman Miriam R. , Nagel Corey , Quiñones Ana R.
Published: April 2022

Background

Non-Hispanic (NH) Black older adults experience substantially higher rates of potentially avoidable hospitalization compared to NH White older adults. This study explores the top three chronic conditions preceding hospitalization and potentially avoidable hospitalization among NH White and NH Black Medicare beneficiaries in the United States.

Methods

Data on 4993 individuals (4,420 NH White and 573 NH Black individuals) aged ≥ 65 years from 2014 Medicare claims were linked with sociodemographic data from previous rounds of the Health and Retirement Study. Conditional inference random forests were used to rank the importance of chronic conditions in predicting hospitalization and potentially avoidable hospitalization separately for NH White and NH Black beneficiaries. Multivariable logistic regression with the top three chronic diseases for each outcome adjusted for sociodemographic characteristics were conducted to quantify the associations.

Results

In total, 22.1% of NH White and 24.9% of NH Black beneficiaries had at least one hospitalization during 2014. Among those with hospitalization, 21.3% of NH White and 29.6% of NH Black beneficiaries experienced at least one potentially avoidable hospitalization. For hospitalizations, chronic kidney disease, heart failure, and atrial fibrillation were the top three contributors among NH White beneficiaries and acute myocardial infarction, chronic obstructive pulmonary disease (COPD), and chronic kidney disease were the top three contributors among NH Black beneficiaries. These chronic conditions were associated with increased odds of hospitalization for both groups. For potentially avoidable hospitalizations, asthma, COPD, and heart failure were the top three contributors among NH White beneficiaries and fibromyalgia/chronic pain/fatigue, COPD, and asthma were the top three contributors among NH Black beneficiaries. COPD and heart failure were associated with increased odds of potentially avoidable hospitalization among NH White beneficiaries, whereas only COPD was associated with increased odds of potentially avoidable hospitalizations among NH Black beneficiaries.

Conclusion

Having at least one hospitalization and at least one potentially avoidable hospitalization was more prevalent among NH Black than NH White Medicare beneficiaries. This suggests greater opportunity for increasing prevention efforts among NH Black beneficiaries. The importance of COPD for potentially avoidable hospitalizations further highlights the need to focus on prevention of exacerbations for patients with COPD, possibly through greater access to primary care and continuity of care.
Utilization and costs of epidermal growth factor receptor mutation testing and targeted therapy in Medicare patients with metastatic lung adenocarcinoma
Authors: Shen Chan , Holguin Rolfy A. Perez , Schaefer Eric , Zhou Shouhao , Belani Chandra P. , Ma Patrick C. , Reed Michael F.
Published: April 2022

Background

Guidelines in 2013 and 2014 recommended Epidermal Growth Factor Receptor (EGFR) testing for metastatic lung adenocarcinoma patients as the efficacy of targeted therapies depends on the mutations. However, adherence to these guidelines and the corresponding costs have not been well-studied.

Methods

We identified 2362 patients at least 65 years old newly diagnosed with metastatic lung adenocarcinoma from January 2013 to December 2015 using the SEER-Medicare database. We examined the utilization patterns of EGFR testing and targeted therapies including erlotinib and afatinib. We further examined the costs of both EGFR testing and targeted therapy in terms of Medicare costs and patient out-of-pocket (OOP) costs.

Results

The EGFR testing rate increased from 38% in 2013 to 51% and 49% in 2014 and 2015 respectively. The testing rate was 54% among the 394 patients who received erlotinib, and 52% among the 42 patients who received afatinib. The median Medicare and OOP costs for testing were $1483 and $293. In contrast, the costs for targeted therapy were substantially higher with median 30-day costs at $6114 and $240 for erlotinib and $6239 and $471 for afatinib.

Conclusion

This population-based study suggests that testing guidelines improved the use of EGFR testing, although there was still a large proportion of patients receiving targeted therapy without testing. The costs of targeted therapy were substantially higher than the testing costs, highlighting the need to improve adherence to testing guidelines in order to improve clinical outcomes while reducing the economic burden for both Medicare and patients.
Clinical phenotyping in sarcoidosis using cluster analysis
Authors: Lin Nancy W. , Arbet Jaron , Mroz Margaret M. , Liao Shu-Yi , Restrepo Clara I. , Mayer Annyce S. , Li Li , Barkes Briana Q. , Schrock Sarah , Hamzeh Nabeel , Fingerlin Tasha E. , Carlson Nichole E. , Maier Lisa A.
Published: April 2022

Background

Most phenotyping paradigms in sarcoidosis are based on expert opinion; however, no paradigm has been widely adopted because of the subjectivity in classification. We hypothesized that cluster analysis could be performed on common clinical variables to define more objective sarcoidosis phenotypes.

Methods

We performed a retrospective cohort study of 554 sarcoidosis cases to identify distinct phenotypes of sarcoidosis based on 29 clinical features. Model-based clustering was performed using the VarSelLCM R package and the Integrated Completed Likelihood (ICL) criteria were used to estimate number of clusters. To identify features associated with cluster membership, features were ranked based on variable importance scores from the VarSelLCM model, and additional univariate tests (Fisher’s exact test and one-way ANOVA) were performed using q-values correcting for multiple testing. The Wasfi severity score was also compared between clusters.

Results

Cluster analysis resulted in 6 sarcoidosis phenotypes. Salient characteristics for each cluster are as follows: Phenotype (1) supranormal lung function and majority Scadding stage 2/3; phenotype (2) supranormal lung function and majority Scadding stage 0/1; phenotype (3) normal lung function and split Scadding stages between 0/1 and 2/3; phenotype (4) obstructive lung function and majority Scadding stage 2/3; phenotype (5) restrictive lung function and majority Scadding stage 2/3; phenotype (6) mixed obstructive and restrictive lung function and mostly Scadding stage 4. Although there were differences in the percentages, all Scadding stages were encompassed by all of the phenotypes, except for phenotype 1, in which none were Scadding stage 4. Clusters 4, 5, 6 were significantly more likely to have ever been on immunosuppressive treatment and had higher Wasfi disease severity scores.

Conclusions

Cluster analysis produced 6 sarcoidosis phenotypes that demonstrated less severe and severe phenotypes. Phenotypes 1, 2, 3 have less lung function abnormalities, a lower percentage on immunosuppressive treatment and lower Wasfi severity scores. Phenotypes 4, 5, 6 were characterized by lung function abnormalities, more parenchymal abnormalities, an increased percentage on immunosuppressive treatment and higher Wasfi severity scores. These data support using cluster analysis as an objective and clinically useful way to phenotype sarcoidosis subjects and to empower clinicians to identify those with more severe disease versus those who have less severe disease, independent of Scadding stage.
Engineering cascade biocatalysis in whole cells for bottom-up synthesis of cello-oligosaccharides: flux control over three enzymatic steps enables soluble production
Authors: Schwaiger Katharina N. , Voit Alena , Wiltschi Birgit , Nidetzky Bernd
Published: April 2022

Background

Soluble cello-oligosaccharides (COS, β‐1,4‐D‐gluco‐oligosaccharides with degree of polymerization DP 2–6) have been receiving increased attention in different industrial sectors, from food and feed to cosmetics. Development of large-scale COS applications requires cost-effective technologies for their production. Cascade biocatalysis by the three enzymes sucrose-, cellobiose- and cellodextrin phosphorylase is promising because it enables bottom-up synthesis of COS from expedient substrates such as sucrose and glucose. A whole-cell-derived catalyst that incorporates the required enzyme activities from suitable co-expression would represent an important step towards making the cascade reaction fit for production. Multi-enzyme co-expression to reach distinct activity ratios is challenging in general, but it requires special emphasis for the synthesis of COS. Only a finely tuned balance between formation and elongation of the oligosaccharide precursor cellobiose results in the desired COS.

Results

Here, we show the integration of cellodextrin phosphorylase into a cellobiose-producing whole-cell catalyst. We arranged the co-expression cassettes such that their expression levels were upregulated. The most effective strategy involved a custom vector design that placed the coding sequences for cellobiose phosphorylase (CbP), cellodextrin phosphorylase (CdP) and sucrose phosphorylase (ScP) in a tricistron in the given order. The expression of the tricistron was controlled by the strong T7lacO promoter and strong ribosome binding sites (RBS) for each open reading frame. The resulting whole-cell catalyst achieved a recombinant protein yield of 46% of total intracellular protein in an optimal ScP:CbP:CdP activity ratio of 10:2.9:0.6, yielding an overall activity of 315 U/g dry cell mass. We demonstrated that bioconversion catalyzed by a semi-permeabilized whole-cell catalyst achieved an industrial relevant COS product titer of 125 g/L and a space–time yield of 20 g/L/h. With CbP as the cellobiose providing enzyme, flux into higher oligosaccharides (DP ≥ 6) was prevented and no insoluble products were formed after 6 h of conversion.

Conclusions

A whole-cell catalyst for COS biosynthesis was developed. The coordinated co-expression of the three biosynthesis enzymes balanced the activities of the individual enzymes such that COS production was maximized. With the flux control set to minimize the share of insolubles in the product, the whole-cell synthesis shows a performance with respect to yield, productivity, product concentration and quality that is promising for industrial production.
AdpA, a developmental regulator, promotes ε-poly-l-lysine biosynthesis in Streptomyces albulus
Authors: Huang Rui , Liu Honglu , Zhao Wanwan , Wang Siqi , Wang Shufang , Cai Jun , Yang Chao
Published: April 2022

Background

AdpA is a global regulator of morphological differentiation and secondary metabolism inStreptomyces,but the regulatory roles of theStreptomycesAdpA family on the biosynthesis of the natural product ε-poly-l-lysine (ε-PL) remain unidentified, and few studies have focused on increasing the production of ε-PL by manipulating transcription factors inStreptomyces.

Results

In this study, we revealed the regulatory roles of different AdpA homologs in ε-PL biosynthesis and morphological differentiation and effectively promoted ε-PL production and sporulation inStreptomycesalbulusNK660 by heterologously expressingadpAfromS.neyagawaensisNRRLB-3092 (adpASn). First, we identified a novel AdpA homolog named AdpASainS.albulusNK660 and characterized its function as an activator of ε-PL biosynthesis and morphological differentiation. Subsequently, four heterologous AdpA homologs were selected to investigate their phylogenetic relationships and regulatory roles inS.albulus, and AdpASnwas demonstrated to have the strongest ability to promote both ε-PL production and sporulation among these five AdpA proteins. The ε-PL yield ofS.albulusheterologously expressingadpASnwas approximately 3.6-fold higher than that of the control strain. Finally, we clarified the mechanism of AdpASnin enhancing ε-PL biosynthesis and its effect on ε-PL polymerization degree using real-time quantitative PCR, microscale thermophoresis and MALDI-TOF–MS. AdpASnwas purified, and its seven direct targets,zwf,tal,pyk2,pta,ack,pepcand a transketolase gene (DC74_2409), were identified, suggesting that AdpASnmay cause the redistribution of metabolic flux in central metabolism pathways, which subsequently provides more carbon skeletons and ATP for ε-PL biosynthesis inS.albulus.

Conclusions

Here, we characterized the positive regulatory roles ofStreptomycesAdpA homologs in ε-PL biosynthesis and their effects on morphological differentiation and reported for the first time that AdpASnpromotes ε-PL biosynthesis by affecting the transcription of its target genes in central metabolism pathways. These findings supply valuable insights into the regulatory roles of theStreptomycesAdpA family on ε-PL biosynthesis and morphological differentiation and suggest that AdpASnmay be an effective global regulator for enhanced production of ε-PL and other valuable secondary metabolites inStreptomyces.
The m6A demethylase ALKBH5 promotes tumor progression by inhibiting RIG-I expression and interferon alpha production through the IKKε/TBK1/IRF3 pathway in head and neck squamous cell carcinoma
Authors: Jin Shufang , Li Mingyu , Chang Hanyue , Wang Ruijie , Zhang Zhiyuan , Zhang Jianjun , He Yue , Ma Hailong
Published: April 2022

Background

N6-methyladenosine (m6A) RNA modification plays a critical role in various physiological and pathological conditions. However, the role of m6A modification in head and neck squamous cell carcinoma (HNSCC) remains elusive.

Methods

In this study, the expression of m6A demethylases was detected by HNSCC tissue microarray. m6A-RNA immunoprecipitation (MeRIP) sequencing and RNA sequencing were used to identify downstream targets of ALKBH5. Comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS) was used to explore the m6A “readers”. Tumor-infiltrating lymphocytes were analyzed in SCC7-bearing xenografts in C3H mice.

Results

Here, we demonstrate the downregulation of m6A status and upregulation of two demethylases in HNSCC. Silencing the m6A demethylase alkB homolog 5, RNA demethylase (ALKBH5) suppresses tumor progression in vitro and in vivo. m6A-RNA immunoprecipitation sequencing reveals that ALKBH5 downregulates the m6A modification of DDX58 mRNA. Moreover, RIG-I, encoded by the DDX58 mRNA, reverses the protumorigenic characteristics of ALKBH5. ChIRP-MS demonstrates that HNRNPC binds to the m6A sites of DDX58 mRNA to promote its maturation. ALKBH5 overexpression inhibits RIG-I-mediated IFNα secretion through the IKKε/TBK1/IRF3 pathway. The number of tumor-infiltrating lymphocytes in C3H immunocompetent mice is reduced by ALKBH5 overexpression and restored by IFNα administration. Upregulation of AKLBH5 negatively correlates with RIG-I and IFNα expression in HNSCC patients.

Conclusions

These findings unveil a novel mechanism of immune microenvironment regulation mediated by m6A modification through the ALKBH5/RIG-I/IFNα axis, providing a rationale for therapeutically targeting epitranscriptomic modulators in HNSCC.
Integrative proteomic characterization of trace FFPE samples in early-stage gastrointestinal cancer
Authors: Li Lingling , Liu Hui , Li Yan , Guo Chunmei , Wang Bing , Shen Dan , Zhang Qiao , Ding Chen
Published: April 2022

Background

The surveillance and therapy of early-stage cancer would be better for patients’ prognosis. However, the extreme trace amount of tissue samples in different stages have limited in portraying the characterization of early-stage cancer. Therefore, we focused on and presented comprehensive proteomic and phosphoproproteomic profiling of the trace FFPE samples from early-stage gastrointestinal cancer, and then explored the potential biomarkers of early-stage gastrointestinal cancer.

Methods

In this study, a quantitative proteomic method with chromatography with mass spectrometry (LC-MS/MS) was used to analyse the proteomic difference between the trace early-stage esophageal squamous cell carcinoma (EESCC) and early-stage duodenum adenocarcinoma cancer (EDAC).

Results

We identified ~ 6000 proteins and > 10,000 phosphosites in single trace FFPE samples. Comparative analysis disclosed the diverse proteomic features of tumor tissues compared with paired normal tissue of EESCC and EDAC, and revealed the difference of EESCC and EDAC was derived from their origin normal tissue. The distinct separation of EESCC and EDAC illustrated the functions of cell cycle (RB1 T373, EGFR T693) in EESCC, and the positive impacts of apoptosis, metabolic processes (MTOR and MTOR S1261) in EDAC. Furthermore, we deconvoluted the immune infiltration of early-stage gastrointestinal cancer, in which higher immune cell signatures were detected in EDAC, and showed the specific cytokines in EESCC and EDAC. We performed kinases-substates relationship analysis and elucidated the specific proteomic kinase characterization of EESCC and EDAC, and proposed the medicative effects and corresponding drugs for EESCC and EDAC at the clinic.

Conclusion

We disclosed the specific immune characterization of the early-stage gastrointestinal cancer, and presented potential makers of EESCC (EGFR, PDGFRB, CDK4, WEE1) and EDAC (MTOR, MAP2K1, MAPK3). This study represents a major stepping stone towards investigating the carcinogenesis mechanism of gastrointestinal cancer, and providing a rich resource for medicative strategy in the clinic.

Graphical Abstract
Evaluating machine learning-powered classification algorithms which utilize variants in the GCKR gene to predict metabolic syndrome: Tehran Cardio-metabolic Genetics Study
Authors: Akbarzadeh Mahdi , Alipour Nadia , Moheimani Hamed , Zahedi Asieh Sadat , Hosseini-Esfahani Firoozeh , Lanjanian Hossein , Azizi Fereidoun , Daneshpour Maryam S.
Published: April 2022

Background

Metabolic syndrome (MetS) is a prevalent multifactorial disorder that can increase the risk of developing diabetes, cardiovascular diseases, and cancer. We aimed to compare different machine learning classification methods in predicting metabolic syndrome status as well as identifying influential genetic or environmental risk factors.

Methods

This candidate gene study was conducted on 4756 eligible participants from the Tehran Cardio-metabolic Genetic study (TCGS). We compared predictive models using logistic regression (LR), Random Forest (RF), decision tree (DT), support vector machines (SVM), and discriminant analyses. Demographic and clinical features, as well as variables regarding common GCKR gene polymorphisms, were included in the models. We used a 10-repeated tenfold cross-validation to evaluate model performance.

Results

50.6% of participants had MetS. MetS was significantly associated with age, gender, schooling years, BMI, physical activity, rs780094, and rs780093 (P < 0.05) as indicated by LR. RF showed the best performance overall (AUC-ROC = 0.804, AUC-PR = 0.776, and Accuracy = 0.743) and indicated BMI, physical activity, and age to be the most influential model features. According to the DT, a person with BMI < 24 and physical activity < 8.8 possesses a 4% chance for MetS. In contrast, a person with BMI ≥ 25, physical activity < 2.7, and age ≥ 33, has 77% probability of suffering from MetS.

Conclusion

Our findings indicated that, on average, machine learning models outperformed conventional statistical approaches for patient classification. These well-performing models may be used to develop future support systems that use a variety of data sources to identify persons at high risk of getting MetS.
Personality disorders (PD) and interpersonal violence (IV) during COVID-19 pandemic: a systematic review
Authors: Di Stefano Ramona , Di Pietro Angelica , Talevi Dalila , Rossi Alessandro , Socci Valentina , Pacitti Francesca , Rossi Rodolfo
Published: April 2022

Not only did the ongoing CoronaVIrus Disease-19 (COVID-19) pandemic cause a massive number of casualties, but also there is growing concern that the burden of its psychological aftermaths will only show up years down the road. This systematic review summarises the existing literature reporting the impact of COVID-19 on personality disorders (PDs)-related violence. MEDLINE and APA PsycINFO were independently searched for relevant studies by two authors. Eligible studies had to be identifiable through database searching, published and fully accessible. This systematic review was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. An initial pool of 241 studies were found, out of which 69 met the selection criteria and were, therefore, included. The majority reported a worse Mental Health Outcome (MHO) during the pandemic as related to dysfunctional personality and positive personality traits predicting a better outcome. Furthermore, increased levels of interpersonal violence (IV) and self-directed violence were reported. Further research should be conducted on the reciprocal interaction of PDs and IV during the time of pandemic. Nevertheless, the dramatic impact of restrictive measures on PDs has still to be appropriately addressed.
Root-TRAPR: a modular plant growth device to visualize root development and monitor growth parameters, as applied to an elicitor response of Cannabis sativa
Authors: Suwanchaikasem Pipob , Idnurm Alexander , Selby-Pham Jamie , Walker Robert , Boughton Berin A.
Published: April 2022

Background

Plant growth devices, for example, rhizoponics, rhizoboxes, and ecosystem fabrication (EcoFAB), have been developed to facilitate studies of plant root morphology and plant-microbe interactions in controlled laboratory settings. However, several of these designs are suitable only for studying small model plants such asArabidopsis thalianaandBrachypodium distachyonand therefore require modification to be extended to larger plant species like crop plants. In addition, specific tools and technical skills needed for fabricating these devices may not be available to researchers. Hence, this study aimed to establish an alternative protocol to generate a larger, modular and reusable plant growth device based on different available resources.

Results

Root-TRAPR (Root-Transparent, Reusable, Affordable three-dimensional Printed Rhizo-hydroponic) system was successfully developed. It consists of two main parts, an internal root growth chamber and an external structural frame. The internal root growth chamber comprises a polydimethylsiloxane (PDMS) gasket, microscope slide and acrylic sheet, while the external frame is printed from a three-dimensional (3D) printer and secured with nylon screws. To test the efficiency and applicability of the system, industrial hemp (Cannabis sativa) was grown with or without exposure to chitosan, a well-known plant elicitor used for stimulating plant defense. Plant root morphology was detected in the system, and plant tissues were easily collected and processed to examine plant biological responses. Upon chitosan treatment, chitinase and peroxidase activities increased in root tissues (1.7- and 2.3-fold, respectively) and exudates (7.2- and 21.6-fold, respectively). In addition, root to shoot ratio of phytohormone contents were increased in response to chitosan. Within 2 weeks of observation, hemp plants exhibited dwarf growth in the Root-TRAPR system, easing plant handling and allowing increased replication under limited growing space.

Conclusion

The Root-TRAPR system facilitates the exploration of root morphology and root exudate ofC. sativaunder controlled conditions and at a smaller scale. The device is easy to fabricate and applicable for investigating plant responses toward elicitor challenge. In addition, this fabrication protocol is adaptable to study other plants and can be applied to investigate plant physiology in different biological contexts, such as plant responses against biotic and abiotic stresses.
Disappointment and frustration, but long-term satisfaction: patient experiences undergoing treatment for a chronic Achilles tendon rupture—a qualitative study
Authors: Nordenholm Anna , Nilsson Niklas , Krupic Ferid , Hamrin Senorski Eric , Nilsson Helander Katarina , Westin Olof , Karlsson Jón
Published: April 2022

Background

Delayed treatment of Achilles tendon ruptures is generally due to either misdiagnosis or patient delay. When the treatment is delayed more than 4 weeks, the rupture is defined as “chronic”, and almost always requires more invasive surgery and longer rehabilitation time compared with acute Achilles tendon ruptures. There is insufficient knowledge of patient experiences of sustaining and recovering from a chronic Achilles tendon rupture.

Methods

To evaluate patients’ experiences of suffering a chronic Achilles tendon rupture, semi-structured group interviews were conducted 4–6 years after surgical treatment using a semi-structured interview guide. The data were analyzed using qualitative content analysis described by Graneheim and Lundman.

Results

The experiences of ten patients (65 ± 14 years, 7 males and 3 females) were summarized into four main categories: (1) “The injury”, where the patients described immediate functional impairments, following either traumatic or non-traumatic injury mechanisms that were misinterpreted by themselves or the health-care system; (2) “The diagnosis”, where the patients expressed relief in receiving the diagnosis, but also disappointment and/or frustration related to the prior misdiagnosis and delay; (3) “The treatment”, where the patients expressed high expectations, consistent satisfaction with the surgical treatment, and addressed the importance of the physical therapist having the right expertise; and (4) “The outcomes”, where the patients expressed an overall satisfaction with the long-term outcome and no obvious limitations in physical activity, although some fear of re-injury emerged.

Conclusions

An Achilles tendon rupture can occur during both major and minor trauma and be misinterpreted by both the assessing health-care professional as well as the patient themselves. Surgical treatment and postoperative rehabilitation for chronic Achilles tendon rupture results in overall patient satisfaction in terms of the long-term outcomes. We emphasize the need for increased awareness of the occurrence of Achilles tendon rupture in patients with an atypical patient history.
Fabrication and characterization of PHEMA–gelatin scaffold enriched with graphene oxide for bone tissue engineering
Authors: Tabatabaee Sara , Baheiraei Nafiseh , Salehnia Mojdeh
Published: April 2022

Background

Growing investigations demonstrate that graphene oxide (GO) has an undeniable impact on repairing damaged bone tissue. Moreover, it has been stated in the literatures that poly(2-hydroxyethyl methacrylate) (PHEMA) and gelatin could provide a biocompatible structure.

Methods

In this research, we fabricated a scaffold using freeze-drying method comprised of PHEMA and gelatin, combined with GO. The validation of the successful fabrication of the scaffolds was performed utilizing Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction assay (XRD). The microstructure of the scaffolds was observed using scanning electron microscopy (SEM). The structural properties of the scaffolds including mechanical strength, hydrophilicity, electrical conductivity, and degradation rate were also evaluated. Human bone marrow‐derived mesenchymal stem cells (hBM-MSCs) were used to evaluate the cytotoxicity of the prepared scaffolds. The osteogenic potential of the GO-containing scaffolds was studied by measuring the alkaline phosphatase (ALP) activity after 7, 14, and 21 days cell culturing.

Results

SEM assay showed a porous interconnected scaffold with approximate pore size of 50–300 μm, appropriate for bone regeneration. The increase in GO concentration from 0.25 to 0.75% w/v exhibited a significant improvement in scaffolds compressive modulus from 9.03 ± 0.36 to 42.82 ± 1.63 MPa. Conventional four-probe analysis confirmed the electrical conductivity of the scaffolds in the semiconductor range. The degradation rate of the samples appeared to be in compliance with bone healing process. The scaffolds exhibited no cytotoxicity using MTT assay against hBM-MSCs. ALP analysis indicated that the PHEMA–Gel–GO scaffolds could efficiently cause the differentiation of hBM-MSCs into osteoblasts after 21 days, even without the addition of the osteogenic differentiation medium.

Conclusion

Based on the results of this research, it can be stated that the PHEMA–Gel–GO composition is a promising platform for bone tissue engineering.
Physician vaccination practices in mild to moderate inborn errors of immunity and retrospective review of vaccine completeness in IEI: results from the Canadian Immunization Research Network
Authors: Suresh Sneha , Zafack Joseline , Pham-Huy Anne , Derfalvi Beata , Sadarangani Manish , McConnell Athena , Tapiéro Bruce , Halperin Scott A. , De Serres Gaston , M Pernica Jeffrey , Top Karina A.
Published: April 2022

Background and objectives

Safety and effectiveness concerns may preclude physicians from recommending vaccination in mild/moderate inborn errors of immunity (IEI). This study describes attitudes and practices regarding vaccination among physicians who care for patients with mild/moderate B cell or mild/moderate combined immunodeficiencies (CID) and vaccination completeness among patients diagnosed with IEIs.

Methods

Canadian physicians caring for children with IEI were surveyed about attitudes and practices regarding vaccination in mild/moderate IEI. Following informed consent, immunization records of pediatric patients with IEI evaluated before 7 years of age were reviewed. Vaccine completeness was defined at age 2 years as 4 doses of diphtheria-tetanus-pertussis (DTaP), 3 doses pneumococcal conjugate (PCV), and 1 dose measles-mumps-rubella (MMR) vaccines. At 7 years 5 doses of DTP and 2 doses MMR were required.

Results

Forty-five physicians from 8 provinces completed the survey. Most recommended inactivated vaccines for B cell deficiency: (84% (38/45) and CID (73% (33/45). Fewer recommended live attenuated vaccines (B cell: 53% (24/45), CID 31% (14/45)). Of 96 patients with IEI recruited across 7 centers, vaccination completeness at age 2 was 25/43 (58%) for predominantly antibody, 3/13 (23%) for CID, 7/35 (20%) for CID with syndromic features, and 4/4 (100%) for innate/phagocyte defects. Completeness at age 7 was 15%, 17%, 5%, and 33%, respectively.

Conclusion

Most physicians surveyed recommended inactivated vaccines in children with mild to moderate IEI. Vaccine completeness for all IEI was low, particularly at age 7. Further studies should address the reasons for low vaccine uptake among children with IEI and whether those with mild-moderate IEI, where vaccination is recommended, eventually receive all indicated vaccines.
Sensitisation to Imbrasia belina (mopane worm) and other local allergens in rural Gwanda district of Zimbabwe
Authors: Ndlovu Vuyelwa , Chimbari Moses , Ndarukwa Pisirai , Sibanda Elopy
Published: April 2022

Background

The prevalence of allergic diseases is increasing in Zimbabwe and the data relate to local as well as exotic allergen sources. As entomophagy, the practice of eating insects, is a recognised source of local allergens, we sought to measure the prevalence of and risk factors for sensitisation to Imbrasia belina (mopane worm), a popular edible insect. This was investigated alongside other locally relevant allergens in a rural community in Gwanda district, south of Zimbabwe.

Methods

A cross sectional study was conducted among 496 adults and children aged 10 years and above in Gwanda district, a mopane worm harvesting area in Zimbabwe. Data on individual characteristics and mopane worm exposure factors were collected using questionnaires. Sensitivity to allergens was assessed by performing skin prick tests at a local clinic using 10 different commercial allergen extracts (Stallergenes, France) and in-house extracts of mopane worm (Imbrasia belina) and mopane leaves (Colophospermum mopane). Data were analysed using Stata version 13 software.

Results

The prevalence of sensitisation to at least one allergen was 31.17% (n = 144). The prevalence of atopy was higher in adults (33.33%) than in children (23.53%) (p = 0.059). The commonest inhalant allergen sources were mopane worm (14.29%), Tyrophagus putrescentiae (14.29%), mopane leaves (13.42%), Alternaria alternata (6.49%) and Dermatophagoides pteronyssinus (6.49%). Polysensitisation was demonstrated in the study population and of the 108 participants (75%) who were sensitised to two or more allergens, 66 (61%) were women. Sensitisation to mopane worm and mopane leaves often clustered with Tyrophagus putrescentiae amongst adults. Adjusted logistic regression analyses between mopane worm sensitisation and self-reported exposure variables showed that sensitisation was more likely amongst mopane worm harvesters (OR = 1.92, 95%CI = 0.77–4.79), those who cooked or roasted mopane worms during harvesting (OR = 2.69, 95%CI = 0.78–9.31) and harvesting without personal protective equipment (PPE) (OR = 2.12, 95%CI = 0.83–5.44) compared to non-harvesters.

Conclusion

Atopic sensitization was common in this mopane worm harvesting community in Gwanda district of Zimbabwe. There was frequent co-sensitisation of mopane worm and mopane leaves with Tyrophagus putrescentiae in children and adults. It is important to determine the clinical relevance of our findings, particularly relating to mopane worm sensitisation.