bluuebunny/crossref_metadata_2025_split huggingface dataset:
Findings from precision oncology in the clinic: rare, novel variants are a significant contributor to scaling molecular diagnostics
Authors: Doig Kenneth D. , Love Christopher G. , Conway Thomas , Seleznev Andrei , Ma David , Fellowes Andrew , Blombery Piers , Fox Stephen B. 
Published: March 2022

Abstract
Background
Next generation sequencing for oncology patient management is now routine in clinical pathology laboratories. Although wet lab, sequencing and pipeline tasks are largely automated, the analysis of variants for clinical reporting remains largely a manual task. The increasing volume of sequencing data and the limited availability of genetic experts to analyse and report on variants in the data is a key scalability limit for molecular diagnostics.

Method
To determine the impact and size of the issue, we examined the longitudinally compiled genetic variants from 48,036 cancer patients over a six year period in a large cancer hospital from ten targeted cancer panel tests in germline, solid tumour and haematology contexts using hybridization capture and amplicon assays. This testing generated 24,168,398 sequenced variants of which 23,255 (8214 unique) were clinically reported.

Results
Of the reported variants, 17,240 (74.1%) were identified in more than one assay which allowed curated variant data to be reused in later reports. The remainder, 6015 (25.9%) were not subsequently seen in later assays and did not provide any reuse benefit. The number of new variants requiring curation has significantly increased over time from 1.72 to 3.73 variants per sample (292 curated variants per month). Analysis of the 23,255 variants reported, showed 28.6% (n = 2356) were not present in common public variant resources and therefore required de novo curation. These in-house only variants were enriched for indels, tumour suppressor genes and from solid tumour assays.

Conclusion
This analysis highlights the significant percentage of variants not present within common public variant resources and the level of non-recurrent variants that consequently require greater curation effort. Many of these variants are unique to a single patient and unlikely to appear in other patients reflecting the personalised nature of cancer genomics. This study depicts the real-world situation for pathology laboratories faced with curating increasing numbers of low-recurrence variants while needing to expedite the process of manual variant curation. In the absence of suitably accurate automated methods, new approaches are needed to scale oncology diagnostics for future genetic testing volumes.
Evaluation of the association between maternal folic acid supplementation and the risk of congenital heart disease: a systematic review and meta-analysis
Authors: Cheng Zhengpei , Gu Rui , Lian Zenglin , Gu Harvest F. 
Published: March 2022

AbstractBackgroundFolic acid (FA), as a synthetic form of folate, has been widely used for dietary supplementation in pregnant women. The preventive effect of FA supplementation on the occurrence and recurrence of fetal neural tube defects (NTD) has been confirmed. Incidence of congenital heart diseases (CHD), however, has been parallelly increasing worldwide. The present study aimed to evaluate whether FA supplementation is associated with a decreased risk of CHD.MethodsWe searched the literature using PubMed, Web of Science and Google Scholar, for the peer-reviewed studies which reported CHD and FA and followed with a meta-analysis. The study-specific relative risks were used as summary statistics for the association between maternal FA supplementation and CHD risk. Cochran'sQandI2statistics were used to test for the heterogeneity.ResultsMaternal FA supplementation was found to be associated with a decreased risk of CHD (OR = 0.82, 95% CI: 0.72–0.94). However, the heterogeneity of the association was high (P < 0.001,I2 = 92.7%). FA supplementation within 1 month before and after pregnancy correlated positively with CHD (OR 1.10, 95%CI 0.99–1.23), and high-dose FA intake is positively associated with atrial septal defect (OR 1.23, 95%CI 0.64–2.34). Pregnant women with irrational FA use may be at increased risk for CHD.ConclusionsData from the present study indicate that the heterogeneity of the association between maternal FA supplementation and CHD is high and suggest that the real relationship between maternal FA supplementation and CHD may need to be further investigated with well-designed clinical studies and biological experiments.
The political economy of health financing reforms in Zimbabwe: a scoping review
Authors: Mhazo Alison T. , Maponga Charles C. 
Published: March 2022

Abstract
Background
Implementation of health financing reforms for Universal Health Coverage (UHC) is inherently political. Despite the political determinants of UHC, health financing reform in Zimbabwe is often portrayed as a technical exercise with a familiar path of a thorough diagnosis of technical gaps followed by detailed prescriptions of reform priorities. In this study, we sought to understand the interaction between political and economic aspects of health financing reforms since the country got its independence in 1980.

Methods
We conducted a scoping review of health financing reforms in Zimbabwe and reviewed 84 relevant sources of information. We then conducted a thematic analysis using an adapted Fox and Reich’s framework of ideas and ideologies, interests and institutions.

Results
We found that ideas, institutions and interests significantly influence health financing reforms in Zimbabwe with implications on health system performance. Reform priorities of the 1980s were influenced by socialist ideologies with an interest to address pervasive health inequities inherited from the colonial racial system. The progress in equity realized in the 1980s was severely disrupted from the 1990s partly due to neo-liberal ideologies which steered interests towards market-oriented reforms. The period from the 2000s is characterized by increasing donor influence on health financing and a cumulative socio-economic collapse that resulted in a sharp and protracted decline in health spending and widening of health inequities.

Conclusion
Health financing reform process in Zimbabwe is heavily influenced by political economy characteristics which favor certain financing arrangements over others with profound implications on health system performance. We concluded that the political economy factors that slow down UHC reforms are not rooted in the ambiguities of ideas on what needs to be done. Instead, the missing link is how to move from intention to action by aligning espoused ideas with interests and institutions which is an inherently political and redistributive process. International and domestic actors involved in UHC in Zimbabwe need to explicitly consider the politics of health financing reforms to improve the implementation feasibility of desired reforms.
Priorities for research on environment, climate and health, a European perspective
Authors: Drakvik Elina , Kogevinas Manolis , Bergman Åke , Devouge Anais , Barouki Robert ,   on behalf of the HERA (Health and Environment Research Agenda) Consortium, Barouki Robert , Kogevinas Manolis , Bergman Åke , Drakvik Elina , Devouge Anaïs , Sarigiannis Denis , Destoumieux-Garzón Delphine , Matthies-Wiesler Franziska , Peters Annette , Zalko Daniel , Villanueva Cristina , Tonne Cathryn , Cardis Elisabeth , Diago-Navarro Elizabeth , Antó Josep M. , Foraster Maria , Nieuwenhuijsen Mark , Straif Kurt , van Veldhoven Karin , Belesova Kristine , Pearce Neil , Haines Andy , Klánová Jana , Šebková Kateřina , Pokorný Lukáš , Hilscherová Klára , Boekhold Sandra , Staatsen Brigit , van der Vliet Nina , Furman Eeva , Paloniemi Riikka , Rekola Aino , Aulake Marianne , Byers Vivienne , Gilmer Alan , Huss Anke , Vermeulen Roel , Slama Rémy , Samson Michel , Albin Maria , Grönlund Åke , Garric Jeanne 
Published: March 2022

AbstractClimate change, urbanisation, chemical pollution and disruption of ecosystems, including biodiversity loss, affect our health and wellbeing. Research is crucial to be able to respond to the current and future challenges that are often complex and interconnected by nature. The HERA Agenda, summarised in this commentary, identifies six thematic research goals in the environment, climate and health fields. These include research to 1) reduce the effects of climate change and biodiversity loss on health and environment, 2) promote healthy lives in cities and communities, 3) eliminate harmful chemical exposures, 4) improve health impact assessment and implementation research, 5) develop infrastructures, technologies and human resources and 6) promote research on transformational change towards sustainability. Numerous specific recommendations for research topics, i.e., specific research goals, are presented under each major research goal. Several methods were used to define the priorities, including web-based surveys targeting researchers and stakeholder groups as well as a series of online and face-to-face workshops, involving hundreds of researchers and other stakeholders. The results call for an unprecedented effort to support a better understanding of the causes, interlinkages and impacts of environmental stressors on health and the environment. This will require breakdown of silos within policies, research, actors as well as in our institutional arrangements in order to enable more holistic approaches and solutions to emerge. The HERA project has developed a unique and exciting opportunity in Europe to consensuate priorities in research and strengthen research that has direct societal impact.
Dermatology workforce over a decade in Saudi Arabia: demographics, distributions, and future challenges
Authors: Alfawzan Abdulrahman , Altalhab Saad , Alkhowailed Mohammad 
Published: March 2022

AbstractBackgroundThe dermatology workforce is an important topic, as many countries are facing an undersupply of dermatologists, while some are expecting a surplus. Therefore, we conducted this study to identify the current dermatology workforce demographics in Saudi Arabia (SA) and the changes in such demographics over the last 10 years to identify future workforce-related challenges.MethodsThis study was conducted in SA, and it included all the practicing dermatologists in the country over the last decade (2010–2020). The number of practicing dermatologists, their gender, their nationality, and dermatology residency candidates and graduates were obtained from the Saudi Commission for Health Specialties (SCFHS). The geographic distribution of dermatologists was obtained from the Ministry of Health Statistical Yearbook 2018.ResultsAs of September 2020, there were 2678 practicing dermatologists in SA at a ratio of 7.82 dermatologists per 100 000 people. Of the 2678 dermatologists, only 24.8% were Saudis. The Saudi dermatologist ratio has been almost constant over 10 years, ranging from 1.3 to 1.9 per 100 000 people. Of all Saudi dermatologists, 42% were female. The number of residents who graduated from the residency program was not consistent for each year and ranged from 4 to 25. The number of dermatologists varied by region, with 9.2 in Riyadh and 3.4 in Najran per 100 000 people.ConclusionsThe results of our study revealed that a quarter of dermatologists in SA are Saudis. In addition, the number of non-Saudi dermatologists has increased in the last 10 years, while the number of Saudi dermatologists to the population has remained almost constant. There is also a geographic maldistribution of dermatologists, with urban areas having a higher number of dermatologists than rural areas. We encourage local studies that can elucidate the factors influencing the workforce, such as the dermatologist appointment waiting time, dermatologists’ working hours, and the geographic maldistribution of dermatologists in the country.
An NF-κB/OVOL2 circuit regulates glucose import and cell survival in non-small cell lung cancer
Authors: Zhang Rui , Geng Guo-Jun , Guo Jian-Guang , Mi Yan-Jun , Zhu Xiao-Lei , Li Ning , Liu Hong-Ming , Lin Jun-Feng , Wang Jian-Weng , Zhao Guang , Ye Guan-Zhi , Li Bo-An , Luo Qi-Cong , Jiang Jie 
Published: March 2022

Abstract
Background
Tumor cells tend to utilize glycolysis rather than aerobic respiration even under aerobic conditions. OVOL2, an inhibitory C2H2 zinc finger transcription factor, is a potential tumor suppressor in cancers. However, the association between OVOL2 and tumor energy metabolism is unknown.

Methods
Western blotting was used to determine the expression of OVOL2 in different non-small cell lung cancer (NSCLC) cell lines and mouse models. The metabolic parameters in NSCLC cells following overexpression or knockdown OVOL2 were examined. To define the mechanism by which OVOL2 regulates aerobic glycolysis, interacting protein of OVOl2 and downstream molecular events were identified by luciferase assay and co-immunoprecipitation. We documented the regulatory mechanism in mouse xenograft models. Finally, clinical relevance of OVOL2, NF-κB signaling and GLUT1 was measured by immunostaining.

Results
OVOL2 is downregulated in NSCLC and overexpression of OVOL2 inhibits the survival of cancer cells. Moreover, OVOL2 directly binds to P65 and inhibits the recruitment of P300 but facilitates the binding of HDAC1 to P65, which in turn negatively regulates NF-κB signaling to suppress GLUT1 translocation and glucose import. In contrast, OVOL2 expression is negatively regulated by NF-κB signaling in NSCLC cells via the ubiquitin–proteasome pathway. Re-expression of OVOL2 significantly compromise NF-κB signaling-induced GLUT1 translocation, aerobic glycolysis in NSCLC cells and mouse models. Immunostaining revealed inverse correlations between the OVOL2 and phosphorylated P65 levels and between the OVOL2 and membrane GLUT1 levels, and a strong correlation between the phosphorylated P65 and membrane GLUT1 levels.

Conclusions
These results suggest a regulatory circuit linking NF-κB and OVOL2, which highlights the role of NF-κB signaling and OVOL2 in the modulation of glucose metabolism in NSCLC.
Evaluation of a Type 2 diabetes risk reduction online program for women with recent gestational diabetes: a randomised trial
Authors: Taylor Rachael , Rollo Megan E. , Baldwin Jennifer N. , Hutchesson Melinda , Aguiar Elroy J. , Wynne Katie , Young Ashley , Callister Robin , Collins Clare E. 
Published: March 2022

Abstract
Background
To evaluate the preliminary efficacy, feasibility and acceptability of the 3-month Body Balance Beyond (BBB) online program among Australian women with overweight/obesity and recent gestational diabetes mellitus.

Methods
Women were  randomised into either: 1) High Personalisation (HP) (access to ‘BBB’ website, video coaching sessions, text message support); 2) Medium Personalisation (MP) (website and text message support); or 3) Low Personalisation (LP) (website only). Generalised linear mixed models were used to evaluate preliminary efficacy, weight, diet quality, physical activity levels, self-efficacy and quality of life (QoL) at baseline and 3-months. Feasibility was assessed by recruitment and retention metrics and acceptability determined via online process evaluation survey at 3-months.

Results
Eighty three women were randomised, with 76 completing the study. Self-efficacy scores showed significant improvements in confidence to resist eating in a variety of situations from baseline to 3-months in HP compared to MP and LP groups (P=.03). The difference in mean QoL scores favoured the HP compared to MP and LP groups (P=.03). Half of the women (HP n=17[81%], MP n=12[75%], LP n=9[56%]) lost weight at 3-months. No significant group-by-time effect were reported for other outcomes. Two-thirds of women in the HP group were satisfied with the program overall and 86% would recommend it to others, compared with 25% and 44% in the MP group, and 14% and 36% in the LP group, respectively.

Conclusions
Video coaching sessions were associated with improvements in QoL scores and self-efficacy, however further refinement of the BBB website and text messages support could improve program acceptability.

Trial registration
Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12619000162112, registered 5 February 2019.
Predicting the number of COVID-19 infections and deaths in USA
Authors: Ebubeogu Amarachukwu Felix , Ozigbu Chamberline Ekene , Maswadi Kholoud , Seixas Azizi , Ofem Paulinus , Conserve Donaldson F. 
Published: March 2022

Abstract
Background
Uncertainties surrounding the 2019 novel coronavirus (COVID-19) remain a major global health challenge and requires attention. Researchers and medical experts have made remarkable efforts to reduce the number of cases and prevent future outbreaks through vaccines and other measures. However, there is little evidence on how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection entropy can be applied in predicting the possible number of infections and deaths. In addition, more studies on how the COVID-19 infection density contributes to the rise in infections are needed. This study demonstrates how the SARS-COV-2 daily infection entropy can be applied in predicting the number of infections within a given period. In addition, the infection density within a given population attributes to an increase in the number of COVID-19 cases and, consequently, the new variants.

Results
Using the COVID-19 initial data reported by Johns Hopkins University, World Health Organization (WHO) and Global Initiative on Sharing All Influenza Data (GISAID), the result shows that the original SAR-COV-2 strain has R0<1 with an initial infection growth rate entropy of 9.11 bits for the United States (U.S.). At close proximity, the average infection time for an infected individual to infect others within a susceptible population is approximately 7 minutes. Assuming no vaccines were available, in the U.S., the number of infections could range between 41,220,199 and 82,440,398 in late March 2022 with approximately, 1,211,036 deaths. However, with the available vaccines, nearly 48 Million COVID-19 cases and 706, 437 deaths have been prevented.

Conclusion
The proposed technique will contribute to the ongoing investigation of the COVID-19 pandemic and a blueprint to address the uncertainties surrounding the pandemic.
Subaxial lordosis loss and influence factors after posterior atlantoaxial fusion
Authors: Liu Shaoqiang , Liu Boling , Liang Guiqing , Chen Qiyong , Wang Huafeng , Lin Yuhan 
Published: March 2022

Abstract
Summary of background data
Cervical sagittal balance is an important evaluation index of cervical physiological function and surgical efficacy. Subaxial kyphosis after atlantoaxial fusion is negatively associated with worse clinical outcomes and higher incidence of lower cervical disk degeneration.

Objectives
This study aimed to confirm the factors that influence subaxial lordosis loss after posterior atlantoaxial fusion.

Methods
We performed a retrospective review of all patients following posterior C1–C2 fusion for atlantoaxial dislocation between January 2015 and December 2017. All charts, records, and imaging studies were reviewed for each case, and preoperative, immediate postoperative, and final follow-up plain films were evaluated. Comparing final follow-up and preoperative C2–C7 angle, patients were divided into two groups for further comparison: subaxial lordosis loss group and subaxial lordosis increase group.

Results
A total of 18 patients were included in the review, with an average radiographic follow-up of 8.4 ± 3.7 months (range 6–17 months). Subaxial lordosis loss was observed in 5 cases (27.8%) at the final follow-up, whereas 13 cases had an increase in subaxial lordosis. The cervical sagittal parameters of preoperative and final follow-up between two groups were compared, the preoperative C2–C7 angle of the subaxial lordosis loss group was bigger than the subaxial lordosis increase group (27.6° ± 10.5° vs 10.5° ± 10.5°, P < 0.05), but there was no statistical difference in other parameters. Univariate chi-square analysis showed that reduction in subaxial lordosis after posterior atlantoaxial fusion was associated with preoperative C2–C7 angle ≥ 20° (χ2 = 4.923, P = 0.026). However, Logistic regression analysis showed that the preoperative C2–C7 angle ≥ 20° was not an independent risk factor (OR = 0.147, P = 0.225).

Conclusion
Our study demonstrates that subaxial lordosis loss may occur after posterior atlantoaxial fusion, and preoperative C2–C7 angle ≥ 20° was a risk factor of postoperative loss of subaxial lordosis.
Heartmate 3 as a bridge to heart transplantation in a patient with congenitally corrected transposition of the great arteries: a case report
Authors: Barac Yaron D. , Ben-Avraham Ben , Hamdan Ashraf , Hirsch Rafael , Ben-Gal Tuvia , Aravot Danny 
Published: March 2022

Abstract
Background
We report the first use of Heartmate 3 (HM3) in a Congenitally corrected Transposition of the Great Arteries (ccTGA) as a Systemic Ventricular Assist Device (SVAD) to treat HF.

Case presentation
A 55 years old man with a Congenitally corrected Transposition of the Great Arteries (ccTGA) a rare condition in which Heart Failure (HF) is a common presentation in adult life and survival without heart transplantation is hardly an option. Systemic Ventricular Assist Device (SVAD) can be an option if an organ does not become available. We present the first ever implantation of HM3 LVAD (Abbott Inc, Chicago IL) implanted to this patient as a bridge to transplantation, demonstrating the safety and feasibility of the procedure. Due to the unique mediastinal configuration, 3D cardiac CT reconstruction should be used for planning the procedure—intra ventricular placement of the inflow as well as mediastinal placemat of the outflow and pump.

Conclusions
This successful first use of HM3 as a SVAD for ccTGA patients, opens a novel treatment option for these patients as a bridge for heart transplant or as definitive treatment.
Developing a post-discharge suicide prevention intervention for children and young people: a qualitative study of integrating the lived-experience of young people, their carers, and mental health clinicians
Authors: Watling David P. , Preece Megan H. W. , Hawgood Jacinta , Bloomfield Sharyn , Kõlves Kairi 
Published: March 2022

AbstractBackgroundSuicide in young people is a leading cause of death. Interventions that are reflexive, tailored, and developed in concert with this at-risk population are needed. This study aimed to integrate lived-experience into the design of a suicide prevention intervention delivered by phone to young people post-discharge from an emergency department (ED) for suicide risk or self-harm.MethodsQualitative study was conducted at the Queensland Children’s Hospital, Brisbane Australia. Four focus groups with young people with lived-experience, parents or carers and ED mental health clinicals were conducted. In total 5 young people with lived-experience of suicidality (17–21 years,Mage = 19.20), 3 parents and carers with a lived-experience of caring for a young person with mental illness, and 10 ED mental health clinicians participated in focus groups. Thefirst phaseof qualitative analysis involved a phenomenological analysis andsecond phaseincluded a deductive content analysis. The paper is following the Consolidated Criteria for Reporting Qualitative Research.ResultsFirst phase, a phenomenological analysis identified three foundational themes to structure future follow-up phone interventions: a person-centred focus, the phone-call dynamic, and the phone-call purpose. Second phase, a deductive content analysis found that participants preferred an intervention that was structured, consistent, and finite. Moreover, an intervention that was authentic, able to facilitate and empower growing independence, and achievable of young people after an ED presentation was desired.ConclusionsParticipants expressed their desire for a responsive, structured, and clearly focused phone call that would recognise the young person and parent/carer’s needs while providing tailored support to ease transition from the ED to available community and family led care.