bluuebunny/crossref_metadata_2025_split huggingface dataset:
A qualitative interview study of Australian physicians on defensive practice and low value care: “it’s easier to talk about our fear of lawyers than to talk about our fear of looking bad in front of each other”
Authors: Ries Nola M. , Johnston Briony , Jansen Jesse 
Published: March 2022

AbstractBackgroundDefensive practice occurs when physicians provide services, such as tests, treatments and referrals, mainly to reduce their perceived legal or reputational risks, rather than to advance patient care. This behaviour is counter to physicians’ ethical responsibilities, yet is widely reported in surveys of doctors in various countries. There is a lack of qualitative research on the drivers of defensive practice, which is needed to inform strategies to prevent this ethically problematic behaviour.MethodsA qualitative interview study investigated the views and experiences of physicians in Australia on defensive practice and its contribution to low value care. Interviewees were recruited based on interest in medico-legal issues or experience in a health service involved in ‘Choosing Wisely’ initiatives. Semi-structured interviews averaged 60 min in length. Data were coded using the Theoretical Domains Framework, which encapsulates theories of behaviour and behaviour change.ResultsAll participants (n = 17) perceived defensive practice as a problem and a contributor to low value care. Behavioural drivers of defensive practice spanned seven domains in the TDF: knowledge, focused on inadequate knowledge of the law and the risks of low value care; skills, emphasising patient communication and clinical decision-making skills; professional role and identity, particularly clinicians’ perception of patient expectations and concern for their professional reputation; beliefs about consequences, especially perceptions of the beneficial and harmful consequences of defensive practice; environmental context and resources, including processes for handling patient complaints; social influences, focused on group norms that encourage or discourage defensive behaviour; and emotions, especially fear of missing a diagnosis. Overall, defensive practice is motivated by physicians’ desire to avoid criticism or scrutiny from a range of sources, and censure from their professional peers can be a more potent driver than perceived legal consequences.ConclusionsThe findings call for strengthening knowledge and skills, for example, to improve clinicians’ understanding of the law and their awareness of the risks of low value care and using effective communication strategies with patients. Importantly, supportive cultures of practice and organisational environments are needed to create conditions in which clinicians feel confident in avoiding defensive practice and other forms of low value care.
Perceptions on using surplus embryos for the treatment of Parkinson’s disease among the Swedish population: a qualitative study
Authors: Grauman Åsa , Drevin Jennifer 
Published: March 2022

Abstract
Background
Human embryonic stem cells are currently used for developing treatment against Parkinson’s disease (PD). However, the use of ES cells is surrounded with moral concerns. Research regarding the public's attitudes can form an important basis for policymaking. The aim was to explore the perceptions of the public on using donated human embryos for developing treatment of Parkinson’s Disease.

Methods
Semi-structured individual qualitative interviews were conducted with 11 members of the general population in Sweden. Interviews were analyzed with thematic content analyses.

Results
Four categories and additional sub-categories; Different views on the embryo requires delicacy, Using embryos to treat Parkinson’s disease, Doing things in the right way, and Communication, media, and public opinion. In general, respondents were positive towards the usage of embryotic stem cells to treat PD, but the usage were conditioned and specific terms were demanded. Informed consent from both donors were required and delicacy and sensitivity when working with embryos were needed.

Conclusions
It was perceived better to use surplus embryos to treat PD increase is than to discard them, also among those who perceived the embryo as “a potential life.” The participants raised several conditions under usage for treatment should be allowed. Even if the embryos otherwise are going to be discarded, usage requires informed consent from the donating couples.
Design and evaluation of a mobile-based nutrition education application for infertile women in Iran
Authors: Langarizadeh Mostafa , Fatemi Aghda Seyed Ali , Nadjarzadeh Azadeh 
Published: March 2022

Abstract
Background
The prevalence of infertility in Iran is higher than the world average. Furthermorte, education and nutrition are among the effective factors in improving the quality of life of women with infertility. According to the significant role of smartphones in people's lives as well as health education, the present study aimed to design and evaluate a mobile-based nutrition education application for infertile women.

Methods
This quantitative research was conducted in two stages. Initially, the educational contents were determined based on a review of the literature. Later, the obtained contents were given to 10 nutritionists and five infertility specialists to determine the necessity of each item. In the next stage, the application prototype was designed based on the results of the first stage and distributed among 220 infertile women. After two months, the Questionnaire of User Interface Satisfaction was administrated to assess the usability of the developed application. The results were analyzed via SPSS software version 20.

Results
According to the nutritionists and infertility specialists, the contents determined for the nutrition educational application were categorized under three general sections of user's demographic data, educational contents, required capabilities. The users' mean score of the application usability was calculated as 7.44 out of 9 indicating a good level of satisfaction.

Conclusions
Nutrition education of women with infertility problems can play a significant role in improving their awareness and treatment outcomes. Due to the increasing use of smartphones, designing a mobile-based nutrition educational application can be of great benefit for women with infertility according to the cultural conditions and characteristics of each community.
Venous thromboembolism risk assessment of surgical patients in Southwest China using real-world data: establishment and evaluation of an improved venous thromboembolism risk model
Authors: Wang Peng , Wang Yao , Yuan Zhaoying , Wang Fei , Wang Hongqian , Li Ying , Wang Chengliang , Li Linfeng 
Published: March 2022

Abstract
Background
Venous thromboembolism (VTE) risk assessment in surgical patients is important for the appropriate diagnosis and treatment of patients. The commonly used Caprini model is limited by its inadequate ability to discriminate between risk stratums on the surgical population in southwest China and lengthy risk factors. The purpose of this study was to establish an improved VTE risk assessment model that is accurate and simple.

Methods
This study is based on the clinical data from 81,505 surgical patients hospitalized in the Southwest Hospital of China between January 1, 2019 and June 18, 2021. Among the population, 559 patients developed VTE. An improved VTE risk assessment model, SW-model, was established through Logistic Regression, with comparisons to both Caprini and Random Forest.

Results
The SW-model incorporated eight risk factors. The area under the curve (AUC) of SW-model (0.807 [0.758, 0.853], 0.804 [0.765, 0.840]), are significantly superior (p = 0.001 and p = 0.044) to those of the Caprini (0.705 [0.652, 0.757], 0.758 [0.719, 0795]) on two test sets, but inferior (p < 0.001 and p = 0.002) to Random Forest (0.854 [0.814, 0.890], 0.839 [0.806, 0.868]). In decision curve analysis, within threshold range from 0.015 to 0.04, the DCA curves of the SW-model are superior to Caprini and two default strategies.

Conclusions
The SW-model demonstrated a higher discriminative capability to distinguish VTE positive in surgical patients compared with the Caprini model. Compared to Random Forest, Logistic Regression based SW-model provided interpretability which is essential in guarantee the procedure of risk assessment transparent to clinicians.
A stepped-wedge randomized trial investigating the effect of the Leadership and Organizational Change for Implementation (LOCI) intervention on implementation and transformational leadership, and implementation climate
Authors: Skar Ane-Marthe Solheim , Braathu Nora , Peters Nadina , Bækkelund Harald , Endsjø Mathilde , Babaii Aida , Borge Randi Hovden , Wentzel-Larsen Tore , Ehrhart Mark G. , Sklar Marisa , Brown C. Hendricks , Aarons Gregory A. , Egeland Karina M. 
Published: March 2022

AbstractBackgroundThis study evaluates the Leadership and Organizational Change for Implementation (LOCI) strategy and its effect on implementation leadership, transformational leadership, and implementation climate.MethodsA stepped wedge cluster randomized study design enrolling 47 first-level leaders from child- and adult-specialized mental health clinics within Norwegian health trusts across three cohorts. All therapists (n = 790) received training in screening of trauma exposure and posttraumatic stress, and a subgroup of therapists (n = 248) received training in evidence-based treatment methods for posttraumatic stress disorder (PTSD). First-level leaders and therapists completed surveys at baseline, 4, 8-, 12-, 16-, and 20-months assessing leadership and implementation climate. General linear mixed-effects models were used to investigate whether the LOCI strategy would lead to greater therapist-rated scores on implementation leadership, transformational leadership, and implementation climate.ResultsAfter introducing the LOCI strategy, there was a significant increase in therapist-rated implementation and transformational leadership and implementation climate. The increase was sustained at all measurement time points compared to non-LOCI conditions, which demonstrated a steady decrease in scores before LOCI.ConclusionsThe LOCI strategy can develop better transformational and implementation leadership skills and contribute to a more positive implementation climate, which may enhance successful EBP implementation. Thus, LOCI can help leaders create an organizational context conducive for effective EBP implementation.Trial registrationRetrospectively registered: ClinicalTrialsNCT03719651, 25th of October 2018.The trial protocol can be accessed fromhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417075/.
Li–Fraumeni syndrome in Tunisian carriers with different and rare tumor phenotype: genotype–phenotype correlation
Authors: Sassi Hela , Meddeb Rym , Cherif Mohamed Aziz , Nasr Chiraz , Riahi Aouatef , Hannachi Samia , Belguith Neila , M’rad Ridha 
Published: March 2022

Abstract
Background
Li–Fraumeni syndrome (LFS) is a rare autosomal hereditary predisposition to multiples cancers, mainly affecting young individuals. It is characterized by a broad tumor spectrum. To our best knowledge, only one Tunisian study with a confirmed LFS was published.

Methods
Our study focused on the clinical, histopathological and genetic results of two patients with rare tumor phenotype and tried to establish genotype–phenotype correlation. The clinical diagnosis was based on Chompret-Bonaiti criteria relative to LFS. Molecular study was assessed using Sanger sequencing of the hotspot germline variants of TP53 gene.

Results
We report 2 Tunisian families fulfilling the clinical criteria of Chompret-Bonaiti. The tumor phenotype was bilateral breast cancer (BC) in 27-year-old woman and multiple tumors for the second proband, with an onset age of 14, 35 and 36 yo for osteosarcoma, BC and esophageal cancer respectively. Each of them had a rare histological type of breast cancer associated with LFS, phyllode tumor and intralobular carcinoma. Both patients had cancer family history. The molecular study showed deleterious heterozygous germline TP53 variants in each index case: The first had a well-known hotspot missense variation c.742C>T p.(R248W) with a rare histological association, explaining genotype phenotype correlation. The second case had a nonsense variation c.159G>A p.(W53*), rare worldwide, extending the phenotype spectrum in LFS. Immunohistochemistry study in tumor samples confirmed the lack of p53 protein expression.

Conclusions
Conclusively, germline TP53 testing is primordial in patients with a family history suggestive of LFS for clinical practice avoiding genotoxic treatments and adapting the surveillance. National database in LFS listing clinical and mutational data is important to set, particularly for variants rarely reported worldwide. Experience from different countries must be integrated to harmonize global protocols for cancer surveillance in LFS.
Did COVID-19 impact Positive Airway Pressure adherence in 2020? A cross-sectional study of 8477 patients with sleep apnea
Authors: Bertelli Fanny , Suehs Carey M. , Mallet Jean-Pierre , Court-Fortune Isabelle , Gagnadoux Frédéric , Borel Jean Christian , Gaubert Olivier , Molinari Nicolas , Bourdin Arnaud , Jaffuel Dany 
Published: March 2022

Abstract
Background
Whether the COVID-19 pandemic impacts Positive Airway Pressure (PAP) adherence over the long-term is unknown and only preliminary short-term data have been reported.

Methods
With the aim of describing the impact of the first and second waves of COVID-19 on PAP adherence during 2020 in France, we designed a cross-sectional study of Sleep-Apnea (SA)-patients under PAP telemonitoring. To examine PAP adherence in adult SA patients, we assessed de-identified data from a non-profit healthcare provider database during the period January 1, 2019 to December 31, 2020. Included patients met the following criteria: (i) PAP-treated for at least 4 months before January 1, 2019 and with continuous PAP during both 2019 and 2020; (ii) ≥ 360 daily PAP telemonitored data per year. For PAP adherence, data were collected using the PAP-software.

Results
8477/10482 patients were finally included in the analysis [72.4% male, median age 70 years (IQ25–75: 61–77], 25.6% < 62 years old, initial Apnea–Hypopnea Index (AHI) of 41 (31–59)/h. Median PAP adherence was 7.21 (6.12–8.10) h/day in 2020 versus 7.12 (6.05–8.02) h/day in 2019, p < 0.001. The median difference in PAP adherence between the first 2020 lockdown and the corresponding 2019 weeks was 9.75 (CI95% 8.75–10.75) min/day, p < 0.001. The median difference in PAP adherence between the second 2020 lockdown and the corresponding 2019 weeks was 5.00 (CI95% 4.00–6.00) min/day, p < 0.001. If we consider the minimal clinically important difference of 30 min for PAP adherence, 30.4% and 26% of the patients increased their PAP adherence by at least 30 min during the first and second lockdowns respectively; 17.6% and 19.3% of the patients lowered their PAP adherence by at least 30 min in the first and second lockdowns, respectively.

Conclusion
During the first and second lockdowns, the COVID-19 pandemic had a clinically irrelevant effect on PAP adherence for the study population. Future studies are needed to describe COVID-19 pandemic impact on PAP adherence not only for long-term PAP-treated SA patients but also for incident cases.
Trial registration The COVADENE study was registered on March 1st, 2021 on ClinicalTrials.gov (Identifier: NCT04775966)
Molecular genetic approaches to decrease the uncontrolled misincorporation of non-canonical branched chain amino acids into recombinant mini-proinsulin expressed in Escherichia coli
Authors: García Ángel Córcoles , Hauptmann Peter , Neubauer Peter 
Published: March 2022

AbstractThe uncontrolled incorporation of non-canonical branched chain amino acids (ncBCAAs) such as norleucine, norvaline and β-methylnorleucine into recombinant proteins in E. coli production processes is a crucial problem in the pharmaceutical industry, since it can lead to the production of altered proteins with non-optimal characteristics. Despite various solutions, to date there are no engineered strains that exhibit a reduced accumulation of these ncBAAs. In this study, novel E. coli K-12 BW25113 strains with exogenous tunable expression of target genes of the BCAA biosynthetic pathway were developed. For this purpose, single gene knock-outs for thrA, ilvA, leuA, ilvIH, ilvBN, ilvGM and ilvC were complemented with plasmids containing the respective genes under control of an arabinose promoter. These clones were screened in a mL-bioreactor system in fed-batch mode under both standard cultivation conditions and with pyruvate pulses, and induction of a min-proinsulin. Screening was performed by comparing the impurity profile of the recombinant mini-proinsulin expressed of each clone with the E. coli BW25113 WT strain, and the most promising clones were cultivated in a 15L Screening showed that up-regulation of ilvC, ilvIH and ilvGM, and downregulation of leuA and ilvBN trigger a reduction of norvaline and norleucine accumulation and misincorporation into mini-proinsulin. The stirred tank bioreactor cultivations confirmed that up-regulation of ilvIH and ilvGM were most effective to reduce the ncBCAA misincorporation. This novel approach for a reduced ncBCAA misincorporation may be solution to this old challenging problem in the large-scale production of human therapeutics.
miR-30a targets STOX2 to increase cell proliferation and metastasis in hydatidiform moles via ERK, AKT, and P38 signaling pathways
Authors: Guo Zhenzhen , Zhu Chenyu , Wang Youhui , Li Zhen , Wang Lu , Fan Jianhui , Xu Yuefei , Zou Na , Kong Ying , Li Dong , Sui Linlin 
Published: March 2022

Abstract
Background
A hydatidiform mole is a condition caused by abnormal proliferation of trophoblastic cells. MicroRNA miR-30a acts as a tumor suppressor gene in most tumors and participates in the development of various cancers. However, its role in hydatidiform moles is not clear.

Methods
Quantitative real-time reverse transcription PCR was used to verify the expression level of miR-30a and STOX2 (encoding storkhead box 2). Flow cytometry assays were performed to detect the cell cycle in cell with different expression levels of miR-30a and STOX2. Cell Cycle Kit-8, 5-ethynyl-2′-deoxyuridine, and colony formation assays were used to detect cell proliferation and viability. Transwell assays was used to test cell invasion and migration. Dual-luciferase reporter assays and western blotting were used to investigate the potential mechanisms involved.

Result
Low miR-30a expression promoted the proliferation, migration, and invasion of trophoblastic cells (JAR and HTR-8). Dual luciferase assays confirmed that STOX2 is a target of miR-30a and resisted the effect of upregulated miR-30a in trophoblastic cells. In addition, downregulation of STOX2 by miR-30a could activate ERK, AKT, and P38 signaling pathways. These results revealed a new mechanism by which ERK, AKT, and P38 activation by miR-30a/STOX2 results in excessive proliferation of trophoblast cells in the hydatidiform mole.

Conclusions
In this study, we found that miR-30a plays an important role in the development of the hydatidiform mole. Our findings indicate that miR-30a might promote the malignant transformation of human trophoblastic cells by regulating STOX2, which strengthens our understanding of the role of miR-30a in regulating trophoblastic cell transformation.
Comparison of total immunoglobulin G antibody responses to different protein fragments of Plasmodium vivax Reticulocyte binding protein 2b
Authors: Bourke Caitlin , Takashima Eizo , Chan Li-Jin , Dietrich Melanie H. , Mazhari Ramin , White Michael , Sattabongkot Jetsumon , Tham Wai-Hong , Tsuboi Takafumi , Mueller Ivo , Longley Rhea 
Published: March 2022

Abstract
Background
Plasmodium vivax is emerging as the dominant and prevalent species causing malaria in near-elimination settings outside of Africa. Hypnozoites, the dormant liver stage parasite of P. vivax, are undetectable to any currently available diagnostic test, yet are a major reservoir for transmission. Advances have been made to harness the naturally acquired immune response to identify recent exposure to P. vivax blood-stage parasites and, therefore, infer the presence of hypnozoites. This in-development diagnostic is currently able to detect infections within the last 9-months with 80% sensitivity and 80% specificity. Further work is required to optimize protein expression and protein constructs used for antibody detection.

Methods
The antibody response against the top performing predictor of recent infection, P. vivax reticulocyte binding protein 2b (PvRBP2b), was tested against multiple fragments of different sizes and from different expression systems. The IgG induced against the recombinant PvRBP2b fragments in P. vivax infected individuals was measured at the time of infection and in a year-long observational cohort; both conducted in Thailand.

Results
The antibody responses to some but not all different sized fragments of PvRBP2b protein are highly correlated with each other, significantly higher 1-week post-P. vivax infection, and show potential for use as predictors of recent P. vivax infection.

Conclusions
To achieve P. vivax elimination goals, novel diagnostics are required to aid in detection of hidden parasite reservoirs. PvRBP2b was previously shown to be the top candidate for single-antigen classification of recent P. vivax exposure and here, it is concluded that several alternative recombinant PvRBP2b fragments can achieve equal sensitivity and specificity at predicting recent P. vivax exposure.