bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of COVID-19 pandemic and lockdown on consultation numbers, consultation reasons and performed services in primary care: results of a longitudinal observational study
Authors: Schäfer Ingmar , Hansen Heike , Menzel Agata , Eisele Marion , Tajdar Daniel , Lühmann Dagmar , Scherer Martin 
Published: June 2021

AbstractObjectivesThe aims of our study were to describe the effect of the COVID-19 pandemic and lockdown on primary care in Germany regarding the number of consultations, the prevalence of specific reasons for consultation presented by the patients, and the frequency of specific services performed by the GP.MethodsWe conducted a longitudinal observational study based on standardised GP interviews in a quota sampling design comparing the time before the COVID-19 pandemic (12 June 2015 to 27 April 2017) with the time during lockdown (21 April to 14 July 2020). The sample included GPs in urban and rural areas 120 km around Hamburg, Germany, and was stratified by region type and administrative districts. Differences in the consultation numbers were analysed by multivariate linear regressions in mixed models adjusted for random effects on the levels of the administrative districts and GP practices.ResultsOne hundred ten GPs participated in the follow-up, corresponding to 52.1% of the baseline. Primary care practices in 32 of the 37 selected administrative districts (86.5%) could be represented in both assessments. At baseline, GPs reported 199.6 ± 96.9 consultations per week, which was significantly reduced during COVID-19 lockdown by 49.0% to 101.8 ± 67.6 consultations per week (p < 0.001). During lockdown, the frequency of five reasons for consultation (-43.0% to -31.5%) and eleven services (-56.6% to -33.5%) had significantly decreased. The multilevel, multivariable analyses showed an average reduction of 94.6 consultations per week (p < 0.001).ConclusionsWe observed a dramatic reduction of the number of consultations in primary care. This effect was independent of age, sex and specialty of the GP and independent of the practice location in urban or rural areas. Consultations for complaints like low back pain, gastrointestinal complaints, vertigo or fatigue and services like house calls/calls at nursing homes, wound treatments, pain therapy or screening examinations for the early detection of chronic diseases were particularly affected.
Adapting the definition of multimorbidity – development of a locality-based consensus for selecting included Long Term Conditions
Authors: Hafezparast Nasrin , Turner Ellie Bragan , Dunbar-Rees Rupert , Vodden Alice , Dodhia Hiten , Reynolds Brian , Reichwein Barbara , Ashworth Mark 
Published: June 2021

Abstract
Background
Defining multimorbidity has proved elusive in spite of attempts to standardise definitions. For national studies, a broad definition is required to capture national diversity. For locally based studies, the definition may need to reflect demographic and morbidity patterns. We aimed to define multimorbidity for an inner city, multi-ethnic, deprived, young age community typical of many large cities.

Methods
We used a scoping literature review to identify the international literature, standards and guidelines on Long Term Condition (LTC) definitions for inclusion in our multimorbidity definition. Consensus was categorised into high, medium or low consensus, depending on the number of literature sources citing each LTC. Findings were presented to a workshop consisting of local health service stakeholders who were asked to select LTCs for inclusion in a second stage review. In the second stage, each LTC was tested against seven evaluation domains: prevalence, impact, preventability, treatment burden, progression to multiple LTCs, impact on younger people, data quality. These domains were used to create 12 target criteria. LTC rankings according to consensus group and target criteria scores were presented to a second workshop for a final decision about LTC inclusion.

Results
The literature review identified 18 literature sources citing 86 LTCs: 11 were excluded because they were LTC clusters. The remainder were allocated into consensus groupings: 13 LTCs were ‘high consensus’ (cited by ≥ 11 sources); 15 were ‘medium consensus’ (cited by 5–10 sources); 47 were ‘low consensus’ (cited by < 5 sources). The first workshop excluded 31 LTCs. The remaining 44 LTCs consisted of: 13 high consensus LTCs, all with high target score (score 6–12); 15 medium consensus LTCs, 11 with high target scores; 16 low consensus LTCs, 6 with high target scores.
The final workshop selected the 12 high consensus conditions, 12 medium consensus LTCs (10 with high target scores) and 8 low consensus LTCs (3 with high target scores), producing a final selection of 32 LTCs.

Conclusions
Redefining multimorbidity for an urban context ensures local relevance but may diminish national generalisability. We describe a detailed LTC selection process which should be generalisable to other contexts, both local and national.
Pregnant women’s experiences of social distancing behavioural guidelines during the Covid-19 pandemic ‘lockdown’ in the UK, a qualitative interview study
Authors: Anderson Emma , Brigden Amberly , Davies Anna , Shepherd Emily , Ingram Jenny 
Published: June 2021

Abstract
Background
Covid-19 triggered the rapid roll-out of mass social distancing behavioural measures for infection control. Pregnant women were categorised as ‘at risk’ requiring extra vigilance with behavioural guidelines. Their understanding and ability to adhere to recommendations was unknown.

Objectives
To complete a behavioural analysis of the determinants of recommended social distancing behaviour in pregnant women, according to the ‘capability, opportunity, motivation and behaviour’ (‘COM-B’) model to inform the development of recommendations/materials to support pregnant women in understanding and adhering to behavioural guidelines.

Design
Qualitative interview study with pregnant women in the Bristol area (UK).

Methods
Semi-structured telephone/videoconference interviews were conducted following a topic guide informed by the COM-B model, transcribed verbatim and subjected to framework analysis. Infographic materials were iteratively produced with stakeholder consultation, to support pregnant women.

Results
Thirty-one women participated (selected for demographic range). Women reported adhering to social distancing recommendations and intended to continue. COM-B analysis identified gaps in understanding around risk, vulnerability, and the extent of required social distancing, as well as facilitators of social distancing behaviour (e.g. social support, motivation to stay safe, home environment/resources). Additional themes around detrimental mental health effects and changes to maternity healthcare from the social distancing measures were identified. Infographic resources (plus midwife report) addressing women’s key concerns were produced and disseminated.

Conclusions
The COM-B model provided useful details of determinants of pregnant women’s adherence to social distancing behaviours. The confusion of what being ‘at risk’ meant and varying interpretation of what was expected indicates a need for greater clarity around categories and guidance. The loss of maternity care and negative mental health effects of social distancing suggest a growing area of unmet health needs to be addressed in future.
A comparison of tobacco product prevalence by different frequency of use thresholds across three US surveys
Authors: Sánchez-Romero Luz María , Cadham Christopher J. , Hirschtick Jana L. , Mattingly Delvon T. , Cho Beomyoung , Fleischer Nancy L. , Brouwer Andrew , Mistry Ritesh , Land Stephanie R. , Jeon Jihyoun , Meza Rafael , Levy David T. 
Published: June 2021

Abstract
Background
With the increasing changes in tobacco use patterns, “current use” definition and the survey used may have important implications for monitoring population use trends.

Methods
Using three US surveys (2014/15 TUS-CPS, NHIS and PATH), we compared the adult (age 18+) prevalence of four product groups (cigarettes, other combustibles, smokeless tobacco, and e-cigarettes) based on three past 30-day frequency of use thresholds: 1+, 10+, and 25+ days. We also examined mutually exclusive single, dual, and polytobacco users as a percentage of total users for each product group.

Results
Regardless of threshold or product, the prevalence was higher in PATH followed by NHIS and TUS-CPS, in some cases by large percentages. The differences in cigarette and smokeless tobacco use prevalence in going from the 1+ to 10+ days and to the 25+ days threshold were minimal. Applying different frequency thresholds had the largest impact on other combustibles prevalence, with a 60% reduction with the 10+ days threshold and a 80% reduction with the 25+ days threshold, compared to the 1+ days threshold, followed by e-cigarettes with 40 and 60% reductions, respectively. The proportion of dual and polytobacco users decreased considerably when using the 10+ vs. the 1+ days threshold and polytobacco use was almost non-existent with the 25+ days threshold.

Conclusion
The estimated prevalence of each tobacco product use depends largely on the survey and frequency of use threshold adopted. The choice of survey and frequency threshold merits serious consideration when monitoring patterns of tobacco use.
End-of-life care preferences among cancer patients in Southern Thailand: a university hospital-based cross-sectional survey
Authors: Pitanupong Jarurin , Janmanee Sahawit 
Published: June 2021

Abstract
Background
End-of-life care preferences may be highly individual, heterogenic, and variable according to culture and belief. This study aimed to explore preferences and factors associated with end-of-life care among Thai cancer patients. Its findings could help optimize the quality of life of palliative cancer patients.

Methods
A cross-sectional study surveyed palliative cancer outpatients at Songklanagarind Hospital from August to November 2020. The questionnaires inquired about: (1) personal and demographic information, (2) experiences with end-of-life care for their relatives, and (3) end-of-life care preferences. To determine end-of life preferences, the data were analyzed using descriptive statistics. The data concerning patient demographics and end-of-life care preferences were compared using Fisher’s exact test.

Results
The majority of the 96 palliative cancer outpatients were female (65.6 %), and the overall mean age was 55.8 ± 11.6 years. More than half of them had an experience of observing someone die (68.8 %), and they were predominantly being conscious until the time of death (68.2 %). Most participants preferred receiving the full truth satisfied with the care their relatives had received in passing away at home surrounded by family (47.0 %) and regarding their illness (99.0 %), being free of uncomfortable symptoms (96.9 %), having their loved ones around (93.8 %), being mentally aware at the last hour (93.8 %), and having the sense of being meaningful in life (92.7 %). Their 3 most important end-of-life care wishes were receiving the full truth regarding their illness, disclosing the full truth regarding their illness to family members, and passing away at home.

Conclusions
In order to optimize the quality of life of palliative cancer patients, end-of-life care should ensure they receive the full truth regarding their illness, experience no distressing symptoms, remain mentally aware at the last hour of life, feel meaningful in life, and pass away comfortably with loved ones around.
Exploring the use of health and wellbeing measures during pregnancy and the first year following birth in women living with pre-existing long-term conditions: qualitative interviews with women and healthcare professionals
Authors: Kelly Laura , Kurinczuk Jennifer J. , Rivero-Arias Oliver , Fitzpatrick Ray , Gibbons Elizabeth , Alderdice Fiona 
Published: June 2021

Abstract
Background
One way in which care for pregnant and postpartum women living with long-term health conditions (LTCs) may be improved is through the adoption of standardised measures to provide evidence of health outcomes and wellbeing from the woman’s perspective.

Aim
The study explores the views of pregnant and postpartum women living with LTCs, and healthcare professionals to better understand the potential value of using standardised health and wellbeing measures within this patient population.

Methods
Qualitative semi-structured telephone interviews were conducted to explore the perceived value of using measures with pregnant and postpartum women living with LTCs within maternity services. Participants were asked to provide feedback on three exemplar measures: the Long Term Conditions Questionnaire, the Wellbeing in Pregnancy Questionnaire and the EuroQol EQ-5D-5L instrument. Thematic analysis was used in the analysis of the transcripts.

Results
Eleven women and 11 healthcare professionals took part in semi-structured interviews. Analysis identified five themes as relevant to the use of measures within maternity services: 1) Improving care, 2) Assessing outcomes, 3) Interpretation and application of data, 4) Engagement challenges and implementation and, 5) Women and healthcare professionals alignment.

Conclusions
Despite varying prior experience and expressing some questions about implementation, respondents were cautiously positive about the use of standardised health and wellbeing measures. Their use offers the opportunity for both affected women and healthcare professionals caring for them to collectively identify and assess important areas of unmet needs and improve outcomes. Incorporating the perspectives of women with LTC’s will help bring awareness to elements of women centred care which health services may seek to address.
Use of the rhizobial type III effector gene nopP to improve Agrobacterium rhizogenes-mediated transformation of Lotus japonicus
Authors: Wang Yan , Yang Feng , Zhu Peng-Fei , Khan Asaf , Xie Zhi-Ping , Staehelin Christian 
Published: June 2021

Abstract
Background
Protocols for Agrobacterium rhizogenes-mediated hairy root transformation of the model legume Lotus japonicus have been established previously. However, little efforts were made in the past to quantify and improve the transformation efficiency. Here, we asked whether effectors (nodulation outer proteins) of the nodule bacterium Sinorhizobium sp. NGR234 can promote hairy root transformation of L. japonicus. The co-expressed red fluorescent protein DsRed1 was used for visualization of transformed roots and for estimation of the transformation efficiency.

Results
Strong induction of hairy root formation was observed when A. rhizogenes strain LBA9402 was used for L. japonicus transformation. Expression of the effector gene nopP in L. japonicus roots resulted in a significantly increased transformation efficiency while nopL, nopM, and nopT did not show such an effect. In nopP expressing plants, more than 65% of the formed hairy roots were transgenic as analyzed by red fluorescence emitted by co-transformed DsRed1. A nodulation experiment indicated that nopP expression did not obviously affect the symbiosis between L. japonicus and Mesorhizobium loti.

Conclusion
We have established a novel protocol for hairy root transformation of L. japonicus. The use of A. rhizogenes LBA9402 carrying a binary vector containing DsRed1 and nopP allowed efficient formation and identification of transgenic roots.
The dosimetric impact of deep learning-based auto-segmentation of organs at risk on nasopharyngeal and rectal cancer
Authors: Guo Hongbo , Wang Jiazhou , Xia Xiang , Zhong Yang , Peng Jiayuan , Zhang Zhen , Hu Weigang 
Published: June 2021

AbstractPurposeTo investigate the dosimetric impact of deep learning-based auto-segmentation of organs at risk (OARs) on nasopharyngeal and rectal cancer.Methods and materialsTwenty patients, including ten nasopharyngeal carcinoma (NPC) patients and ten rectal cancer patients, who received radiotherapy in our department were enrolled in this study. Two deep learning-based auto-segmentation systems, including an in-house developed system (FD) and a commercial product (UIH), were used to generate two auto-segmented OARs sets (OAR_FD and OAR_UIH). Treatment plans based on auto-segmented OARs and following our clinical requirements were generated for each patient on each OARs sets (Plan_FD and Plan_UIH). Geometric metrics (Hausdorff distance (HD), mean distance to agreement (MDA), the Dice similarity coefficient (DICE) and the Jaccard index) were calculated for geometric evaluation. The dosimetric impact was evaluated by comparing Plan_FD and Plan_UIH to original clinically approved plans (Plan_Manual) with dose-volume metrics and 3D gamma analysis. Spearman’s correlation analysis was performed to investigate the correlation between dosimetric difference and geometric metrics.ResultsFD and UIH could provide similar geometric performance in parotids, temporal lobes, lens, and eyes (DICE,p > 0.05). OAR_FD had better geometric performance in the optic nerves, oral cavity, larynx, and femoral heads (DICE,p < 0.05). OAR_UIH had better geometric performance in the bladder (DICE,p < 0.05). In dosimetric analysis, both Plan_FD and Plan_UIH had nonsignificant dosimetric differences compared to Plan_Manual for most PTV and OARs dose-volume metrics. The only significant dosimetric difference was the max dose of the left temporal lobe for Plan_FD vs. Plan_Manual (p = 0.05). Only one significant correlation was found between the mean dose of the femoral head and its HD index (R = 0.4,p = 0.01), there is no OARs showed strong correlation between its dosimetric difference and all of four geometric metrics.ConclusionsDeep learning-based OARs auto-segmentation for NPC and rectal cancer has a nonsignificant impact on most PTV and OARs dose-volume metrics. Correlations between the auto-segmentation geometric metric and dosimetric difference were not observed for most OARs.
Patient-derived cell lines and orthotopic mouse model of peritoneal carcinomatosis recapitulate molecular and phenotypic features of human gastric adenocarcinoma
Authors: Song Shumei , Xu Yan , Huo Longfei , Zhao Shuangtao , Wang Ruiping , Li Yuan , Scott Ailing W. , Pizzi Melissa Pool , Wang Ying , Fan Yibo , Harada Kazuto , Jin Jiankang , Ma Lang , Yao Xiaodan , Shanbhag Namita D. , Gan Qiong , Roy-Chowdhuri Sinchita , Badgwell Brian D. , Wang Zhenning , Wang Linghua , Ajani Jaffer A. 
Published: June 2021

Abstract
Background
Gastric adenocarcinoma with peritoneal carcinomatosis (PC) is therapy resistant and leads to poor survival. To study PC in depth, there is an urgent need to develop representative PC-derived cell lines and metastatic models to study molecular mechanisms of PC and for preclinical screening of new therapies.

Methods
PC cell lines were developed from patient-derived PC cells. The tumorigenicity and metastatic potential were investigated by subcutaneously (PDXs) and orthotopically. Karyotyping, whole-exome sequencing, RNA-sequencing, and functional studies were performed to molecularly define the cell lines and compare genomic and phenotypic features of PDX and donor PC cells.

Results
We established three PC cell lines (GA0518, GA0804, and GA0825) and characterized them in vitro. The doubling times were 22, 39, and 37 h for GA0518, GA0804, and GA0825, respectively. Expression of cancer stem cell markers (CD44, ALDH1, CD133 and YAP1) and activation of oncogenes varied among the cell lines. All three PC cell lines formed PDXs. Interestingly, all three PC cell lines formed tumors in the patient derived orthotopic (PDO) model and GA0518 cell line consistently produced PC in mice. Moreover, PDXs recapitulated transcriptomic and phenotypic features of the donor PC cells. Finally, these cell lines were suitable for preclinical testing of chemotherapy and target agents in vitro and in vivo.

Conclusion
We successfully established three patient-derived PC cell lines and an improved PDO model with high incidence of PC associated with malignant ascites. Thus, these cell lines and metastatic PDO model represent excellent resources for exploring metastatic mechanisms of PC in depth and for target drug screening and validation by interrogating GAC for translational studies.
Metformin induces Ferroptosis by inhibiting UFMylation of SLC7A11 in breast cancer
Authors: Yang Jingjing , Zhou Yulu , Xie Shuduo , Wang Ji , Li Zhaoqing , Chen Lini , Mao Misha , Chen Cong , Huang Aihua , Chen Yongxia , Zhang Xun , Khan Noor Ul Hassan , Wang Linbo , Zhou Jichun 
Published: June 2021

Abstract
Background
Ferroptosis is a newly defined form of regulated cell death characterized by the iron-dependent accumulation of lipid peroxidation and is involved in various pathophysiological conditions, including cancer. Targeting ferroptosis is considered to be a novel anti-cancer strategy. The identification of FDA-approved drugs as ferroptosis inducers is proposed to be a new promising approach for cancer treatment. Despite a growing body of evidence indicating the potential efficacy of the anti-diabetic metformin as an anti-cancer agent, the exact mechanism underlying this efficacy has not yet been fully elucidated.

Methods
The UFMylation of SLC7A11 is detected by immunoprecipitation and the expression of UFM1 and SLC7A11 in tumor tissues was detected by immunohistochemical staining. The level of ferroptosis is determined by the level of free iron, total/lipid Ros and GSH in the cells and the morphological changes of mitochondria are observed by transmission electron microscope. The mechanism in vivo was verified by in situ implantation tumor model in nude mice.

Results
Metformin induces ferroptosis in an AMPK-independent manner to suppress tumor growth. Mechanistically, we demonstrate that metformin increases the intracellular Fe2+ and lipid ROS levels. Specifically, metformin reduces the protein stability of SLC7A11, which is a critical ferroptosis regulator, by inhibiting its UFMylation process. Furthermore, metformin combined with sulfasalazine, the system xc− inhibitor, can work in a synergistic manner to induce ferroptosis and inhibit the proliferation of breast cancer cells.

Conclusions
This study is the first to demonstrate that the ability of metformin to induce ferroptosis may be a novel mechanism underlying its anti-cancer effect. In addition, we identified SLC7A11 as a new UFMylation substrate and found that targeting the UFM1/SLC7A11 pathway could be a promising cancer treatment strategy.
The brain transcriptome of the wolf spider, Schizocosa ocreata
Authors: Stribling Daniel , Chang Peter L. , Dalton Justin E. , Conow Christopher A. , Rosenthal Malcolm , Hebets Eileen , Graze Rita M. , Arbeitman Michelle N. 
Published: June 2021

Abstract
Objectives
Arachnids have fascinating and unique biology, particularly for questions on sex differences and behavior, creating the potential for development of powerful emerging models in this group. Recent advances in genomic techniques have paved the way for a significant increase in the breadth of genomic studies in non-model organisms. One growing area of research is comparative transcriptomics. When phylogenetic relationships to model organisms are known, comparative genomic studies provide context for analysis of homologous genes and pathways. The goal of this study was to lay the groundwork for comparative transcriptomics of sex differences in the brain of wolf spiders, a non-model organism of the pyhlum Euarthropoda, by generating transcriptomes and analyzing gene expression.

Data description
To examine sex-differential gene expression, short read transcript sequencing and de novo transcriptome assembly were performed. Messenger RNA was isolated from brain tissue of male and female subadult and mature wolf spiders (Schizocosa ocreata). The raw data consist of sequences for the two different life stages in each sex. Computational analyses on these data include de novo transcriptome assembly and differential expression analyses. Sample-specific and combined transcriptomes, gene annotations, and differential expression results are described in this data note and are available from publicly-available databases.