bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interpreting Breast Cancer Mortality Trends Related to Introduction of Mammography Screening: A Simulation Study
Authors: Heggland Torunn , Vatten Lars Johan , Opdahl Signe , Weedon-Fekjær Harald 
Published: October 2022

Background. Several studies have evaluated the effect of mammography screening on breast cancer mortality based on overall breast cancer mortality trends, with varied conclusions. The statistical power of such trend analyses is, however, not carefully studied. Methods. We estimated how the effect of screening on overall breast cancer mortality is likely to unfold. Because a screening effect is based on earlier treatment, screening can affect only new incident cases after screening introduction. To evaluate the likelihood of detecting screening effects on overall breast cancer mortality time trends, we calculated the statistical power of joinpoint regression analysis on breast cancer mortality trends around screening introduction using simulations. Results. We found that a very gradual increase in population-level screening effect is expected due to prescreening incident cases. Assuming 25% effectiveness of a biennial screening program in reducing breast cancer mortality among women 50 to 69 y of age, the expected reduction in overall breast cancer mortality was 3% after 2 y and reached a long-term effect of 18% after 20 y. In common settings, the statistical power to detect any screening effects using joinpoint regression analysis is very low (<50%), even in an artificial setting of constant risk of baseline breast cancer mortality over time. Conclusions. Population effects of screening on breast cancer mortality emerge very gradually and are expected to be considerably lower than the effects reported in trials excluding women diagnosed before screening. Studies of overall breast cancer mortality time trends have too low statistical power to reliably detect screening effects in most populations. Implications. Researchers and policy makers evaluating mammography screening should avoid using breast cancer mortality trend analysis that does not separate pre- and postscreening incident cases. Highlights Population-level mammography screening effects on breast cancer mortality emerge gradually following screening introduction, resulting in very low statistical power of trend analysis. Researchers and policy makers evaluating mammography screening should avoid relying on population-wide breast cancer mortality trends. Expected mammography screening effects at population level are lower than those from screening trials, as many cases of breast cancer fall outside the screening age range.
Regular medication as a risk factor for intracranial aneurysms: A comparative case–control study
Authors: Jabbarli Ramazan , Darkwah Oppong Marvin , Chihi Mehdi , Dinger Thiemo Florin , Said Maryam , Rodemerk Jan , Dammann Philipp , Schmidt Börge , Deuschl Cornelius , Guberina Nika , Wrede Karsten H. , Sure Ulrich 
Published: October 2022

Background: Previous medical history strongly contributes to the genesis of intracranial aneurysms (IA). A possible impact of regular medication on the occurrence of abdominal aortic aneurysms has been reported. Aim: To evaluate the value of regular medication on the risk of development and rupture of IA. Methods: Data on medication use and related comorbidities were obtained from the institutional IA registry. A 1:1 age- and sex-matched patient sample was collected from the population-based Heinz Nixdorf Recall Study with individuals from the same area. Results: In the analysis comparing IA cohort ( n = 1960) with the matched normal population ( n = 1960), the use of statins (adjusted odds ratio, 1.34 [95% confidence interval 1.02–1.78]), antidiabetics (1.46 [1.08–1.99]), and calcium channel blockers (1.49 [1.11–2.00]) was independently associated with higher risk of IA, whereas uricostatics (0.23 [0.14–0.38]), aspirin (0.23 [0.13–0.43]), beta-blockers (0.51 [0.40–0.66]), and angiotensin-converting enzyme inhibitors (0.38 [0.27–0.53]) were related to lower risk of IA. In the multivariable analysis within the IA cohort ( n = 2446), SAH patients showed higher drug exposure with thiazide diuretics (2.11 [1.59–2.80]), but lower prevalence of remaining antihypertensive medication—beta-blockers (0.38 [0.30–0.48]), calcium channel blockers (0.63 [0.48–0.83]), angiotensin-converting enzyme inhibitors (0.56 [0.44–0.72]), and angiotensin-1 receptor blockers (0.33 [0.24–0.45]). Patients with ruptured IA were less likely to be treated with statins (0.62 [0.47–0.81]), thyroid hormones (0.62 [0.48–0.79]), and aspirin (0.55 [0.41–0.75]). Conclusions: Regular medication might impact the risks related to the development and rupture of IA. Further clinical trials are required to clarify the effect of regular medication on IA genesis.
Factors Associated with Multi-Biologic Use in Psoriasis Patients at an Academic Medical Center and Review of Biologic Survival
Authors: Hadeler Edward , Kumar Sugandh , Yeroushalmi Samuel , Hong Julie , Wallace Elizabeth , Han George , Mosca Megan , Bartholomew Erin , Chung Mimi , Hakimi Marwa , Reddy Soumya , Scher Jose , Bhutani Tina , Gondo George , Armstrong April , Bell Stacie , Liao Wilson 
Published: October 2022

Background Despite their impressive efficacy in phase 3 trials, biologic agents for psoriasis (PsO) may lose efficacy over time. The factors associated with loss of efficacy have yet to be fully elucidated. Objective We aimed to identify factors associated with PsO patients using multiple biologics in comparison to patients who used 1 biologic. We also reviewed the literature comparing the survival of different biologic agents for PsO. Methods We examined clinical data from 222 psoriasis patients at the University of California San Francisco, of whom 51 reported use of 3 or more biologics and of whom 171 reported use of only a single biologic agent at the time of enrollment into a research database from 2006-2020. This study was IRB-approved at UCSF (#10-02830) and all subjects provided written informed consent. We performed univariate and multivariate regression analysis to identify significant demographic features, clinical features, and co-morbidities associated with multi-biologic use. We performed a literature review of studies comparing psoriasis biologic survival at 1, 2, and 5 years and factors associated with single biologic failure. Results In univariate analysis, duration of PsO, initial presentation of PsO on the gluteal cleft, erythrodermic psoriasis, and acne were associated with using 3 or more biologics. In multivariate analysis, duration of PsO, erythrodermic psoriasis, and acne remained significant. Our review of biologic survival revealed differences according to biologic class. Conclusion We identified novel factors associated with multi-biologic use in PsO. Further studies in this area are needed to achieve a precision medicine approach.
Third wave COVID-19 delta variant breakthrough infection in a Hispanic-dominant suburb of Miami, Florida: ethical dilemma and vaccination hesitancy
Authors: Kara Sam , Lazovic Gavrilo , Chohan Farah , Lawrence Jannel A. , Sukaina Mahnoor , Edaki Omoyeme , Nedd Kester 
Published: October 2022

Background and Aims: The peak of the third wave of COVID-19 infection was in the summer (August–September) of 2021, dominated by the Delta variant. Florida was the epicenter of the third wave with more than 151,449 cases in the first week of August with a positivity rate of 20%. The purpose of this study is to identify the percentage of COVID-19 infection in vaccinated patients in a minority population in south Florida and to elucidate the relationship, if any, between demographics and breakthrough infections, the rate of vaccine hesitancy, as well as the willingness to receive the monoclonal antibody REGEN-COV for the treatment of COVID-19. Methods: This cross-sectional study was performed at the Emergency Department, Larkin Community Hospital Palm Spring Campus, located in Hialeah, the fourth largest city in Florida. Hialeah is dominated (94.7%) by Hispanics and Latinos. This city represents a cross-sectional sample of US cities in general and Florida in specific. We enrolled 127 COVID-19 PCR-positive patients. Results: The infection in vaccinated patients (breakthrough) was found to be about one in three (34%). Despite the high infection rate and mounting death toll, about 73% of our unvaccinated patients answered no to the question ‘knowing the consequences of being infected with COVID-19 and the fact that you are positive, would you have chosen to be vaccinated earlier?’ However, about 27% of these patients agreed to receive the vaccine and 20.5% received the monoclonal antibody REGEN-COV. Conclusions: Our study revealed that vaccine hesitancy in South Florida continues to be a major challenge, especially with the emergence of mutations including Delta plus and Omicron.
The hierarchy of multiple stressors’ effects on benthic invertebrates: a case study from the rivers Erft and Niers, Germany
Authors: Markert Nele , Guhl Barbara , Feld Christian K. 
Published: October 2022

Abstract
Background
A variety of anthropogenic stressors influences the ecological status of rivers wordwide. Important stressors include elevated concentrations of nutrients, salt ions, heavy metals and other pollutants, habitat degradation and flow alteration. Some stressors tend to remain underrepresented in multiple-stressor studies, which in particular is apparent for micropollutants (e.g. pesticides, pharmaceuticals) and alterations of the flow regime. This case study analysed and compared the effects of 19 different stressor variables on benthic macroinvertebrates in the two German rivers Erft and Niers (Federal State of North Rhine-Westphalia, Germany). The stressors variables were assigned to four stressor groups (physico-chemical stress, mixture toxicity of 42 micropollutants, hydrological alteration and morphological degradation) and were put into a hierarchical context according to their relative impact on the macroinvertebrate community using redundancy analysis and subsequent variance partitioning.

Results
The results suggest a strong and unique effect of physico-chemical stress, yet at the same time reveal also a strong joint effect of physico-chemical and hydrological stressor variables. Morphological degradation showed subordinate effects. Notably, only a minor share of the explained variance was attributed to the mixture toxicity of micropollutants in these specific catchments.

Conclusions
The stressor hierarchy indicates that management measures for improving the ecological status still need to address water quality issues in both rivers. The strong joint effect of physico-chemical stress and hydrological alteration might imply a common source of both stressor groups in these two catchment areas: lignite mining drainage, urban area and effluents of wastewater treatment plants. The findings point at the important role of alterations in the flow regime, which often remain unconsidered in hydro-morphological surveys.
A graph-based approach for the visualisation and analysis of bacterial pangenomes
Authors: Harling-Lee Joshua D. , Gorzynski Jamie , Yebra Gonzalo , Angus Tim , Fitzgerald J. Ross , Freeman Tom C. 
Published: October 2022

Abstract
Background
The advent of low cost, high throughput DNA sequencing has led to the availability of thousands of complete genome sequences for a wide variety of bacterial species. Examining and interpreting genetic variation on this scale represents a significant challenge to existing methods of data analysis and visualisation.

Results
Starting with the output of standard pangenome analysis tools, we describe the generation and analysis of interactive, 3D network graphs to explore the structure of bacterial populations, the distribution of genes across a population, and the syntenic order in which those genes occur, in the new open-source network analysis platform, Graphia. Both the analysis and the visualisation are scalable to datasets of thousands of genome sequences.

Conclusions
We anticipate that the approaches presented here will be of great utility to the microbial research community, allowing faster, more intuitive, and flexible interaction with pangenome datasets, thereby enhancing interpretation of these complex data.
Revealing the characteristics of ZIKV infection through tissue-specific transcriptome sequencing analysis
Authors: Chen Zhi-lu , Yin Zuo-jing , Qiu Tian-yi , Chen Jian , Liu Jian , Zhang Xiao-yan , Xu Jian-qing 
Published: October 2022

Abstract
Background
Recently, Zika virus (ZIKV) re-emerged in India and was potentially associated with microcephaly. However, the molecular mechanisms underlying ZIKV pathogenesis remain to be explored.

Results
Herein, we performed a comprehensive RNA-sequencing analysis on ZIKV-infected JEG-3, U-251 MG, and HK-2 cells versus corresponding uninfected controls. Combined with a series of functional analyses, including gene annotation, pathway enrichment, and protein–protein interaction (PPI) network analysis, we defined the molecular characteristics induced by ZIKV infection in different tissues and invasion time points. Data showed that ZIKV infection and replication in each susceptible organ commonly stimulated interferon production and down-regulated metabolic-related processes. Also, tissue-specific immune responses or biological processes (BPs) were induced after ZIKV infection, including GnRH signaling pathway in JEG-3 cells, MAPK signaling pathway in U-251 MG cells, and PPAR signaling pathway in HK-2 cells. Of note, ZIKV infection induced delayed antiviral interferon responses in the placenta-derived cell lines, which potentially explains the molecular mechanism by which ZIKV replicates rapidly in the placenta and subsequential vertical transmission occurs.

Conclusions
Together, these data may provide a systemic insight into the pathogenesis of ZIKV infection in distinct human tissue-derived cell lines, which is likely to help develop prophylactic and therapeutic strategies against ZIKV infection.
Transcriptome analysis of MYB transcription factors family and PgMYB genes involved in salt stress resistance in Panax ginseng
Authors: Liu Mingming , Li Ke , Sheng Shichao , Wang Mingyu , Hua Panpan , Wang Yanfang , Chen Ping , Wang Kangyu , Zhao Mingzhu , Wang Yi , Zhang Meiping 
Published: October 2022

Abstract
Background
As the king of all herbs, the medicinal value of ginseng is self-evident. The perennial nature of ginseng causes its quality to be influenced by various factors, one of which is the soil environment. During plant growth and development, MYB transcription factors play an important role in responding to abiotic stresses and regulating the synthesis of secondary metabolites. However, there are relatively few reports on the MYB transcription factor family in Panax ginseng.

Results
This study identified 420 PgMYB transcripts under 117 genes ID in the Jilin ginseng transcriptome database. Phylogenetic analysis showed that PgMYB transcripts in Jilin ginseng were classified into 19 functional subclasses. The GO annotation result indicated that the functional differentiation of PgMYB transcripts was annotated to 11 functional nodes at GO Level 2 in ginseng. Expression pattern analysis of PgMYB transcripts based on the expression data (TPM) that PgMYB transcripts were revealed spatiotemporally specific in expression patterns. We performed a weighted network co-expression network analysis on the expression of PgMYB transcripts from different samples. The co-expression network containing 51 PgMYB transcripts was formed under a soft threshold of 0.85, revealing the reciprocal relationship of PgMYB in ginseng. Treatment of adventitious roots of ginseng with different concentrations of NaCl revealed four up-regulated expression of PgMYB transcripts that can candidate genes for salt resistance studies in ginseng.

Conclusions
The present findings provide data resources for the subsequent study of the functions of MYB transcription factor family members in ginseng, and provide an experimental basis for the anti-salt functions of MYB transcription factors in Panax ginseng.
Changes in R-wave amplitude at implantation are associated with gender and orientation of insertable cardiac monitor: observations from the confirm Rx™ body posture and physical activity study
Authors: Swale Matthew , Paul Vincent , Delacroix Sinny , Young Glenn , McSpadden Luke , Ryu Kyungmoo , Di Fiore David , Santos Maria , Tan Isabel , Conradie Andre , Duong MyNgan , Schwarz Nisha , Worthley Stephen , Pavia Stephen 
Published: October 2022

Abstract
Background
Insertable cardiac monitors (ICMs) are small subcutaneously implanted devices that detect changes in R-wave amplitudes (RWAs), effective in arrhythmia-monitoring. Although ICMs have proven to be immensely successful, electrical artefacts are frequent and can lead to misdiagnosis. Thus, there is a growing need to sustain and increase efficacy in detection rates by gaining insight into various patient-specific factors such as body postures and activities.

Methods
RWAs were measured in 15 separate postures, including supine, lying on the right-side (RS) or left-side (LS) and sitting, and two separate ICM orientations, immediately after implantation of Confirm Rx™ ICM in 99 patients.

Results
The patients (53 females and 46 males, mean ages 66.62 ± 14.7 and 66.40 ± 12.25 years, respectively) had attenuated RWAs in RS, LS and sitting by ~ 26.4%, ~ 27.8% and ~ 21.2% respectively, compared to supine. Gender-based analysis indicated RWAs in RS (0.32 mV (0.09–1.03 mV), p < 0.0001) and LS (0.37 mV (0.11–1.03 mV), p = 0.004) to be significantly attenuated compared to supine (0.52 mV (0.20–1.03 mV) for female participants. Similar attenuation was not evident for male participants. Further, parasternally oriented ICMs (n = 44), attenuated RWAs in RS (0.37 mV(0.09–1.03 mV), p = 0.05) and LS (0.34 mV (0.11–1.03 mV), p = 0.02) compared to supine (0.48 mV (0.09–1.03 mV). Similar differences were not observed in participants with ICMs in the 45°-relative-to-sternum (n = 46) orientation. When assessing the combined effect of gender and ICM orientation, female participants demonstrated plausible attenuation in RWAs for RS and LS postures compared to supine, an effect not observed in male participants.

Conclusion
This is the first known study depicting the effects on RWA due to body postures and activities immediately post-implantation with an overt impact by gender and orientation of ICM. Future work assessing the cause of gender-based differences in RWAs may be critical.
Trial registration: Clinical Trials, NCT03803969. Registered 15 January 2019 – Retrospectively registered, https://clinicaltrials.gov/NCT03803969
Infrastructure challenges to doing health research “where populations with the most disease live” in Covid times—a response to Rai et al. (2021)
Authors: MacLellan Jennifer , Turnbull Joanne , Pope Catherine 
Published: October 2022

Abstract
Background
The failure of randomised controlled trials to adequately reflect areas of highest health need have been repeatedly highlighted. This has implications for the validity and generalisability of findings, for equity and efficiency, but also for research capacity-building. Rai et al. (BMC Med Res Methodol 21:80, 2021) recently argued that the poor alignment between UK clinical research activity (specifically multi-centre RCTs) and local prevalence of disease was, in part, the outcome of behaviour and decision-making by Chief Investigators involved in trial research. They argued that a shift in research culture was needed. Following our recent multi-site mixed methods evaluative study about NHS 111 online we identify some of the additional structural barriers to delivering health research “where populations with the most disease live”, accounting for the Covid-19 disruption to processes and delivery.

Methods
The NHS 111 study used a mixed-method research design, including interviews with healthcare staff and stakeholders within the primary, urgent and emergency health care system, and a survey of users and potential users of the NHS 111 online service. This paper draws on data collated by the research team during site identification and selection, as we followed an action research cycle of planning, action, observation and reflection. The process results were discussed among the authors, and grouped into the two themes presented.

Results
We approached 22 primary and secondary care sites across England, successfully recruiting half of these. Time from initial approach to first participant recruitment in successful sites ranged from one to ten months. This paper describes frontline bureaucratic barriers to research delivery and recruitment in the local Clinical Research Network system and secondary care sites carrying large research portfolios, alongside the adaptive practices of research practitioners that mitigate these.

Conclusions
This paper augments the recommendations of Rai et al., describing delays encountered during the COVID-19 pandemic, and suggesting in addition to cultural change, it may be additionally important to dismantle infrastructural barriers and improve support to research teams so they can conduct health research “where populations with the most disease live”.
Moyamoya associated with Turner syndrome in a patient with type 2 spinocerebellar ataxia—Occam’s razor or Hickam’s dictum: a case report
Authors: Nóbrega Paulo Ribeiro , da Costa Francisco Bruno Santana , Rodrigues Pedro Gustavo Barros , de Maria Frota Vasconcelos Thais , Soares Danyela Martins Bezerra , Araújo Jéssica Silveira , Dias Daniel Aguiar , Sobreira-Neto Manoel Alves , de Paiva Anderson Rodrigues Brandão , Braga-Neto Pedro , Kok Fernando , Fontenele Eveline Gadelha Pereira 
Published: October 2022

Abstract
Background
Turner syndrome (TS) is a rare condition associated with a completely or partially missing X chromosome that affects 1 in 2500 girls. TS increases the risk of autoimmune diseases, including Graves’ disease (GD). Moyamoya disease is a rare cerebral arteriopathy of unknown etiology characterized by progressive bilateral stenosis of the internal carotid artery and its branches. Both TS and GD have been associated with Moyamoya. Type 2 spinocerebellar ataxia (SCA2) is an autosomal dominant cerebellar ataxia caused by a CAG repeat expansion in ATXN2. We present the first case of Moyamoya syndrome in a patient with a previous diagnosis of TS and GD who tested positive for SCA2 and had imaging findings compatible with an overlap of SCA2 and Moyamoya.

Case presentation
A 43-year-old woman presented with mild gait imbalance for 2 years. Her family history was positive for type 2 spinocerebellar ataxia (SCA2). She had been diagnosed with Turner Syndrome (45,X) and Graves disease three years before. Brain MRI revealed bilateral frontal and parietal cystic encephalomalacia in watershed zones, atrophy of pons, middle cerebellar peduncles and cerebellum. MR angiography showed progressive stenosis of both internal carotid arteries with lenticulostriate collaterals, suggestive of Moya-Moya disease. Molecular analysis confirmed the diagnosis of SCA2.

Conclusions
With increased availability of tools for genetic diagnosis, physicians need to be aware of the possibility of a single patient presenting two or more rare diseases. This report underscores the modern dilemmas created by increasingly accurate imaging techniques and available and extensive genetic testing.