bluuebunny/crossref_metadata_2025_split huggingface dataset:
338Modelling the population distribution of patient-reported outcomes using electronic health records: a UK study
Authors: Yu Dahai , Jordan Kelvin , Bailey James , Peat George , Wilkie Ross 
Published: September 2021

Abstract

Background
Patient Reported Outcome Measures (PROM) collected in surveys allow understanding of the health at the population-level. We aimed to test the feasibility of estimating health status as measured by PROMs through ecological prediction models which use local linked survey and primary care electronic health records (EHR) and applying the models to national EHR.

Methods
3,710 musculoskeletal consulters registered in 11 general practiced in North Staffordshire, UK and consented the linkage of their survey PROM (high impact pain, (HICP)) with EHR were included in this study. HICP was modelled by EHR predictors covering demographic, lifestyle risk factors, musculoskeletal diagnostic/problems, analgesic prescriptions, comorbidities, and deprivation. Final set of predictors were selected through backward elimination (p &gt; 0.1). Individual-level prediction models (binary logistic regression) were fitted and evaluated in terms of model fit statistics (AIC, BIC, R-square), discrimination (C-statistics) and calibration-slope with internal validation. The final model was cross-mapped to a national UK primary EHR database (Clinical Practice Research Database) to obtain national population estimates of high impact pain.

Results
The C-statistics and calibration-slope of the final model was 0.77 (95% confidence interval: 0.70-0.79) and 1.00 (0.92-1.08), respectively. The estimated HICP was 51.2% overall among 49,788 UK musculoskeletal consulters and matched hypothesised variation by gender, age, deprivation and geographical regions.

Conclusions
Estimation of population-level health status as measured by PROM using EHR appears feasible and has potential application in assessing health inequalities. Further independent external validation studies are warranted.

Key messages
Primary care EHR data could be modelled to predict population-level PROMs.
1256Psychological impacts of COVID-19 pandemic on individuals living with multiple sclerosis: a rapid systematic review
Authors: Zarghami Amin , Hussain Akhtar , Campbell Julie , Ezegbe Chigozie , van der Mei Ingrid , Taylor Bruce , Claflin Suzi 
Published: September 2021

Abstract

Background
People living with multiple sclerosis (PwMS) are considered potentially vulnerable to the mental health effects of the COVID-19 pandemic, as they may be subject to increased social isolation. We aimed to systematically review the current evidence on the impact of the COVID-19 pandemic on mental health outcomes among PwMS.

Methods
We searched four major databases (Medline, EMBASE, PsychInfo and Scopus). We included peer-reviewed primary research studies using validated quality of life (QoL) and psychometric screening tools reporting data on the prevalence of mental health disorders, the severity of psychological symptoms and contributing demographic and clinical factors for PwMS during the COVID-19 pandemic.

Results
Our initial search yielded 121 records; 12 articles were included. Most were conducted during the peak of the pandemic-related lockdown in the host country via an online platform. The included studies used a variety of outcome assessment tools and study designs. The main mental health outcomes were depression, anxiety, stress, sleep quality and QoL. As a result, although the prevalence of mental health issues such as depression and anxiety appear to be high among PwMS during the pandemic, the impact of the pandemic on mental health among PwMS remains unclear.

Conclusions
Although mental health issues such as anxiety and depression appear fairly common among PwMS during the pandemic, the relationship between the pandemic and mental health among PwMS remains unclear.

Key messages
Despite a high prevalence of mental health issues among PwMS during the pandemic, the relationship between the pandemic and mental health remains unclear.
212Dose-response association and interaction between physical activity and sedentary time on premature rupture of membranes
Authors: Zhan Yongle , Jiang Yu 
Published: September 2021

Abstract

Background
Premature rupture of membranes (PROM) is a common pregnancy complication with multifactorial etiology. However, associations between physical activity (PA) and PROM are still unclear. Therefore, this study aims to explore the dose-response relationship and interactions between PA frequency, sedentary time (ST) and PROM.

Methods
Data on 6848 pregnant women were obtained from the Chinese Pregnant Women Cohort Study. Participants were recruited from July 2017 to November 2018 and were followed up until delivery. The International Physical Activity Questionnaire-Short Form was used to assess the frequency of PA and ST. Logistic regression and restricted cubic spline (RCS) model were used for data analyses.

Results
Women with frequencies of over 4 days/week of moderate-intensity PA (OR:1.50, 95%CI:1.01∼2.23) and light-intensity PA (OR:1.19, 95%CI:1.04∼1.37) had higher risks of PROM respectively. The RCS model showed that the risk for PROM was significant with frequencies of over 2 days/week of vigorous-intensity PA, over 5 days/week of moderate-intensity PA or over 5 days/week of light-intensity PA (ORs with 95%CI &gt;1). Interactions analyses showed that risks for PROM increased with frequencies of moderate-intensity and light-intensity PA both over 4 days/week (OR:1.80, 95%CI:1.17∼2.77), or with a frequency of light-intensity PA of over 4 days/week and ST of over 6 hours/day (OR:1.36, 95%CI:1.10∼1.69).

Conclusions
It is necessary to propose a suitable recommendation of frequency and intensity of PA, and identify and propose the corresponding intervention ways to reduce and prevent PROM occurrence during pregnancy.

Key messages
There is a dose-response relationship and interaction between PA and ST on PROM.
1506Flexible parametric survival models investigating factors associated with diabetes-related foot ulcer time-to-healing
Authors: Zhang Yuqi , Cramb Susanna , McPhail Steven , Pacella Rosana , van Netten Jaap , Cheng Qinglu , Derhy Patrick , Kinnear Ewan , Lazzarini Peter 
Published: September 2021

Abstract

Background
Diabetes-related foot ulcers (DFU) take months to heal, reduce patient’s quality-of-life, and induce large healthcare expenditure. Various factors have been identified to influence DFU healing at fixed periods, however, data on factors associated with time-to-healing is scarce.

Methods
Patients presenting with DFU to Diabetic Foot Services across Queensland, Australia between July 2011 and December 2017 were included and had their demographics, disease history and treatments examined at baseline. Outcome of interest was healing of all ulcers within two-year follow-up time. Time-to-healing and associated factors were examined using flexible parametric survival models, which easily enabled including time-varying coefficients and predicting proportions healed.

Results
Of 4,709 included patients (median age 63 years, 69.5% male, 10.5% Indigenous), median time-to-healing was 112 days, and 68% healed within two years. Younger age (&lt;60 years), geographical remoteness, smoking, neuropathy, deep ulcers, infection, not receiving offloading, and no recent podiatry treatment were independently associated with longer time-to-healing. Time-varying effects of peripheral artery disease and ulcer size were identified for the first time: both had a negative influence on healing with effects diminishing after six months. The predicted proportions healed, for example, within six months is 65.0% (63.3-66.7) for people residing in a major city, 54.6% (52.6-56.8) in regional area, and 40.3% (34.6-47.1) in remote area.

Conclusions
This study identified novel and confirmatory factors influencing time-to-healing over 24 months in a large real-world cohort of people with diabetes-related foot ulcers. Visualizing the adjusted predicted proportion healed revealed the influence each factor had on healing rates over time.

Key messages
Flexible parametric survival model provided flexibility in investigating time-varying effects and outcome prediction in those with diabetes-related foot ulcer healing.
An Artificial Intelligence System for the Detection of Bladder Cancer via Cystoscopy: A Multicenter Diagnostic Study
Authors: Wu Shaoxu , Chen Xiong , Pan Jiexin , Dong Wen , Diao Xiayao , Zhang Ruiyun , Zhang Yonghai , Zhang Yuanfeng , Qian Guang , Chen Hao , Lin Haotian , Xu Shizhong , Chen Zhiwen , Zhou Xiaozhou , Mei Hongbing , Wu Chenglong , Lv Qiang , Yuan Baorui , Chen Zeshi , Liao Wenjian , Yang Xuefan , Chen Haige , Huang Jian , Lin Tianxin 
Published: September 2021

Abstract

Background
Cystoscopy plays an important role in bladder cancer (BCa) diagnosis and treatment, but its sensitivity needs improvement. Artificial intelligence has shown promise in endoscopy, but few cystoscopic applications have been reported. We report a Cystoscopy Artificial Intelligence Diagnostic System (CAIDS) for BCa diagnosis.

Methods
In total, 69 204 images from 10 729 consecutive patients from 6 hospitals were collected and divided into training, internal validation, and external validation sets. The CAIDS was built using a pyramid scene parsing network and transfer learning. A subset (n = 260) of the validation sets was used for a performance comparison between the CAIDS and urologists for complex lesion detection. The diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values and 95% confidence intervals (CIs) were calculated using the Clopper-Pearson method.

Results
The diagnostic accuracies of the CAIDS were 0.977 (95% CI = 0.974 to 0.979) in the internal validation set and 0.990 (95% CI = 0.979 to 0.996), 0.982 (95% CI = 0.974 to 0.988), 0.978 (95% CI = 0.959 to 0.989), and 0.991 (95% CI = 0.987 to 0.994) in different external validation sets. In the CAIDS vs urologists’ comparisons, the CAIDS showed high accuracy and sensitivity (accuracy = 0.939, 95% CI = 0.902 to 0.964; sensitivity = 0.954, 95% CI = 0.902 to 0.983) with a short latency of 12 seconds, much more accurate and quicker than the expert urologists.

Conclusions
The CAIDS achieved accurate BCa detection with a short latency. The CAIDS may provide many clinical benefits, from increasing the diagnostic accuracy for BCa, even for commonly misdiagnosed cases such as flat cancerous tissue (carcinoma in situ), to reducing the operation time for cystoscopy.
The value of alien roadside trees for epiphytic lichen species along an urban pollution gradient
Authors: Möller Theresa , Oldeland Jens , Schultz Matthias 
Published: September 2021

Abstract
Alien tree species have been introduced to Europe and often used as roadside trees. Currently, preference is given to species that are adapted to urban climate and drier conditions. Native epiphytic lichens are adapted to local tree species; however, little is known whether a shift toward more alien roadside trees would affect the diversity of epiphytic lichens within cities. We considered three genera of roadside trees that are common in Hamburg (Germany) Acer, Tilia, and Quercus, each with a native and an alien species per genus. Species numbers, frequency and diversity of epiphytic lichens were assessed and compared. Tree locations were grouped according to three classes of increasing traffic volume as a proxy for air pollution. Mean bark pH values have been recorded for each tree individual. The species pairs Quercus robur/rubra and Acer platanoides/saccharinum showed significant differences in the diversity and abundance of lichens, with the alien species showing lower values. The species pair Tilia cordata/tomentosa did not show any significant differences. The number of nitrogen-tolerant lichen species differed little among all tree species. Lichen species richness decreased with increasing traffic volume for all tree species pairs, thus demonstrating the inhibiting effect of traffic on the occurrence of lichens. Bark pH differed little between the species pairs yet high traffic volume resulted in an increased bark pH. In conclusion, two out of three alien species had negative effects on lichen diversity. Further tree species should be assessed to better estimate the effect of alien roadside trees on lichen diversity.
A Tale of Two Bridges: The Poetry and Politics of Infrastructure in Nineteenth-Century Wales
Authors: Koehler Karin 
Published: September 2021

Abstract
Drawing on Brian Larkin’s concept of ‘infrastructural poetics’, this article considers and compares a selection of English- and Welsh-language poems, by writers including Eliza Mary Hamilton, Frederick Faber, Richard Llwyd, and Eben Fardd, about two nineteenth-century infrastructures that transformed North Wales and Great Britain’s relationship to Ireland: the Menai Suspension Bridge (1826), and the Britannia Tubular Bridge (1850). I argue that these non-canonical poems complement perspectives derived from parliamentary records, official reports, technical planning documents, scientific manuals, and journalism, enhancing our understanding of the nineteenth-century infrastructural imagination. Specifically, building on the association of infrastructural development and modernity, I explore how the poems under discussion participate in nineteenth-century negotiations about Wales’s place and future in the United Kingdom, and how these negotiations evolved between 1819 and 1852. I show that, although Wales was the site of impressive engineering feats and accelerating industrial extraction, English-language poems present the Menai Bridge in picturesque terms, drawing on popular images of the Celtic fringe that evoke timeless, ideal beauty. Anglophone verse about Britannia Bridge, by contrast, focuses explicitly on the infrastructure’s technological modernity but claims it as an English landmark. Both strategies, I suggest, effect an erasure of Wales – as a distinct cultural and political entity – from a future conceived as Anglo-British. Poems written in Welsh, and the work of Welsh writers in English, complicate this picture, not because they reject British nationalism and imperialism, but because they seek to embed a modern Welsh nation more centrally within those political and ideological frameworks.
Accelerated expansion induced by dark matter with two charges
Authors: Hansen Steen H 
Published: September 2021

ABSTRACT
The accelerated expansion of the Universe has been established through observations of supernovae, the growth of structure, and the cosmic microwave background. The most popular explanation is Einstein's cosmological constant, or dynamic variations hereof. A recent paper demonstrated that if dark matter particles are endowed with a repulsive force proportional to the internal velocity dispersion of galaxies, then the corresponding acceleration of the Universe may follow that of a cosmological constant fairly closely. However, no such long-range force is known to exist. A concrete example of such a force is derived here, by equipping the dark matter particles with two new dark charges. This result lends support to the possibility that the current acceleration of the Universe may be explained without the need for a cosmological constant.
Rituximab and mepolizumab combination therapy for glucocorticoid-resistant myocarditis related to eosinophilic granulomatosis with polyangiitis
Authors: Higashitani Kana , Yoshimi Ryusuke , Sato Yuichiro , Watanabe Toshiyuki , Ihata Atsushi 
Published: September 2021

ABSTRACT
Eosinophilic granulomatosis with polyangiitis (EGPA), which belongs to the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides, is characterised by eosinophil-rich granulomatous inflammation and small- to medium-sized vessel vasculitis associated with bronchial asthma and eosinophilia. It sometimes causes severe organ damage, of which myocardial damage is one of the most important for determining the prognosis. A case of EGPA-associated myocarditis that was refractory to glucocorticoid therapy and responded successfully to rituximab (RTX) and mepolizumab (MPZ) combination therapy is presented. A 46-year-old woman was diagnosed with EGPA-associated myocarditis due to pre-existing asthma, eosinophilia, mononeuritis multiplex, and eosinophilic myocarditis by myocardial biopsy. Transthoracic echocardiography showed thickening of the cardiac wall, pericardial effusion, and left ventricular hypokinesis. Although the myocarditis was refractory to methylprednisolone pulse therapy followed by oral high-dose prednisolone, the disease activity reached remission with the successful tapering of glucocorticoid after initiation of the RTX and MPZ combination therapy. Combination therapy with RTX and MPZ can be a good treatment option for EGPA-associated myocarditis for which it is difficult to give intravenous cyclophosphamide due to cardiac dysfunction.
Zinc trafficking 1. Probing the roles of proteome, metallothionein, and glutathione
Authors: Mahim Afsana , Karim Mohammad , Petering David H 
Published: September 2021

Abstract
The cellular trafficking pathways that conduct zinc to its sites of binding in functional proteins remain largely unspecified. In this study, the hypothesis was investigated that nonspecific proteomic binding sites serve as intermediates in zinc trafficking. Proteome from pig kidney LLC-PK1 cells contains a large concentration of such sites, displaying an average conditional stability constant of 1010-11, that are dependent on sulfhydryl ligands to achieve high-affinity binding of zinc. As a result, the proteome competes effectively with induced metallothionein for Zn2+ upon exposure of cells to extracellular Zn2+ or during in vitro direct competition. The reaction of added Zn2+ bound to proteome with apo-carbonic anhydrase was examined as a potential model for intracellular zinc trafficking. The extent of this reaction was inversely dependent upon proteome concentration and under cellular conditions thought to be negligible. The rate of reaction was strictly first order in both Zn2+ and apo-carbonic anhydrase, and also considered to be insignificant in cells. Adding the low molecular weight fraction of cell supernatant to the proteome markedly enhanced the speed of this reaction, a phenomenon dependent on the presence of glutathione (GSH). In agreement, inclusion of GSH accelerated the reaction in a concentration-dependent manner. The implications of abundant high-affinity binding sites for Zn2+ within the proteome are considered in relation to their interaction with GSH in the efficient delivery of Zn2+ to functional binding sites and in the operation of fluorescent zinc sensors as a tool to observe zinc trafficking.
Whole-exome sequencing identifiesFOXL2,FOXA2andFOXA3as candidate genes for monogenic congenital anomalies of the kidneys and urinary tract
Authors: Zheng Bixia , Seltzsam Steve , Wang Chunyan , Schierbaum Luca , Schneider Sophia , Wu Chen-Han Wilfred , Dai Rufeng , Connaughton Dervla M , Nakayama Makiko , Mann Nina , Stajic Natasa , Mane Shrikant , Bauer Stuart B , Tasic Velibor , Nam Hyun Joo , Shril Shirlee , Hildebrandt Friedhelm 
Published: September 2021

AbstractBackgroundCongenital anomalies of the kidneys and urinary tract (CAKUT) constitute the most common cause of chronic kidney disease in the first three decades of life. Variants in four Forkhead box (FOX) transcription factors have been associated with CAKUT. We hypothesized that other FOX genes, if highly expressed in developing kidneys, may also represent monogenic causes of CAKUT.MethodsWe here performed whole-exome sequencing (WES) in 541 families with CAKUT and generated four lists of CAKUT candidate genes: (A) 36 FOX genes showing high expression during renal development, (B) 4 FOX genes known to cause CAKUT to validate list A, (C) 80 genes that we identified as unique potential novel CAKUT candidate genes when performing WES in 541 CAKUT families and (D) 175 genes identified from WES as multiple potential novel CAKUT candidate genes.ResultsTo prioritize potential novel CAKUT candidates in the FOX gene family, we overlapped 36 FOX genes (list A) with lists C and D of WES-derived CAKUT candidates. Intersection with list C identified a de novo FOXL2 in-frame deletion in a patient with eyelid abnormalities and ureteropelvic junction obstruction, and a homozygous FOXA2 missense variant in a patient with horseshoe kidney. Intersection with list D identified a heterozygous FOXA3 missense variant in a CAKUT family with multiple affected individuals.ConclusionsWe hereby identified FOXL2, FOXA2 and FOXA3 as novel monogenic candidate genes of CAKUT, supporting the utility of a paralog-based approach to discover mutated genes associated with human disease.
Climate change and nephrology
Authors: Sasai Fumihiko , Roncal-Jimenez Carlos , Rogers Keegan , Sato Yuka , Brown Jared M , Glaser Jason , Garcia Gabriela , Sanchez-Lozada Laura Gabriela , Rodriguez-Iturbe Bernardo , Dawson Jaime Butler , Sorensen Cecilia , Hernando Ana Andres , Gonzalez-Quiroz Marvin , Lanaspa Miguel , Newman Lee S , Johnson Richard J 
Published: September 2021

Abstract
Climate change should be of special concern for the nephrologist, as the kidney has a critical role in protecting the host from dehydration, but it is also a favorite target of heat stress and dehydration. Here we discuss how rising temperatures and extreme heat events may affect the kidney. The most severe presentation of heat stress is heat stroke, which can result in severe electrolyte disturbance and both acute and chronic kidney disease (CKD). However, lesser levels of heat stress also have multiple effects, including exacerbating kidney disease and precipitating cardiovascular events in subjects with established kidney disease. Heat stress can also increase the risk for kidney stones, cause multiple electrolyte abnormalities and induce both acute and chronic kidney disease. Recently there have been multiple epidemics of CKD of uncertain etiology in various regions of the world, including Mesoamerica, Sri Lanka, India and Thailand. There is increasing evidence that climate change and heat stress may play a contributory role in these conditions, although other causes, including toxins, could also be involved. As climate change worsens, the nephrologist should prepare for an increase in diseases associated with heat stress and dehydration.
Telomerase as a therapeutic target in glioblastoma
Authors: Aquilanti Elisa , Kageler Lauren , Wen Patrick Y , Meyerson Matthew 
Published: September 2021

Abstract
Glioblastoma is the most common primary malignant brain tumor in adults and it continues to have a dismal prognosis. The development of targeted therapeutics has been particularly challenging, in part due to a limited number of oncogenic mutations and significant intra-tumoral heterogeneity. TERT promoter mutations were first discovered in melanoma and later found to be present in up to 80% of glioblastoma samples. They are also frequent clonal alterations in this tumor. TERT promoter mutations are one of the mechanisms for telomerase reactivation, providing cancers with cellular immortality. Telomerase is a reverse transcriptase ribonucleoprotein complex that maintains telomere length in cells with high proliferative ability. In this article, we present genomic and pre-clinical data that support telomerase as a potential “Achilles’ heel” for glioblastoma. We also summarize prior experience with anti-telomerase agents and potential new approaches to tackle this target.