bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction and early biomarkers of cognitive decline in Parkinson disease and atypical parkinsonism: a population-based study
Authors: Bäckström David , Granåsen Gabriel , Mo Susanna Jakobson , Riklund Katrine , Trupp Miles , Zetterberg Henrik , Blennow Kaj , Forsgren Lars , Domellöf Magdalena Eriksson 
Published: March 2022

Abstract
The progression of cognitive decline is heterogeneous in the three most common idiopathic parkinsonian diseases: Parkinson disease, multiple system atrophy and progressive supranuclear palsy. The causes for this heterogeneity are not fully understood, and there are no validated biomarkers that can accurately identify patients who will develop dementia and when. In this population-based, prospective study, comprehensive neuropsychological testing was performed repeatedly in new-onset, idiopathic parkinsonism. Dementia was diagnosed until 10 years and participants (N = 210) were deeply phenotyped by multimodal clinical, biochemical, genetic and brain imaging measures. At baseline, before the start of dopaminergic treatment, mild cognitive impairment was prevalent in 43.4% of the patients with Parkinson disease, 23.1% of the patients with multiple system atrophy and 77.8% of the patients with progressive supranuclear palsy. Longitudinally, all three diseases had a higher incidence of cognitive decline compared with healthy controls, but the types and severity of cognitive dysfunctions differed. In Parkinson disease, psychomotor speed and attention showed signs of improvement after dopaminergic treatment, while no such improvement was seen in other diseases. The 10-year cumulative probability of dementia was 54% in Parkinson disease and 71% in progressive supranuclear palsy, while there were no cases of dementia in multiple system atrophy. An easy-to-use, multivariable model that predicts the risk of dementia in Parkinson disease within 10 years with high accuracy (area under the curve: 0.86, P &lt; 0.001) was developed. The optimized model adds CSF biomarkers to four easily measurable clinical features at baseline (mild cognitive impairment, olfactory function, motor disease severity and age). The model demonstrates a highly variable but predictable risk of dementia in Parkinson disease, e.g. a 9% risk within 10 years in a patient with normal cognition and CSF amyloid-β42 in the highest tertile, compared with an 85% risk in a patient with mild cognitive impairment and CSF amyloid-β42 in the lowest tertile. Only small or no associations with cognitive decline were found for factors that could be easily modifiable (such as thyroid dysfunction). Risk factors for cognitive decline in multiple system atrophy and progressive supranuclear palsy included signs of systemic inflammation and eye movement abnormalities. The predictive model has high accuracy in Parkinson disease and might be used for the selection of patients into clinical trials or as an aid to improve the prevention of dementia.
A Randomized Clinical Trial of Human Papillomavirus Test-and-Treat as Compared to Cytology-Based Screening for Prevention of Cervical Cancer Among Women With Human Immunodeficiency Virus: AIDS Clinical Trials Group Protocol A5282
Authors: Wilkin Timothy , Chen Huichao , Sahasrabuddhe Vikrant , Matining Roy , Mngqibisa Rosie , Chinula Lameck , Mbilizi Yamikani , Magure Tsitsi , Omoz-Oarhe Ayotunde E , Rassool Mohammed , Riviere Cynthia , Bhosale Rhamesh , Godbole Sheela , Naranjo Reena , Coombs Robert , Michelow Pamela , Godfrey Catherine , Firnhaber Cynthia 
Published: March 2022

Abstract

Background
Cytology-based cervical cancer screening followed by confirmation and treatment of biopsy-proven high-grade squamous intraepithelial lesions (bHSIL) is difficult to implement in resource-constrained settings. We hypothesized that high-risk human papillomavirus (hrHPV) testing followed by immediate cryotherapy of women with hrHPV (HPV screen-and-treat) may improve outcomes.

Methods
Randomized, open-label, phase 2, multinational clinical trial enrolling women with human immunodeficiency virus (HIV) age 18 or older with cervical hrHPV and having no cervical lesions or lesions appropriate for cryotherapy. Women were randomized to immediate cryotherapy (Arm A) or cytology-based screening (Arm B). For Arm A, cervical biopsies were obtained followed by cervical cryotherapy, and in Arm B, women with abnormal cytology underwent colposcopy followed by loop electroexcision procedure (LEEP) if bHSIL was detected. Women were followed through 30 months. The primary outcome was time to bHSIL detected from Month 6 through study completion.

Results
In total, 288 women (145 in Arm A, 143 in Arm B) were randomized: median age 35 years, 84% on antiretroviral therapy, median CD4 501 cells/mm3. In Arm A, 39 (27%) of women had bHSIL at entry, and in Arm B, 88 (62%) had abnormal cytology, 22 (15%) were diagnosed with bHSIL, 12 (8%) underwent LEEP. In follow-up, 30 (21%) and 31 (22%) developed bHSIL; time to bHSIL was similar between arms (P=.94). The prevalence of hrHPV at Month 6 was similar between arms (61% and 70%, P=.13).

Conclusions
HPV test-and-treat was not associated with improved bHSIL outcomes as compared to cytology-based screening. More effective treatment options are required to improve outcomes from screen-and-treat programs.

Clinical Trials Registration
NCT01315363.
Clinical Course and Impact of Immune Checkpoint Inhibitor Colitis Resembling Microscopic Colitis
Authors: Fredrick Thomas W , Ramos Guilherme P , Braga Neto Manuel B , Kane Sunanda , Faubion William A , Loftus Edward V , Pardi Darrell S , Pasha Shabana F , Farraye Francis A , Zhang Lizhi , Raffals Laura E 
Published: March 2022

Abstract

Background
Microscopic colitis (MC) is suspected to result from increased immune activity in gut mucosa. Immune checkpoint inhibitors (ICIs) treat cancer by activating the immune system, and further investigation is needed regarding their role in the development of MC.

Methods
A retrospective case series investigated cases of endoscopically and histologically confirmed MC developing after administration of ICIs. Clinical notes and medication administration records were reviewed for demographics, symptom duration, and treatment response.

Results
Nineteen cases of de novo MC were identified, with 95% of cases requiring steroid treatment, 53% presenting with hospitalization, and colitis-related mortality in 1 individual. Symptom onset occurred a median of 160 days after initiation of ICI therapy and 53 days after their most recent dose of therapy. Patients had a median of 125 days of symptoms, and ICI therapy was held in 70% of individuals due for treatment.

Conclusions
MC can develop after ICI administration, and presents with severe symptoms, often requiring hospitalization and steroid treatment. In certain individuals this can require a prolonged treatment course of steroid therapy or immunomodulators. Individuals developing diarrhea after ICI therapy warrant thorough workup including endoscopy and rapid treatment initiation given the disease severity observed in this series.
Transcatheter aortic valve replacement in a patient with critical bicuspid aortic stenosis and cardiogenic shock: case report
Authors: El Tahlawy Walid , Bader Feras , Traina Mahmoud Idris , Edris Ahmad 
Published: March 2022

Abstract

Background
Cardiogenic shock (CS) is associated with significant morbidity and mortality (27–51%). Little is known about the feasibility and safety of emergency transcatheter aortic valve replacement (TAVR) for critical aortic stenosis (AS) in acute myocardial infarction (AMI) with CS.

Case summary
A 57-year-old male with history of tobacco dependence and diabetes mellitus presented with acute posterior ST-segment elevation myocardial infarction and CS. The patient initially underwent successful primary percutaneous intervention to an anomalous circumflex artery coming off the right cusp. It was noted to have advanced CS out of proportion to his coronary anatomy. Echocardiographic assessment noted critical AS. Heart team decided to perform percutaneous aortic balloon valvuloplasty under support of extracorporeal membrane oxygenation. Percutaneous aortic balloon valvuloplasty was performed and was complicated by severe aortic regurgitation (AR). A balloon-expandable transcatheter heart valve was then placed with resolution of AR and stabilization of the patient. Then, the patient was subsequently decannulated within a week then was able to go home after 47 days (32 days intensive care unit). His course was notable for a minor stroke due to initial period of hypotension and CS. He was extubated and remained hospitalized for several weeks participating in rehabilitation. Follow-up echo showed a well-seated and functioning transcatheter heart valve. His left ventricular systolic function improved from 21% to 45%.

Conclusion
Emergency TAVR is feasible and can be performed in a patient with AMI and CS. Early initiation of mechanical support allowed the patient to receive definitive treatment. The multidisciplinary heart team is essential and reflected in the ultimate outcome of our patient.
Sex differences in associations of comorbidities with incident cardiovascular disease: focus on absolute risk
Authors: Dronkers Just , Meems Laura M G , van Veldhuisen Dirk J , Meyer Sven , Kieneker Lyanne M , Gansevoort Ron T , Bakker Stephan J L , Rienstra Michiel , de Boer Rudolf A , Suthahar Navin 
Published: March 2022

Abstract

Aim
To examine sex differences in associations of obesity, type-2 diabetes, hypertension, and atrial fibrillation (AF) with incident cardiovascular disease (CVD), focusing on absolute risk measures.

Methods and results
We included a total of 7994 individuals (mean age 49.1 years; 51.2% women) without prior CVD from the PREVEND (Prevention of Renal and Vascular End-stage Disease) cohort with a median follow-up of 12.5 years. Using Poisson regression, we calculated the increase in absolute as well as relative CVD risk associated with a comorbidity using incidence rate differences (IRD = IRcomorbidity−IRno-comorbidity) and incidence rate ratios (IRR = IRcomorbidity/IRno-comorbidity), respectively. Sex differences were presented as women-to-men differences (WMD = IRDwomen−IRDmen) and women-to-men ratios (WMR = IRRwomen/IRRmen). Absolute CVD risk was lower in women than in men (IRwomen: 6.73 vs. IRmen: 14.58 per 1000 person-years). While increase in absolute CVD risk associated with prevalent hypertension was lower in women than in men [WMD: −6.12, 95% confidence interval: (−9.84 to −2.40), P = 0.001], increase in absolute CVD risk associated with prevalent obesity [WMD: −4.25 (−9.11 to 0.61), P = 0.087], type-2 diabetes [WMD: −1.04 (−14.36 to 12.29), P = 0.879] and AF [WMD: 18.39 (−39.65 to 76.43), P = 0.535] did not significantly differ between the sexes. Using relative risk measures, prevalent hypertension [WMR: 1.49%, 95% confidence interval: (1.12–1.99), P = 0.006], type-2 diabetes [WMR: 1.73 (1.09–2.73), P = 0.019], and AF [WMR: 2.53 (1.12–5.70), P = 0.025] were all associated with higher CVD risk in women than in men.

Conclusion
Increase in absolute risk of developing CVD is higher in hypertensive men than in hypertensive women, but no substantial sex-related differences were observed among individuals with obesity, type-2 diabetes and AF. On a relative risk scale, comorbidities, in general, confer a higher CVD risk in women than in men.
GeneCup: mining PubMed and GWAS catalog for gene–keyword relationships
Authors: Gunturkun Mustafa H , Flashner Efraim , Wang Tengfei , Mulligan Megan K , Williams Robert W , Prins Pjotr , Chen Hao 
Published: March 2022

Abstract
Interpreting and integrating results from omics studies typically requires a comprehensive and time consuming survey of extant literature. GeneCup is a literature mining web service that retrieves sentences containing user-provided gene symbols and keywords from PubMed abstracts. The keywords are organized into an ontology and can be extended to include results from human genome-wide association studies. We provide a drug addiction keyword ontology that contains over 300 keywords as an example. The literature search is conducted by querying the PubMed server using a programming interface, which is followed by retrieving abstracts from a local copy of the PubMed archive. The main results presented to the user are sentences where gene symbol and keywords co-occur. These sentences are presented through an interactive graphical interface or as tables. All results are linked to the original abstract in PubMed. In addition, a convolutional neural network is employed to distinguish sentences describing systemic stress from those describing cellular stress. The automated and comprehensive search strategy provided by GeneCup facilitates the integration of new discoveries from omic studies with existing literature. GeneCup is free and open source software. The source code of GeneCup and the link to a running instance is available at https://github.com/hakangunturkun/GeneCup.
Independent Size Expansions and Intron Proliferation in Red Algal Plastid and Mitochondrial Genomes
Authors: van Beveren Fabian , Eme Laura , López-García Purificación , Ciobanu Maria , Moreira David 
Published: March 2022

Abstract
Proliferation of selfish genetic elements has led to significant genome size expansion in plastid and mitochondrial genomes of various eukaryotic lineages. Within the red algae, such expansion events are only known in the plastid genomes of the Proteorhodophytina, a highly diverse group of mesophilic microalgae. By contrast, they have never been described in the much understudied red algal mitochondrial genomes. Therefore, it remains unclear how widespread such organellar genome expansion events are in this eukaryotic phylum. Here, we describe new mitochondrial and plastid genomes from 25 red algal species, thereby substantially expanding the amount of organellar sequence data available, especially for Proteorhodophytina, and show that genome expansions are common in this group. We confirm that large plastid genomes are limited to the classes Rhodellophyceae and Porphyridiophyceae, which, in part, are caused by lineage-specific expansion events. Independently expanded mitochondrial genomes—up to three times larger than typical red algal mitogenomes—occur across Proteorhodophytina classes and a large shift toward high GC content occurred in the Stylonematophyceae. Although intron proliferation is the main cause of plastid and mitochondrial genome expansion in red algae, we do not observe recent intron transfer between different organelles. Phylogenomic analyses of mitochondrial and plastid genes from our expanded taxon sampling yielded well-resolved phylogenies of red algae with strong support for the monophyly of Proteorhodophytina. Our work shows that organellar genomes followed different evolutionary dynamics across red algal lineages.
Excess mortality in Israel associated with COVID-19 in 2020–2021 by age group and with estimates based on daily mortality patterns in 2000–2019
Authors: Peretz Chava , Rotem Naama , Keinan-Boker Lital , Furshpan Avner , Green Manfred , Bitan Michal , Steinberg David M 
Published: March 2022

AbstractBackgroundWe aimed to build a basic daily mortality curve in Israel based on 20-year data accounting for long-term and annual trends, influenza-like illness (ILI) and climate factors among others, and to use the basic curve to estimate excess mortality during 65 weeks of the COVID-19 pandemic in 2020–2021 stratified by age groups.MethodsUsing daily mortality counts for the period 1 January 2000 to 31 December 2019, weekly ILI counts, daily climate and yearly population sizes, we fitted a quasi-Poisson model that included other temporal covariates (a smooth yearly trend, season, day of week) to define a basic mortality curve. Excess mortality was calculated as the difference between the observed and expected deaths on a weekly and periodic level. Analyses were stratified by age group.ResultsBetween 23 March 2020 and 28 March 2021, a total of 51 361 deaths were reported in Israel, which was 12% higher than the expected number for the same period (expected 45 756 deaths; 95% prediction interval, 45 325–46 188; excess deaths, 5605). In the same period, the number of COVID-19 deaths was 6135 (12% of all observed deaths), 9.5% larger than the estimated excess mortality. Stratification by age group yielded a heterogeneous age-dependent pattern. Whereas in ages 90+ years (11% excess), 100% of excess mortality was attributed to COVID-19, in ages 70–79 years there was a greater excess (21%) with only 82% attributed to COVID-19. In ages 60–69 and 20–59 years, excess mortality was 14% and 10%, respectively, and the number of COVID-19 deaths was higher than the excess mortality. In ages 0–19 years, we found 19% fewer deaths than expected.ConclusionThe findings of an age-dependent pattern of excess mortality may be related to indirect pathways in mortality risk, specifically in ages &lt;80 years, and to the implementation of the lockdown policies, specifically in ages 0–19 years with lower deaths than expected.
Nonlinear dimension reduction for surrogate modeling using gradient information
Authors: Bigoni Daniele , Marzouk Youssef , Prieur Clémentine , Zahm Olivier 
Published: March 2022

Abstract
We introduce a method for the nonlinear dimension reduction of a high-dimensional function $u:{\mathbb{R}}^d\rightarrow{\mathbb{R}}$, $d\gg 1$. Our objective is to identify a nonlinear feature map $g:{\mathbb{R}}^d\rightarrow{\mathbb{R}}^m$, with a prescribed intermediate dimension $m\ll d$, so that $u$ can be well approximated by $f\circ g$ for some profile function $f:{\mathbb{R}}^m\rightarrow{\mathbb{R}}$. We propose to build the feature map by aligning the Jacobian $\nabla g$ with the gradient $\nabla u$, and we theoretically analyze the properties of the resulting $g$. Once $g$ is built, we construct $f$ by solving a gradient-enhanced least squares problem. Our practical algorithm uses a sample $\{{\textbf{x}}^{(i)},u({\textbf{x}}^{(i)}),\nabla u({\textbf{x}}^{(i)})\}_{i=1}^N$ and builds both $g$ and $f$ on adaptive downward-closed polynomial spaces, using cross validation to avoid overfitting. We numerically evaluate the performance of our algorithm across different benchmarks, and explore the impact of the intermediate dimension $m$. We show that building a nonlinear feature map $g$ can permit more accurate approximation of $u$ than a linear $g$, for the same input data set.
Factors associated with tungiasis among school-age children in Kwale County, rural Kenya
Authors: Mwai Judy , Nyole Diana , Abdi Mohamed H , Omogi Jarim 
Published: March 2022

Abstract

Background
The parasitic disease tungiasis, caused by the flea Tunga penetrans, remains an important public health problem among children and the elderly. The study assessed the factors influencing prevention and control of tungiasis infection among school-age children in Kwale County, Kenya.

Methods
A cross-sectional survey was conducted in five villages in Lunga Lunga subcounty among 538 children ages 5–14 y. The study employed a mobile application tool in collecting sociodemographic, knowledge, perception and practice data on prevention and control of tungiasis with frequencies and bivariate and multivariate regression analysis used.

Results
The prevalence of tungiasis was found to be 62.1% (328/528), with fathers’ education level, place of residence and wearing shoes being factors associated with infection. Those who wore shoes were less likely to be infected compared with those who did not (odds ratio 0.059 [95% confidence interval 0.29 to 0.12]). Children living in Dzombo B and Kinyungu were less likely to be infected with tungiasis compared with those living in Bandu, holding other factors constant.

Conclusion
Creating awareness of the cause of tungiasis remains of key public importance. Hygiene promotion, including wearing of shoes and the general cleanliness of the environment at the community level, needs to be implemented.
Developing a COVID-19 WHO Clinical Progression Scale inpatient database from electronic health record data
Authors: Ramaswamy Priya , Gong Jen J , Saleh Sameh N , McDonald Samuel A , Blumberg Seth , Medford Richard J , Liu Xinran 
Published: March 2022

Abstract

Objective
There is a need for a systematic method to implement the World Health Organization’s Clinical Progression Scale (WHO-CPS), an ordinal clinical severity score for coronavirus disease 2019 patients, to electronic health record (EHR) data. We discuss our process of developing guiding principles mapping EHR data to WHO-CPS scores across multiple institutions.

Materials and Methods
Using WHO-CPS as a guideline, we developed the technical blueprint to map EHR data to ordinal clinical severity scores. We applied our approach to data from 2 medical centers.

Results
Our method was able to classify clinical severity for 100% of patient days for 2756 patient encounters across 2 institutions.

Discussion
Implementing new clinical scales can be challenging; strong understanding of health system data architecture was integral to meet the clinical intentions of the WHO-CPS.

Conclusion
We describe a detailed blueprint for how to apply the WHO-CPS scale to patient data from the EHR.
In or out of the game? Exploring the perseverance of female managers leaving consultancy and its implications
Authors: Taminiau Yvette , Teelken Christine , Berkhof Nina , Kuyt Tjarda 
Published: March 2022

AbstractIn the Big 4 accountancy/consultancy firms, many female consultants leave their organization at the (senior) management level. Based on 31 in-depth interviews with Dutch consultants and alumni consultants at various senior levels, we analyzed the main reasons why women leave before reaching the top of the organization, the so-called ‘leaking pipeline’. We found two main reasons for female consultants to drop out. First, at manager level, consultants are required to change their role and skillset, such as increasing their internal visibility (presenteeism) by self-promotion, strategies that evidently suit male consultants better, while secondly, the transition to a management function often coincides with a phase in which women start to have children. Since that period often coincides with reaching the function of (senior) manager, more women than men decide to leave the consultancy organizations, because they are not able to balance their work–life with further career progress. These outcomes are not new by themselves, but highlight once again the persistence of the promotion game, based on impression management and visibility. But what is new is that we discuss our findings critically, reflecting and contrasting this promotion game with the current needs of millennials with respect to work, career, and work–life balance. If this generation is not interested in ‘playing this game’, it means that the current HR policy of Big 4 accountancy/consultancy firms is obsolete. We propose a number of new approaches to reflect and reconsider this persistent problem.