bluuebunny/crossref_metadata_2025_split huggingface dataset:
CAFE: a software suite for analysis of paired-sample transposon insertion sequencing data
Authors: Abramova Anna , Osińska Adriana , Kunche Haveela , Burman Emil , Bengtsson-Palme Johan 
Published: December 2020

Abstract

Summary
Sequencing of transposon insertion libraries is used to determine the relative fitness of individual mutants at a large scale. However, there is a lack of tools for specifically analyzing data from such experiments with paired sample designs. Here, we introduce CAFE—Coefficient-based Analysis of Fitness by read Enrichment—a software package that can analyze data from paired transposon mutant sequencing experiments, generate fitness coefficients for each gene and condition and perform appropriate statistical testing on these fitness coefficients.

Availability and implementation
CAFE is implemented in Perl and R. The source code is freely available for download under the MIT License from https://github.com/bengtssonpalme/cafe and http://microbiology.se/software/cafe/

Supplementary information
Supplementary data are available at Bioinformatics online.
PC2P: parameter-free network-based prediction of protein complexes
Authors: Omranian Sara , Angeleska Angela , Nikoloski Zoran 
Published: December 2020

Abstract

Motivation
Prediction of protein complexes from protein–protein interaction (PPI) networks is an important problem in systems biology, as they control different cellular functions. The existing solutions employ algorithms for network community detection that identify dense subgraphs in PPI networks. However, gold standards in yeast and human indicate that protein complexes can also induce sparse subgraphs, introducing further challenges in protein complex prediction.

Results
To address this issue, we formalize protein complexes as biclique spanned subgraphs, which include both sparse and dense subgraphs. We then cast the problem of protein complex prediction as a network partitioning into biclique spanned subgraphs with removal of minimum number of edges, called coherent partition. Since finding a coherent partition is a computationally intractable problem, we devise a parameter-free greedy approximation algorithm, termed Protein Complexes from Coherent Partition (PC2P), based on key properties of biclique spanned subgraphs. Through comparison with nine contenders, we demonstrate that PC2P: (i) successfully identifies modular structure in networks, as a prerequisite for protein complex prediction, (ii) outperforms the existing solutions with respect to a composite score of five performance measures on 75% and 100% of the analyzed PPI networks and gold standards in yeast and human, respectively, and (iii,iv) does not compromise GO semantic similarity and enrichment score of the predicted protein complexes. Therefore, our study demonstrates that clustering of networks in terms of biclique spanned subgraphs is a promising framework for detection of complexes in PPI networks.

Availability and implementation
https://github.com/SaraOmranian/PC2P.

Supplementary information
Supplementary data are available at Bioinformatics online.
A method for subtype analysis with somatic mutations
Authors: Liu Meiling , Liu Yang , Wu Michael C , Hsu Li , He Qianchuan 
Published: December 2020

Abstract

Motivation
Cancer is a highly heterogeneous disease, and virtually all types of cancer have subtypes. Understanding the association between cancer subtypes and genetic variations is fundamental to the development of targeted therapies for patients. Somatic mutation plays important roles in tumor development and has emerged as a new type of genetic variations for studying the association with cancer subtypes. However, the low prevalence of individual mutations poses a tremendous challenge to the related statistical analysis.

Results
In this article, we propose an approach, subtype analysis with somatic mutations (SASOM), for the association analysis of cancer subtypes with somatic mutations. Our approach tests the association between a set of somatic mutations (from a genetic pathway) and subtypes, while incorporating functional information of the mutations into the analysis. We further propose a robust p-value combination procedure, DAPC, to synthesize statistical significance from different sources. Simulation studies show that the proposed approach has correct type I error and tends to be more powerful than possible alternative methods. In a real data application, we examine the somatic mutations from a cutaneous melanoma dataset, and identify a genetic pathway that is associated with immune-related subtypes.

Availability and implementation
The SASOM R package is available at https://github.com/rksyouyou/SASOM-pkg. R scripts and data are available at https://github.com/rksyouyou/SASOM-analysis.

Supplementary information
Supplementary data are available at Bioinformatics online.
Neurofilament light predicts neurological outcome after subarachnoid haemorrhage
Authors: Garland Patrick , Morton Matt , Zolnourian Ardalan , Durnford Andrew , Gaastra Ben , Toombs Jamie , Heslegrave Amanda J , More John , Zetterberg Henrik , Bulters Diederik O , Galea Ian 
Published: December 2020

AbstractTo improve outcome prediction following subarachnoid haemorrhage (SAH), we sought a biomarker integrating early brain injury and multiple secondary pathological processes in a prospective study of 42 non-traumatic SAH patients and 19 control individuals. Neurofilament light (NF-L) was elevated in CSF and serum following SAH. CSF and serum NF-L on Days 1–3 post-SAH strongly predicted modified Rankin score at 6 months, independent of World Federation of Neurosurgical Societies (WFNS) score. NF-L from Day 4 onwards also had a profound impact on outcome. To link NF-L to a SAH-specific pathological process, we investigated NF-L’s relationship with extracellular haemoglobin. Most CSF haemoglobin was not complexed with haptoglobin, yet was able to be bound by exogenous haptoglobin i.e. haemoglobin was scavengeable. CSF scavengeable haemoglobin was strongly predictive of subsequent CSF NF-L. Next, we investigated NF-L efflux from the brain after SAH. Serum and CSF NF-L correlated positively. The serum/CSF NF-L ratio was lower in SAH versus control subjects, in keeping with glymphatic efflux dysfunction after SAH. CSF/serum albumin ratio was increased following SAH versus controls. The serum/CSF NF-L ratio correlated negatively with the CSF/serum albumin ratio, indicating that transfer of the two proteins across the blood–brain interface is dissociated. In summary, NF-L is a strong predictive marker for SAH clinical outcome, adding value to the WFNS score, and is a promising surrogate end point in clinical trials.
HGFDB: a collective database of helmeted guinea fowl genomics
Authors: Li Xuzhen , Li Zhi , Shen Quankuan , Pan Yunbin , Dong Xiao , Xu Zetan , Duan Shengchang , Li Yunfei , Du Yuan , Chen Shanshan , Ma Zhaocheng , Dong Yang 
Published: December 2020

Abstract
As a vigorous and hardy and an almost disease-free game bird, the domestic helmeted guinea fowl (Numida meleagris, hereafter HGF) has attracted considerable attention in a large number of genetic study projects. However, none of the current/recent avian databases are related to this agriculturally and commercially important poultry species. To address this data gap, we developed Helmeted Guinea Fowl Database (HGFDB), which manages and shares HGF genomic and genetic data. By processing the data of genome assembly, sequencing reads and genetic variations, we organized them into eight modules, which correspond to ‘Home’, ‘Genome’, ‘Re-sequence’, ‘Gene’, ‘Variation’, ‘Download’, ‘Tools’ and ‘Help’, HGFDB provides the most comprehensive view of the HGF genome to date and will be relevant for future studies on HGF structural and functional genomics and genetic improvement.
Database URL: http://hgfdb.ynau.edu.cn/
A case report of a transcarotid transcatheter aortic valve implantation with concomitant carotid endarterectomy
Authors: Sultan Sherif , Pate Gordon , Hynes Niamh , Mylotte Darren 
Published: December 2020

Abstract

Background
Transcarotid transcatheter aortic valve implantation (TAVI) is a worthwhile substitute in patients who might otherwise be inoperable; however, it is applied in &lt;10% of TAVI cases. In patients with established carotid artery stenosis, the risk of complications is increased with the transcarotid access route.

Case summary
We report a case of concomitant transcarotid TAVI and carotid endarterectomy (CEA) in a patient with bovine aortic arch and previous complex infrarenal EndoVascular Aortic Repair (EVAR). The integrity and positioning of the previous EVAR endograft was risked by transfemoral access. The right subclavian artery was only 4.5 mm and the left subclavian was totally occluded so transcarotid access was chosen. The patient recovered well, with no neurological deficit and was discharged home after 72 h. He was last seen and was doing well 6 months post-procedure.

Discussion
In patients with severe aortoiliac disease, or previous aortic endografting, transfemoral access for TAVI can be challenging or even prohibitive. Alternative access sites such as transapical or transaortic are associated with added risk because they carry increased risk of major adverse cardiovascular events, longer intensive care unit and hospital stay, and increased cost. A transcaval approach for TAVI has also been reported but was not suitable for our patient due to prior EVAR. Concomitant TAVI via transcarotid access and CEA can be successful in experienced hands. This case highlights the importance of a team-based approach to complex TAVI cases in high-risk patients with complex vascular access.
Sporadic late-onset nemaline myopathy: a case report of a treatable cause of cardiac failure
Authors: Turnquist Casmir , Grogono Joanna C , Hofer Monika , Pitcher Alex 
Published: December 2020

Abstract

Background
Sporadic late-onset nemaline myopathy (SLONM) is a rare, acquired, adult-onset myopathy, characterized by proximal muscle weakness and the pathognomonic feature of nemaline rods in muscle fibres. Sporadic late-onset nemaline myopathy is associated with cardiac pathology in case reports and small case series, but the severity of cardiac disease is generally mild and rarely requires specific treatment. This case report describes severe heart failure as an early feature of SLONM, which responded to specific treatments, and highlights SLONM as a potentially reversible cause of heart failure.

Case summary
A 65-year-old woman presented with progressive muscle weakness and a dramatic loss of muscle bulk in her thighs, followed by progressive effort breathlessness over an 18-month period. She required a wheelchair to ambulate. A diagnosis of SLONM was made on histopathological assessment of a muscle biopsy along with electron microscopy. An echocardiogram showed a severely dilated and impaired left ventricle. She was treated with standard heart failure medications and autologous stem cell transplantation, which resulted in improvement of both her cardiac and muscle function, and allowed her to walk again and resume near-normal functional performance status.

Discussion
Cardiomyopathy can be a relatively early and life-threatening feature of SLONM and even in severe cases can be effectively treated with standard heart failure medications and autologous stem cell transplantation.
Atrial fibrillation in low- and middle-income countries: a narrative review
Authors: Santos Itamar S , Goulart Alessandra C , Olmos Rodrigo D , Thomas G Neil , Lip Gregory Y H , Lotufo Paulo A , Benseñor Isabela M ,   the NIHR Global Health Group on Atrial Fibrillation Management, Arasalingam Ajini , Benseñor Isabela , Brocklehurst Peter , Cheng Kar Keung , Feng Mei , Goulart Alessandra C , Greenfield Sheila , Guo Yutao , Guruparan Mahesan , Gusso Gustavo , Hao Wang , Humphreys Lindsey , Kumarendran Balachandran , Jolly Kate , Jowett Sue , Lancashire Emma , Lane Deirdre A , Li Xuewen , Li Yanguang , Lip Gregory Y H , Lobban Trudie , Lotufo Paulo , Manseki-Holland Semira , Moore David , Nirantharakumar Krishnarajah , Olmos Rodrigo , Santos Itamar S , Shantsila Alena , Szmigin Isabelle , Subaschandren Kumaran , Surenthirakumaran Rajendra , Neil Thomas G , Wang Jingya 
Published: December 2020

AbstractPreventing premature non-communicable disease mortality necessitates a thorough review of one of the most important risk factors for stroke, which is atrial fibrillation (AF). The latter and AF-related stroke are still considered to be problems of high-income countries and are frequently overlooked in low- and middle-income countries (LMICs). In this narrative review, we provide an overview of studies that evaluated at least one of the following determinants of AF burden in LMICs: current epidemiology and trends, stroke prevention, health outcomes, and economic burden. Studies focusing on samples close to the general population (including community- and primary care-based samples) indicate sex-specific prevalence rates up to 7.4% in LMICs. Although AF prevalence is still higher in high-income countries than LMICs, the gap in AF burden between these two groups has been reducing in the past three decades. Oral anticoagulant (OAC) therapy for stroke prevention is underused in LMICs, and there are little data on OAC therapy in relation to stroke risk scores, such as CHA2DS2-VASc. Available data also points to higher morbidity and mortality for patient with AF in LMICs than their counterparts in high-income countries. Data on the consequent economic burden in LMICs is scarce, but it is reasonable to consider it will follow the same trend as that observed for health outcomes. Raising the visibility of AF as a public health problem in LMICs is necessary as a first step to providing adequate care for patients with this condition.
The Impact of the COVID-19 Epidemic on Older Adults in Rural and Urban Areas in Mexico
Authors: Rivera-Hernandez Maricruz , Ferdows Nasim B , Kumar Amit 
Published: December 2020

Abstract

Objectives
Mexico is among the countries in Latin America hit hardest by coronavirus disease 2019 (COVID-19). A large proportion of older adults in Mexico have high prevalence of multimorbidity and live in poverty with limited access to health care services. These statistics are even higher among adults living in rural areas, which suggest that older adults in rural communities may be more susceptible to COVID-19. The objectives of the article were to compare clinical and demographic characteristics for people diagnosed with COVID-19 by age group, and to describe cases and mortality in rural and urban communities.

Method
We linked publicly available data from the Mexican Ministry of Health and the Census. Municipalities were classified based on population as rural (&lt;2,500), semirural (≥2,500 and &lt;15,000), semiurban (≥15,000 and &lt;100,000), and urban (≥100,000). Zero-inflated negative binomial models were performed to calculate the total number of COVID-19 cases, and deaths per 1,000,000 persons using the population of each municipality as a denominator.

Results
Older adults were more likely to be hospitalized and reported severe cases, with higher mortality rates. In addition, rural municipalities reported a higher number of COVID-19 cases and mortality related to COVID-19 per million than urban municipalities. The adjusted absolute difference in COVID-19 cases was 912.7 per million (95% confidence interval [CI]: 79.0–1746.4) and mortality related to COVID-19 was 390.6 per million (95% CI: 204.5–576.7).

Discussion
Urgent policy efforts are needed to mandate the use of face masks, encourage handwashing, and improve specialty care for Mexicans in rural areas.
Developing a New Behavioral Framework for Dementia Care Partner Resilience: A Mixed Research Synthesis
Authors: Zhou Yuanjin , O’Hara Avery , Ishado Emily , Borson Soo , Sadak Tatiana 
Published: December 2020

Abstract

Background and Objectives
Caring for a person living with dementia requires resilience, the capacity to recover and grow from challenging situations. Despite the increasing interest in assessing and promoting resilience for dementia care partners, behaviors that indicate this attribute are not well known. The aim of this study was to synthesize the literature to identify resilience-related behaviors and develop a new framework for future validation and intervention research.

Research Design and Methods
We searched English-language peer-reviewed articles (January 1991–June 2019) reporting qualitative or quantitative descriptions of resilience-related behaviors among dementia care partners. Thematic analysis was used to categorize behaviors into domains, identify the relationships among them, and generate a thematic map.

Results
Sixteen articles were identified according to predefined inclusion criteria. Four domains emerged: (a) problem–response behaviors (problem-solving, problem-distancing); (b) self-growth behaviors (self-care activities, spiritual-related activities, and developing and maintaining meaningful social relationships); (c) help-related behaviors (help-seeking and help-receiving); and (d) learning-related behaviors (learning from others and reflection). Definitions of each domain, identification of corresponding behaviors, and formulation of Care Partner Resilience (CP-R) behavioral framework were informed by mixed research synthesis results and other relevant literature.

Discussion and Implications
The CP-R framework emerged as a result of a new focus on identifying and cultivating strengths instead of evaluating strain and burden. It serves as a useful foundation for understanding the impact of specific behaviors on dementia care partner resilience. Once validated, this framework will inform the development of future measures, research, interventions, and policies for dementia care partners.
Findings of Sequential Pilot Trials of Aliviado Dementia Care to Inform an Embedded Pragmatic Clinical Trial
Authors: Lin Shih-Yin , Schneider Catherine E , Bristol Alycia A , Clancy Maureen , Sprague Sara A , Aldridge Melissa , Cortes Tara , Goldfeld Keith S , Kutner Jean S , Mitchell Susan L , Shega Joseph W , Wu Bei , Zhu Carolyn W , Brody Abraham A 
Published: December 2020

Abstract

Background and Objectives
Many investigators of Alzheimer’s disease and related dementias (AD/ADRD) are unfamiliar with the embedded pragmatic clinical trials (ePCTs) and the indispensable pilot phase preceding ePCTs. This paper provides a much-needed example for such a pilot phase and discusses implementation barriers and additional infrastructure and implementation strategies developed in preparation for a nationwide AD/ADRD ePCT.

Research Design and Methods
Two pilot trials were conducted in 2 hospices sequentially to refine and test Aliviado Dementia Care—Hospice Edition, a complex quality improvement intervention for advanced dementia symptom management. Readiness for the subsequent full-scale ePCT was assessed by three milestones: ≥80% training completion rate (“feasibility”), ≥80% posttraining survey respondents indicating intention for practice changes (“applicability”), and at least 1 Aliviado care plan/assessment instrument administered in ≥75% of dementia patients admitted to home hospice within 1-month posttraining (“fidelity”).

Results
Participants included 72 interdisciplinary team members and 11 patients with AD/ADRD across the pilots. Feasibility, applicability, and fidelity outcomes (92%, 93%, and 100%, respectively) all surpassed the preestablished milestones (80%, 80%, and 75%). Main implementation challenges were related to hospice staff turnover, integration of the Aliviado toolbox materials within the electronic health records, and hospices’ limited research experience and infrastructure.

Discussion and Implications
This pilot phase demonstrated feasibility, applicability, and fidelity required to proceed to the full-scale ePCT. Our study findings and discussions of additional infrastructure and implementation strategies developed following the pilot phase can inform researchers and clinicians interested in conducting AD/ADRD-related pilot studies for ePTCs or quality improvement initiatives.

Clinical Trials Registration Number
NCT03681119
Highly biocompatible super-resolution fluorescence imaging using the fast photoswitching fluorescent protein Kohinoor and SPoD-ExPAN with L
p-regularized image reconstruction
Authors: Wazawa Tetsuichi , Arai Yoshiyuki , Kawahara Yoshinobu , Takauchi Hiroki , Washio Takashi , Nagai Takeharu 
Published: December 2020

Abstract
Far-field super-resolution fluorescence microscopy has enabled us to visualize live cells in great detail and with an unprecedented resolution. However, the techniques developed thus far have required high-power illumination (102–106 W/cm2), which leads to considerable phototoxicity to live cells and hampers time-lapse observation of the cells. In this study we show a highly biocompatible super-resolution microscopy technique that requires a very low-power illumination. The present technique combines a fast photoswitchable fluorescent protein, Kohinoor, with SPoD-ExPAN (super-resolution by polarization demodulation/excitation polarization angle narrowing). With this technique, we successfully observed Kohinoor-fusion proteins involving vimentin, paxillin, histone and clathrin expressed in HeLa cells at a spatial resolution of 70–80 nm with illumination power densities as low as ~1 W/cm2 for both excitation and photoswitching. Furthermore, although the previous SPoD-ExPAN technique used L1-regularized maximum-likelihood calculations to reconstruct super-resolved images, we devised an extension to the Lp-regularization to obtain super-resolved images that more accurately describe objects at the specimen plane. Thus, the present technique would significantly extend the applicability of super-resolution fluorescence microscopy for live-cell imaging.
Inefficiencies in phase II to phase III transition impeding successful drug development in glioblastoma
Authors: Balasubramanian Adithya , Gunjur Ashray , Hafeez Umbreen , Menon Siddharth , Cher Lawrence M , Parakh Sagun , Gan Hui Kong 
Published: December 2020

Abstract

Background
Improving outcomes of patients with glioblastoma (GBM) represents a significant challenge in neuro-oncology. We undertook a systematic review of key parameters of phase II and III trials in GBM to identify and quantify the impact of trial design on this phenomenon.

Methods
Studies between 2005 and 2019 inclusive were identified though MEDLINE search and manual bibliography searches. Phase II studies (P2T) were restricted to those referenced by the corresponding phase III trials (P3T). Clinical and statistical characteristics were extracted. For each P3T, corresponding P2T data was “optimally matched,” where same drug was used in similar schedule and similar population; “suboptimally matched” if dis-similar schedule and/or treatment setting; or “lacking.” Phase II/III transition data were compared by Pearson Correlation, Fisher’s exact or chi-square testing.

Results
Of 20 P3Ts identified, 6 (30%) lacked phase II data. Of the remaining 14 P3T, 9 had 1 prior P2T, 4 had 2 P2T, and 1 had 3 P2T, for a total of 20 P3T-P2T pairs (called dyads). The 13 “optimally matched” dyads showed strong concordance for mPFS (r2 = 0.95, P &lt; .01) and mOS (r2 = 0.84, P &lt; .01), while 7 “suboptimally matched” dyads did not (P &gt; .05). Overall, 7 P3Ts underwent an ideal transition from P2T to P3T. “Newly diagnosed” P2Ts with mPFS &lt; 14 months and/or mOS&lt; 22 months had subsequent negative P3Ts. “Recurrent” P2Ts with mPFS &lt; 6 months and mOS&lt; 12 months also had negative P3Ts.

Conclusion
Our findings highlight the critical role of optimally designed phase II trials in informing drug development for GBM.