bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNAglib: a python package for RNA 2.5 D graphs
Authors: Mallet Vincent , Oliver Carlos , Broadbent Jonathan , Hamilton William L , Waldispühl Jérôme 
Published: December 2021

AbstractSummaryRNA 3D architectures are stabilized by sophisticated networks of (non-canonical) base pair interactions, which can be conveniently encoded as multi-relational graphs and efficiently exploited by graph theoretical approaches and recent progresses in machine learning techniques. RNAglib is a library that eases the use of this representation, by providing clean data, methods to load it in machine learning pipelines and graph-based deep learning models suited for this representation. RNAglib also offers other utilities to model RNA with 2.5 D graphs, such as drawing tools, comparison functions or baseline performances on RNA applications.Availability and implementationThe method is distributed as a pip package, RNAglib. Data are available in a repository and can be accessed on rnaglib's web page. The source code, data and documentation are available at https://rnaglib.cs.mcgill.ca.Supplementary informationSupplementary data are available at Bioinformatics online.
Deep learning-based brain transcriptomic signatures associated with the neuropathological and clinical severity of Alzheimer’s disease
Authors: Wang Qi , Chen Kewei , Su Yi , Reiman Eric M. , Dudley Joel T. , Readhead Benjamin 
Published: December 2021

AbstractBrain tissue gene expression from donors with and without Alzheimer’s disease has been used to help inform the molecular changes associated with the development and potential treatment of this disorder. Here, we use a deep learning method to analyse RNA-seq data from 1114 brain donors from the Accelerating Medicines Project for Alzheimer’s Disease consortium to characterize post-mortem brain transcriptome signatures associated with amyloid-β plaque, tau neurofibrillary tangles and clinical severity in multiple Alzheimer’s disease dementia populations. Starting from the cross-sectional data in the Religious Orders Study and Memory and Aging Project cohort (n = 634), a deep learning framework was built to obtain a trajectory that mirrors Alzheimer’s disease progression. A severity index was defined to quantitatively measure the progression based on the trajectory. Network analysis was then carried out to identify key gene (index gene) modules present in the model underlying the progression. Within this data set, severity indexes were found to be very closely correlated with all Alzheimer’s disease neuropathology biomarkers (R ∼ 0.5, P &lt; 1e−11) and global cognitive function (R = −0.68, P &lt; 2.2e−16). We then applied the model to additional transcriptomic data sets from different brain regions (MAYO, n = 266; Mount Sinai Brain Bank, n = 214), and observed that the model remained significantly predictive (P &lt; 1e−3) of neuropathology and clinical severity. The index genes that significantly contributed to the model were integrated with Alzheimer’s disease co-expression regulatory networks, resolving four discrete gene modules that are implicated in vascular and metabolic dysfunction in different cell types, respectively. Our work demonstrates the generalizability of this signature to frontal and temporal cortex measurements and additional brain donors with Alzheimer’s disease, other age-related neurological disorders and controls, and revealed that the transcriptomic network modules contribute to neuropathological and clinical disease severity. This study illustrates the promise of using deep learning methods to analyse heterogeneous omics data and discover potentially targetable molecular networks that can inform the development, treatment and prevention of neurodegenerative diseases like Alzheimer’s disease.
The Anti-Circumsporozoite Antibody Response of Children to Seasonal Vaccination With the RTS,S/AS01E Malaria Vaccine
Authors: Sagara Issaka , Zongo Issaka , Cairns Matthew , Yerbanga Rakiswendé Serge , Mahamar Almahamoudou , Nikièma Frédéric , Tapily Amadou , Sompougdou Frédéric , Diarra Modibo , Zoungrana Charles , Issiaka Djibrilla , Haro Alassane , Sanogo Koualy , Aziz Sienou Abdoul , Kaya Mahamadou , Traore Seydou , Thera Ismaila , Diarra Kalifa , Dolo Amagana , Kuepfer Irene , Snell Paul , Milligan Paul , Ockenhouse Christian , Ofori-Anyinam Opokua , Tinto Halidou , Djimde Abdoulaye , Ouedraogo Jean Bosco , Dicko Alassane , Chandramohan Daniel , Greenwood Brian 
Published: December 2021

AbstractBackgroundA trial in African children showed that combining seasonal vaccination with the RTS,S/AS01E vaccine with seasonal malaria chemoprevention reduced the incidence of uncomplicated and severe malaria compared with either intervention given alone. Here, we report on the anti-circumsporozoite antibody response to seasonal RTS,S/AS01E vaccination in children in this trial.MethodsSera from a randomly selected subset of children collected before and 1 month after 3 priming doses of RTS,S/AS01E and before and 1 month after 2 seasonal booster doses were tested for anti-circumsporozoite antibodies using enzyme-linked immunosorbent assay. The association between post-vaccination antibody titer and incidence of malaria was explored.ResultsA strong anti-circumsporozoite antibody response to 3 priming doses of RTS,S/AS01E was seen (geometric mean titer, 368.9 enzyme-linked immunosorbent assay units/mL), but titers fell prior to the first booster dose. A strong antibody response to an annual, pre-malaria transmission season booster dose was observed, but this was lower than after the primary vaccination series and lower after the second than after the first booster dose (ratio of geometric mean rise, 0.66; 95% confidence interval [CI], .57–.77). Children whose antibody response was in the upper tercile post-vaccination had a lower incidence of malaria during the following year than children in the lowest tercile (hazard ratio, 0.43; 95% CI, .28–.66).ConclusionsSeasonal vaccination with RTS,S/AS01E induced a strong booster antibody response that was lower after the second than after the first booster dose. The diminished antibody response to the second booster dose was not associated with diminished efficacy.Clinical Trials RegistrationNCT03143218.
Multimodal temporary mechanically circulatory assistance for primary graft dysfunction after heart transplantation: a case report
Authors: Immohr Moritz B , Lichtenberg Artur , Akhyari Payam , Boeken Udo 
Published: December 2021

Abstract

Background
Primary graft dysfunction (PGD) remains a serious complication after heart transplantation (HTx). Although there is no therapy available, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) may be a bailout strategy in selected cases. Especially in patients with severe biventricular failure, chances of survival remain poor.

Case summary
Here, we report a case of a 56-year-old patient suffering from severe PGD after HTx with biventricular failure (ejection fraction &lt; 20%) who was successfully bridged to recovery of the donor graft by temporary multimodal mechanically circulatory assistance by combining both, VA-ECMO and a microaxial pump (Impella®, Abiomed, Inc., Danvers, MA, USA), a concept also referred as ECMELLA. During ECMELLA support, the patient experienced multiple severe thoracic bleeding complications with need for four re-thoracotomies and temporary open chest situation. Nevertheless, ventricular function recovered and the patient could be weaned from mechanical circulatory support after 12 days. During follow-up, the patient recovered and was successfully discharged. After the following rehabilitation, the patient now shows no persistent signs of heart failure with normal biventricular function of the cardiac graft.

Discussion
ECMELLA may offer a therapeutic option for patients with severe PGD after HTx. Special awareness and further studies addressing targeted anticoagulation strategies for patients on dual-mechanical support are needed to diminish the incidence of bleeding complications.
Identifying a therapeutic target for vancomycin against staphylococci in young infants
Authors: Gwee Amanda , Duffull Stephen B. , Daley Andrew J. , Lim Michelle , Germano Susie , Bilal Hajira , Hall Samantha , Curtis Nigel , Zhu Xiao 
Published: December 2021

Abstract

Objectives
To determine the therapeutic target of vancomycin in young infants with staphylococcal infections.

Methods
Retrospective data were collected for infants aged 0 to 90 days with CoNS or MRSA bacteraemia over a 4 year period at the Royal Children’s Hospital Melbourne, Australia. Vancomycin broth microdilution MICs were determined. A published pharmacokinetic model was externally validated using the study dataset and a time-to-event (TTE) pharmacodynamic model developed to link the AUC of vancomycin with the event being the first negative blood culture. Simulations were performed to determine the trough vancomycin concentration that correlates with a 90% PTA of the target AUC24.

Results
Thirty infants, 28 with CoNS and 2 with MRSA bacteraemia, who had 165 vancomycin concentrations determined were included. The vancomycin broth microdilution MIC was determined for 24 CoNS and 1 MRSA isolate, both with a median MIC of 1 mg/L (CoNS range = 0.5–4.0). An AUC0–24 target of ≥300 mg/L·h or AUC24–48 of ≥424 mg/L·h. increased the chance of bacteriological cure by 7.8- and 7.3-fold, respectively. However, AUC0–24 performed best in the pharmacokinetic-pharmacodynamic model. This correlates with 24 to 48 h trough concentrations of &gt;15–18 mg/L and &gt;10–15 mg/L for 6- and 12-hourly dosing, respectively, and can be used to guide vancomycin therapy in this population.

Conclusions
An AUC0–24 ≥300 mg/L·h or AUC24–48 ≥424 mg/L·h was associated with an increase in bacteriological cure in young infants with staphylococcal bloodstream infections.
Evaluating the dose, indication and agreement with guidelines of antimicrobial use in companion animal practice with natural language processing
Authors: Hur Brian , Hardefeldt Laura Y. , Verspoor Karin M. , Baldwin Timothy , Gilkerson James R. 
Published: December 2021

Abstract

Background
As antimicrobial prescribers, veterinarians contribute to the emergence of MDR pathogens. Antimicrobial stewardship programmes are an effective means of reducing the rate of development of antimicrobial resistance. A key component of antimicrobial stewardship programmes is selecting an appropriate antimicrobial agent for the presenting complaint and using an appropriate dose rate for an appropriate duration.

Objectives
To describe antimicrobial usage, including dose, for common indications for antimicrobial use in companion animal practice.

Methods
Natural language processing (NLP) techniques were applied to extract and analyse clinical records.

Results
A total of 343 668 records for dogs and 109 719 records for cats administered systemic antimicrobials from 1 January 2013 to 31 December 2017 were extracted from the database. The NLP algorithms extracted dose, duration of therapy and diagnosis completely for 133 046 (39%) of the records for dogs and 40 841 records for cats (37%). The remaining records were missing one or more of these elements in the clinical data. The most common reason for antimicrobial administration was skin disorders (n = 66 198, 25%) and traumatic injuries (n = 15 932, 19%) in dogs and cats, respectively. Dose was consistent with guideline recommendations in 73% of cases where complete clinical data were available.

Conclusions
Automated extraction using NLP methods is a powerful tool to evaluate large datasets and to enable veterinarians to describe the reasons that antimicrobials are administered. However, this can only be determined when the data presented in the clinical record are complete, which was not the case in most instances in this dataset. Most importantly, the dose administered varied and was often not consistent with guideline recommendations.
Biological Variation of Donor-Derived Cell-Free DNA in Stable Lung Transplant Recipients
Authors: Keller Michael , Mutebi Cedric , Shah Pali , Levine Deborah , Aryal Shambhu , Iacono Aldo , Timofte Irina , Mathew Joby , Varghese Anu , Giner Cassandra , Agbor-Enoh Sean 
Published: December 2021

Abstract

Background
Prior studies demonstrate that donor-derived cell-free DNA (dd-cfDNA) in lung transplant recipients may serve as a marker of allograft injury for detecting allograft rejection and infection. Clinical interpretation of dd-cfDNA requires understanding its biological variation in stable lung transplant patients in order to identify abnormal results suggesting underlying allograft dysfunction. This study establishes the biological variation and reference change values (RCV) of dd-cfDNA in stable lung transplant recipients using an analytically validated assay with an established analytic coefficient of variation (CVA).

Methods
The AlloSure® assay, a targeted, sequencing-based approach, was used to measure plasma dd-cfDNA in a cohort of lung transplant patients at 4 centers that used dd-cfDNA to monitor for allograft dysfunction in preference to surveillance transbronchial biopsy. Patients with stable allograft function and ≥3 dd-cfDNA samples were included. Intraindividual coefficient of variation (CVI), interindividual CV (CVG), index of individuality (II) and the RCV were calculated.

Results
Thirty-five patients with a combined 124 dd-cfDNA samples were included in the final analysis. The median dd-cfDNA was 0.31% (interquartile range 0.18%-0.68%), the 97.5th percentile and 95th percentile were 1.3% and 1.0%, respectively. In 30 stable patients with an average of 3.7 tests, the CVI was 25%, CVG 53%, II 0.47, and RCV 70%.

Conclusion
In stable lung transplant patients, fluctuations in dd-cfDNA levels of up to 70% or levels less than 1% are within normal biological variation. With further validation, these thresholds may be incorporated into surveillance monitoring algorithms to identify potentially abnormal results indicating allograft dysfunction.
Bilateral cochlear implantation in a young patient with xeroderma pigmentosum (XP-D) and progressive sensorineural hearing loss—How to do it?
Authors: Woodun H , Woodun H , Vedachalam R Vetrivel , Fassihi H , Achar P 
Published: December 2021

Abstract
Xeroderma pigmentosum (XP), a rare genetic skin condition, causes ultraviolet (UV)-induced neoplasms and possible neurological deficits including sensorineural hearingloss.
We present the first case in literature of bilateral cochlear implantation (CI) in a patient with XP-D with neurodegeneration. Multi-disciplinary team members (national XP team, dermatologist, anaesthetist, theatre team, biophysicists) were involved. UV exposure from equipment and areas where the 14-year-old patient would track was measured. Maximum possible surgery was performed under operating headlights to limit higher-UV microscope exposure. Its bulb light intensity was reduced to achieve safe UV level (0–10 μW/cm2). Skin was protected under surgical drapes. Challenges included drilling unpredicted hard thick bone under low-intensity light and requiring bulkier Nucleus®-7 processor due to unanticipated increased scarring. A delayed left facial weakness was resolved with steroids. He is undergoing hearing rehabilitation.
This highlights challenges of CI in XP. Its impact in preserving cognition and on neurodegeneration should also be observed.
The impact of language in conflicts over urban coyotes
Authors: Draheim Megan M , Crate Susan A , Parsons E C M , Rockwood Larry L 
Published: December 2021

Abstract
Wildlife managers and others charged with resolving human-coyote conflict in urban and suburban areas cannot focus solely on ecology and coyote behavior. The perceptions of the people living in the affected communities play a significant role in the resolution of human-coyote conflict. In this study, we explore how residents of two communities in suburban Denver, CO, USA, mentally processed, made sense of, and acted upon human–coyote interactions in the face of conflict. By conducting interviews and using qualitative content analysis to explore existing documents, we examined how the use of language reflected and exacerbated the conflict over coyote management. Themes of violence, crime and war ran throughout our data. Anger and accusations of extremism were prevalent. Closely tied to the violent language and imagery used was a discussion of tolerance and intolerance, taking what is generally human-centric language and using it with wildlife. In addition, labeling coyotes as not belonging in an area (although they are a native species) further increased the urge to protect family and pets from the perception of the threat against ‘the other’, sometimes expressed in inflammatory language. Political and other messaging can either enhance or reduce a sense of threat, and we found that the language used in this debate enhanced the perceived threat of both coyotes and policy opponents. Finding ways to defuse this language could be a step toward a greater understanding of how to live with local wildlife in a way that minimizes harm to people and to the animals.
Regulation of heat shock proteins 70 and their role in plant immunity
Authors: Berka Miroslav , Kopecká Romana , Berková Veronika , Brzobohatý Břetislav , Černý Martin 
Published: December 2021

Abstract
Heat shock proteins 70 (HSP70s) are steadily gaining more attention in the field of plant biotic interactions. Though their regulation and activity in plants are much less well characterized than are those of their counterparts in mammals, accumulating evidence indicates that the role of HSP70-mediated defense mechanisms in plant cells is indispensable. In this review, we summarize current knowledge of HSP70 post-translational control in plants. We comment on the phytohormonal regulation of HSP70 expression and protein abundance, and identify a prominent role for cytokinin in HSP70 control. We outline HSP70s’ subcellular localizations, chaperone activity, and chaperone-mediated protein degradation. We focus on the role of HSP70s in plant pathogen-associated molecular pattern-triggered immunity and effector-triggered immunity, and discuss the contribution of different HSP70 subfamilies to plant defense against pathogens.
Cardiovascular burden in systemic sclerosis: QRISK3 versus Framingham for risk estimation
Authors: Di Battista Marco , Barsotti Simone , Della Rossa Alessandra , Mosca Marta 
Published: December 2021

ABSTRACT

Objectives
To compare two algorithms for cardiovascular (CV) risk estimation in systemic sclerosis (SSc) patients, investigating correlations with disease characteristics.

Methods
Traditional CV risk factors and SSc-specific characteristics were assessed in a cohort of SSc patients. Framingham and QRISK3 algorithms were used to estimate the risk of developing a CV disease over the next 10 years.

Results
Seventy-two SSc patients were enrolled. Among those 56 without previous CV events, Framingham reported a median risk score of 9.6%, classifying 24 (42.9%) subjects at high risk. QRISK3 showed a median risk score of 15.8%, with 36 (64.3%) patients considered at high risk. Both algorithms revealed a significant role of some traditional risk factors and a noteworthy potential protective role of endothelin receptor antagonists (p = .003). QRISK3 was also significantly influenced by some SSc-specific characteristics, such as limited cutaneous subset (p = .01), interstitial lung disease (p = .04), and non-ischemic heart involvement (p = .03), with the first two maintaining statistical significance in the multivariate analysis (p = .02).

Conclusions
QRISK3 classifies more SSc patients at high risk to develop CV diseases than Framingham, reflecting the influence of some SSc-specific characteristics. If its predictive accuracy were prospectively verified, the use of QRISK3 as a tool in the early detection of SSc patients at high CV risk should be recommended.
Centre variation in mortality following post-hospitalization acute kidney injury: analysis of a large national cohort
Authors: Peracha Javeria , Pitcher David , Santhakumaran Shalini , Steenkamp Retha , Fotheringham James , Day Jamie , Medcalf James F , Nitsch Dorothea , Lipkin Graham W , McKane William S 
Published: December 2021

ABSTRACT

Background
Routine monitoring of outcomes for patients with acute kidney injury (AKI) is important to drive ongoing quality improvement in patient care. In this study we describe the development of a case mix-adjusted 30-day mortality indicator for patients with post-hospitalization AKI (PH-AKI) across England to facilitate identification of any unwarranted centre variation in outcomes.

Methods
We utilized a routinely collected national dataset of biochemically detected AKI cases linked with national hospitals administrative and mortality data. A total of 250 504 PH-AKI episodes were studied across 103 National Health Service hospital trusts between January 2017 and December 2018. Standardized mortality ratios (SMRs) were calculated for each trust using logistic regression, adjusting for age, sex, primary diagnosis, comorbidity score, AKI severity, month of AKI and admission method.

Results
The mean 30-day mortality rate was high, at 28.6%. SMRs for 23/103 trusts were classed as outliers, 12 above and 11 below the 95% confidence limits. Patients with PH-AKI had mortality rates &gt;5 times higher than the overall hospitalized population in 90/136 diagnosis groups and &gt;10 times higher in 60/136 groups. Presentation at trusts with a co-located specialist nephrology service was associated with a lower mortality risk, as was South Asian or Black ethnicity. Deprivation, however, was associated with higher mortality.

Conclusions
This is the largest multicentre analysis of mortality for patients with biochemically ascertained PH-AKI to date, demonstrating once again the considerable risk associated with developing even mild elevations in serum creatinine. Mortality rates varied considerably across centres and those identified as outliers will now need to carefully interrogate local care pathways to understand and address the reasons for this, with national policy required to tackle the identified health disparities.
Aiming for Zero: Reducing Transmission of Coronavirus Disease 2019 in the D.C. Department of Corrections
Authors: Epting Mallory E , Pluznik Jacob A , Levano Samantha R , Hua Xinyi , Fung Isaac C H , Jordan Beth , O’Donovan Eleni , Robinson Kissa M , Chakraborty Reena , Yousefi Bahram , Michel Ciara J , Bowden Chava J , Kapadia Aman , Riback Lindsey R , Mangla Anil T , Akiyama Matthew J , Spaulding Anne C 
Published: December 2021

Abstract

Background
Washington, District of Columbia lowered severe acute respiratory syndrome coronavirus 2 transmission in its large jail while community incidence was still high

Methods
Coordinated clinical and operational interventions brought new cases to near zero.

Results
Aggressive infection control and underlying jail architecture can promote correctional coronavirus disease 2019 management.

Conclusions
More intensive monitoring could help confirm that in-house transmission is truly zero.
Superior Outcomes With Continuing Tenofovir Versus Switching to Zidovudine in Second-Line Antiretroviral Therapy in Haiti
Authors: Pierre Samuel , Bocharova Iryna , Nguyen Catherine , Homeus Fabienne , Julmiste Gaetane , Macius Youry , Rouzier Vanessa , Severe Patrice , Marcelle Deschamps Marie , Moise Colette Guiteau , Bellot Clovy , Wu Johnny , Rivera Vanessa R , Sun Rochelle , Pape Jean W , Liautaud Bernard , Koenig Serena P 
Published: December 2021

Abstract
We compared viral suppression rates between patients who continued tenofovir disoproxil fumarate (TDF)/lamivudine (3TC) vs switched to zidovudine (ZDV)/3TC in combination with a boosted protease inhibitor after failure of first-line efavirenz/TDF/3TC. We found higher rates of viral suppression with continued TDF/3TC compared with switching to ZDV/3TC.