bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors for the accuracy of the initial diagnosis of malaria cases in China: a decision-tree modelling approach
Authors: Li Gang , Zhang Donglan , Chen Zhuo , Feng Da , Cai Xinyan , Chen Xiaoyu , Tang Shangfeng , Feng Zhanchun 
Published: January 2022

AbstractBackgroundEarly accurate diagnosis and risk assessment for malaria are crucial for improving patients’ terminal prognosis and preventing them from progressing to a severe or critical stage. This study aims to describe the accuracy of the initial diagnosis of malaria cases with different characteristics and the factors that affect the accuracy in the context of the agenda for a world free of malaria.MethodsA retrospective study was conducted on 494 patients admitted to hospitals with a diagnosis of malaria from January 2014 through December 2016. Descriptive statistics were calculated, and decision tree analysis was performed to predict the probability of patients who may be misdiagnosed.ResultsOf the 494 patients included in this study, the proportions of patients seeking care in county-level, prefecture-level and provincial-level hospitals were 27.5% (n = 136), 26.3% (n = 130) and 8.3% (n = 41), respectively; the proportions of patients seeking care in clinic, township health centre and Centres for Disease Control and Prevention were 25.9% (n = 128), 4.1% (n = 20), and 7.9% (n = 39), respectively. Nearly 60% of malaria patients were misdiagnosed on their first visit, and 18.8% had complications. The median time from onset to the first visit was 2 days (IQR: 0-3 days), and the median time from the first visit to diagnosis was 3 days (IQR: 0–4 days). The decision tree classification of malaria patients being misdiagnosed consisted of six categorical variables: healthcare facilities for the initial diagnosis, time interval between onset and initial diagnosis, region, residence type, insurance status, and age.ConclusionsInsufficient diagnostic capacity of healthcare facilities with lower administrative levels for the first visit was the most important risk factor in misdiagnosing patients. To reduce diagnostic errors, clinicians, government decision-makers and communities should consider strengthening the primary care facilities, the time interval between onset and initial diagnosis, residence type, and health insurance status.
Impact of nutritional status on heart failure mortality: a retrospective cohort study
Authors: Abdoul Carime Nafiz , Cottenet Jonathan , Clerfond Guillaume , Eschalier Romain , Quilliot Didier , Eicher Jean-Christophe , Joly Bertrand , Quantin Catherine 
Published: January 2022

AbstractBackgroundChronic heart failure (CHF) is one of the most common causes of mortality in industrialized countries despite regular therapeutic advances. Numerous factors influence mortality in CHF patients, including nutritional status. It is known that malnutrition is a risk factor for mortality, whereas obesity may play a protective role, a phenomenon dubbed the “obesity paradox”. However, the effect of the obesity-malnutrition association on mortality has not been previously studied for CHF. Our aim was to study the effect of nutritional status on overall mortality in CHF patients.MethodsThis retrospective, multicenter study was based on a French nationwide database (PMSI). We included all CHF patients aged ≥18 years admitted to all public and private hospitals between 2012 and 2016 and performed a survival analysis over 1 to 4 years of follow-up.ResultsMalnutrition led to a significant decrease in life expectancy in CHF patients when compared with normal nutritional status (aHR=1.16 [1.14-1.18] at one year and aHR=1.04 [1.004-1.08] at four years), obese, and obese-malnutrition groups. In contrast, obesity led to a significant increase in life expectancy compared with normal nutritional status (aHR=0.75 [0.73-0.78] at one year and aHR=0.85 [0.81-0.90] at four years), malnutrition, and obese-malnutrition groups. The mortality rate was similar in patients presenting both malnutrition and obesity and patients with normal nutritional status.ConclusionsOur results indicate that the protective effect on mortality observed in obese CHF patients seems to be linked to fat massincrease. Furthermore, malnourished obese and normal nutritional status patients had similar mortality rates. Further studies should be conducted to confirm our results and to explore the physiopathological mechanisms behind these effects.
New approach for genomic characterisation of equine sarcoid-derived BPV-1/-2 using nanopore-based sequencing
Authors: Gysens Lien , Vanmechelen Bert , Haspeslagh Maarten , Maes Piet , Martens Ann 
Published: January 2022

Abstract
Background
Bovine papillomavirus (BPV) types 1 and 2 play a central role in the etiology of the most common neoplasm in horses, the equine sarcoid. The unknown mechanism behind the unique variety in clinical presentation on the one hand and the host dependent clinical outcome of BPV-1 infection on the other hand indicate the involvement of additional factors. Earlier studies have reported the potential functional significance of intratypic sequence variants, along with the existence of sarcoid-sourced BPV variants. Therefore, intratypic sequence variation seems to be an important emerging viral factor. This study aimed to give a broad insight in sarcoid-sourced BPV variation and explore its potential association with disease presentation.

Methods
In order to do this, a nanopore sequencing approach was successfully optimized for screening a wide spectrum of clinical samples. Specimens of each tumour were initially screened for BPV-1/-2 by quantitative real-time PCR. A custom-designed primer set was used on BPV-positive samples to amplify the complete viral genome in two multiplex PCR reactions, resulting in a set of overlapping amplicons. For phylogenetic analysis, separate alignments were made of all available complete genome sequences for BPV-1/-2. The resulting alignments were used to infer Bayesian phylogenetic trees.

Results
We found substantial genetic variation among sarcoid-derived BPV-1, although this variation could not be linked to disease severity. Several of the BPV-1 genomes had multiple major deletions. Remarkably, the majority of them cluster within the region coding for late viral genes. Together with the extensiveness (up to 603 nucleotides) of the described deletions, this suggests an altered function of L1/L2 in disease pathogenesis.

Conclusions
By generating a significant amount of complete-length BPV genomes, we succeeded to introduce next-generation sequencing into veterinary research focusing on the equine sarcoid, thus facilitating the first report of both nanopore-based sequencing of complete sarcoid-sourced BPV-1/-2 and the simultaneous nanopore sequencing of multiple complete genomes originating from a single clinical sample.
Diagnostic accuracy of calprotectin in periprosthetic joint infection: a diagnostic meta-analysis
Authors: Xing Jisi , Li Jiahao , Yan Zijian , Li Yijin , Liu Xiaofang , He Lilei , Xu Ting , Wang Changbing , Zhao Lilian , Jie Ke 
Published: January 2022

Abstract
Background
Periprosthetic joint infection (PJI) is considered to be one of the most challenging complications of joint replacement, which remains unpredictable. As a simple and emerging biomarker, calprotectin (CLP) has been considered to be useful in ruling out PJI in recent years. The purpose of this study was to investigate the accuracy and sensitivity of CLP in the diagnosis of PJI.

Methods
We searched and screened the publications from PubMed, Web of Science, EMBASE, and Cochrane Library from database establishment to June 2021. Subsequently, Stata version 16.0 software was used to combine the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), operating characteristic curve, and area under the curve (AUC). Heterogeneity across articles was evaluated by the I2 statistics. Finally, sources of heterogeneity were detected by subgroup analysis based on study design, detection method, sample size, and cutoff values.

Results
A total of 7 studies were included in our study, comprising 525 patients. The pooled sensitivity, specificity, PLR, and NLR of CLP for PJI diagnosis were 0.94(95% CI 0.87–0.98), 0.93(95% CI 0.87–0.96), 13.65(95% CI 6.89–27.08), and 0.06(95% CI 0.02–0.15), respectively, while the DOR and AUC were 222.33(95% CI 52.52–941.11) and 0.98 (95% CI 0.96–0.99), respectively.

Conclusion
Synovial CLP is a reliable biomarker and can be used as a diagnostic criterion for PJI in the future. However, the uncertainty resulting from the poor study numbers and sample sizes limit our ability to definitely draw conclusions on the basis of our study.
Constitutively active SARM1 variants that induce neuropathy are enriched in ALS patients
Authors: Bloom A. Joseph , Mao Xianrong , Strickland Amy , Sasaki Yo , Milbrandt Jeffrey , DiAntonio Aaron 
Published: January 2022

Abstract
Background
In response to injury, neurons activate a program of organized axon self-destruction initiated by the NAD+ hydrolase, SARM1. In healthy neurons SARM1 is autoinhibited, but single amino acid changes can abolish autoinhibition leading to constitutively active SARM1 enzymes that promote degeneration when expressed in cultured neurons.

Methods
To investigate whether naturally occurring human variants might disrupt SARM1 autoinhibition and potentially contribute to risk for neurodegenerative disease, we assayed the enzymatic activity of all 42 rare SARM1 alleles identified among 8507 amyotrophic lateral sclerosis (ALS) patients and 9671 controls. We then intrathecally injected mice with virus expressing SARM1 constructs to test the capacity of an ALS-associated constitutively active SARM1 variant to promote neurodegeneration in vivo.

Results
Twelve out of 42 SARM1 missense variants or small in-frame deletions assayed exhibit constitutive NADase activity, including more than half of those that are unique to the ALS patients or that occur in multiple patients. There is a > 5-fold enrichment of constitutively active variants among patients compared to controls. Expression of constitutively active ALS-associated SARM1 alleles in cultured dorsal root ganglion (DRG) neurons is pro-degenerative and cytotoxic. Intrathecal injection of an AAV expressing the common SARM1 reference allele is innocuous to mice, but a construct harboring SARM1V184G, the constitutively active variant found most frequently among the ALS patients, causes axon loss, motor dysfunction, and sustained neuroinflammation.

Conclusions
These results implicate rare hypermorphic SARM1 alleles as candidate genetic risk factors for ALS and other neurodegenerative conditions.
Achieving robust somatic mutation detection with deep learning models derived from reference data sets of a cancer sample
Authors: Sahraeian Sayed Mohammad Ebrahim , Fang Li Tai , Karagiannis Konstantinos , Moos Malcolm , Smith Sean , Santana-Quintero Luis , Xiao Chunlin , Colgan Michael , Hong Huixiao , Mohiyuddin Marghoob , Xiao Wenming 
Published: January 2022

Abstract
Background
Accurate detection of somatic mutations is challenging but critical in understanding cancer formation, progression, and treatment. We recently proposed NeuSomatic, the first deep convolutional neural network-based somatic mutation detection approach, and demonstrated performance advantages on in silico data.

Results
In this study, we use the first comprehensive and well-characterized somatic reference data sets from the SEQC2 consortium to investigate best practices for using a deep learning framework in cancer mutation detection. Using the high-confidence somatic mutations established for a cancer cell line by the consortium, we identify the best strategy for building robust models on multiple data sets derived from samples representing real scenarios, for example, a model trained on a combination of real and spike-in mutations had the highest average performance.

Conclusions
The strategy identified in our study achieved high robustness across multiple sequencing technologies for fresh and FFPE DNA input, varying tumor/normal purities, and different coverages, with significant superiority over conventional detection approaches in general, as well as in challenging situations such as low coverage, low variant allele frequency, DNA damage, and difficult genomic regions
ABBaH teens: Activity Breaks for Brain Health in adolescents: study protocol for a randomized crossover trial
Authors: Heiland Emerald G. , Kjellenberg Karin , Tarassova Olga , Fernström Maria , Nyberg Gisela , Ekblom Maria M. , Helgadottir Björg , Ekblom Örjan 
Published: January 2022

Abstract
Background
Physical activity breaks are widely being implemented in school settings as a solution to increase academic performance and reduce sitting time. However, the underlying physiological mechanisms suggested to improve cognitive function from physical activity and the frequency, intensity, and duration of the breaks remain unknown. This study will investigate the effects of frequent, short physical activity breaks during prolonged sitting on task-related prefrontal cerebral blood flow, cognitive performance, and psychological factors. Additionally, the moderating and mediating effects of arterial stiffness on changes in cerebral blood flow will be tested.

Methods
This is a protocol for a randomized crossover study that will recruit 16 adolescents (13–14 years old). Participants will undergo three different conditions in a randomized order, on three separate days, involving sitting 80 min with a different type of break every 17 min for 3 min. The breaks will consist of (1) seated social breaks, (2) simple resistance activities, and (3) step-up activities. Before and after the 80-min conditions, prefrontal cerebral blood flow changes will be measured using functional near-infrared spectroscopy (primary outcome), while performing working memory tasks (1-, 2-, and 3-back tests). Arterial stiffness (augmentation index and pulse wave velocity) and psychological factors will also be assessed pre and post the 80-min interventions.

Discussion
Publication of this protocol will help to increase rigor in science. The results will inform regarding the underlying mechanisms driving the association between physical activity breaks and cognitive performance. This information can be used for designing effective and feasible interventions to be implemented in schools.

Trial registration
www.ClinicalTrials.gov, NCT04552626. Retrospectively registered on September 21, 2020.
Anti-infection roles of miR-155-5p packaged in exosomes secreted by dendritic cells infected with Toxoplasma gondii
Authors: Jiang Dan , Wu Shuizhen , Xu Liqing , Xie Guantai , Li Dongliang , Peng Hongjuan 
Published: January 2022

Abstract
Background
Toxoplasma gondii is a zoonotic intracellular protozoon that is estimated to infect about 30% of the world’s population, resulting in toxoplasmosis in immunocompromised patients and adverse outcomes in cases of primary infection during pregnancy. Exosomes are tubular vesicles secreted by cells, and function in intercellular communication. It has been reported that the exosomes secreted by T. gondii-infected immune cells transmit infection signals to the uninfected cells. However, the mechanism and effect of the exosome transmission are still vague. We therefore investigated the function of the exosomes transmitted from DC2.4 cells infected with the T. gondii RH strain (Tg-DC-Exo) to the uninfected cells, as well as their roles in anti-infection.

Methods
We conducted exosome isolation and identification with ultracentrifugation, transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot (WB) analysis. Exosome uptake by recipient cells was identified by PKH67 assay. The signal transmission and the abundance of miR-155-5p were determined using transwell assay and qRT-PCR. For detection of immune responses, cytokine secretion was evaluated. The T. gondii B1 gene was determined to evaluate tachyzoite proliferation.

Results
We observed that Toxoplasma infection upregulated miR-155-5p expression in DC2.4 cell-secreted exosomes, and those exosomes could be ingested by murine macrophage RAW264.7 cells. Tg-DC-Exo and miR-155-5p stimulated host proinflammatory immune responses including increased production of proinflammatory cytokines IL-6 and TNF-α, and proinflammatory marker-inducible nitric oxide synthase (iNOS). The NF-κB pathway was activated by downregulation of SOCS1, leading to inhibition of T. gondii tachyzoite proliferation in RAW264.7 cells.

Conclusions
Our findings provide a novel mechanism for how infected cells transmit infection signals to the uninfected cells through exosome secretion after T. gondii infection, followed by inflammatory responses and anti-infection reactions, which may help us develop a new strategy for toxoplasmosis prevention, especially in immunocompromised patients.

Graphical Abstract
The association between psoriatic arthritis and venous thromboembolism: a population-based cohort study
Authors: Gazitt Tal , Pesachov Jacob , Lavi Idit , Elias Muna , Haddad Amir , Feldhamer Ilan , Cohen Arnon Dov , Saliba Walid , Zisman Devy 
Published: January 2022

Abstract
Background
Although the risk of cardiovascular disease has been discussed extensively in both psoriasis (PsO) and psoriatic arthritis (PsA), very few studies have addressed the occurrence of venous thromboembolic (VTE) events among PsO patients, and even fewer in PsA. Thus, our goal was to assess the association between PsA and VTE events using a large population-based database.

Methods
This retrospective cohort study includes all 5,275 patients with newly diagnosed PsA from the largest health care provider in Israel between January 2003 and December 2018. Identified PsA patients were matched by age, sex, ethnicity, and index date with 21,011 controls without PsA from the same database. Both groups were followed through June 30, 2019 for the occurrence of VTE event. Cox proportional hazard regression models were used to assess the association between PsA and VTE.

Results
PsA cohort consisted of 53.2% females with mean age of 51.7±15.4 Sixty-two patients (1.2%) were diagnosed with VTE in the PsA group and 176 patients (0.8%) in the control group (p=0.023, HR=1.40, 95% CI 1.05-1.87). However, there was no increased risk of VTE among PsA patients on multivariable analysis (p=0.16, HR=1.27, 95% CI 0.91-1.80). Within the PsA group, patients with VTE were more often of older age and with history of VTE.

Conclusions
This study suggests that the increased risk of VTE in PsA patients appears to be related to the underlying comorbidities and not independently associated with PsA. Age and previous history of VTE were the only risk factors associated with increased risk of VTE in patients with PsA. Addressing VTE risk is recommended especially in the era of Janus kinase inhibitors.
Prospecting the plant growth–promoting activities of endophytic bacteria Franconibacter sp. YSD YN2 isolated from Cyperus esculentus L. var. sativus leaves
Authors: Wang Saisai , Wang Jinbin , Zhou Yifan , Huang Yanna , Tang Xueming 
Published: January 2022

Abstract
Purpose
Plant growth–promoting (PGP) bacteria are an environment-friendly alternative to chemical fertilizers for promoting plant growth and development. We isolated and characterized a PGP endophyte, YSD YN2, from the leaves of Cyperus esculentus L. var. sativus.

Methods
Specific PGP characteristics of this strain, such as phosphate solubilization ability, potassium-dissolving ability, siderophore and indole-3-acetic acid (IAA) production, and salt tolerance, were determined in vitro. In addition, positive mutants were screened using the atmospheric and room temperature plasma (ARTP) technology, with IAA level and organic phosphate solubility as indices. Furthermore, the effect of the positive mutant on seed germination, biomass production, and antioxidant abilities of greengrocery seedling was evaluated, and the genome was mined to explore the underlying mechanisms.

Results
The strain YSD YN2 showed a good performance of PGP characteristics, such as the production of indole acetic acid and siderophores, solubilization ability of phosphate, and potassium-dissolving ability. It was recognized through 16S rRNA sequencing together with morphological and physiological tests and confirmed as Franconibacter sp. The strain exposed to a mutation time of 125 s by ARTP had the highest IAA and organic phosphate (lecithin) concentrations of 9.25 mg/L and 16.50 mg/L, 50.41% and 30.54% higher than those of the initial strain. Inoculation of mutant strain YSD YN2 significantly increased the seed germination, plant growth attributes, and the activities of peroxidase (POD) and superoxide dismutase (SOD), respectively, but decreased the content of malondialdehyde (MDA) significantly compared with the control. Furthermore, genome annotation and functional analysis were performed through whole-genome sequencing, and PGP-related genes were identified.

Conclusion
Our results indicated that the mutant strain YSD YN2 with PGP characteristics is a potential candidate for the development of biofertilizers.
Dot blot immunochemical and infrared analyses of the adhesive layer applied to the painting Imago Pietatis by Domenico Morone
Authors: Cattò Cristina , Parodi Valentina , Chiodelli Alice , Cappitelli Francesca , Bruni Silvia 
Published: January 2022

Abstract
Purpose
To investigate the nature of the materials used in the adhesive layer of the Imago Pietatis painting (end of the fifteenth century—beginning of the sixteenth century) by Domenico Morone as a prerequisite for its restoration.

Methods
Micro-FTIR spectra of the animal glue and a polished cross-section were acquired by a Jasco IRT3000 spectrometer, equipped with a 32× Cassegrain objective. A dot blot immunoassay was used to characterise a minor component of the adhesive layer.

Results
Micro-FTIR was used as an effective diagnostic tool to detect the major component of the adhesive layer and the binder of the paint. Despite the ageing, the complex matrix and the micro-size of the sample, using a dot blot immunoassay, it was possible to quantify 3.7 ± 2.0 ng of ovalbumin per microgram of sample (corresponding to 0.004 ± 0.002% of the weight).

Conclusions
The findings were in line with conservation practices described in the old treatises, confirming the correct interpretation of the adhesive layer compounds added to the painting and suggesting for the cleaning the use of an anionic water-soluble surfactant highly effective in the removing of proteinaceous materials.