bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of glycogen storage disease type I on adult daily life: a survey
Authors: Garbade Sven F. , Ederer Viviane , Burgard Peter , Wendel Udo , Spiekerkoetter Ute , Haas Dorothea , Grünert Sarah C. 
Published: September 2021

Abstract
Background
Glycogen storage disease type I (GSD I) is a rare autosomal recessive disorder of carbohydate metabolism characterized by recurrent hypoglycaemia and hepatomegaly. Management of GSD I is demanding and comprises a diet with defined carbohydrate intake and the use of complex carbohydrates, nocturnal tube feeding or night-time uncooked cornstarch intake, regular blood glucose monitoring and the handling of emergency situations. With improved treatment, most patients nowadays survive into adulthood. Little research has been performed on the impact of GSD I on daily life, especially in adult patients.

Results
In this multi-centre study we assessed the impact of GSD I on adult daily life in 34 GSD I patients (27 GSD Ia, 7 GSD Ib) between 17 and 54 years (median 26 years) using a self-designed questionnaire that specifically focused on different aspects of daily life, such as job situation, social life, sports, travelling, composition of the household, night-time and day-time dietary management and disease monitoring as well as the patient’s attitude towards the disease. At the time of investigation, the majority of patients either attended school or university or were employed, while 3 patients (9%) were out of work. Most patients ranked GSD I as a disease with moderate severity and disease burden. Dietary treatment was considered challenging by many, but the vast majority of patients considered life with GSD I as well-manageable.

Conclusions
Although the management of GSD I poses a significant burden on daily life, most patients live an independent adult life, have a positive attitude towards their disease and seem to cope well with their situation.
Pilot investigation of circulating angiogenic and inflammatory biomarkers associated with vascular malformations
Authors: Wetzel-Strong Sarah E. , Weinsheimer Shantel , Nelson Jeffrey , Pawlikowska Ludmila , Clark Dewi , Starr Mark D. , Liu Yingmiao , Kim Helen , Faughnan Marie E. , Nixon Andrew B. , Marchuk Douglas A. 
Published: September 2021

Abstract
Background
Vascular malformations in the central nervous system are difficult to monitor and treat due to their inaccessible location. Angiogenic and inflammatory proteins are secreted into the bloodstream and may serve as useful biomarkers for identifying patients at risk for complications or with certain disease phenotypes.

Methods
A validated multiplex protein array consisting of 26 angiogenic and inflammatory biomarkers (Angiome) was assessed in plasma isolated from healthy controls and patients with either sporadic brain arteriovenous malformation (BAVM), familial cerebral cavernous malformation (CCM), or hereditary hemorrhagic telangiectasia (HHT). These samples were obtained from archives of ongoing research studies at the University of California San Francisco and through prospective collection at the Toronto HHT Centre at St. Michael’s Hospital.

Results
We compared circulating biomarker levels from each patient group to healthy controls and analyzed each pairwise combination of patient groups for differences in biomarker levels. Additionally, we analyzed the HHT samples to determine the association between biomarker levels and the following HHT-specific phenotypes, BAVM, pulmonary arteriovenous malformation (PAVM), liver vascular malformation (LVM), and gastrointestinal (GI) bleeding. Compared to controls, levels of SDF1 were significantly elevated in HHT patients (Proportional Increase [PI] = 1.87, p < 0.001, q = 0.011). Levels of sENG were significantly reduced in HHT patients compared to controls (PI = 0.56, p < 0.001, q < 0.001), reflecting the prevalence of HHT1 patients in this cohort. Levels of IL6 (PI = 3.22, p < 0.001, q < 0.001) and sTGFβR3 (PI = 0.70, p = 0.001, q < 0.029) differed significantly in CCM patients compared to controls. Compared to controls, ten of the biomarkers were significantly different in sporadic BAVM patients (q-values < 0.05). Among the pairwise combinations of patient groups, a significant elevation was observed in TGFβ1 in CCM patients compared to sporadic BAVM patients (PI = 2.30, p < 0.001, q = 0.034). When examining the association of circulating biomarker levels with HHT-specific phenotypes, four markers were significantly lower in HHT patients with BAVM (q-values < 0.05), and four markers were significantly higher in patients with LVM (q-values < 0.05).

Conclusions
This pilot study suggests that the profile of circulating angiogenic and inflammatory biomarkers may be unique to each type of vascular malformation. Furthermore, this study indicates that circulating biomarkers may be useful for assessing phenotypic traits of vascular malformations.
Addressing the COVID-19 emergency during the ongoing political and economic crisis in Fragile Lebanon: a call to action
Authors: Lobkowicz Ludmila , Lahoud Julien , Bou-Orm Ibrahim 
Published: September 2021

AbstractThis Letter to the Editor aims to reflect on the current challenges to increase the coverage of COVID-19 vaccination in the fragile and conflict-affected setting of Lebanon, which is currently experiencing one of the biggest economic crises globally as well as a recent surge in COVID-19 cases. Addressing the supply- and demand-related factors affecting vaccination would increase COVID-19 vaccine coverage and prevent the complete collapse of an already overwhelmed Lebanese health care system.
Evaluation of different approaches for missing data imputation on features associated to genomic data
Authors: Petrazzini Ben Omega , Naya Hugo , Lopez-Bello Fernando , Vazquez Gustavo , Spangenberg Lucía 
Published: September 2021

Abstract
Background
Missing data is a common issue in different fields, such as electronics, image processing, medical records and genomics. They can limit or even bias the posterior analysis. The data collection process can lead to different distribution, frequency, and structure of missing data points. They can be classified into four categories: Structurally Missing Data (SMD), Missing Completely At Random (MCAR), Missing At Random (MAR) and Missing Not At Random (MNAR). For the three later, and in the context of genomic data (especially non-coding data), we will discuss six imputation approaches using 31,245 variants collected from ClinVar and annotated with 13 genome-wide features.

Results
Random Forest and kNN algorithms showed the best performance in the evaluated dataset. Additionally, some features show robust imputation regardless of the algorithm (e.g. conservation scores phyloP7 and phyloP20), while other features show poor imputation across algorithms (e.g. PhasCons). We also developed an R package that helps to test which imputation method is the best for a particular data set.

Conclusions
We found that Random Forest and kNN are the best imputation method for genomics data, including non-coding variants. Since Random Forest is computationally more challenging, kNN remains a more realistic approach. Future work on variant prioritization thru genomic screening tests could largely profit from this methodology.
Combinational blockade of MET and PD-L1 improves pancreatic cancer immunotherapeutic efficacy
Authors: Li Enliang , Huang Xing , Zhang Gang , Liang Tingbo 
Published: September 2021

Abstract
Background
Dysregulated expression and activation of receptor tyrosine kinases (RTKs) are associated with a range of human cancers. However, current RTK-targeting strategies exert little effect on pancreatic cancer, a highly malignant tumor with complex immune microenvironment. Given that immunotherapy for pancreatic cancer still remains challenging, this study aimed to elucidate the prognostic role of RTKs in pancreatic tumors with different immunological backgrounds and investigate their targeting potential in pancreatic cancer immunotherapy.

Methods
Kaplan–Meier plotter was used to analyze the prognostic significance of each of the all-known RTKs to date in immune “hot” and “cold” pancreatic cancers. Gene Expression Profiling Interactive Analysis-2 was applied to assess the differential expression of RTKs between pancreatic tumors and normal pancreatic tissues, as well as its correlation with immune checkpoints (ICPs). One hundred and fifty in-house clinical tissue specimens of pancreatic cancer were collected for expression and correlation validation via immunohistochemical analysis. Two pancreatic cancer cell lines were used to demonstrate the regulatory effects of RTKs on ICPs by biochemistry and flow cytometry. Two in vivo models bearing pancreatic tumors were jointly applied to investigate the combinational regimen of RTK inhibition and immune checkpoint blockade for pancreatic cancer immunotherapy.

Results
MET was identified as a pancreatic cancer-specific RTK, which is significantly associated with prognosis in both immune “hot” and “cold” pancreatic cancers. MET was observed to be highly upregulated in pancreatic cancer tissues, and positively correlated with PD-L1 levels. Elevated MET and PD-L1 expressions were closely associated with lymph node metastasis, tumor TNM stage, and overall survival in pancreatic cancer. Mechanistically, MET could interact with PD-L1, and maintain its expression level in multiple ways. MET deficiency was found to facilitate lymphocyte infiltration into pancreatic tumors. Finally, significant benefits of combining MET inhibition with PD-1/PD-L1 blockage were verified in both orthotopic and subcutaneous mouse models of pancreatic cancer.

Conclusions
This study systematically investigated the potential effectiveness of a novel pancreatic cancer immunotherapy targeting RTKs, and revealed the function of MET in PD-L1 regulation as well as the combined therapeutic efficacy of MET and PD-L1 in pancreatic cancer.
The efficacy and safety of Anyu Peibo Capsule in the treatment of patients with major depressive disorder in China: study protocol for a randomized placebo-controlled trial
Authors: Huang Jingjing , Yu Yimin , Jiang Yi , Chen Wu , Li Yan , Shen Yifeng , Zheng Qingshan , Li Huafang 
Published: September 2021

Abstract
Background
Major depressive disorder is the second leading cause of years lost to disability worldwide. Anyu Peibo Capsule has been shown to be effective and safe in phase II trials.

Methods
This clinical study is a multi-center, randomized, double-blinded, placebo-controlled, parallel-group, phase III trial of Anyu Peibo Capsule in China. The aim is to test whether the administration of Anyu Peibo Capsule compared to placebo improves clinical outcomes in adults (aged 18 to 65 years) with MDD. Patients will receive an 8-week treatment of Anyu Peibo Capsule 1.6 g per day or placebo. The primary outcome will be the change from baseline in the total score for the Montgomery-Asberg Depression Rating Scale at the end of the 8-week treatment.

Discussion
The trial aims to provide pivotal evidence for the efficacy and safety of Anyu Peibo Capsule in patients with major depressive disorder.

Trial registration
ClinicalTrials.govNCT04210973. Registered on December 26, 2019
Effects of intrinsic-foot-muscle exercise combined with the lower extremity resistance training on postural stability in older adults with fall risk: study protocol for a randomised controlled trial
Authors: Lai Zhangqi , Pang Hongbo , Hu Xiaoyue , Dong Kun , Wang Lin 
Published: September 2021

Abstract
Background
Falls are one of the most common accidents in older adults, often leading to injury, disability and quality-of-life declines. Foot core function contributes to postural stability in most static postures and dynamic activities. As efficient foot core training, the intrinsic-foot-muscle exercise has been proposed to improve postural control. However, the effects of the exercise on postural stability in the elderly remain unclear. Therefore, this study attempts to investigate the effect of 12-week intrinsic-foot-muscle exercise on postural stability in older adults with fall risk.

Methods
We will conduct a prospective, single-blind randomised controlled trail on 120 older adults with fall risk. Participants will be randomly assigned to an intrinsic-foot-muscle exercise combining the lower extremity resistance training group (IFM group), an extrinsic-foot-muscle exercise combining the lower extremity resistance training group (EFM group) and a control group. The control group will perform lower extremity resistance training. The IFM and EFM groups will be given additional short-foot exercise or towel-curl exercise training, respectively. After the intervention, participants will be followed up for another 12 weeks with no active intervention. The outcome measures will include the postural stability measurements, self-reported postural stability, number of falls, intrinsic-foot-muscle strength and foot arch function. Furthermore, adverse events will be recorded and analysed. If any participant withdraws from the trial, an intention-to-treat analysis will be performed.

Discussion
The trial is designed to investigate the efficacy of a 12-week intrinsic foot muscle training combined with the lower extremity resistance training on postural stability outcomes in elderly people with fall risk. The trial will also examine the comprehensive outcomes of postural stability during static standing and dynamic movements. The function of intrinsic foot muscle to support the arch will also be evaluated. Important features of this trial mainly include intervention setting, outcome measure selection and study duration. The results of this study will determine the effectiveness and provide scientific evidence to establish comprehensive fall prevention intervention.

Trial registration
Chinese Clinical Trial Registry ChiCTR2000033623. Registered on 7 June 2020. http://www.chictr.org.cn/showproj.aspx?proj=54741
Latrocimicinae completes the phylogeny of Cimicidae: meeting old morphologic data rather than modern host phylogeny
Authors: Hornok Sándor , Szentiványi Tamara , Takács Nóra , Kovács Áron Botond , Glaizot Olivier , Christe Philippe , Fasel Nicolas , Gyuranecz Miklós , Kontschán Jenő 
Published: September 2021

AbstractThe family Cimicidae includes obligate hematophagous ectoparasites (bed bugs and their relatives) with high veterinary/medical importance. The evolutionary relationships of Cimicidae and their hosts have recently been reported in a phylogenetic context, but in the relevant study, one of the six subfamilies, the bat-specific Latrocimicinae, was not represented. In this study the only known species of Latrocimicinae, i.e.,Latrocimex spectans, was analyzed with molecular and phylogenetic methods based on four (two nuclear and two mitochondrial) genetic markers. The completed subfamily-level phylogeny of Cimicidae showed that Latrocimicinae is most closely related to Haematosiphoninae (ectoparasites of birds and humans), with which it shares systematically important morphologic characters, but not hosts. Moreover, in the phylogenetic analyses, cimicid bugs that are known to infest phylogenetically distant bat hosts clustered together (e.g.,LeptocimexandStricticimexwithin Cacodminae), while cimicid subfamilies (Latrocimicinae, Primicimicinae) that are known to infest bat hosts from closely related superfamilies clustered distantly. In conclusion, adding Latrocimicinae significantly contributed to the resolution of the phylogeny of Cimicidae. The close phylogenetic relationship between Latrocimicinae and Haematosiphoninae is consistent with long-known morphologic data. At the same time, phylogenetic relationships of genera within subfamilies are inconsistent with the phylogeny of relevant hosts.Graphical abstract
Caffeine improves work durability and physical performance in anaerobic exercises among active adults in Tripoli Lebanon
Authors: Tayba Zeina , Sacre Yonna , Attieh Randa , Mannan Haider 
Published: September 2021

Abstract
Background
People worldwide have a high intake of caffeine. Active adults are among the group of people who have always been interested in caffeine as an ergogenic aid. This study aims at examining the association between caffeine consumption and perceived performance (aerobic and anaerobic exercises) among active people attending different gyms in Tripoli, Lebanon.

Methods
A cross-sectional study was conducted on 206 participants attending seven gyms in Tripoli. Participants were recruited using simple random sampling for a face-to-face individual interview. Data were collected using a semi-structured questionnaire. Data have been coded, entered, and analyzed using SPSS software.

Results
The prevalence rate of active people practicing both aerobic and anaerobic exercises is 63.6%. More than half of our sample (54.8%) has been working out for a duration of more than 6 months and 84.6% of respondents spend at least 30 min during their workouts. Caffeine consumption was popular in our sample with 92.2% indicating that they use caffeinated products. The findings of this study showed an association between anaerobic exercise and caffeine, perceived as physical performance enhancer and work durability enhancer. Yet no association was found between aerobic exercise and caffeine consumption.

Conclusions
Perhaps, future research could focus on the safe doses of caffeine that could be given for anaerobic exercises to have an ergogenic effect. This could help us to build scientific guidelines for caffeine’s association with sports performance.
RAPD and ERIC-PCR coupled with HRM for species identification of non-dysenteriae Shigella species; as a potential alternative method
Authors: Pakbin Babak , Basti Afshin Akhondzadeh , Khanjari Ali , Azimi Leila , Brück Wolfram Manuel , Karimi Abdollah 
Published: September 2021

AbstractObjectiveSpecies identification ofShigellaisolates are so prominent for epidemiological studies and infection prevention strategies. We developed and evaluated RAPD and ERIC-PCR coupled with HRM for differentiation of non-dysenteriaeShigellaspecies as potential alternative methods. After isolation of eighteenShigellastrains from faecal specimens collected from children under 2 years of age with diarrhea (n = 143), the species of the isolates were identified by slide agglutination assay. Also, species were identified using developed RAPD-PCR-HRM and ERIC-PCR-HRM techniques. Differentiation of the data sets was measured by principal component analysis as a dimension reduction method. Then, sensitivity and specificity of the methods were evaluated.ResultsWe found RAPD-PCR-HRM method with high sensitivity and specificity (100 and 85% respectively) to identify non-dysenteriaeShigellaspecies in clinical specimens. However, sensitivity and specificity of ERIC-PCR-HRM were evaluated 33 and 46% respectively and significantly lower than that of RAPD-PCR-HRM assay. Regardless of inherent poor reproducibility of DNA fingerprinting-based methods, RAPD-PCR-HRM assay can be considered as a potential alternative method to identify non-dysenteriae species ofShigellain clinical specimens. As we observed in the current study, HRM technique is more rapid, inexpensive, and sensitive than gel electrophoresis method to characterize PCR amplicons.
Leukotriene receptor antagonist use and cognitive decline in normal cognition, mild cognitive impairment, and Alzheimer’s dementia
Authors: Xiong Lisa Y. , Ouk Michael , Wu Che-Yuan , Rabin Jennifer S. , Lanctôt Krista L. , Herrmann Nathan , Black Sandra E. , Edwards Jodi D. , Swardfager Walter 
Published: September 2021

Abstract
Background
Leukotriene receptor antagonists (LTRAs) alleviate Alzheimer’s disease (AD) pathology and improve cognition in animal models; however, clinical evidence is limited. This study aimed to explore the associations between the use of LTRAs (montelukast or zafirlukast) and cognitive performance in people with normal cognition, mild cognitive impairment (MCI), or AD dementia. We hypothesized that LTRA use would be associated with better cognitive performance over time.

Methods
This longitudinal observational study used data from the National Alzheimer’s Coordinating Center. Within groups of participants with normal cognition, MCI, or AD dementia, LTRA users were matched 1:3 to non-users using propensity score matching. Cognitive domains including immediate and delayed memory (Wechsler Memory Scale Revised-Logical Memory IA and IIA), psychomotor processing speed (Digit Symbol Substitution Test), and language (animal naming, vegetable naming, and Boston Naming Test) were compared between users and non-users in mixed-effects linear or Poisson regression models.

Results
In AD dementia, LTRA use was associated with a slower decline in psychomotor processing speed, as measured by the Digit Symbol Substitution Test (Β = 1.466 [0.253, 2.678] symbols/year, n = 442), and language, as measured by animal naming (Β = 0.541 [0.215, 0.866] animals/year, n = 566), vegetable naming (B = 0.309 [0.056, 0.561] vegetables/year, n = 565), and the Boston Naming Test (B = 0.529 [0.005, 1.053] items/year, n = 561). Effect sizes were small but persisted after controlling for a 10% false discovery rate. LTRA use was not associated with changes in memory performance in AD, nor was it associated with changes in cognitive performance in people with normal cognition or MCI. In a post hoc analysis, LTRA use was associated with a slower decline in clinical progression in MCI (B = −0.200 [−0.380, −0.019] points/year, n = 800) and AD dementia (B = −0.321 [−0.597, −0.046] points/year, n = 604) as measured by CDR Sum of Boxes.

Conclusions
The use of LTRAs was associated with preserved function in non-amnestic cognitive domains in AD dementia. The role of leukotrienes and their receptors in cognitive decline warrants further investigation and the leukotriene pathway may represent a target for AD treatment.
Influence of Trichoderma asperellum and Bacillus subtilis as biocontrol and plant growth promoting agents on soil microbiota
Authors: Senkovs Maris , Nikolajeva Vizma , Makarenkova Galina , Petrina Zaiga 
Published: September 2021

Abstract
Purpose
The manipulation of soil microbiota can involve changes in microbial diversity and microbial activities, and it is carried out for practical purposes. The microbial diversity can be modified by the inoculation of beneficial microorganisms into soil or by agricultural management practices. This study provides information on the influence of introducing beneficial soil microorganisms on soil indigenous microbiota. The aim of this study was to determine how biocontrol and plant growth promoting agents Trichoderma asperellum and Bacillus subtilis and their consortium affect indigenous soil microbiota without placing emphasis on the plant as a determinant of change.

Methods
Experimental soil samples were treated with B. subtilis and T. asperellum and their consortium. The shift of number of bacterial and fungal CFUs in soil was determined. Biolog EcoPlate assay demonstrated the metabolic activity of microorganisms in soil. The concentration of Trichoderma genus, Firmicutes, Gammaproteobacteria and Acidobacteria DNA in soil samples was determined by molecular methods. A correlation analysis was performed between microbiological and molecular data.

Results
Soil treatment with T. asperellum, B. subtilis and the plant pathogenic fungus Botrytis cinerea changed the number of CFUs and amplified DNA fragments of certain taxa. The study showed that added microorganisms did not significantly affect the metabolic diversity of the community and Shannon-Wiener biodiversity index but change the utilization of carbohydrates, complex carbon compounds and organic phosphorus compounds.

Conclusion
Introduced biocontrol and plant growth promoting agents T. asperellum and B. subtilis survive in soil during a 60-day experiment and influence composition and functionality of indigenous populations. Whereas B. subtilis and T. asperellum and their consortium are inhibitors of the pathogenic fungus B. cinerea, this could further positively affect specific crops.