bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fucosidosis in Tunisian patients: mutational analysis and homology-based modeling of FUCA1 enzyme
Authors: Chkioua Latifa , Amri Yessine , Chaima Sahli , Fenni Ferdawes , Boudabous Hela , Ben Turkia Hadhami , Messaoud Taieb , Tebib Neji , Laradi Sandrine 
Published: August 2021

Abstract
Background
Fucosidosis is an autosomal recessive lysosomal storage disease caused by defective alpha-l-fucosidase (FUCA1) activity, leading to the accumulation of fucose-containing glycolipids and glycoproteins in various tissues. Clinical features include angiokeratoma, progressive psychomotor retardation, neurologic signs, coarse facial features, and dysostosis multiplex.

Methods
All exons and flanking intron regions of FUCA1 were screened by direct sequencing to identify mutations and polymorphisms in three unrelated families with fucosidosis. Bioinformatics tools were then used to predict the impacts of novel alterations on the structure and function of proteins. Furthermore, the identified mutations were localized onto a 3D structure model using the DeepView Swiss-PdbViewer 4.1 software, which established a function-structure relationship of the FUCA1 proteins.

Results
Four novel mutations were identified in this study. Two patients (P1 and P2) in Families 1 and 2 who had the severe phenotype were homoallelic for the two identified frameshift mutations p.K57Sfs*75 and p.F77Sfs*55, respectively. The affected patient (P3) from Family 3, who had the milder phenotype, was heterozygous for the novel missense mutation p.G332E and the novel splice site mutation c.662+5g>c. We verified that this sequence variation did not correspond to a polymorphism by testing 50 unrelated individuals. Additionally, 16 FUCA1 polymorphisms were identified. The structure prediction analysis showed that the missense mutation p.G332E would probably lead to a significant conformational change, thereby preventing the expression of the FUCA1 protein indeed; the 3D structural model of the FUCA1 protein reveals that the glycine at position 332 is located near a catalytic nucleophilic residue. This makes it likely that the enzymatic function of the protein with p.G332E is severely impaired.

Conclusion
These are the first FUCA1 mutations identified in Tunisia that cause the fucosidosis disease. Bioinformatics analysis allowed us to establish an approximate structure–function relationship for the FUCA1 protein, thereby providing better genotype/phenotype correlation knowledge.
Genetic diversity and epidemiology of human rhinovirus among children with severe acute respiratory tract infection in Guangzhou, China
Authors: Li Wanwei , Yu Bo , Zhou Jijian , Wang Yanlan , Xue Bao , Pan Jialong , Ran Yanhong , Yang Xiaoping , Wang Xiaoping , Yang Fang , Li Hongjian 
Published: August 2021

Abstract
Background
Human rhinovirus (HRV) is one of the major viruses of acute respiratory tract disease among infants and young children. This work aimed to understand the epidemiological and phylogenetic features of HRV in Guangzhou, China. In addition, the clinical characteristics of hospitalized children infected with different subtype of HRV was investigated.

Methods
Hospitalized children aged < 14 years old with acute respiratory tract infections were enrolled from August 2018 to December 2019. HRV was screened for by a real-time reverse-transcription PCR targeting the viral 5′UTR.

Results
HRV was detected in 6.41% of the 655 specimens. HRV infection was frequently observed in children under 2 years old (57.13%). HRV-A and HRV-C were detected in 18 (45%) and 22 (55%) specimens. All 40 HRV strains detected were classified into 29 genotypes. The molecular evolutionary rate of HRV-C was estimated to be 3.34 × 10–3 substitutions/site/year and was faster than HRV-A (7.79 × 10–4 substitutions/site/year). Children who experienced rhinorrhoea were more common in the HRV-C infection patients than HRV-A. The viral load was higher in HRV-C detection group than HRV-A detection group (p = 0.0148). The median peak symptom score was higher in patients with HRV-C infection as compared to HRV-A (p = 0.0543), even though the difference did not significance.

Conclusion
This study revealed the molecular epidemiological characteristics of HRV in patients with respiratory infections in southern China. Children infected with HRV-C caused more severe disease characteristics than HRV-A, which might be connected with higher viral load in patients infected with HRV-C. These findings will provide valuable information for the pathogenic mechanism and treatment of HRV infection.
Safe by design (SbD) and nanotechnology: a much-discussed topic with a prudence?
Authors: Gulumian Mary , Cassee Flemming R. 
Published: August 2021

AbstractSafe-by-Design (SbD) has been put forward as a concept to assure that only safe nanomaterials will reach the market and that safety aspects have already been considered in a very early stage of the innovation process. In practice, several laboratory test have been proposed to screen newly developed nanomaterials and nano-enabled products to assess their hazardous nature. These tests need to have sufficient predictive power for possible adverse effects on human health, not only due to acute (peak) exposures, but also for long-term (low dose) exposures as these materials may accumulate over time in organs and tissues.
Effect of osteoporotic conditions on the development of peritumoral brain edema after LINAC-based radiation treatment in patients with intracranial meningioma
Authors: Kang Sang Mook , Kim Jae Min , Cheong Jin Hwan , Ryu Je Il , Won Yu Deok , Kim Young Soo , Han Myung-Hoon 
Published: August 2021

Abstract
Purpose
Disruption of the tumor-brain barrier in meningioma is a crucial factor in peritumoral brain edema (PTBE). We previously reported the possible effect of osteoporosis on the integrity of the arachnoid trabeculae because both the bone and the arachnoid trabeculae are composed of type 1 collagen. We hypothesized that osteoporotic conditions may be associated with PTBE occurrence after radiation treatment in patients with meningioma.

Methods
A receiver operating characteristic curve analysis was used to identify the optimal cut-off values of mean skull Hounsfield unit for predicting osteopenia and osteoporosis in patients from our registry. Multivariate Cox regression analysis was used to determine whether possible osteoporosis independently predicted PTBE development in patients with meningioma after radiation.

Results
A total of 106 intracranial meningiomas were included for the study. All patients received linear accelerator-based radiation therapy in our hospital over an approximate 6-year period. Multivariate Cox regression analysis identified that hypothetical osteoporosis was an independent predictive factor for the development of PTBE in patients with meningioma after linear accelerator-based radiation treatment (hazard ratio 5.20; 95% confidence interval 1.11–24.46; p = 0.037).

Conclusions
Our study suggests that possible osteoporotic conditions may affect PTBE development after linear accelerator-based radiation treatment for intracranial meningioma. However, due to the study’s small number of patients, these findings need to be validated in future studies with larger cohorts, before firm recommendations can be made.

Graphic abstract
Comprehensive analysis of metabolism-related lncRNAs related to the progression and prognosis in osteosarcoma from TCGA
Authors: Chen Xingyin , Ye Zhengyun , Lou Pan , Liu Wei , Liu Ying 
Published: August 2021

Abstract
Background
Osteosarcoma is one of the most common malignant neoplasms in children and adolescents. Studies have shown that metabolism-related pathways are vital for the development and metastasis of osteosarcoma. Long non-coding RNA (lncRNA) plays a key role in the occurrence and progression of cancer in a variety of ways. However, the detailed molecular mechanisms of metabolism-related lncRNA in osteosarcoma remain to be deeply elucidated.

Methods
In this study, all metabolism-related mRNAs and lncRNAs in osteosarcoma were extracted and identified based on transcriptomic data from the TCGA database. Usingsurvival analysis, univariate and multivariate independent prognostic analysis, gene set enrichment analysis, and nomogram, a prognostic signature with metabolic lncRNAs as prognostic factors was constructed.

Results
Nine prognostic factors included lncRNA AC009779.2, lncRNA AL591895.1, lncRNA AC026271.3, lncRNA LPP-AS2, lncRNA LINC01857, lncRNA AP005264.1, lncRNA LINC02454, lncRNA AL133338.1, and lncRNA AC135178.5, respectively. Survival analysis indicated that alterations of specific lncRNA expression were strongly correlated with poor prognosis in osteosarcoma. Univariate and multivariate independent prognostic analysis showed that the prognostic signature had a good independent predictive ability for patient survival. The results of GSEA suggested that these predictors may be involved in the metabolism of certain substances or energy in cancer. The nomogram was further drawn for clinical guidance and assistance in clinical decision-making.

Conclusions
This study identified multiple metabolism-related lncRNAs, which may be novel therapeutic targets for osteosarcoma, and contributed to better explore the specific metabolic regulatory mechanisms of lncRNA in osteosarcoma.
Investigation of timing of surgery and other factors possibly influencing outcome in dogs with acute thoracolumbar disc extrusion: a retrospective study of 1501 cases
Authors: Immekeppel Almut , Rupp Stefan , Demierre Stanislas , Rentmeister Kai , Meyer-Lindenberg Andrea , Goessmann Julia , Bali Monty Siddartha , Schmidli-Davies Fenella , Forterre Franck 
Published: August 2021

Abstract
Background
Intervertebral disc extrusions in the thoracolumbar region are a common spinal neurologic disorder in dogs and usually considered a neurological emergency. Several factors, like timing of surgery, have previously been analysed in order to determine the effect on outcome and time of recovery. Most studies have investigated one defined population of dogs and the influence of a single factor on the overall outcome. In this retrospective study, a large cohort of dogs and the influence of one or combinations of several factors on outcome and time of recovery were analysed.

Results
The bivariate analysis demonstrated a significant association between the following variables and the time of recovery: the time span between the onset of clinical signs and surgery (Cramers Phi $$\varphi^{\prime}$$

φ
′

= 0.14; P = 0.003), the grade of severity ($$\varphi^{\prime}$$

φ
′

= 0.23; P < 0.001) and the implementation of physical rehabilitation ($$\varphi^{\prime}$$

φ
′

= 0.2; P < 0.001). However, the analysis of a multivariable regression model demonstrated that a significant correlation only exists between the time span between the onset of clinical signs and surgery and the overall outcome (P = 0.007), as well as between the grade of severity and the time of recovery (P < 0.001). The percentage of dogs with lacking deep pain perception (DPP) that had to be euthanised due to their neurological condition, decreased from 20.0 to 2.9% when physical rehabilitation was implemented. Additionally, the proportion of dogs (same group) that improved to reach an ambulatory status increased from 80.0 to 91.4%.

Conclusion
The results of the bivariate analysis demonstrated several correlations between some variables and overall outcome or time of recovery, whereas the multivariable regression model demonstrated only two associations. The time span between the onset of clinical signs and surgery was significantly associated with the overall outcome. We therefore suggest that a surgical intervention should be performed without unreasonable delay. Due to the correlation between the grade of severity and time of recovery, owners of dogs with more severe neurological deficits prior to surgery should be informed about the presumably prolonged time of recovery.
Phase 1 clinical trial of the PI3Kδ inhibitor YY-20394 in patients with B-cell hematological malignancies
Authors: Jiang Bo , Qi Junyuan , Song Yuqin , Li Zengjun , Tu Meifeng , Ping Lingyan , Liu Zongliang , Bao Hanying , Xu Zusheng , Qiu Lugui 
Published: August 2021

AbstractYY-20394, an oral phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor, was investigated in a first-in-human study of patients with relapsed or refractory B-cell malignancies. During dose escalation, 25 patients received 20–200 mg of YY-20394 daily. The primary outcome measures were tolerability and dose-limiting toxicity (DLT). The secondary outcomes were pharmacokinetic parameters, progression-free survival (PFS) and the objective response rate (ORR). Since no patients experienced DLT, the maximum tolerated dose (MTD) was not reached. The majority (≥ 5%) of drug-related adverse events were ≥ grade III, being neutropenia (44.0%), pneumonia (16.0%), hyperuricemia (12.0%), lymphocythemia (8.0%), leukopenia (8.0%) and pneumonitis (8.0%). The overall ORR was 64.0% (95% confidence interval (CI): 45.2, 82.8%) including 5 patients with complete remission (CR), 11 with partial remission (PR), 2 with stable disease (SD) and 7 with progressive disease (PD), while the disease control rate (DCR) was 72.0% (95% CI: 54.4, 89.6%). The ORR of 10 patients with follicular lymphoma was 90%. The median PFS time was 255 days. One PR patient with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who received 40 mg q.d. had a durable response of around 36 months. The median PFS time of 10 patients with follicular lymphoma was 300 days. A recommended phase 2 dose of 80 mg q.d. was established. Considering that YY-20394 was well-tolerated with promising preliminary efficacy, further development is warranted.Trial registration clinicaltrials.gov, NCT03757000, retrospectively registered, November 28, 2018, https://clinicaltrials.gov/ct2/show/NCT03757000?term=NCT03757000&draw=2&rank=1.
Incidence of delayed bleeding in patients on antiplatelet therapy after mild traumatic brain injury: a systematic review and meta-analysis
Authors: Colombo Giorgio , Bonzi Mattia , Fiorelli Elisa , Jachetti Alessandro , Bozzano Viviana , Casazza Giovanni , Solbiati Monica , Costantino Giorgio 
Published: August 2021

AbstractBackgroundThe scientific evidence regarding the risk of delayed intracranial bleeding (DB) after mild traumatic brain injury (MTBI) in patients administered an antiplatelet agent (APA) is scant and incomplete. In addition, no consensus exists on the utility of a routine repeated head computed tomography (CT) scan in these patients.ObjectiveThe aim of this study was to evaluate the risk of DB after MTBI in patients administered an APA.MethodsA systematic review and meta-analysis of prospective and retrospective observational studies enrolling adult patients with MTBI administered an APA and who had a second CT scan performed or a clinical follow-up to detect any DB after a first negative head CT scan were conducted. The primary outcome was the risk of DB in MTBI patients administered an APA. The secondary outcome was the risk of clinically relevant DB (defined as any DB leading to neurosurgical intervention or death).ResultsSixteen studies comprising 2930 patients were included in this meta-analysis. The pooled absolute risk for DB was 0.77% (95% CI 0.23–1.52%), ranging from 0 to 4%, with substantial heterogeneity (I2 = 61%). The pooled incidence of clinically relevant DB was 0.18%. The subgroup of patients on dual antiplatelet therapy (DAPT) had an increased DB risk, compared to the acetylsalicylic acid (ASA)-only patients (2.64% vs. 0.22%; p = 0.04).ConclusionOur systematic review showed a very low risk of DB in MTBI patients on antiplatelet therapy. We believe that such a low rate of DB could not justify routine repeated CT scans in MTBI patients administered a single APA. We speculate that in the case of clinically stable patients, a repeated head CT scan could be useful for select high-risk patients and for patients on DAPT before discharge.
Composition analysis and microencapsulation of Eucommia ulmoides seed oil
Authors: Huirong Zhang , huina Zhang , Nifeng Chen , Li Li 
Published: August 2021

Abstract
Background
Eucommia ulmoides seed oil is a functional health oil with a high content of unsaturated fatty acids. However, excessively high content of unsaturated fatty acids can cause E. ulmoides seed oil to easily spoil. Microencapsulation technology can effectively encapsulate substances, thereby prolonging the spoilage time of oil products.

Methods
In the present study, E. ulmoides seed oil from different manufacturers were analyzed by Agilent 7890B-5977A gas chromatography–mass spectrometry. Encapsulation efficiency, yield rate, and scanning electron microscopy results between microcapsules prepared use different wall materials and different methods (spray drying and complex coagulation) were compared to determine the best preparation process for microcapsules. The Wantong 892 professional oil oxidation stability tester was used to measure the induced oxidation time of the E. ulmoides seed oil and microcapsules.

Conclusion
E. ulmoides seed oil comprises > 80% unsaturated fatty acids with a high α-linolenic acid content, followed by linoleic acid. The most promising combination was chitosan:gum arabic at 1:8 as the wall material and complex coagulation. The best preparation had a wall material concentration, stirring speed, aggregation pH, and core-to-wall ratio of 2.5%, 500 rpm, 4.2, and 1:4, respectively. Microcapsules prepared under these conditions exhibited higher yield and encapsulation efficiency (94.0% and 73.3%, respectively). The induced oxidation time of the E. ulmoides seed oil and microcapsules were 3.8 h and 13.9 h, respectively, indicating that microencapsulation can increase the oxidation induction time of this oil.
Unbiased proteomic mapping of the LINE-1 promoter using CRISPR Cas9
Authors: Briggs Erica M. , Mita Paolo , Sun Xiaoji , Ha Susan , Vasilyev Nikita , Leopold Zev R. , Nudler Evgeny , Boeke Jef D. , Logan Susan K. 
Published: August 2021

Abstract
Background
The autonomous retroelement Long Interspersed Element-1 (LINE-1) mobilizes though a copy and paste mechanism using an RNA intermediate (retrotransposition). Throughout human evolution, around 500,000 LINE-1 sequences have accumulated in the genome. Most of these sequences belong to ancestral LINE-1 subfamilies, including L1PA2-L1PA7, and can no longer mobilize. Only a small fraction of LINE-1 sequences, approximately 80 to 100 copies belonging to the L1Hs subfamily, are complete and still capable of retrotransposition. While silenced in most cells, many questions remain regarding LINE-1 dysregulation in cancer cells.

Results
Here, we optimized CRISPR Cas9 gRNAs to specifically target the regulatory sequence of the L1Hs 5’UTR promoter. We identified three gRNAs that were more specific to L1Hs, with limited binding to older LINE-1 sequences (L1PA2-L1PA7). We also adapted the C-BERST method (dCas9-APEX2 Biotinylation at genomic Elements by Restricted Spatial Tagging) to identify LINE-1 transcriptional regulators in cancer cells. Our LINE-1 C-BERST screen revealed both known and novel LINE-1 transcriptional regulators, including CTCF, YY1 and DUSP1.

Conclusion
Our optimization and evaluation of gRNA specificity and application of the C-BERST method creates a tool for studying the regulatory mechanisms of LINE-1 in cancer. Further, we identified the dual specificity protein phosphatase, DUSP1, as a novel regulator of LINE-1 transcription.
Pre-implantation alcohol exposure induces lasting sex-specific DNA methylation programming errors in the developing forebrain
Authors: Legault L. M. , Doiron K. , Breton-Larrivée M. , Langford-Avelar A. , Lemieux A. , Caron M. , Jerome-Majewska L. A. , Sinnett D. , McGraw S. 
Published: August 2021

Abstract
Background
Prenatal alcohol exposure is recognized for altering DNA methylation profiles of brain cells during development, and to be part of the molecular basis underpinning Fetal Alcohol Spectrum Disorder (FASD) etiology.  However, we have negligible information on the effects of alcohol exposure during pre-implantation, the early embryonic window marked with dynamic DNA methylation reprogramming, and on how this may rewire the brain developmental program.

Results
Using a pre-clinical in vivo mouse model, we show that a binge-like alcohol exposure during pre-implantation at the 8-cell stage leads to surge in morphological brain defects and adverse developmental outcomes during fetal life. Genome-wide DNA methylation analyses of fetal forebrains uncovered sex-specific alterations, including partial loss of DNA methylation maintenance at imprinting control regions, and abnormal de novo DNA methylation profiles in various biological pathways (e.g., neural/brain development).

Conclusion
These findings support that alcohol-induced DNA methylation programming deviations during pre-implantation could contribute to the manifestation of neurodevelopmental phenotypes associated with FASD.
Rationale and study design of a randomized, placebo-controlled, double-blind phase 2b trial to evaluate efficacy, safety, and tolerability of an oral glutaminyl cyclase inhibitor varoglutamstat (PQ912) in study participants with MCI and mild AD—VIVIAD
Authors: Vijverberg E. G. B. , Axelsen T. M. , Bihlet A. R. , Henriksen K. , Weber F. , Fuchs K. , Harrison J. E. , Kühn-Wache K. , Alexandersen P. , Prins N. D. , Scheltens Philip 
Published: August 2021

Abstract
Background
Varoglutamstat (formerly PQ912) is a small molecule that inhibits the activity of the glutaminyl cyclase to reduce the level of pyroglutamate-A-beta (pGluAB42). Recent studies confirm that pGluAB42 is a particular amyloid form that is highly synaptotoxic and plays a significant role in the development of AD.

Methods
This paper describes the design and methodology behind the phase 2b VIVIAD-trial in AD. The aim of this study is to evaluate varoglutamstat in a state-of-the-art designed, placebo-controlled, double-blind, randomized clinical trial for safety and tolerability, efficacy on cognition, and effects on brain activity and AD biomarkers. In addition to its main purpose, the trial will explore potential associations between novel and established biomarkers and their individual and composite relation to disease characteristics.

Results
To be expected early 2023

Conclusion
This state of the art phase 2b study will yield important results for the field with respect to trial methodology and for the treatment of AD with a small molecule directed against pyroglutamate-A-beta.

Trial registration
ClinicalTrials.gov Identifier: NCT04498650