bluuebunny/crossref_metadata_2025_split huggingface dataset:
LRRC4 functions as a neuron-protective role in experimental autoimmune encephalomyelitis
Authors: Zhang Yan , Li Di , Zeng Qiuming , Feng Jianbo , Fu Haijuan , Luo Zhaohui , Xiao Bo , Yang Huan , Wu Minghua 
Published: May 2021

Abstract
Background
Leucine rich repeat containing 4 (LRRC4), also known as netrin-G ligand-2 (NGL-2), belongs to the superfamily of LRR proteins and serves as a receptor for netrin-G2. LRRC4 regulates the formation of excitatory synapses and promotes axon differentiation. Mutations in LRRC4 occur in Autism Spectrum Disorder (ASD) and intellectual disability. Multiple sclerosis (MS) is a chronic neuroinflammatory disease with spinal cords demyelination and neurodegeneration. Here, we sought to investigate whether LRRC4 is involved in spinal cords neuron-associated diseases.

Methods
LRRC4 was detected in the CNS of experimental autoimmune encephalomyelitis (EAE) mice by the use of real-time PCR and western blotting. LRRC4−/− mice were created and immunized with myelin oligodendrocyte glycoprotein peptide (MOG)35–55. Pathological changes in spinal cords of LRRC4−/− and WT mice 15 days after immunization were examined by using hematoxylin and eosin (H&E), Luxol Fast Blue (LFB) staining and immunohistochemistry. The number of Th1/Th2/Th17/Treg cells in spleens and blood were measured with flow cytometry. Differential gene expression in the spinal cords from WT and LRRC4−/− mice was analyzed by using RNA sequencing (RNA-seq). Adeno-associated virus (AAV) vectors were used to overexpress LRRC4 (AAV-LRRC4) and were injected into EAE mice to assess the therapeutic effect of AAV-LRRC4 ectopic expression on EAE.

Results
We report that LRRC4 is mainly expressed in neuron of spinal cords, and is decreased in the spinal cords of the EAE mice. Knockout of LRRC4 have a disease progression quickened and exacerbated with more severe myelin degeneration and infiltration of leukocytes into the spinal cords. We also first found that Rab7b is high expressed in EAE mice, and the deficiency of LRRC4 induces the elevated NF-κB p65 by up-regulating Rab7b, and up-regulation of IL-6, IFN-γ and down-regulation of TNF-α, results in more severe Th1 immune response in LRRC4−/− mice. Ectopic expression of LRRC4 alleviates the clinical symptoms of EAE mice and protects the neurons from immune damages.

Conclusions
We identified a neuroprotective role of LRRC4 in the progression of EAE, which may be used as a potential target for auxiliary support therapeutic treatment of MS.
Decline in attentional inhibition among migraine patients: an event‐related potential study using the Stroop task
Authors: Su Min , Wang Rongfei , Dong Zhao , Zhao Dengfa , Yu Shengyuan 
Published: May 2021

Abstract
Background
As a disorder of brain dysfunction, migraine has been associated with cognitive decline. However, no consistent results with respect to the attention function in migraineurs have been found, and the relationship between attentional inhibition and migraine is also unclear. In this study, the attentional inhibition function was evaluated using event-related potentials (ERPs) while migraine patients and healthy controls were performing the color–word Stroop task.

Methods
In this study, 75 migraine patients and 41 age-, gender-, and education-matched healthy controls were enrolled. The Stroop task was performed, and both behavioral and ERP data were analyzed.

Results
As to the behavioral data, the migraine group had a longer reaction time compared to the control group, but no difference in Stroop effect was observed. With respect to ERP components, the amplitudes of both early and late medial frontal negativity (MFN) were decreased in the migraine group. Additionally, obvious differences in the early MFN and sustained potential (SP) amplitudes were found between patients with and without allodynia.

Conclusions
At the behavioral level, migraine patients exhibited decreased executive ability but no obvious decline in inhibition. By contrast, a decline in attentional inhibition during the migraine interictal phase was confirmed by the analysis of ERP components, mainly those associated with changes in the conflict-monitoring stage, independent of confounding factors such as age, education, medication and mood disorders. Migraine patients with allodynia exhibited some significant differences in early MFN and SP compared to those without, supporting the hypothesis that migraine chronification aggravates the decline in attentional inhibition.
Galcanezumab for the prevention of high frequency episodic and chronic migraine in real life in Italy: a multicenter prospective cohort study (the GARLIT study)
Authors:   for the GARLIT Study Group, Vernieri Fabrizio , Altamura Claudia , Brunelli Nicoletta , Costa Carmelina Maria , Aurilia Cinzia , Egeo Gabriella , Fofi Luisa , Favoni Valentina , Pierangeli Giulia , Lovati Carlo , Aguggia Marco , d’Onofrio Florindo , Doretti Alberto , Di Fiore Paola , Finocchi Cinzia , Rao Renata , Bono Francesco , Ranieri Angelo , Albanese Maria , Cevoli Sabina , Barbanti Piero 
Published: May 2021

Abstract
Background
The clinical benefit of galcanezumab, demonstrated in randomized clinical trials (RCTs), remains to be quantified in real life. This study aimed at evaluating the effectiveness, safety and tolerability of galcanezumab in the prevention of high-frequency episodic migraine (HFEM) and chronic migraine (CM) in a real-life setting.

Methods
This multicenter prospective observational cohort study was conducted between November 2019 and January 2021 at 13 Italian headache centers. Consecutive adult HFEM and CM patients clinically eligible were enrolled and treated with galcanezumab subcutaneous injection 120 mg monthly with the first loading dose of 240 mg. The primary endpoint was the change in monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM patients after 6 months of therapy (V6). Secondary endpoints were the Numerical Rating Scale (NRS), monthly painkiller intake (MPI), HIT-6 and MIDAS scores changes, ≥50% responder rates (RR), the conversion rate from CM to episodic migraine (EM) and Medication Overuse (MO) discontinuation.

Results
One hundred sixty-three patients (80.5% female, 47.1 ± 11.7 years, 79.8% CM) were included. At V6, MMDs reduced by 8 days in HFEM and MHDs by 13 days in CM patients (both p < .001). NRS, MPI, HIT-6 and MIDAS scores significantly decreased (p < .001). Ten patients (6.1%) dropped out for inefficacy and classified as non-responders. Patients with ≥50%RRs, i.e. responders, were 76.5% in the HFEM and 63.5% in the CM group at V6. Among CM patients, the V6 responders presented a lower body mass index (p = .018) and had failed a lower number of preventive treatments (p = .013) than non-responders. At V6, 77.2% of CM patients converted to EM, and 82.0% ceased MO. Adverse events, none serious, were reported in up to 10.3% of patients during evaluation times.

Conclusions
Galcanezumab in real life was safe, well tolerated and seemed more effective than in RCTs. Normal weight and a low number of failed preventives were positively associated with galcanezumab effectiveness in CM patients.

Trial registration
ClinicalTrials.govNCT04803513.
Enhanced Patterned Cocatalyst TiO2/Fe2O3 Photoanodes for Water-Splitting
Authors: Hung Wei-Hsuan , Teng Yung-Jen , Tseng Chuan-Ming , Nguyen Hien Thi Thai 
Published: May 2021

AbstractIn this study, we used a hot-pressing process to enhance the photocatalytic properties of TiO2/Fe2O3 bimetallic oxide with a periodic patterned structure on the surface to increase photon absorption for photocatalysis in the oxygen evolution reaction for water splitting. The hot-pressed samples show that combining the two metal oxides improves the absorption band edge of the electrode at different wavelengths. The patterned structure obtained using the hot-pressing process successfully improves photon absorption, resulting in a two-fold enhancement compared with a flat surface electrode.
Controllable Spin Switching in a Single-Molecule Magnetic Tunneling Junction
Authors: Zhang Zhengzhong , Wang Ya , Wang Haiou , Liu Hao , Dong Liming 
Published: May 2021

AbstractA new type of spin-current filter is proposed that consists of a single-molecule magnet (SMM) coupled to two normal metal electrodes. It is shown that this tunneling junction can generate a highly spin-polarized current, whose spin polarization can be switched by means of magnetic fields and gate voltages applied to the SMM. This spin switching in the SMM tunnel junction arises from spin-selective single-electron resonant tunneling via the lowest unoccupied molecular orbit of the SMM. The electron current spectrum is still spin polarized in the absence of an external magnetic field, which can help to judge whether the molecule’s spin state has reached the ground-state doublet $$|\pm S\rangle$$

|
±
S
⟩

. This device can be realized with current technologies and may have practical use in spintronics and quantum information.
The evaluation of using new trachea and skin manikins for practicing emergency anterior neck access
Authors: Prathep Sumidtra , Jitpakdee Wilasinee , Pitathawatchai Pittayapon , Anuntaseree Sittichoke 
Published: May 2021

AbstractEmergency anterior neck access may be performed if intubation and ventilation fail. Practicing this life-saving procedure with manikins before facing a real-life emergency anterior neck access is required to do this procedure successfully when we encounter a difficult airway situation. The current manikins are expensive and thus are sometimes difficult to acquire in low-cost settings such as Thailand. We devise a cost-effective training manikin using less expensive materials but retaining the simple design of the trachea and skin areas which are flexible polyurethane (PU) foam and silicone, but which still had the same utility as the current manikins. Five items were evaluated, and then scores were rated by experienced physicians from 1 to 5 points for each item, 1 being the least and 5 the highest. The mean score concerning the appropriate size of the manikins was 4.55 ± 0.56. The mean score of the ease of use for practicing was 4.58 ± 0.59. The mean score of the similarity of the skin of the manikins to human skin was 3.85 ± 0.66. The mean score of the similarity of the trachea of the manikins to the human trachea was 3.80 ± 0.69. The mean score of the sensation of inserting the tube in the manikin compared to a real trachea was 3.90 ± 0.67. The mean overall benefit score of practicing on the manikins was 4.38 ± 0.45. Our trial indicates that this low-cost and simply designed manikin can be useful for practicing emergency airway management procedures to save patients who are struggling with lack of oxygen or intubation failure or failure of ventilation or other airway equipment such as endotracheal intubation and supraglottic airway devices (SGA).
Analysing the impact of the COVID-19 outbreak on everyday travel behaviour in Germany and potential implications for future travel patterns
Authors: Kolarova Viktoriya , Eisenmann Christine , Nobis Claudia , Winkler Christian , Lenz Barbara 
Published: May 2021

Abstract
Introduction
The global Coronavirus (COVID-19) pandemic is having a great impact on all areas of the everyday life, including travel behaviour. Various measures that focus on restricting social contacts have been implemented in order to reduce the spread of the virus. Understanding how daily activities and travel behaviour change during such global crisis and the reasons behind is crucial for developing suitable strategies for similar future events and analysing potential mid- and long-term impacts.

Methods
In order to provide empirical insights into changes in travel behaviour during the first Coronavirus-related lockdown in 2020 for Germany, an online survey with a relative representative sample for the German population was conducted a week after the start of the nationwide contact ban. The data was analysed performing descriptive and inferential statistical analyses.

Results and Discussion
The results suggest in general an increase in car use and decrease in public transport use as well as more negative perception of public transport as a transport alternative during the pandemic. Regarding activity-related travel patterns, the findings show firstly, that the majority of people go less frequent shopping; simultaneously, an increase in online shopping can be seen and characteristics of this group were analysed. Secondly, half of the adult population still left their home for leisure or to run errands; young adults were more active than all other age groups. Thirdly, the majority of the working population still went to work; one out of four people worked in home-office. Lastly, potential implications for travel behaviour and activity patterns as well as policy measures are discussed.
Exploring the evolutionary characteristics between cultivated tea and its wild relatives using complete chloroplast genomes
Authors: Peng Jiao , Zhao Yunlin , Dong Meng , Liu Shiquan , Hu Zhiyuan , Zhong Xiaofen , Xu Zhenggang 
Published: April 2021

AbstractBackgroundCultivated tea is one of the most important economic and ecological trees distributed worldwide. Cultivated tea suffer from long-term targeted selection of traits and overexploitation of habitats by human beings, which may have changed its genetic structure. The chloroplast is an organelle with a conserved cyclic genomic structure, and it can help us better understand the evolutionary relationship ofCamelliaplants.ResultsWe conducted comparative and evolutionary analyses on cultivated tea and wild tea, and we detected the evolutionary characteristics of cultivated tea. The chloroplast genome sizes of cultivated tea were slightly different, ranging from 157,025 to 157,100 bp. In addition, the cultivated species were more conserved than the wild species, in terms of the genome length, gene number, gene arrangement and GC content. However, comparingCamellia sinensisvar. sinensis andCamellia sinensisvar. assamica with their cultivars, the IR length variation was approximately 20 bp and 30 bp, respectively. The nucleotide diversity of 14 sequences in cultivated tea was higher than that in wild tea. Detailed analysis on the genomic variation and evolution ofCamellia sinensisvar. sinensis cultivars revealed 67 single nucleotide polymorphisms (SNPs), 46 insertions/deletions (indels), and 16 protein coding genes with nucleotide substitutions, whileCamellia sinensisvar. assamica cultivars revealed 4 indels. In cultivated tea, the most variable gene wasycf1. The largest number of nucleotide substitutions, five amino acids exhibited site-specific selection, and a 9 bp sequence insertion were found in theCamellia sinensisvar. sinensis cultivars. In addition, phylogenetic relationship in theycf1tree suggested that theycf1gene has diverged in cultivated tea. BecauseC. sinensisvar. sinensis and its cultivated species were not tightly clustered.ConclusionsThe cultivated species were more conserved than the wild species in terms of architecture and linear sequence order. The variation of the chloroplast genome in cultivated tea was mainly manifested in the nucleotide polymorphisms and sequence insertions. These results provided evidence regarding the influence of human activities on tea.
The complete mitochondrial genome of the intertidal spider (Desis jiaxiangi) provides novel insights into the adaptive evolution of the mitogenome and the evolution of spiders
Authors: Li Fan , Lv Yunyun , Wen Zhengyong , Bian Chao , Zhang Xinhui , Guo Shengtao , Shi Qiong , Li Daiqin 
Published: April 2021

Abstract
Background
Although almost all extant spider species live in terrestrial environments, a few species live fully submerged in freshwater or seawater. The intertidal spiders (genus Desis) built silk nests within coral crevices can survive submerged in high tides. The diving bell spider, Argyroneta aquatica, resides in a similar dynamic environment but exclusively in freshwater. Given the pivotal role played by mitochondria in supplying most energy for physiological activity via oxidative phosphorylation and the environment, herein we sequenced the complete mitogenome of Desis jiaxiangi to investigate the adaptive evolution of the aquatic spider mitogenomes and the evolution of spiders.

Results
We assembled a complete mitogenome of the intertidal spider Desis jiaxiangi and performed comparative mitochondrial analyses of data set comprising of Desis jiaxiangi and other 45 previously published spider mitogenome sequences, including that of Argyroneta aquatica. We found a unique transposition of trnL2 and trnN genes in Desis jiaxiangi. Our robust phylogenetic topology clearly deciphered the evolutionary relationships between Desis jiaxiangi and Argyroneta aquatica as well as other spiders. We dated the divergence of Desis jiaxiangi and Argyroneta aquatica to the late Cretaceous at ~ 98 Ma. Our selection analyses detected a positive selection signal in the nd4 gene of the aquatic branch comprising both Desis jiaxiangi and Argyroneta aquatica. Surprisingly, Pirata subpiraticus, Hypochilus thorelli, and Argyroneta aquatica each had a higher Ka/Ks value in the 13 PCGs dataset among 46 taxa with complete mitogenomes, and these three species also showed positive selection signal in the nd6 gene.

Conclusions
Our finding of the unique transposition of trnL2 and trnN genes indicates that these genes may have experienced rearrangements in the history of intertidal spider evolution. The positive selection signals in the nd4 and nd6 genes might enable a better understanding of the spider metabolic adaptations in relation to different environments. Our construction of a novel mitogenome for the intertidal spider thus sheds light on the evolutionary history of spiders and their mitogenomes.
A case report of acute Leriche syndrome: aortoiliac occlusive disease due to embolization from left ventricular thrombus caused by myocarditis
Authors: Mohamed Abudi , Mattsson Gustav , Magnusson Peter 
Published: April 2021

Abstract
Background
Leriche syndrome is the triad of symptoms consisting of claudication, erectile dysfunction, and absence of femoral pulses. Inflammatory disease of the heart muscle, myocarditis, may occur because of immune system activation, drug exposure or infections.

Case presentation
A 31-year-old man with no previous medical history presented to the emergency department with acute back pain that had started suddenly during weightlifting, which was initially misdiagnosed as spinal disc herniation. The patient returned four hours later and a thoracoabdominal computed tomography showed a large thrombus in the aortoiliac region creating a total occlusion. Vascular surgery with embolectomy was immediately performed. Further investigation with echocardiography revealed deteriorated systolic dysfunction with marked hypokinesia and two large thrombi in the left ventricle. Cardiac magnetic resonance imaging showed late contrast enhancement of the inferolateral and septal regions, which indicated a recent myocarditis.

Conclusion
Myocarditis can result in multiple embolization with diverse organ manifestation including total occlusion of the aortoiliac arteries, which required urgent embolectomy.
Delayed emergency healthcare seeking behaviour by Dutch emergency department visitors during the first COVID-19 wave: a mixed methods retrospective observational study
Authors: Nab Maaike , van Vehmendahl Robyn , Somers Inne , Schoon Yvonne , Hesselink Gijs 
Published: May 2021

Abstract
Background
Emergency department (ED) visits due to non-coronavirus disease 2019 (COVID-19) conditions have drastically decreased since the outbreak of the COVID-19 pandemic. This study aimed to identify the magnitude, characteristics and underlying motivations of ED visitors with delayed healthcare seeking behaviour during the first wave of the pandemic.

Methods
Between March 9 and July 92,020, adults visiting the ED of an academic hospital in the East of the Netherlands received an online questionnaire to collect self-reported data on delay in seeking emergency care and subsequent motivations for this delay. Telephone interviews were held with a subsample of respondents to better understand the motivations for delay as described in the questionnaire. Quantitative data were analysed using descriptive statistics. Qualitative data were thematically analysed.

Results
One thousand three hundred thirty-eight questionnaires were returned (34.0% response). One in five respondents reported a delay in seeking emergency care. Almost half of these respondents (n = 126; 45.4%) reported that the pandemic influenced the delay. Respondents reporting delay were mainly older adults (mean 61.6; ±13.1 years), referred to the ED by the general practitioner (GP; 35.1%) or a medical specialist (34.7%), visiting the ED with cardiac problems (39.7%). The estimated median time of delay in receiving ED care was 3 days (inter quartile range 8 days). Respectively 46 (16.5%) and 26 (9.4%) respondents reported that their complaints would be either less severe or preventable if they had sought for emergency care earlier. Delayed care seeking behaviour was frequently motivated by: fear of contamination, not wanting to burden professionals, perceiving own complaints less urgent relative to COVID-19 patients, limited access to services, and by stay home instructions from referring professionals.

Conclusions
A relatively large proportion of ED visitors reported delay in seeking emergency care during the first wave. Delay was often driven by misperceptions of the accessibility of services and the legitimacy for seeking emergency care. Public messaging and close collaboration between the ED and referring professionals could help reduce delayed care for acute needs during future COVID-19 infection waves.
Clinical and therapeutic features and prognostic factors of metastatic colorectal cancer over age 80: a retrospective study
Authors: Hisada Hiroyuki , Takahashi Yu , Kubota Manabu , Shimura Haruhisa , Itobayashi Ei , Shimura Kenji , Nakamura Akira 
Published: May 2021

Abstract
Background
Colorectal cancer (CRC) is one of the most common cancers in the world. The number of elderly patients with CRC increases due to aging of the population. There are few studies that examined chemotherapy and prognostic factors in metastatic colorectal cancer (mCRC) patients aged ≥ 80 years. We assessed the efficacy of chemotherapy and prognostic factors among patients with mCRC aged ≥ 80 years.

Methods
We retrospectively analyzed clinical and laboratory findings of 987 patients newly diagnosed with CRC at Asahi General Hospital (Chiba, Japan) between January 2012 and December 2016. The Kaplan–Meier method was used for the overall survival (OS) and the log-rank test was used to identify difference between patients. A multivariate Cox proportional hazard regression analysis was performed to determine the hazard ratios and 95% confidence intervals (CIs) of prognostic factors among super-elderly patients.

Results
In total, 260 patients were diagnosed with mCRC (super-elderly group: n = 43, aged ≥ 80 years and younger group, n = 217, aged < 80 years). The performance status and nutritional status were worse in the super-elderly group than in the younger group. The OS of super-elderly patients who received chemotherapy was worse than that of younger patients (18.5 vs. 28.8 months; P = 0.052), although the difference was not significant. The OS of patients who received chemotherapy tended to be longer than that of those who did not; however, there were no significant differences in OS in the super-elderly group (18.5 vs. 8.4 months P = 0.33). Multivariate analysis revealed that carcinoembryonic antigen levels ≥ 5 ng/mL (hazard ratio: 2.27; 95% CI 1.09–4.74; P = 0.03) and prognostic nutritional index ≤ 35 (hazard ratio: 8.57; 95% CI 2.63–27.9; P = 0.0003) were independently associated with poor OS in the super-elderly group.

Conclusions
Patients with mCRC aged ≥ 80 years had lower OS than younger patients even though they received chemotherapy. Carcinoembryonic antigen and prognostic nutritional index were independent prognostic factors in super-elderly patients with mCRC, but chemotherapy was not.
Trial registration: retrospectively registered.