bluuebunny/crossref_metadata_2025 huggingface dataset:
Two Year Progression of Working Memory Impairments In Early Relapsing-Remitting Multiple Sclerosis: Appraisal of Working Memory Profiles And Measurement Sensitivity
Authors: Clough Meaghan , Bartholomew Jade , White Owen , Fielding Joanne
Published: June 2021

Working memory (WMem) impairments are a devastating symptom of Multiple Sclerosis (MS) that manifest as distinct profiles depending upon the type of impairment. It is unknown what WMem impairment profiles occur in early MS and how best to diagnose and measure their progression.88 participants (63 early relapsing-remitting MS, 25 healthy controls) were reviewed annually for two years (baseline, +1 year, +2 years) and completed five WMem tasks: oculomotor (OM) n-back-visual spatial sketchpad; digit-span forwards-phonological loop; California Verbal Learning Test (CVLT)-episodic buffer; digit-span backwards- central executive; symbol digit modalities test (SDMT)-cognitive processing speed. 65% of RRMS patients exhibited visual-spatial WMem impairments followed by 32% for episodic, 30% phonological loop, 24% central executive, 11% cognitive processing speed. These manifested alone (51%) or in combination (48%), with combined impairments the best marker of general WMem impairment. Significant progression in visual-spatial impairments was found for 24% of RRMS patients, with the OM n­-back maintaining sensitivity to general WMem impairment and progression. No other WMem subcomponent progressed or task maintained sensitivity. The results of this study provides crucial knowledge for the creation of interventions to treat WMem impairment in early RRMS, providing key targets for treatment and endpoints for determining efficacy.
Helmet Wearing Behavior Where People Often Ride Motorcycle in Ethiopia: a Cross-sectional Study
Authors: Bedru Delwana , Teshome Firanbon , Kebede Yohannes , Birhanu Zewdie
Published: June 2021

Background: Road traffic accidents are a major global concern which affects all people regardless of their age, sex, wealth, among others. Injuries and deaths due to motorcycle are highly increasing, especially in developing countries. Wearing helmet has been shown to significantly reduce deaths and injuries due to motorcycle accidents.Objectives: To assess magnitude of helmet wearing and its determinants among motorcycle riders in Sawula and Bulky towns, Gofa zone, Southern Ethiopia.Methods: 422 motorcycle drivers were sampled in a cross-sectional study conducted from 15, April to 25, May, 2020 in Sawula and Bulky towns, where people often drive motorcycle. Stratified sampling technique was used to recruit the sampled drivers in a face to face interview. Data were entered into EPI-data version 3.1 and exported to Statistical Package for the Social Sciences (SPSS) version 23 to manage analysis. Descriptive analyses like frequency, percentage, mean and standard deviation were carried out as necessary. Logistic regression models were fitted to identify the predictors of helmet wearing. Adjusted odds ratios (AOR) with 95% confidence intervals (CI) were used to determine the presence and strength of association.Results: A total of 403 motorcycle drivers participated in the study which gives a 95.5% response rate. Of the total of 403 motorcycle riders, only 12.4% (95% CI, 9.2 to 15.6%) of them wore a helmet while driving a motorcycle. Having license [AOR 3.51(95% C.I 1.56-7.89)], driving strips >10Km [AOR 2.53(95% C.I 1.08-5.91)], History of accident[AOR 2.71(95% C.I 1.32-5.55)], driving experience of >=10 years[AOR 2.98 (95% C.I 1.25-7.09)] and high perceived susceptibility to accident [AOR 3.10(95% C.I 1.29-7.46)] had statistically significant association with helmet wearing comparted to their counterpart.Conclusion: This study highlighted that helmet wearing was very low. Having a license, driving strips, exposure to accident, driving experience, and accident risk perception were determinants of helmet wearing. These determinants imply that helmet wearing was directly or indirectly relies on motorcycle drivers’ knowledge and perceptions about accident and helmet wearing. Therefore, we advise all stakeholders to conduct awareness creation campaigns and give focus on mandatory helmet wearing.
HER2 G776S Mutation Promotes Oncogenic Potential in Colorectal Cancer Cells when Accompanied by Loss of APC Function
Authors: Mitani Yosuke , Ohashi Shinya , Kikuchi Osamu , Nakai Yukie , Ida Tomomi , Mizumoto Ayaka , Yamamoto Yoshihiro , Saito Tomoki , Kataoka Shigeki , Matsubara Junichi , Yamada Atsushi , Kanai Masashi , Matsumoto Shigemi , Sakai Hiroaki , Yoshikawa Kiyotsugu , Nakamura Eijiro , Muto Manabu
Published: June 2021

Background

Clinical cancer genome sequencing detects oncogenic variants that are potential targets for cancer treatment, but it also detects variants of unknown significance that may interact and affect the pathophysiology of the tumor; however, these interactions are not fully understood. In this study, we examined the interactions of a minor HER2 mutation (G776S) and APC mutations, which were detected by cancer genome sequencing of samples from a patient with colorectal cancer.
Methods

We transfected HER2-G776S mutant- or HER2 wild type- expressing vectors into several cell lines, HeLa, FHC, CACO-2 and COLO-320, to evaluate their effects on HER2 phosphorylation and kinase activity, HER2 downstream signaling (phosphorylation of AKT and MAPK), and anchorage-independent growth ability. APC- knockout cells and APC overexpressing cells were established to investigate the effect of APC function on the HER2 signaling pathway. We also evaluated the efficacy of a HER2 tyrosine kinase inhibitor on xenograft tumors derived from HER2-G776S transfected cells.
Results

HER2 G776S mutation increased the kinase activity and phosphorylation of HER2 protein, but these effects were weaker than those of the other HER2 driver mutation. HER2 G776S did not activate HER2-downstream signal pathways, such as ERK and AKT phosphorylation, in cells with wild-type APC (HeLa and FHC cells). By contrast, HER2 G776S increased the activation of HER2 downstream signaling, especially ERK phosphorylation, and anchorage-independent cell growth in cells with an APC mutation (CACO-2 and COLO-320) and APC-knockout HeLa cells. Wild-type APC overexpression in HER2 G776S-transfected COLO-320 cells neutralized ERK phosphorylation. Loss of APC function increased Wnt pathway activity but also increased RAS–GTP, which increased ERK phosphorylation triggered by HER2 G776S transfection. Afatinib, a pan-HER tyrosine kinase inhibitor, inhibited tumor growth of HER2 G776S-transfected COLO-320 xenografts
Conclusions

HER2 G776S mutation acts as a weak oncogenic driver, but it also increases HER2–ERK signaling activity by increasing RAS–GTP production when APC function is simultaneously impaired. These results suggest that even weakly active mutations may be therapeutic targets, and the use of this strategy may contribute to the development of HER2-targeted therapy for colorectal cancer.
Unilateral Vocal Cord Paralysis Case Related to COVID-19
Authors: Korkmaz Müge Özçelik , Güven Mehmet
Published: June 2021

Introduction: Although the most common neuro-otolaryngological findings associated with COVID-19 infection are chemosensory changes, it should be known that these patients may present with different clinical findings.Case summary: We present a 57-year-old woman who developed progressive hoarseness while suffering from COVID-19 infection without a history of chronic disease or any other etiological cause. Laryngeal fiberscopy revealed left vocal cord fixed at the cadaveric position and there was 5-6 mm intraglottic gap during phonation. No other etiological cause was found in the examinations performed with detailed ear nose throat examination, neurological evaluations and imaging methods. Injection laryngoplasty was applied to the patient, and voice therapy was initiated, resulting in significant improvement in voice quality.Discussion: The mechanism of the idiopatic vocal cord paralysis remains unclear, it is suspected to be related to COVID-19 neuropathy, because the patient had no preexisting vascular risk factors or evidence of other neurologic disease on neuroimaging. Laryngeal nerve palsies may represent part of the neurologic spectrum of COVID-19.Conclusion: The possibility of the peripheral nerves damage caused by SARS-CoV-2, vocal cord paralysis should be considered when voice changes occur during COVID 19 infection.
Prognostic Significance of Intra-tumoral Budding in Serous Ovarian Carcinomas
Authors: Hachisuga Toru , Murakami Midori , Harada Hiroshi , Ueda Taeko , Kurita Tomoko , Kagami Seiji , Yoshino Kiyoshi , Tajiri Ryosuke , Hisaoka Masanori
Published: June 2021

Intra-tumoral budding (ITB) has been well demonstrated to be an independent risk factor for adverse outcomes in colorectal carcinoma. This study investigated the prognostic significance of ITB in serous ovarian carcinomas (SOCs). The medical records and slides of 84 SOCs, including 13 with neoadjuvant chemotherapy (NAC), were retrospectively reviewed. The following clinicopathological parameters were noted: age at the diagnosis, CA125 level, 2014 FIGO stage, architectural grade, nuclear grade, presence of ITB, lymphovascular space invasion (LVSI), mitotic index and lymph node metastasis. ITB was found in 65 (77.4%) of the 84 SOCs. The presence of ITB was significantly correlated with a higher level of CA125, an advanced 2014 FIGO stage, a worse architectural grade, and the presence of LVSI. The median progression-free survival (PFS) was 20 months in women with SOC with ITB and 38 months in women with SOC without ITB (P<0.01), and their median overall survival (OS) was 52 months and 72 months (P=0.05). The multivariate analysis revealed that ITB was not an independent prognostic factor. ITB is a cost-effective prognostic indicator for women with SOC and ITB in ovarian tumor tissue is considered a useful histological biomarker of the progression of SOCs.
Plasma Inflammatory Cytokines and Depressed Patients With Comorbid Pain: Improvement by Ketamine
Authors: Zhou Yanling , Wang Chengyu , Lan Xiaofeng , Li Hanqiu , Chao Ziyuan , Ning Yuping
Published: June 2021

Background: Depression and pain frequently coexist clinically. Ketamine has analgesic and antidepressant effects, but few studies have evaluated individual differences in antidepressant outcomes to repeated ketamine in depressed patients with comorbid pain. Our aims were to determine the difference in ketamine’s antidepressant effects in depressed patients with or without pain and then to examine whether inflammatory cytokines might contribute to ketamine’s effect. Methods: Seventy-eight patients with major depressive disorder received six infusions of ketamine. Plasma levels of 19 inflammatory cytokines were assessed at baseline and post-infusion (day 13 and day 26) using the Luminex assay. Plasma inflammatory cytokines of sixty healthy controls (HCs) were also examined. Results: At baseline, the levels of GM-CSF, IL-1β and IL-6 were higher in pain group than in non-pain and HC groups. Pain group had better antidepressant outcomes than non-pain group. Pain group showed a greater decrease in IL-6 at day 13 and a greater decrease in IL-10, MIP-3α, IL-1β, IL-5 and IL-6 at day 26 than non-pain group. In the pain group, the changes in IL-6 levels were associated with improvement in pain intensity (β=0.347, t=2.159, P=0.038) and depressive symptoms (β=0.590, t=4.201, P<0.001) at day 13. The Sobel test showed indirect effects between decreases in IL-6 levels and improvement in depressive symptoms (Z=2.026, P=0.043).Conclusion: This study suggested that an elevated inflammatory response plays a key role in individual differences in depressed patients with or without pain. Ketamine showed great antidepressant and analgesic effects in depressed patients with pain, which may be related to its anti-inflammatory effect.
Local and global energy barriers for chiral domain walls in synthetic antiferromagnet-ferromagnet lateral junctions
Authors: Yoon Jiho , Yang See-Hun , Jeon Jae-Chun , Migliorini Andrea , Kostanovskiy Ilya , Parkin Stuart
Published: June 2021

The current induced manipulation of chiral spin textures is of great interest for both fundamental research and technological applications1–3. Of particular interest are magnetic non-volatile memories formed from synthetic antiferromagnetic racetracks in which chiral composite domain walls (DWs), that act as data bits, can be efficiently moved by current4. However, overcoming the trade-off between energy efficiency, namely a low threshold current density to move the domain walls, and high thermal stability, remains a major challenge for the development of integrated chips with high reliability and low power consumption. Here we show that chiral DWs5–7 in a synthetic antiferromagnet-ferromagnet lateral junction, formed by local plasma oxidation, are highly stable against large magnetic fields whilst the DWs can be efficiently moved across the junction by current. Our approach takes advantage of the locality of current-driven torque on the small volume of a chiral DW and the globality of field-torque in the energy landscape, thereby leading to fundamentally distinct energy barriers for motion and stability. We find that the threshold current can be further decreased by tilting the junction across the racetrack while not affecting the high DW stability. Furthermore, we demonstrate that chiral DWs can be robustly confined within a ferromagnet region sandwiched on both their sides by synthetic antiferromagnets and yet can be readily injected into these regions by current. Our findings break the aforementioned trade-off between efficiency and stability, allowing for diverse and versatile DW-based memory, and logic, and beyond.
The “Pink Pattern” Visualized in Magnifying Endoscopy with Narrow-Band Imaging is a New Feature of Early Gastric Differentiated Cancer——A Bridge Between Endoscopic Image and Histopathological Change
Authors: Chen Shengsen , Yu Jiangping , Ruan Rongwei , Tao Yali , Cui Zhao , Li Yandong , Shen Cheng , Jin Jiayan , Chen Ming , Jin Chaohui , Wang Shi
Published: June 2021

Background

A pink color change found occasionally by us under the magnifying endoscopy with narrow-band imaging (ME-NBI) may be a special feature of early gastric cancer (EGC), and it was named as “pink pattern”. The purposes of this study were to reveal the relationship between the “pink pattern” and the cytopathological changes of gastric cancer cells, and explore whether the pink pattern was useful for the diagnosis of EGC.
Methods

The color features of ME-NBI images and pathological images on gastric cancerous mucosal surface were extracted and quantized, and then the cosine similarity was calculated to evaluate the correlation between the pink pattern and the nucleus-to-plasm ratio of cancerous epithelial cells. Two diagnostic tests were performed by 12 endoscopists using stored ME-NBI images of 185 gastric lesions to investigate the diagnostic efficiency of “pink pattern” for EGC. The diagnostic values such as area under curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) between test 1 and test 2 were compared.
Results

The cosine similarity in 20 lesions between the color values of ME-NBI images and pathological images was at least 0.744. The median AUC, accuracy, sensitivity, specificity, PPV and NPV of test 2 were significantly improved compared with that of test 1 in all endoscopists, junior and experienced groups.
Conclusions

The “pink pattern” visualized in ME-NBI images is highly correlated with the nucleus-to-plasma ratio change of gastric epithelial cells, and it can be considered as a useful marker for the diagnosis of the differentiated EGC.
Observation of elastic spin with chiral meta-sources
Authors: Yuan Weitao , Yang Chenwen , Zhang Danmei , Long Yang , Pan Yongdong , Zhong Zheng , Chen Hong , Zhao Jinfeng , Ren Jie
Published: June 2021

Directional routing of one-way classical wave has raised tremendous interests about spin-related phenomena in topological metamaterials. This sparks specifically the elastic wave study of synthesizing pseudo-spin degree-of-freedom in meta-structures for implementing topological phononic devices to perform robust elastic wave manipulations. Unlike pseudo-spin in mathematical sense, the physically intrinsic spin angular momentum of elastic wave is predicted quite recently which exhibits selective excitation of unidirectional wave propagation even in conventional solids. However, due to the grand challenge of building up chiral elastic sources, the experimental observation of intrinsic spin of elastic wave and relevant properties is still missing. Here, we successfully measure the elastic spin in two typical elastic modes, i.e. Rayleigh and Lamb waves, by adopting the elaborately designed chiral meta-sources that excite locally rotating displacement polarizations. In both systems, we observe the unidirectional routing of chiral elastic waves, characterize the different elastic spins along different directions, and demonstrate the spin-momentum locking in broad frequency ranges. We also find the selective one-way Lamb wave carries opposite elastic spin on two plate surfaces in additional to the source chirality. The observation of elastic spin and related intriguing phenomena paves a new way for chiral elasticity, miniature on-chip devices, and spin-sensitive sensors.
What Is the Optimal Strategy for Drain Removal After Mastectomy and Axillary Surgery in Breast Cancer Patients? A Multicentre, Three-arm Randomized Clinical Trial
Authors: Wen Nan , Ouyang Chibin , Hu xiaoxia , Hou Lingmi , He Liqiong , Liu Chaodong , Xie Yanyan , Du Zhenggui
Published: June 2021

PurposeThe best strategy for drain removal after mastectomy and axillary surgery in breast cancer patients has remained controversial. We conducted a multicentre, three-arm randomized clinical trial to determine the optimal strategy.MethodsA total of 187 eligible breast cancer patients who underwent mastectomy and axillary surgery were randomized into 10 ml (n=62), 20 ml (n=63) and 30 ml (n=63) groups for drain removal on the first day when the output decreased to corresponding volume/24 h. The drain duration, total drain duration, incidence of seroma, quality of life (QoL), outpatient visit times, healthcare costs and postoperative complications were evaluated.ResultsThe median axillary drain durations and total drain durations were all significantly different between three groups (both p<0.001). The incidences of seroma were 31.1%, 38.3% and 52.1%, and the difference between the 30 ml and 10 ml groups was significant (RR=2.41). 20 ml group reported significantly better QoL in terms of physical functioning (PF) at the 2-week (30 ml vs 20 ml, HR:-14.18) and 3-week (20 ml vs 10 ml, HR: 11.65) follow-up and role functioning (RF) at the 2-week follow-up (20 ml vs 10 ml, HR: 18.15). No between-group differences were found in QoL, outpatient visits, costs or complications.ConclusionThe 20 ml group had a moderate drain duration, total drain duration and incidence of seroma but a significant advantage over the other two groups in terms of PF and RF, with relatively low outpatient costs and comparable postoperative complication rates. These findings could aid in clinical decision-making regarding drain removal timing.
miR-186-5p Prevents Hepatocellular Carcinoma Progression Through Targeting METTL3 to Regulate m6A-Mediated Stabilization of FSTL5
Authors: Zhang DengYong , Chen FangFang , Ma ShuoShuo , Zhou YongChun , Sun Wanliang , Wang Dongdong , Chang ShiRu , Lu Zheng
Published: June 2021

Background: Hepatocellular carcinoma (HCC) processes in multi-steps which involves the sophisticated interactions of genetics, epigenetics, and transcriptional changes. According to before investigations, methyltransferase-like 3 (METTL3)-mediated m6A modification regulates the development of various cancers by regulating gene stability. However, the studies focusing on miRNA’s regulatory effect of N6-methyladenosine (m6A) modification on HCC progression are still limited. Methods: Immunochemistry (IHC) staining detected the histopathological changes in the tumor tissues. Cell Counting Kit-8 (CCK-8), clone formation, and transwell assay investigated the changes in cancer cell proliferation, invasion, and migration. The RNA m6A level was confirmed by methylated RNA immunoprecipitation. The RNA stability assay indicated the half-life (t1/2) of RNA in HCC cells. The prognosis of the indicated patients’ cohort was analyzed using the cancer genome atlas (TCGA) datasets. Luciferase report analysis was used to study the potential binding between microRNA (miRNA) and mRNA. A mice tumor transplant model was further established to study the changes in tumor progression. Results: Follistatin-like 5 (FSTL5) was found to be significantly downregulated in HCC, and it inhibited the further progression of HCC. The RNA stability analysis indicated that the mRNA t1/2 gene of HCC cells was shortened. Besides, METTL3 reduced the stability of FSTL5 mRNA in a m6A-YTH domain family 2(YTHDF2)-dependent manner. Functional experiments revealed that the downregulated METTL3 inhibited the HCC progression by up-regulating FSTL5 in vitro and in vivo. Luciferase report analysis confirmed that miR-186-5p directly targeted the METTL3. Additionally, miR-186-5p inhibited the proliferation, migration, and invasion of HCC cells by downregulating METTL3. We identified that miR-186-5p prevented the HCC progression by targeting METTL3 to regulate m6A-mediated FSTL5 stabilization. Conclusions: The miR-186-5p/METTL3/YTHDF2/FSTL5 axis perhaps point out a new direction for the targeted therapy of HCC.
RSHL: a Ranging and Speed Measurement Method by Jointing Hyperbolic Frequency Modulation and Linear Frequency Modulation
Authors: Liu Peng , Song Caixia
Published: June 2021

In the waveform design, the distance measurement and resolution are a pair of irreconcilable contradictions. Linear Frequency Modulation (LFM) can alleviate this contradiction. LFM is widely used in radar and sonar, however, its Doppler tolerance is not ideal. Hyperbolic Frequency Modulation (HFM) signal has a particularly strong tolerance towards Doppler frequency shift. However, when the unidirectionally modulated HFM signal is in distance measurement, the Doppler delay of the matched filtering output cannot be eliminated, and there is a ranging error. After the echo signal of the combined HFM+LFM signal is matched filtering, the Doppler-induced delay is the same but opposite in direction, and the delay is closely related to the frequency, bandwidth, and pulse width of the transmitted signal. By using the combined signals, the ranging error in the ranging of single modulated HFM signal or LFM signal can be eliminated. In this paper, a Ranging and Speed measurement method by jointing Hyperbolic frequency modulation and Linear frequency modulation (RSHL) is proposed, which employs the same frequency band of positive and negative frequency modulation signals for speed measurement and ranging. In RSHL method, the signal parameters of the combined LFM+HFM signal can be set independently and no longer depend on each other. Therefore, the pulse width and frequency band in the combined LFM+HFM signal can be controlled independently, which can optimize the transmission signal form, reduce the operation cost, improve the measurement accuracy, and make full use of frequency band resources or pulse width resources.
Investigating the Age of Becoming a Smoker and Its Related Factors Among Student Population: a Web-based Study
Authors: Habibi Peyman , Shekari Farhad , mohammadpoorasl Asghar , Chattu Vijay Kumar , Gilani Neda
Published: June 2021

Background: Preventing smoking at an early age is one of the primary solutions to reduce the likelihood of becoming a smoker in adulthood. This study aimed to investigate the age of becoming a smoker and its related factors and to assess the change in the age trend of becoming a smoker among students in Iran.Methods: A cross-sectional web-based survey was performed from July to August 2019 in Tabriz, Iran. A proportional cluster sampling in all universities of the city was implemented, according to the number of students in each university. The data were collected from 3640 students via an online survey questionnaire. Data analyses were performed by using Stata (version 16). The statistical level of significance was set at 0.05. Results: The average (±SD) age of becoming a smoker in the students was 18.8 (6 2.6) years. The age of becoming a smoker has decreased over time. A linear regression model showed that male and undergraduate students become smokers 0.77 and 0.50 years earlier than other students, respectively (P <0.001). Older age, being single, and later smoking initiation increase the average age of becoming a smoker by 0.2 years, 0.77 years, and 0.54 years, respectively (P <0.001).Conclusion: The age of becoming a smoker has decreased over time. Prevention programs should target males and undergraduate students. Furthermore, since students have become smokers earlier than their peers in the past, there is a direct relationship between smoking initiation and the age of becoming a smoker.
Decision rules for determining terrestrial movement and the consequences for filtering high-resolution GPS tracks – A case study using the African Lion (Panthera leo)
Authors: Gunner Richard Michael , Wilson Rory P , Holton Mark D , Hopkins Phil , Bell Stephen H , Marks Nikki J , Bennett Nigel C , Ferreira Sam , Govender Danny , Viljoen Pauli , Bruns Angela , Schalkwyk O. Louis van , Bertelsen Mads F , Duarte Carlos M , Rooyen Martin C van , Tambling Craig J , Goppert Aoife , Diesel Delmar , Scantlebury D. Michael
Published: June 2021

The combined use of Global Positioning System (GPS) technology and motion sensors within the discipline of movement ecology has increased over recent years. This is particularly the case for instrumented wildlife, with many studies now opting to record parameters at high (infra-second) sampling frequency. However, the detail with which GPS loggers can elucidate fine-scale movement depends on the precision and accuracy of fixes, with accuracy (specifically, location error and fix success rate) being affected by signal reception. We hypothesised that animal behaviour was the main factor affecting fix inaccuracy (particularly for collar-mounted tags sampling at high frequency). In conjunction to this, inherent GPS positional noise (‘jitter’), would be most apparent during GPS fixes for non-moving locations, thereby producing disproportionate error during rest periods. A Movement Verified Filtering (MVF) protocol was constructed to compare GPS-derived speed data to dynamic body acceleration (DBA). This was collected by a simultaneously deployed tri-axial accelerometer, to provide a computationally quick method for identifying genuine travelling movement. This method was tested on 11 free-ranging lions ( Panthera leo ) within the Kgalagadi Transfrontier park in the Kalahari Desert, fitted with collar-mounted GPS units and tri-axial motion sensors (Daily Diary; DD) recording at 1 and 40 Hz, respectively. The findings support the hypothesis and show that distance moved estimates were, on average, overestimated by > 80 % prior to GPS screening. We present the conceptual and mathematical protocols for screening fix inaccuracy within high resolution GPS datasets. We demonstrate the importance that MVF has for avoiding inaccurate and biased estimates of movement and caution the accuracy of findings from previous studies that employed minimal GPS pre-processing . Throughout, we address the applicability of comparing fine-scale indices of GPS- and motion sensor-borne data in tandem to qualify animal behaviour.
The E3 Ubiquitin Ligase RBCK1 Promotes The Invasion and Metastasis of Hepatocellular Carcinoma By Destroying The PPARγ/PGC1α Complex
Authors: Xu Zheng , Shao Jun , Zhang Wenming , Liu Xiuxia , Zhang Shouhua , Du Yunyan , Yan Xia , Xu Debin , Peng Xiaogang , Chen Leifeng
Published: June 2021

Background: The disruption of tumour cell metabolism can inhibit tumour metastasis, indicating that aerobic glycolysis is central to tumour development. However, the key factors responsible for mediating aerobic glycolysis in hepatocellular carcinoma (HCC) remain unknown. Methods: This study investigated the function and clinical significance of RBCK1 protein expression in HCC. We analyzed RBCK1 expression from the TCGA-LIHC dataset and surgical specimens of 216 HCC patients. The correlation between the clinical characteristics and prognosis was also determined. Furthermore, over-expression and knockdown experiments of RBCK1 were developed to explore their effects on HCC cell migration, invasion and aerobic glycolysis. Moreover, a molecular mechanism of RBCK1 promotes HCC metastasis was explored.Results: Here, we observed that RBCK1 expression was significantly upregulated in HCC tissues. Our clinical study showed that high RBCK1 expression significantly correlated with poor tumour survival and distant invasion. Functional assays using HCC cells revealed that RBCK1 promoted migration and invasion by enhancing the Warburg effect, and that GLUT1 was critical for RBCK1-mediated aerobic glycolysis. Furthermore, RBCK1-mediated regulation of WNT/β-catenin/GLUT1 pathway-induced HCC cell migration and aerobic glycolysis was dependent on the destruction of the PPARγ/PGC1α complex. Mechanistically, RBCK1 promoted PPARγ ubiquitination and degradation, causing RBCK1 overexpression to enhance the transcriptional activity of WNT/β-catenin. This consequently upregulated the expression of GLUT1-mediated aerobic glycolysis in HCC cells, promoting tumour cell metastasis and invasion.Conclusion: Altogether, our findings identify a mechanism used by HCC cells to survive the nutrient-poor tumour microenvironment and also provide insight into the role of RBCK1 in HCC cell adaptation to metabolic stresses.
Differential Effects of Elevated Nest Temperature and Parasitism on the Gut Microbiota of Wild Avian Hosts
Authors: Ingala Melissa R , Albert Lauren , Addesso Alyssa , Watkins Mackenzie J. , Knutie Sarah A.
Published: June 2021

Background: Changes in wild animal gut microbiotas may influence host health and fitness. While many studies have shown correlations between gut microbiota structure and external factors, few studies demonstrate causal links between environmental variables and microbiota shifts. Here, we use a fully factorial experiment to test the effects of elevated ambient temperature and natural nest parasitism by nest flies (Protocalliphora sialia) on the microbiotas of two species of wild birds, the eastern bluebird (Sialia sialis) and the tree swallow (Tachycineta bicolor).Results: We find that bacterial communities from the nestlings of each host species show differential response to both heat and parasitism, with gut microbiotas of eastern bluebirds more disrupted by heat and parasitism than those of tree swallows. Thus, we find that eastern bluebirds are unable to maintain stable associations with their gut bacteria in the face of both elevated temperature and parasitism. In contrast, tree swallow gut microbiotas are not significantly impacted by either heat or nest parasitism.Conclusions: Our results suggest that excess heat (e.g., as a result of climate change) may destabilize natural host-parasite-microbiota systems, with the potential to affect host fitness and survival in the anthropocene.
Efficacy and Safety of Traditional Chinese Medicine (Lianhua Qingwen) for Coronavirus Disease 2019: a Systematic Review and Meta-analysis
Authors: He YongHong , Qiang Li , Wang SongPing , Deng Jun , Huan Lan
Published: June 2021

Background: The coronavirus disease 2019(COVID-19) had become an epidemic and spread across the world, lead to severe respiratory failure and death. Traditional Chinese Medicine(TCM), Such as Lianhua Qingwen has been widely used in the prevention and treatment of COVID-19, This systematic review and meta-analysis will assess the effects of traditional Chinese herbal medicine(Lianhua Qingwen) in COVID-19 pneumonia from the randomized controlled trials(RCTs) and case control studies(CCSs).Method: we search the literatures in databases inculding PubMed, Embase, Web of science, Cochrane Library, Wanfang, Chinese Science and Technology Periodical Database (VIP), Chinese Biomedical Literature Database (CBM) and China National Knowledge Infrastructure(CNKI), setting the date from December 1, 2019, to June 1, 2021, Cochrane Risk of Bias tool and the Newcastle-Ottawa Scale were used to assess the quality of randomized controlled trials. All analyses were conducted by Stata 14.0.Results: nine studies with 1163 patients(616males) were included, six were RCTs, three are CCSs. Compared with patients treated by western medicine alone, patients treated by Lianhua Qingwen combined with western medicine have a higher overall effective rate[RR=1.20, 95%CI1.20(1.11, 1.31), P=0.000], cardinal symptom disappearance rate[disappearance rate of fever: OR:3.64, 95%CI(1.57, 8.47), P=0.001;disappearance rate of cough: OR:1.97, 95%CI(1.45, 2.68), P=0.001; disappearance rate of fatigue: OR:2.55, 95%CI(1.09, 5.99), P=0.032] and CT recovery rate[RR:1.25, 95%CI(1.13,1.38), P=0.000], reduce the rate of the progress into severe diseases of COVID-19 patients[RR:0.43, 95%CI(0.30, 0.62), P=0.000], with more shorter duration of fever[WMD=-1.07，95%CI(-1.77, -0.37), P=0.003], The including studies described that Lianhua Qingwen did not increase the adverse drug reactions.Conclusion: Lianhua Qingwen may have advantages in improving the clinical effective rate and cardinal symptom disappearance rate. Besides, it also had an excellent effect on the improvement of the chest CT and the proportion reducing of progress into severe clinical disease, which could be used as an effective therapy for COVID-19.
Quantify each Dendritic Cell Subsets along with Normal Thymus Tissues in Different Ages
Authors: Li Yan , Chen Pei , Huang Hao , Feng Huiyu , Ran Hao , Liu Weibin
Published: June 2021

BackgroundDendritic cells (DCs) in the thymus are involved in central tolerance formation, but they also play other roles in the thymus. In this study, thymuses of different ages were collected for observation after tissue sectioning and staining. The area of cortex and medulla parts of the thymus in the sections and the density of different subsets of DCs in the thymus were also calculated. ResultsWe found that, along with the increasing age, the thymic cortex atrophies faster, leading to a gradual rise in the medullary's surface area ratio to that of the cortex with an increase in age. The medullary's surface area ratio to cortex can be used as an indirect reference to reflect the thymus hyperplasia. The density of DCs in the thymus showed different changes with the increasing age, and the density of plasmacytoid DCs (pDCs) in the thymus gradually increased with aging, suggesting that pDCs may play an essential role in the thymus in addition to central tolerance.Conclusions﻿These findings complement our knowledge about the DCs’ subsets in the thymus along with physical ageing and help us understand the full function of DCs in the thymus beyond central tolerance.
Comprehensive Longitudinal Analysis of the Five Sisters Hot Springs in Yellowstone National Park Reveals a Dynamic Thermoalkaline Environment
Authors: Peach Jesse T , Mueller Rebecca C , Skorupa Dana J , Mesle Margaux M , Kanta Sutton , Boltinghouse Eric , Sharon Bailey , Copiè Valerie , Bothner Brian , Peyton Brent M
Published: June 2021

Research focused on microbial populations of thermoalkaline springs has been driven in a large part by the lure of discovering functional enzymes with industrial applications in high-pH and high temperature environments. However, the fundamental ecology of these springs has largely been overlooked. To better understand the functional outcomes of interactions between the geochemistry and the microbial community of thermoalkaline springs, we conducted a three-year study of the Five Sisters (FS) springs that included high-resolution geochemical measurements, 16S rRNA sequencing of the bacterial and archaeal community, and mass spectrometry based extracellular and intracellular small molecule characterization. By combining all four datasets, we completed a comprehensive analysis of the intricate thermoalkaline spring system. Over the course of the study, the microbial population responded to changing environmental conditions, with archaeal populations decreasing in both relative abundance and diversity when compared to bacterial populations. Decreases in the relative abundance of Archaea were associated with environmental changes that included decreased availability of specific nitrogen and sulfur containing extracellular small molecules. The multi-factorial analysis suggests a complex and dynamic environment with an elastic microbial community that responded to geochemical and extracellular small molecule transitions.
Improvement of Surface Quality based on Magnetorheological Fluids Flexible Fixture During Milling Thin-walled Parts
Authors: Zhang Yong , Gao Shan , Yang Ning , Jiang Xiaohui , Zhao Guokuan , Liu Xiao
Published: June 2021

Aerospace thin-walled parts have the characteristics of low stiffness and complex structure, which are easily deformed by machine tool vibration, cutting force and heat during machining. The traditional fixture is in point contact with the workpiece, and the workpiece bears uneven force, which results in poor surface quality and low precision of the part. Therefore, it is urgent to improve the machining efficiency and surface quality of workpiece. According to the performance of magnetorheological fluid, a magnetorheological flexible fixture is designed to completely wrap the parts so as to make them bear uniform force, improve the stiffness of the system and inhibit flutter. Firstly, the stiffness distribution of thin-walled parts, flexible fixtures and fixture-workpiece system is studied in this paper. It can be seen that the symmetrical center stiffness of magnetorheological flexible fixtures is relatively low. Through milling experiments with single process parameters, it is found that when the rotational speed, cutting depth and feed speed change, the composite clamping effect is better than the traditional clamping effect, in which with the increase of rotational speed, the vibration acceleration in Ax, Ay and Az directions decreases by 25.16%, 26.87% and 10.78% respectively; When the cutting depth increases, Ay decreases by 23.12% at the maximum. When the feed speed changes, it decreases by 15.78%. Finally, based on the case of milling thin-walled parts with magnetorheological flexible fixture, it is obtained that the coaxiality of composite clamped thin-walled parts decreases by 13.85%, and the maximum decrease of cylindricity is 36.73%. Roughness value Rz decreases by 80.47% at the maximum. In summary, the above results have verified that the machining quality of the magnetorheological flexible fixture is better.
Flavivirus Infection Induce a Golgi Stress Response in Vertebrate and Mosquito Cells
Authors: Viettri Mercedes , Zambrano José L. , Rosales-Ramirez Romel , Gutierrez-Escolano Ana Lorena , Ludert Juan E
Published: June 2021

The stress of the Golgi apparatus is an autoregulatory mechanism that is induced to compensate for greater demand in the Golgi functions. Few examples of Golgi stress responses due to physiological stimuli are known. Furthermore, the impact on this organelle of viral infections that occupy the vesicular transport during replication is unknown. In this work, we evaluated if a Golgi stress response is triggered during dengue and Zika viruses replication, two flaviviruses whose replicative cycle is heavily involved with the Golgi complex, in vertebrate and mosquito cells. Using GM-130 as a Golgi marker, and treatment with monensin as a positive control for the induction of the Golgi stress response, a significant expansion of the Golgi cisternae was observed in BHK-21, Vero E6 and mosquito cells infected with either virus. Activation of the TFE3 pathway was observed in the infected cells as indicated by the translocation from the cytoplasm to the nucleus of TFE3. Of note, no sign of activation of the stress response was observed in CRFK cells infected with Feline Calicivirus (FCV), a virus released by cell lysis, not requiring vesicular transport. Finally, dilatation of the Golgi complex and translocation of TFE3 was observed in vertebrate cells expressing dengue and Zika viruses NS1, but not NS3. These results indicated that infections by dengue and Zika viruses induce a Golgi stress response in vertebrate and mosquito cells due to the increased demand on Golgi complex imposed by virion and NS1 processing and secretion.
The Attitude of Patients with Progressive Ataxias Towards Clinical Trials
Authors: Thomas-Black Gilbert , Dumitrascu Andrada , Garcia-Moreno Hector , Vallortigara Julie , Greenfield Julie , Hunt Barry , Walther Susan , Wells Mackenzie , Lynch David , Montgomery Hugh , Giunti Paola
Published: June 2021

Background: The development of new therapies may rely on the conduct of human experimentation as well as later clinical trials of therapeutic interventions. Ethical considerations seek to protect the patient from risk but few have sought to ascertain the attitude to such risk of patients with progressive debilitating or terminal conditions, for which no mitigating or curative therapies exist. Such understanding is also important if recruitment is to be maximized. We therefore sought to define the motivations for and barriers to trial participation amongst patients with progressive ataxias, as well as their condition-specific trial preferences. Methods: We conducted an online survey consisting of 29 questions covering four key domains (demographics, personal motivation, drug therapy and study design) relating to the design of clinical trials. Two major ataxia charities, Ataxia UK and the Friedreich’s Ataxia Research Alliance (FARA) sent the survey to their members. Responses were analysed by disease and by ambulatory status.Results: Of 342 respondents, 204 reported a diagnosis of Friedreich’s ataxia (FRDA), 55 inherited cerebellar ataxia (CA) and 70 idiopathic CA. The most important symptoms to be addressed by a trial were considered to be balance problems and ambulation, although these were superseded by speech problems in wheelchair users. Common motivations for participation were potential benefits to self and others. Reasons for non-participation included concerns about side effects, and the burden and cost of travel. Financial reimbursement for expenses was reported to be likely to increase trial engagement, Phase two trials were the most popular to participate in, and the use of a placebo arm was seen as a disincentive. Across all disease subgroups, drug repurposing trials proved popular and just under 70% of participants would be prepared to undergo intrathecal drug administration.Conclusions: Knowledge of motivations for and barriers to trial participation as well as the acceptability of investigations, time commitments and routes of drug administration should inform better, more patient focused trial design. This in turn may improve recruitment and retention of participants to future trials.
Heterogeneous clinical features in Cockayne syndrome-A patients with the same mutation and in siblings
Authors: CHIKHAOUI Asma , Kraoua Ichraf , Calmels Nadège , Bouchoucha Sami , Obringer Cathy , Zayoud Khouloud , Montagne Benjamin , M'rad Ridha , Abdelhak Sonia , Laugel Vincent , Ricchetti Miria , Turki Ilhem , Yacoub-Youssef Houda
Published: June 2021

Background

Cockayne syndrome (CS) is a rare autosomal recessive disorder caused by mutations in ERCC6/CSB or ERCC8/CSA that participate in transcription-coupled nucleotide excision repair (TC-NER) of UV-induced DNA damage. CS patients display a large heterogeneity of clinical symptoms and severities, the reason of which is not fully understood, and little data is available for affected siblings. CS is largely undiagnosed in North Africa.
Methods

We report here the clinical description as well as genetic and functional characterization of eight North African CS patients, including siblings. These patients, who belonged to six unrelated families, underwent complete clinical examination and biochemical analyses. Sanger sequencing was performed for the recurrent mutation in five families, and targeted gene sequencing for one patient of the other family. We also performed RRS (Recovery RNA Synthesis) to confirm the functional impairment of DNA repair in the identified mutations.
Results

Six out of eight patients carried a homozygous indel mutation (c.598_600delinsAA) in exon 7 of ERCC8, and displayed a variable clinical spectrum, including between siblings, despite sharing the same mutation. The other two patients were Tunisian siblings who carried a homozygous splice-site variant in ERCC8 (c.843 + 1 G > C). They presented more severe clinical manifestations, which are in general rarely associated with CSA mutations, leading to gastrostomy and hepatic damage. Impaired TC-NER was confirmed by RRS in six tested patients.
Conclusions

This study provides the first deep characterization of case series of rare CS-A patients in North Africa. They carry mutations described to date only in this region and the Middle-East. We also provide the largest characterization of unrelated patients, as well as siblings, with the same mutation, providing a framework for dissecting elusive genotype-phenotype correlations in CS.
Evolution of the Earth Microbial Co-occurrence Network
Authors: Lv Xiaofei , Stirling Erinne , Zhao Kankan , Wang Yiling , Ma Bin , Xu Jianming
Published: June 2021

Background: Co-occurrence pattern provides vital insight into complex microbial interactions of microbiomes. Although network analysis offers useful tools for describing microbial co-occurrence pattern, evolution of co-occurrence networks remains largely uncharacterized. Here, we simulated the evolution of the Earth microbial co-occurrence network and estimated topological fitness of its nodes based on the degree growth exponent.Results: We showed that the Earth microbial co-occurrence network evolved following Bianconi-Barabasi model. The Earth microbial co-occurrence network had reached to a stable status with around 500 nodes. Degree growth exponent was the major determinant of accumulated degree of taxa. The positive correlation between topological fitness and gene numbers in corresponding genomes suggests the intrinsic feature of topological fitness. The gamma distribution of topological fitness suggests the extinction of taxa with low topological fitness. We then examined the impact of node extinction and decay, finding that the link acquisition of hub nodes was not affected.Conclusions: This study glimpses the evolution feature of Earth microbial co-occurrence network and provides a framework for predicting potential hubs in the evolving network in future.
Lysosome Lipid Signaling from the Periphery to Neurons Regulates Longevity
Authors: Savini Marzia , Duffy Jonathon , Folick Andrew , Lee Yi-Tang , Hu Pei-Wen , Neve Isaiah , Jin Feng , Zhang Qinghao , Tillman Matthew , Ye Youqiong , Mair William , Wang Jin , Han Leng , Ortlund Eric , Wang Meng
Published: June 2021

Lysosomes are key cellular organelles that metabolize extra- and intracellular substrates. Alterations in lysosomal metabolism are implicated in aging-associated metabolic and neurodegenerative diseases. However, how lysosomal metabolism actively coordinates the metabolic and nervous systems to regulate aging remains unclear. Here, we report a fat-to-neuron lipid signaling pathway induced by lysosomal metabolism and its longevity promoting role in Caenorhabditis elegans. We discovered that lysosomal lipolysis in peripheral fat storage tissue up-regulates the neuropeptide signaling pathway in the nervous system to promote longevity. This cell-non-autonomous regulation requires the secretion from the fat storage tissue of a lipid chaperone protein LBP-3 and polyunsaturated fatty acids (PUFAs). LBP-3 binds to specific PUFAs, and acts through a nuclear hormone receptor NHR-49 and neuropeptide NLP-11 in neurons to extend lifespan. Together, these results reveal lysosomes as a signaling hub to coordinate metabolism and aging, and lysosomal signaling mediated inter-tissue communication in promoting longevity.