bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Mutation of KCNJ1 Identified in an Affected Child with Nephrolithiasis
Authors: Wu Qinghua , Yang Saisai , Shi Huirong , Lou Chihhong , Ren Shumin , Jiao Zhihui , Wang Cong , Kong Xiangdong 
Published: January 2022

Abstract
Nephrolithiasis is not common in children, but the incidence is gradually increased in these years. Urinary tract malformations, urinary infection, dietary habits, geographic region and genetic factor are involved in the etiology of nephrolithiasis. For the affected child, it is especially important to elucidate the etiology, which may provide an accurate diagnosis, a personalized therapy and effective follow-up strategy. Here to seek the etiology of a ten-year old boy incidentally found with nephrolithiasis, next generation sequencing (NGS) including a panel with 248 genes involved in hereditary kidney diseases was performed for the boy and identified two mutations of KCNJ1, c.89G>A (p.C30Y) and c.65G>T (p.R22M), and the later was a novel missense mutation originated from his father. The child was confirmed with type II Bartter syndrome (BS) caused by KCNJ1 mutations. Our study suggests that BS may be difficult to get diagnosed at early stage based on clinical manifestations or biochemical laboratory tests, and NGS is an efficient way to determine the etiology and provide further treatment and guide fertility counselling for the affected family.
A histone modification-based synthetic circuit to engineer temporal gene expression in Arabidopsis floral meristems
Authors: Pelayo Margaret , Sawada Haruka , Matsushita Kasumi , He Zemiao , Looi Liang Sheng , Katagiri Naoya , Yamaguchi Nobutoshi , Ito Toshiro 
Published: January 2022

Abstract
The termination of floral meristems is regulated by the MADS domain transcription factor AGAMOUS (AG) by passively diluting the H3K27me3 mark along the KNUCKLES (KNU) coding sequence. How many other downstream genes are similarly regulated by this intrinsic epigenetic timer and whether it can be harnessed for engineering synthetic circuits are unknown. Here, we describe a biotimer gene regulatory network downstream of AG and manipulate the timing of KNU expression through a synthetic system. We manipulated temporal gene expression using the del region from the KNU coding sequence, which is decorated by H3K27me3-marked nucleosomes. Increasing the number of del copies delayed and reduced KNU expression in a PRC2- and cell cycle-dependent manner. We propose that PRC2 deposits H3K27me3, while cell divisions dilute H3K27me3 accumulation on the extended KNU coding sequence. Our results shed light on temporal transitions governing flower development and provide a novel tool for tunable gene expression.
Finite Time Adaptive Smooth Non Linear Sliding Mode Control for Second Order Dynamic Systems
Authors: González-Prieto José Antonio 
Published: January 2022

Abstract
In this paper, a feedback control law that employs an adaptive smooth nonlinear approximation of the Super-Twisting ( STW ) algorithm is presented in order to generate a smooth control law capable of regulating in finite time a second-order system that is affected by unknown disturbances and uncertainties. A nonlinear sliding surface is created in order to set the desired dynamics of the response, so that the control law is proposed to establish global properties of stability for unperturbed and perturbed systems. More specifically, the method entails determining parameters that eliminate chattering in noise-free models by means of a simple cut-off frequency design parameter approach. Therefore, the approach is characterized by its simplicity and robustness. A second order mechanical system is used to demonstrate the effectiveness of the proposed approach.
Longitudinal Mapping of White Matter Tractography Changes in Huntington’s Disease: The IMAGE-HD Study.
Authors: Tan Brendan , Shishegar Rosita , Oldham Stuart , Fornito Alex , Poudel Govinda , Georgiou-Karistianis Nellie 
Published: January 2022

Abstract
The striatum is the principal site of disease pathology in Huntington’s disease and contains neural connections to numerous cortical brain regions. Studies examining abnormalities to neural connections find that white matter integrity is compromised in HD; however, further regional, and longitudinal investigation is required. This paper is the first longitudinal investigation into region-based white-matter integrity changes in Huntington’s Disease. The aim of this study was to better understand how disease progression impacts white matter tracts connecting the striatum to the prefrontal and motor cortical regions in HD. We used existing neuroimaging data from IMAGE-HD, comprised of 25 pre-symptomatic, 27 symptomatic, and 25 healthy controls at three separate time points (baseline, 18-months, 30-months). Fractional anisotropy, axial diffusivity and radial diffusivity were derived as measures of white matter microstructure. The anatomical regions of interest were identified using the Desikan-Killiany brain atlas. A Group by Time repeated measures ANCOVA was conducted for each tract of interest and for each measure. We found significantly lower fractional anisotropy and significantly higher radial diffusivity in the symptomatic group , compared to both the pre-symptomatic group and controls (the latter two groups did not differ from each other), in the rostral middle frontal and superior frontal tracts; as well as significantly higher axial diffusivity in the rostral middle tracts only. We did not find a Group by Time interaction for any of the white matter integrity measures. These findings demonstrate that whilst the microstructure of white matter tracts, extending from the striatum to these regions of interest, are compromised during the symptomatic stages of Huntington’s disease, 36-month follow-up did not show progressive changes in these measures. Additionally, no correlations were found between clinical measures and tractography changes, indicating further investigations into the relationship between tractography changes and clinical symptoms in Huntington’s disease are required.
Embolization of Arteriovenous Malformations in Floor of Mouth with Ethanol and Coil-Assisted Dominant Outflow Vein Occlusion
Authors: Su Lixin , Wang Deming , Zheng Lianzhou , Li Xiao , Fan Xindong , Yang Xitao 
Published: January 2022

Abstract
Purpose
To evaluate the outcomes and safety of embolization of the arteriovenous malformations (AVMs) in the floor of the mouth with ethanol combined with coil-assisted dominant outflow vein (DOV) occlusion.
Materials and methods
Between January 2017 and June 2018, 10 consecutive patients with AVMs in the floor of the mouth and DOVs who underwent ethanol embolization combined with DOV occlusion were enrolled. All patients completed the course of clinical follow-up (range: 14–37 months; mean: 24.8 months). Indications, techniques, complications, and outcomes were reviewed.
Results
The patients underwent 24 ethanol embolization procedures (range: 1–4; mean, 1.9) with 22 detachable coils and 139 nester coils. 5 patients (50%) exhibited complete response, and the 5 (50%) exhibited partial response. The minor complications, including mucosal blistering and ulcers, occurred in 3 patients (30%), but with spontaneous recovery. 3 patients (30%) had coil exposure heal with minor debridement. No major complications were observed during the study.
Conclusion
Ethanol embolization combined with coil-assisted DOV occlusion has the potential to treat the AVMs in floor of mouth with acceptable risk of complications.
MilR3, a Unique SARP Family Pleiotropic Regulator in Streptomyces Bingchenggensis
Authors: Yan Yu-Si , Yang Yun-Qi , Zou Li-Sha , Zhang Ling , Xia Hai-Yang 
Published: January 2022

Abstract
Streptomyces bingchenggensis is the main industrial producer of milbemycins, which are a group of 16-membered macrocylic lactones with excellent acaricidal, insecticidal and anthelmintic activities. In past decades, scientists tried a lot to solve its low productivity. But less understanding the regulatory network of milbemycin biosynthesis limited the generation of high producing strains with regulatory rewiring approach. SARPs（Streptomyces Antibiotic Regulatory Proteins）family regulators are widely distributed and play key roles in regulating antibiotics production in actinobacteria. In this paper, MilR3 (encoded by sbi_06842) has been screened out for significantly affecting milbemycin production from all the 19 putative SARP family regulators in S. bingchenggensis with the DNase-deactivated Cpf1-based integrative CRISPRi system. Interestingly, milR3 is about 7 Mb away from milbemycin biosynthetic gene cluster and adjacent to a putative type II PKS （the core minimal PKS encoding genes are sbi_06843, sbi_06844 and sbi_06845）gene cluster, which was proved to be responsible for producing a yellow pigment. The quantitative real-time PCR (qRT-PCR) analysis proved that MilR3 positively affected the transcription of milR, milA1, milA2, milA4, milF, milR3 and sbi_06844 in both clusters. Unlike previous “small” SARP family regulators played pathway specific roles, MilR3 was probably a unique SARP family regulator and played a pleotropic role. MilR3 was an upper-level regulator in MilR3-MilR cascade. This study firstly illustrated the co-regulatory role of this unique SARP regulator. This greatly enrich our understanding of SARPs and lay a solid foundation for milbemycin yield enhancement in the near future.
CT-Based Skeletal Muscle Loss for Predicting Poor Survival in Patients With Hepatocellular Carcinoma Experiencing Curative Hepatectomy Plus Adjuvant Transarterial Chemoembolization:a Preliminary Retrospective Study
Authors: Yang Siwei , Zhang Zhiyuan , Su Tianhao , Yu Jianan , Cao Shasha , Wang Haochen , Jin Long 
Published: January 2022

Abstract
Background To evaluate the prognostic value of skeletal muscle index (SMI) and its change in patients with hepatocellular carcinoma (HCC) experiencing curative hepatectomy plus adjuvant transarterial chemoembolization (TACE). Methods and Methods A total of 62 patients with HCC who underwent adjuvant TACE after curative hepatectomy were analysed retrospectively. Skeletal muscle area at the third lumbar level was quantitated using computed tomography images and was normalized for height squared to obtain skeletal muscle index (SMI). Skeletal muscle loss (SML) over six months was computed with two SMIs before and after hepatectomy plus adjuvant TACE. Correlation analyses were preformed to investigate factors associated with SML. The curves of cause-specific survival (CSS) were analysed using the Kaplan-Meier method. A Cox proportional hazards model was used to assess prognostic factors. Results Low SMI was diagnosed in 23(37.1%) patients preoperatively. The median SML standardized by 6 months was -1.6% in the entire cohort. Liver cirrhosis and microvascular invasion correlated negatively with SML respectively (r=-0.320, P=0.002; r=-0.243, P=0.021). Higher SML (<-2.42%) predicted a significant reduction in CSS (P=0.001), whereas low SMI did not(P=0.687). Following the multivariate analysis for CSS, AFP> 400 ng/ml (HR, 5.643; 95%CI, 3.608-17.833; P<0.001) and SML<-2.42% (HR, 6.586; 95%CI, 3.610-22.210; P<0.001) were independent predictors for poor CSS.Conclusions Skeletal muscle loss during hepatectomy plus adjuvant TACE was remarkable. Higher SML was an independent risk factor for CSS in patients with HCC, especially those with liver cirrhosis.
Low Transcriptomic of PTPRCv1 and CD3E Is an Independent Predictor of Mortality in HIV and Tuberculosis Co–infected Patient
Authors: Gebremicael Gebremedhin , Gebreegziaxier Atsbeha , Kassa Desta 
Published: January 2022

Abstract
Background: Assessing immunological profiles from HIV-TB co-infection is essential to predict mortality, to facilitate the development of effective assays, the discovery of novel therapeutic targets and to conduct new interventions appropriately.Methods: Expression levels of 105 immune-related genes were measured at baseline of enrolment from 9 death HIV and TB coinfected study participants during follow-up and 18 survived groups for 2 years and matched controls, using focused gene expression profiling by dual-color Reverse-Transcription Multiplex Ligation-dependent Probe Amplification assay. Gene expression levels were also measured at six months and 18th month follow-up.Results: Eleven of the 105 selected genes were differentially expressed between death individuals and survivor matched controls. IL4δ2 was significantly higher expressed in death groups than survivor matched controls, whereas CD3E, IL7R, PTPRCv1, CCL4, GNLY, BCL2, CCL5, NOD1, TLR3 and NLRP13 had significantly lower expression levels in death groups compared to survivor matched controls. The expression of PTPRCv1, CD3E, CCL5, IL7R, NOD1, IL4δ2 and GNLY at baseline could accurately predict the mortality from TB-HIV co-infection.Conclusions: The expression of PTPRCv1, CD3E, CCL5 and IL7R host genes in peripheral blood of patients with TB-HIV coinfected can potentially be used as predictor of mortality in Ethiopian setting. Anti-TB treatment might be less likely to restore gene expression in the level expression of death groups. Therefore, other new therapeutic that can restore these gene (PTPRCv1, CD3E, IL7R and CCL5) in the death groups at baseline might be needed to save lives.
Are Travel Bans the Answer to Stopping the Spread of COVID-19 Variants? Lessons from a Multi-Country SIR Model
Authors: Docquier Frédéric , Golenvaux Nicolas , Schaus Pierre 
Published: January 2022

Abstract
Background: Detections of mutations of the SARS-CoV-2 virus gave rise to new packages of interventions. Among them, international travel restrictions have been one of the fastest and most visible responses to limit the spread of the variants. While inducing large economic losses, the epidemiological consequences of such travel restrictions are highly uncertain. They may be poorly effective when the new highly transmissible strain of the virus already circulates in many regions. Assessing the effectiveness of travel bans is difficult given the paucity of data on daily cross-border mobility and on existing variant circulation. The question is topical and timely as the new omicron variant -- classified as a variant of concern by WHO -- has been detected in Southern Africa, and perceived as (potentially) more contagious than previous strains. In this study, we develop a multi-country compartmental model of the SIR type. We use it to simulate the spread of a new variant across European countries, and to assess the effectiveness of unilateral and multilateral travel bans. Results: Multilateral travel bans do not buy much time, by increasing the time until the infection curve peaks by a few weeks at best. This can be achieved with drastic travel bans only, and this fails to stop the propagation when the virus is already circulating in the country, or in regions not included in the travel bans. Conclusion: Given their huge economic and freedom-killing consequences, travel bans have negligible effects on the timing and severity of the infection response. Managing new waves of COVID-19 with local sanitary measures applicable to cross-border movers is the most effective option. It induces better epidemiological outcomes and smaller economic cost for all parties concerned.
PALB2 Correlates with Adverse Prognosis and Promotes Tumor Progression in Chordoma
Authors: Xiong Yujia , Li Mingxuan , Sheng Yutao , Ma Tianshun , Bai Jiwei , Zhang yazhuo 
Published: January 2022

Abstract
Objective:This study aimed to study the role of PALB2 on the prognosis of skull base chordoma patients and the proliferation, migration, and invasion of chordoma cells. Methods:187 patients with primary skull base chordoma were involved in the study. Immunohistochemical analysis was used to measure the PALB2protein expression. Kaplan-Meier analysis, univariate and multivariate Cox analysis were used to evaluate the impact of PALB2 on patient prognosis. A nomogram was established for predicting the progressionfree survival of chordoma patients. Cell counting kit-8,colony formation, transwellmigration, and invasionassays were used to assess the proliferation, migration, and invasion of chordoma cells with PALB2 knockdown. TIMER 2.0 was used to explore the expression and prognostic role of PALB2 in cancers.Results:High PALB2 expression indicated anadverse prognosis in chordoma. A nomogram involved PALB2,degree of resection, pathology, and Al-mefty classification could accurately predict the progressionfree survival of chordoma patients. The proliferation, migration, and invasion of chordoma cells significantly decreased after PALB2 knockdown. Additionally, PALB2 showed high expression in various cancers and was associated with a poor prognosis.Conclusion: In summary, our results reveal that high PALB2 expression indicates a poor prognosis of chordoma patients and promotes the malignant phenotypes of chordoma cells in vitro.
DUB1 Suppresses Hippo Signaling Via Modulating TAZ Protein in Gastric Cancer
Authors: Wang Dehai , Li Zhongbo , Li Xin , Yan Cheng , Yang Huijie , Zhuang Ting , Wang Xiao , Zang Yifeng , Liu Ziping , Wang Tianshi , Jia Ruixia , Su Peng , Zhu Jian , Ding Yinlu 
Published: January 2022

Abstract
Background

The Hippo pathway functions as a tumor-suppressor pathway in human cancers, while the dys-function of Hippo pathway is frequently observed in malignancies. Although the YAP/TAZ activity is tightly controlled by the phosphorylation cascade of MST-LATS-YAP/TAZ axis, it is still unclear why YAP/TAZ protein is activated in human cancers, even Hippo pathway is still active. Besides phosphorylation, recent studies implicate that several post-translational modifications also play critical roles in modulating TAZ function, including ubiquitination.
Methods

We work on the ER alpha positive breast cancer cell lines and performed western blots, real-time PCR, immuno-precipitation assay, in vitro ubiquitin assay and xenograft mice studies
Results

Here, by a DUB (Deubiquitinases) siRNA screening library, we discovered DUB1 as a critical modulator to facilitate gastric cancer stemness and progression, which deubiquitinated and activated TAZ protein. We also identified DUB1 was elevated in gastric cancer, which correlated with TAZ activation and poor survival. DUB1 associated with TAZ protein and deubiquitinated TAZ at several lysine sites, which subsequently stabilized and facilitated TAZ function.
Conclusions

Our study revealed a novel deubiquitinase of Hippo/TAZ axis and one possible therapeutic target for Hippo-driven gastric cancer.
Novel self-assembled isonicotinic acid derivative and zinc porphyrin dyads and applications in dye sensitized solar cells
Authors: Wu Yu , Wang Qiumin , Wang Fang , Cheng Mei , Liu Jiacheng , Li Renzhi 
Published: January 2022

Abstract
A new self-assemblies based on double-deck dyes ZnTPP-Wi (i=1-3) were synthesized and applied in dye-sensitized solar cells (DSSCs). Anchoring molecules (Wi i=1-3) consisting of phenyl carboxyl acid and cyanoacetic acid group. Capping layer dyes ZnTPP with anchoring molecules formed dyads by the coordination bonds of Zn-to-ligand self-assemblies solar cells devices. We herein report a consisting acylamide and cyanoacetic acid group W3 as an anchoring molecule for the axial coordination with upper zinc porphyrin ZnTPP. W3 was synthesized by introducing acylamide and cyanoacetic acid groups may inhibit adverse dye aggregation and improving electrons are effectively injected into the TiO2 semiconductor surface. Thus, W3 anchoring molecules can be used to fabricate efficient solar cells with ZnTPP porohyrin dye, achieving good photoelectric performance, indicative of their general applicability in fabricating good-performance DSSCs. The assembled modes were also verified by transmission electron microscopy (TEM). The photoelectrochemical efficiencies for dye ZnTPP-W3 are best than those of self-assembly dyes prevailingly ascribed to larger Jsc and Voc.
Mst1-Nrf2 regulates myocardial injury in type 2 diabetic mice through autophagy
Authors: Wang Jun , Li Guangwei , Wang Na , Wang Lulu , Jin Li , Xiao Wei 
Published: January 2022

Abstract
Purpose This paper presents the effect of Mst1-Nrf2 on myocardial injury in type 2 diabetic mice through autophagy. Method C57BL/6N wild-type mice, Mst1 knockout mice and Mst1 knockout mice interfered by Keap1-Nrf2 pathway inhibitors are divided into wild group, Mst1 group, Mst1-Nrf2 group, diabetic cardiomyopathy group (DCM), DCM+Mst1 group and DCM+ Mst1-Nrf2 group. Each group contains 5 mice. Mice in DCM group, DCM+Mst1 group and DCM+Mst1-Nrf2 group are given high-glucose and high-fat diet for 4 weeks, then intraperitoneally injected 40mg/kg streptozotocin(STZ). Meanwhile, high-glucose and high-fat diet is continued for 8 weeks. Body weight and fasting blood glucose are measured every week. Mice in Mst1-Nrf2 group and mice in DCM+Mst1-Nrf2 group are given interference of Keap1-Nrf2 pathway inhibitors, and intraperitoneally injected for 4 weeks at a dose of 5mmol/L. Results After 8 weeks of STZ injection, the body weight of mice in DCM+Mst1 group and mice in DCM+ Mst1-Nrf2 group increases and fasting blood glucose level decreases, the differences are statistically significant (P<0.01). Compared with the wild group, the fasting glucose level of mice in Mst1 group and Mst1-Nrf2 group decreases after 8 weeks (P<0.01). Compared with the wild group, the degree of myocardial fibrosis in Mst1 group and Mst1-Nrf2 group is significantly reduced, while the level of myocardial fibrosis in DCM group is significantly increased (P < 0.01). After 8 weeks of STZ injection, the degree of myocardial fibrosis in DCM+Mst1 group and DCM+ Mst1-Nrf2 group is significantly reduced. Compared with the wild group, the expression of myocardial Beclin1 protein in Mst1 group and Mst1-Nrf2 group is significantly increased (P < 0.01); Compared with DCM group, myocardial Beclin1 protein expression is significantly increased in DCM+Mst1 group and DCM+Mst1-Nrf2 group(P< 0.01). Compared with the wild group, the expression of p62 protein in myocardium of Mst1 group and Mst1-Nrf2 group is significantly decreased (P < 0.01). Compared with DCM group, the expression of p62 protein in myocardium of DCM+Mst1 group and DCM+Mst1-Nrf2 group is decreased significantly (P< 0.01). Compared with the wild group, myocardial Nrf2 protein expression in Mst1 group and Mst1-Nrf2 group is significantly increased (P < 0.01). Compared with DCM group, myocardial Nrf2 protein expression of mice in DCM+Mst1 group and DCM+ Mst1-Nrf2 group is significantly increased (P < 0.01). Conclusion Mst1-Nrf2 promotes autophagy in type 2 diabetic mice and inhibits the progression of diabetic cardiomyopathy.
Oxygen regulates ILC3 antigen presentation potential and pregnancy-related hormone actions
Authors: Einenkel Rebekka , Ehrhardt Jens , Zygmunt Marek , Muzzio Damián Oscar 
Published: January 2022

Abstract
Early pregnancy is marked by placentation and embryogenesis, which take place under physiological low oxygen concentrations. This oxygen condition is crucial for many aspects of placentation, trophoblast function, vascularization and immune function. Recently, a new family of innate lymphoid cells has been found to be expressed at the fetomaternal interface. Among these, type 3 innate lymphoid cells (ILC3) are important antigen presenting cells in the context of MHCII. The expression of MHCII on ILC3s during pregnancy is reduced. We tested the hypothesis that low oxygen concentrations reduce the potential of ILC3s to present antigens promoting fetal tolerance.Using an in vitro approach, NCR+ ILC3s generated from cord blood stem cell precursors were incubated under different O2 concentrations in the presence or absence of the pregnancy-related hormones hCG and TGF‑β1. The expression of MHCII, accessory molecules and an activation marker were assessed by flow cytometry. We observed that 1 % O2 reduced the expression of the MHCII molecule HLA-DR as compared to 21 % O2 and modulated the relative effects of hCG and TGF‑β1. Our data indicate that low oxygen concentrations reduce the antigen presentation potential of NCR+ ILC3s and suggest that it may promote fetal tolerance during the first trimester of pregnancy.