bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term vitamin D deficiency promotes renal fibrosis and functional impairment in middle-aged male mice
Authors: Zhang Zhi-Hui , Luo Biao , Xu Shen , Zhang Zhi-Cheng , Xing Wei-Yang , Chen Yuan-Hua , Zhang Cheng , Wang Hua , Xie Dong-Dong , Xu De-Xiang 
Published: August 2020

AbstractRenal fibrosis is common especially in the elderly population. Recently, we found that vitamin D deficiency caused prostatic hyperplasia. This study aimed to investigate whether vitamin D deficiency promotes renal fibrosis and functional impairment. All mice except controls were fed with vitamin D-deficient (VDD) diets, beginning from their early life. The absolute and relative kidney weights on postnatal week 20 were decreased in VDD diet-fed male pups but not in female pups. A mild pathological damage was observed in VDD diet-fed male pups but not in females. Further analysis showed that VDD-induced pathological damage was aggravated, accompanied by renal dysfunction in 40-week-old male pups. An obvious collagen deposition was observed in VDD diet-fed 40-week-old male pups. Moreover, renal α-smooth muscle actin (α-SMA), a marker of epithelial–mesenchymal transition (EMT), and Tgf-β mRNA were up-regulated. The in vitro experiment showed that 1,25-dihydroxyvitamin D3 alleviated transforming growth factor-β1 (TGF-β1)-mediated down-regulation of E-cadherin and inhibited TGF-β1-evoked up-regulation of N-cadherin, vimentin and α-SMA in renal epithelial HK-2 cells. Moreover, 1,25-dihydroxyvitamin D3 suppressed TGF-β1-evoked Smad2/3 phosphorylation in HK-2 cells. These results provide experimental evidence that long-term vitamin D deficiency promotes renal fibrosis and functional impairment, at least partially, through aggravating TGF-β/Smad2/3-mediated EMT in middle-aged male mice.
Democracy, Autocracy, and Emergency Threats: Lessons for COVID-19 From the Last Thousand Years
Authors: Stasavage David 
Published: August 2020

AbstractOur experience with COVID-19 has yet to show that either democracies or autocracies are unambiguously better at dealing with this threat. What the pandemic has instead demonstrated is that these two forms of government each have specific strengths and weaknesses when it comes to dealing with external emergencies. In autocracies centralization of power allows for decisive action, but their ability to maintain secrecy means that they can also suppress information and ignore a problem. In a democracy greater transparency makes it hard to cover up a threat, but the decentralization of power that is inherent to a democracy can lead to a slow and potentially ineffective response. Using both current and historical comparisons between China and western countries, I show that these different patterns have deep roots, dating back a thousand years or more. I then consider three alternative proposals for democracies to be able to act more decisively: allowing for rule by decree, devolving responsibility to localities, and investing in preventative state capacity. History shows that the latter of these three is the safest and most effective strategy, but for it to work voters must reward politicians for investing in prevention. Unfortunately, this reward cannot be assumed.
The Song Remains the Same: International Relations After COVID-19
Authors: Drezner Daniel W. 
Published: August 2020

AbstractSince the onset of COVID-19, there has been a surfeit of commentary arguing that 2020 will have transformative effects on world politics. This paper asks whether, decades from now, the pandemic will be viewed as an inflection point. Critical junctures occur when an event triggers a discontinuous shift in key variables or forces a rapid acceleration of preexisting trends. Pandemics have undeniably had this effect in the far past. A welter of economic and medical developments, however, have strongly muted the geopolitical impact of pandemics in recent centuries. A review of how the novel coronavirus has affected the distribution of power and interest in its first six months suggests that COVID-19 will not have transformative effects on world politics. Absent a profoundex postshift in hegemonic ideas, 2020 is unlikely to be an inflection point.
The Warden procedure for partial anomalous pulmonary venous connection in children: 10 years experience in 65 cases
Authors: Alkady Hesham , Elnaggar Ahmed , Eldegwy Mahmoud , Nosair Abdallah 
Published: August 2020

AbstractIntroduction:In this study, we share our experience in the Warden procedure for the repair of partial anomalous pulmonary venous connections (PAPVCs) draining high in the superior caval vein in 65 cases of the paediatric age group over a period of 10 years.Patients and methods:In total, 65 patients receiving the Warden procedure for the repair of high PAPVCs (draining above the cavoatrial junction) over a period of 10 years starting from January, 2010 to January, 2020 were included in this study.Results:In total, 34 were males (52.3%) and 31 were females (47.7%). The mean age was 3.47 ± 1.4 years, while the mean weight was 17.3 ± 5.3 kilograms. The mean bypass time was 84.2 ± 13.9 minutes and the mean cross clamp time was 54.8 ± 12.9 minutes. The mean intensive care unit stay was 2.14 ± 0.89 days, while the mean hospital stay was 5.9 ± 1.4 days. There was no in-hospital mortality or persistent sinus node dysfunction necessitating permanent pacemaker. In total, 62 patients (95%) could be followed up for a mean period of 7.8 ± 1.2 years after discharge. During the follow-up period, no stenosis was detected in the Warden anastomosis or the rerouted pulmonary veins and only one case of late mortality (1.6%) occurred due to a non-cardiac cause.Conclusion:The Warden procedure is a safe approach for the repair of high PAPVCs (above the cavoatrial junction) in the paediatric age group with good long-term results and low incidence of complications like sinus node dysfunction as well as pulmonary vein and superior caval vein obstruction.
Stability of food insecurity status in paediatric primary care
Authors: Courts Kelly A , Hubbard Rebecca A , Kersten Hans B , Klusaritz Heather 
Published: August 2020

AbstractObjective:The American Academy of Pediatrics recommends screening for food insecurity (FI) at all well-child visits due to well-documented negative effects of experiencing FI in childhood. Before age 3, children have twelve recommended primary care visits at which screening could occur. Little is known regarding the stability of FI status at this frequency of screening.Design:Data derived from electronic health records were used to retrospectively examine the stability of household FI status. Age-stratified (infantv. toddler) analyses accounted for age-based differences in visit frequency. Regression models with time since last screening as the predictor of FI transitions were estimated via generalised estimating equations adjusting for age and race/ethnicity.Setting:A paediatric primary care practice in Philadelphia.Participants:3451 distinct patients were identified whose health record documented two or more household FI screens between April 1, 2012 and July 31, 2018 and were aged 0–3 years at first screen.Results:Overall, 9·5 % of patients had a transition in household FI status, with a similar frequency of transitioning from food insecure to secure (5·0 %) and from food secure to insecure (4·5 %). Families of toddlers whose last screen was more than a year ago were more likely to experience a transition to FI compared with those screened 0–6 months prior (OR 1·91 (95 % CI 1·05, 3·47)).Conclusions:Screening more than annually may not contribute substantially to the identification of transitions to FI.
Treatment of metastatic castration resistant prostate cancer with radium-223: a retrospective study at a US tertiary oncology center
Authors: McKay Rana R. , Silver Rebecca , Bhak Rachel H. , Korves Caroline , Cheng Mu , Appukkuttan Sreevalsa , Simmons Stacey J. , Duh Mei Sheng , Taplin Mary-Ellen 
Published: August 2020

Abstract
Background
Guidelines for optimal sequencing of radium-223 and chemotherapy for metastatic castration resistant prostate cancer (mCRPC) do not exist. This study evaluated treatment patterns and overall survival (OS) among patients with mCRPC treated with radium-223 in an academic clinical setting.

Methods
A retrospective study was conducted of bone metastases-predominant mCRPC patients treated with radium-223. Treatment patterns from 2013 to 2018 were evaluated in patients treated with radium-223 pre- vs. post-chemotherapy. OS was examined using Kaplan–Meier medians and 95% confidence intervals.

Results
In total, 220 patients were treated with radium-223 (64 pre-chemotherapy, 83 post-chemotherapy, 73 no chemotherapy). Mean radium-223 injections per patient was 5.3 and 4.3 in the pre- vs. post-chemotherapy cohorts, respectively (p < 0.001). The number of chemotherapy cycles was similar for chemotherapy given pre- or post-radium-223. Mean line of mCRPC therapy of radium-223 was 3rd and 5th when given pre- and post-chemotherapy, respectively (p < 0.001). 41.8% patients were treated with radium-223 in combination with another mCRPC therapy, commonly abiraterone acetate (43.5%) or enzalutamide (52.2%). The majority received combination therapy for the duration of radium-223 treatment; 20.7% started another agent after radium-223 initiation; 20.7% initiated radium-223 while on established therapy. Median OS from first mCRPC treatment was 39.4 months (95% CI 33.0, 48.8) for patients with radium-223 pre-chemotherapy vs. 37.4 months (95% CI 32.0, 43.5) post-chemotherapy (and 35.2 months [95% CI 27.9, 43.3] vs. 32.0 months [95% CI 26.9, 36.0] for patients with radium-223 combination vs. monotherapy).

Conclusions
This retrospective analysis of patients treated with radium-223 demonstrates that administration of radium-223 pre-chemotherapy increased likelihood of completion of radium-223 treatment. Radium-223 given pre- or post-chemotherapy and with or without combination therapy did not result in significant differences in OS. Additional studies are needed to determine the optimal sequencing strategy of mCRPC in the modern era.
An invasive beetle–fungus complex is maintained by fungal nutritional-compensation mediated by bacterial volatiles
Authors: Liu Fanghua , Wickham Jacob D , Cao Qingjie , Lu Min , Sun Jianghua 
Published: August 2020

Abstract
Mutualisms between symbiotic microbes and animals have been well documented, and nutritional relationships provide the foundation for maintaining beneficial associations. The well-studied mutualism between bark beetles and their fungi has become a classic model system in the study of symbioses. Despite the nutritional competition between bark beetles and beneficial fungi in the same niche due to poor nutritional feeding substrates, bark beetles still maintain mutualistic associations with beneficial fungi over time. The mechanism behind this phenomenon, however, remains largely unknown. Here, we demonstrated the bark beetle Dendroctonus valens LeConte relies on the symbiotic bacterial volatile ammonia, as a nitrogen source, to regulate carbohydrate metabolism of its mutualistic fungus Leptographium procerum to alleviate nutritional competition, thereby maintaining the stability of the bark beetle–fungus mutualism. Ammonia significantly reduces competition of L. procerum for carbon resources for D. valens larval growth and increases fungal growth. Using stable isotope analysis, we show the fungus breakdown of phloem starch into d-glucose by switching on amylase genes only in the presence of ammonia. Deletion of amylase genes interferes with the conversion of starch to glucose. The acceleration of carbohydrate consumption and the conversion of starch into glucose benefit this invasive beetle–fungus complex. The nutrient consumption–compensation strategy mediated by tripartite beetle–fungus–bacterium aids the maintenance of this invasive mutualism under limited nutritional conditions, exacerbating its invasiveness with this competitive nutritional edge.
Presence of toxin-antitoxin systems in picocyanobacteria and their ecological implications
Authors: Fucich Daniel , Chen Feng 
Published: August 2020

Abstract
Picocyanobacteria (mainly Synechococcus and Prochlorococcus) contribute significantly to ocean’s primary production. Toxin-Antitoxin (TA) systems present in bacteria and archaea are known to regulate cell growth in response to environmental stresses. However, little is known about the presence of TA systems in picocyanobacteria. This study investigated complete genomes of Synechococcus and Prochlorococcus to understand the prevalence of TA systems in picocyanobacteria. Using the TAfinder software, Type II TA systems were predicted in 27 of 33 (81%) Synechococcus strains, but none of 38 Prochlorococcus strains contain TA genes. Synechococcus strains with larger genomes tend to contain more putative type II TA systems. The number of TA pairs varies from 0 to 42 in Synechococcus strains isolated from various environments. A linear correlation between the genome size and the number of putative TA systems in both coastal and freshwater Synechococcus was established. In general, open ocean Synechococcus contain no or few TA systems, while coastal and freshwater Synechococcus contain more TA systems. The type II TA systems inhibit microbial translation via ribonucleases and allow cells to enter the “dormant” stage in adverse environments. Inheritance of TA genes in freshwater and coastal Synechococcus could confer a recoverable persister mechanism important to survive in variable environments.
TRIM22 activates NF-κB signaling in glioblastoma by accelerating the degradation of IκBα
Authors: Ji Jianxiong , Ding Kaikai , Luo Tao , Zhang Xin , Chen Anjing , Zhang Di , Li Gang , Thorsen Frits , Huang Bin , Li Xingang , Wang Jian 
Published: August 2020

AbstractNF-κB signaling plays a critical role in tumor growth and treatment resistance in GBM as in many other cancers. However, the molecular mechanisms underlying high, constitutive NF-κB activity in GBM remains to be elucidated. Here, we screened a panel of tripartite motif (TRIM) family proteins and identified TRIM22 as a potential activator of NF-κB using an NF-κB driven luciferase reporter construct in GBM cell lines. Knockout ofTRIM22using Cas9-sgRNAs led to reduced GBM cell proliferation, whileTRIM22overexpression enhanced proliferation of cell populations, in vitro and in an orthotopic xenograft model. However, two TRIM22 mutants, one with a critical RING-finger domain deletion and the other with amino acid changes at two active sites of RING E3 ligase (C15/18A), were both unable to promote GBM cell proliferation over controls, thus implicating E3 ligase activity in the growth-promoting properties of TRIM22. Co-immunoprecipitations demonstrated that TRIM22 bound a negative regulator of NF-κB, NF-κB inhibitor alpha (IκBα), and accelerated its degradation by inducing K48-linked ubiquitination. TRIM22 also formed a complex with the NF-κB upstream regulator IKKγ and promoted K63-linked ubiquitination, which led to the phosphorylation of both IKKα/β and IκBα. Expression of a non-phosphorylation mutant, srIκBα, inhibited the growth-promoting properties of TRIM22 in GBM cell lines. Finally, TRIM22 was increased in a cohort of primary GBM samples on a tissue microarray, and high expression of TRIM22 correlated with other clinical parameters associated with progressive gliomas, such as wild-type IDH1 status. In summary, our study revealed that TRIM22 activated NF-κB signaling through posttranslational modification of two critical regulators of NF-κB signaling in GBM cells.
Aquaporin 1 promotes sensitivity of anthracycline chemotherapy in breast cancer by inhibiting β-catenin degradation to enhance TopoIIα activity
Authors: Chong Wei , Zhang Huikun , Guo Zhifang , Yang Limin , Shao Ying , Liu Xiaoli , Zhao Yawen , Wang Zhe , Zhang Ming , Guo Caixia , Fu Li , Ma Yongjie , Gu Feng 
Published: August 2020

AbstractAnthracyclines are a class of conventional and commonly used frontline chemotherapy drugs to treat breast cancer. However, the anthracycline-based regimens can only reduce breast cancer mortality by 20–30%. Furthermore, there is no appropriate biomarker for predicting responses to this kind of chemotherapy currently. Here we report our findings that may fill this gap by showing the AQP1 (Aquaporin1) protein as a potential response predictor in the anthracycline chemotherapy. We showed that breast cancer patients with a high level of AQP1 expression who underwent the anthracycline treatment had a better clinical outcome relative to those with a low level of AQP1 expression. In the exploration of the underlying mechanisms, we found that the AQP1 and glycogen synthase kinase-3β (GSK3β) competitively interacted with the 12 armadillo repeats of β-catenin, followed by the inhibition of the β-catenin degradation that led to β-catenin’s accumulation in the cytoplasm and nuclear translocation. The nuclear β-catenin interacted with TopoIIα and enhanced TopoIIα’s activity, which resulted in a high sensitivity of breast cancer cells to anthracyclines. We also found, the miR-320a-3p can attenuate the anthracycline’s chemosensitivity by inhibiting the AQP1 expression. Taken together, our findings suggest the efficacy of AQP1 as a response predictor in the anthracycline chemotherapy. The application of our study includes, but is not limited to, facilitating screening of the most appropriate breast cancer patients (who have a high AQP1 expression) for better anthracycline chemotherapy and improved prognosis purposes.
Phosphorylation of cyclophilin D at serine 191 regulates mitochondrial permeability transition pore opening and cell death after ischemia-reperfusion
Authors: Hurst Stephen , Gonnot Fabrice , Dia Maya , Crola Da Silva Claire , Gomez Ludovic , Sheu Shey-Shing 
Published: August 2020

AbstractThe mitochondrial permeability transition pore (mPTP) plays a critical role in the pathogenesis of cardiovascular diseases, including ischemia/reperfusion injury. Although the pore structure is still unresolved, the mechanism through which cyclophilin D (CypD) regulates mPTP opening is the subject of intensive studies. While post-translational modifications of CypD have been shown to modulate pore opening, specific phosphorylation sites of CypD have not yet been identified. We hypothesized here that phosphorylation of CypD on a serine residue controls mPTP opening and subsequent cell death at reperfusion. We combined in silico analysis with in vitro and genetic manipulations to determine potential CypD phosphorylation sites and their effect on mitochondrial function and cell death. Importantly, we developed an in vivo intramyocardial adenoviral strategy to assess the effect of the CypD phosphorylation event on infarct size. Our results show that although CypD can potentially be phosphorylated at multiple serine residues, only the phosphorylation status at S191 directly impacts the ability of CypD to regulate the mPTP. Protein-protein interaction strategies showed that the interaction between CypD and oligomycin sensitivity-conferring protein (OSCP) was reduced by 45% in the phosphoresistant S191A mutant, whereas it was increased by 48% in the phosphomimetic S191E mutant cells. As a result, the phosphoresistant CypD S191A mutant was protected against 18 h starvation whereas cell death was significantly increased in phosphomimetic S191E group, associated with mitochondrial respiration alteration and ROS production. As in vivo proof of concept, in S191A phosphoresistant rescued CypD-KO mice developed significantly smaller infarct as compared to WT whereas infarct size was drastically increased in S191E phosphomimetic rescued mice. We conclude that CypD phosphorylation at S191 residue leads to its binding to OSCP and thus sensitizes mPTP opening for the subsequent cell death.
LncRNA CDKN2B-AS1/miR-141/cyclin D network regulates tumor progression and metastasis of renal cell carcinoma
Authors: Dasgupta Pritha , Kulkarni Priyanka , Majid Shahana , Hashimoto Yutaka , Shiina Marisa , Shahryari Varahram , Bhat Nadeem S. , Tabatabai Laura , Yamamura Soichiro , Saini Sharanjot , Tanaka Yuichiro , Dahiya Rajvir 
Published: August 2020

AbstractThe molecular heterogeneity of renal cell carcinoma (RCC) complicates the therapeutic interventions for advanced metastatic disease and thus its management remains a significant challenge. This study investigates the role of the lncRNA CDKN2B-AS1 and miR-141-3p interactions in the progression and metastasis of kidney cancer. Human renal cancer cell lines (ACHN and Caki1), normal RPTEC cells, tissue cohorts, and a series of in vitro assays and in vivo mouse model were used for this study. An overexpression of CDKN2B-AS1 was observed in RCC compared to normal samples in TCGA and our in-house SFVAMC tissue cohorts. Reciprocally, we observed reduced expression of miR-141 in RCC compared to normal in the same cohorts. CDKN2B-AS1 shares regulatory miR-141 binding sites with CCND1 and CCND2 genes. Direct interactions of CDKN2B-AS1/miR-141/Cyclin D1–D2 were confirmed by RNA immunoprecipitation and luciferase reporter assays indicating that CDKN2B-AS1/miR-141/Cyclin D1–D2 acts as a ceRNA network in RCC. Functionally, attenuation of CDKN2B-AS1 and/or overexpression of miR-141 inhibited proliferation, clonogenicity, migration/invasion, induced apoptosis in vitro and suppressed tumor growth in xenograft mouse model. Further, overexpression of CDKN2B-AS1 is positively correlated with poor overall survival of RCC patients. Expression of miR-141 also robustly discriminated malignant from non-malignant tissues and its inhibition in normal RPTEC cells induced pro-cancerous characteristics. CDKN2B-AS1 attenuation or miR-141 overexpression decreased CCND1/CCND2 expression, resulting in reduced RAC1/pPXN that are involved in migration, invasion and epithelial–mesenchymal transition. This study, for the first time, deciphered the role of CDKN2B-AS1/miR-141/Cyclin D axis in RCC and highlights this network as a promising therapeutic target for the regulation of EMT driven metastasis in RCC.
Structure of an antagonist-bound ghrelin receptor reveals possible ghrelin recognition mode
Authors: Shiimura Yuki , Horita Shoichiro , Hamamoto Akie , Asada Hidetsugu , Hirata Kunio , Tanaka Misuzu , Mori Kenji , Uemura Tomoko , Kobayashi Takuya , Iwata So , Kojima Masayasu 
Published: August 2020

AbstractGhrelin is a gastric peptide hormone with important physiological functions. The unique feature of ghrelin is its Serine 3 acyl-modification, which is essential for ghrelin’s activity. However, it remains to be elucidated why the acyl-modification of ghrelin is necessary for activity. To address these questions, we solved the crystal structure of the ghrelin receptor bound to antagonist. The ligand-binding pocket of the ghrelin receptor is bifurcated by a salt bridge between E124 and R283. A striking feature of the ligand-binding pocket of the ghrelin receptor is a wide gap (crevasse) between the TM6 and TM7 bundles that is rich in hydrophobic amino acids, including a cluster of phenylalanine residues. Mutagenesis analyses suggest that the interaction between the gap structure and the acyl acid moiety of ghrelin may participate in transforming the ghrelin receptor into an active conformation.