bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-oncogene PTPN13 inactivation by hepatitis B virus X protein counteracts IGF2BP1 to promote hepatocellular carcinoma progression
Authors: Yan Yongcong , Huang Pinbo , Mao Kai , He Chuanchao , Xu Qiaodong , Zhang Mengyu , Liu Haohan , Zhou Zhenyu , Zhou Qiming , Zhou Qianlei , Ou Bing , Liu Qinghua , Lin Jianhong , Chen Ruibin , Wang Jie , Zhang Jianlong , Xiao Zhiyu 
Published: October 2020

AbstractHepatitis B x protein (HBx) affects cellular protein expression and participates in the tumorigenesis and progression of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Metabolic reprogramming contributed to the HCC development, but its role in HBV-related HCC remains largely unclear. Tyrosine-protein phosphatase nonreceptor type 13 (PTPN13) is a significant regulator in tumor development, however, its specific role in hepatocarcinogenesis remains to be explored. Here, we found that decreased PTPN13 expression was associated with HBV/HBx. Patients with low PTPN13 expression showed a poor prognosis. Functional assays revealed that PTPN13 inhibited proliferation and tumorigenesis in vitro and in vivo. Further mechanistic studies indicated that HBx inhibited PTPN13 expression by upregulating the expression of DNMT3A and interacting with DNMT3A. Furthermore, we found that DNMT3A bound to the PTPN13 promoter (−343 to −313 bp) in an epigenetically controlled manner associated with elevated DNA methylation and then inhibited PTPN13 transcription. In addition, we identified IGF2BP1 as a novel PTPN13-interacting gene and demonstrated that PTPN13 influences c-Myc expression by directly and competitively binding to IGF2BP1 to decrease the intracellular concentration of functional IGF2BP1. Overexpressing PTPN13 promoted c-Myc mRNA degradation independent of the protein tyrosine phosphatase (PTP) activity of PTPN13. Importantly, we discovered that the PTPN13-IGF2BP1-c-Myc axis was important for cancer cell growth through promoting metabolic reprogramming. We verified the significant negative correlations between PTPN13 expression and c-Myc, PSPH, and SLC7A1 expression in clinical HCC tissue samples. In summary, our findings demonstrate that PTPN13 is a novel regulator of HBV-related hepatocarcinogenesis and may play an important role in HCC. PTPN13 may serve as a prognostic marker and therapeutic target in HBV-related HCC patients.
Survival of patients with deficient mismatch repair metastatic colorectal cancer in the pre-immunotherapy era
Authors: Wensink G. Emerens , Elferink Marloes A. G. , May Anne M. , Mol Linda , Hamers Patricia A. H. , Bakker Sandra D. , Creemers Geert-Jan , de Groot Jan Willem B. , de Klerk Gerty J. , Haberkorn Brigitte C. M. , Haringhuizen Annebeth W. , Hoekstra Ronald , Hunting J. Cornelis B. , Kerver Emile D. , Mathijssen-van Stein Danielle , Polée Marco B. , Pruijt Johannes F. M. , Quarles van Ufford-Mannesse Patricia , Radema Sandra , Rietbroek Ronald C. , Simkens Lieke H. J. , Tanis Bea C. , ten Bokkel Huinink Daan , Tjin-A-Ton Manuel L. R. , Tromp-van Driel Cathrien S. , Troost Monique M. , van de Wouw Agnes J. , van den Berkmortel Franchette W. P. J. , van der Pas Anke J. M. , van der Velden Ankie M. T. , van Dijk Marjan A. , van Dodewaard-de Jong Joyce M. , van Druten Edith B. , van Voorthuizen Theo , Jan Veldhuis Gerrit , Verheul Henk M. W. , Vestjens Hanneke J. H. M. J. , Vincent Jeroen , Kranenburg Onno W. , Punt Cornelis J. A. , Vink Geraldine R. , Roodhart Jeanine M. L. , Koopman Miriam 
Published: October 2020

AbstractBackgroundMetastatic colorectal cancer patients with deficient mismatch repair (dMMR mCRC) benefit from immunotherapy. Interpretation of the single-arm immunotherapy trials is complicated by insignificant survival data during systemic non-immunotherapy. We present survival data on a large, comprehensive cohort of dMMR mCRC patients, treated with or without systemic non-immunotherapy.MethodsTwo hundred and eighty-one dMMR mCRC patients (n = 54 from three prospective Phase 3 CAIRO trials;n = 227 from the Netherlands Cancer Registry). Overall survival was analysed from diagnosis of mCRC (OS), from initiation of first-line (OS1) and second-line (OS2) systemic treatment. Cox regression analysis examined prognostic factors. As comparison for OS 2746 MMR proficient mCRC patients were identified.ResultsOf 281 dMMR patients, 62% received first-line and 26% second-line treatment. Median OS was 16.0 months (13.8–19.6) with antitumour therapy and 2.5 months (1.8–3.5) in untreated patients. OS1 was 12.8 months (10.7–15.2) and OS2 6.2 months (5.4–8.9) in treated dMMR patients. Treated dMMR patients had a 7.6-month shorter median OS than pMMR patients.ConclusionAvailable data from immunotherapy trials lack a control arm with standard systemic treatment. Given the poor outcome compared to the immunotherapy results, our data strongly suggest a survival benefit of immunotherapy in dMMR mCRC patients.
Droplet-digital PCR reveals frequent mutations in TERT promoter region in breast fibroadenomas and phyllodes tumours, irrespective of the presence of MED12 mutations
Authors: Otsuji Kazutaka , Sasaki Takeshi , Tanabe Masahiko , Seto Yasuyuki 
Published: October 2020

Abstract
Background
Breast fibroadenoma (FA) and phyllodes tumour (PT) often have variations of gene mediator complex subunit 12 (MED12) and mutations in the telomerase reverse transcriptase promoter region (TERTp). TERTp mutation is usually tested by Sanger sequencing. In this study, we compared Sanger sequencing and droplet-digital PCR (ddPCR) to measure TERTp mutations in FA and PT samples.

Methods
FA and PT samples were collected from 82 patients who underwent surgery at our institution from 2005 to 2016. MED12 mutations for all cases and TERTp mutations for 17 tumours were detected by Sanger sequencing. ddPCR was performed to analyse TERTp mutation in all cases.

Results
A total of 75 samples were eligible for analysis. Sanger sequencing detected MED12 mutations in 19/44 FA (42%) and 21/31 PT (68%). Among 17 Sanger sequencing-tested samples, 2/17 (12%) were TERTp mutation-positive. In ddPCR analyses, a significantly greater percentage of PT (19/31, 61%) was TERTp mutation-positive than was FA (13/44, 30%; P = 0.0046). The mutation positivity of TERTp and MED12 did not correlate, in either FA or PT.

Conclusions
ddPCR was more sensitive for detecting TERTp mutation than Sanger sequencing, being able to elucidate tumorigenesis in FA and PT.
Crystal structure of caspase-11 CARD provides insights into caspase-11 activation
Authors: Liu Muziying , Zhou Kang , Xu Zhihao , Ma Huan , Cao Xiaocong , Yin Xueying , Zeng Weihong , Zahid Ayesha , Fu Sicheng , Ni Kang , Ye Xiaodong , Zhou Ying , Bai Li , Zhou Rongbin , Jin Tengchuan 
Published: October 2020

AbstractMurine caspase-11 is the centerpiece of the non-canonical inflammasome pathway that can respond to intracellular LPS and induce pyroptosis. Caspase-11 contains two components, an N-terminal caspase recruitment domain (CARD) and a C-terminal catalytic domain. The aggregation of caspase-11 is thought to promote the auto-processing and activation of caspase-11. However, the activation mechanism of caspase-11 remains unclear. In this study, we purified the caspase-11 CARD fused to an MBP tag and found it tetramerizes in solution. Crystallographic analysis reveals an extensive hydrophobic interface formed by the H1–2 helix mediating homotypic CARD interactions. Importantly, mutations of the helix H1–2 hydrophobic residues abolished the tetramerization of MBP-tagged CARD in solution and failed to induce pyroptosis in cells. Our study provides the first evidence of the homotypic interaction mode for an inflammatory caspase by crystal model. This finding demonstrates that the tetramerization of the N-terminal CARD can promote releasing of the catalytic domain auto-inhibition, leading to the caspase-11 activation.
A scoping review of adoption of climate-resilient crops by small-scale producers in low- and middle-income countries
Authors: Acevedo Maricelis , Pixley Kevin , Zinyengere Nkulumo , Meng Sisi , Tufan Hale , Cichy Karen , Bizikova Livia , Isaacs Krista , Ghezzi-Kopel Kate , Porciello Jaron 
Published: October 2020

AbstractClimate-resilient crops and crop varieties have been recommended as a way for farmers to cope with or adapt to climate change, but despite the apparent benefits, rates of adoption by smallholder farmers are highly variable. Here we present a scoping review, using PRISMA-P (Preferred Reporting Items for Systematic review and Meta-Analysis Protocols), examining the conditions that have led to the adoption of climate-resilient crops over the past 30 years in lower- and middle-income countries. The descriptive analysis performed on 202 papers shows that small-scale producers adopted climate-resilient crops and varieties to cope with abiotic stresses such as drought, heat, flooding and salinity. The most prevalent trait in our dataset was drought tolerance, followed by water-use efficiency. Our analysis found that the most important determinants of adoption of climate-resilient crops were the availability and effectiveness of extension services and outreach, followed by education levels of heads of households, farmers’ access to inputs—especially seeds and fertilizers—and socio-economic status of farming families. About 53% of studies reported that social differences such as sex, age, marital status and ethnicity affected the adoption of varieties or crops as climate change-adaptation strategies. On the basis of the collected evidence, this study presents a series of pathways and interventions that could contribute to higher adoption rates of climate-resilient crops and reduce dis-adoption.
A scoping review of feed interventions and livelihoods of small-scale livestock keepers
Authors: Baltenweck Isabelle , Cherney Debbie , Duncan Alan , Eldermire Erin , Lwoga Edda Tandi , Labarta Ricardo , Rao Elizaphan James Oburu , Staal Steven , Teufel Nils 
Published: October 2020

AbstractLivestock support the livelihoods of one billion people in Africa, Asia and Latin America, but the productivity of animals remains low, reducing the potential of the sector to support higher incomes and better nutrition. Improved livestock feeding has been identified as the most important step towards higher productivity. This scoping review assessed the evidence for the uptake of improved ruminant livestock feed options, the effect of this uptake on livestock productivity and the degree to which this improves smallholder farmer livelihoods. In total, 22,981 papers were identified, of which 73 papers were included in the final analysis after a rigorous double-blind screening review. Only papers that reported farmers’ decision to use a new feed intervention were selected, thereby excluding feeding trials and participatory feed assessments. Of the 73 papers, only 6 reported combined evidence of adoption, effect on productivity and livelihood changes. A total of 58 papers looked at adoption, 19 at productivity change and 22 at livelihood change. This scoping review highlights the gap in evidence for the adoption of new livestock feeding practices and provides recommendations to support farmers’ uptake of feed interventions.
Whole genome sequencing data of multiple individuals of Pakistani descent
Authors: Khan Shahid Y. , Ali Muhammad , Lee Mei-Chong W. , Ma Zhiwei , Biswas Pooja , Khan Asma A. , Naeem Muhammad Asif , Riazuddin Saima , Riazuddin Sheikh , Ayyagari Radha , Hejtmancik J. Fielding , Riazuddin S. Amer 
Published: October 2020

AbstractHere we report whole genome sequencing of four individuals (H3, H4, H5, and H6) from a family of Pakistani descent. Whole genome sequencing yielded 1084.92, 894.73, 1068.62, and 1005.77 million mapped reads corresponding to 162.73, 134.21, 160.29, and 150.86 Gb sequence data and 52.49x, 43.29x, 51.70x, and 48.66x average coverage for H3, H4, H5, and H6, respectively. We identified 3,529,659, 3,478,495, 3,407,895, and 3,426,862 variants in the genomes of H3, H4, H5, and H6, respectively, including 1,668,024 variants common in the four genomes. Further, we identified 42,422, 39,824, 28,599, and 35,206 novel variants in the genomes of H3, H4, H5, and H6, respectively. A major fraction of the variants identified in the four genomes reside within the intergenic regions of the genome. Single nucleotide polymorphism (SNP) genotype based comparative analysis with ethnic populations of 1000 Genomes database linked the ancestry of all four genomes with the South Asian populations, which was further supported by mitochondria based haplogroup analysis. In conclusion, we report whole genome sequencing of four individuals of Pakistani descent.
A naturalistic neuroimaging database for understanding the brain using ecological stimuli
Authors: Aliko Sarah , Huang Jiawen , Gheorghiu Florin , Meliss Stefanie , Skipper Jeremy I. 
Published: October 2020

AbstractNeuroimaging has advanced our understanding of human psychology using reductionist stimuli that often do not resemble information the brain naturally encounters. It has improved our understanding of the network organization of the brain mostly through analyses of ‘resting-state’ data for which the functions of networks cannot be verifiably labelled. We make a ‘Naturalistic Neuroimaging Database’ (NNDb v1.0) publically available to allow for a more complete understanding of the brain under more ecological conditions during which networks can be labelled. Eighty-six participants underwent behavioural testing and watched one of 10 full-length movies while functional magnetic resonance imaging was acquired. Resulting timeseries data are shown to be of high quality, with good signal-to-noise ratio, few outliers and low movement. Data-driven functional analyses provide further evidence of data quality. They also demonstrate accurate timeseries/movie alignment and how movie annotations might be used to label networks. The NNDb can be used to answer questions previously unaddressed with standard neuroimaging approaches, progressing our knowledge of how the brain works in the real world.
Spotlight on the invasion of a carabid beetle on an oceanic island over a 105-year period
Authors: Lebouvier Marc , Lambret Philippe , Garnier Alexia , Convey Peter , Frenot Yves , Vernon Philippe , Renault David 
Published: October 2020

AbstractThe flightless beetle Merizodus soledadinus, native to the Falkland Islands and southern South America, was introduced to the sub-Antarctic Kerguelen Islands in the early Twentieth Century. Using available literature data, in addition to collecting more than 2000 new survey (presence/absence) records of M. soledadinus over the 1991–2018 period, we confirmed the best estimate of the introduction date of M. soledadinus to the archipelago, and tracked subsequent changes in its abundance and geographical distribution. The range expansion of this flightless insect was initially slow, but has accelerated over the past 2 decades, in parallel with increased local abundance. Human activities may have facilitated further local colonization by M. soledadinus, which is now widespread in the eastern part of the archipelago. This predatory insect is a major threat to the native invertebrate fauna, in particular to the endemic wingless flies Anatalanta aptera and Calycopteryx moseleyi which can be locally eliminated by the beetle. Our distribution data also suggest an accelerating role of climate change in the range expansion of M. soledadinus, with populations now thriving in low altitude habitats. Considering that no control measures, let alone eradication, are practicable, it is essential to limit any further local range expansion of this aggressively invasive insect through human assistance. This study confirms the crucial importance of long term biosurveillance for the detection and monitoring of non-native species and the timely implementation of control measures.
Sulcal morphology of ventral temporal cortex is shared between humans and other hominoids
Authors: Miller Jacob A. , Voorhies Willa I. , Li Xiang , Raghuram Ishana , Palomero-Gallagher Nicola , Zilles Karl , Sherwood Chet C. , Hopkins William D. , Weiner Kevin S. 
Published: October 2020

AbstractHominoid-specific brain structures are of particular importance in understanding the evolution of human brain structure and function, as they are absent in mammals that are widely studied in the extended neuroscience field. Recent research indicates that the human fusiform gyrus (FG), which is a hominoid-specific structure critical for complex object recognition, contains a tertiary, longitudinal sulcus (mid-fusiform sulcus, MFS) that bisects the FG into lateral and medial parallel gyri. The MFS is a functional and architectonic landmark in the human brain. Here, we tested if the MFS is specific to the human FG or if the MFS is also identifiable in other hominoids. Using magnetic resonance imaging and cortical surface reconstructions in 30 chimpanzees and 30 humans, we show that the MFS is also present in chimpanzees. The MFS is relatively deeper and cortically thinner in chimpanzees compared to humans. Additional histological analyses reveal that the MFS is not only present in humans and chimpanzees, but also in bonobos, gorillas, orangutans, and gibbons. Taken together, these results reveal that the MFS is a sulcal landmark that is shared between humans and other hominoids. These results require a reconsideration of the sulcal patterning in ventral temporal cortex across hominoids, as well as revise the compensation theory of cortical folding.
Boron improves cardiac contractility and fibrotic remodeling following myocardial infarction injury
Authors: Bouchareb Rihab , Katz Michael , Saadallah Najla , Sassi Yassine , Ali Shakir , Lebeche Djamel 
Published: October 2020

AbstractMyocardial fibrosis is a major determinant of clinical outcomes in heart failure (HF) patients. It is characterized by the emergence of myofibroblasts and early activation of pro-fibrotic signaling pathways before adverse ventricular remodeling and progression of HF. Boron has been reported in recent years to augment the innate immune system and cell proliferation, which play an important role in the repair and regeneration of the injured tissue. Currently, the effect of boron on cardiac contractility and remodeling is unknown. In this study, we investigated, for the first time, the effect of boron supplementation on cardiac function, myocardial fibrosis, apoptosis and regeneration in a rat model myocardial infarction (MI)-induced HF. MI was induced in animals and borax, a sodium salt of boron, was administered for 7 days, p.o., 21 days post-injury at a dose level of 4 mg/kg body weight. Transthoracic echocardiographic analysis showed a significant improvement in systolic and diastolic functions with boron treatment compared to saline control. In addition, boron administration showed a marked reduction in myocardial fibrosis and apoptosis in the injured hearts, highlighting a protective effect of boron in the ischemic heart. Interestingly, we observed a tenfold increase of nuclei in thin myocardial sections stained positive for the cell cycle marker Ki67 in the MI boron-treated rats compared to saline, indicative of increased cardiomyocyte cell cycle activity in MI hearts, highlighting its potential role in regeneration post-injury. We similarly observed increased Ki67 and BrdU staining in cultured fresh neonatal rat ventricular cardiomyocytes. Collectively, the results show that boron positively impacted MI-induced HF and attenuated cardiac fibrosis and apoptosis, two prominent features of HF. Importantly, boron has the potential to induce cardiomyocyte cell cycle entry and potentially cardiac tissue regeneration after injury. Boron might be beneficial as a supplement in MI and may be a good candidate substance for anti-fibrosis approach.
Enhanced energy density of PVDF-based nanocomposites via a core–shell strategy
Authors: Xu JingJing , Fu Chao , Chu Huiying , Wu Xianyou , Tan Zhongyang , Qian Jing , Li Weiyan , Song Zhongqian , Ran Xianghai , Nie Wei 
Published: October 2020

AbstractIn recent years, high energy density polymer capacitors have attracted a lot of scientific interest due to their potential applications in advanced power systems and electronic devices. Here, core–shell structured TiO2@SrTiO3@polydamine nanowires (TiO2@SrTiO3@PDA NWs) were synthesized via a combination of surface conversion reaction and in-situ polymerization method, and then incorporated into the poly(vinylidene fluoride) (PVDF) matrix. Our results showed that a small amount of TiO2@SrTiO3@PDA NWs can simultaneously enhance the breakdown strength and electric displacement of nanocomposite (NC) films, resulting in improved energy storage capability. The 5 wt% TiO2@SrTiO3@PDA NWs/PVDF NC demonstrates 1.72 times higher maximum discharge energy density compared to pristine PVDF (10.34 J/cm3 at 198 MV/m vs. 6.01 J/cm3 at 170 MV/m). In addition, the NC with 5 wt% TiO2@SrTiO3@PDA NWs also demonstrates an excellent charge–discharge efficiency (69% at 198 MV/m). Enhanced energy storage performance is due to hierarchical interfacial polarization among their multiple interfaces, the large aspect ratio as well as surface modification of the TiO2@SrTiO3 NWs. The results of this study provide guidelines and a foundation for the preparation of the polymer NCs with an outstanding discharge energy density.
Motor cortical circuits contribute to crossed facilitation of trunk muscles induced by rhythmic arm movement
Authors: Chiou Shin-Yi , Morris Laura , Gou Weidong , Alexander Emma , Gay Eliot 
Published: October 2020

AbstractTraining of one limb improves performance of the contralateral, untrained limb, a phenomenon known as cross transfer. It has been used for rehabilitation interventions, i.e. mirror therapy, in people with neurologic disorders. However, it remains unknown whether training of the upper limb can induce the cross-transfer effect to the trunk muscles. Using transcranial magnetic stimulation over the primary motor cortex (M1) we examined motor evoked potentials (MEPs) in the contralateral erector spinae (ES) muscle before and after 30 min of unilateral arm cycling in healthy volunteers. ES MEPs were increased after the arm cycling. To understand the origin of this facilitatory effect, we examined short-interval intracrotical inhibition (SICI) and cervicomedullary MEPs (CMEPs) in neural populations controlling in the ES muscle. Notably, SICI reduced after the arm cycling, while CMEPs remained the same. Using bilateral transcranial direct current stimulation (tDCS) in conjunction with 20 min of the arm cycling, the amplitude of ES MEPs increased to a similar extent as with 30 min of the arm cycling alone. These findings demonstrate that a single session of unilateral arm cycling induces short-term plasticity in corticospinal projections to the trunk muscle in healthy humans. The changes are likely driven by cortical mechanisms.