bluuebunny/crossref_metadata_2025_split huggingface dataset:
A circular RNA activated by TGFβ promotes tumor metastasis through enhancing IGF2BP3-mediated PDPN mRNA stability
Authors: Li Ke , Guo Jiawei , Ming Yue , Chen Shuang , Zhang Tingting , Ma Hulin , Fu Xin , Wang Jin , Liu Wenrong , Peng Yong 
Published: October 2023

AbstractMetastasis is the leading cause of cancer-related death, where TGFβ-induced epithelial-mesenchymal transition (EMT) process confers on cancer cells increased metastatic potential. However, the involvement of circRNAs in this process is still obscure. Here, we identify a TGFβ-induced circRNA called circITGB6 as an indispensable factor during the TGFβ-mediated EMT process. circITGB6 is significantly upregulated in metastatic cancer samples and its higher abundance is closely correlated to worse prognosis of colorectal cancer (CRC) patients. Through gain- and loss-of-function assays, circITGB6 is found to potently promote EMT process and tumor metastasis in various models in vitro and in vivo. Mechanistically, circITGB6 enhances the mRNA stability of PDPN, an EMT-promoting gene, by directly interacting with IGF2BP3. Notably, interfering circITGB6 with PEI-coated specific siRNA effectively represses liver metastasis. Therefore, our study reveals the function of a TGFβ-regulated circRNA in tumor metastasis and suggests that targeting circITGB6 is a promising strategy for cancer therapy.
Enhanced clinical assessment of hematologic malignancies through routine paired tumor and normal sequencing
Authors: Ptashkin Ryan N. , Ewalt Mark D. , Jayakumaran Gowtham , Kiecka Iwona , Bowman Anita S. , Yao JinJuan , Casanova Jacklyn , Lin Yun-Te David , Petrova-Drus Kseniya , Mohanty Abhinita S. , Bacares Ruben , Benhamida Jamal , Rana Satshil , Razumova Anna , Vanderbilt Chad , Balakrishnan Rema Anoop , Rijo Ivelise , Son-Garcia Julie , de Bruijn Ino , Zhu Menglei , Lachhander Sean , Wang Wei , Haque Mohammad S. , Seshan Venkatraman E. , Wang Jiajing , Liu Ying , Nafa Khedoudja , Borsu Laetitia , Zhang Yanming , Aypar Umut , Suehnholz Sarah P. , Chakravarty Debyani , Park Jae H. , Abdel-Wahab Omar , Mato Anthony R. , Xiao Wenbin , Roshal Mikhail , Yabe Mariko , Batlevi Connie Lee , Giralt Sergio , Salles Gilles , Rampal Raajit , Tallman Martin , Stein Eytan M. , Younes Anas , Levine Ross L. , Perales Miguel-Angel , van den Brink Marcel R. M. , Dogan Ahmet , Ladanyi Marc , Berger Michael F. , Brannon A. Rose , Benayed Ryma , Zehir Ahmet , Arcila Maria E. 
Published: October 2023

AbstractGenomic profiling of hematologic malignancies has augmented our understanding of variants that contribute to disease pathogenesis and supported development of prognostic models that inform disease management in the clinic. Tumor only sequencing assays are limited in their ability to identify definitive somatic variants, which can lead to ambiguity in clinical reporting and patient management. Here, we describe the MSK-IMPACT Heme cohort, a comprehensive data set of somatic alterations from paired tumor and normal DNA using a hybridization capture-based next generation sequencing platform. We highlight patterns of mutations, copy number alterations, and mutation signatures in a broad set of myeloid and lymphoid neoplasms. We also demonstrate the power of appropriate matching to make definitive somatic calls, including in patients who have undergone allogeneic stem cell transplant. We expect that this resource will further spur research into the pathobiology and clinical utility of clinical sequencing for patients with hematologic neoplasms.
XMAP: Cross-population fine-mapping by leveraging genetic diversity and accounting for confounding bias
Authors: Cai Mingxuan , Wang Zhiwei , Xiao Jiashun , Hu Xianghong , Chen Gang , Yang Can 
Published: October 2023

AbstractFine-mapping prioritizes risk variants identified by genome-wide association studies (GWASs), serving as a critical step to uncover biological mechanisms underlying complex traits. However, several major challenges still remain for existing fine-mapping methods. First, the strong linkage disequilibrium among variants can limit the statistical power and resolution of fine-mapping. Second, it is computationally expensive to simultaneously search for multiple causal variants. Third, the confounding bias hidden in GWAS summary statistics can produce spurious signals. To address these challenges, we develop a statistical method for cross-population fine-mapping (XMAP) by leveraging genetic diversity and accounting for confounding bias. By using cross-population GWAS summary statistics from global biobanks and genomic consortia, we show that XMAP can achieve greater statistical power, better control of false positive rate, and substantially higher computational efficiency for identifying multiple causal signals, compared to existing methods. Importantly, we show that the output of XMAP can be integrated with single-cell datasets, which greatly improves the interpretation of putative causal variants in their cellular context at single-cell resolution.
Impact of COVID-19 on mortality in coastal Kenya: a longitudinal open cohort study
Authors: Otiende M. , Nyaguara A. , Bottomley C. , Walumbe D. , Mochamah G. , Amadi D. , Nyundo C. , Kagucia E. W. , Etyang A. O. , Adetifa I. M. O. , Brand S. P. C. , Maitha E. , Chondo E. , Nzomo E. , Aman R. , Mwangangi M. , Amoth P. , Kasera K. , Ng’ang’a W. , Barasa E. , Tsofa B. , Mwangangi J. , Bejon P. , Agweyu A. , Williams T. N. , Scott J. A. G. 
Published: October 2023

AbstractThe mortality impact of COVID-19 in Africa remains controversial because most countries lack vital registration. We analysed excess mortality in Kilifi Health and Demographic Surveillance System, Kenya, using 9 years of baseline data. SARS-CoV-2 seroprevalence studies suggest most adults here were infected before May 2022. During 5 waves of COVID-19 (April 2020-May 2022) an overall excess mortality of 4.8% (95% PI 1.2%, 9.4%) concealed a significant excess (11.6%, 95% PI 5.9%, 18.9%) among older adults ( ≥ 65 years) and a deficit among children aged 1–14 years (−7.7%, 95% PI −20.9%, 6.9%). The excess mortality rate for January 2020-December 2021, age-standardised to the Kenyan population, was 27.4/100,000 person-years (95% CI 23.2-31.6). In Coastal Kenya, excess mortality during the pandemic was substantially lower than in most high-income countries but the significant excess mortality in older adults emphasizes the value of achieving high vaccine coverage in this risk group.
Shade-induced RTFL/DVL peptides negatively regulate the shade response by directly interacting with BSKs in Arabidopsis
Authors: Huang Sha , Ma Yu , Xu Yitian , Lu Pengfei , Yang Jie , Xie Yu , Gan Jianhua , Li Lin 
Published: October 2023

AbstractFor shade-intolerant species, shade light indicates the close proximity of neighboring plants and triggers the shade avoidance syndrome (SAS), which causes exaggerated growth and reduced crop yield. Here, we report that non-secreted ROT FOUR LIKE (RTFL)/DEVIL (DVL) peptides negatively regulate SAS by interacting with BRASSINOSTEROID SIGNALING KINASEs (BSKs) and reducing the protein level of PHYTOCHROME INTERACTING FACTOR 4 (PIF4) in Arabidopsis. The transcription of at least five RTFLs (RTFL13/16/17/18/21) is induced by low R:FR light. The RTFL18 (DVL1) protein is stabilized under low R:FR conditions and localized to the plasma membrane. A phenotype analysis reveals that RTFL18 negatively regulates low R:FR-promoted petiole elongation. BSK3 and BSK6 are identified as partners of RTFL18 through binding assays and structural modeling. The overexpression of RTFL18 or knockdown of BSK3/6 reduces BRASSINOSTEROID signaling and reduces low R:FR-stabilized PIF4 levels. Genetically, the overexpression of BSK3/6 and PIF4 restores the petiole phenotype acquired by RTFL18-overexpressing lines. Collectively, our work characterizes a signaling cascade (the RTFLs-BSK3/6-PIF4 pathway) that prevents the excessive activation of the shade avoidance response in Arabidopsis.
Lateral hypothalamic proenkephalin neurons drive threat-induced overeating associated with a negative emotional state
Authors: You In-Jee , Bae Yeeun , Beck Alec R. , Shin Sora 
Published: October 2023

AbstractPsychological stressors, like the nearby presence of a predator, can be strong enough to induce physiological/hormonal alterations, leading to appetite changes. However, little is known about how threats can alter feeding-related hypothalamic circuit functions. Here, we found that proenkephalin (Penk)-expressing lateral hypothalamic (LHPenk) neurons of mice exposed to predator scent stimulus (PSS) show sensitized responses to high-fat diet (HFD) eating, whereas silencing of the same neurons normalizes PSS-induced HFD overconsumption associated with a negative emotional state. Downregulation of endogenous enkephalin peptides in the LH is crucial for inhibiting the neuronal and behavioral changes developed after PSS exposure. Furthermore, elevated corticosterone after PSS contributes to enhance the reactivity of glucocorticoid receptor (GR)-containing LHPenk neurons to HFD, whereas pharmacological inhibition of GR in the LH suppresses PSS-induced maladaptive behavioral responses. We have thus identified the LHPenk neurons as a critical component in the threat-induced neuronal adaptation that leads to emotional overconsumption.
A phosphoinositide switch mediates exocyst recruitment to multivesicular endosomes for exosome secretion
Authors: Liu Di-Ao , Tao Kai , Wu Bin , Yu Ziyan , Szczepaniak Malwina , Rames Matthew , Yang Changsong , Svitkina Tatyana , Zhu Yueyao , Xu Fengyuan , Nan Xiaolin , Guo Wei 
Published: October 2023

AbstractExosomes are secreted to the extracellular milieu when multivesicular endosomes (MVEs) dock and fuse with the plasma membrane. However, MVEs are also known to fuse with lysosomes for degradation. How MVEs are directed to the plasma membrane for exosome secretion rather than to lysosomes is unclear. Here we report that a conversion of phosphatidylinositol-3-phosphate (PI(3)P) to phosphatidylinositol-4-phosphate (PI(4)P) catalyzed sequentially by Myotubularin 1 (MTM1) and phosphatidylinositol 4-kinase type IIα (PI4KIIα) on the surface of MVEs mediates the recruitment of the exocyst complex. The exocyst then targets the MVEs to the plasma membrane for exosome secretion. We further demonstrate that disrupting PI(4)P generation or exocyst function blocked exosomal secretion of Programmed death-ligand 1 (PD-L1), a key immune checkpoint protein in tumor cells, and led to its accumulation in lysosomes. Together, our study suggests that the PI(3)P to PI(4)P conversion on MVEs and the recruitment of the exocyst direct the exocytic trafficking of MVEs for exosome secretion.
α-Synuclein aggregates amplified from patient-derived Lewy bodies recapitulate Lewy body diseases in mice
Authors: Uemura Norihito , Marotta Nicholas P. , Ara Jahan , Meymand Emily S. , Zhang Bin , Kameda Hiroshi , Koike Masato , Luk Kelvin C. , Trojanowski John Q. , Lee Virginia M.-Y. 
Published: October 2023

AbstractExtraction of α-Synuclein (αSyn) aggregates from Lewy body disease (LBD) brains has been widely described yet templated fibrillization of LB-αSyn often fails to propagate its structural and functional properties. We recently demonstrated that aggregates amplified from LB-αSyn (ampLB) show distinct biological activities in vitro compared to human αSyn preformed fibrils (hPFF) formed de novo. Here we compare the in vivo biological activities of hPFF and ampLB regarding seeding activity, latency in inducing pathology, distribution of pathology, inclusion morphology, and cell-type preference. Injection of ampLB into mice expressing only human αSyn (male Thy1:SNCA/Snca–/– mice) induced pathologies similar to those of LBD subjects that were distinct from those induced by hPFF-injection or developing spontaneously with aging. Importantly, αSyn aggregates in ampLB-injected Thy1:SNCA/Snca–/– mice maintained the unique biological and conformational features of original LB-αSyn. These results indicate that ampLB-injection, rather than conventional PFF-injection or αSyn overexpression, faithfully models key aspects of LBD.
Structural titration reveals Ca2+-dependent conformational landscape of the IP3 receptor
Authors: Paknejad Navid , Sapuru Vinay , Hite Richard K. 
Published: October 2023

AbstractInositol 1,4,5-trisphosphate receptors (IP3Rs) are endoplasmic reticulum Ca2+ channels whose biphasic dependence on cytosolic Ca2+ gives rise to Ca2+ oscillations that regulate fertilization, cell division and cell death. Despite the critical roles of IP3R-mediated Ca2+ responses, the structural underpinnings of the biphasic Ca2+ dependence that underlies Ca2+ oscillations are incompletely understood. Here, we collect cryo-EM images of an IP3R with Ca2+ concentrations spanning five orders of magnitude. Unbiased image analysis reveals that Ca2+ binding does not explicitly induce conformational changes but rather biases a complex conformational landscape consisting of resting, preactivated, activated, and inhibited states. Using particle counts as a proxy for relative conformational free energy, we demonstrate that Ca2+ binding at a high-affinity site allows IP3Rs to activate by escaping a low-energy resting state through an ensemble of preactivated states. At high Ca2+ concentrations, IP3Rs preferentially enter an inhibited state stabilized by a second, low-affinity Ca2+ binding site. Together, these studies provide a mechanistic basis for the biphasic Ca2+-dependence of IP3R channel activity.
Efficient photocatalytic production of hydrogen peroxide using dispersible and photoactive porous polymers
Authors: Wang Shengdong , Xie Zhipeng , Zhu Da , Fu Shuai , Wu Yishi , Yu Hongling , Lu Chuangye , Zhou Panke , Bonn Mischa , Wang Hai I. , Liao Qing , Xu Hong , Chen Xiong , Gu Cheng 
Published: October 2023

AbstractDeveloping efficient artificial photocatalysts for the biomimetic photocatalytic production of molecular materials, including medicines and clean energy carriers, remains a fundamentally and technologically essential challenge. Hydrogen peroxide is widely used in chemical synthesis, medical disinfection, and clean energy. However, the current industrial production, predominantly by anthraquinone oxidation, suffers from hefty energy penalties and toxic byproducts. Herein, we report the efficient photocatalytic production of hydrogen peroxide by protonation-induced dispersible porous polymers with good charge-carrier transport properties. Significant photocatalytic hydrogen peroxide generation occurs under ambient conditions at an unprecedented rate of 23.7 mmol g–1 h–1 and an apparent quantum efficiency of 11.3% at 450 nm. Combined simulations and spectroscopies indicate that sub-picosecond ultrafast electron “localization” from both free carriers and exciton states at the catalytic reaction centers underlie the remarkable photocatalytic performance of the dispersible porous polymers.
Mapping the spatial heterogeneity of global land use and land cover from 2020 to 2100 at a 1 km resolution
Authors: Zhang Tianyuan , Cheng Changxiu , Wu Xudong 
Published: October 2023

AbstractA fine global future land use/land cover (LULC) is critical for demonstrating the geographic heterogeneity of earth system dynamics and human-earth interaction. In this study, we produced a 1 km global future LULC dataset that takes into account future climate and socio-economic changes as well as the impact of simulated results of the former year on temporally adjacent periods. By incorporating the variations in climatic and socio-economic factors, we differentiated LULC suitability probabilities for historical and future periods across representative SSP-RCP scenarios. Then, by using an improved cellular automata model-PLUS to simulate the patch-level changes of various land classes, we iteratively downscaled water-basin-level LULC demands in various future scenarios to a spatial resolution of 1 km. Our dataset achieves a high degree of simulation accuracy (Kappa = 0.94, OA = 0.97, FoM = 0.10) and precisely captures the spatial-temporal heterogeneity of global LULC changes under the combined effects of climate change and socio-economic development. This robust and fine-scale LULC dataset provides valuable spatially-explicit information essential for earth system modeling and intricate dynamics between anthropogenic activities and the environment.
Shared biomarkers and immune cell infiltration signatures in ulcerative colitis and nonalcoholic steatohepatitis
Authors: Wang Wenxin , Gao Xin , Kang Ning , Wang Chen , Li Chenyang , Yu Huan , Zhang Xiaolan 
Published: October 2023

AbstractThe coexistence of ulcerative colitis (UC) and nonalcoholic steatohepatitis (NASH) involves a intricate interplay, though the precise pathophysiological mechanisms remain elusive. To shed light on this, our study endeavors to unravel the shared gene signatures and molecular mechanisms by employing quantitative bioinformatics analysis on a publicly available RNA-sequencing database. Gene expression profiles of UC (GSE87466) and NASH (GSE89632) were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed using R software. After identifying common DEGs, functional enrichment analysis, protein–protein interaction (PPI) network analysis and module construction were performed to obtain candidate hub genes. GSE47908 for UC and GSE159676 for NASH were selected to validate the obtained candidate genes. A total of 119 common DEGs were found in NASH and UC patients. Functional and pathway analyses emphasized that viral infection, inflammation and immune response were enriched in these two diseases. After module construction and validation, CD2, CD8A, GNLY, IFI44, NKG7 and OAS2 were identified as hub genes. 6 hub genes and their combined prediction scores were found with an impressive accuracy and sensitivity. Functional estimation, gene set enrichment analysis and immune infiltration signature identification showed notable associations of the six hub genes with T cells, natural killer cells and type I interferon levels. In addition, we constructed UC combined with NASH mice model successfully with significantly higher expression of hub genes in both liver and colonic tissues than those in control group. Our study elucidates 6 hub genes of UC and NASH, which may participate in immune, inflammatory and antiviral effects. These findings provide some potential biochemical markers for further exploration of UC coexistence with NASH.
The impact of over-distraction on adjacent segment pathology and cage subsidence in anterior cervical discectomy and fusion
Authors: Hsueh Lan-Li , Yeh Yu-Cheng , Lu Meng-Ling , Luo Chi-An , Chiu Ping-Yeh , Lai Po-Liang , Niu Chi-Chien 
Published: October 2023

AbstractOver-distraction has been shown to be a risk factor for cage subsidence and postoperative neck pain after anterior cervical discectomy and fusion (ACDF). Biomechanical studies have demonstrated increased adjacent segment intradiscal pressure after ACDF. The purpose of this study is to determine if over-distraction of the index disc has an effect on adjacent segment pathology. A consecutive series of 145 patients who received primary ACDF for cervical degenerative pathologies from January 2010 to December 2017 were retrospectively reviewed. The patients were divided into: (1) Over-distraction group (postoperative–preoperative index disc height ≥ 2 mm), and (2) No-distraction group (postoperative–preoperative index disc height < 2 mm). Outcome measures included radiographic parameters, Japanese Orthopaedic Association (JOA) score, and incidences of cage subsidence, radiological and clinical adjacent segment pathologies (RASP and CASP) were compared between the two groups preoperatively, postoperatively, and at the final follow-up. The two groups were comparable with respect to age, follow-up length, JOA score, incidence of CASP, and radiographic parameters. The Over-distraction group (83 patients; 115 levels) had smaller preoperative index disc height (4.5 vs. 5.2 mm, p < 0.001), but taller postoperative index disc height (7.7 vs. 6.6 mm, p < 0.001) than No-distraction group (62 patients; 90 levels) Furthermore, significantly higher incidences of cage subsidence (47% vs. 31%, p = 0.04) and RASP (any progression: 48% vs. 15%, p < 0.001; progress ≥ 2 grades: 25% vs. 7%, p = 0.001) were observed in the Over-distraction group. The multivariate analysis indicated that over-distraction and multilevel fusion were independent risk factors for RASP. There were no clinical outcome differences between the Over-distraction group and the No-distraction group in ACDF. Over-distraction of the index level of ≥ 2 mm should be avoided because it significantly increases the incidences of RASP and cage subsidence.
Fuzzy logic control for watering system
Authors: Neugebauer Maciej , Akdeniz Cengiz , Demir Vedat , Yurdem Hüseyin 
Published: October 2023

AbstractA two-dimensional finite element (FEM) model was developed to simulate water propagation in soil during irrigation. The first dimension was water distribution depth in soil, and the second dimension was time. The developed model was tested by analyzing water distribution in a conventional (clock-controlled) irrigation model. The values in the conventional model were calculated based on the literature. The results were consistent with the results obtained from the model. In the next step, a fuzzy logic model for irrigation control was developed. The input variables were ambient temperature, soil moisture content and time of day (which is related to solar radiation and evapotranspiration), and the output variable was irrigation intensity. The fuzzy logic control (FLC) model was tested by simulating water distribution in soil and comparing water consumption in both models. The study demonstrated that the depth of the soil moisture sensor affected water use in the fuzzy logic-controlled irrigation system relative to the conventional model. Water consumption was reduced by around 12% when the soil moisture sensor was positioned at an optimal depth, but it increased by around 20% when sensor depth was not optimal. The extent to which the distribution of fuzzy variables affects irrigation performance was examined, and the analysis revealed that inadequate distribution of fuzzy variables in the irrigation control system can increase total water consumption by up to 38% relative to the conventional model. It can be concluded that a fuzzy logic-controlled irrigation system can reduce water consumption, but the system’s operating parameters should be always selected based on an analysis of local conditions to avoid an unintended increase in water use. A well-designed FLC can decrease water use in agriculture (thus contributing to rational management of scarce water resources), decrease energy consumption, and reduce the risk of crop pollution with contaminated groundwater.