bluuebunny/crossref_metadata_2025_split huggingface dataset:
JEM: A joint test to estimate the effect of multiple genetic variants on DNA methylation
Authors: Sarnowski Chloé , Huan Tianxiao , Jain Deepti , Liu Chunyu , Yao Chen , Joehanes Roby , Levy Daniel , Dupuis Josée 
Published: October 2020

AbstractMultiple methods have been proposed to aggregate genetic variants in a gene or a region and jointly test their association with a trait of interest. However, these joint tests do not provide estimates of the individual effect of each variant. Moreover, few methods have evaluated the joint association of multiple variants with DNA methylation. We propose a method based on linear mixed models to estimate the joint and individual effect of multiple genetic variants on DNA methylation leveraging genomic annotations. Our approach is flexible, can incorporate covariates and annotation features, and takes into account relatedness and linkage disequilibrium (LD). Our method had correct Type‐I error and overall high power for different simulated scenarios where we varied the number and specificity of functional annotations, number of causal and total genetic variants, frequency of genetic variants, LD, and genetic variant effect. Our method outperformed the family Sequence Kernel Association Test and had more stable estimations of effects than a classical single‐variant linear mixed‐effect model. Applied genome‐wide to the Framingham Heart Study data, our method identified 921 DNA methylation sites influenced by at least one rare or low‐frequency genetic variant located within 50 kilobases (kb) of the DNA methylation site.
The impact of mental and physical multimorbidity on healthcare utilization and health spending in China: A nationwide longitudinal population‐based study
Authors: Zhao Yang , Zhang Puhong , Oldenburg Brian , Hall Teresa , Lu Shurong , Haregu Tilahun Nigatu , He Li 
Published: October 2020

AbstractBackgroundIn China, little evidence exists on the effect of mental and physical multimorbidity on individuals and the health system. This study aims to examine the prevalence of mental–physical multimorbidity and its impact on health service utilization and health expenditures.MethodsWe conducted a panel study using two waves of data (in 2011 and 2015) from the China Health and Retirement Longitudinal Study, including 10,181 participants aged 45 years and older. Generalized linear regression models were used to assess the association of multimorbidity with total health expenditure and out‐of‐pocket expenditure (OOPE) on outpatient and inpatient care. Random‐effects logistic regression models were used to examine the impact of multimorbidity on outpatient visits, admission to hospital and incidence of catastrophic health expenditure (CHE).ResultsOverall, 3210 participants (31.53% of 10,181) had mental–physical multimorbidity in 2015 in China. Compared to patients with a single physical disease, individuals with physical‐mental multimorbidity had over 150% of the increase in the number of outpatient visits and days of hospitalization. The percentage change of OOPE for outpatient and inpatient care was 156.8% and 163.6%, respectively. Mental–physical multimorbidity was associated with an increased likelihood of experiencing CHE (OR = 2.205, 95% CI = 2.048, 2.051).ConclusionMultimorbidity, particularly mental–physical multimorbidity, is associated with higher levels of health service use and a greater financial burden to individuals in China. Healthcare system needs to shift from single‐disease models to new financing and service delivery models to more effectively manage mental–physical multimorbidity.
Adult neurogenesis alters response to an aversive distractor in a labyrinth maze without affecting spatial learning or memory
Authors: Schoenfeld Timothy J. , Smith Jesse A. , Sonti Anup N. , Cameron Heather A. 
Published: October 2020

AbstractAdult neurogenesis has been implicated in learning and memory of complex spatial environments. However, new neurons also play a role in nonmnemonic behavior, including the stress response and attention shifting. Many commonly used spatial tasks are very simple, and unsuitable for detecting neurogenesis effects, or are aversively motivated, making it difficult to dissociate effects on spatial learning and memory from effects on stress. We have therefore created a novel complex spatial environment, the flex maze, to enable reward‐mediated testing of spatial learning in a flexibly configurable labyrinth. Using a pharmacogenetic method to completely inhibit neurogenesis in adulthood, we found that rats lacking new neurons (TK rats) and wild type controls completed and remembered most mazes equally well. However, control rats were slower to complete peppermint‐scented mazes than other mazes, while neurogenesis‐deficient rats showed no effect of mint on maze behavior, completing these mazes significantly faster than control rats. Additional testing found that wild type and TK rats showed similar detection of, avoidance of, and glucocorticoid response to the mint odor. These results suggest that spatial learning and memory in a labyrinth task is unaffected by the loss of new neurons, but that these cells affect the ability of an aversive stimulus to distract rats from completing the maze.
Demyelinating brain lesions developing in a patient with chronic lymphocytic leukemia shortly after treatment with a fludarabine containing regimen
Authors: Kreiniz Natalia , Garty‐Ofir Maya , Bejar Jacob , Polliack Aaron , Tadmor Tamar 
Published: October 2020

AbstractAutoimmune manifestations are known to occur in patients with chronic lymphocytic leukemia (CLL) and of these hemolytic anemia and immune thrombocytopenia are the most well recognized. Autoimmunity may also be triggered by some of the therapeutic agents used like purine analoges and these events may sometimes be severe and even fatal. Non‐hematological autoimmune stigmata occur far less frequently and are rarely encountered. Here we report a 59 year‐old‐woman, with CLL, who complained of recurrent headache starting 1 month after completing 6 cycles of fludarabine, cyclophosphamide, and rituximab combination therapy. Computed tomography scan of the brain showed a contrast enhancing lesion of 1 cm in diameter, with surrounding edema in the right frontal lobe. Brain MRI revealed ring enhancing lesions in the right frontal lobe and some additional small lesions in the left parietal lobe. Brain biopsy showed an inflammatory demyelinating lesion, not associated with JC virus. The patient subsequently improved after steroid therapy. Currently, after 2 years of follow‐up, she remains in complete hematologic remission, has no neurological deficits, and is carefully followed by a team of neurologists and hematologists. Treating physicians should be aware of this rare autoimmune inflammatory demyelinating lesion which can occur in patients with CLL during the course of treatment and that may be linked to treatment with purine analogues like fludarabine.
Identifying non‐stationary and long‐term river–aquifer interactions as a response to large climatic patterns and anthropogenic pressures using wavelet analysis (Mancha Oriental Aquifer, Spain)
Authors: Dountcheva Iordanka , Sanz David , Cassiraga Eduardo , Galabov Vassil , Gómez‐Alday Juan José 
Published: October 2020

AbstractThe objective of this study was to analyse periodicities and the long‐term variability of monthly Júcar River–Mancha Oriental Aquifer interactions (RAI) and regionally measured precipitation (PP) with special focus on the correlations between these local hydrological variables and the large climatic patterns governing the Iberian Peninsula, represented by their teleconnection indices – the North Atlantic Oscillation index (NAOi) and the Western Mediterranean Oscillation index (WeMOi). To that end, wavelet analysis has been applied since it not only provides insight into the time‐series dynamics but also permits statistical interpretation and correlation analysis. As a result, several periodicities have been detected: intermittent semi‐annual periodicity in PP and the NAOi and annual periodicity in the RAI, NAOi and WeMOi time series. Long cycles (approximately 14 years) are also observed in the PP and WeMOi time series. The cross‐wavelet spectra show a correlation between the RAI and the rest of the variables on the semi‐annual and the annual scales, while wavelet coherence detects common behaviour with longer cycles – 5–6 years between the NAOi and the RAI and cycles of both 1–5 years and 7–10 years between PP and the RAI. Furthermore, results show that the periodicities in the teleconnection indices and precipitation propagate into the RAI with certain lead times: 3 months between the RAI and PP and 6 months between the RAI and the NAOi. The results indicate that the detected periodicities and the coherence between the studied variables could have applications in strategic planning on a river basin scale, taking into account the propagation times and the frequency scale. This methodological approach can be applied into strategic water resource planning independently of the geographical location of the hydrogeological system, the basin size and the climate region.
Myeloid tumor necrosis factor and heme oxygenase‐1 regulate the progression of colorectal liver metastases during hepatic ischemia‐reperfusion
Authors: Germanova Desislava , Keirsse Jiri , Köhler Arnaud , Hastir Jean‐François , Demetter Peter , Delbauve Sandrine , Elkrim Yvon , Verset Laurine , Larbanoix Lionel , Preyat Nicolas , Laurent Sophie , Nedospasov Sergei , Donckier Vincent , Van Ginderachter Jo A. , Flamand Véronique 
Published: October 2020

AbstractThe liver ischemia‐reperfusion (IR) injury that occurs consequently to hepatic resection performed in patients with metastases can lead to tumor relapse for not fully understood reasons. We assessed the effects of liver IR on tumor growth and the innate immune response in a mouse model of colorectal (CR) liver metastasis. Mice subjected to liver ischemia 2 days after intrasplenic injection of CR carcinoma cells displayed a higher metastatic load in the liver, correlating with Kupffer cells (KC) death through the activation of receptor‐interating protein 3 kinase (RIPK3) and caspase‐1 and a recruitment of monocytes. Interestingly, the immunoregulatory mediators, tumor necrosis factor‐α (TNF‐α) and heme oxygenase‐1 (HO‐1) were strongly upregulated in recruited monocytes and were also expressed in the surviving KC following IR. Using TNFflox/flox LysMcre/wt mice, we showed that TNF deficiency in macrophages and monocytes favors tumor progression after IR. The antitumor effect of myeloid cell‐derived TNF involved direct tumor cell apoptosis and a reduced expression of immunosuppressive molecules such as transforming growth factor‐β, interleukin (IL)‐10, inducible nitric oxyde synthase (iNOS), IL‐33 and HO‐1. Conversely, a monocyte/macrophage‐specific deficiency in HO‐1 (HO‐1flox/flox LysMcre/wt) or the blockade of HO‐1 function led to the control of tumor progression post‐liver IR. Importantly, host cell RIPK3 deficiency maintains the KC number upon IR, inhibits the IR‐induced innate cell recruitment, increases the TNF level, decreases the HO‐1 level and suppresses the tumor outgrowth. In conclusion, tumor recurrence in host undergoing liver IR is associated with the death of antitumoral KC and the recruitment of monocytes endowed with immunosuppressive properties. In both of which HO‐1 inhibition would reinforce their antitumoral activity.
A three‐dimensional asymmetric power HEAVY model
Authors: Yfanti Stavroula , Chortareas Georgios , Karanasos Menelaos , Noikokyris Emmanouil 
Published: October 2020

AbstractThis article proposes the three‐dimensional HEAVY system of daily, intra‐daily, and range‐based volatility equations. We augment the bivariate model with a third volatility metric, the Garman–Klass estimator, and enrich the trivariate system with power transformations and asymmetries. Most importantly, we derive the theoretical properties of the multivariate asymmetric power model and explore its finite‐sample performance through a simulation experiment on the size and power properties of the diagnostic tests employed. Our empirical application shows that all three power transformed conditional variances are found to be significantly affected by the powers of squared returns, realized measure, and range‐based volatility as well. We demonstrate that the augmentation of the HEAVY framework with the range‐based volatility estimator, leverage and power effects improves remarkably its forecasting accuracy. Finally, our results reveal interesting insights for investments, market risk measurement, and policymaking.
Momentary task‐values and expectations predict engagement in science among Finnish and Chilean secondary school students
Authors: Salmela‐Aro Katariina , Upadyaya Katja , Cumsille Patricio , Lavonen Jari , Avalos Beatrice , Eccles Jacquelynne 
Published: October 2020

While expectancy‐value‐cost theory predicts that students' task values play an important part in academic engagement, these associations have rarely been tested in science education and are even less studied in authentic classroom situations. The present study examined to what extent momentary task‐values, expectations and costs are associated with students' momentary academic engagement in science classes. Momentary academic engagement was operationalised as energy (give up), dedication (grit) and absorption (flow) components of engagement. Finnish (N = 5891 beeps, 307 students) and Chilean (N = 1931 beeps, 157 students) secondary school students participated in the study using Experience Sampling Method via smartphones. When signalled, students responded to questions via smartphones concerning their momentary task values, expectations, costs and components of engagement in the current activity. The research questions were analysed with multilevel path modelling. The results showed that, for both samples task‐values, expectations and costs were related to energy, dedication and absorption components of engagement in science classes. High momentary task‐values were positively associated with momentary flow and grit; high momentary expectations were positively associated with high grit and low giving up in both samples; and high momentary challenge showed as increases in feelings of giving up.
Partial nephrectomy for a Bosniak IV cystic renal mass mimicking a simple renal cyst adjacent to a solid renal tumor
Authors: Oka Toshiki , Hatano Koji , Okuda Yohei , Asakura Toshihisa , Nakai Yasutomo , Nakayama Masashi , Kakimoto Ken‐ichi , Kubo Chiaki , Nakatsuka Shin‐ichi , Nishimura Kazuo 
Published: October 2020

IntroductionRenal tumors are often associated with renal cysts. Meanwhile, in some cases there are challenging issues of how to diagnose renal cystic tumors and to decide surgical procedures.Case presentationA 75‐year‐old man was referred to our department for a 21‐mm tumor by his left kidney. Contrast‐enhanced computed tomography showed an intense contrast uptake the tumor, which was adjacent to a 64‐mm unilocular renal cyst with no contrasting effects. It was clinically diagnosed as renal cell carcinoma, stage T1aN0M0, and treated with robot‐assisted partial nephrectomy, for both the solid tumor and the adjacent cyst. Pathological findings revealed a tumor cell clump within the cyst wall, concurrent with the renal cell carcinoma. The patient has remained free of disease at 1 year after surgery.ConclusionA partial nephrectomy that includes the entire cyst wall should be considered for renal tumor associated with unilocular renal cyst.
Recent advances in semitransparent perovskite solar cells
Authors: Mujahid Muhammad , Chen Chen , Zhang Jian , Li Chuannan , Duan Yu 
Published: October 2020

AbstractThe environmental challenges across the world step up the researcher's interest in different energy resources. Semitransparent perovskite solar cells (ST‐PSCs) could expedite generation of electricity as well as shows reassuring its significance in flexible electronics and building‐integrating photovoltaic as so forth in the next decade. It is highly recommended to endorse the relevance of semitransparent solar devices to fulfill the required level of energy even by using the roofs and windows of the buildings. In this review article, we pay more attention to recent developments of ST‐PSCs. Herein, a succinct overview of latest research about semitransparent solar cell technologies and ST‐PSCs is summarized. Moreover, the strategies to enhance the transparency of solar cells are described utilizing structure, transparent electrodes, perovskite film formation, tandem solar cells, color tuning, and human eye perception. Last but not least is that the serious concerns about stability of ST‐PSCs are vividly reviewed.image
Therapeutic thrombocytapheresis in myeloproliferative neoplasms: A single‐institution experience
Authors: Nguyen Thanh Ha , Bach Khanh Quoc , Vu Hung Quang , Nguyen Nhat Quoc , Duong Thien Doan , Wheeler Jennifer 
Published: October 2020

AbstractThrombocytosis is usually seen in myeloproliferative neoplasms (MPNs) and associated with thrombohemorrhagic complications. Therapeutic thrombocytapheresis using an automatic cell separator can help to achieve prompt platelet count reduction to decrease the rate of thrombotic events. In this study, we report a single center's experience in managing MPN patients with thrombocytapheresis prior to chemotherapy. Thrombocytapheresis procedures were performed in 185 MPN patients with thrombocytosis between January 2016 and June 2017. The median percentage reduction of platelets was 44.5% and the median percentage removal efficiency was 65.2% for 83 procedures where the waste bag was sampled. Procedures were generally well tolerated with few patients having mild adverse events (13 out of 185 patients).
Self‐esteem and binge eating: Do patients with binge eating disorder endorse more negatively worded items of the Rosenberg Self‐Esteem Scale?
Authors: Lo Coco Gianluca , Salerno Laura , Ingoglia Sonia , Tasca Giorgio A. 
Published: October 2020

AbstractObjectiveSelf‐esteem is a core aspect of eating disorder symptomatology. This study aims to examine whether method effects associated with negatively worded items of the Rosenberg Self‐Esteem Scale (RSES) may interact the negative self‐evaluations experienced by patients with obesity and binge eating disorder (BED). We also examined whether negatively worded items were associated with psychological distress and eating symptoms.MethodFive hundred thirty three female outpatients (mean age: 42.59) with BED (n = 160) or obesity without BED (n = 373) completed the RSES and measures of interpersonal problems, psychological distress, and eating symptoms.ResultsPatients with BED responded more strongly to the negatively worded items of the RSES than those with obesity. The RSES negatively worded item factor was negatively associated with higher interpersonal problems, psychological distress, and binge eating.ConclusionsPatients with BED may be more responsive to negatively phrased items on the RSES consistent with their negative self‐evaluations and self‐perceptions.
Borderline personality disorder and childhood trauma: Exploring the buffering role of self‐compassion and self‐esteem
Authors: Pohl Sina , Steuwe Carolin , Mainz Verena , Driessen Martin , Beblo Thomas 
Published: October 2020

AbstractObjectivesThe aim of the present study was to investigate whether patients with borderline personality disorder (BPD) show lower self‐compassion and self‐esteem than healthy controls and whether patients’ self‐compassion and self‐esteem moderate the association between childhood trauma and the severity of their BPD symptoms.MethodSelf‐reported self‐compassion, self‐esteem, and the current severity of BPD symptoms were assessed in 35 female patients with BPD and 35 age‐matched control participants. Further, traumatic childhood experiences were recorded in the patient group.ResultsPatients with BPD reported significantly lower self‐compassion and self‐esteem compared to healthy controls. In addition, self‐compassion but not self‐esteem moderated the positive correlation between childhood trauma and the severity of BPD symptoms.DiscussionSelf‐compassion appears to buffer the negative consequences of childhood traumatization. Therefore, cultivating self‐compassion may be an important therapeutic aim for patients with BPD.
TRIM4 interacts with TRPM8 and regulates its channel function through K423‐mediated ubiquitination
Authors: Huang Yuan , Li Shunyao , Jia Zhenhua , Li Shi , He Wenzao , Zhou Cefan , Zhang Rui , Xu Rui , Sun Bo , Ali Declan William , Michalak Marek , Chen Xing‐Zhen , Tang Jingfeng 
Published: October 2020

AbstractTransient receptor potential melastatin member 8 (TRPM8), a Ca2+‐permeable nonselective cation channel activated by cold and cooling agents, mediates allodynia. Dysfunction or abnormal expression of TRPM8 has been found in several human cancers. The role of ubiquitination in the regulation of TRPM8 function remains poorly understood. Here, we identified the ubiquitin (Ub)‐ligase E3, tripartite motif‐containing 4 (TRIM4), as a novel interaction partner of TRPM8 and confirmed that the TRIM4–TRPM8 interaction was mediated through the SPRY domain of TRIM4. Patch‐clamp assays showed that TRIM4 negatively regulates TRPM8‐mediated currents in HEK293 cells. Moreover, TRIM4 reduced the expression of TRPM8 on the cell surface by promoting the K63‐linked ubiquitination of TRPM8. Further analyses revealed that the TRPM8 N‐terminal lysine residue at 423 was the major ubiquitination site that mediates its functional regulation by TRIM4. A Ub‐activating enzyme E1, Ub‐like modifier‐activating enzyme 1 (UBA1), was also found to interact with TRPM8, thereby regulating its channel function and ubiquitination. In addition, knockdown of UBA1 impaired the regulation of TRPM8 ubiquitination and function by TRIM4. Thus, this study demonstrates that TRIM4 downregulates TRPM8 via K423‐mediated TRPM8 ubiquitination and requires UBA1 to regulate TRPM8.
Circular RNA CircCDH13 contributes to the pathogenesis of osteoarthritis via CircCDH13/miR‐296‐3p/PTEN axis
Authors: Zhou Zhibin , Ma Jun , Lu Jiajia , Chen Aimin , Zhu Lei 
Published: October 2020

AbstractCircular RNAs (circRNAs) are involved in a variety of human diseases; however, the function of circRNAs in osteoarthritis (OA) remains largely unknown. In this study, we investigated the role of CircCDH13 in OA and its underlying mechanisms. CircRNA expression profiles in OA and normal cartilage tissues were detected by microarray. The expression pattern, functional role, and mechanisms of CircCDH13 in OA were studied in vitro and in vivo. Gain‐of‐function and loss‐of‐function approaches were used to demonstrate the participation of CircCDH13 in OA. The regulatory relationship between CircCDH13 and miR‐296‐3p and miR‐296‐3p and phosphatase and tensin homolog (PTEN) was predicted by bioinformatics and verified by RNA pulldown and luciferase assay. Adeno‐associated virus was also used to reveal the role and mechanisms of CircCDH13 in destabilization of medial meniscus (DMM)‐induced OA mice. The upregulation of CircCDH13 in OA cartilage tissues significantly induces chondrocyte apoptosis, promotes extracellular matrix (ECM) catabolism, and inhibits ECM anabolism. Mechanistically, CircCDH13 contributes to OA pathogenesis by functioning as a sponge of miR‐296‐3p and regulating the miR‐296‐3p‐PTEN pathway. Silencing of CircCDH13 in vivo markedly alleviated DMM‐induced OA in mice. Our study revealed an important role of CircCDH13 in OA pathogenesis. Silencing of CircCDH13 could reduce chondrocyte apoptosis, inhibit ECM catabolism, and promote ECM anabolism through the miR‐296‐3p‐PTEN pathway. It provides a potential target for developing effective interventions in treating OA.