bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of RIPK1 mediated cell death in acute on chronic liver failure
Authors: Kondo Takayuki , Macdonald Stewart , Engelmann Cornelius , Habtesion Abeba , Macnaughtan Jane , Mehta Gautam , Mookerjee Rajeshwar P. , Davies Nathan , Pavesi Marco , Moreau Richard , Angeli Paolo , Arroyo Vicente , Andreola Fausto , Jalan Rajiv 
Published: December 2021

AbstractAcute-on-chronic liver failure (ACLF) is characterized predominantly by non-apoptotic forms of hepatocyte cell death. Necroptosis is a form of programmed lytic cell death in which receptor interacting protein kinase (RIPK) 1, RIPK3 and phosphorylated mixed lineage kinase domain-like (pMLKL) are key components. This study was performed to determine the role of RIPK1 mediated cell death in ACLF. RIPK3 plasma levels and hepatic expression of RIPK1, RIPK3, and pMLKL were measured in healthy volunteers, stable patients with cirrhosis, and in hospitalized cirrhotic patients with acutely decompensated cirrhosis, with and without ACLF (AD). The role of necroptosis in ACLF was studied in two animal models of ACLF using inhibitors of RIPK1, necrostatin-1 (NEC-1) and SML2100 (RIPA56). Plasma RIPK3 levels predicted the risk of 28- and 90-day mortality (AUROC, 0.653 (95%CI 0.530–0.776), 0.696 (95%CI 0.593–0.799)] and also the progression of patients from no ACLF to ACLF [0.744 (95%CI 0.593–0.895)] and the results were validated in a 2nd patient cohort. This pattern was replicated in a rodent model of ACLF that was induced by administration of lipopolysaccharide (LPS) to bile-duct ligated rats and carbon tetrachloride-induced fibrosis mice administered galactosamine (CCL4/GalN). Suppression of caspase-8 activity in ACLF rodent model was observed suggesting a switch from caspase-dependent cell death to necroptosis. NEC-1 treatment prior to administration of LPS significantly reduced the severity of ACLF manifested by reduced liver, kidney, and brain injury mirrored by reduced hepatic and renal cell death. Similar hepato-protective effects were observed with RIPA56 in a murine model of ACLF induced by CCL4/GalN. These data demonstrate for the first time the importance of RIPK1 mediated cell death in human and rodent ACLF. Inhibition of RIPK1 is a potential novel therapeutic approach to prevent progression of susceptible patients from no ACLF to ACLF.
TCF4 and HuR mediated-METTL14 suppresses dissemination of colorectal cancer via N6-methyladenosine-dependent silencing of ARRDC4
Authors: Wang Hao , Wei Wei , Zhang Zhong-Yuan , Liu Yao , Shi Bin , Zhong Wen , Zhang Hou-Shun , Fang Xin , Sun Chun-Lei , Wang Jia-Bei , Liu Lian-Xin 
Published: December 2021

AbstractMetastasis remains the major obstacle to improved survival for colorectal cancer (CRC) patients. Dysregulation of N6-methyladenosine (m6A) is causally associated with the development of metastasis through poorly understood mechanisms. Here, we report that METTL14, a key component of m6A methylation, is functionally related to the inhibition of ARRDC4/ZEB1 signaling and to the consequent suppression of CRC metastasis. We unveil METTL14-mediated m6A modification profile and identify ARRDC4 as a direct downstream target of METTL14. Knockdown of METTL14 significantly enhanced ARRDC4 mRNA stability relying on the “reader” protein YHTDF2 dependent manner. Moreover, we demonstrate that TCF4 can induce METTL14 protein expression, and HuR suppress METTL14 expression by directly binding to its promoter. Clinically, our results show that decreased METTL14 is correlated with poor prognosis and acts as an independent predictor of CRC survival. Collectively, our findings propose that METTL14 functions as a metastasis suppressor, and define a novel signaling axis of TCF4/HuR-METTL14-YHTDF2-ARRDC4-ZEB1 in CRC, which might be potential therapeutic targets for CRC.
A Japanese boy with double diagnoses of 2p15p16.1 microdeletion syndrome and RP2-associated retinal disorder
Authors: Yamazawa Kazuki , Shimizu Kenji , Ohashi Hirofumi , Haruna Hidenori , Inoue Satomi , Murakami Haruka , Matsunaga Tatsuo , Iwata Takeshi , Tsunoda Kazushige , Fujinami Kaoru 
Published: December 2021

Abstract2p15p16.1 microdeletion syndrome is a recently recognized congenital disorder characterized by developmental delay and dysmorphic features. RP2-associated retinal disorder (RP2-RD) is an X-linked inherited retinal disease with a childhood onset caused by a loss-of-function variant in the RP2 gene. Here, we describe a 14-year-old boy with double diagnoses of 2p15p16.1 microdeletion syndrome and RP2-RD. The recurrence risk of each condition and the indication for potential therapeutic options for RP2-RD are discussed.
An intergenerational androgenic mechanism of female intrasexual competition in the cooperatively breeding meerkat
Authors: Drea Christine M. , Davies Charli S. , Greene Lydia K. , Mitchell Jessica , Blondel Dimitri V. , Shearer Caroline L. , Feldblum Joseph T. , Dimac-Stohl Kristin A. , Smyth-Kabay Kendra N. , Clutton-Brock Tim H. 
Published: December 2021

AbstractFemale intrasexual competition can be intense in cooperatively breeding species, with some dominant breeders (matriarchs) limiting reproduction in subordinates via aggression, eviction or infanticide. In males, such tendencies bidirectionally link to testosterone, but in females, there has been little systematic investigation of androgen-mediated behaviour within and across generations. In 22 clans of wild meerkats (Suricata suricatta), we show that matriarchs 1) express peak androgen concentrations during late gestation, 2) when displaying peak feeding competition, dominance behaviour, and evictions, and 3) relative to subordinates, produce offspring that are more aggressive in early development. Late-gestation antiandrogen treatment of matriarchs 4) specifically reduces dominance behaviour, is associated with infrequent evictions, decreases social centrality within the clan, 5) increases aggression in cohabiting subordinate dams, and 6) reduces offspring aggression. These effects implicate androgen-mediated aggression in the operation of female sexual selection, and intergenerational transmission of masculinised phenotypes in the evolution of meerkat cooperative breeding.
Heterocellular OSM-OSMR signalling reprograms fibroblasts to promote pancreatic cancer growth and metastasis
Authors: Lee Brian Y. , Hogg Elizabeth K. J. , Below Christopher R. , Kononov Alexander , Blanco-Gomez Adrian , Heider Felix , Xu Jingshu , Hutton Colin , Zhang Xiaohong , Scheidt Tamara , Beattie Kenneth , Lamarca Angela , McNamara Mairéad , Valle Juan W. , Jørgensen Claus 
Published: December 2021

AbstractPancreatic ductal adenocarcinoma (PDA) is a lethal malignancy with a complex microenvironment. Dichotomous tumour-promoting and -restrictive roles have been ascribed to the tumour microenvironment, however the effects of individual stromal subsets remain incompletely characterised. Here, we describe how heterocellular Oncostatin M (OSM) - Oncostatin M Receptor (OSMR) signalling reprograms fibroblasts, regulates tumour growth and metastasis. Macrophage-secreted OSM stimulates inflammatory gene expression in cancer-associated fibroblasts (CAFs), which in turn induce a pro-tumourigenic environment and engage tumour cell survival and migratory signalling pathways. Tumour cells implanted in Osm-deficient (Osm−/−) mice display an epithelial-dominated morphology, reduced tumour growth and do not metastasise. Moreover, the tumour microenvironment of Osm−/− animals exhibit increased abundance of α smooth muscle actin positive myofibroblasts and a shift in myeloid and T cell phenotypes, consistent with a more immunogenic environment. Taken together, these data demonstrate how OSM-OSMR signalling coordinates heterocellular interactions to drive a pro-tumourigenic environment in PDA.
Protein engineering strategies for rational immunogen design
Authors: Caradonna Timothy M. , Schmidt Aaron G. 
Published: December 2021

AbstractAntibody immunodominance refers to the preferential and asymmetric elicitation of antibodies against specific epitopes on a complex protein antigen. Traditional vaccination approaches for rapidly evolving pathogens have had limited success in part because of this phenomenon, as elicited antibodies preferentially target highly variable regions of antigens, and thus do not confer long lasting protection. While antibodies targeting functionally conserved epitopes have the potential to be broadly protective, they often make up a minority of the overall repertoire. Here, we discuss recent protein engineering strategies used to favorably alter patterns of immunodominance, and selectively focus antibody responses toward broadly protective epitopes in the pursuit of next-generation vaccines for rapidly evolving pathogens.
Scalp hair sweating as a predictor of hair cortisol level in human compared to obesity and other confounders
Authors: Abdulateef Darya S. 
Published: December 2021

AbstractInconsistent results were found throughout the literature regarding factors affecting hair cortisol levels. Hair cortisol level in humans was not studied for its associations to scalp hair sweating or hair wash frequency in a patient-based way. Factors affecting hair cortisol levels must be precisely known in order to interpret the results correctly. The aims of the study are to assess if BMI, Perceived Stress Scale (PSS), hair wash frequency, and sweating with scalp hair affect hair cortisol levels. It will assess which of these factors are more significant predictors of hair cortisol levels. In a study on healthy adults, information about history, socio-demographics, PSS, hair wash frequency, hair treatment, and scalp hair sweating were collected, and hair samples were taken and analyzed for their hair cortisol level. Associations of hair cortisol levels with each of the variables were investigated and significant predictors of hair cortisol levels among the variables were found. Mean hair cortisol level in the study participants was 16.84 pg/mg hair. Hair cortisol has a significant positive association with weight, BMI, PSS, and scalp hair sweating, p < 0.05. Scalp hair sweating significantly predicts hair cortisol levels by 12.3%, while other variables did not significantly predict hair cortisol levels, p < 0.05. Scalp hair sweating significantly predicts hair cortisol levels. Age, hair wash frequency, hair treatment, and stressful events have no associations with hair cortisol levels. Although BMI and PSS are associated with hair cortisol levels, they do not significantly predict it. Obesity is significantly associated with profuse sweating, thus the increase in hair cortisol levels in obese individuals could partly be the result of a higher incidence of sweating in these individuals. Thus, scalp hair sweating should be taken into consideration during the study and interpretation of hair cortisol levels.
Functional random forests for curve response
Authors: Fu Guifang , Dai Xiaotian , Liang Yeheng 
Published: December 2021

AbstractThe rapid advancement of functional data in various application fields has increased the demand for advanced statistical approaches that can incorporate complex structures and nonlinear associations. In this article, we propose a novel functional random forests (FunFor) approach to model the functional data response that is densely and regularly measured, as an extension of the landmark work of Breiman, who introduced traditional random forests for a univariate response. The FunFor approach is able to predict curve responses for new observations and selects important variables from a large set of scalar predictors. The FunFor approach inherits the efficiency of the traditional random forest approach in detecting complex relationships, including nonlinear and high-order interactions. Additionally, it is a non-parametric approach without the imposition of parametric and distributional assumptions. Eight simulation settings and one real-data analysis consistently demonstrate the excellent performance of the FunFor approach in various scenarios. In particular, FunFor successfully ranks the true predictors as the most important variables, while achieving the most robust variable sections and the smallest prediction errors when comparing it with three other relevant approaches. Although motivated by a biological leaf shape data analysis, the proposed FunFor approach has great potential to be widely applied in various fields due to its minimal requirement on tuning parameters and its distribution-free and model-free nature. An R package named ’FunFor’, implementing the FunFor approach, is available at GitHub.
Degradation dynamics of quantum dots in white LED applications
Authors: Chen Hsiao-Chien , Shabir Abdul , Tan Cher Ming , Singh Preetpal , Lin Jia-Hung 
Published: December 2021

AbstractQuantum Dots (QDs) are being investigated in a hybrid white light LED structure which inculcates phosphor in the package with a blue LED chip as the light source recently. In this work, Zn doped CdS QD with ZnS shell together with green light emission phosphor is used. Upon prolonged operation, degradation of the LEDs due to the degradation of QDs is observed, which can limit its practical applications. The degradation includes intensity reduction as well as blue shift of the emitted wavelength from the white light. Three stages of degradation are observed, namely an enhancement state where light intensity is found to increase, followed by a rapid degradation stage where light intensity decreases rapidly, and finally a slower degradation stage where the degradation rate of light intensity slows down and continues till the end of the test. Through various detail material analysis, with confirmation from the density functional theory (DFT) calculations, we find that the degradation of the LEDs is due to the time evolving degradation of CdS core structure, beginning from the oxidation of sulfur vacancy of CdS QDs by the nearby oxygen atoms as a result of imperfection of the ZnS protective coating around the QDs in the presence of blue light. This oxidation renders a transformation of CdS into CdO at the initial stage. The final stage is the formation of CdSO4 via some intermediate processes.
Synthesis of non-phosphorylated epoxidised corn oil as a novel green flame retardant thermoset resin
Authors: Cabo Maurelio , M. N. Prabhakar , Song Jung-il 
Published: December 2021

AbstractThis study aimed to produce a new potential flame retardant thermoset resin from epoxidised corn oil through a one-pot method using liquid inorganic catalysed with hydrogen peroxide. Using a gas chromatography–mass selective detector, attenuated total reflectance-fourier transform infrared spectroscopy, proton nuclear magnetic resonance imaging, optical microscopy, and scanning emission microscopy, we synthesised a bio-based resin based on newly designed parameters. The flame retardant capacity was fully established using thermogravimetric analysis and a micro calorimeter. The produced epoxidised corn oil had a relative percentage conversion of oxirane of approximately 91.70%, wherein the amount of double bonds converted into epoxides was calculated. A significant reduction from 17 to 40% in peak heat rate release (pHRR) and 26–30% in total heat release was observed, confirming its flame retardant property. Thus, the potential of epoxidised corn oil was demonstrated.
Dynamics of inter-farm transmission of highly pathogenic avian influenza H5N6 integrating vehicle movements and phylogenetic information
Authors: Yoo Dae-Sung , Chun Byung chul , Kim Younjung , Lee Kwang-Nyeong , Moon Oun-Kyoung 
Published: December 2021

AbstractHighly pathogenic avian influenza (HPAI) in poultry holdings commonly spreads through animal trade, and poultry production and health-associated vehicle (PPHaV) movement. To effectively control the spread of disease, it is essential that the contact structure via those movements among farms is thoroughly explored. However, few attempts have been made to scrutinize PPHaV movement compared to poultry trade. Therefore, our study aimed to elucidate the role of PPHaV movement on HPAI transmission. We performed network analysis using PPHaV movement data based on a global positioning system, with phylogenetic information of the isolates during the 2016–2017 HPAI H5N6 epidemic in the Republic of Korea. Moreover, the contribution of PPHaV movement to the spread of HPAI was estimated by Bayesian modeling. The network analysis revealed that there was the relationship between phylogenetic clusters and the contact network via PPHaV movement. Furthermore, the similarity of farm poultry species and the shared integrators between inter-linked infected premises (IPs) were associated with ties within the same phylogenetic clusters. Additionally, PPHaV movement among phylogenetically clustered IPs was estimated to contribute to approximately 30% of HPAI H5N6 infections in IPs on average. This study provides insight into how HPAI spread via PPHaV movement and scientific basis for control strategies.
An atypical class of non-coding small RNAs is produced in rice leaves upon bacterial infection
Authors: Reshetnyak Ganna , Jacobs Jonathan M. , Auguy Florence , Sciallano Coline , Claude Lisa , Medina Clemence , Perez-Quintero Alvaro L. , Comte Aurore , Thomas Emilie , Bogdanove Adam , Koebnik Ralf , Szurek Boris , Dievart Anne , Brugidou Christophe , Lacombe Severine , Cunnac Sebastien 
Published: December 2021

AbstractNon-coding small RNAs (sRNA) act as mediators of gene silencing and regulate plant growth, development and stress responses. Early insights into plant sRNAs established a role in antiviral defense and they are now extensively studied across plant–microbe interactions. Here, sRNA sequencing discovered a class of sRNA in rice (Oryza sativa) specifically associated with foliar diseases caused by Xanthomonas oryzae bacteria. Xanthomonas-induced small RNAs (xisRNAs) loci were distinctively upregulated in response to diverse virulent strains at an early stage of infection producing a single duplex of 20–22 nt sRNAs. xisRNAs production was dependent on the Type III secretion system, a major bacterial virulence factor for host colonization. xisRNA loci overlap with annotated transcripts sequences, with about half of them encoding protein kinase domain proteins. A number of the corresponding rice cis-genes have documented functions in immune signaling and xisRNA loci predominantly coincide with the coding sequence of a conserved kinase motif. xisRNAs exhibit features of small interfering RNAs and their biosynthesis depend on canonical components OsDCL1 and OsHEN1. xisRNA induction possibly mediates post-transcriptional gene silencing but they do not broadly suppress cis-genes expression on the basis of mRNA-seq data. Overall, our results identify a group of unusual sRNAs with a potential role in plant–microbe interactions.
Electrical response of retinal ganglion cells in an N-methyl-N-nitrosourea-induced retinal degeneration porcine model
Authors: Cha Seongkwang , Choi Kwang-Eon , Ahn Jungryul , Yoo Minsu , Jeong Yurim , Kim Seong-Woo , Goo Yong Sook 
Published: December 2021

AbstractRetinal prosthesis is regarded as the treatment for vision restoration in the blind with retinal degeneration (RD) due to the loss of photoreceptors. A strategy for retinal prosthesis is to electrically activate surviving neurons. The retina’s response to electrical stimulation in a larger RD model has not been studied yet. Therefore, in this study, we investigated electrically evoked retinal responses in a previously validated N-methyl-N-nitrosourea (MNU)-induced porcine RD model. Electrically evoked responses were evaluated based on the number of retinal ganglion cell (RGC) spikes via multichannel recordings. Stimulation pulses were applied to degenerative and wild-type retinas with pulse modulation. Compared to wild-type retinas, degenerative retinas showed higher threshold values of pulse amplitude and pulse duration. The rate of increase in the number of RGC spikes relative to stimulus intensity was lower in degenerative retinas than in normal retinas. In severely degenerated retinas, few RGCs showed electrically evoked spikes. Our results suggest that the degenerative porcine retina requires a higher charge than the normal porcine retina. In the early stage of RD, it is easier to induce RGC spikes through electrical stimulation using retinal prosthesis; however, when the degeneration is severe, there may be difficulty recovering patient vision.
Hypoalbuminemia affects one third of acute pancreatitis patients and is independently associated with severity and mortality
Authors: Ocskay Klementina , Vinkó Zsófia , Németh Dávid , Szabó László , Bajor Judit , Gódi Szilárd , Sarlós Patrícia , Czakó László , Izbéki Ferenc , Hamvas József , Papp Mária , Varga Márta , Török Imola , Mickevicius Artautas , Sallinen Ville , Maldonado Elena Ramirez , Galeev Shamil , Mikó Alexandra , Erőss Bálint , Imrei Marcell , Hegyi Péter Jenő , Faluhelyi Nándor , Farkas Orsolya , Kanizsai Péter , Miseta Attila , Nagy Tamás , Hágendorn Roland , Márton Zsolt , Szakács Zsolt , Szentesi Andrea , Hegyi Péter , Párniczky Andrea 
Published: December 2021

AbstractThe incidence and medical costs of acute pancreatitis (AP) are on the rise, and severe cases still have a 30% mortality rate. We aimed to evaluate hypoalbuminemia as a risk factor and the prognostic value of human serum albumin in AP. Data from 2461 patients were extracted from the international, prospective, multicentre AP registry operated by the Hungarian Pancreatic Study Group. Data from patients with albumin measurement in the first 48 h (n = 1149) and anytime during hospitalization (n = 1272) were analysed. Multivariate binary logistic regression and Receiver Operator Characteristic curve analysis were used. The prevalence of hypoalbuminemia (< 35 g/L) was 19% on admission and 35.7% during hospitalization. Hypoalbuminemia dose-dependently increased the risk of severity, mortality, local complications and organ failure and is associated with longer hospital stay. The predictive value of hypoalbuminemia on admission was poor for severity and mortality. Severe hypoalbuminemia (< 25 g/L) represented an independent risk factor for severity (OR 48.761; CI 25.276–98.908) and mortality (OR 16.83; CI 8.32–35.13). Albumin loss during AP was strongly associated with severity (p < 0.001) and mortality (p = 0.002). Hypoalbuminemia represents an independent risk factor for severity and mortality in AP, and it shows a dose-dependent relationship with local complications, organ failure and length of stay.