bluuebunny/crossref_metadata_2025_split huggingface dataset:
A composite single-nucleotide polymorphism prediction signature for extranodal natural killer/T-cell lymphoma
Authors: Tian Xiao-Peng , Ma Shu-Yun , Young Ken H. , Ong Choon Kiat , Liu Yan-Hui , Li Zhi-Hua , Zhai Qiong-Li , Huang Hui-Qiang , Lin Tong-Yu , Li Zhi-Ming , Xia Zhong-Jun , Zhong Li-Ye , Rao Hui-Lan , Li Mei , Cai Jun , Zhang Yu-Chen , Zhang Fen , Su Ning , Li Peng-Fei , Zhu Feng , Xu-Monette Zijun Y. , Wong Esther Kam Yin , Ha Jeslin Chian Hung , Khoo Lay Poh , Ai Le , Cheng Run-Fen , Lim Jing Quan , de Mel Sanjay , Ng Siok-Bian , Lim Soon Thye , Cai Qing-Qing 
Published: March 2021

Abstract
Current prognostic scoring systems based on clinicopathologic variables are inadequate in predicting the survival and treatment response of extranodal natural killer/T-cell lymphoma (ENKTL) patients undergoing nonanthracyline-based treatment. We aimed to construct a classifier based on single-nucleotide polymorphisms (SNPs) for improving predictive accuracy and guiding clinical decision making. Data from 722 patients with ENKTL from international centers were analyzed. A 7-SNP–based classifier was constructed using LASSO Cox regression in the training cohort (n = 336) and further validated in the internal testing cohort (n = 144) and in 2 external validation cohorts (n = 142 and n = 100). The 7-SNP–based classifier showed good prognostic predictive efficacy in the training cohort and the 3 validation cohorts. Patients with high- and low-risk scores calculated by the classifier exhibited significantly different progression-free survival (PFS) and overall survival (OS) (all P &lt; .001). The 7-SNP–based classifier was further proved to be an independent prognostic factor by multivariate analysis, and its predictive accuracy was significantly better than clinicopathological risk variables. Application of the 7-SNP–based classifier was not affected by sample types. Notably, chemotherapy combined with radiotherapy significantly improved PFS and OS vs radiotherapy alone in high-risk Ann Arbor stage I patients, whereas there was no statistical difference between the 2 therapeutic modalities among low-risk patients. A nomogram was constructed comprising the classifier and clinicopathological variables; it showed remarkably better predictive accuracy than either variable alone. The 7-SNP–based classifier is a complement to existing risk-stratification systems in ENKTL, which could have significant implications for clinical decision making for patients with ENKTL.
Current evidence for COVID-19 therapies: a systematic literature review
Authors: Welte Tobias , Ambrose Lucy J. , Sibbring Gillian C. , Sheikh Shehla , Müllerová Hana , Sabir Ian 
Published: March 2021

Effective therapeutic interventions for the treatment and prevention of coronavirus disease 2019 (COVID-19) are urgently needed. A systematic review was conducted to identify clinical trials of pharmacological interventions for COVID-19 published between 1 December 2019 and 14 October 2020. Data regarding efficacy of interventions, in terms of mortality, hospitalisation and need for ventilation, were extracted from identified studies and synthesised qualitatively.In total, 42 clinical trials were included. Interventions assessed included antiviral, mucolytic, antimalarial, anti-inflammatory and immunomodulatory therapies. Some reductions in mortality, hospitalisation and need for ventilation were seen with interferons and remdesivir, particularly when administered early, and with the mucolytic drug, bromhexine. Most studies of lopinavir/ritonavir and hydroxychloroquine did not show significant efficacy over standard care/placebo. Dexamethasone significantly reduced mortality, hospitalisation and need for ventilationversusstandard care, particularly in patients with severe disease. Evidence for other classes of interventions was limited. Many trials had a moderate-to-high risk of bias, particularly in terms of blinding; most were short-term and some included low patient numbers.This review highlights the need for well-designed clinical trials of therapeutic interventions for COVID-19 to increase the quality of available evidence. It also emphasises the importance of tailoring interventions to disease stage and severity for maximum efficacy.
Clinical and radiological outcomes of total hip arthroplasty in patients affected by Paget’s disease: a combined registry and single-institution retrospective observational study
Authors: Di Martino Alberto , Coppola Maria Antonietta Rita , Bordini Barbara , Stefanini Niccolò , Geraci Giuseppe , Pilla Federico , Traina Francesco , Faldini Cesare 
Published: March 2021

AbstractBackgroundTotal hip arthroplasty (THA) in patients with Paget’s disease can be associated with technical difficulties related to deformities and altered mechanical bone properties, and hypervascularity leads to significative intra-operative bleeding. The purpose of this registry and single-institution study was to investigate overall survival and causes of failure of THA in pagetic patients, together with an analysis of the clinical and radiological complications.Material and methodsRegistry-based survival and complication analysis, type of fixation, intra- and post-operative complications, clinical (pharmacological history, blood transfusions, Harris hip score [HHS]) and radiographic (cup orientation, stem axial alignment, osteolysis around the cup and the stem and heterotopic ossification [HO]) data were reviewed.ResultsIn total, 66 patients (27 males and 39 females, mean age at surgery 71.1 years for males and 74.8 years for female) from the registry study presented a 10-year survival of 89.5%. In the institutional study, involving 26 patients (14 males and 12 females, 69 years average) and 29 THAs, hip function improved significantly. Average cup orientation was 40.5°, while varus stem alignment was 13.8%. In total, 52% of hips had heterotopic ossifications. Peri-acetabular osteolysis was in 13.8% of implants and in 45% of hips was found around the stem. Allogenic and autologous blood transfusion rate were 68.2% and 31.8%, respectively, with an average transfusion of 2 units of blood (range 1–6 units). HHS improved by an average of 34 points, with excellent result in 64.3% of patients. Two implants failed, one due to traumatic ceramic head fracture 64 months after surgery, and one due to mobilization of the cup on the second post-operative day.ConclusionTHA surgery in Paget’s patients is a safe procedure, and implant survival is only partly affected by bone remodelling and choice of fixation. The post-operative functional outcome is largely similar to that of other patients. Bleeding-related complications are the main complications; a careful pharmacological strategy should be recommended to decrease the risk of transfusions and of HO development.Level of evidenceLevel III
An In-Situ Reaction Route to Molecular Level Dispersed Bisimide and ZnO Nanorod Hybrids with Efficient Photo-Induced Charge Transfer
Authors: Lv Chunzheng , He Lirong , Tang Jiahong , Yang Feng , Zhang Chuhong 
Published: March 2021

AbstractAs an important photoconductive hybrid material, perylene/ZnO has attracted tremendous attention for photovoltaic-related applications, but generally faces a great challenge to design molecular level dispersed perylenes/ZnO nanohybrids due to easy phase separation between perylenes and ZnO nanocrystals. In this work, we reported an in-situ reaction method to prepare molecular level dispersed H-aggregates of perylene bisimide/ZnO nanorod hybrids. Surface photovoltage and electric field-induced surface photovoltage spectrum show that the photovoltage intensities of nanorod hybrids increased dramatically for 100 times compared with that of pristine perylene bisimide. The enhancement of photovoltage intensities resulting from two aspects: (1) the photo-generated electrons transfer from perylene bisimide to ZnO nanorod due to the electric field formed on the interface of perylene bisimide/ZnO; (2) the H-aggregates of perylene bisimide in ZnO nanorod composites, which is beneficial for photo-generated charge separation and transportation. The introduction of ordered self-assembly thiol-functionalized perylene-3,4,9,10-tetracarboxylic diimide (T-PTCDI)/ ZnO nanorod composites induces a significant improvement in incident photo-to-electron conversion efficiency. This work provides a novel mentality to boost photo-induced charge transfer efficiency, which brings new inspiration for the preparation of the highly efficient solar cell.
Immune-related genes of the larval Holotrichia parallela in response to entomopathogenic nematodes Heterorhabditis beicherriana LF
Authors: Li Ertao , Qin Jianhui , Feng Honglin , Li Jinqiao , Li Xiaofeng , Nyamwasa Innocent , Cao Yazhong , Ruan Weibin , Li Kebin , Yin Jiao 
Published: March 2021

Abstract
Background
Entomopathogenic nematodes (EPNs) emerge as compatible alternatives to conventional insecticides in controlling Holotrichia parallela larvae (Coleoptera: Scarabaeidae). However, the immune responses of H. parallela against EPNs infection remain unclear.

Results
In present research, RNA-Seq was firstly performed. A total of 89,427 and 85,741 unigenes were achieved from the midgut of H. parallela larvae treated with Heterorhabditis beicherriana LF for 24 and 72 h, respectively; 2545 and 3156 unigenes were differentially regulated, respectively. Among those differentially expressed genes (DEGs), 74 were identified potentially related to the immune response. Notably, some immune-related genes, such as peptidoglycan recognition protein SC1 (PGRP-SC1), pro-phenoloxidase activating enzyme-I (PPAE-I) and glutathione s-transferase (GST), were induced at both treatment points. Bioinformatics analysis showed that PGRP-SC1, PPAE-I and GST were all involved in anti-parasitic immune process. Quantitative real-time PCR (qRT-PCR) results showed that the three immune-related genes were expressed in all developmental stages; PGRP-SC1 and PPAE-I had higher expressions in midgut and fat body, respectively, while GST exhibited high expression in both of them. Moreover, in vivo silencing of them resulted in increased susceptibility of H. parallela larvae to H. beicherriana LF.

Conclusion
These results suggest that H. parallela PGRP-SC1, PPAE-I and GST are involved in the immune responses to resist H. beicherriana LF infection. This study provides the first comprehensive transcriptome resource of H. parallela exposure to nematode challenge that will help to support further comparative studies on host-EPN interactions.
Structural and functional analysis of tomato sterol C22 desaturase
Authors: Gutiérrez-García Laura , Arró Montserrat , Altabella Teresa , Ferrer Albert , Boronat Albert 
Published: March 2021

Abstract
Background
Sterols are structural and functional components of eukaryotic cell membranes. Plants produce a complex mixture of sterols, among which β-sitosterol, stigmasterol, campesterol, and cholesterol in some Solanaceae, are the most abundant species. Many reports have shown that the stigmasterol to β-sitosterol ratio changes during plant development and in response to stresses, suggesting that it may play a role in the regulation of these processes. In tomato (Solanum lycopersicum), changes in the stigmasterol to β-sitosterol ratio correlate with the induction of the only gene encoding sterol C22-desaturase (C22DES), the enzyme specifically involved in the conversion of β-sitosterol to stigmasterol. However, despite the biological interest of this enzyme, there is still a lack of knowledge about several relevant aspects related to its structure and function.

Results
In this study we report the subcellular localization of tomato C22DES in the endoplasmic reticulum (ER) based on confocal fluorescence microscopy and cell fractionation analyses. Modeling studies have also revealed that C22DES consists of two well-differentiated domains: a single N-terminal transmembrane-helix domain (TMH) anchored in the ER-membrane and a globular (or catalytic) domain that is oriented towards the cytosol. Although TMH is sufficient for the targeting and retention of the enzyme in the ER, the globular domain may also interact and be retained in the ER in the absence of the N-terminal transmembrane domain. The observation that a truncated version of C22DES lacking the TMH is enzymatically inactive revealed that the N-terminal membrane domain is essential for enzyme activity. The in silico analysis of the TMH region of plant C22DES revealed several structural features that could be involved in substrate recognition and binding.

Conclusions
Overall, this study contributes to expand the current knowledge on the structure and function of plant C22DES and to unveil novel aspects related to plant sterol metabolism.
TNF-α - mediated peripheral and central inflammation are associated with increased incidence of PND in acute postoperative pain
Authors: Zhao Yu-fan , Yang Hui-wen , Yang Ting-shun , Xie Wenxiu , Hu Zhong-hua 
Published: March 2021

Abstract
Background
Acute postoperative pain plays an important role in the perioperative neurocognitive disorders (PND). The pathogenesis of PND is still unknown, but it is generally believed that peripheral and central nervous system inflammation play an important role, and acute postoperative pain is also thought to aggravate postoperative inflammatory response. The aim of the present study is to explore the effect of acute postoperative pain on peripheral and central nervous system inflammation and related cognitive impairment behaviour in elderly rats after surgery.

Methods
Rats were assigned into four groups: control, surgery for internal fixation for tibial fracture, surgery with analgesia using intraperitoneal morphine, and morphine without surgery. Pain was assessed by the Subjective Pain Scale. The spatial memory of rats was assessed by the Morris water maze (delayed matching task) from the second day to the seventh day after surgery (POD2-POD7). In part of the rats, the pro-inflammatory cytokines TNF-α in plasma, the medial prefrontal cortex (mPFC), and the hippocampus were determined by ELISA on the POD2. The activation of microglia and the expression of c-Fos in the hippocampal CA1 regions and mPFC were detected by the immunohistochemical method on the POD2.

Results
Acute postoperative pain and spatial memory impairment occurred after operation, and postoperative analgesia could significantly improve the both parameters. Additionally, on the POD2, the levels of TNF-α in plasma, hippocampus and mPFC were significantly increased, while the activation of microglia cells and the expression c-Fos in the hippocampal CA1 regions and mPFC were significantly increased. And postoperative analgesia with morphine significantly inhibited the above reactions.

Conclusion
Our data suggest that acute postoperative pain increases the incidence of perioperative neurocognitive disorders. Peripheral and central nervous system inflammation may be involved in this cognitive impairment. And reducing the intensity of acute postoperative pain may be one of the main preventive strategies for PND.
Acute cannabis intoxication in the emergency department: the effect of legalization
Authors: Baraniecki Robert , Panchal Puru , Malhotra Danya Deepsee , Aliferis Alexandra , Zia Zaka 
Published: March 2021

Abstract
Background
On October 17, 2018, the Cannabis Act decriminalized the recreational use of cannabis in Canada. This study seeks to determine how legalization of cannabis has impacted emergency department (ED) visits for acute cannabis intoxication.

Methods
We conducted a retrospective chart review at an academic ED in Hamilton, Ontario. We assessed all visits with a cannabis-related ICD-10 discharge code 6 months before and after legalization (October 17, 2018) to determine cases of acute cannabis intoxication. The primary outcome was the rate of ED visits. Secondary outcomes included number of visits distributed by age, length of stay, co-ingestions, and clinical course in the emergency department (investigations and treatment).

Results
There was no difference in the overall rate of ED visits following legalization (2.44 vs. 2.94 visits/1000, p = 0.27). However, we noted a 56% increase in visits among adults aged 18–29 (p = 0.03). Following legalization, a larger portion of patients required observation without interventions (25% vs 48%, p < 0.05). Bloodwork and imaging studies decreased (53% vs. 12%, p < 0.05; 29% vs. 2%, p < 0.05); however, treatment with benzodiazepines increased (24% vs. 51%, p < 0.05).

Conclusions
Legalization was not associated with a change in the rate of cannabis-related ED visits in our study. More research is needed regarding changing methods of cannabis ingestion and trends among specific age groups.
Understanding patient journey in ulcerative colitis prior to biologic initiation: a 5-year exploration
Authors: Wang Yiting , Makadia Rupa , Knoll Christopher , Hardin Jill , Voss Erica A. , Fife Daniel , Davis Kourtney , Sloan Sheldon 
Published: March 2021

Abstract
Background
There has been a more pronounced shift toward earlier, more aggressive therapies in Crohn’s disease than in ulcerative colitis (UC). The aim of this study was to describe the pre-biologic treatment and health care experience, including co-morbidities and overall health care utilization, for UC patients who initiated biologic therapies, in the 5 years prior to the initiation of the first biologic agent.

Methods
UC patients who initiated a biologic agent approved for UC between 9/15/2005 and 1/30/2018 were identified from the IBM® MarketScan® Commercial Database, a large US database. The date of the first recorded UC biologic exposure was defined as the index date, and ≥ 5 years of pre-index records were required to evaluate patients’ treatment, disease progression and overall health care utilization prior to initiating biologic agents.

Results
Among the 1891 eligible patients, treatment with oral corticosteroids, 5-aminosalicylates, and other non-biologic immunomodulators, all increased progressively across the 5 years prior to the index. From within year-five to within year-one prior to the index, the median duration of oral corticosteroid treatment increased from 34 to 88 days per year and the proportion of patients who experienced more extensive/pancolitis disease increased from 16 to 59%. Overall, the frequency of all-cause health care visits also increased.

Conclusions
Patients with UC experienced increasing morbidity and treatment burden in the 5 years prior to initiating biologic therapy. To achieve reduced corticosteroids in UC management, better risk stratification is needed to help identify patients for more timely biologic treatment.
Increased mucosal IL-12 expression is associated with relapse of ulcerative colitis
Authors: Uchiyama Kazuhiko , Takagi Tomohisa , Mizushima Katsura , Kajiwara-Kubota Mariko , Kashiwagi Saori , Toyokawa Yuki , Tanaka Makoto , Hotta Yuma , Kamada Kazuhiro , Ishikawa Takeshi , Konishi Hideyuki , Kishimoto Mitsuo , Naito Yuji , Itoh Yoshito 
Published: March 2021

AbstractBackgroundThe role of IL-12/23 in the pathogenesis of ulcerative colitis (UC) is unclear. We analyzed mucosal IL-12/23 expression and its relationship with endoscopic severity, histological activity, and UC relapse.MethodsRectal biopsies were collected from 70 UC patients with clinical remission. IL-12, IL-23, IFN-γ, IL-17A, and IL-17F mRNA expression was measured by real-time PCR. Endoscopic severity and histological activity were evaluated using the Mayo endoscopic subscore (MES) and the Geboes score, respectively.ResultsThe longest follow-up period was 51 months. Thirty-four patients relapsed during the study period. Samples from these subsequently relapsed patients formed the “relapse” group, while those from patients that did not relapse formed the “remission” group. IL-12 (P = 0.0003) and IL-23 (P = 0.014) mRNA expression was significantly higher in the relapse than the remission group. Expression of IL-23 (P = 0.015) but not IL-12 (P = 0.374) was correlated with MES. However, in patients with an MES of 0 and 1, IL-12 expression was statistically higher in the relapse than the remission group (P = 0.0015,P = 0.0342). IL-12 and IL-23 expression did not vary significantly between histologically active and inactive mucosa; both were higher in histologically inactive patients in the remission group (IL-12:P = 0.0002, IL-23:P = 0.046).ConclusionsRectal IL-12 and IL-23 expression was elevated in the relapse group, but IL-12 was more strongly associated with UC relapse, irrespective of endoscopic severity and histological activity. Mucosal IL-12 was elevated in patients with deep mucosal healing. Our results suggest an important role of IL-12 in UC pathogenesis and the molecular mechanism of UC relapse.
First-line oral antiviral therapies showed similar efficacies in suppression of serum HBcrAg in chronic hepatitis B patients
Authors: Mak Lung-Yi , Wong Danny Ka-Ho , Cheung Ka-Shing , Seto Wai-Kay , Fung James , Yuen Man-Fung 
Published: March 2021

Abstract
Background
Serum hepatitis B core-related antigen (HBcrAg) is a potential surrogate marker for intra-hepatic covalently-closed circular DNA in chronic hepatitis B (CHB). We aimed to study the profiles of serum HBcrAg in CHB patients treated with first-line nucleos(t)ide analogues (NA): entecavir (ETV), tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF).

Method
Serum HBcrAg was measured in 120 treatment-naïve CHB patients receiving one of the 3 NAs (ETV: TDF: TAF = 60: 26: 34) using the Lumipulse G HBcrAg assay in a Lumipulse G1200 analyzer (Fujirebio Inc, Toyko, Japan). Serum HBcrAg levels were measured at week 0, week 48 and week 96 of NA therapy.

Results
Among the 120 patients, 67 (55.8%) were hepatitis B e antigen (HBeAg) positive. Both tenofovir and ETV led to significantly lower serum HBcrAg at week 48 and week 96 compared to week 0. There were no significant differences for the magnitude of median HBcrAg decline at week 96 between tenofovir and ETV in HBeAg-positive (2.28 vs. 1.65 log U/mL, p > 0.05) and HBeAg-negative (0.83 vs. 0.54 log U/mL, p > 0.05) patients. TDF and TAF produced no significant differences in the magnitude of median HBcrAg decline at week 96 (HBeAg-positive: 2.63 vs. 1.83, respectively; HBeAg-negative: 1.04 vs. 0.40, respectively; both p > 0.05).

Conclusion
Magnitude of reduction of HBcrAg levels after 2-year first-line treatment did not differ statistically among the current first-line NAs, although HBcrAg reduction was numerically greater in tenofovir-treated group. More long-term studies are essential to determine whether tenofovir exerts a more pronounced effect on HBcrAg.