bluuebunny/crossref_metadata_2025_split huggingface dataset:
The wound severity of animal bite victims visiting rabies prevention clinics and the influencing factors in Central China: a cross-sectional investigation
Authors: Li Dandan , Liao Hanlin , Chen Fan , Jiang Qingqing , Wang Tiantian , Lu Zuxun , Liu Qiaoyan , Cao Shiyi 
Published: November 2021

Abstract
Background
Animal bites are a major public health problem. The more serious the bite wound is, the higher the risk of developing rabies is. This study aimed to investigate the severity of wounds among animal bite victims and identify the influencing factors in Wuhan, China.

Methods
A cross-sectional study was conducted among 1015 animal bite victims visiting rabies prevention clinics. We performed a face-to-face interview to collect information on the exposure category of the bite wound, the type of the offending animal, exposure-to-risk situations, etc. Factors associated with exposure categories were identified by multivariate logistic regression analysis.

Results
Five hundred and sixty-four (55.57%) cases were category III exposures, 418 (41.18%) were category II exposures, and 33 (3.25%) were category I exposures. People who were hurt by their own domestic animals (odds ratio [OR] = 1.55, 95% confidence interval [CI]: 1.14–2.10), and those exposed to animals unvaccinated against rabies (OR = 1.45, 95% CI: 1.08–1.95) had a higher risk for category III exposures. Respondents who did not know the fatality of rabies were more likely to be injured seriously compared to those who knew that rabies is fatal, and the OR was 1.40 (95% CI, 1.05–1.86).

Conclusions
This study showed that factors associated with the severity of bite wounds mainly included types of the offending animal, vaccination status of the animal, and knowledge of rabies fatality. Educational programs and awareness-raising campaigns should be provided to decrease severe animal bites, especially targeting pet owners and those with limited rabies knowledge.
Gallstone disease and nonalcoholic fatty liver disease in patients with type 2 diabetes: a cross-sectional study
Authors: Lu Ye , Hu Lili , Song Jing , Wan Jing , Chen Haibing , Yin Jun 
Published: November 2021

Abstract
Background
Nonalcoholic fatty liver disease (NAFLD) and gallstone disease (GSD) often coexist in the general population owing to shared risk factors. This study explored the relationship between NAFLD and GSD in patients with type 2 diabetes.

Methods
We conducted a retrospective cross-sectional analysis of 4325 patients with type 2 diabetes. GSD and NAFLD were confirmed using ultrasonography. GSD was defined as either asymptomatic gallstones or previous cholecystectomy, and each was analyzed separately.

Result
There was no significant difference in the prevalence of GSD between patients with and without NAFLD (23.8% vs. 21.2%, P = 0.15). After case–control matching (1:1) of baseline data such as age, sex, duration of diabetes, and HbA1c between patients with and without NAFLD, there was still no significant difference in the prevalence of GSD (25.5% vs. 23.6%, P = 0.15). The prevalence of NAFLD in patients with asymptomatic gallstones was lower than that of patients without GSD (38.6% vs. 47.3%, P < 0.001), whereas the prevalence in those who had undergone cholecystectomy was much higher (61.2% vs. 47.3%, P < 0.001). The ratio of cholecystectomy to asymptomatic gallstone in patients with or without NAFLD was 1.97 and 0.79, respectively. The rate of cholecystectomy was higher in the patients with NAFLD than in those without NAFLD (15.8% vs. 9.3%, P < 0.001), consistent with the result after case–control matching (17.3% vs. 11.2%, P < 0.001). Multivariate logistic regression analysis, after adjusting for numerous potential confounding factors, revealed that GSD (OR = 1.241, 95%CI: 1.036–1.488, P = 0.002) and cholecystectomy (OR = 1.946, 95%CI: 1.546–2.445, P < 0.001) were both strongly associated with NAFLD. However, asymptomatic gallstone (OR = 0.663, 95%CI: 0.513–0.856, P = 0.002) seemed to be negatively correlated with NAFLD.

Conclusions
The prevalence of GSD was similar in patients with type 2 diabetes with and without NAFLD. The higher proportion of cholecystectomy and lower proportion of asymptomatic gallstones in patients with NAFLD suggests that NAFLD may increase the risk of complications of GSD.
Impact of cement type and abutment height on pull-off force of zirconia reinforced lithium silicate crowns on titanium implant stock abutments: an in vitro study
Authors: Müller Lisa , Rauch Angelika , Reissmann Daniel R. , Schierz Oliver 
Published: November 2021

Abstract
Background
Pull-off forces of cement-retained zirconia reinforced lithium silicate (ZLS) in implant-supported single crowns on stock titanium abutments with respect to abutment height and implant cement were evaluated and compared.

Methods
Pull-off force of ZLS crowns on stock titanium abutments was evaluated concerning dental cement and abutment height. A total sample size of 64 stock abutments with heights of 3 mm (n = 32) and 5 mm (n = 32) was used. The ZLS crowns were cemented with four different types of cement (one temporary, two semi-permanent, and one permanent). After cementation, water storage, and thermocycling each sample was subjected to a pull-off test using a universal testing machine.

Results
The temporary cement showed the least pull-off force regardless of abutment height (3/5 mm: means 6 N/23 N), followed by the semi-permanent methacrylate-infiltrated zinc oxide cement (28 N/55 N), the semi-permanent methacrylate-based cement (103 N/163 N), and the permanent resin composite cement (238 N/820 N). Results of all types of cement differed statistically significantly from each other (p ≤ .012). The type of implant cement has an impact on the pull-off force of ZLS crowns and titanium abutments.

Conclusions
Permanent cements present higher retention than semi-permanent ones, and temporary cements present the lowest values. The abutment height had a subordinate impact.
Rapidly liver-clearable rare-earth core–shell nanoprobe for dual-modal breast cancer imaging in the second near-infrared window
Authors: Wei Zhuxin , Duan Guangxin , Huang Baoxing , Qiu Shanshan , Zhou Dandan , Zeng Jianfeng , Cui Jiabin , Hu Chunhong , Wang Ximing , Wen Ling , Gao Mingyuan 
Published: November 2021

Abstract
Background
Fluorescence imaging as the beacon for optical navigation has wildly developed in preclinical studies due to its prominent advantages, including noninvasiveness and superior temporal resolution. However, the traditional optical methods based on ultraviolet (UV, 200–400 nm) and visible light (Vis, 400–650 nm) limited by their low penetration, signal-to-noise ratio, and high background auto-fluorescence interference. Therefore, the development of near-infrared-II (NIR-II 1000–1700 nm) nanoprobe attracted significant attentions toward in vivo imaging. Regrettably, most of the NIR-II fluorescence probes, especially for inorganic NPs, were hardly excreted from the reticuloendothelial system (RES), yielding the anonymous long-term circulatory safety issue.

Results
Here, we develop a facile strategy for the fabrication of Nd3+-doped rare-earth core–shell nanoparticles (Nd-RENPs), NaGdF4:5%Nd@NaLuF4, with strong emission in the NIR-II window. What’s more, the Nd-RENPs could be quickly eliminated from the hepatobiliary pathway, reducing the potential risk with the long-term retention in the RES. Further, the Nd-RENPs are successfully utilized for NIR-II in vivo imaging and magnetic resonance imaging (MRI) contrast agents, enabling the precise detection of breast cancer.

Conclusions
The rationally designed Nd-RENPs nanoprobes manifest rapid-clearance property revealing the potential application toward the noninvasive preoperative imaging of tumor lesions and real-time intra-operative supervision.

Graphical abstract
Cell-derived extracellular vesicles and membranes for tissue repair
Authors: Ding Yuan , Li Yanjie , Sun Zhongquan , Han Xin , Chen Yining , Ge Yao , Mao Zhengwei , Wang Weilin 
Published: November 2021

AbstractHumans have a limited postinjury regenerative ability. Therefore, cell-derived biomaterials have long been utilized for tissue repair. Cells with multipotent differentiation potential, such as stem cells, have been administered to patients for the treatment of various diseases. Researchers expected that these cells would mediate tissue repair and regeneration through their multipotency. However, increasing evidence has suggested that in most stem cell therapies, the paracrine effect but not cell differentiation or regeneration is the major driving force of tissue repair. Additionally, ethical and safety problems have limited the application of stem cell therapies. Therefore, nonliving cell-derived techniques such as extracellular vesicle (EV) therapy and cell membrane-based therapy to fulfil the unmet demand for tissue repair are important. Nonliving cell-derived biomaterials are safer and more controllable, and their efficacy is easier to enhance through bioengineering approaches. Here, we described the development and evolution from cell therapy to EV therapy and cell membrane-based therapy for tissue repair. Furthermore, the latest advances in nonliving cell-derived therapies empowered by advanced engineering techniques are emphatically reviewed, and their potential and challenges in the future are discussed.
Graphical Abstract
Cargo proteins in extracellular vesicles: potential for novel therapeutics in non-alcoholic steatohepatitis
Authors: Kim Jimin , Lee Seul Ki , Jeong Seon-Yeong , Cho Hye Jin , Park Joonghoon , Kim Tae Min , Kim Soo 
Published: November 2021

Abstract
Background
Extracellular vesicles (EVs) are recognized as novel cell-free therapeutics. Non-alcoholic steatohepatitis (NASH) remains a critical health problem. Herein, we show that EVs from pan peroxisome proliferator-activated receptor agonist-primed induced mesenchymal stem cell (pan PPAR-iMSC-EVs) has unique cargo protein signatures, and demonstrate its therapeutic function in NASH.

Results
A unique protein signatures were identified in pan PPAR-iMSC-EVs against those from non-stimulated iMSC-EVs. NASH mice receiving pan PPAR-iMSC-EVs showed reduced steatotic changes and ameliorated ER stress and mitochondiral oxidative stress induced by inflammation. Moreover, pan PPAR-iMSC-EVs promoted liver regeneration via inhibiting apoptosis and enhancing proliferation.

Conclusions
We conclude that our strategy for enriching unique cargo proteins in EVs may facilitate the development of novel therapeutic option for NASH.

Graphical Abstract
Engineered extracellular vesicles derived from primary M2 macrophages with anti-inflammatory and neuroprotective properties for the treatment of spinal cord injury
Authors: Zhang Chuanjie , Li Daoyong , Hu Hengshuo , Wang Zhe , An Jinyu , Gao Zhanshan , Zhang Kaihua , Mei Xifan , Wu Chao , Tian He 
Published: November 2021

Abstract
Background
Uncontrollable inflammation and nerve cell apoptosis are the most destructive pathological response after spinal cord injury (SCI). So, inflammation suppression combined with neuroprotection is one of the most promising strategies to treat SCI. Engineered extracellular vesicles with anti-inflammatory and neuroprotective properties are promising candidates for implementing these strategies for the treatment of SCI.

Results
By combining nerve growth factor (NGF) and curcumin (Cur), we prepared stable engineered extracellular vesicles of approximately 120 nm from primary M2 macrophages with anti-inflammatory and neuroprotective properties (Cur@EVs−cl−NGF). Notably, NGF was coupled with EVs by matrix metalloproteinase 9 (MMP9)-a cleavable linker to release at the injured site accurately. Through targeted experiments, we found that these extracellular vesicles could actively and effectively accumulate at the injured site of SCI mice, which greatly improved the bioavailability of the drugs. Subsequently, Cur@EVs−cl−NGF reached the injured site and could effectively inhibit the uncontrollable inflammatory response to protect the spinal cord from secondary damage; in addition, Cur@EVs−cl−NGF could release NGF into the microenvironment in time to exert a neuroprotective effect against nerve cell damage.

Conclusions
A series of in vivo and in vitro experiments showed that the engineered extracellular vesicles significantly improved the microenvironment after injury and promoted the recovery of motor function after SCI. We provide a new method for inflammation suppression combined with neuroprotective strategies to treat SCI.

Graphical Abstract
Impact of oral anticoagulation therapy on postoperative atrial fibrillation outcomes: a systematic review and meta-analysis
Authors: Fragão-Marques Mariana , Teixeira Francisco , Mancio Jennifer , Seixas Nair , Rocha-Neves João , Falcão-Pires Inês , Leite-Moreira Adelino 
Published: November 2021

Abstract
Background
Post-operative atrial fibrillation (POAF) is the most common complication after cardiac surgery. Recent studies had shown this phenomenon is no longer considered transitory and is associated with higher risk of thromboembolic events or death. The aim of this study was to systematically review and analyze previous studies comparing oral anticoagulation therapy with no anticoagulation, regarding these long-term outcomes.

Methods
PubMed/MEDLINE, EMBASE, Web of Science and Cochrane Database were systematically searched to identify the studies comparing the risk of stroke, or thromboembolic events or mortality of POAF patients who received anticoagulation compared with those who were not anticoagulated. Incidence of stroke, thromboembolic events and all-cause mortality were evaluated up to 10 years after surgery. Time-to-event outcomes were collected through hazard ratio (HR) along with their variance and the early endpoints using frequencies or odds ratio (OR). Random effect models were used to compute statistical combined measures and 95% confidence intervals (CI). Heterogeneity was evaluated through Q statistic-related measures of variance (Tau2, I2, Chi-squared test).

Results
Eight observational cohort studies were selected, including 15,335 patients (3492 on Oral Anticoagulants (OAC) vs 11,429 without OAC) that met the inclusion criteria for qualitative synthesis. Patients had a wide gender distribution (38.6–82.3%), each study with a mean age above 65 years (67.5–85). Vitamin K antagonists were commonly prescribed anticoagulants (74.3–100%). OAC was associated with a protective impact on all-cause mortality at a mean of 5.0 years of follow-up (HR is 0.85 [0.72–1.01]; p = 0.07; I2 = 48%). Thromboembolic events did not differ between the two treatment arms (HR 0.68 [0.40–1.15], p = 0.15).

Conclusion
Current literature suggests a possibly protective impact of OAC therapy for all-cause mortality in patients with new-onset atrial fibrillation after cardiac surgery. However, it does not appear to impact thromboembolism rate.
Overexpression of E3 ubiquitin ligase Cbl attenuates endothelial dysfunction in diabetes mellitus by inhibiting the JAK2/STAT4 signaling and Runx3-mediated H3K4me3
Authors: Jin Qingsong , Lin Liangyan , Zhao Tiantian , Yao Xiaoyan , Teng Yaqin , Zhang Dongdong , Jin Yongjun , Yang Meizi 
Published: November 2021

Abstract
Background
Diabetes mellitus (DM), a most common chronic disease, is featured with impaired endothelial function and bioavailability of nitric oxide (NO), while E3 ubiquitin ligase appears to alleviate endothelial dysfunction as a promising option for DM treatment. Herein, we aimed to determine whether E3 ubiquitin ligase casitas B-lineage lymphoma (Cbl) alleviates endothelial dysfunction in DM rats by JAK2/STAT4 pathway.

Methods
A rat model of DM was developed through intraperitoneal injection of streptozotocin, followed by collection of aortic tissues to determine the expression of Cbl, JAK2, runt-related transcription factor 3 (Runx3) and STAT4. Human umbilical vein endothelial cells (HUVECs) were cultured in high glucose (HG) condition to induce DM as an in vitro model. With gain- and loss-function method, we assessed the aberrantly expressed Cb1 on endothelial dysfunction, NO production and apoptosis of HUVECs.

Results
Cbl was reduced in DM rat tissues and HG-induced HUVECs, where JAK2, Runx3 and STAT4 were elevated. It was found that overexpression of Cbl alleviated endothelial dysfunction by increasing NO production and restoring vasodilation and suppressing apoptosis of HUVECs. Mechanistically, Cb1 enhanced JAK2 ubiquitination and decreased JAK2 and STAT4 expression, where STAT4 improved Runx3 expression by regulating histone H3 lysine 4 trimethylation level. Overexpression of JAK2 and STAT4, or Runx3 increased apoptosis of HUVECs, abrogating the effect of Cb1 on endothelial function.

Conclusion
In conclusion, Cbl alleviates endothelial dysfunction by inactivation of the JAK2/STAT4 pathway and inhibition of Runx3 expression in DM. These evidence might underlie novel Cbl-based treatment against DM in the future.
CD4+ effector T cells accelerate Alzheimer’s disease in mice
Authors: Machhi Jatin , Yeapuri Pravin , Lu Yaman , Foster Emma , Chikhale Rupesh , Herskovitz Jonathan , Namminga Krista L. , Olson Katherine E. , Abdelmoaty Mai Mohamed , Gao Ju , Quadros Rolen M. , Kiyota Tomomi , Jingjing Liang , Kevadiya Bhavesh D. , Wang Xinglong , Liu Yutong , Poluektova Larisa Y. , Gurumurthy Channabasavaiah B. , Mosley R. Lee , Gendelman Howard E. 
Published: November 2021

Abstract
Background
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by pathological deposition of misfolded self-protein amyloid beta (Aβ) which in kind facilitates tau aggregation and neurodegeneration. Neuroinflammation is accepted as a key disease driver caused by innate microglia activation. Recently, adaptive immune alterations have been uncovered that begin early and persist throughout the disease. How these occur and whether they can be harnessed to halt disease progress is unclear. We propose that self-antigens would induct autoreactive effector T cells (Teffs) that drive pro-inflammatory and neurodestructive immunity leading to cognitive impairments. Here, we investigated the role of effector immunity and how it could affect cellular-level disease pathobiology in an AD animal model.

Methods
In this report, we developed and characterized cloned lines of amyloid beta (Aβ) reactive type 1 T helper (Th1) and type 17 Th (Th17) cells to study their role in AD pathogenesis. The cellular phenotype and antigen-specificity of Aβ-specific Th1 and Th17 clones were confirmed using flow cytometry, immunoblot staining and Aβ T cell epitope loaded haplotype-matched major histocompatibility complex II IAb (MHCII-IAb–KLVFFAEDVGSNKGA) tetramer binding. Aβ-Th1 and Aβ-Th17 clones were adoptively transferred into APP/PS1 double-transgenic mice expressing chimeric mouse/human amyloid precursor protein and mutant human presenilin 1, and the mice were assessed for memory impairments. Finally, blood, spleen, lymph nodes and brain were harvested for immunological, biochemical, and histological analyses.

Results
The propagated Aβ-Th1 and Aβ-Th17 clones were confirmed stable and long-lived. Treatment of APP/PS1 mice with Aβ reactive Teffs accelerated memory impairment and systemic inflammation, increased amyloid burden, elevated microglia activation, and exacerbated neuroinflammation. Both Th1 and Th17 Aβ-reactive Teffs progressed AD pathology by downregulating anti-inflammatory and immunosuppressive regulatory T cells (Tregs) as recorded in the periphery and within the central nervous system.

Conclusions
These results underscore an important pathological role for CD4+ Teffs in AD progression. We posit that aberrant disease-associated effector T cell immune responses can be controlled. One solution is by Aβ reactive Tregs.

Graphical Abstract
Immune reactivity and host modulatory roles of two novel Haemonchus contortus cathepsin B-like proteases
Authors: Bakshi Mariam , Tuo Wenbin , Aroian Raffi V. , Zarlenga Dante 
Published: November 2021

AbstractBackgroundHaemonchus contortusis a blood-feeding, gastrointestinal nematode (GIN) that causes significant economic losses to the small ruminant industry worldwide. Despite extensive efforts, our understanding of the molecular mechanisms used by GIN to evade host immune responses is limited. Cathepsin B-like proteins (CBPs) are members of the cysteine protease family and are involved in parasite invasion and thus provide viable vaccine candidates.MethodsIn silico comparative analysis was used to identify conserved proteins among a subset of clade V parasitic nematodes with emphasis on blood-feeding worms, among which CBPs appeared prominently. We identified and characterized two novel CBPs designated Hc-CBP-1 and Hc-CBP-2. Rabbit anti-recombinant (r) Hc-CBP-1 and rHc-CBP-2 were used to detect the presence of native proteins in the excretory secretory products (ESP) and in worm tissues of adultH. contortus. Peptide arrays of rHc-CBP-1 and rHc-CBP-2 were screened with the homologous and heterologous anti-sera and with sera from dexamethasone-treated (Dex+) and non-treated (Dex−)H. contortus-infected animals to identify key immunogenic peptides. Gene transcription of Hc-cbp-1and Hc-cbp-2was also performed onH. contortus-infected animals treated with Dex+. Finally, the mature recombinant proteins were used to assess their abilities to modulate cell functions.ResultsImmunohistochemistry showed that both Hc-CBP-1 and Hc-CBP-2 are present on the brush borders of the intestine; Hc-CBP-2 was also present in the hypodermis of the body wall. Peptide displays screened with rabbit anti-rHc-CBP-1 and anti-rHc-CBP-2 revealed regions within the proteins where dominant and overlapping epitopes prevailed. ELISA results were consistent with only Hc-CBP-1 being present inH. contortusadult ESPs.H. contortusfrom Dex+animals exhibited a threefold increase in Hc-cbp-2transcript while Hc-cbp-1expression did not change. In contrast, comparisons of immunoreactivities of rHc-CBP-1 and rHc-CBP-2 peptide arrays to sera from Dex+and Dex−animals primarily showed changes in Hc-CBP-1 binding. Lastly, rHc-CBP-1 suppressed mRNA expression of bovine peripheral blood mononuclear cell cytokines/activation markers, including TNFα, IL-1, IL-6 and CD86.ConclusionsThese results suggest that as secreted and cryptic proteins, respectively, Hc-CBP-1 and Hc-CBP-2 influence cellular and immunological activities that have interesting dynamics during infection and may provide viable immune-related targets for attenuatingH. contortusinfectivity.Graphic Abstract
High-frequency oscillations detected by electroencephalography as biomarkers to evaluate treatment outcome, mirror pathological severity and predict susceptibility to epilepsy
Authors: Sun Yueqian , Ren Guoping , Ren Jiechuan , Wang Qun 
Published: November 2021

AbstractHigh-frequency oscillations (HFOs) in the electroencephalography (EEG) have been extensively investigated as a potential biomarker of epileptogenic zones. The understanding of the role of HFOs in epilepsy has been advanced considerably over the past decade, and the use of scalp EEG facilitates recordings of HFOs. HFOs were initially applied in large scale in epilepsy surgery and are now being utilized in other applications. In this review, we summarize applications of HFOs in 3 subtopics: (1) HFOs as biomarkers to evaluate epilepsy treatment outcome; (2) HFOs as biomarkers to measure seizure propensity; (3) HFOs as biomarkers to reflect the pathological severity of epilepsy. Nevertheless, knowledge regarding the above clinical applications of HFOs remains limited at present. Further validation through prospective studies is required for its reliable application in the clinical management of individual epileptic patients.