bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective effect of hawthorn vitexin on the ethanol-injured DNA of BRL-3A hepatocytes
Authors: Ding Chengshi , Shen Henglun , Tian Zhongjing , Kang Meiling , Ma Jing , He Qing , Wang Jinglong , Zhang Yingxia , Deng Yanmei , Wang Deya 
Published: December 2021

Abstract
Vitexin is a natural active ingredient in hawthorn leaves, which has a wide range of anti-tumor effects. This study was conducted to assess the protective effect of hawthorn vitexin on the ethanol-injured DNA of hepatocytes in vitro and to explore its mechanism. The effect of different concentrations of hawthorn vitexin on ethanol-injured hepatocytes was detected via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method to study the protective effect of hawthorn vitexin on ethanol-injured DNA damage in hepatocytes. Single-cell gel electrophoresis was used to observe the effect of hawthorn vitexin on ethanol-induced DNA damage in hepatocytes, and the Olive tail moment was measured. Cell physiological and biochemical indexes, such as superoxide dismutase activity, malonaldehyde content, and glutathione peroxidase activity, were detected with kits. The mRNA expression of the superoxide dismutase gene was measured via real-time quantitative polymerase chain reaction. It was showed that 0.2, 0.4, and 0.8 mg mL−1 hawthorn vitexin could significantly repair hepatocyte growth and ethanol-induced DNA damage. This effect was closely related to the improvement in superoxide dismutase, malonaldehyde, and glutathione peroxidase. Hawthorn vitexin could be used to repair ethanol-injured hepatocytes through antioxidation effects, and showed potential for the treatment of liver injury.
Platelet-associated parameters in patients with psoriasis
Authors: Li Li , Yu Jianxiu , Zhou Zhongwei 
Published: December 2021

Abstract

Background:
The relationship between platelet-associated parameters and psoriasis has been controversial. The purpose of our meta-analysis was to assess whether platelet count, platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), and platelet distribution width (PDW) are associated with psoriasis.

Methods:
We performed a thorough documentation retrieval via PubMed, EMBASE, and Web of Science until June 2021. Pooled standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated using a random-effects model.

Results:
Overall, 22 studies involving 1749 patients with psoriasis and 1538 healthy controls were selected for the meta-analysis. The outcomes showed that platelet count presented non-significant differences between psoriatic patients and normal individuals (SMD = 0.12, 95% CI =  −0.07 to 0.32, P = .210), while PLR (SMD = 0.28, 95% CI = 0.03–0.53, P = .031), MPV (SMD = 0.55, 95% CI = 0.30–0.79, P < .001), and PDW (SMD = 0.29, 95% CI = 0.03–0.55, P = .027) were remarkably greater in the psoriatic patients than in the healthy individuals, and similar results were found in subgroup analyses. The analytical results of susceptibility revealed that the outcomes were robust, and no evidence of substantial publication bias was identified.

Conclusion:
Patients with psoriasis present significantly higher PLR, MPV, and PDW than healthy individuals, suggesting that psoriasis is accompanied by low-grade systemic inflammation and platelet activation.
A promising prognostic signature for lung adenocarcinoma (LUAD) patients basing on 6 hypoxia-related genes
Authors: Luo Jie , Du Xiaotian 
Published: December 2021

Abstract

Background:
Hypoxia signaling plays a critical role in the development of lung adenocarcinoma (LUAD). We herein aimed to explore the prognostic value of hypoxia-related genes and construct the hypoxia-related prognostic signature for LUAD patients.

Methods:
A total of 26 hypoxia-related genes were collected. Five hundred thirteen and 246 LUAD samples were obtained from the Cancer Genome Atlas and Gene Expression Omnibus databases, respectively. Univariate Cox regression and LASSO Cox regression analyses were conducted to screen the hypoxia-related genes associated with the prognosis of LUAD patients, which would be used for constructing prognosis predictive model for LUAD patients. Multivariate Cox regression analysis was done to determine the independent prognostic factors. The Nomogram model was constructed to predict the prognosis of LUAD patients.

Results:
Based on 26 hypoxia-related genes, LUAD samples could be divided into 4 clusters with different prognoses. Among which, 6 genes were included to construct the Risk Score and the LUAD patients with higher Risk Score had worse prognosis. Besides, the Nomogram based on all the independent risk factors could relatively reliably predict the survival probability. And 9 types of immune cells’ infiltration was significantly differential between high and low risk LUAD patients.

Conclusion:
The Risk Score model based on the 6 crucial hypoxia-related genes could relatively reliably predict the prognosis of LUAD patients.
Case report of concomitant avulsion fractures of the medial meniscus and posterior cruciate ligament
Authors: Cengiz Bertan , Karaoglu Sinan 
Published: December 2021

Abstract

Rationale:
Posterior cruciate ligament (PCL) is the strongest ligament of the knee, and avulsion fractures of PCL are a very rare type of injury. These injuries occur as a result of high-energy traumas, and different accompanying pathologies may be seen. However, tibial avulsion fracture of the PCL associated with a medial meniscus (MM) avulsion fracture has never been reported before. We want to present this unique type of posteromedial knee injury as a case report.

Patient concern:
A 42-year-old man presented with severe pain and swelling due to a ski injury.

Diagnosis:
Concomitant avulsion fractures of PCL and MM were detected after imaging.

Interventions:
Both avulsion fractures were treated with open reduction and fixation with lag screws using the posterior approach.

Outcomes:
No complications were encountered, and the painless full range of motion and weight-bearing was achieved at the third month after the operation.

Lessons:
Anatomical reduction and stable fixation of these intra-articular fractures are essential for the stability of the knee. The posterior approach should be kept in mind to access these types of fractures safely. Care should be taken in terms of other injuries that may accompany the PCL avulsion fractures caused by high-energy traumas.
Evaluation of the effectiveness and safety of icariin in the treatment of knee osteoarthritis
Authors: Liu Lang , Zhao Changwei , Zhao Shuang , Xu Hanxun , Peng Zeyu , Zhang Binghua , Cai Wenjun , Mo Yifang , Zhao Wenhai 
Published: December 2021

Abstract

Background:
Knee osteoarthritis (KOA) is a chronic degenerative disease involving cartilage and surrounding tissues. It causes a huge burden to social and medical resources and seriously affects people's living and working ability. In recent years, people have become increasingly interested in the application of Chinese medicine monomers to treat KOA. Among them, icariin plays an important role in the clinical treatment of KOA. Therefore, to evaluate the effectiveness and safety of icariin in the treatment of KOA, we conducted this study to provide a new basis for the clinical treatment of KOA.

Methods:
We propose a systematic search of the PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and China Biomedical databases for all randomized controlled trials examining the use of icariin in the treatment of KOA patients up to October 20, 2021. The screening and data extraction processes will be performed independently by 2 researchers. We will use the Cochrane risk bias assessment tool to evaluate the quality of the studies that met the inclusion criteria. The data will be statistically analyzed using RevMan5.3 software.

Result:
This study will provide high-quality evidence for the effectiveness and safety of icariin in the treatment of KOA.

Conclusion:
The purpose of this study was to explore the efficacy of icariin in the treatment of KOA and to provide clinicians and patients with new treatment strategies.

INPLASY registration number:
INPLASY2021110015.
Sex-related differences in mortality, acute kidney injury, and respiratory failure among critically ill patients with COVID-19
Authors: Toth-Manikowski Stephanie M. , Caldwell Jillian , Joo Min , Chen Jinsong , Meza Natalie , Bruinius Jacob , Gupta Shruti , Hannan Mary , Kagalwalla Mustafa , Madrid Samantha , Melamed Michal L. , Pacheco Esther , Srivastava Anand , Viamontes Christopher , Lash James P. , Leaf David E. , Ricardo Ana C. 
Published: December 2021

Abstract
Although the number of deaths due to coronavirus disease 2019 (COVID-19) is higher in men than women, prior studies have provided limited sex-stratified clinical data.
We evaluated sex-related differences in clinical outcomes among critically ill adults with COVID-19.
Multicenter cohort study of adults with laboratory-confirmed COVID-19 admitted to intensive care units at 67 U.S. hospitals from March 4 to May 9, 2020. Multilevel logistic regression was used to evaluate 28-day in-hospital mortality, severe acute kidney injury (AKI requiring kidney replacement therapy), and respiratory failure occurring within 14 days of intensive care unit admission.
A total of 4407 patients were included (median age, 62 years; 2793 [63.4%] men; 1159 [26.3%] non-Hispanic White; 1220 [27.7%] non-Hispanic Black; 994 [22.6%] Hispanic). Compared with women, men were younger (median age, 61 vs 64 years, less likely to be non-Hispanic Black (684 [24.5%] vs 536 [33.2%]), and more likely to smoke (877 [31.4%] vs 422 [26.2%]). During median follow-up of 14 days, 1072 men (38.4%) and 553 women (34.3%) died. Severe AKI occurred in 590 men (21.8%), and 239 women (15.5%), while respiratory failure occurred in 2255 men (80.7%) and 1234 women (76.5%). After adjusting for age, race/ethnicity and clinical variables, compared with women, men had a higher risk of death (OR, 1.50, 95% CI, 1.26–1.77), severe AKI (OR, 1.92; 95% CI 1.57–2.36), and respiratory failure (OR, 1.42; 95% CI, 1.11–1.80).
In this multicenter cohort of critically ill adults with COVID-19, men were more likely to have adverse outcomes compared with women.
Do patients at high risk for Hepatitis C receive recommended testing? A retrospective cohort study of statewide Medicaid claims linked with OneFlorida clinical data
Authors: Mkuu Rahma S. , Shenkman Elizabeth A. , Muller Keith E. , Huo Tianyao , Salloum Ramzi G. , Cabrera Roniel , Zarrinpar Ali , Thomas Emmanuel , Szurek Sarah M. , Nelson David R. 
Published: December 2021

Abstract
Hepatitis C virus (HCV) infection is a leading risk factor for hepatocellular carcinoma.
We employed a retrospective cohort study design and analyzed 2012–2018 Medicaid claims linked with electronic health records data from the OneFlorida Data Trust, a statewide data repository containing electronic health records data for 15.07 million Floridians from 11 health care systems. Only adult patients at high-risk for HCV (n = 30,113), defined by diagnosis of: HIV/AIDS (20%), substance use disorder (64%), or sexually transmitted infections (22%) were included. Logistic regression examined factors associated with meeting the recommended sequence of HCV testing.
Overall, 44.1% received an HCV test. The odds of receiving an initial test were significantly higher for pregnant females (odds ratio [OR]1.99; 95% confidence interval [CI] 1.86–2.12; P < .001) and increased with age (OR 1.01; 95% CI 1.00–1.01; P < .001).Among patients with low Charlson comorbidity index (CCI = 1), non-Hispanic (NH) black patients (OR 0.86; 95% CI 0.81–0.9; P < .001) had lower odds of getting an HCV test; however, NH black patients with CCI = 10 had higher odds (OR 1.41; 95% CI 1.21–1.66; P < .001) of receiving a test. Of those who tested negative during initial testing, 17% received a second recommended test after 6 to 24 months. Medicaid-Medicare dual eligible patients, those with high CCI (OR 1.14; 95% CI 1.11–1.17; P < .001), NH blacks (OR 1.93; 95% CI 1.61–2.32; P < .001), and Hispanics (OR 1.49; 95% CI 1.08–2.06; P = .02) were significantly more likely to have received a second HCV test, while pregnant females (OR 0.71; 95% CI 0.57–0.89; P = .003), had lower odds of receiving it. The majority of patients who tested positive during the initial test (97%) received subsequent testing.
We observed suboptimal adherence to the recommended HCV testing among high-risk patients underscoring the need for tailored interventions aimed at successfully navigating high-risk individuals through the HCV screening process. Future interventional studies targeting multilevel factors, including patients, clinicians and health systems are needed to increase HCV screening rates for high-risk populations.
Shoulder pain across more movements is not related to more rotator cuff tendon findings in people with chronic shoulder pain diagnosed with subacromial pain syndrome
Authors: Alaiti Rafael Krasic , Caneiro J.P. , Gasparin Juliana T. , Chaves Thais Cristina , Malavolta Eduardo A. , Gracitelli Mauro E.C. , Meulders Ann , Costa Marcelo Fernandes da 
Published: December 2021

Abstract

Introduction:
People with chronic shoulder pain commonly report pain during arm movements in daily-life activities. Pain related to movement is commonly viewed as an accurate representation of tissue damage. Thus, when a person reports pain across a variety of movements, this is often understood as indicative of greater damage.

Objectives:
We aimed to investigate if movement-related pain that occurs across a wider variety of movements was associated with the number or severity of rotator cuff tendons reported as abnormal on a magnetic resonance imaging (MRI). To answer this question, this study was designed in 3 phases.

Methods:
We recruited 130 individuals with chronic shoulder pain diagnosed with subacromial pain syndrome. First, a list of daily functional activities commonly reported as painful by people with chronic shoulder pain was generated from 3 well-established outcome measures with 30 individuals and a measurement tool was developed with data from further 100 individuals, which demonstrated to have acceptable content validity, construct validity, internal consistency, interrater reliability, and structural validity. Multiple linear regression was then used to evaluate the hypotheses of the study. A direct acyclic graph was used to select variables for linear regression modelling.

Results:
There was no association between movement-related pain occurrence across movements and the MRI findings.

Conclusion:
Our study provides evidence that neither the number of rotator cuff tendons reported as abnormal nor the severity of each tendon imaging finding were associated with pain occurrence across movements and activities commonly perceived as painful by people with chronic shoulder pain.
Spinal integration of hot and cold nociceptive stimuli by wide-dynamic-range neurons in anesthetized adult rats
Authors: Gieré Clémence , Melchior Meggane , Dufour André , Poisbeau Pierrick 
Published: December 2021

Abstract

Introduction:
Early neuronal processing of thermal noxious information relies mostly on molecular detectors of the transient receptor potential family expressed by specific subpopulation of sensory neurons. This information may converge to second-order wide-dynamic-range (WDR) neurons located in the deep layer of the dorsal horn of the spinal cord.

Method:
Using a micro-Peltier thermode thermal contact stimulator II delivering various cold and hot noxious stimulations, we have characterized the extracellular electrophysiological responses of mechanosensitive WDR neurons in anesthetized adult male and female Wistar rats.

Results:
Most of the WDR neurons were activated after hot and cold noxious stimulations, at mean temperature thresholds corresponding to 43 and 20°C, respectively. If the production of action potential was not different in frequency between the 2 thermal modalities, the latency to observe the first action potential was significantly different (cold: 212 ms; hot: 490 ms, unpaired Student t-test: t = 8.041; df = 32; P < 0.0001), suggesting that different fiber types and circuits were involved. The temporal summation was also different because no facilitation was seen for cold noxious stimulations contrary to hot noxious ones.

Conclusion:
Altogether, this study helps better understand how short-lasting and long-lasting hot or cold noxious stimuli are integrated by mechanosensitive WDR neurons. In our experimental conditions, we found WDR neurons to be nociceptive specific for C-fiber–mediated hot stimuli. We also found that cold nonnoxious and noxious information, triggered at glabrous skin areas, are likely taken in charge by A-type sensory neurons. This study will be helpful to establish working hypothesis explaining the thermal pain symptoms displayed by animal models and patients in a translational extent.
Farnesol abrogates biofilm- and efflux pump- associated genes in drug resistant Candida auris strains
Authors: Srivastava Vartika , Ahmad Aijaz 
Published: December 2021

Background:

Candida auris, a decade old Candida species, has been identified globally as a significant nosocomial multidrug resistant (MDR) pathogen responsible for causing invasive outbreaks. Biofilms and over expression of efflux pumps such as Major Facilitator Superfamily and ATP Binding Cassette are known to cause multidrug resistance in Candida species, including C. auris. Therefore, targeting these factors may prove an effective approach to combat MDR in C. auris.

Methods:
In this study, 25 clinical isolates of C. auris from different hospitals of South Africa were used. Antifungal susceptibility profile of all the isolates against commonly used drugs was determined following CLSI recommended guidelines. Rhodamine-6-G extracellular efflux and intracellular accumulation assays were used to study active drug efflux mechanism. We further studied the role of farnesol in modulating development of biofilms and drug efflux in C. auris. Down-regulation of biofilm- and efflux pump- associated genes by farnesol was also investigated. CLSM analysis for examining C. auris biofilm architecture among treated and untreated isolates.

Results:
Most of the isolates (twenty-two) were found resistant to FLZ whereas five were resistant to AmB. All the isolates were found capable of biofilm formation and ornamented with active drug efflux mechanism. The MIC for planktonic cells ranged from 62.5-125 mM and for sessile cells was 125 mM (0 h and 4 h biofilm) and 500 mM (12 h and 24 h biofilm), CLSM studies also confirmed these findings. Farnesol also blocked efflux pumps and down-regulated biofilm- and efflux pump- associated genes.

Conclusion:
Modulation of biofilm- and efflux pump- associated genes by farnesol represent a promising approach in combating C. auris infection.
Precise editing using CRISPR-Cas9 to explore the contribution of clinically-derived mutations to antifungal resistance in the pathogenic yeast Candida parapsilosis
Authors: Hartuis Sophie , Robert Estelle , Lombardi Lisa , Butler Geraldine , Le Pape Patrice , Morio Florent 
Published: December 2021

Introduction

Candida parapsilosis is both a commensal/saprophytic yeast of the human skin and an opportunistic pathogen which can be responsible for life-threatening infections. The increasing reports of clonal outbreaks involving azole-resistant C. parapsilosis in the clinical setting is worrisome and urges for a better understanding of antifungal resistance in this species. Previous studies have identified mutations in key genes which can explain acquired fluconazole resistance. Reverse genetics approaches are now warranted to confirm their involvement and to determine whether they can affect other clinically-licensed antifungals. Here, we used a CRISPR-Cas9 technique to study the relative contributions of clinically-derived mutations to antifungal resistance and provide answers to these questions.

Materials and Methods
Six clinically-derived mutations were selected (ERG11Y132F, ERG11K143R,ERG11R398I, TAC1G650E, MRR1G583R, ERG3G111R) to be engineered in two C. parapsilosis fluconazole-susceptible backgrounds (ATCC22019, STZ5) using a previously described CRISPR-Cas9 method. In vitro susceptibility of the transformants to fluconazole, voriconazole, posaconazole, isavuconazole and micafungin was determined by Etest®.

Results/Discussion
The impact on fluconazole susceptibility was highly variable depending on the residue/gene involved, but roughly similar between the two genetic backgrounds. All but two(ERG11R398I, ERG3G111R) conferred fluconazole resistance, though the highest MIC increase was observed for MRR1G583R (≥650 fold). As expected in a diploid species, we noted an impact of allelic dosage. Some kind of cross-resistance to the other azoles was noted from some mutations, although the impact was lower for posaconazole and isavuconazole, except for MRR1G583R which led to multi-azole resistance. Finally, ERG3G111R increased tolerance to both azoles and echinocandins.
The effect of acquired triazole resistance on abiotic stress tolerance and virulence in Candida auris micro evolved strains
Authors: Bohner Flora , Papp Csaba , Varga Mónika , Szekeres András , Tóth Renáta , Gacser Attila 
Published: December 2021

Recently, C. auris become one of the most prominent members of the genus Candida. Since its occurrence, several C. auris outbreaks have been reported worldwide. These outbreaks were associated with isolates displaying decreased susceptibility towards fluconazole, the first-line agent for prophylaxis. Fluconazole is the most frequently used antifungal drug to treat bloodstream Candida infections.
The physiological effects of acquired antifungal resistance was investigated in this species using fluconazole, posaconazole and voriconazole resistant mutant strains generated by the in vitro microevolution method. Alterations in antifungal susceptibility and cross resistance were determined by the microdilution method, utilizing azoles (fluconazole, voriconazole, posaconazole), echinocandins (caspofungin, micafungin, anidulafungin) and a polyene (amphotericin B). Changes in the abiotic stress tolerance was examined by spotting assay, using osmotic stressors, cell wall perturbants and a membrane detergent. To evaluate the impact of the acquired resistance on sterol biosynthesis, ergosterol composition of all generated mutant strains were examined. A potential relationship between virulence and acquired antifungal resistance was also studied both in vitro and in vivo. Phagocytosis of the generated strains by J774.2 mouse macrophage-like cells was measured and analyzed by flow cytometry. In the murine infection model fungal burden of the triazole evolved strains was determined in spleen, kidney, liver and brain and compared to the fungal burden associated with the initial azole susceptible strain. Significant differences in virulence of the initial and the generated strains was observed suggesting a potential connection between the virulence and antifungal susceptibility of the emerging fungal pathogen, C. auris.