bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct Oral Anticoagulants as Successful Treatment of Heparin-Induced Thrombocytopenia: A Parisian Retrospective Case Series
Authors: Carré Julie , Guérineau Hippolyte , Le Beller Christine , Mauge Laëtitia , Huynh Benoit , Nili Roya , Planquette Benjamin , Clauser Sylvain , Smadja David M. , Helley Dominique , Lillo-Le Louet Agnès , Gendron Nicolas , Calmette Leyla 
Published: August 2021

Background: Heparin-induced thrombocytopenia (HIT) is a prothrombotic life-threatening disorder caused by an adverse reaction to heparin exposure. In this context, it is imperative to stop heparin immediately and to replace it by a non-heparin anticoagulant therapy. Despite their advantages, the use of direct oral anticoagulants (DOACs) is only emerging for HIT treatment, and their use remains rare.Objective: To improve our knowledge on the emerging role of DOACs as treatment of HIT and give an overview of our local practices in this context.Patients/Methods: This is a multi-centric retrospective case series of HIT patients referred to our Parisian pharmacovigilance network and treated with DOACs.Results: We report the cases of seven patients from four healthcare centers, diagnosed with HIT (4T score ≥ 4, positive anti-PF4/heparin immunoassay and positive serotonin-release assay) and treated with DOACs. After a few days on substitutive parenteral treatment (n = 6) or directly at HIT diagnosis (n = 1), these patients were treated with either rivaroxaban (n = 6) or apixaban (n = 1) during acute HIT phase. Mean time to platelet count recovery after heparin discontinuation was 3.3 days (range 3–5). No patient experienced major or clinically relevant non-major bleeding or thrombosis that could be related to DOAC treatment during follow-up.Conclusions: Our cases studies are consistent with recent guidelines credit to the potential and safe use of DOAC during acute HIT in clinically stable patients.
Ten-Year Changes in Bloodstream Infection With Acinetobacter Baumannii Complex in Intensive Care Units in Eastern China: A Retrospective Cohort Study
Authors: Meng Xiao , Fu Jintao , Zheng Yue , Qin Weidong , Yang Hongna , Cao Dongming , Lu Haining , Zhang Lu , Du Zhiguo , Pang Jiaojiao , Li Wei , Guo Haipeng , Du Juan , Li Chen , Wu Dawei , Wang Hao 
Published: August 2021

Background: There is little evidence on the changing prevalence, microbiological profile, and outcome of nosocomial Acinetobacter baumannii complex (ABC)-caused bloodstream infection (ABCBSI) specified in intensive care units (ICUs) in long-term studies, especially in China.Objective: We aimed to investigate changes in incidence, antibiotic resistance, therapy, and prognosis of ABCBSI in ICUs in eastern China during 2009–2018.Methods: A multicenter retrospective cohort study was conducted, and microbiological and clinical data for patients with ABCBSI acquired in nine adult ICUs in eastern China from 2009 to 2018.Results: A total of 202 cases were enrolled. For the years 2009–2010, 2011–2012, 2013–2014, 2015–2016, and 2017–2018, the incidence of ABCBSI increased significantly, as did the percentage of pan-drug-resistant isolates and resistant rates to most of antimicrobial agents; the percentage of drug-sensitive isolates decreased (all P &lt; 0.05). The frequency of treatment with carbapenems and tigecycline increased, and that of cephalosporins decreased. Compared with those in the first years (2009–2012), ABCBSI patients in the lattermost years (2017–2018) were less often treated with appropriate empirical therapy, more often underwent pneumonia-related ABCBSI and mechanical ventilation support, and had higher 28-day mortality rates. Multivariate Cox regression indicated that increase in the degree of ABC antibiotics resistance, pneumonia-related ABCBSI, and septic shock were risk factors of 28-day mortality and associated with significant lower survival days.Conclusions: The past decade has witnessed a marked increase in the incidence of ABCBSI and in antibiotic resistance, with increasing pneumonia-related infections and worrisome mortality in ICUs in China. Controlling increasing resistance and preventing nosocomial pneumonia may play important roles in combatting these infections.
Retrospective Analysis of the Clinical Efficacy of N-Acetylcysteine in the Treatment of Hepatitis B Virus Related Acute-on-Chronic Liver Failure
Authors: Wang Meng-Lan , Yin Xiu-Jun , Li Xue-Lian , Wang Fa-Da , Zhou Jing , Tao Ya-Chao , Wang Yong-Hong , Wu Dong-Bo , Chen En-Qiang 
Published: August 2021

Objective: HBV-related acute-on-chronic liver failure (HBV-ACLF) has a high mortality due to severe intrahepatic cholestasis and coagulation dysfunction, thus new treatment measures are urgently needed to improve the therapeutic effect. This study aimed to observe the efficacy of N-acetylcysteine (NAC) in the treatment of HBV-ACLF.Methods: The data of patients with HBV-ACLF admitted to West China Hospital from October 2019 to August 2020 were collected retrospectively, and they were divided into treatment group and control group according to whether they had received additional NAC treatment. The improvement of biochemistry, coagulation function and disease severity score after 14 days of hospitalization were analyzed between two groups.Results: A total of 90 HBV-ACLF patients were included, including 42 patients in treatment group and 48 patients in control group. Compared with baseline, serum TBil, DBil, TBA, GGT and ALP in two groups both decreased significantly, while PTA increased significantly. Interesting, the decrease of serum TBil, DBil and TBA and the increase of PTA in treatment group were all significantly than these in control group. Additionally, more patients in treatment group than control group changed from CTP grade C to grade B. Subgroup analysis of CTP grade C patients showed that the decrease of serum TBil, DBil and TBA and the increase of PTA in treatment group were significantly than these in control group.Conclusion: The NAC treatment may help to improve intrahepatic cholestasis and coagulation dysfunction of HBV-ACLF.
Comparison of Carrier and de novo Pathogenic Variants in a Chinese DMD/BMD Cohort
Authors: Lin Jinfu , Li Huan , Liao Ziyu , Wang Liang , Zhang Cheng 
Published: August 2021

Background: Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked recessively inherited neuromuscular disorders caused by deletions, duplications, or small mutations in the DMD gene. With advances in prenatal diagnosis decreasing the number of affected offspring from carrier mothers, the frequency of de novo variants could increase. Therefore, determining the differences between the carrier and de novo variants of the DMD gene, which are rarely explored, is important for trial planning and genetic diagnosis in the future.Methods: A total of 440 patients, 349 of whom had DMD and 91 had BMD, diagnosed in our department between 2012 and 2019, along with their respective mothers, were included in this study. Multiplex ligation-dependent probe amplification was used to detected deletions and duplications in patients and their mothers. Small mutations were detected using next-generation sequencing in the patients, followed by Sanger sequencing in the mothers.Results: Deletions, duplications, and small mutations were identified in 204, 46, and 99 of the 349 patients with DMD and in 50, 10, and 31 of the 91 patients with BMD, respectively. De novo deletions were more concentrated in hotspot regions than carrier deletions of DMD/BMD. No clear bias was observed in the variant distribution between carriers, de novo duplications, and small mutations in DMD/BMD. The carrier frequency of DMD (61.6%) was lower than that of BMD (69.2%), but the difference was not statistically significant. The carrier frequency of deletions of the DMD gene (51.2%) was significantly lower than those of duplications (75%) and small mutations (81.5%).Conclusion: Compared to de novo deletions, deletions from carrier mothers had a wider distribution. Moreover, there was no significant difference between the carrier frequencies of DMD and BMD. Duplications and small mutations were more commonly inherited, while deletions were present de novo.
Impact of Temporal Visual Flicker on Spatial Contrast Sensitivity in Myopia
Authors: Ye Jie , Sinha Pawan , Hou Fang , He Xianghang , Shen Meixiao , Lu Fan , Shao Yilei 
Published: August 2021

PurposeTo investigate whether short-term exposure to high temporal frequency full-field flicker has an impact on spatial visual acuity in individuals with varying degrees of myopia.MethodsThirty subjects (evenly divided between control and experimental groups) underwent a 5-min exposure to full-field flicker. The flicker rate was lower than critical flicker frequency (CFF) for the experimental group (12.5 Hz) and significantly higher than CFF for the controls (60 Hz). Spatial contrast sensitivity function (CSF) was measured before and immediately after flicker exposure. We examined whether the post flicker CSF parameters were different from the pre-exposure CSF values in either of the subject groups. Additionally, we examined the relationship between the amount of CSF change from pre to post timepoints and the degree of subjects’ myopia. The CSF parameters included peak frequency, peak sensitivity, bandwidth, truncation, and area under log CSF (AULCSF).ResultsThere was no significant difference of all five pre-exposure CSF parameters between the two groups at baseline (P = 0.333 ∼ 0.424). Experimental group subjects exhibited significant (P &lt; 0.005) increases in peak sensitivity and AULCSF, when comparing post-exposure results to pre-exposure ones. Controls showed no such enhancements. Furthermore, the extent of these changes in the experimental group was correlated significantly with the participants’ refractive error (P = 0.005 and 0.018, respectively).ConclusionOur data suggest that exposure to perceivable high-frequency flicker (but, not to supra-CFF frequencies) enhances important aspects of spatial contrast sensitivity, and these enhancements are correlated to the degree of myopia. This finding has implications for potential interventions for cases of modest myopia.
The Effects of NT-1044, a Novel AMPK Activator, on Endometrial Cancer Cell Proliferation, Apoptosis, Cell Stress and In Vivo Tumor Growth
Authors: Roque Dario R. , Zhang Lu , Wysham Weiya Z. , Han Jianjun , Sun Wenchuan , Yin Yajie , Livingston James N. , Batchelor Ken W. , Zhou Chunxiao , Bae-Jump Victoria L. 
Published: August 2021

ObjectivesAnti-diabetic biguanide drugs such as metformin may have anti-tumorigenic effects by behaving as AMPK activators and mTOR inhibitors. Metformin requires organic cation transporters (OCTs) for entry into cells, and NT-1044 is an AMPK activator designed to have greater affinity for two of these transporters, OCT1 and OCT3. We sought to compare the effects of NT-1044 on cell proliferation in human endometrial cancer (EC) cell lines and on tumor growth in an endometrioid EC mouse model.MethodsCell proliferation was assessed in two EC cell lines, ECC-1 and Ishikawa, by MTT assay after exposure to NT-1044 for 72 hours of treatment. Apoptosis was analyzed by Annexin V-FITC and cleaved caspase 3 assays. Cell cycle progression was evaluated by Cellometer. Reactive oxygen species (ROS) were measured using DCFH-DA and JC-1 assays. For the in vivo studies, we utilized the LKB1fl/flp53fl/fl mouse model of endometrioid endometrial cancer. The mice were treated with placebo or NT-1044 or metformin following tumor onset for 4 weeks.ResultsNT-1044 and metformin significantly inhibited cell proliferation in a dose-dependent manner in both EC cell lines after 72 hours of exposure (IC50 218 μM for Ishikawa; 87 μM for ECC-1 cells). Treatment with NT-1044 resulted in G1 cell cycle arrest, induced apoptosis and increased ROS production in both cell lines. NT-1044 increased phosphorylation of AMPK and decreased phosphorylation of S6, a key downstream target of the mTOR pathway. Expression of the cell cycle proteins CDK4, CDK6 and cyclin D1 decreased in a dose-dependent fashion while cellular stress protein expression was induced in both cell lines. As compared to placebo, NT-1044 and metformin inhibited endometrial tumor growth in obese and lean LKB1fl/flp53fl/fl mice.ConclusionsNT-1044 suppressed EC cell growth through G1 cell cycle arrest, induction of apoptosis and cellular stress, activation of AMPK and inhibition of the mTOR pathway. In addition, NT-1044 inhibited EC tumor growth in vivo under obese and lean conditions. More work is needed to determine if this novel biguanide will be beneficial in the treatment of women with EC, a disease strongly impacted by obesity and diabetes.
Methyl Jasmonate and Sodium Nitroprusside Jointly Alleviate Cadmium Toxicity in Wheat (Triticum aestivum L.) Plants by Modifying Nitrogen Metabolism, Cadmium Detoxification, and AsA–GSH Cycle
Authors: Kaya Cengiz , Ugurlar Ferhat , Ashraf Muhammad , Noureldeen Ahmed , Darwish Hadeer , Ahmad Parvaiz 
Published: August 2021

The principal intent of the investigation was to examine the influence of joint application of methyl jasmonate (MeJA, 10 μM) and a nitric oxide–donor sodium nitroprusside (SNP, 100 μM) to wheat plants grown under cadmium (Cd as CdCl2, 100 μM) stress. Cd stress suppressed plant growth, chlorophylls (Chl), and PSII maximum efficiency (Fv/Fm), but it elevated leaf and root Cd, and contents of leaf proline, phytochelatins, malondialdehyde, and hydrogen peroxide, as well as the activity of lipoxygenase. MeJA and SNP applied jointly or singly improved the concentrations of key antioxidant biomolecules, e.g., reduced glutathione and ascorbic acid and the activities of the key oxidative defense system enzymes such as catalase, superoxide dismutase, dehydroascorbate reductase, glutathione S-transferase, and glutathione reductase. Exogenously applied MeJA and SNP jointly or singly also improved nitrogen metabolism by activating the activities of glutamine synthetase, glutamate synthase, and nitrate and nitrite reductases. Compared with individual application of MeJA or SNP, the combined application of both showed better effect in terms of improving plant growth and key metabolic processes and reducing tissue Cd content, suggesting a putative interactive role of both compounds in alleviating Cd toxicity in wheat plants.Main findingsThe main findings are that exogenous application of methyl jasmonate and nitric oxide–donor sodium nitroprusside alleviated the cadmium (Cd)–induced adverse effects on growth of wheat plants grown under Cd by modulating key physiological processes and up-regulating enzymatic antioxidants and the ascorbic acid–glutathione cycle–related enzymes.
Causes and Characteristics of Children Unintentional Injuries in Emergency Department and Its Implications for Prevention
Authors: Gong Hairong , Lu Guoping , Ma Jian , Zheng Jicui , Hu Fei , Liu Jing , Song Jun , Hu Shenjie , Sun Libo , Chen Yang , Xie Li , Zhang Xiaobo , Duan Leilei , Xu Hong 
Published: August 2021

Background: Child unintentional injuries have become a hot topic worldwide, and substantial regional disparities existed in causes and characteristics. To date, limited data are available to investigate the causes and characteristics of child unintentional injuries from hospitals for children in China.Methods: A cross-sectional study was conducted between January 2017 and December 2018 in Shanghai, China. Patients aged &lt;18 years with an unintentional injury presented to the emergency department were enrolled. Demographic information, Pediatric Risk for Mortality III score, and outcome variables were retrieved from electronic health records (EHRs). Frequencies and proportions of categorical variables and means and SDs of continuous variables are presented. Chi-square test and Student's t-test were used for the comparison between groups, as appropriate. Logistic regression analysis was used to estimate potential risk factors for admission to the hospital.Results: A total of 29,597 cases with unintentional injuries were identified between January 2017 and December 2018, with boys vs. girls ratio of 1.75. Preschool children account for approximately two-thirds of unintentional injuries in the emergency department. A distinctive pattern of mechanisms of unintentional injuries between gender was documented, and sports injury was significantly higher in boys than in girls (10.2 vs. 7.8%). Compared with Canadian Emergency Department Triage and Acuity Scale (CTAS) Grade 3 patients, Grade 2 [odds ratio (OR) = 2.99, 95% CI = 1.93–4.63, P &lt; 0.001] and Grade 1 (OR = 74.85, 95% CI = 12.93–433.14, P &lt; 0.001) patients had higher risk of inhospital admission. For causes of injuries, compared with falling, foreign body and poison had a lower risk of inhospital admission, while transport injury (OR = 1.31, 95% CI = 1.07–1.59, P = 0.008) and high fall injury (OR = 2.58. 95% CI =1.48–4.49, P &lt; 0.001) had a significantly higher risk of admission.Conclusions: There was a significant relationship between age-groups and unintentional injuries between gender, with decreased injuries among girls growing up older. Preventive measures should be taken to reduce transport injury and high fall injury, which had a significantly higher risk of admission.
Relationship Between Cancer Related Fatigue, Physical Activity Related Health Competence, and Leisure Time Physical Activity in Cancer Patients and Survivors
Authors: Koeppel Maximilian , Körbi Carlotta , Winkels Renate M. , Schmitz Kathryn H. , Wiskemann Joachim 
Published: August 2021

Background: A large body of evidence supports the positive effects of leisure time physical activity (LTPA) and exercise on cancer survivors. However, only a fraction of survivors manages to attain international PA recommendations. This can be attributed to several external and internal barriers toward PA those patients seem to encounter, with cancer related fatigue (CRF) being the most reported internal barrier. Nevertheless, self-efficacy and knowledge about the utilization of LTPA can serve as facilitators of PA, which also correspond to certain constituents of physical activity related health competence (PAHCO). Since PAHCO is not investigated in cancer survivors we investigated if PAHCO can mediate the negative relationship between CRF and LTPA.Methods: We surveyed 398 cancer survivors with different cancer types and therapy status. The patients completed the EORTC QLQ-FA12 (EORTC FA12) to assess CRF, the PAHCO questionnaire to assess PAHCO and the SQUASH to assess LTPA. We followed a two-step structural equation modeling approach. The first step established the measurement model, in the second step we fitted the mediation model. Since 163 patients chose not to answer the SQUASH, the mediation model was only fitted to the data of the remaining 235 participants.Results: The proposed measurement model of the PAHCO offered an excellent fit. We found small to moderate positive associations between the PAHCO dimensions and the LTPA, and negative moderate relationships between the PAHCO and the EORTC FA12 dimensions. We did not observe a relationship between the EORTC FA12 dimensions and the LTPA (p &gt; 0.05). The hypothesized mediation models did not display an appropriate fit.Conclusion: The PAHCO confirmed its factorial validity; furthermore, it appears to have a positive relationship to LTPA. Therefore, integrating psycho-educational aspects can be beneficial in order to increase the PAHCO in exercise interventions. Because of the cross-sectional character of this study, causal conclusions are not suitable, therefore the longitudinal relationships of LTPA, CRF, and PAHCO require further investigation.
Proposed Update to the Taxonomy of Pestiviruses: Eight Additional Species within the Genus Pestivirus, Family Flaviviridae
Authors: Postel Alexander , Smith Donald B. , Becher Paul 
Published: August 2021

Pestiviruses are plus-stranded RNA viruses belonging to the family Flaviviridae. They comprise several important pathogens like classical swine fever virus and bovine viral diarrhea virus that induce economically important animal diseases. In 2017, the last update of pestivirus taxonomy resulted in demarcation of 11 species designated Pestivirus A through Pestivirus K. Since then, multiple new pestiviruses have been reported including pathogens associated with disease in pigs or small ruminants. In addition, pestivirus sequences have been found during metagenomics analysis of different non-ungulate hosts (bats, rodents, whale, and pangolin), but the consequences of this pestivirus diversity for animal health still need to be established. To provide a systematic classification of the newly discovered viruses, we analyzed the genetic relationship based on complete coding sequences (cds) and deduced polyprotein sequences and calculated pairwise distances that allow species demarcation. In addition, phylogenetic analysis was performed based on a highly conserved region within the non-structural protein NS5B. Taking into account the genetic relationships observed together with available information about antigenic properties, host origin, and characteristics of disease, we propose to expand the number of pestivirus species to 19 by adding eight additional species designated Pestivirus L through Pestivirus S.
GPs’ perceptions of their relationship with the pharmaceutical industry: a qualitative study
Authors: Larkin James , Pericin Ivana , Collins Maurice , Smith Susan M , Byrne David , Moriarty Frank 
Published: August 2021

BackgroundThe pharmaceutical industry invests heavily in promoting medications to physicians. This promotion may influence physicians’ prescribing behaviour and lead to inappropriately increased prescribing rates.AimTo understand GPs’ experience of interacting with the pharmaceutical industry, and explore their views and perceptions of the impact of this interaction in general practice in Ireland.Design & settingA qualitative design was used, and GPs practicing in Ireland were eligible.MethodA combination of purposive and snowball sampling techniques was applied and semi-structured interviews were conducted. Thematic analysis was used to develop themes from the data.ResultsTwenty-one GPs and one GP trainee participated. Five themes were developed: 1) GP and pharmaceutical industry interface; 2) the industry’s methods of influence; 3) the uncomfortable relationship between GPs and industry; 4) GPs’ perceptions of being unconsciously influenced; and 5) GPs’ lack of knowledge of relevant regulations.Participants interacted with pharmaceutical representatives in their surgery and through continuing professional development (CPD). Reported methods of influence included biased information and the offer of gifts. Most participants felt their prescribing was unconsciously influenced. A minority felt that they were only influenced in a way that improved their prescribing.ConclusionThe study shows that there can be a lack of clarity among GPs about relevant regulations and about the potential impact on prescribing of interactions with the pharmaceutical industry. Education of trainees and GPs has the potential to address this. Restrictions on interactions with the pharmaceutical industry may also play a role, although alternative CPD funding sources would need to be established.