bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biocide-Induced Emergence of Antibiotic Resistance in Escherichia coli
Authors: Merchel Piovesan Pereira Beatriz , Wang Xiaokang , Tagkopoulos Ilias 
Published: February 2021

Biocide use is essential and ubiquitous, exposing microbes to sub-inhibitory concentrations of antiseptics, disinfectants, and preservatives. This can lead to the emergence of biocide resistance, and more importantly, potential cross-resistance to antibiotics, although the degree, frequency, and mechanisms that give rise to this phenomenon are still unclear. Here, we systematically performed adaptive laboratory evolution of the gut bacteria Escherichia coli in the presence of sub-inhibitory, constant concentrations of ten widespread biocides. Our results show that 17 out of 40 evolved strains (43%) also decreased the susceptibility to medically relevant antibiotics. Through whole-genome sequencing, we identified mutations related to multidrug efflux proteins (mdfA and acrR), porins (envZ and ompR), and RNA polymerase (rpoA and rpoBC), as mechanisms behind the resulting (cross)resistance. We also report an association of several genes (yeaW, pyrE, yqhC, aes, pgpA, and yeeP-isrC) and specific mutations that induce cross-resistance, verified through mutation repairs. A greater capacity for biofilm formation with respect to the parent strain was also a common feature in 11 out of 17 (65%) cross-resistant strains. Evolution in the biocides chlorophene, benzalkonium chloride, glutaraldehyde, and chlorhexidine had the most impact in antibiotic susceptibility, while hydrogen peroxide and povidone-iodine the least. No cross-resistance to antibiotics was observed for isopropanol, ethanol, sodium hypochlorite, and peracetic acid. This work reinforces the link between exposure to biocides and the potential for cross-resistance to antibiotics, presents evidence on the underlying mechanisms of action, and provides a prioritized list of biocides that are of greater concern for public safety from the perspective of antibiotic resistance.Significance StatementBacterial resistance and decreased susceptibility to antimicrobials is of utmost concern. There is evidence that improper biocide (antiseptic and disinfectant) use and discard may select for bacteria cross-resistant to antibiotics. Understanding the cross-resistance emergence and the risks associated with each of those chemicals is relevant for proper applications and recommendations. Our work establishes that not all biocides are equal when it comes to their risk of inducing antibiotic resistance; it provides evidence on the mechanisms of cross-resistance and a risk assessment of the biocides concerning antibiotic resistance under residual sub-inhibitory concentrations.
Arm-Hand Boost Therapy During Inpatient Stroke Rehabilitation: A Pilot Randomized Controlled Trial
Authors: Meyer Sarah , Verheyden Geert , Kempeneers Kristof , Michielsen Marc 
Published: February 2021

Objective: It was the aim to assess feasibility, safety, and potential efficacy of a new intensive, focused arm-hand BOOST program and to investigate whether there is a difference between early vs. late delivery of the program in the sub-acute phase post stroke.Methods: In this pilot RCT, patients with stroke were randomized to the immediate group (IG): 4 weeks (4 w) BOOST +4 w CONTROL or the delayed group (DG): 4 w CONTROL +4 w BOOST, on top of their usual inpatient care program. The focused arm-hand BOOST program (1 h/day, 5x/week, 4 weeks) consisted of group exercises with focus on scapula-setting, core-stability, manipulation and complex ADL tasks. Additionally, 1 h per week the Armeo®Power (Hocoma AG, Switzerland) was used. The CONTROL intervention comprised a dose-matched program (24 one-hour sessions in 4 w) of lower limb strengthening exercises and general reconditioning. At baseline, after 4 and 8 weeks of training, the Fugl-Meyer assessment upper extremity (FMA-UE), action research arm test (ARAT), and stroke upper limb capacity scale (SULCS) were administered.Results: Eighteen participants (IG: n = 10, DG: n = 8) were included, with a median (IQR) time post stroke of 8.6 weeks (5–12). No adverse events were experienced. After 4 weeks of training, significant between-group differences were found for FMA-UE (p = 0.003) and SULCS (p = 0.033) and a trend for ARAT (p = 0.075) with median (IQR) change scores for the IG of 9 (7–16), 2 (1–3), and 12.5 (1–18), respectively, and for the DG of 0.5 (−3 to 3), 1 (0–1), and 1.5 (−1 to 9), respectively. In the IG, 80% of patients improved beyond the minimal clinical important difference of FMA-UE after 4 weeks, compared to none of the DG patients. Between 4 and 8 weeks of training, patients in the DG tend to show larger improvements when compared to the IG, however, between-group comparisons did not reach significance.Conclusions: Results of this pilot RCT showed that an intensive, specific arm-hand BOOST program, on top of usual care, is feasible and safe in the sub-acute phase post stroke and suggests positive, clinical meaningful effects on upper limb function, especially when delivered in the early sub-acute phase post stroke.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT04584177
The Clinical Outcomes and Toxicities of Induction Chemotherapy Followed by Concurrent Chemoradiotherapy Plus Adjuvant Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma
Authors: Zou Rui , Yuan Jing-Jing , Li Qiang , Ding Jian-Wu , Liao Bing , Tu Zi-Wei , Hu Rong-Huan , Gong Dan , Hu Jia-Li , Zeng Lei 
Published: February 2021

PurposeTo analyze the outcomes and toxicities of induction chemotherapy (ICT) followed by concurrent chemoradiotherapy (CCRT) plus adjuvant chemotherapy (ACT) in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC).MethodsRetrospective analysis of 163 patients with LA-NPC referred from August 2015 to December 2018 was carried out. All patients underwent platinum-based ICT followed by CCRT plus ACT.ResultsThe median follow-up time was 40 months, ranging from 5 to 69 months. The 3-year disease-free survival (DFS), overall survival (OS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates were 80.8, 90.0, 91.6, and 87.4%, respectively. The most frequent acute grade 3/4 adverse events were leukopenia (66.8%), neutropenia (55.8%), mucositis (41.1%), thrombocytopenia (27.0%), and anemia (14.7%).ConclusionICT followed by CCRT plus ACT did not seemingly enhance DFS and OS in LA-NPC patients compared to the addition of ICT to CCRT (historical controls). In contrast, ICT followed by CCRT plus ACT had more acute adverse events than ICT followed by CCRT. Longer-term clinical studies are required to examine the treatment outcomes and late toxicities.
Machine Learning Based on Multi-Parametric MRI to Predict Risk of Breast Cancer
Authors: Tao Weijing , Lu Mengjie , Zhou Xiaoyu , Montemezzi Stefania , Bai Genji , Yue Yangming , Li Xiuli , Zhao Lun , Zhou Changsheng , Lu Guangming 
Published: February 2021

PurposeMachine learning (ML) can extract high-throughput features of images to predict disease. This study aimed to develop nomogram of multi-parametric MRI (mpMRI) ML model to predict the risk of breast cancer.MethodsThe mpMRI included non-enhanced and enhanced T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), apparent diffusion coefficient (ADC), Ktrans, Kep, Ve, and Vp. Regions of interest were annotated in an enhanced T1WI map and mapped to other maps in every slice. 1,132 features and top-10 principal components were extracted from every parameter map. Single-parametric and multi-parametric ML models were constructed via 10 rounds of five-fold cross-validation. The model with the highest area under the curve (AUC) was considered as the optimal model and validated by calibration curve and decision curve. Nomogram was built with the optimal ML model and patients’ characteristics.ResultsThis study involved 144 malignant lesions and 66 benign lesions. The average age of patients with benign and malignant lesions was 42.5 years old and 50.8 years old, respectively, which were statistically different. The sixth and fourth principal components of Ktrans had more importance than others. The AUCs of Ktrans, Kep, Ve and Vp, non-enhanced T1WI, enhanced T1WI, T2WI, and ADC models were 0.86, 0.81, 0.81, 0.83, 0.79, 0.81, 0.84, and 0.83 respectively. The model with an AUC of 0.90 was considered as the optimal model which was validated by calibration curve and decision curve. Nomogram for the prediction of breast cancer was built with the optimal ML models and patient age.ConclusionNomogram could improve the ability of breast cancer prediction preoperatively.
Influence of Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphism on High-Dose Methotrexate-Related Toxicities in Pediatric Non-Hodgkin Lymphoma Patients
Authors: Lu Suying , Zhu Xiaoqin , Li Wei , Chen Huimou , Zhou Dalei , Zhen Zijun , Sun Feifei , Huang Junting , Zhu Jia , Wang Juan , Zhang Yizhuo , Sun Xiaofei 
Published: February 2021

PurposeThis retrospective study aimed to investigate the relationships between the methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C and high-dose methotrexate (HD-MTX)-related toxicities in pediatric non-Hodgkin lymphoma (NHL) patients.Patients and MethodsWe reviewed the medical records of 93 NHL patients aged under 18 years who received HD-MTX therapy at the dose of 5 g/m2 with 24-h infusion at Sun Yat-sen University Cancer Center between 2014 and 2019.ResultsThere were 61 males and 32 females, with a median age of 8.8 years (0.9–15.8 years). The tumor types included lymphoblastic lymphoma (n = 38), Burkitt’s lymphoma (n = 31), anaplastic large cell lymphoma (n = 18), diffuse large B-cell lymphoma (n = 6). Overall, 355 courses of HD-MTX therapy were prescribed. All patients were rescued with calcium folinate 12 h after the end of MTX infusion. We found that plasma MTX levels &gt; 0.2 μmol/L at 48 h post-infusion increased the risk of developing oral mucositis (2.4% VS. 9.5%, P = 0.018). Also, patients carrying the C677T and T677T genotypes had tendencies to be more susceptible to oral mucositis (P = 0.034). Patients harboring mutant 677T allele were more likely to develop leucopenia (38.5 vs. 50.3%, P = 0.025) and thrombocytopenia (22.0 vs. 32.4%, P = 0.028). For polymorphism A1298C, the mutant genotype played a protective role in vomiting (11.1 vs. 4.3%, P = 0.018) but increased the risk of anemia (23.8 vs. 41.7%, P &lt; 0.001) and leucopenia (38.1 vs. 50.3%, P = 0.021).ConclusionChildhood NHL patients harboring C677T genotype were more vulnerable to oral mucositis, leucopenia, and thrombocytopenia, while those with A1298C genotype were at a decreased risk of vomiting and more likely to develop anemia and leucopenia.
Antinuclear Antibodies With a Nucleolar Pattern Are Associated With a Significant Reduction in the Overall Survival of Patients With Leukemia: A Retrospective Cohort Study
Authors: Wang Rong , Zhao Huijuan , Liu Yang , Kang Bing , Cai Jun 
Published: February 2021

ObjectiveAntinuclear antibodies (ANAs) have been reported to be associated with cancers. However, the role of different ANA patterns in cancers is poorly understood, especially in leukemia. This study aimed to investigate the association between ANA patterns and the outcome of leukemia in a retrospective cohort.MethodsA total of 429 adult patients initially diagnosed with leukemia at Henan Provincial People’s Hospital from January 2014 to December 2018 were included in this study, including information on patients without positive ANAs at the time of initial diagnosis, preexisting autoimmune diseases, infectious diseases, etc. The data were retrieved up to December 2020. The final sample included 196 adult patients. The risk of death outcome according to ANA patterns was estimated using multivariable Cox proportional hazards models and the overall survival for ANA patterns was analyzed using Kaplan–Meier curve.ResultsANAs with a nucleolar pattern versus negative ANA were associated with a two-fold increased risk of death outcome in leukemia, independent of sex, age, leukemia immunophenotype, cytogenetic abnormality, treatment, and blood transfusion. Further analysis revealed that the association was more significant in elder patients (≥60 years) and patients treated with tyrosine kinase inhibitor or chemotherapy (P for interaction = 0.042 and 0.010). Notably, the patients with a nucleolar pattern had shorter survival than the patients with a non-nucleolar pattern or without ANA (p &lt; 0.001).ConclusionANAs with a nucleolar pattern are a significant predictor of poor prognosis, providing clues for prognostic assessment in patients with leukemia.
Therapeutic Cancer Vaccination With a Peptide Derived From the Calreticulin Exon 9 Mutations Induces Strong Cellular Immune Responses in Patients With CALR-Mutant Chronic Myeloproliferative Neoplasms
Authors: Handlos Grauslund Jacob , Holmström Morten Orebo , Jørgensen Nicolai Grønne , Klausen Uffe , Weis-Banke Stine Emilie , El Fassi Daniel , Schöllkopf Claudia , Clausen Mette Borg , Gjerdrum Lise Mette Rahbek , Breinholt Marie Fredslund , Kjeldsen Julie Westerlin , Hansen Morten , Koschmieder Steffen , Chatain Nicolas , Novotny Guy Wayne , Petersen Jesper , Kjær Lasse , Skov Vibe , Met Özcan , Svane Inge Marie , Hasselbalch Hans Carl , Andersen Mads Hald 
Published: February 2021

BackgroundThe calreticulin (CALR) exon 9 mutations that are identified in 20% of patients with Philadelphia chromosome negative chronic myeloproliferative neoplasms (MPN) generate immunogenic antigens. Thus, therapeutic cancer vaccination against mutant CALR could be a new treatment modality in CALR-mutant MPN.MethodsThe safety and efficacy of vaccination with the peptide CALRLong36 derived from the CALR exon 9 mutations was tested in a phase I clinical vaccination trial with montanide as adjuvant. Ten patients with CALRmut MPN were included in the trial and received 15 vaccines over the course of one year. The primary end point was evaluation of safety and toxicity of the vaccine. Secondary endpoint was assessment of the immune response to the vaccination epitope (www.clinicaltrials.gov identifier NCT03566446).ResultsPatients had a median age of 59.5 years and a median disease duration of 6.5 years. All patients received the intended 15 vaccines, and the vaccines were deemed safe and tolerable as only two grade three AE were detected, and none of these were considered to be related to the vaccine. A decline in platelet counts relative to the platelets counts at baseline was detected during the first 100 days, however this did not translate into neither a clinical nor a molecular response in any of the patients. Immunomonitoring revealed that four of 10 patients had an in vitro interferon (IFN)-γ ELISPOT response to the CALRLong36 peptide at baseline, and four additional patients displayed a response in ELISPOT upon receiving three or more vaccines. The amplitude of the immune response increased during the entire vaccination schedule for patients with essential thrombocythemia. In contrast, the immune response in patients with primary myelofibrosis did not increase after three vaccines.ConclusionTherapeutic cancer vaccination with peptide vaccines derived from mutant CALR with montanide as an adjuvant, is safe and tolerable. The vaccines did not induce any clinical responses. However, the majority of patients displayed a marked T-cell response to the vaccine upon completion of the trial. This suggests that vaccines directed against mutant CALR may be used with other cancer therapeutic modalities to enhance the anti-tumor immune response.
Multi-Institutional Retrospective Study of Radiotherapy for Hepatocellular Carcinoma in the Caudate Lobe
Authors: Lee Sung Uk , Yoon Sang Min , Cheng Jason Chia-Hsien , Kim Tae Hyun , Kim Bo Hyun , Park Jin-hong , Jung Jinhong , Tsai Chiao-Ling , Chiang Yun , Park Joong-Won 
Published: February 2021

Background: No studies evaluating the clinical outcomes of radiotherapy (RT) for hepatocellular carcinoma (HCC) in the caudate lobe have been available to date. The purpose of this study was to evaluate the effectiveness and safety of RT for HCC in the caudate lobe.Material and Methods: Seventy patients with HCC in the caudate lobe treated with RT from a multi-institutional database were included in this study. The median equivalent dose in 2 Gy (EQD2) was 80.0 Gy10 (range, 31.3–99.3), and freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) rates were evaluated.Results: The median time of follow-up was 47.9 months (range, 3.4–127), and the 5-year FFLP, PFS, and OS rates were 80.6% [95% confidence interval (CI), 70.8–91.8], 13.8% (95% CI, 7.5–25.4), and 51.3% (95% CI, 39.9–66.1), respectively. In the multivariate analysis, the radiation dose was significantly associated with the FFLP rate [hazard ratio (HR), 0.57 per 10 Gy10 increase, p = 0.001], and the status of FFLP was significantly associated with OS (HR, 2.694, p = 0.014). The overall rate of ≥grade 3 adverse events was 5.7% (4 of 70), and RT-related mortality was not observed.Conclusion: RT for HCC in the caudate lobe showed promising FFLP and OS rates with safe toxicity profiles. These findings suggest that RT may be a promising treatment option for HCC in the caudate lobe.
Low Doses of Psilocybin and Ketamine Enhance Motivation and Attention in Poor Performing Rats: Evidence for an Antidepressant Property
Authors: Higgins Guy A. , Carroll Nicole K. , Brown Matt , MacMillan Cam , Silenieks Leo B. , Thevarkunnel Sandy , Izhakova Julia , Magomedova Lilia , DeLannoy Ines , Sellers Edward M. 
Published: February 2021

Long term benefits following short-term administration of high psychedelic doses of serotonergic and dissociative hallucinogens, typified by psilocybin and ketamine respectively, support their potential as treatments for psychiatric conditions such as major depressive disorder. The high psychedelic doses induce perceptual experiences which are associated with therapeutic benefit. There have also been anecdotal reports of these drugs being used at what are colloquially referred to as “micro” doses to improve mood and cognitive function, although currently there are recognized limitations to their clinical and preclinical investigation. In the present studies we have defined a low dose and plasma exposure range in rats for both ketamine (0.3–3 mg/kg [10–73 ng/ml]) and psilocybin/psilocin (0.05–0.1 mg/kg [7–12 ng/ml]), based on studies which identified these as sub-threshold for the induction of behavioral stereotypies. Tests of efficacy were focused on depression-related endophenotypes of anhedonia, amotivation and cognitive dysfunction using low performing male Long Evans rats trained in two food motivated tasks: a progressive ratio (PR) and serial 5-choice (5-CSRT) task. Both acute doses of ketamine (1–3 mg/kg IP) and psilocybin (0.05–0.1 mg/kg SC) pretreatment increased break point for food (PR task), and improved attentional accuracy and a measure of impulsive action (5-CSRT task). In each case, effect size was modest and largely restricted to test subjects characterized as “low performing”. Furthermore, both drugs showed a similar pattern of effect across both tests. The present studies provide a framework for the future study of ketamine and psilocybin at low doses and plasma exposures, and help to establish the use of these lower concentrations of serotonergic and dissociative hallucinogens both as a valid scientific construct, and as having a therapeutic utility.
Maximal Strength, Sprint, and Jump Performance in High-Level Female Football Players Are Maintained With a Customized Training Program During the COVID-19 Lockdown
Authors: Pedersen Sigurd , Johansen Dag , Casolo Andrea , Randers Morten B. , Sagelv Edvard H. , Welde Boye , Winther Andreas Kjæreng , Pettersen Svein Arne 
Published: February 2021

IntroductionThe COVID-19 outbreak with partial lockdown has inevitably led to an alteration in training routines for football players worldwide. Thus, coaches had to face with the novel challenge of minimizing the potential decline in fitness during this period of training disruption.MethodsIn this observational pre- to posttest study involving Norwegian female football players (18.8 ± 1.9 years, height 1.68 ± 0.4 m, mass 61.3 ± 3.7 kg), we investigated the effects of a prescribed home-based and group-based intervention, implemented during the COVID-19 lockdown, on maximal muscular force production and high velocity variables. Specifically, maximal partial squat strength one repetition maximum (1RM), counter movement jump (CMJ) and 15 m sprint time were assessed 1 week prior to the lockdown and 12 weeks after the onset of lockdown. We also collected training content and volume from the prescribed training program and self-reported perceived training quality and motivation toward training.ResultsWe observed no change in 1RM [pretest: 104 ± 12 kg, posttest: 101 ± 11 kg (P= 0.28)], CMJ height [pretest: 28.1 ± 2.3 cm, posttest: 26.8 ± 1.9 (P= 0.09)], and 15 m sprint time [pretest: 2.60 ± 0.08 s, posttest: 2.61 ± 0.07 s (P= 0.52)].ConclusionOur findings suggest that a prescribed home-based and group-based intervention with increased training time devoted to strength, jump, and sprint ability, and regulated to obtain a sufficient infection control level is feasible and effective to preserve strength, jumping, and sprinting abilities of high-level female football players during a ∼ 3-month period of a pandemic-induced lockdown.
Gambling Marketing Strategies and the Internet: What Do We Know? A Systematic Review
Authors: Guillou-Landreat Morgane , Gallopel-Morvan Karine , Lever Delphine , Le Goff Delphine , Le Reste Jean-Yves 
Published: February 2021

Background: The gambling industry has developed many types of gambling on Internet in recent years. Gambling is a social activity for a majority of the world population, but problem gambling (PG) can emerge. The trajectories of gamblers from initiation to PG development are influenced by many variables, including individual and environmental variables and also variables linked to the gambling characteristics. Marketing has been reported to influence gamblers' perceptions and behaviors, but this is not as clear for digital marketing. Digital gambling marketing is broad, ranging from the marketing of gambling websites to communication and advertising on the social media and networks. The objective of this article was to fill this gap by conducting a systematic literature review in order to answer the following questions: (1) What are the strategies of digital gambling marketing? (2) What is the effect of this exposure on gambling representations, intentions and practices?Method: A systematic review was conducted following the PRISMA guidelines on Pubmed database (Medline) from February 2020 to March 2020 and Scopus. Existing papers published between January 2000 and February 2020 were identified by searching with this algorithm: (((“internet”[MeSH Major Topic] OR (communications[All Fields] AND media[All Fields])) OR (“social media”[MeSH Terms] OR (“social”[All Fields] AND “media”[All Fields]) OR “social media”[All Fields])) AND “gambling”[MeSH Major Topic]) AND (“marketing”[MeSH Terms] OR “marketing”[All Fields]), in title, keywords or abstract.Results: Ninety-one candidate studies were selected, 21 studies were selected for the systematic review. Sport appeared as a specific target of online gambling marketing. A growing range of platforms for online sport betting and the development of strategies on the social media were identified. Regarding content, a systematic association between sport and gambling was highlighted. Vulnerable populations, such as young people, appeared to be at high risk of exposure to gambling marketing.Conclusion: Little data is available on the strategies of digital gambling marketing or on exposure to it. Sport could be the first target for future research to understand how the industry is targeting specific populations, and what influence these strategies could have on PG development.