bluuebunny/crossref_metadata_2025 huggingface dataset:
Melatonin Confers Heavy Metal Tolerance of a Dark Septate Endophyte (DSE) Exophiala Pisciphila Via Lowering Oxidative Stress and Heavy Metal Accumulation
Authors: Yu Yang , Teng Zhaowei , Mou Zongmin , Lv Yan , Li Tao , Chen Suiyun , Zhao Dake , Zhao Zhiwei
Published: August 2020

Background: The high antioxidant capacity of melatonin contributing to heavy metal tolerance for plants and animals is widely studied, while researches on microorganisms especially in filamentous fungi are rare. One typical dark septate endophyte (DSE), Exophiala pisciphila, showed significant resistance to heavy metals.Results: In this study, exogenous melatonin was verified to reduce heavy metal damage via relieving oxidative stress, activating antioxidant systems, and decreasing heavy metal accumulation in E. pisciphila. Melatonin biosynthesis enzyme genes were upregulated under heavy metal stress. Furthermore, the overexpression of E. pisciphila TDC1 (EpTDC1) and E. pisciphila ASMT1 (EpASMT1) responsible for melatonin biosynthesis in Escherichia coli and Arabidopsis thaliana, enhanced heavy metal stress tolerance for the two organisms by lowering the oxidative stress and reducing the Cd accumulation in the whole plants, especially in the roots.Conclusions: Our results indicate that melatonin confers heavy metal resistance in E. pisciphila by lowering oxidative stress and heavy metal accumulation.
Tutor uncertainty in dealing with unprofessional behaviours of medical students and trainees: a mixed methods study
Authors: Kelly Dervla , O'Doherty Diane , Harney Sarah , Slattery Natasha , Crowley Louise , McKeague Helena
Published: August 2020

Background: Despite acknowledgement of medical students’ expected professional behaviours and attitudes, there remains widespread reluctance to report students that behave inappropriately. Existing literature focuses on why faculty fail to fail, overlooking the clinical teachers who deal with students day to day. We investigated how clinical teachers address inappropriate behaviours and attitudes in students and trainees.Methods: A mixed methods study was carried out consisting of a survey and two focus groups with clinical teachers. Seventeen clinical teachers from the at University of Limerick School of Medicine, Ireland, took part in the survey (n=22%) and eight clinical teachers participated in two focus groups during the 2018-2019 academic year.Results: Findings suggested that 59% of tutors would take a different approach in regards to professional identity formation (PIF) between addressing unprofessional behaviours witnessed in medical students and trainees. 88% of tutors said they intervened on a professionalism issue with 52% saying ‘once in a while’ In contrast to the survey, tutors in the focus groups expressed a lack of confidence in addressing some behaviors due to a lack of time, not seeing the outcome of process/remediation etc. Tutors indicated a strong preference for case-based training on assessing PIF.Conclusions: We found tutors typically work closely with students on a day-to-day basis and manage unprofessionalism issues. Clinical tutors valued regular communication about policies and procedures about appropriate conduct as well as support, advice and/or oversight from independent member of the university staff. This research also highlights the need for training designed for busy clinical tutors as a distinct type of medical teacher.
Risk Factors and Incidence of Suction Loss during Small Incision Lenticule Extraction (SMILE) in 8487 eyes
Authors: Huang Tian-Ze , Shen Ling , Yu Xiao-Ning , Jin Hong-Ying
Published: August 2020

Background: To report the incidence and risk factors of suction loss during small incision lenticule extraction (SMILE).Methods: This retrospective comparative case control study included 8487 eyes of 4261 patients. Patients underwent SMILE surgery between January 2014 and September 2019 were included. Videos of suction loss were reviewed, and the direct causes of suction loss were noted. An independent samples t-test was used for comparisons between the suction loss group and the control group. A binary logistic regression model was used to determine the possible significant risk factors that might increase the likelihood of suction loss during SMILE surgery.Results: Suction loss occurred in 31 (0.37%) eyes of 30 patients; 23 (74%) cases occurred in the right eye (the first operative eye) and 8 (26%) cases occurred in the left eye. Among the 30 patients, 23 (76.7%) were male and 7 (23.3%) were female. The incidence in the six consecutive years were 0%, 2.13%, 0.34%, 0.24%, 0.22%, and 0.23%. Head and eye movements during surgery caused suction loss in 15 (48.4%) and 16 (51.6%) eyes, respectively. Comparison between the suction loss group and the control group showed that the first operative eye and male gender are at a significantly high risk for suction loss (p < 0.05).Conclusions: Surgical experience may influence the incidence of suction loss during SMILE surgery. The two events that easily led to suction loss were head and eye movements. The risk factors were first operative eye and male gender.Trial registration: Retrospectively registered. ChiCTR-ORC-17011040. Registered 1 April 2017. Name of registry: The observation of clinical results after corneal refractive surgery. Data of enrolment of the first participant to the trial: 1 January 2014.
Longitudinal Speech Biomarkers for Automated Alzheimer's Detection
Authors: Laguarta Jordi , Hueto Ferran , Rajasekaran Prithvhi , Sarma Sanjay , Subirana Brian
Published: August 2020

Background: We introduce a novel speech processing framework, the MIT CBMM Open Voice Brain Model (OVBM), combining implementations of the 4 modules of intelligence: The brain OS chunks and overlaps audio samples and transfers CNN features from the sensory stream and cognitive core creating a multi-modal graph neural network of symbolic compositional models for the target task.Methods: Our approach consists of pre-training models to extract acoustic features from selected biomarkers and then leverage transfer learning to combine the biomarker feature extractors into a graph neural network to provide an explainable diagnsotic for Alzheimer's Dementia (AD) using speech recordings.Results: We apply OVBM to the automated diagnostic of Alzheimer's Dementia patients, achieving above state-of-the-art accuracy of 93.8% using only raw audio, while extracting a personalized subject saliency map to track relative disease progression of 16 explainable biomarkers.Conclusion: By using independent biomarker models, OVBM lets health experts explore biomarker features and whether there are common biomarkers features between AD and other diseases like COVID-19. We present a novel lungs and respiratory tract biomarker created using 200.000+ cough samples to pre-train a model discriminating English from Catalan coughs. Transfer Learning is subsequently used to transfer features from this model with various other biomarker OVBM models. This strategy yielded consistent improvements in ADdetection, no matter the combination used. This cough dataset sets a new benchmark as largest audio health dataset with 30.000+ subjects participating in April 2020, demonstrating for the rst time cough cultural bias.
Prognostic significance of a combined gene expression analysis in EpCAM(+) CTCs in metastatic breast cancer based on a long follow-up
Authors: Strati Areti , Nikolaou Michael , Georgoulias Vasilis , Lianidou Evi S.
Published: August 2020

Background In metastatic breast cancer (MBC) the molecular characterization of Circulating Tumor Cells (CTCs) provides a unique tool to understand metastasis-biology and therapy-resistance. We evaluated the prognostic significance of gene expression in EpCAM(+) CTCs in 46 MBC patients based on a long follow-up. Methods We selected a panel consisting of stem cell markers (CD24, CD44, ALDH1), the mesenchymal marker TWIST1, receptors (ESR1, PGR, HER2, EGFR) and the epithelial marker CK-19. Singleplex RT-qPCR was used for TWIST1 and CK-19 and multiplex RT-qPCR for a) CD24, CD44, ALDH1, HPRT and b) ESR1, PR, HER2, EGFR. A group of 19 healthy donors (HD) was used as control. Results Univariate (p=0.001) and multivariate analysis (p=0.002) revealed the prognostic value of combined gene expression of CK-19(+), CD44high/CD24-/low, ALDH1high/CD24-/low and HER2 over-expression for overall survival (OS). The Kaplan–Meier estimates of OS were significantly different in patients positive for CK-19 (p = 0.028), CD44high/CD24-/low (p = 0.002), ALDH1high/CD24-/low (p = 0.007) and HER2-positive (p = 0.022). Conclusions Our results indicate that combined gene expression analysis in EpCAM(+) CTCs provides prognostic information in MBC but need to be further confirmed in a prospective study, including a larger and well-defined patient cohort.
Changes in hemodialysis catheter management after introduction of the end-stage renal disease prospective payment system
Authors: Roetker Nicholas S. , Guo Haifeng , Decker-Palmer Marquita , Peng Yi , Wetmore Jamaes
Published: August 2020

Background
We investigated whether implementation of the end-stage renal disease prospective payment system (ESRD PPS) was associated with changes in thrombolytic therapy use and other aspects of catheter management in hemodialysis (HD) patients.
Methods
Using quarterly, period prevalent cohorts of patients undergoing maintenance HD with a catheter in the US Renal Data System (2008–2015), we studied rates of claims for within- and outside-HD-unit thrombolytic use, and thrombus/fibrin sheath removal, and rates of delayed HD treatment after ESRD PPS implementation, January 1, 2011. Associations between PPS implementation and change in trend of rates of each outcome were assessed using covariate-adjusted Poisson regression, using a piecewise linear function for quarter-time (with breakpoint at PPS implementation).
Results
Among an average of 69,428 quarterly catheter users, rates of claims for within-HD-unit thrombolytic use declined from 236.6 (Q1-2008) to 81.4 (Q4-2012) per 100 person-years (P < 0.0001, PPS association with change in trend); rates of claims for thrombus/fibrin sheath removal procedures increased from 3.9 (Q1-2008) to 8.8 (Q3-2015) per 100 person-years (P = 0.0001, PPS association with change in trend). Rates of delayed HD treatment increased from 1.6 (Q2-2008) to 2.3 (Q3-2015) per patient-quarter, although PPS implementation was associated with a decrease in this rising trend (1.6% increase per quarter pre-PPS, 1.2% post-PPS; P < 0.0001, change in trend).
Conclusions
After PPS implementation, thrombolytic use decreased and thrombus/fibrin sheath removal increased. The increasing trend in delayed HD treatment appeared to slow after PPS implementation, but delayed sessions continued to increase year over year for unclear reasons.
Social work responses and household-level determinants of coronavirus preparedness in rural Ethiopia
Authors: Addis Yonnas , Abate Dubale , Batista João
Published: August 2020

Background: The novel coronavirus (2019-nCOV) arisen in Ethiopia in early March at its capital city (Addis Ababa) and is now spreading to different administrative regions of the country. This study aimed to assess the attentiveness of the rural community to COVID 19, social work response, and major factors that affect rural community preparedness and response to COVID 19 in Ethiopia. A probit model was used to identify these major factors that affect rural households’ preparedness for the pandemic. Results: Rural households recognize little about COVID 19 and in response, a few community groups, which consist of youth and university students, religious leaders, and elders were engaged to reduce the consequence of COVID 19. Results from the probit model employed indicate that literacy status (household head and family member), gender, age, and economical status of the households; extension information on COVID 19, cash income from non/off-farm activities, participation in community groups, and ownership of mobile phone with a household all influence households preparedness. The main barriers include a lack of information on COVID 19 and financial constraints.Conclusions: Commitment to preparedness and response to COVID 19 by the rural community increases with enhancing proper information dissemination system and applicable support. Thus, much more attention needs to be given by a government and other stakeholders to reduce the venerability of the rural community in Ethiopia.
The Effect of Dietary Antioxidant Supplementation in Patients with Cataract and Glaucoma
Authors: Himori Noriko , Yanagimachi Maki Inoue , Omodaka Kazuko , Shiga Yukihiro , Tsuda Satoru , Kunikata Hiroshi , Nakazawa Toru
Published: August 2020

Background: Oxidative stress may be a key risk factor for cataract and glaucoma, and many previous reports have suggested that antioxidants could be a promising treatment. Here, we investigated the effects of a novel supplement containing three food-derived antioxidants (hesperidin, crocetin, and tamarindus indica) on markers of oxidative stress in patients with these conditions. Methods: This study had a prospective, single arm design. Fifty Japanese subjects with cataract and glaucoma were recruited and asked to refrain from the use of vitamin or carotenoid supplements for 2 weeks before the study. The subjects took 4 tablets together with ample water twice a day for 8 weeks, stopped the treatment, and were then followed for an additional 8 weeks. The subjects were examined at four-week intervals, for a total of 5 examinations. We measured biological antioxidant potential (BAP) with a free radical analyzer. Clinical laboratory data, including malondialdehyde (MDA) and superoxide dismutase (SOD), were measured in venous blood samples. Clinical parameters were also recorded. The Mann-Whitney U test and Fisher’s exact test were used to determine the significance of differences between groups. Other comparisons used a one-way analysis of variance (ANOVA) followed by the Student’s t-test or Dunnett’s test.Results: BAP was significantly elevated at weeks 8, 12, and 16 (P = 0.007, P = 0.035, P = 0.015). The MDA level was significantly reduced at week 8 (P = 0.019). BAP changes were recorded by subtracting the value at week 8 from week 0. Multiple regression analysis revealed that SOD, total bilirubin and diabetes were independent contributing factors to the change in BAP (P = 0.039, P = 0.019, P = 0.013). There were no supplement-related adverse events or abnormal results in blood testing in any of the patients.Conclusion: Our study found that an 8-week oral course of antioxidant supplementation was effective in patients with a low antioxidative stress level. Dietary supplementation holds promise in the treatment of systemic oxidative stress-related diseases.Trial registration: UMIN-CTR UMIN 000032050
Dietary κ-carrageenan facilitates gut microbiota-mediated intestinal inflammation
Authors: Wu Wei , Zhou Jiawei , Chen Juanjuan , Han Hui , Liu Jingwangwei , Niu Tingting , Chen Haimin , Wang Feng
Published: August 2020

Background: After nearly half a century, the inflammatory effects of carrageenan (CGN), a ubiquitous food additive, remain controversial. Little is known about its impact on the gut microbiota and intestinal homeostasis.Results: Mice fed κ-CGN showed no significant inflammatory symptoms, but showed altered colonic microbiota composition, thereby decreasing bacteria-derived short-chain fatty acids (SCFAs) and increased penetrability of the mucus layer. In mice administered the pathogenic bacterium Citrobacter rodentium, inflammation and mucosal damage were further aggravated in the presence of κ-CGN. Mucus layer defects and altered SCFA levels could be reproduced by fecal transplantation from κ-CGN-fed mice, but not from germ-free κ-CGN-fed mice. These symptoms could be partially repaired by administering the probiotics Bifidobacterium longum NCC-2705 and Faecalibacterium prausnitzii.Conclusions: We report a novel evidence that κ-CGN may not be directly inflammatory, but creates an environment that favors inflammation by perturbation of gut microbiota composition and then facilitates expansion of pathogens, which may be partially reversed by the introduction of probiotics.
Incidence of inherited metabolic disorders in southern Israel: A comparison between consanguinity and non-consanguinity communities
Authors: Hazan Guy , Hershkovitz Eliyahu , Staretz-Chacham O
Published: August 2020

Background: Inherited metabolic disorders (IMDs) are group of rare monogenic diseases, usually derived from reduced or absent activity in a single metabolic pathway. Most of the IMDs are inherited in an autosomal recessive manner. The incidence of IMDs varies from country to country and within different ethnic groups, but data is still scarce. Consanguinity rate among populations is highly contributor factor for IMDs incidence. There are no reports comparing the incidence of IMD in consanguineous and non-consanguineous populations from the same geographic region with the same diagnostic capabilities. Our study objective is to compare the incidence of IMDs between between the relatively low consanguineous Jewish population and the consanguineous Bedouin population, both living in the southern of Israel.Results: During 1990–2017 there were 393,772 live births in the Negev district, of Southern of Israel. Among them 187,049 were of Jewish origin while 206,723 were of Bedouin-Muslim origin. A total of 223 children were diagnosed in this study period with IMDs. Among those 223 children with IMD, 33 were of Jewish origin while the other 190 children were of Bedouin-Muslim origin. The overall incidence for IMDs of the overall Negev population was 56.6/100,000 live birth. The incidence for IMD's among the Bedouin population was significantly higher than among Jewish population.Conclusions: IMDs are extremely more common in the consanguineous Bedouin compared with the relatively non-consanguineous Jewish population of Southern Israel. Health policy makers should consider these data and prepare educational and genetic counselling problems accordingly.
Resuscitation Fluid Types in Sepsis, Surgical, and Trauma Patients: A Systematic Review and Sequential Network Meta-analyses
Authors: Tseng Chien-Hua , Chen Tzu-Tao , Wu Mei-Yi , Chan Ming-Cheng , Shih Ming-Chieh , Tu Yu-Kang
Published: August 2020

Background: Crystalloids and different component colloids, used for volume resuscitation, are sometimes associated with serious adverse events (AEs). Clinical trial findings for such fluid types in different patients’ conditions are conflicting. Whether the mortality benefit of balanced crystalloid than saline can be infer from sepsis to other patient group is uncertain, and other AEs is not comprehensive. This study aims to compare the survival benefits and AEs of seven fluid types with network meta-analysis in sepsis, surgical, trauma, and traumatic brain injury patients. Methods: Searched databases (PubMed, EMBASE, and Cochrane CENTRAL) and reference lists of relevant articles occurred from inception until January 2020. Studies on critically ill adults requiring fluid resuscitation were included. Intervention studies reported on balanced crystalloid, saline, iso-oncotic albumin, hyperoncotic albumin, low molecular weight hydroxyethyl starch (L-HES), high molecular weight HES, and gelatin. Network meta-analyses were conducted using random-effects model to calculate odds ratio (OR) and mean difference. Risk of Bias tool 2.0 was used to assess bias. CINeMA (Confidence in Network Meta-Analysis) web application was used to rate confidence in synthetic evidence. Results: Fifty-eight trials (n=26,351 patients) were identified. Seven fluid types were evaluated. Among patients with sepsis and surgery, balanced crystalloids and albumin achieved better survival, fewer renal AEs, and smaller blood transfusion volumes than saline and L-HES. In those with sepsis, balanced crystalloids reduced mortality more than saline (OR, 0.84; 95% CI 0.74 to 0.95) and L-HES (OR, 0.81; 95% CI 0.69 to 0.95) and reduced renal AEs more than L-HES (OR, 0.80; 95% CI 0.65 to 0.99). However, they required the largest resuscitation volume among all fluid types, especially in trauma patients. In patients with traumatic brain injury, saline and L-HES achieved lower mortality than albumin and balanced crystalloids; especially saline was superior to iso-oncotic albumin (OR, 0.55; 95% CI 0.35 to 0.87).Conclusions: For sepsis and surgical patients, we recommend balanced crystalloids and albumin, rather than L-HES and saline. For traumatic brain injury patients, we recommend saline or L-HES, rather than iso-oncotic albumin or balanced crystalloids. These findings could guide physicians’ fluid selection.Trial registry: PROSPERO website, registration number: CRD42018115641).
Association Between Betel Nut and Presence of Diverticulum: A Cross-Sectional Study
Authors: Liu Yu-Hong , chen Wei-liang
Published: August 2020

Background: Current studies reporting multiple systemic effect of betel nut (BN) chewing have little analysis on colonic system. The aim of our study was to analyze the association between BN chewing and diverticulosis.Method: This cross-sectional study is conducted from 2010 to 2016 at a medical center in Taiwan. 5586 eligible participants were enrolled in our study (all of them underwent colonoscopy, and 349 with diverticulosis). The BN chewing behavior was recorded from assessment of personal history. The diverticulosis was categorized by the presence or not according to the colonoscopies done by trained physicians from health examinations in Tri-Service General Hospital. A logistic regression model with adjusted models, with covariates from Directed Acyclic Graph, was used to determine the association between BN chewing and diverticulosis. We also analyzed the association between different exposures, including cigarette, alcohol, and BN, and diverticulosis. Results: Our study included 3161 males and 2425 females with significantly higher prevalence rates of BN chewing behavior among males than females (11.1% versus 0.3%). In men group, BN chewing had adjusted odd ratio: 1.65(95% CI:1.12-2.44) on the presence of diverticulosis. Among the combination of exposures of cigarette, alcohol and BN, only the group exposed to all showed significant association between diverticulosis with adjusted OR: 1.909(95% CI: 1.188-3.065). Further subgroup analysis displayed adjusted OR: 2.310(95% CI:1.245-4.287) in obesity Taiwanese male.Conclusion: BN chewing is independently associated with diverticulosis in Taiwanese male.
There is a Third Condition Aside from Survival and Death That Affects Outcome Statistics: Terminal Discharge
Authors: Xu Jianqiao , Chen Yongqiang , Wang Jiang , Yang Guixiu , Yan Peng , Duan Zhimei , Mo Guoxin , Xie Lixin
Published: August 2020

Background: Some patients discharged automatically are classified as terminal discharge, while their clinical outcome is survival, disrupting the results of clinical research.Methods: The data of this study were taken from inpatients who were admitted to the ICU of the First Medical Center of the People's Liberation Army General Hospital. We collected the data regarding medications used over the three days before discharge from the group of patients who survived and the group of patients who died, and the outcomes of all patients were recalculated by three classification algorithms (AdaBoosting, Pearson correlation coefficient, observed to expected ratio-weighted cosine similarity). Our basic assumption is that if the classification result is death but the actual in-hospital outcome is survival, the associated patient was likely terminally discharged.Results: The coincidence rate of the outcomes calculated by the AdaBoosting algorithm was 98.1%, the coincidence rate calculated by the Pearson correlation coefficient was 61.1%, and the coincidence rate calculated by the observed to expected ratio-weighted cosine similarity was 93.4%. When the three classification methods were combined, the accuracy reached 98.56%.Conclusion: The combination of clinical rules and classification methods has a synergistic effect on judgments of patients’ discharge outcomes, greatly saving time on manual retrieval and reducing the negative influence of statistics or rules.
Coping Strategies and Perceived Barriers of women hospitality workplaces employees to sexual harassment in Bahir Dar city, Northwest Ethiopia: A Ground Theory Approach
Authors: Worke Mulugeta Dile , Debelew Gurmesa Tura , Koricha Zewdie Birhanu
Published: August 2020

Background: Coping strategies of sexual harassment are determined by the person, environment, and cognitive reappraisal. Consequently, the issue of how women victims cope with the problem is still unsettled worldwide. Women were disproportionately victims of sexual harassment in the hospitality industries, and the issue of response is at an earlier phase in low and middle-income countries, and particularly in Ethiopia. Thus, this study was aimed to develop a context speciﬁc and data-driven coping strategy framework for sexual harassment victimization against women working in the hospitality workplaces.Methods: We conducted a qualitative, grounded theory approach to guide the study process. The data were collected from women, managers, cashiers, and customers. We use a semi-structured, specific audience, and focus group discussion guides. A constant comparative approach was used to summarize data and describe meanings. ATLAS. ti version 8.4.24 software package was used for data coding categorizing, and visualizing networks.Results: The analysis provided a context speciﬁc coping strategic framework, which consists of, closely interconnected, four dimensions practiced by women hospitality employees. The dimensions were normalization, engagement, help-seeking, and detachment with the respective barriers. The normalization dimension encompasses silence, acceptance, denial, refusal, grief, and tolerance. Likewise, the engagement dimension consists of confrontation, negotiation, retaliation/threatening, and discrimination of the perpetrators. The help-seeking dimension also involves elements such as discussing with friends, complaining to supervisors, consulting professionals, and accusing the perpetrators. Finally, the detachment dimension entails job-hopping, job withdrawal, work withdrawal, and distancing. A variety of barriers deterred all dimensions. However, normalization was facilitated by some factors, and adverse outcomes ended the engagement dimension of coping.Conclusion: The sexual harassment coping capacities of women employees have been unclear, which left no whole for the stakeholders to intervene. The new coping strategic framework can serve as a valuable guide to design context-speciﬁc interventions that make the women and the stakeholders prevent sexual harassment, decrease the barriers, and alleviate effects.
Chromosome segregation in B. subtilis is highly heterogeneous
Authors: Najjar Nina El , Graumann Peter
Published: August 2020

Objective
The bacterial cell cycle comprises initiation of replication and ensuing elongation, concomitant chromosome segregation (in some organisms with a delay termed cohesion), and finally cell division. By quantifying the number of origin and terminus regions in exponentially growing Bacillus subtilis cells, and after induction of DNA damage, we aimed at determining cell cycle parameters at different growth rates at a single cell level.
Results
B. subtilis cells are mostly mero-oligoploid during fast growth and diploid during slow growth. However, we found that the number of replication origins and of termini is highly heterogeneous within the cell population at two different growth rates, and that even at slow growth, a majority of cells attempts to maintain more than a single chromosome at all times of the cell cycle. Heterogeneity of chromosome copy numbers may reflect different subpopulations having diverging growth rates even during exponential growth conditions. Cells continued to initiate replication and segregate chromosomes after induction of DNA damage, as judged by an increase in origin numbers per cell, showing that replication and segregation are relatively robust against cell cycle perturbation.
Implementing cancer-screening programs by training primary care physicians in India – Findings from the National Institute of Cancer Prevention Research Project ECHO for Cancer Prevention
Authors: Adsul Prajakta , Nethan Suzanne Tanya , deCortina Sasha Herbst , Dhanasekaran Kavitha , Hariprasad Roopa
Published: August 2020

BackgroundIn an effort to address the growing cancer burden, the Government of India introduced a national program for screening and prevention of the most common cancers (oral, breast, and cervical) in 2016. To support the screening program, the National Institute for Cancer Prevention Research (NICPR) adopted the Project ECHO (Extension for Community Healthcare Outcomes) model for training health care providers in cancer screening. Very few studies examine the impact of the ECHO model on provider behavior or health outcomes related to cancer screening. We assess the change in knowledge and, skills among primary care physicians attending NICPR ECHO trainings and the impact of the training program on the implementation of cancer screening services.MethodsPrior to the start of the online phase and upon completion of the 14 weeks, trainees answered a 23-item questionnaire (administered online via SurveyMonkey). We conducted a descriptive and bivariate analysis of the pre-post assessments conducted on trainees participating in the online phase and where available report on the weekly quizzes and the hands-on workshop assessments.ResultsSix hundred forty-one medical officers have participated in the trainings, across nine cohorts of trainees and this study presents data from 116 primary care physicians that completed both the pre- and post-assessments, trained from May 2019 to February 2020. Almost two-thirds had completed medical training (MD equivalent) (69.7%) and 85% were working in government healthcare facilities. Trainees reported statistically significant improvements before and after the online phase, when queried specifically on knowledge and skills using visual vignettes about oral and cervical cancer screening. Trainees did not report significant changes in the provision of cancer-screening services after completing the program. ConclusionsStudy findings support the effectiveness of the training program in reaching primary care physicians across the country and improving their knowledge and skills related to screening for breast, oral, and cervical cancer. After the training, very few primary care physicians mentioned implementing cancer screening services highlighting barriers that require further study and development of complementary implementation strategies. Study findings could inform the development and refinement of training for cancer-screening programs in low- and middle-income countries.
Effect of the Versatile Bifunctional Chelator AAZTA5 on the Radiometal Labelling properties and the in vitro performance of a Gastrin Releasing Peptide Receptor Antagonist
Authors: Hofstetter Michael , Moon Euy Sung , D'Angelo Fabio , Geissbühler Lucien , Alberts Ian , Afshar-Oromieh Ali , Rösch Frank , Rominger Axel , Gourni Eleni
Published: August 2020

Background: Gastrin Releasing Peptide receptor (GRPr)-based radioligands, mainly antagonists, have shown great promise for diagnostic imaging of GRPr-positive cancers, such as prostate and breast.The present study aims at developing and evaluating a versatile GRPr-based probe for both PET / SPECT imaging as well as intraoperative and therapeutic applications. The influence of the versatile chelator AAZTA5 on the radiometal labelling properties and the in vitro performance of the generated radiotracers were thoroughly investigated.The GRPr-based antagonist D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 was functionalized with the chelator 6-[Bis(carboxymethyl)amino]-1,4-bis(carboyxmethyl)-6-methyl-1,4-diazepane (AAZTA5) through the spacer 4-amino-1-carboxymethyl-piperidine (Pip) to obtain AAZTA5-Pip-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (LF1). LF1 was radiolabelled with 68Ga (PET), 111In (SPECT, intraoperative applications) and 177Lu (therapy, SPECT). In vitro evaluation included stability studies, determination of lipophilicity, protein-binding studies, determination of Kd and Bmax as well as internalization studies using the epithelial human prostate cancer cell line PC3. In vitro monotherapy as well as combination therapy studies were further performed to assess its applicability as a theranostic compound.Results: LF1 was labelled with 68Ga, 111In and 177Lu within 5 min at room temperature (RT). The molar activities (Am) were ranging between 50-60 MBq/nmol for 68Ga-LF1, 10-20 MBq/nmol for 111In-LF1 and 177Lu-LF1. The radiotracers were found to be stable for a period of 4 h post labeling exhibiting a hydrophilic profile with an average of a LogDoctanol/PBS of -3, while the bound activity to the human serum protein was approximately 10%. 68/natGa-LF1, 177/natLu-LF1 and 111/natIn-LF1 exhibited high affinity for the PC3 cells, with Kd values of 16.27±2.45 nM, 10.25±2.73 nM and 5.16±1.94 nM, respectively, and the required concentration of the radiotracers to saturate the receptors (Bmax) was between 0.5 and 0.8 nM which corresponds to approximately 4 x 105 receptors per cell. Low specific internalization rate was found in cell culture, while the total specific cell surface bound uptake always exceeded the internalized activity. In vitro therapy studies showed that combination of 177Lu-LF1 with rapamycin inhibit the growth of PC3 cells more efficiently compared to 177Lu-LF1 alone.Conclusion: Encouraged by these promising in vitro data, preclinical evaluation of the LF1 precursor are planned in tumour models in vivo.
Allogeneic Human Neural Stem Cells for Improved Therapeutic Delivery to Peritoneal Ovarian Cancer.
Authors: Batalla-Covello Jennifer , Abidi Wafa , Ngai Hoi Wa , Hyde Caitlyn , Machado Diana , Majid Asma Abdul , Hammad Mohamed , Flores Linda , Copeland Gregory , Dellinger Thanh , Han Ernest , Berlin Jacob , Aboody Karen , Mooney Rachael
Published: August 2020

Background: Immortalized, clonal HB1.F3.CD21 human neural stem/progenitor cells (NSCs), loaded with therapeutic cargo prior to intraperitoneal (IP) injection, have been shown to improve the delivery and efficacy of therapeutic agents in pre-clinical models of stage III ovarian cancer. In previous studies, the distribution and efficacy of the NSC-delivered cargo has been examined; however, the fate of the NSCs has not yet been explored. Methods: To monitor NSC tropism, we used an unconventional method of quantifying endocytosed gold nanorods to overcome the weaknesses of existing cell-tracking technologies. Results: Here, we report efficient tumor tropism of HB1.F3.CD21 NSCs, showing that they primarily distribute to the tumor stroma surrounding individual tumor foci within 3 hours after injection, reaching up to 95% of IP metastases without localizing to healthy tissue. Furthermore, we demonstrate that these NSCs are non-tumorigenic and non-immunogenic within the peritoneal setting. Conclusions: Their efficient tropism, combined with their promising clinical safety features and potential for cost-effective scale-up, positions this NSC line as a practical, off-the-shelf platform to improve the delivery of a myriad of peritoneal cancer therapeutics.
Improving Tumoral Acidic pH-Responsive Drug Efficiency Based on GO@Au Nanocomposite
Authors: Tang Mingqing , Xin Pengliang , Lin Hongjun , Li Huangen
Published: August 2020

Background: to accurately deliver drugs to the lesion site and realize its timed and quantitative release is the focus of tumor therapy. In this paper, a tumor targeted near-infrared light controlled release drug delivery system integrating hyperthermia and chemotherapy was successfully constructed by combining tumor hyperthermia and chemotherapy. Results: by hydrothermal method, Au nanoparticles were firstly loaded onto the GO surface to obtain GO@Au nanocomposites, then PEG was loaded onto the GO@Au by pH sensitive hydrazone bond to obtain GO@Au-PEG, and DOX is finally loaded onto the GO surface via π-π stacking. The target controlled release drug delivery system showed good tumor targeting property, can be the efficient transfer of drug to the tumor cells, and the tumor cells in near-infrared light control of DOX release. In vivo tumor inhibition experiments in mice, the targeted drug delivery system showed obvious tumor inhibition characteristics and had good effects of hyperthermia and chemotherapy. Conclusions: therefore, this tumor targeted near-infrared controlled release drug delivery system has great potential in tumor therapy.
The lncRNA MIR31HG regulates the senescence associated secretory phenotype
Authors: Montes Marta , Lubas Michael , Arendrup Frederic S , Mentz Bettina , Rohatgi Neha , Tumas Sarunas , Harder Lea M , Skanderup Anders J , Andersen Jens S , Lund Anders H
Published: August 2020

Senescent cells secrete cytokines, chemokines and growth factors collectively known as the senescence-associated secretory phenotype (SASP) which can reinforce senescence and activate the immune response. However, it can also negatively impact neighbouring tissues facilitating tumor progression. We have previously shown that in proliferating cells the nuclear long non-coding RNA (lncRNA) MIR31HG inhibits p16/CDKN2A expression through interaction with polycomb repressor complexes (PRC1/2) and that during BRAF-induced senescence MIR31HG is overexpressed and translocates to the cytoplasm. Here, we show that MIR31HG regulates the expression of a subset of SASP components during BRAF-induced senescence. The SASP secreted from senescent cells depleted for MIR31HG fails to induce paracrine invasion without affecting the growth inhibitory effect. Mechanistically, MIR31HG interacts with YBX1 facilitating its phosphorylation at serine 102 (p-YBX1S102) by the kinase RSK. p-YBX1S102 induces IL1A translation which acts as upstream regulator inducing the transcription of the other SASP mRNAs. Our results suggest a dual role for MIR31HG in senescence depending on its cellular localization and points to the lncRNA as a potential therapeutic target in the treatment of senescence-related pathologies.
Tissue dose estimation after extravasation of 177Lu-DOTATATE  
Authors: Tylski Perrine , Pina-Jomir Géraldine , Bournaud-Salinas Claire , Jalade Patrice
Published: August 2020

Background. Extravasation of radiopharmaceuticals used for vectorized internal radiotherapy can lead to severe tissue damage (1). Clinical management of these extravasations requires the preliminary estimation of the dose distribution in the extravasation area. Data are scarce regarding the dose estimation in the literature. This work presents a methodology for estimating the dose distribution after an extravasation occurred in September 2017, in the arm of a patient during a 7.4 GBq infusion of Lutathera ® (AAA). Methods. A local quantification procedure initially developed for renal dosimetry was used. A calibration factor was determined and verified by phantom study. Extravasation volume of interest and its variation in time were determined using 4 whole body (WB) planar acquisitions performed at 2h (T2h), 5h (T5h), 20h (T20h) and 26h (T26h) after the beginning of the infusion and three SPECT/CT thoracic acquisitions at T5h, T20h and T26h. For better estimation of initial extravasation volume, 3 volumes were defined on SPECT images using a 3D activity threshold. Cumulated activities and associated absorbed doses (D1, D2, D3) were calculated in the 3 volumes using the MIRD formalism.Results. Volumes estimated using 3D threshold were V1= 1000 mL, V2=400 mL and V3=180 mL. Cumulated activities were evaluated using a mono exponential fit on activities calculated on SPECT images. Estimated local absorbed doses in V1, V2 and V3 were D1 = 2.8 Gy, D2 = 5.4 Gy and D3 = 7.8 Gy. Evolution in time of local activity in the extravasation area was consistent with an effective local period (Teff) of 3 hours.Conclusions. Rapid local doses estimation was permitted thank to knowledge of the calibration factor determined previous to accidental extravasation. Luthatera® lymphatic drainage was quick in the arm (Teff = 3h). Estimated doses were in the lower range of deterministic effects and far under soft tissue necrosis threshold. Thus no surgical rinse was proposed. The patient did not show any clinical consequence of theses extravasation.
Characteristics of registered systematic reviews on traditional Chinese medicine for COVID-19
Authors: Lian Rongna , Gao Ya , Zhang Ruinian , Xie Dairong , Zhang Yi , Zhang Mei , Zhang Junhua , Tian Jinhui
Published: August 2020

Background: Characteristics of registered systematic reviews (SRs) on traditional Chinese medicine (TCM) for coronavirus disease 2019 (COVID-19) remain unclear. This study aimed to analyze research collaboration, interventions, and outcomes in registered SRs of TCM associated with COVID-19.Methods: PROSPERO was searched to obtain SRs of TCM related to COVID-19 up to July 1, 2020. VOSviewer 1.6.14 software was used to generate network maps for countries, institutions, and provinces.Results: A total of 80 SRs were included, which were registered by 81 institutions from 6 countries. China (76, 95.00%) was the country with the highest output. 21 provinces in China contributed to the registration of SRs, Sichuan (25, 30.12%), Beijing (13, 15.66%), and Shaanxi (7, 8.43%) were the top three productive provinces. The top three productive institutions were Chengdu University of traditional Chinese medicine (18, 24.66%), Shaanxi University of traditional Chinese medicine (7, 9.59%), and Beijing University of traditional Chinese medicine (6, 8.22%). Collaborations among countries, provinces, and institutions were sparse. Interventions investigated included traditional Chinese medicine, integrated Chinese and Western medicine, acupuncture, and Taijiquan, but the description was brief, and no specific implementation plan was provided. The most frequently used primary outcome was clinical efficiency (45, 56.25%), and the most frequently used secondary outcome was the adverse event (50, 62.5%). The expression of the outcomes was not standardized.Conclusions: Although there were some collaborations between provinces and institutions, cooperation between countries should be further strengthened. The identified deficiencies in interventions and outcomes should be given more attention by future researchers.
Prediction of fasting plasma glucose and glycated haemoglobin using machine learning based on tongue features
Authors: Li Jun , Huang Jingbin , Tu Liping , Cui Longtao , Cui Ji , Ma Xuxiang , Jiang Tao , Yao Xinghua , Li Jiacai , Shi Yulin , Bi Zijuan , Wang Yu , Fu Hongyuan , Wang Jue , Lin Yenting , Pai ChingHsuan , Guo Xiaojing , Zhou Changle , Hu Xiaojuan , Xu Jiatuo
Published: August 2020

Background

Given tongue features and basic features, this study aimed to develop and assess a non-invasive machine learning model to perform regression prediction on fasting plasma glucose and glycated haemoglobin which will help optimize diabetes risk warning.
Methods

We collected the basic features, tongue features and blood features of the subjects. Using machine learning algorithms to analyze these data, we built models to predict fasting plasma glucose and glycated haemoglobin. Then the performance of the models was evaluated through 5-fold cross-validation results and test set results.
Results

The results of cross validation on the training set showed that given non-invasive input features, the minimum average mean square error of fasting plasma glucose and glycated haemoglobin prediction was 1.227 and 0.438. Our non-invasive fasting plasma glucose prediction model with tongue features and basic features combined achieved a minimum mean square error of 0.601 and a maximum coefficient of determination of 0.606 on the test set. The glycated haemoglobin prediction model product a minimum mean square error of 0.272 and a maximum coefficient of determination of 0.539 on the test set. The Clarke’s Error Grid Analysis showed that the non-invasive blending model had 90.83% of points in zone A and 8.49% of points in zone B on the test set.
Conclusions

We developed an effective non-invasive method for estimating fasting plasma glucose and glycated haemoglobin from tongue features and basic features combined, which may help identify individuals at high risk for diabetes.
Inhibition of Cronobacter Sakazakii Biofilm Formation and Expression of Virulence Factors by Coenzyme Q0
Authors: Guan Ning , Shi Yiqi , Tong Haoyu , Yang Yanpeng , Li Jiahui , Guo Du , Wang Yutang , Xia Xiaodong , Shi Chao
Published: August 2020

Objectives：Here, we investigated the inhibitory effects of coenzyme Q0 (CoQ0) on biofilm formation and the expression of virulence genes by Cronobacter sakazakii. Results：We found that the minimum inhibitory concentration of CoQ0 against C. sakazakii strains ATCC29544 and ATCC29004 was 100 μg/mL, while growth curve assays showed that sub-inhibitory concentrations (SICs) of CoQ0 for both strains were 6.4, 3.2, 1.6 and 0.8 μg/mL. Assays exploring the inhibition of specific biofilm formation showed that SICs of CoQ0 inhibited biofilm formation by C. sakazakii in a dose-dependent manner, which was confirmed by scanning electron microscopy and confocal laser scanning microscopy analyses. CoQ0 inhibited the swimming and swarming motility of C. sakazakii and reduced its ability to adhere to and invade HT-29 cells. In addition, CoQ0 impeded the ability of C. sakazakii to survive and replicate within RAW 264.7 cells. Finally, real time polymerase chain reaction analysis confirmed that nine C. sakazakii genes associated with biofilm formation and virulence were down-regulated in response to CoQ0 treatment. Conclusion：Overall, our findings suggest that CoQ0 is a promising antibiofilm agent and provide new insights for the prevention and control of infections caused by C. sakazakii.