bluuebunny/crossref_metadata_2025 huggingface dataset:
Creating a Value Dashboard for Orthopaedic Surgical Procedures
Authors: Reilly Clifford A. , Doughty Hayden P. , Werth Paul M. , Rockwell Connor W. , Sparks Michael B. , Jevsevar David S.
Published: August 2020

Background:

Value-based health-care delivery is a framework for restructuring our health-care systems with the goal of providing better outcomes for patients at lower cost. Value is determined by patient health outcomes per dollar spent on health services. We sought to develop a value dashboard that could be used to easily track and improve the value of total hip and knee arthroplasty (THA and TKA).

Methods:

We created a value dashboard for TKAs and THAs at our institution. Value was defined as quality of outcomes per dollar spent. The dashboard for each procedure displayed the average value by surgeon, compared with institutional averages for physical function scores and cost. Quality metrics were determined by weighted surgeon ranking using a modified Delphi process and included both clinical and patient-reported outcomes, as measured by the mean change in the Patient-Reported Outcomes Measurement Information System Global-10 (PROMIS-10) physical function score, mean change in the Hip disability and Osteoarthritis Outcome Score-Joint Replacement (HOOS-JR) or the Knee injury and Osteoarthritis Outcome Score-Joint Replacement (KOOS-JR), mean change in the modified Single Assessment Numeric Evaluation (SANE) score, complication rate, periprosthetic joint infection (PJI) rate, and 30-day readmission rate. Average direct costs per surgeon were used. Data from January 2017 through April 2018 were included to ensure 1-year follow-up.

Results:

Six surgeons were included in the value dashboard for TKA, and 5 were included in the THA dashboard. The value for TKA by surgeon ranged from 7% below to 12% above the institutional benchmark. The value for THA by surgeon ranged from 12% below to 7% above the institutional benchmark.

Conclusions:

The proposed dashboard utilizes value in a health-care framework and could be used for comparing and improving value for THA and TKA. This dashboard successfully combined patient outcome metrics and direct costs of surgical procedures. Future studies should focus on involving patients in this process and using national data to create benchmarks, which could provide a more accurate representation of value than using institutional averages.
The Detection of TB Lungs with Microscopic and the Rapid Molecular Test Methods
Authors: Tamtyas Fifi Isti , Rini Chylen Setiyo
Published: August 2020

Mycobacterium tuberculosis is a cause of tuberculosis (TB ) disease. In this research Mycobacterium tuberculosis can be detected using the Microscopic and Real-Time PCR. This research aims are to know the difference in the results of the examination Mycobacterium tuberculosis with microscopic method and Real-Time PCR. This research used an experimental research design and was tested using the Chi Square test. This results showed at significant difference (p=0.000) detection of pulmonary TB disease by microscopic and Real-Time PCR methods
Worse treatment response to neoadjuvant chemoradiotherapy in young patients with locally advanced rectal cancer
Authors: Zhang Yiyi , Yan Liangliang , Wu Yong , Xu Meifang , Liu Xing , Guan Guoxian
Published: August 2020

Background: To evaluate the impact of age on the efficacy of neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer (LARC).Method: LARC patients undergoing NCRT and radical surgery from 2011 to 2018 were divided into young (<40 years) and old (≥40 years) groups. Multivariate analyses were performed to identify predictive factors for pathological complete response (pCR). Predictive nomograms and decision curve analysis were used to compare the models including/excluding age groups. Immunohistochemical analysis was performed to detect CD133 expression in LARC patients.Result: A total of 901 LARC patients were analyzed. The young group was associated with poorly differentiated tumors, more metastatic lymph nodes, higher perineural invasion, and a lower tumor regression grade (P = 0.008; P < 0.001; P < 0.001; P = 0.003). Logistic regression analysis demonstrated that age <40 years (HR = 2.190, P = 0.044), tumor size (HR = 0.538, P < 0.001), pre-NCRT cN stage (HR = 0.570, P = 0.036), and post-NCRT CEA level (HR = 0.877, P = 0.001) were significantly associated with pCR. Predictive nomograms and decision curve analysis demonstrated that the predictive ability of models including the age group was superior to that of models excluding the age group. Higher CD133 expression was more common in young LARC patients.Conclusion: Young patients with LARC were associated with lower pCR rates following NCRT. The ability of the predictive model was greater when based on the age group. Young LARC patients were associated with a higher CD133+ tumor stem cell burden, which contributed to the lower pCR rates.
Fabrication of Electronically integrated, mass-manufactured, microscopic robots
Authors: Miskin Marc Z. , Cortese Alejandro J. , Dorsey Kyle , Esposito Edward P. , Reynolds Michael F. , Liu Qingkun , Cao Michael , Muller David A. , McEuen Paul L. , Cohen Itai
Published: August 2020

We have developed a fabrication process that can be used to build millions of microscopic, electronically-integrated robots. Our procedure includes steps for building silicon microelectronics, building components for actuation, encapsulation steps, and a process for releasing the robots into aqueous environments. Each step is carried out massively in parallel, allowing us to build over a million robots on a single 4-inch wafer. Broadly, the new actuators and fabrication protocols presented here offer a generic platform and can be used to make a wide range of silicon-based, functional robotic systems that are too small to be resolved by the naked eye.
MicroRNA bta-miR-365-3p inhibits proliferation but promotes differentiation of primary bovine myoblasts by targeting the activin A receptor type I
Authors: Hao Dan , Wang Xiaogang , Wang Xiao , Thomsen Bo , Yang Yu , Lan Xianyong , Huang Yongzhen , Chen Hong
Published: August 2020

Background: MicroRNAs act as post-transcriptional regulators that repress translation or degrades mRNA transcripts. Each microRNA has many mRNA targets and each mRNA may be targeted by several microRNAs. Skeletal muscles express a plethora of microRNA genes that regulate muscle development and function by controlling the expression of protein-coding target genes. To expand our understanding of the role of microRNA, specifically bta-miR-365-3p, in muscle biology, we studied its function in regulating primary bovine myoblast proliferation and differentiation.Results: We first show that bta-miR-365-3p is predominantly expressed in skeletal muscle and heart tissue in Chinese Qinchuan beef cattle. Quantitative PCR and western blotting showed that overexpression of bta-miR-365-3p significantly reduced the levels of cyclinD1 (CCND1), cyclin dependent kinase 2 (CDK2) and proliferating cell nuclear antigen (PCNA) but stimulated the expression of muscle differentiation markers MYOD1, MYOG, both at mRNA and protein level. Moreover, downregulation of bta-miR-365-3p increased the expression of CCND1, CDK2 and PCNA but decreased the expression of MYOD1 and MYOG at both mRNA and protein levels. Furthermore, flow cytometry, EdU proliferation assays and immunostaining showed that increased levels of bta-miR-365-3p suppressed cell proliferation but promoted myotube formation, whereas a decreased level of bta-miR-365-3p had opposite consequences. Finally, we determined that activin A receptor type I (ACVR1) is a direct target of bta-miR-365-3p. Thus, dual luciferase gene reporter assays demonstrated that bta-miR-365-3p can bind to the 3'UTR of ACVR1 gene to regulate its expression. Consistently, knock-down of ACVR1 was associated with reduced CDK2, CCND1 and PCNA expression but increased MYOG and MYOD1 expression both at mRNA and protein level.Conclusion: Collectively these data suggest that bta-miR-365-3p represses proliferation but promotes differentiation of bovine myoblasts through a mechanism involving downregulation of ACVR1.
Characterization of a rhodanese homologue from Haemonchus contortus and its immune-modulatory effects on goat immune cells in vitro
Authors: Wang Yujian , Ehsan Muhammad , Huang Jianmei , Aimulajiang Kalibixiati , Yan RuoFeng , Song XiaoKai , Xu LiXin , Li Xiangrui
Published: August 2020

Background: Modulation of the host immune response by nematode parasites has been widely reported. Rhodaneses (thiosulfate: cyanide sulfurtransferases) are present in a wide range of organisms, such as archaea, bacteria, fungi, plants and animals. Previously, it was reported that a rhodanese homologue could be bound by goat peripheral blood mononuclear cells (PBMCs) in vivo.Methods: In the present study, we cloned and produced a recombinant rhodanese protein originating from Haemonchus contortus (rHCRD), a parasitic nematode of small ruminants. rHCRD was co-incubated with goat PBMCs to assess its immunomodulatory effects on proliferation, apoptosis and cytokine secretion.Results: We verified that the natural HCRD protein localized predominantly to the bowel wall and body surface of the parasite. We further demonstrated that serum produced by goats artificially infected with H. contortus successfully recognized rHCRD, which bound to goat PBMCs. rHCRD suppressed proliferation of goat PBMCs stimulated by concanavalin A but did not induce apoptosis in goat PBMCs. The production of TNF-α and IFN-γ decreased significantly, whereas secretion of IL-10 and TGF-β1 increased, in goat PBMCs after exposure to rHCRD. rHCRD also inhibited phagocytosis by goat monocytes. Moreover, rHCRD downregulated the expression of major histocompatibility complex (MHC)-II on goat monocytes in a dose-dependent manner, but did not alter MHC-I expression.Conclusions: These results propose a possible immunomodulatory target that may help illuminate the interactions between parasites and their hosts at the molecular level and reveal innovative protein species as candidate drug and vaccine targets.
­­The Combined Outcomes of the COVID-19 Pandemic and a Collapsing Economy on Mental Well-Being: A Cross-Sectional Study
Authors: Sacre Hala , Hajj Aline , Badro Danielle A , Selwan Carla Abou , Aoun Randa , Salameh Pascale
Published: August 2020

Objective: To examine the outcomes of COVID-19 and a collapsing economy on mental well-being (MWB) of the general Lebanese population.Design/methods: This cross-sectional study enrolled 502 adults in May 2020.Results: MWB had a mean of 14.80. Female gender, university education, fear of COVID-19, fear of poverty, verbal violence at home, and chronic disease were associated with lower MWB. Better family satisfaction and financial situation were correlated with better MWB. Among workers/looking for a job: physical exercise was associated with better MWB, while previous waterpipe smoking, being self-employed before the crisis, working from home, closure of the institution, and worrying about long-term effects of the crisis on employment status were associated lower MWB. The fear of COVID-19 was not associated with MWB.Practical Implications: The Lebanese government should implement a reliable crisis management strategy that outlines stabilization and recovery measures to help people navigate through this period with minimal impact on mental, physical, and overall quality of life.
Evaluation of three-dimensional acromiohumeral distance in the standing position and comparison with its conventional measuring methods
Authors: Yoshida Yuki , Matsumura Noboru , Yamada Yoshitake , Yamada Minoru , Yokoyama Yoichi , Matsumoto Morio , Nakamura Masaya , Nagura Takeo , Jinzaki Masahiro
Published: August 2020

Background: Narrowing of the acromiohumeral distance (AHD) implies a rotator cuff tear. However, conventional AHD measurements using two-dimensional (2D) imaging or with the patient in the supine position might differ from that while standing during daily activity. This study aimed to evaluate the three-dimensional (3D) actual distance between the acromion and humeral head in the standing position and compare the AHD values with those obtained using conventional measuring methods.Methods: Computed tomography (CT) images of 166 shoulders from 83 healthy volunteers (31 male and 52 female; mean age 40.1 ± 5.8 years; age range, 30–49 years) were prospectively acquired in the supine and standing positions using conventional and upright CT scanners, respectively. The minimum distance between the acromion and humeral head on the 3D surface models was considered as the 3D AHD. We measured the 2D AHD on anteroposterior digitally reconstructed radiographs. The AHD values were compared between the supine and standing positions and between the 2D and 3D measurements.Results: The mean values of 2D AHD were 8.8 ± 1.3 mm (range, 5.9–15.4 mm) in the standing position and 8.1 ± 1.2 mm (range, 5.3–14.3 mm) in the supine position. The mean values of 3D AHD were 7.3 ± 1.4 mm (range, 4.7–14.0 mm) in the standing position and 6.6 ± 1.2 mm (range, 4.4–13.7 mm) in the supine position. The values of 3D AHD were significantly lower than those of 2D AHDs in both the standing and supine positions (P < 0.001). The values of 2D and 3D AHDs were significantly lower in the supine position than in the standing position (P < 0.001). Conclusions: This study evaluated the 3D AHD of normal shoulders in the standing position using an upright CT scanner. The present results indicated that assessments in the supine position can underestimate the value of the AHD compared with those made in the standing position and that assessments using 2D analysis can overestimate the value.
EML4-ALK induces cellular senescence in mortal normal human cells and promotes anchorage-independent growth in hTERT-transduced normal human cells
Authors: Miyanaga Akihiko , Matsumoto Masaru , Beck Jessica A. , Horikawa Izumi , Oike Takahiro , Okayama Hirokazu , Tanaka Hiromi , Burkett Sandra S. , Robles Ana I. , Khan Mohammed , Lissa Delphine , Seike Masahiro , Gemma Akihiko , Mano Hiroyuki , Harris Curtis C.
Published: August 2020

Background: Chromosomal inversions involving anaplastic lymphoma kinase (ALK) and echinoderm microtubule associated protein like 4 (EML4) generate a fusion protein EML4-ALK in non-small cell lung cancer (NSCLC). The understanding of EML4-ALK function can be improved by a functional study using normal human cells.Methods: Here we for the first time conduct such study to examine the effects of EML4-ALK on cell proliferation, cellular senescence, DNA damage, gene expression profiles and transformed phenotypes.Results: The lentiviral expression of EML4-ALK in mortal, normal human fibroblasts caused, through its constitutive ALK kinase activity, an early induction of cellular senescence with accumulated DNA damage, upregulation of p16INK4A and p21WAF1, and senescence-associated b-galactosidase (SA-β-gal) activity. In contrast, when EML4-ALK was expressed in normal human fibroblasts transduced with telomerase reverse transcriptase (hTERT), which is activated in the vast majority of NSCLC, the cells showed accelerated proliferation and acquired anchorage-independent growth ability in soft-agar medium, without accumulated DNA damage, chromosome aberration, nor p53 mutation. EML4-ALK induced the phosphorylation of STAT3 in both mortal and hTERT-transduced cells, but RNA sequencing analysis suggested that the different signaling pathways contributed to the different phenotypic outcomes in these cells. While EML4-ALK also induced anchorage-independent growth in hTERT-immortalized human bronchial epithelial cells in vitro, the expression of EML4-ALK alone did not cause detectable in vivo tumorigenicity in immunodeficient mice.Conclusions: Our data indicate that the expression of hTERT is critical for EML4-ALK to manifest its in vitro transforming activity in human cells. This study provides the isogenic pairs of human cells with and without EML4-ALK expression.
Temporal genetic variation and dispersal patterns of Aedes albopictus (Diptera: Culicidae) in three different climatic regions of China
Authors: Gao Jian , Zhang Hengduan , Guo Xiaoxia , Xing Dan , Dong YanDe , Lan CeJie , Wang Ge , Li ChaoJie , Li ChunXiao , Zhao TongYan
Published: August 2020

Background:Aedes albopictus is an indigenous primary vector for Dengue and Zika viruses in China. Compared with its insecticide resistance, biology, and vector competence, little is known about its genetic variation, which corresponds to environmental variations. Thus, the present study examines how Ae. albopictus varies among different climatic regions in China and deciphers its potential dispersal patterns.Methods:The genetic variation and population structure of 17 Ae. albopictus populations collected from three climatic regions of China were investigated with 11 microsatellite loci and the mitochondrial COI gene.Results:Of 44 isolated microsatellite markers, 11 pairs were chosen for genotyping analysis and had an average PIC value of 0.713, representing high polymorphism. The number of alleles was high in each population, with the ne value increasing from the temperate region (3.876) to the tropical region (4.144). Twenty-five COI haplotypes were detected, and the highest diversity was observed in the tropical region. The mean Ho value (ca. 0.557) of all the regions was significantly lower than the mean He value (ca. 0.684), with nearly all populations significantly departing from HWE and displaying significant population expansion (p-value < 0.05). Two genetically isolated groups and three haplotype clades were evaluated via STRUCTURE and haplotype phylogenetic analyses, and the tropical populations were significantly isolated from those in the other regions. Most genetic variation in Ae. albopictus was detected within populations and individuals at 31.40% and 63.04%, respectively, via the AMOVA test, and a relatively significant positive correlation was observed among only the temperate populations via IBD analysis (R2 = 0.6614, p = 0.048). Recent dispersions were observed among different Ae. albopictus populations, and four major migration trends with high gene flow (Nm>0.4) were reconstructed between the tropical region and the other two regions. Environmental factors, especially temperature and rainfall, may be the leading causes of genetic diversity in different climatic regions.Conclusions:Continuous dispersion contributes to the similarity of Ae. albopictus populations across different climatic regions, and environmental factors, especially temperature and rainfall, may be the leading causes of genetic variation.
Stress and Burnout in Postgraduate Physiotherapy Students: A Mixed Methods Observational Cohort Study
Authors: Brooke Tess , Brown Makaela , Orr Robin , Gough Suzanne
Published: August 2020

Background and Purpose: The impact of stress and burnout in students is an emerging topic. When students perceive that they are unable to cope with stressors, there is increased potential for burnout. To maximise students’ higher educational institution (HEI) outcomes, students must be able to effectively cope with stressful demands. Research suggests physiotherapy students, in particular, suffer from a high risk of stress and burnout, however limited research exists on postgraduate, pre-registration, physiotherapy students. The purpose of this study was to determine perceived stress, burnout and associated coping strategies across three time points in the first year of a post-graduate, pre-registration physiotherapy program. Subjects: All first year Doctor of Physiotherapy (DPHTY) students at Bond University 2019 were invited to participate. Methods: A mixed methods observational cohort design was implemented in one Australian HEI to determine stress, burnout and coping strategies across 3 time points. The 51-item self-administered questionnaire consisted of demographics, the Coping Self Efficacy (CSE) Scale and Maslach Burnout Inventory – General Survey for Students (MBI-GS (S)), and open-ended questions.Results: A response rate of 62% (n=38) was achieved. There were no differences in stress and burnout scores between sexes, nor differences in stress and burnout over time. Highest median CSE scores were seen at T1, with highest median MBI-GS (S) cynicism (CYN) scores at T2, exhaustion (EX) at T1 and T2, and professional efficacy (PE) at T1 and T2. The greatest mean CSE changes were seen from T1-T2 and T1-T3, and PE greatest changes from T2-T3 and T1-T3. No strong correlation was found between stress and burnout. Curriculum coursework was a frequently reported stressor, along with clinical placement and transition periods. Coping strategies utilized by students were both positive and maladaptive. Positive strategies included sporting activities, baking, listening to music, and social connections, whereas maladaptive strategies included alcohol consumption, excessive eating and gaming. Conclusion: Student consistently identified periods of stress and burnout, with curriculum coursework in particular being a trigger. Findings acknowledge the need for further investigation on sources of perceived stress, burnout and coping mechanisms to optimise student welfare and enhance HEI outcomes.
Severity-associated markers and assessment model for predicting the severity of COVID-19: a retrospective study in Hangzhou, China
Authors: Qi Jianjiang , He Di , Yang Dagan , Wang Mengyan , Ma Wenjun , Cui Huaizhong , Ye Fei , Wang Fei , Xu Jinjian , Li Zhijian , Liu Chuntao , Wu Jing , Qi Kexin , Wu Rui , Huang Jinsong , Liu Shourong , Zhu Yimin
Published: August 2020

Background: The severity of COVID-19 associates with the clinical decision making and the prognosis of COVID-19 patients, therefore, early identification of patients who are likely to develop severe or critical COVID-19 is critical in clinical practice. The aim of this study was to screen severity-associated markers and construct an assessment model for predicting the severity of COVID-19.Methods: 172 confirmed COVID-19 patients were enrolled from two designated hospitals in Hangzhou, China. Ordinal logistic regression was used to screen severity-associated markers. Least Absolute Shrinkage and Selection Operator (LASSO) regression was performed for further feature selection. Assessment models were constructed using logistic regression, ridge regression, support vector machine and random forest. The area under the receiver operator characteristic curve (AUROC) was used to evaluate the performance of different models.Results: Age, comorbidity, fever, and 18 biochemical markers (C-reactive protein, lactate dehydrogenase, D-dimer, albumin, etc) were associated with the severity of COVID-19 (all P values <0.05). By LASSO regression, eight markers were included for the assessment model construction. The ridge regression model had the best performance with AUROCs of 0.930 (95% CI, 0.914-0.943) and 0.827 (95% CI, 0.716-0.921) in the internal and external validations, respectively. A risk score, established based on the ridge regression model, had good discrimination in all patients with an AUROC of 0.897 (95% CI 0.845-0.940), and a well-fitted calibration curve. Using the optimal cutoff value of 71, the sensitivity and specificity were 87.1% and 78.1%, respectively. A web-based assessment system was developed based on the risk score. Conclusions: A panel of clinical markers were associated with the severity of COVID-19. An assessment model with eight markers would help clinicians to detect the patients who are likely to develop severe or critical COVID-19 at admission.
Development and launch of the first Obstetrics and Gynaecology Master of Medicine residency training programme in Botswana
Authors: Luckett Rebecca , Nassali Mercy , Melese Tadele , Moreri-Ntshabele Badani , Moloi Thabo , Hofmeyr Justus , Chobanga Kudrra , Masunge Japhter , Makhema Joe , Pollard Maisie , Ricciotti Hope , Ramogola-Masire Doreeen , Bazzett-Matabele Lisa
Published: August 2020

Background: Sub-Saharan Africa (SSA) faces a severe shortage of Obstetrician Gynaecologists (OBGYNs). While the Lancet Commission for Global Surgery recommends 20 OBGYNs per 100,000 population, Botswana has only 40 OBGYNs for a population of 2.3 million. We describe the development of the first OBGYN Master of Medicine (MMed) training programme in Botswana to address this human resource shortage.Methods: We developed a 4-year OBGYN MMed programme at the University of Botswana (UB) using the Kern's approach. We benchmarked curriculum content, learning outcomes, competencies, assessment strategies and research requirements with regional and international programmes. We engaged relevant local stakeholders and developed international collaborations to support in-country subspecialty training.Results: The OBGYN MMed curriculum was completed and approved by all relevant UB bodies within ten months during which time additional staff were recruited and programme financing was assured. The programme was advertised immediately; 26 candidates applied for four positions, and all selected candidates accepted. The programme was launched in January 2020 with government salary support of all residents. The clinical rotations and curricular development have been rolled out successfully. The first round of continuous assessment of residents was performed and internal programme evaluation was conducted. The national accreditation process was initiated.Conclusion: Training OBGYNs in-country has many benefits to health systems in SSA. Curricula can be adjusted to local resource context yet achieve international standards through thoughtful design and purposeful collaborations.
Radotinib Enhances Cytarabine (Ara-C)-Induced Acute Myeloid Leukemia Cell Death
Authors: Heo Sook-Kyoung , Noh Eui-Kyu , Yu Ho-Min , Kim Do Kyoung , Seo Hye Jin , Lee Yoo Jin , Cheon Jaekyung , Koh SuJin , Min Young Joo , Choi Yunsuk , Jo Jae-Cheol
Published: August 2020

Background: Acute myeloid leukemia (AML) is a heterogeneous disease that frequently relapses after standard chemotherapy. Therefore, there is a need for the development of novel chemotherapeutic agents that could treat AML effectively. Radotinib, an oral BCR-ABL tyrosine kinase inhibitor, was developed as a drug for the treatment of chronic myeloid leukemia. Previously, we reported that radotinib exerts increased cytotoxic effects towards AML cells. However, little is known about the effects of combining radotinib with Ara-C, a conventional chemotherapeutic agent for AML, with respect to cell death and cell cycle distribution in AML cells. Methods: Synergistic anti-cancer effects of radotinib and Ara-C in AML cells including HL60, HEL92.1.7, THP-1 and bone marrow cells from AML patients have been examined. Diverse cell biological assays such as cell viability assay, Annexin V-positive cells, caspase-3 activity, cell cycle distribution, and related signaling pathway have been performed. We also confirmed synergistic effects of radotinib and Ara-C on the xenograft model in vivo. Results: The combination of radotinib and Ara-C was found to induce AML cell apoptosis, which involved the mitochondrial pathway. In brief, combined radotinib and Ara-C significantly induced Annexin V-positive cells, cytosolic cytochrome C, and the pro-apoptotic protein Bax in AML cells including HL60, HEL92.1.7, and THP-1. In addition, mitochondrial membrane potential and Bcl-xl protein were markedly decreased by radotinib and Ara-C. Moreover, this combination induced caspase-3 activity. Cleaved caspase-3, 7, and 9 levels were also increased by combined radotinib and Ara-C. Additionally, radotinib and Ara-C co-treatment induced G0/G1 arrest via the induction of CDKIs such as p21 and p27 and the inhibition of CDK2 and cyclin E. Thus, radotinib/Ara-C induces mitochondrial-dependent apoptosis and G0/G1 arrest via the regulation of the CDKI–CDK–cyclin cascade in AML cells. In addition, our results showed that combined treatment with radotinib and Ara-C inhibits AML cell growth, including tumor volumes and weights in vivo. Also, the combination of radotinib and Ara-C can sensitize cells to chemotherapeutic agents such as daunorubicin or idarubicin in AML cells. Conclusions: Therefore, our results can be concluded that radotinib in combination with Ara-C possesses a strong anti-AML activity.
Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer and Choroidal Metastases: Long-Term Outcome and Response to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors
Authors: Bouchez Clémentine , Pluvy Johan , Soussi Ghassen , Nguenang Marina , Brosseau Solenn , Tourne Morgan , Collin Mégane , Théou-Anton Nathalie , Guyard Alice , Ammar Jamila , Khalil Antoine , Zalcman Gérard , Gounant Valérie
Published: August 2020

Background: Although previously reported, little is known about choroidal metastasis in Epidermal Growth Factor Receptor (EGFR)-mutant Non-small cell lung cancer (NSCLC). Methods: In this single-center retrospective cohort including 83 consecutive metastatic EGFR-mutant NSCLC patients, from Sept. 2015 to Oct. 2018, six exhibited symptomatic choroidal metastases. All brain MRI scans performed in the EGFR-mutant patients were reviewed, with one case of asymptomatic choroidal metastasis identified. Kaplan-Meier analysis and log-rank test were conducted to assess median overall survival (OS) from diagnosis for the two groups, with or without choroidal metastases.Results: Prevalence of choroidal metastases in EGFR-mutated NSCLCs was 8.4% (7/83). Five were women, and four current or former smokers. Molecular analysis showed three tumors with exon 19 deletion, three with L858R mutation, and one with complex exon 21 mutation. The choroidal metastases were symptomatic in six/seven patients. Visual disturbances decreased in all but one symptomatic cases upon EGFR TKI, and the choroidal response was maintained over time. Median follow-up was 42.2 mo (95%CI [37.2 - 47.1]). Median OS in the choroidal metastasis group was 23.4 mo (95%CI [0.1 - 51.4]) versus 27.9 mo (95%CI [16.9 - 38.9]) in the non-choroidal metastasis group (p=0.32). In the choroidal metastasis group, 2-year and 5-year OS were 47.6% and 0%, respectively, versus 55.8% and 26.3% in the non-choroidal metastasis subset.Conclusions: Choroidal metastases in NSCLC EGFR-mutant patients are rare but should be systematically suspected in case of visual disturbance. TKIs are efficient for treating visual symptoms. Whether choroidal metastases confer a worse prognosis remains unclear owing to the third-generation EGFR TKI osimertinib first-line registration.
Risk Of Dengue Transmission In Urban Areas Of Malang, Indonesia
Authors: Rakhmani Alidha Nur , Zuhriyah Lilik
Published: August 2020

Background. Larvae monitoring through community participation is one of dengue prevention programs to control mosquito larvae. Entomology index could be an indicator of the existence of mosquito larvae in an area. This study aimed to determine the entomology index in the urban areas in Malang city and key container which could be the breeding ground of mosquito.Methods. This study was a surveillance study conducted in five subdistricts in Malang city from November 2017 to April 2018. A semi-structured questionnaire delivered using interviews to 400 respondents was used to explore the practice of Dengue prevention behavior. Observations were performed to examine the mosquito larva existence among the houses of health volunteers.Results. Density figure in Malang was indicated as moderate density that had range 2-5 . Blimbing subdistrict had the highest House Index (HI) value, which was 30.3% with Container Index (CI) value of 10.6% and Breteau Index (BI) value of 36,3 %. The most common positive Controllable Containers were bathroom tub/container (8.5%) and the water reservoir of a refrigerator (3%).Conclusion. Urban area in Malang has a moderate risk of transmitting dengue fever whose highest risk area was Blimbing subdistrict. There is need health promotion more or strict policy to the community also health volunteers to observe bathroom containers and water reservoir of refrigerator.
Assessing How Health Information Needs of Individuals With Colorectal Cancer Are Met Across the Care Continuum: an International Cross-Sectional Survey
Authors: Dau Hallie , Safari Abdollah , Din Khalid Saad El , McTaggart-Cowan Helen , Loree Jonathan M. , Gill Sharlene , De Vera Mary A.
Published: August 2020

Background: Studies evaluating health information needs in colorectal cancer (CRC) lack specificity in terms of study samples involving patients. We assessed how health information needs of individuals with CRC are met across the care continuum.Methods: We administered an international, online based survey. Participants were eligible for the study if they: 1) were 18 years of age or older; 2) received a diagnosis of CRC; and 3) were able to complete the online health survey in English, French, Spanish, or Mandarin. We grouped participants according to treatment status. The survey comprised sections: 1) demographic and cancer characteristics; 2) health information needs; and 3) health status and quality of life. We used multivariable regression models to identify factors associated with having health information needs met and evaluated impacts on health-related outcomes.Results: We analyzed survey responses from 1,041 participants including 258 who were currently undergoing treatment and 783 who had completed treatment. Findings suggest that information needs regarding CRC treatments were largely met. However, we found unmet information needs regarding psychosocial impacts of CRC. This includes work/employment, mental health, sexual activity, and nutrition and diet. We did not identify significant predictors of having met health information needs, however, among participants undergoing treatment, those with colon cancer were more likely to have met health information needs regarding their treatments as compared to those with rectal cancer (0.125; 95% CI, 0.00 to 0.25; p-value = 0.051). Conclusions: Our study provides a comprehensive assessment of health information needs among individuals with CRC across the care continuum.
Sorafenib as a Second-Line Treatment in Metastatic Renal Cell Carcinoma in Mexico: A Prospective Cohort Study
Authors: Martin-Aguilar Ana Elena , Núñez-López Haidé Nayeli , Ramirez-Sandoval Juan C.
Published: August 2020

Background: Sequential inhibition of the vascular endothelial growth factor (VEGF) pathway with sorafenib could be useful for patients with metastatic renal cell carcinoma (RCC). Our aim was to determine the activity and tolerability of sorafenib as a second-line therapy in advanced RCC initially treated with a different VEGF-tyrosine kinase inhibitor (TKI).Methods: A prospective observational cohort in Mexico (2012–2019). We included 148 subjects with metastatic RCC and who had progression despite treatment with sunitinib (n = 144) or pazopanib (n = 4). The primary end-point was time to disease progression as evaluated every 12–16 weeks.Results: The mean age of the cohort was 58 years (interquartile range [IQR] 48-68), 104 (70%) were men, and 51 (35%) had a favorable prognosis according to the IMDC (International Metastatic RCC Database Consortium) prognostic model. The median progression-free survival (PFS) and overall-survival after the introduction of sorafenib treatment was 8.5 months (95% confidence interval [CI]: 6.8–10.2) and 40.1 months (95% CI: 35.2–45.0) respectively. The median overall survival from RCC diagnosis to death was 71 months (95% CI: 63.9–79.4). On multivariate analyses, age >65 years was associated with a longer PFS (HR 0.57; 95% CI: 0.35-0.93; p = 0.025). The median PFS in subjects aged >65 years was longer compared to subjects ≤65 years (14.0 [95% CI: 9.2–17.9] vs. 7.2 months [95% CI: 5.5–8.9]; p = 0.018). Adverse events grade ≥3 associated with sorafenib occurred in 42 (28%) patients.Conclusion: Sequential inhibition of VEGF with sorafenib as a second-line treatment may benefit patients with metastatic RCC, especially in subjects >65 years old.
Fabrication of Polylactic Acid/Paclitaxel Nano Fibers by Electrospinning for Cancer Therapeutics
Authors: Yu C. H. , Chan Vincent , Li Chuan , Hsieh J. H. , Lin P. H. , Tsai Ya-Hui , Chen Yun
Published: August 2020

Background: Polylactic acid (PLA) is a thermoplastic and biodegradable polyester, largely derived from renewable resources such as corn starch, cassava starch and sugarcane. However, PLA is only soluble in a narrow range of solvents such as tetrahydrofuran, dioxane, chlorinated solvents and heated benzene. The limited choices of solvent for PLA dissolution have imposed singificant challenges in the development of specifically engineered PLA nanofibers with electrospinning techniques.Methods: Generally, the electrospun polymeric materials have been rendered with unique properties such as high porosity and complex geometry while maintaining its biodegradability and biocompatibility for emerging biomedical applications. In this study, a new drug delivery system composed of PLA nanofibers with encapsulated paclitaxel was developed by the electrospinning of the respective nanofibers on top of a spin-coated thin film with the same chemical compositions. Our unique approach is meant for promoting strong bonding between PLA-based nanofibers and their respective films in order to improve the prolonged release properties and composite film stability within a fluctuative phyiochemical environment during cell culture.Results: PLA/paclitaxel nanofiber supported on respective polymeric films were probed by scanning electronic microscope, Fourier transform infrared spectrometer and water contact measurement for determining their surface morphologies, fibers’ diameters, molecular vibrational modes, and wettability, respectively. Moreover, PLA/paclitaxel nanofibers supported on respective spin-coated films at different loadings of paclitaxel were evaluated for their abilities in killing human colorectal carcinoma cells (HCT-116). More importantly, MTT assays showed that regardless of the concentrations of paclitaxel, the growth of HCT-116 was effectively inhibited by the prolonged release of paclitaxel from PLA/paclitaxel nanofibers.Conclusions: An effective prolonged delivery system based on PLA nanofiber has demonstrated exciting potentials for emerging applications in cancer therapeutics.
Wearable Sensors for Turning Assessment to Discriminate Frailty Syndrome Among Community-Dwelling Older Adults
Authors: Chiu Huei-Ling , Tsai Chen-Ying , Liu Yu-Lin , Kang Chun-Wei , Lee Shu-Chun
Published: August 2020

The authors have withdrawn this preprint due to erroneous posting.
Medical Practice Differences Among Internal Medicine Fellows During in-hospital Emergency Department 24-hour Shifts
Authors: Repusic Marina , Zeljkovic Matea Kolacevic , Babacanli Alen , Olujic Vida , Radovanic Sandra , Sikic Aljosa , Radeljic Vjekoslav , Bulj Nikola , Pavlovic Nikola , Dula Kristijan , Manola Sime , zeljkovic ivan
Published: August 2020

Background There are limited data which show how Emergency Department (ED)-specific knowledge and skills are acquired throughout the internal medicine fellowship, especially during 24-hour shifts. The aim of the study was to assess the differences in medical practice between fellows among different fellowship-years in ED settings. Methods We conducted a cross-sectional, retrospective study at a large university hospital using data on every ED examination done during 2016. All data were taken from the hospital information system. We compared 1st-year fellows with all older fellows, as well as 5th-year fellows with all younger fellows. Results In 2016, 55 fellows had ≥ 15 24-hour shifts with 3 attending fellows during one shift. A total of 19’916 patients were examined by attending fellows in the ED. When compared to 2nd-year fellows, 1st-year fellows examined more patients brought to ED by out-of-hospital emergency medical team and had significantly higher share of examined patients per 24-hour shift with lower length of stay. When compared to 5th-year fellows, 1st-year fellows examined older patients, but had lower share of examined patients during one 24-hour shift and participated in fewer CPR cases. When compared to younger fellows, 5th-year fellows participated in more CPR cases and had higher proportion of patients admitted to hospital. Conclusion To our knowledge, this is the first report on the ED medical practice differences among fellows of different fellowship-year. When compared to other fellows, 1st-year fellows participated less in CPR cases, but were faster in providing medical care in ED. 5th-year fellows had the highest proportion of patients admitted to hospital and more CPR cases.
CD247 Functions as a Prognostic Biomarker for Cutaneous Malignant Melanoma Based on the Analysis of Tumor-immune Microenvironment
Authors: ma yi , Chen Shu-Shu , Feng Yan-Yan , Ma Ru-Yi , Wang Huan-Liang
Published: August 2020

Background: Cutaneous malignant melanoma (CMM) is among the most lethal cancers. The tumour microenvironment (TME) is closely linked with tumorigenesis, metastasis, and prognosis.Methods: We employed the ESTIMATE algorithm to calculate immune and stromal scores of malignant melanoma tissues from the Cancer Genome Atlas dataset, respectively, and determine core prognosis gene signature examined by COX proportional hazards model. Functional enrichment annotation, the Kyoto Encyclopedia of Genes and Genomes pathways, the Protein-Protein Interaction network, Weighted Gene Co-expression Network Analysis and overall survival analysis were used to formulate potential function of these genes that involved in immune-linked biological processes. CIBERSORT algorithm was used to estimate the abundances of immune cell types in CMM samples. Finally, the OncoLnc platform, the Gene Expression Profiling Interactive Analysis resources, and the Human Protein Atlas database were applied to validate our results. Results：908 differential expressed genes and ten hub genes were screened, and GO annotation indicated that immune response and inflammatory response were firmly involved in CMM tumorigenesis and progression. CD247, identified as the most significant prognostic biomarker, highly expressed in tumor samples and possessed a better prognosis than low expressed samples. The correlation analysis of immune cells infiltration unveiled that CD8+ T cell and Macrophages were intense significant to CMM patients' prognosis. Survival analysis suggested that ten hub genes and infiltrated immune cells are linked to the prognosis of CMM. ConnectiveMap analysis strongly indicated that L-securinine may be a promising candidate medicine for CMM patients.Conclusions: we deeply analyzed the immune-linked genes with the tumour microenvironment, and labeled CD247 as the most intriguing prognostic biomarker for CMM, which may bring better clinical outcomes for CMM patients.
Diabetes impacts liver stiffness in chronic hepatitis C patients with and without virological cure: a longitudinal study
Authors: Pontual Daniela Malta , Nabuco Leticia Cancella , Luiz Ronir Raggio , Cardoso Ana Carolina , Perez Renata M. , Villela-Nogueira Cristiane Alves
Published: August 2020

Background: Transient elastography is controversial as a follow-up tool in chronic hepatitis C (CHC) patients. The aim was to assess the variation of liver stiffness measures and its associated factors on a cohort of CHC individuals composed of naïve, sustained virological response (SVR) and non-responder patients (NR).Methods: This was a longitudinal study in CHC patients who were followed with clinical, laboratorial and serial elastography (Fibroscan®). The rate of progression of liver stiffness was calculated and the associated factors for progression were assessed by multiple linear regression analysis. Results: Four hundred and six patients were included: 29% naïve, 24% NR and 47% SVR who were followed for 44 (35-53) months. There was a significant decrease in liver stiffness among SVR patients [11.8 (9.2) kPa vs 8.8 (8.4) kPa (p<0.001)], a trend for liver stiffness increasing in NR group [6.6 (5.2) kPa vs 7.1 (4.5) kPa; p=0.069)] and no change of liver stiffness in naïve group [6.3 (3.0) vs 6.0 (3.8); p=0.22]. The related factors for liver stiffness progression were lack of SVR (p=0.002) and diabetes (p=0.05). In non-diabetic SVR group, a negative rate of progression (- 0.047 kPa/month) was found compared to the highest rate in diabetic non-responder patients (+ 0.044 kPa/month). Diabetics with SVR showed a rate of (+) 0.037 kPa/month while in non-diabetic non-responder patients the ratio was (+) 0.028 kPA/month.Conclusion: Despite SVR, liver stiffness in diabetic patients progresses, suggesting that a close follow-up of diabetic patients should remain even after SVR.
Molecular Detection, not Extended Culture Incubation, Contributes to Diagnosis of Fungal Infection
Authors: Zhu Alex , Qi Chao
Published: August 2020

Background. Despite of low sensitivity, fungal culture remains one of the key methods for diagnosing and treatment of fungal infections as it identifies etiology at genus and species level and offers susceptibility testing. The Manual of Clinical Microbiology recommends that fungal cultures screening for all pathogens should routinely be held for 4 weeks to maximize the recovery of slow growing species. Information on the optimal fungal culture time in the era of expansion of immunocompromised populations is lacking. The goal is to review our experience with fungal culture in order to determine the optimal culture incubation time; to review our experience of broad-range ITS PCR for diagnosis of culture negative fungal infections. Methods. Fungal culture and ITS PCR results from January 1, 2013 to December 31, 2017 were reviewed.Results. Ninety six percent of positive cultures (4058) were detected in the first seven days of incubation. During the second week of incubation, 2.8% of positives (111) were detected from day 8 to 10, and 1.7% (71) were detected from day 11 to 14. Only 0.1% of positive culture were detected in the third week of incubation, and no positive culture was detected in the fourth week of incubation. No Clinical significance of fungal isolates recovered after 14 days. Clinical significant pathogens were detected in 0.2% culture negative samples.Conclusion. Extending culture incubation beyond two weeks did not generate clinical relevant results. When culture failed to make laboratory diagnosis, ITS PCR produced clinical significant results.