bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of Criminal Cases against Physicians Charged with Opioid-Related Offenses Reported in the US News Media, 1995-2019
Authors: Berman Julia B , Li Guohua
Published: August 2020

Background: Pharmaceutical companies and drug distributors are intensely scrutinized in numerous lawsuits for their role in instigating the opioid epidemic. Many individual physicians have also been held accountable for activities related to prescribing opioid medications. The purpose of this study was to examine the epidemiologic patterns of criminal cases against physicians charged with opioid-related offenses reported in the US news media. Methods: We searched the Nexis Uni® database for news media reports on physicians who had been arrested, indicted or criminally charged for illegally prescribing opioids between January 1995 and December 2019. Data collected from the news media reports include defendant’s age, sex, clinical specialty, type of crime and legal consequences. Results: The annual number of criminal cases against physicians charged with opioid-related offenses reported in the US news media increased from 0 in 1995 to 42 in 2019. Of the 372 physician defendants in these criminal cases, 90.1% were male, 27.4% were 65 years and older, and 23.4% were charged in Florida. Of the 358 physician defendants with known clinical specialty, 245 (68.4%) practiced in internal medicine, family medicine, or pain management. Drug trafficking was the most commonly convicted crime (accounting for 54.2% of all convicted cases), followed by fraud (19.1%), money laundering (11.0%) and manslaughter (5.6%). Of the 244 convicted physicians with known sentences, 85.0% were sentenced to prison with an average prison term of 127.3 ± 120.3 months.Conclusions: The US news media has reported on an increasing number of opioid-related criminal cases against physicians from a wide variety of clinical specialties. The most commonly convicted crime in these cases is drug trafficking, followed by fraud, money laundering, and manslaughter.
Using short read sequencing to characterise balanced reciprocal translocations in pigs
Authors: Bouwman Aniek C. , Derks Martijn F.L. , Broekhuijse Marleen L.W.J. , Harlizius Barbara , Veerkamp Roel F.
Published: August 2020

Background A balanced constitutional reciprocal translocation (RT) is a mutual exchange of terminal segments of two non-homologous chromosomes without any loss or gain of DNA in germline cells. Carriers of balanced RTs are viable individuals with no apparent phenotypical consequences. These animals produce, however, unbalanced gametes and show therefore reduced fertility and offspring with congenital abnormalities. This cytogenetic abnormality is usually detected using chromosome staining techniques. The aim of this study was to test the possibilities of using paired end short read sequencing for detection of balanced RTs in boars and investigate their breakpoints and junctions. Results Balanced RTs were recovered in a blinded analysis, using structural variant calling software DELLY, in 6 of the 7 carriers with 30 fold short read paired end sequencing. In 15 non-carriers we did not detect any RTs. Reducing the coverage to 20 fold, 15 fold and 10 fold showed that at least 20 fold coverage is required to obtain good results. One RT was not detected using the blind screening, however, a highly likely RT was discovered after unblinding. This RT was located in a repetitive region, showing the limitations of short read sequence data. The detailed analysis of the breakpoints and junctions suggested three junctions showing microhomology, three junctions with blunt-end ligation, and three micro-insertions at the breakpoint junctions. The RTs detected also showed to disrupt genes. Conclusions We conclude that paired end short read sequence data can be used to detect and characterize balanced reciprocal translocations, if sequencing depth is at least 20 fold coverage. However, translocations in repetitive areas may require large fragments or even long read sequence data.
Insights on mental health when living with rheumatoid arthritis: A descriptive qualitative study of threads on the Reddit website
Authors: Park Jamie Yea Eun , Howren Alyssa M. , Davidson Eileen , De Vera Mary A
Published: August 2020

Background: Reddit is a highly visited social news and discussion website where individuals anonymously ask questions, post opinions and share experiences, which provide a valuable pool of publicly available data. Our objective was to systematically search and analyze threads on the social news website, Reddit, to understand experiences of individuals with rheumatoid arthritis (RA) regarding their mental health. Methods: We conducted a patient-oriented descriptive qualitative study. We identified threads from two subreddits, “r/Thritis” and “r/Rheumatoid”, using keywords such as “mood”, “mental health”, “stressed”, “depressed”, “anxious” over a 1-year period between June 2018 and June 2019. For included threads, we extracted the title, original post, and corresponding comments and responses. We applied thematic analysis using an inductive approach. Results: Of 81 threads identified, we included 27. We identified four themes: 1) Navigating the management of RA explores how the physical impacts of the disease, lack of health resources/support and the complexity of medications affect mental health; 2) Experiencing impact on relationships and social isolation includes experiencing misconceptions of RA, feeling misunderstood and feeling guilt; 3) Experiencing loss , touches on the helplessness brought by challenges with performing self-defining activities such as self-care, work, and childbearing/parenting; and finally, 4) Experiencing emotional struggles captures how tension between fighting through and despair has led some to suicide ideation and thoughts of death. Conclusions: Online forums and communities such as Reddit have created opportunities for individuals with RA to share experiences on mental health matters, which they may not necessarily be able to share with others.
Knowledge about syphilis and its oral manifestations among dental students: a cross-sectional study from Brazil, 2019
Authors: Filho Antonio Carlos Pacheco , Garbin Artênio José Isper , Pires Natália Cupertino , Pacheco Karina Tonini dos Santos , Garbin Cléa Adas Saliba
Published: August 2020

Background: Clinical manifestations of the syphilis can occur in the mouth and in the perioral region. This study aimed to investigate the knowledge about syphilis and its oral manifestations among dental students and to discuss the role of the dentist in prevention and control of this disease. Methods: This is a cross-sectional study carried out with 171 dentistry students enrolled in the second, third, fourth and fifth years in the first semester of 2019 from the Federal University of Espírito Santo, Brazil. Data collection was performed by a questionnaire containing 16 questions answered by students in classroom. Analyses of absolute and relative frequency were performed. To perform association among variables, the Chi-square test (or Fisher's exact test with Yates correction) was performed with 5% significance level. Results: Overall, 169 students participated in the study. Only 40 (46.4%) students correctly answered the question about disease stages. Almost all participants answered that syphilis has oral manifestations; however, only 44 (25.7%) answered the question correctly. Regarding differential diagnoses of other oral lesions, only 63 (37.3%) reported knowledge on this subject. There was a statistically significant association between student’s educational level and knowledge about the etiological agent (p<0.0001), clinical manifestations (p<0.0001), disease stages (p<0.0001), oral manifestations (p<0.0001) and drugs (p = 0.005) related to the disease. Conclusions: Participants showed important gaps in their knowledge about syphilis and its oral manifestations. Our findings, together with the increased number of new cases of the disease in the world, reinforce the need for training dental professionals with knowledge about early diagnosis, effective treatment and follow-up of syphilis cases.
Palliative Care in the Pre-Hospital Service In Brazil: Experiences of Health Professionals
Authors: Boaventura Jacqueline Resende , Pessalacia Juliana Dias Reis , Ribeiro Aridiane Alves , de Souza Fabiana Bolela , Neto Priscila Kelly da Silva , Marinho Maristela Rodrigues
Published: August 2020

Background: An integrated care network between emergency, specialized and primary care services can prevent repeated hospitalizations and the institutionalized death of terminally ill patients in palliative care (PC). To identify the perception of professionals in a pre-hospital care (PHC) service about the outcomes of the assistance provided to patients eligible for PC. Methods: Study with a qualitative approach, of interpretative nature, based on the perspective of Ricouer's Dialectical Hermeneutics. Results: Three central themes emerged out of the professionals' speeches: (1) unpreparedness of the team, (2) decision making, and (3) dysthanasia. Conclusions: It is necessary to invest in professional training associated with PC in the home context and its peculiarities, adopt a specific policy for PC that involves all levels of care, including PHC, and adopt a unified information system, as well as more effective procedures that favor the respect for the patients' will, without generating dissatisfaction to the team and the family.
Genetic Determinants Of Clinical Phenotype In Hypertrophic Cardiomyopathy 
Authors: Velicki Lazar , Jakovljevic Djordje G , Preveden Andrej , Golubovic Miodrag , Bjelobrk Marija , Ilic Aleksandra , Stojsic Snezana , Barlocco Fausto , Tafelmeier Maria , Okwose Nduka , Tesic Milorad , Brennan Paul , Ristic Arsen , Popovic Dejana , MacGowan Guy A , Filipovic Nenad , Maier Lars S. , Olivotto Iacopo
Published: August 2020

Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations.Methods: As a part of the international multidisciplinary SILICOFCM project (www.silicofcm.eu) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography.Results: The most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a significantly higher number of patients with a positive family history of HCM (46% vs. 7%; p=0.014). There was a numerically higher prevalence of atrial fibrillation in the MYH7 group (60% vs. 35%, p=0.085). Laboratory analyses revealed normal levels of creatinine (85.5±18.3 vs. 81.3±16.4 µmol/l; p=0.487) and blood urea nitrogen (10.2±15.6 vs. 6.9±3.9 mmol/l; p=0.472) which were similar in both groups. The systolic anterior motion presence was significantly more frequent in patients caring MYH7 mutation (33% vs. 10%; p=0.025), as well as mitral leaflet abnormalities (40% vs. 19%; p=0.039). Calcifications of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p=0.001). The difference in diastolic function, i.e. E/e’ ratio between the two groups was also noted (MYBPC3 8.8±3.3, MYH7 13.9±6.9, p=0.079).Conclusions: Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.
Prevalence and Molecular Characterization of Group B Streptococcus in Pregnant Women from Hospitals in Ohangwena and Oshikoto Regions of Namibia.
Authors: Moyo Sylvester Rodgers , Haimbodi Erastus Lafimana , Mukesi Munyaradzi
Published: August 2020

BackgroundThe main purpose of this study was to investigate the prevalence rate, antimicrobial susceptibility patterns and molecular characteristics of Streptococcus agalactiae isolated from pregnant women at 35 weeks of gestation and above, who attended antenatal screening at selected hospitals in Ohangwena and Oshikoto regions of Namibia.ResultsTwelve (5.7%) of women screened were colonised by GBS, of which 25.0% were colonised rectovaginally, 58.0% vaginally and 17.0% rectally. No significant association was reported between GBS colonisation and maternal age, habitat, marital status, education, employment, parity, still births and miscarriages (P values >0.05). Antimicrobial susceptibility was reported at 100% for ampicillin, penicillin & ceftriaxone. Resistance to tetracycline was reported at 100%. Tetracycline resistance gene tet(M) was present in 88.9% of the isolates only and none of the isolates presented with tet(O). Polysaccharide capsular type Ia was found in 9(50%) and Ib was found in 1(5.5%) of the total isolates. The remaining isolates were not typeable using PCR.ConclusionStreptococcus agalactiae’s positive rate was 5.7% among the pregnant women examined. Socio-demographic and obstetric factors had no influence on GBS colonisation (P values >0.05). No resistance was reported to ampicillin, penicillin and ceftriaxone. No sensitivity was reported to tetracycline. Fifty (50%) of the isolates were capsular type Ia, 5.5% were type Ib and 44.4% were not typeable using PCR.
Cyclotron-based production of 68Ga, [68Ga]GaCl3, and [68Ga]Ga-PSMA-11 from a liquid target
Authors: Rodnick Melissa E , Sollert Carina , Stark Daniela , Clark Mara , Katsifis Andrew , Hockley Brian G , Parr D. Christian , Frigell Jens , Henderson Bradford D , Abghari-Gerst Monica , Piert Morand R , Fulham Michael J , Eberl Stefan , Gagnon Katherine , Scott Peter J. H.
Published: August 2020

Purpose: To optimize the direct production of 68Ga on a cyclotron, via the 68Zn(p,n)68Ga reaction using a liquid cyclotron target. We Investigated the yield of cyclotron-produced 68Ga, extraction of [68Ga]GaCl3 and subsequent [68Ga]Ga-PSMA-11 labeling using an automated synthesis module.Methods: Irradiations of a 1.0 M solution of [68Zn]Zn(NO3)2 in dilute (0.2-0.3 M) HNO3 were conducted using GE PETtrace cyclotrons and GE 68Ga liquid targets. The proton beam energy was degraded to a nominal 14.3 MeV to minimize the co-production of 67Ga through the 68Zn(p,2n)67Ga reaction without unduly compromising 68Ga yields. We also evaluated the effects of varying beam times (50-75 min) and beam currents (27-40 μA). Crude 68Ga production was measured. The extraction of [68Ga]GaCl3 was performed using a 2 column solid phase method on the GE FASTlab Developer platform. Extracted [68Ga]GaCl3 was used to label [68Ga]Ga-PSMA-11 that was intended for clinical use.Results: The decay corrected yield of 68Ga at EOB was typically >3.7 GBq (100 mCi) for a 60 min beam, with irradiations of [68Zn]Zn(NO3)2 at 0.3 M HNO3. Target/chemistry performance was more consistent when compared with 0.2 M HNO3. Radionuclidic purity of 68Ga was typically >99.8% at EOB and met the requirements specified in the European Pharmacopoeia (<2% combined 66/67Ga) for a practical clinical product shelf-life. The activity yield of [68Ga]GaCl3 was typically >50% (~1.85 GBq, 50 mCi); yields improved as processes were optimized. Labeling yields for [68Ga]Ga-PSMA-11 were near quantitative (~1.67 GBq, 45mCi) at EOS. Cyclotron produced [68Ga]Ga-PSMA-11 underwent full quality control, stability and sterility testing , and was implemented for human use at the University of Michigan as an Investigational New Drug through the US FDA and also at the Royal Prince Alfred Hospital (RPA).Conclusion: Direct cyclotron irradiation of a liquid target provides clinically relevant quantities of [68Ga]Ga-PSMA-11 and is a viable alternative to traditional 68Ge/68Ga generators.
Epidemiologic profile of viral hepatitis B and C in North of Iran: Results from PERSIAN Guilan Cohort Study (PGCS)
Authors: Mansour-Ghanaei Fariborz , Joukar Farahnaz , Naghipour Mohammadreza , Hassanipour Soheil , Yeganeh Sara , Sepehrimanesh Masood , Fathalipour Mohammad
Published: August 2020

Objective
Hepatitis B (HBV) and C (HCV) viruses are two severe infectious diseases with a high global health impact. This study aimed to evaluate the prevalence of HBV and HCV in the Prospective Epidemiological Research Studies of the Iranian Adults (PERSIAN) Guilan Cohort Study through immunological and molecular methods.
Results
The blood samples were obtained from 10520 enrolled participants. Complete biochemical and hematological assessments plus urine analysis were done. The presence of HBsAg, anti-HBs, anti-HBc, and anti-HCV antibodies for all participants and HBeAg and anti-HBe antibody for HBV positive patients were evaluated. HBV genomic DNA and HCV genomic RNA were extracted from positive serum samples. The real-time PCR assay was done to quantify HBV and HCV genomes. HCV genotyping was also performed. The HBV and HCV prevalence was 0.24% (95% CI, 0.16% to 0.35%) and 0.11% (95% CI, 0.06% to 0.19%), respectively. Rural participants were significantly more HBV positive than urban peoples (P = 0.045) while male individuals were significantly more HCV positive than female participants (P = 0.013). Our detected HBV and HCV prevalence were lower than other cities/provinces of Iran, which may be due to lifestyle or other unknown reasons.
WITHDRAWN: Organizational Change Readiness, Service Innovation, And Corporate Image In Improving Port Competitiveness In Indonesia
Authors: Hutapea John Gunung
Published: August 2020

Purpose: The purpose of this research is to test and explain the effect of Organizational readiness for change, Service Innovation, and Corporate Image on Perceived opportunity and challengeDesign/Method: The instrument in this research was in the form of questionnaires contained a number of statements developed from the instrument grid. The scale used is a Likert Scale. Inferential analysis is used to analyze sample data and the results are applied to the population. The research model with inferential analysis uses a Structural Equation Modeling (SEM) analysis with the WarpPLS approach, expected to answer the statements of problem and be able to test the desired hypothesis. Findings: The model development in this research was based on the background, statements of problem, conceptual framework and research hypotheses. The model referred to is “Complete and Comprehensive Port.” Its development was carried out through studying and synthesizing various sources. The most important source is the results of literature review in the form of theoretical developments and research results, then continued with compilation. Originality: The use of Organizational Change Readiness, Service Innovation, and Corporate Image in improving Port Competitiveness is seen as one of the novelty in this research, specifically the use of the Organizational Change Readiness variable which is often used in high-flexibility companies but now used in port companies.
WITHDRAWN: Knowledge, Preventative Practices and Depression of Chinese University Students in Korea and China During the COVID-19 Pandemic: An Online Cross-Sectional Study
Authors: ‍Zhao Bo , Kong Fanlei , Nam Eun Woo
Published: August 2020

(1) Background: To investigate the knowledge, preventative practices and depression of Chinese university students living in Korea (‘International Group’) and Mainland China (‘Mainland Group’) during the Coronavirus Disease 2019 (COVID-19) outbreak, and furtherly explore the determinants of depression among these students; (2) Methods: The study was conducted using an online questionnaire tool designed by the Yonsei Global Health Center, with preventative knowledge and practice questions on COVID-19, as well as PHQ-9 (used to diagnose depression for patients). 420 college students were finally included in the analysis (171 students in Korea and 249 students in mainland China). This data was collected from March 23 to April 12, 2020; (3) Results: Majority of these students had a good level of knowledge of COVID-19. The ‘International Group’ did better than the ‘Mainland Group’ students regarding preventative practices, but the percentage with mild depression was higher among the ‘International Group’. Highly concerned about family members, highly concerned about getting COVID-19, and having a suspicion of contact with patients increased the depression state among the subjects. Meanwhile, taking preventative behaviors more comprehensively decreased the depression state of both groups; (4) Conclusions: During the pandemic of COVID-19, the depression status of ‘International Group’ students was significantly severer than that in ‘Mainland Group’. While the depression status of these two groups’ students was correlated to highly concerning family members and getting COVID-19 and having a suspicion of contact with patients. Therefore, psychological counseling and education programs are needed in order to support and improve the mental health of ‘international group’s students.
Identifying Barriers to Condom Use Among Female Sex Workers: a Systematic Review and Meta-analysis
Authors: Omidi Tahereh , Mohammadian-khoshnoud Maryam , Mohammadi Younes
Published: August 2020

Background: Many studies have shown a lot of factors which are as barriers to the condom use among female sex workers (FSWs). However, there is not a comprehensive study to report the number and magnitude of these barriers. This study aimed to resolve this gap by comprehensive systematic review and meta-analysis. Methods: We have searched the electronic databases include Web of Science, PubMed, and Scopus until September 2019. For each database we formulated a separate search strategy using keywords such as “condom use” and “sex worker” and the related synonyms. Epidemiological epidemiology addressed the factors associated with unprotected sex for the female sex worker. The heterogeneity across studies and probability of publication bias was investigated by I2 statistic and Begg's and Egger's tests respectively. The pooled effect size were expressed as odds ratio (OR) with 95% confidence intervals (CI) using a random-effects model.Results: Out of 5854 studies obtained in initial search, 35 studies with sample size 14218 participants had eligibility criteria which were included in the final analysis. Ten factors include marital status, alcohol use, history of violence, history of sexual abuse, history of STIs, STIs knowledge, HIV risk perception, drug use, knowledge about the condom use, condom use self-efficacy were identified in those studies. History of sexual abuse with OR=1.87 and the knowledge on AIDS with OR=1.07 had the strongest association and weakest association with condom use respectively. Conclusion: Many factors with different degrees of association influence on the condom use among female sex workers. However, history of sexual abuse, a history of violence, and HIV risk perception were considered as the major determinants of the condom use. The structural interventions, policy change and empowerment of female sex workers are recommended to increase consistent condom use in FSWs.
Double tract reconstruction reduces reflux esophagitis and improves quality of life after radical proximal gastrectomy for patients with upper gastric or esophagogastric adenocarcinoma
Authors: Ji Xin , Jin Cheng-Gen , Ji Ke , Zhang Ji , Wu Xiao-Jiang , Zong Xiang-Long , Jia Zi-Yu , Fu Tao , Fan Biao , Wang An-Qiang , Bu Zhao-De , Ji Jiafu
Published: August 2020

Background: The aim of the present study was to compare the difference between double tract reconstruction and esophagogastrostomy after proximal gastrectomy.Methods: Patients who underwent radical proximal gastrectomy with esophagogastrostomy or double tract reconstruction from December 2014 to May 2019 were included in this study.Results: Sixty-four patients were included in this study and divided into two groups according to reconstruction method. The two groups were well balanced in terms of length of postoperative hospital stay, blood loss volume, postoperative complications, and 5-year disease-free survival (DFS). The operation duration in the double tract reconstruction group was longer than that in the esophagogastrostomy group (240 min vs 195 min, P = 0.001). The rates of postoperative reflux esophagitis in the double tract reconstruction group and esophagogastrostomy group were 8.0% and 30.8%, respectively (P = 0.032). The multivariable logistic regression analysis showed that the reconstruction method was the only independent risk factor for reflux esophagitis (P = 0.004). Patients in the double tract reconstruction group had better global health status (P < 0.001) and emotional functioning (P < 0.001), and complained less about nausea and vomiting (P < 0.001), pain (P = 0.039), insomnia (P = 0.003), and appetite loss (P < 0.001) based on the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire. Regarding the EORTC QLQ-STO22 questionnaire, patients in the double tract reconstruction group complained less about dysphagia (P = 0.030), pain (P = 0.008), reflux (P < 0.001), eating (P < 0.001), anxiety (P < 0.001), dry mouth (P = 0.007), and taste (P = 0.001). The multiple linear regression analysis showed that reconstruction method, postoperative complications, reflux esophagitis, and operation duration had a linear relationship with the global health status score.Conclusions: Double tract reconstruction after proximal gastrectomy was comparable with esophagogastrostomy in terms of perioperative safety and 5-year DFS. Double tract reconstruction could better prevent reflux esophagitis and improve quality of life. There was a linear relationship between global health status score and reconstruction method, reflux esophagitis, postoperative complications, and operation duration.
Metformin With Neoadjuvant Chemoradiation to Improve Pathologic Response in Rectal Cancer: a Pilot Phase I/II Trial
Authors: Wong Shun , Chu William , Ashamalla Shady , Fenech Darlene , Berry Scott , Kiss Alex , Koritzinsky Marianne
Published: August 2020

Background: Neoadjuvant radiotherapy with or without chemotherapy decreases the risk of local recurrence after surgery for stage II or III rectal cancer. Emerging data suggest that diabetic patients on metformin may have improved cancer outcome after radiotherapy. We asked if metformin given concurrently with long course chemoradiation (CRT) may improve pathologic complete response (pCR) in non-diabetic rectal cancer patients. A single-institutional pilot study was performed to build a confidence interval for the pCR rate and to determine the sample size for a phase 2 trial.Methods: Non-diabetic patients with biopsy confirmed adenocarcinoma of the rectum, and deemed candidates for long course neoadjuvant CRT were invited to participate. Radiation consisted of 50.4 Gy in 28 daily fractions. Capecitabine (825 mg/m2 twice daily, Monday-Friday) was self-administered during the 28 days of radiation only. The primary outcome was pCR. The study was designed to accrue 15 participants to construct a confidence interval (CI) for the pCR rate. Results: A total of 16 patients were accrued from January 2017 to May 2018. One patient withdrew from the study prior to CRT. Only grade 1 or 2 adverse events were observed from the intervention. Three patients had a clinical complete response (cCR) and did not have surgical resection. Of the 12 patients who underwent surgery, there were two pCRs. For the combined pCR/cCR rate of 33% (95% CI 19-47%), a total of 85 patients will be required to yield a 95% CI with a 10% margin of error. Conclusions: Adding metformin to neoadjuvant CRT for rectal cancer does not appear to enhance toxicities. These results will be used to refine the design and conduct of a future phase 2 trial to determine whether adding metformin to CRT improves pCR/cCR rates. Trial registration: NCT03053544. Registered December 20, 2016, https://clinicaltrials.gov/ct2/show/record/NCT03053544
Engineering of the Bacillus subtilis PhoD signal peptide to direct high-level, Tat-specific export of a single-chain antibody fragment to the periplasm in Eschericha coli
Authors: Jawara Chillel , Richards Kirsty L , Peswani Amber R , Walker Kelly L , Nascimento Lara , Robinson Colin
Published: August 2020

Background : Numerous high-value proteins have been produced in E. coli, and a favoured strategy is to export the protein of interest to the periplasm by means of an N-terminal signal peptide. While the Sec pathway has been extensively used for this purpose, the Tat pathway has potential because it transports fully-folded heterologous proteins. Most studies on the Tat pathway have used the E. coli TorA signal peptide to direct export, because it is highly Tat-specific, unlike many Tat signal peptides which can also function as Sec signal peptides. However, the TorA signal peptide is prone to degradation in the cytoplasm, leading to reduced export rates in some cases. Here, we have tested a range of alternative signal peptides for their ability to direct Tat-dependent export of a single-chain antibody fragment (scFv). Results : We show that the signal peptides of E. coli AmiC, MdoD and YcbK direct efficient export of the scFv by both the Tat and Sec pathways, which may be a disadvantage when Tat-specific export is required. The same applies to the Tat signal peptide of Bacillus subtilis PhoD, which likewise directs efficient export by Sec. We engineered the PhoD signal peptide by introduction of a Lys or Asn residue in the C-terminal domain of the signal peptide, and we show that this substitution renders the signal peptide Tat-specific. These signal peptides, designated PhoDk and PhoDn, direct efficient export of scFv in shake flask and fed-batch fermentation studies, reaching export levels that are well above those obtained with the TorA signal peptide. Culturing in ambr250 bioreactors was used to fine-tune the growth conditions, and the net result was export of the scFv by the Tat pathway at levels of approximately 1g protein/L culture. Conclusions : The new PhoDn and PhoDk signal peptides have significant potential for the export of heterologous proteins by the Tat system.
Development and validation of a set of novel and robust 4-lncRNA-based nomogram predicting prostate cancer survival by bioinformatics analysis
Authors: Zhang Peng , Wang Aiyu , Dong Liming , Zhang Xuefeng
Published: August 2020

Background and Objective:

There is significant heterogeneity between cellular composition and patient outcome in prostate cancer (PCa). Accumulating evidence shows that long noncoding RNAs (lncRNAs) possess great potential in the diagnosis and prognosis of PCa with biological and clinical significance. Therefore, this study aimed to construct an lncRNA-based signature to more accurately predict the prognosis of different PCa patients, so as to improve patient management and prognosis.
Methods

The Cancer Genome Atlas (TCGA) database was used to download RNA-seq expression data together with the clinical information of 499 PCa tissue samples as well as 52 corresponding non-carcinoma tissue samples. Differently expressed lncRNAs (DElncRNAs) were selected based on tumor tissues and non-carcinoma samples. Through univariate and multivariate Cox regression analysis, this study constructed a 4 lncRNAs-based prognosis nomogram for the classification and prediction of survival risk in patients with PCa. The receiver operating characteristic (ROC) curve was plotted for detecting and validating our prediction model sensitivity and specificity. In addition, univariate as well as multivariate Cox regression was conducted to examine whether the constructed lncRNA signature’s prediction ability was independent of additional clinicopathological variables (like age, Gleason score, N stage, T stage and M stage) among PCa cases. Possible biological functions for those prognostic lncRNAs were predicted through gene ontology (GO) together with Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis on those 4 protein-coding genes (PCGs) related to lncRNAs.
Results

A total of 451 differently expressed lncRNAs (DElncRNAs) related to the overall survival (OS) rate for PCa cases were screened from 3838 lncRNAs in the TCGA database. Four lncRNAs (HOXB-AS3, YEATS2-AS1, LINC01679, PRRT3-AS1) were extracted after univariate as well as multivariate COX regression analysis for classifying patients into high and low-risk groups by different OS rates. As suggested by ROC analysis, our proposed model showed high sensitivity and specificity. Independent prognostic capability of the model from other clinicopathological factors was indicated through further analysis. Based on functional enrichment, those action sites for prognostic lncRNAs were mostly located in the extracellular matrix and cell membrane, and their functions are mainly associated with the adhesion, activation and transport of the components across the extracellular matrix or cell membrane.
Conclusion

Our current study successfully identifies a novel four-lncRNA candidate, which can provide more convincing evidence for prognosis in addition to the traditional clinicopathological indicators to predict the PCa survival, and laying the foundation for offering potentially novel therapeutic treatment. Additionally, this study sheds more lights on the PCa-related molecular mechanisms.
Implementation of Medicine Take-back Concept at Community Level in Nepal: a Feasibility Study
Authors: Sapkota Binaya , Giri Anil , Bhatta Bigyan , Awasthi Krishna , Bhurtyal Kiran , Joshi Bimala , Joshi Khem Raj
Published: August 2020

Background: Medications are not always completely consumed as purchased from pharmacy due to lack of awareness, forgetfulness. So, most households may have leftover, unwanted, unused and expired (UUE) medicines. They may lead to health hazards and environment pollution. The present study was aimed to analyze feasibility of implementation of medicine take-back in select communities of Nepal.Methods: Exploratory study was conducted among adults (total 400) in Kathmandu, Lalitpur, Kaski, Kanchanpur and Kailali districts from July 2017 to January 2018. Study sites and participants were selected by simple random sampling and respondents were interviewed about their awareness about medicine disposal techniques, possible hazards and their willingness to support take-back program using semi-structured questionnaire. Multinomial logistic regression analysis was applied to explore the relationship of various take-back related outcomes with the predictors. The p-value less than 0.05 was statistically significant at 95% confidence level. Results: The multinomial logistic regression analysis showed that there was significant relationship of health hazards (rashes and diarrhea) among the farmers, engineers, nurse and lawyers (p value <0.01 in each). Land pollution and effect on health of children was significantly related with the inappropriate disposal of medicines such as site of disposal (p value <0.01), river (p value 0.02), garbage (p value 0.04), and dumping site (p value 0.01). The analysis of the willingness to follow take-back program with the techniques of support showed significant relationship with the establishment of collection center and participation on seminar (p value <0.01). Conclusions: Most participants kept UUE medicines in home, disposed with household rubbish and flushed down the sink. They were interested to support take-back, if implemented in their community but the main constraint was the budget. Hence, take-back concept could be initiated and implemented on government funding or other external sources.
Evaluation of Convalescent Plasma Versus Standard of Care for the Treatment of COVID-19 in Hospitalized Patients: study protocol for a phase 2 randomized, open-label, controlled, multicenter trial
Authors: Diago-Sempere Elena , Sancho-López Aranzazu , Bueno Jose Luis , Múñez-Rubio Elena , Torres Ferran , de Molina Rosa Malo , Fernández-Cruz Ana , de Diego Isabel Salcedo , Velasco-Iglesias Ana , Payares-Herrera Concepción , Casas-Flecha Inmaculada , Avendaño-Solá Cristina , Palomino Rafael Duarte , Ramos-Martínez Antonio , Ruiz-Antorán Belén
Published: August 2020

Background: COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. At the time this clinical trial was planned, there were no available vaccine or therapeutic agents with proven efficacy, but the severity of the condition prompted the use of several pharmacological and non-pharmacological interventions. It has long been hypothesized that the use of convalescent plasma (CP) from infected patients who have developed an effective immune response is likely to be an option for the treatment of patients with a variety of severe acute respiratory infections (SARI) of viral etiology. The aim of this study is to assess the efficacy and safety of convalescent plasma in adult patients with severe COVID-19 pneumonia. Methods/Design: The ConPlas-19 study is a multicenter, randomized, open-label controlled trial. The protocol has been prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. The study has been planned to include 278 adult patients hospitalized with severe COVID-19 infection not requiring mechanical ventilation (invasive or non-invasive). Subjects are randomly assigned in a 1:1 ratio (139 per treatment arm), stratified by center, to receive intravenously administered CP (single infusion) plus SOC or SOC alone, and are to be followed for 30 days. The primary endpoint of the study is the proportion of patients that progress to categories 5, 6 or 7 (on the 7-point ordinal scale proposed by the WHO) at day 15. Interim analyses for efficacy and/or futility will be conducted once 20%, 40%, and 60% of the planned sample size are enrolled and complete D15 assessment.Discussion: This clinical trial is designed to evaluate the efficacy and safety of passive immunotherapy with convalescent plasma for the treatment of adult patients hospitalized with COVID-19. The results of this study are expected to contribute to establishing the potential place of CP in the therapeutics for a new viral disease. Trial registration: Trial registration at clinicaltrials.gov; Registration Number: NCT04345523; https://clinicaltrials.gov/ct2/show/NCT04345523; Registered on 30 March, 2020. First posted date: April 14, 2020.
The Radionics Features Could Be Used to Predict the Distinct Metastases in Nasopharyngeal Carcinoma Patients
Authors: Li Meige , Feng Ziyou , Yang Fang , Zhan ZeJiang , Ye Haiwen , Zhang Guoyi
Published: August 2020

Objectives

For NPC patients, distant metastasis is now the main reason for treatment failure. The patients with distinct metastases need different therapeutic regimen and have distinct prognosis. Radiomics might help us predict the type of metastases effectively.
Methods

The MRI data of seventy non-metastatic NPC patients who develop distant metastasis within five years after treatment were collected and 4410 radiomics features for each patient were extracted by PyRadiomics. Every radiomics feature were compared among patients with distinct metastases and tested by the receiver operating characteristic curve.
Results

Twenty features have significant differences between the bone metastases cohort and lung metastases cohort, two features have significant differences between the bone metastases cohort and liver metastases cohort, one feature has significant differences between the bone metastases cohort and multiple metastases cohort and sixty-seven features have significant differences between the lung metastases cohort and liver metastases cohort. Six T2WI features could identified lung metastases from bone metastases and liver metastases effectively (AUC = 0.851 ~ 0.896), two T1WI features and one CE T1WI feature could respectively identified bone metastases from liver metastases and multiple metastases effectively (AUC = 0.779 ~ 0.821).
Conclusion

The results indicate that the radionics features could reflect some of the characteristics of distinct metastases and have potential to be used as predictor of distinct metastases.
Homebound by COVID19: The Benefits and Consequences of Non-pharmaceutical Intervention Strategies
Authors: Oruc Buse Eylul , Baxter Arden , Keskinocak Pinar , Asplund John , Serban Nicoleta
Published: August 2020

Background. Recent research has been conducted by various countries and regions on the impact of non-pharmaceutical interventions (NPIs) on reducing the spread of COVID19. This study evaluates the tradeoffs between potential benefits (e.g., reduction in infection spread and deaths) of NPIs for COVID19 and being homebound (i.e., refraining from community/workplace interactions).Methods. An agent-based simulation model to project the disease spread and estimate the number of homebound people and person-days under multiple scenarios, including combinations of shelter-in-place, voluntary quarantine, and school closure in Georgia from March 1 to September 1, 2020.Results. Compared to no intervention, under voluntary quarantine, voluntary quarantine with school closure, and shelter-in-place with school closure scenarios 3.43, 19.8, and 200+ homebound adult-days were required to prevent one infection, with the maximum number of adults homebound on a given day in the range of 121K-268K, 522K-567K, 5,377K-5,380K, respectively.Conclusions. Voluntary quarantine combined with school closure significantly reduced the number of infections and deaths with a considerably smaller number of homebound person-days compared to shelter-in-place.
Immediate impact of stay-at-home orders to control COVID-19 transmission on mental well-being in Bangladeshi adult population: Patterns, Explanations, and future directions
Authors: Ali Mohammad , Ahsan Gias U. , Khan Risliana , Khan Hasinur Rahman , Hossain Ahmed
Published: August 2020

Objective
We aim to evaluate the immediate impacts of COVID-19 stay-at-home orders on the mental well-being of Bangladeshi adults. We recruited 1404 healthy adults following the Bangladesh government's lockdown announcement. A questionnaire comprising the Warwick Edinburgh Mental Well-being Scale was used to define mental health.
Results
The overall mean score for well-being was 42.4, indicating that 51.9% of adults suffered from poor mental health. And within that 48% of males and 57% of females were depressed. The mean scores for government workers, unemployed workers, and business employees were 45.1, 39.6, and 39.5, respectively. Confounding adjustments in multivariable linear regression models revealed that married women, unemployed and business communities, and individuals returning to villages were heavily depressed. Stay-at-home orders had significant repercussions on mental health and created a gender disparity in depression among adults. Suggestions include promoting mental health for women, unemployed, and business individuals. Married women need to be taken into special consideration as their mental well-being is worse. Older people (50 years of age and over) reported a high day-to-day variation in their mental health. These results should be factored in when discussing the mental health of adults and communities to cope with quarantine.
The Effect of Temperature Upon Transmission Of COVID-19 Australia And Egypt Case Study.
Authors: Anis Adly
Published: August 2020

BackgroundSeveral previous studies have recognized the effect of air temperature on the survival and transmission of viruses and germs. The current study investigated the effect of air temperature on the transmission of coronavirus covid-19 by monthly temperature averages maps analyzing.MethodsThe study demonstrated the relationship between temperature and transmission speed of Covid-19 virus, It confirmed that the most appropriate average temperature for virus activity and transmission ranges between 13-24 ° C, by analyzing the maps of monthly temperature averages in Egypt and Australia.ResultsThe study reached, through cartographic analysis, to confirm the relationship between temperature and increase in the number of confirmed cases of covid-19, This study confirmed that the most appropriate average temperature for virus activity and transmission ranges between 13-24 ° C, by analyzing the maps of monthly temperature averages in Egypt and Australia. But the effect of the climate does not prevent the virus from being transmitted from one person to another through close contact or use of personal tools infected with the Corona virus, or crowding in air-conditioned places.Therefore, failure of individuals to follow the instructions for social distance and wearing a mask will lead to the transmission of the virus, even in hot climates.ConclusionsResults support that the most appropriate average temperature for the survival transmission of COVID-19 ranges between 13-24 ° C. Australia and Egypt are models to confirm the relationship between temperature and COVID-19 activity and spread.
The Painful Anterior Apprehension Test – An Indication Of Occult Shoulder Instability
Authors: Ng Yau Hong , Law Gin Way , Ng Zhaowen Dennis , Tan Jun Hao , Wong Keng Lin Francis , Kumar V Prem
Published: August 2020

Background To evaluate the clinical relevance of the painful anterior apprehension test in shoulder instability. Methods We performed a retrospective study of 155 patients that underwent arthroscopic anterior Bankart repair between 2014–2016. Exclusion criteria were previous ipsilateral shoulder surgery, bony Bankart lesions, glenohumeral osteoarthritis and concomitant surgery involving rotator cuff tears, biceps tendon pathology and SLAP lesions. The study cohort was divided into 3 groups: apprehension test with apprehension only, apprehension test with pain only, and apprehension test with both apprehension and pain. Patient demographics, clinical characteristics, radiological imaging, arthroscopy findings and surgical outcomes (Constant, ASES, SF-36 scores) were evaluated. Results 115 (74.2%) had apprehension only, 26 (16.8%) had pain only and 14 (9.0%) had pain and apprehension with the apprehension test. Univariate analysis showed significant differences between the groups in patients with traumatic shoulder dislocation (p=0.028), patients presenting with pain (p=0.014) and patients presenting with recurrent dislocations (p=0.046). Patients with a purely painful apprehension test were more likely to have a traumatic shoulder dislocation, more likely to present only with pain, and less likely to present with recurrent shoulder dislocations. Multivariate analysis showed that none of these factors alone were significant as single predictors for shoulder instability. All 3 groups were otherwise similar in patient profile, MRI and arthroscopic assessments, and clinical outcomes of surgery. Excellent clinical outcomes were achieved in all groups with no difference in preoperative and postoperative scores across all groups at all time points. Conclusions The painful apprehension test may suggest underlying shoulder instability.