bluuebunny/crossref_metadata_2025 huggingface dataset:
Is it the time to implement the routine use of distress thermometer among Egyptian patients with newly diagnosed cancer?
Authors: Aziz Nashwa Abd El- , Khallaf Salah , Abozaid Waleed , Elgohary Ghada , El-Fattah Ola Abd , Elhawary Mai , Khaled Safaa , El-Haffez Azza Abd , Kamel Ehab , Mohamed Sherif
Published: August 2020

Background: The distress thermometer (DT) is an effective tool for identifying distress among cancer patients worldwide. However, DT has not been studied in Egyptian patients. We aimed to study the prevalence of distress among Egyptian patients with different types of cancers using DT.Methods: A total of 550 patients with newly diagnosed hematological and solid cancers who were followed up at 3 Oncology Centers in Egypt were enrolled. They completed a sociodemographic and clinical status questionnaire, the DT and the Problem List (PL) scale.Results: At a DT cut-off score of ≥4, 46% of patients had significant distress, which was related to the tumor site and stage. The most frequent problems reported were treatment decision (64.4%), worry (47%), and fears (44.5%). In univariate logistic regression analysis, participants who had significant distress described 23 out of 36 problems in the practical, family, emotional, and physical areas. After adjustment to sociodemographic and clinical characteristics, multivariable analysis confirmed that insurance, depression, fear, sadness, worry, loss of interest in usual activity, and sleep were independent factors associated with significant distress in cancer patientsConclusions: Almost half of Egyptian patients newly diagnosed with cancer reported significant distress. Those who had significant distress described extra problems in the practical, family, emotional, and physical areas. We recommend the routine use of DT for screening Egyptian patients with cancer, as well as the involvement of the psycho-oncology and social services, at the time of their initial diagnosis.
Outcomes of Cardiac Resynchronization Therapy in Patients with Hypothyroidism and Heart Failure
Authors: YANG MEI , Li Xuping , III John C. Morris , Liang Jinjun , Deshmukh Abhishek J. , Hodge David , Li Yi-Gang , Cha Yong-Mei
Published: August 2020

Background Hypothyroidism is known to be associated with adverse clinical outcomes in heart failure. The association between hypothyroidism and cardiac resynchronization therapy outcomes in patients with severe heart failure is not clear. Methods The study included 1,316 patients who received cardiac resynchronization therapy between 2002 and 2015. Baseline demographics and cardiac resynchronization therapy outcomes, including left ventricular ejection fraction, New York Heart Association class, appropriate implantable cardioverter-defibrillator therapy, and all-cause mortality, were collected from the electronic health record. Results Of the study cohort, 350 patients (26.6%) were classified as the hypothyroidism group. The median duration of follow-up was 3.6 years (interquartile range, 1.7-6.2). Hypothyroidism was not associated with a higher risk of all-cause mortality in patients receiving CRT for heart failure. The risk of appropriate implantable cardioverter-defibrillator therapy significantly increased in association with increased baseline thyroid -stimulating hormone level in the entire cohort (hazard ratio, 1.23 per 5mIU/L increase; 95% CI, 1.01-1.5; P=0.04) as well as in the hypothyroid group (hazard ratio, 1.44 per 5mIU/L increase; 95% CI, 1.13-1.84; P=0.004). Conclusions CRT improves cardiac function in hypothyroid patients. The ventricular arrhythmic events requiring ICD therapies are associated with baseline TSH level, which might be considered as an important biomarker to stratify the risk of sudden death for patients with heart failure and hypothyroidism.
The Relationship of Nursing Home Price and Quality of Life
Authors: Raes Sarah , Vandepitte Sophie , De Smedt Delphine , Wynendaele Herlinde , DeJonghe Yannai , Trybou Jeroen
Published: August 2020

Background: Knowledge about the relationship between the residents’ Quality Of Life (QOL) and the nursing home price is currently lacking. Therefore, this study investigates the relationship between 11 dimensions of QOL and nursing homes price in Flemish nursing homes.Methods: The data used in this cross-sectional study were collected by the Flemish government from years 2014 to 2017 and originates from 659 Flemish nursing homes. From 2014 to 2016, data on the QOL of 21,756 residents was assessed with the InterRAI instrument. This instrument contains 11 QOL dimensions. Multiple linear regression analyses were conducted to examine the research question.Results: The multiple linear regressions indicated that a 10 euro increase in the daily nursing home price is associated with a significant decrease (P < 0.001) of 0.1 in 5 dimensions of QOL (access to services, comfort and environment, food and meals, respect, and safety and security). Hence, our results indicate that the association between price and QOL is very small. When conducting a subgroup analysis based on ownership type, the earlier found results remained only statistically significant for private nursing homes.Conclusion: Our findings show that nursing home price is of limited importance with respect to resident QOL. Contrary to popular belief, our study demonstrates a limited negative effect of price on QOL. Further research that includes other indicators of QOL is needed to allow policymakers and nursing home managers to improve nursing home residents’ QOL.
Medicinal Dietary Plants of the Yi in Mile, Yunnan, China
Authors: Sun Jingxian , Xiong Yong , Li Yanhong , Yang Qingsong , Chen Yijian , Jiang Mengyuan , Li Yukui , Li Hongrui , Bi Zizhen , Huang Xiangzhong , Lu Shugang
Published: August 2020

Background: The Yi is the largest ethnic group in Yunnan Province (China), with a population of five millions. The Yi people tend to live in mountainous areas, and their culture includes a unique dietary system for treating and protecting people against illnesses. Medicinal plants occupy an essential place in the Yi diet because they play a key role in health and the prevention and treatment of diseases. However, few studies have addressed these medicinal dietary plants and their importance in the Yi’s daily lives. The aim of this study was to (1) investigate the medicinal dietary plants used by the Yi in Mile City, (2) document the traditional knowledge held about these plants, (3) identify species with important cultural significance to the Yi in Mile City, and (4) analyze the special preparation methods and consumption habits of these plants. Methods: Field investigations were performed in six villages in Mile City, Honghe Hani and Yi Autonomous Prefecture, Yunnan, from July 2017 to May 2018. Information was collected using direct observation, semi -structured interviews, key informant interviews, individual discussions and focus group discussions. The use -value (UV) and frequency of utilization index (FUI) of these plants were analyzed. Plant samples and voucher specimens were collected for taxonomic identification.Results: This study documented 124 species belonging to 62 families and 102 genera. These plants included: angiosperms (117 spp.), gymnosperms (3), pteridophytes (2), lichens (1), and fungi (1). The 20 species with the highest UV were noted as being particularly important to the Yi people’s daily life in Mile City. The primary medicinal preparation method for plants recorded in the study was decoction. The most commonly used plant parts were fruits and roots. The most frequently used edible parts were fruits, and the most frequently used medicinal parts were roots. The medicinal parts were used to treat diseases such as rheumatism, oedemas, kidney deficiency, spleen deficiency, gastritis, parasites and so on. Conclusion: A wide variety of medicinal dietary plants are used by the Yi people in Mile City. Those plants, which have both rich nutritional and medicinal value, occupy an essential part of the Yi dietary and medicine culture. Ethnobotanical surveys of medicinal dietary plants provide a theoretical reference for the conservation and sustainable use of the plant resources and could contribute to the protection of the Yi food culture and traditional medicine in Mile City. In addition, this information provides a sound basis for developing and using Yi ethnic medicine and health products.
Phase II Multicenter Randomized Controlled Clinical Trial on the Efficacy of Intra-articular Injection of Autologous Bone Marrow Mesenchymal Stem Cells with Platelet Rich Plasma for the Treatment of Knee Osteoarthritis
Authors: Lamo-Espinosa José María , Blanco Juan F. , Sánchez Mikel , Moreno Victoria , Granero-Moltó Froilán , Sánchez-Guijo Fermín , Crespo-Cullel Íñigo , Mora Gonzalo , Vicente Diego Delgado San , Pompei-Fernández Orlando , Aquerreta Jesús Dámaso , Núñez-Córdoba Jorge María , Vitoria María , Valentí-Azcárate Andrés , Andreu Enrique J. , Cañizo María del Consuelo del , Valentí-Nin Juan Ramón , Prósper Felipe
Published: August 2020

Background

Mesenchymal stromal cells are a safe and promising option to treat knee osteoarthritis as previously demonstrated in different clinical trials. However, their efficacy, optimal dose and addition of adjuvants must be determined. Here, we evaluated the clinical effects of a dose of 100x10 6 bone marrow mesenchymal stromal cells (BM-MSCs) in combination with Platelet Rich Plasma (PRGF ® ) as adjuvant in a randomized clinical trial.

Methods

A phase II, multicenter, randomized clinical trial with active control was conducted. Sixty patients diagnosed with knee OA were randomly assigned to 3 weekly doses of PRGF ® or intraarticular administration of 100x10 6 cultured autologous BM-MSCs plus PRGF ® . Patients were followed up for 12 months, and pain and function were assessed using VAS and WOMAC and by measuring the knee range of motion range. X-ray and magnetic resonance imaging analyses were performed to analyze joint damage.

Results

No adverse effects were reported after BM-MSC administration or during follow-up. According to VAS, the mean value (SD) for PRGF ® and BM-MSC with PRGF ® went from 5 (1.8) to 4.5 (2.2) (p=0.389) and from 5.3 (1.9) to 3.5 (2.5) (p=0.01), respectively at 12 months.. In WOMAC, the mean (SD) baseline and 12-month overall WOMAC scores in patients treated with PRGF ® was 31.9 (16.2) and 22.3 (15.8) respectively (p=0.002) while that for patients treated with BM-MSC plus PRGF ® was 33.4 (18.7) and 23.0 (16.6) (p=0.053). Although between groups statistically significances have been not detected, only patients being treated with BM-MSC plus PRGF ® could be considered as a OA treatment responders following OARSI criteria. X-ray and MRI (WORMS protocol) revealed no changes in knee joint space width or joint damage.

Conclusions

Treatment with BM-MSC associated with PRGF ® was shown to be a viable therapeutic option for osteoarthritis of the knee, with clinical improvement at the end of follow-up. Further phase III clinical trials would be necessary to confirm the efficacy.
Population structure and geographical segregation of Cryptosporidium parvum IId subtypes in cattle in China
Authors: Zhang Zhenjie , Hu Suhui , Zhao Wentao , Guo Yaqiong , Li Na , Zheng Zezhong , Zhang Longxian , Kvac Martin , Xiao Lihua , Feng Yaoyu
Published: August 2020

Background: Cryptosporidium parvum is a zoonotic pathogen worldwide. Extensive genetic diversity and complex population structures exist in C. parvum in different geographical regions and hosts. Unlike the IIa subtype family, which is responsible for most zoonotic C. parvum infections in industrialized countries, IId is identified as the dominant subtype family in farm animals, rodents and humans in China. Thus far, the population genetic characteristics of IId subtypes in calves in China are not clear.Methods: In the present study, 46 C. parvum isolates from dairy and beef cattle in six provinces and regions in China were characterized using sequence analysis of eight genetic loci, including msc6-7, rpgr, msc6-5, dz-hrgp, chom3t, hsp70, mucin1 and gp60. They belonged to three IId subtypes in the gp60 gene, including IIdA20G1 (n = 17), IIdA19G1 (n = 24) and IIdA15G1 (n = 5). The data generated were analyzed for population genetic structures of C. parvum using DnaSP and LIAN and subpopulation structures using STRUCTURE, RAxML, Arlequin, GENALEX and Network.Results: Seventeen multilocus genotypes were identified. The results of linkage disequilibrium analysis indicated the presence of an epidemic genetic structure in the C. parvum IId population. When isolates of various geographical areas were treated as individual subpopulations, maximum likelihood inference of phylogeny, pairwise genetic distance analysis, substructure analysis, principal components analysis and network analysis all provided evidence for geographical segregation of subpopulations in Heilongjiang, Hebei and Xinjiang. In contrast, isolates from Guangdong, Shanghai and Jiangsu were genetically similar to each other.Conclusions: Data from the multilocus analysis have revealed a much higher genetic diversity of C. parvum than gp60 sequence analysis. Despite an epidemic population structure, there is an apparent geographical segregation in C. parvum subpopulations within China.
Development of a double-recombinant antibody sandwich ELISA for quantitative detection of epsilon toxoid concentration in inactivated Clostridium perfringens vaccines
Authors: Alibeiki Maryam , Golchin Mehdi , Tabatabaei Mohammad
Published: August 2020

Background: Epsilon toxin (ETX) causes a commonly fatal enterotoxemia in domestic animals. Also, ETX causes serious economic losses to animal husbandry. In this study, we selected several clones against ETX using repertoires displayed on filamentous phage. Anti-ETX specific clones were enriched by binding to immobilized antigen, followed by elution and re-propagation of phage. After multiple rounds of binding selection, ELISA analysis showed that most isolated clones had high affinity and specificity for ETX.Results: Two recombinant monoclonal antibodies against ETX were isolated by phage display technology. B1 phage VH antibody isolated from DAb library and G2 soluble scFv antibody isolated from Tomlinson I+J libraries have been applied as the capture and detection antibodies for developing an ETX sandwich ELISA test, respectively.Conclusions: Designed ETX sandwich ELISA could be a valuable tool for quantitative detection of ETX in inactivated commercial vaccines against enterotoxemia.
Oxidative stress mediates the apoptosis and epigenetic modification of the Bcl-2 promoter via DNMT1 in a cigarette smoke-induced emphysema model
Authors: Zeng Huihui , Li Tiao , He Xue , Cai Shan , Luo Hong , Chen Ping , Chen Yan
Published: August 2020

Background: Emphysema is a crucial pathological characteristic of chronic obstructive pulmonary disease (COPD). Oxidative stress, apoptosis and epigenetic mechanisms contribute to the pathogenesis of emphysema. However, an attempt to accurately identify whether these mechanisms interact with each other and how they are triggered has never been conducted.Method: The total reactive oxygen species (ROS) level, pulmonary apoptosis and B-cell lymphoma/ leukemia-2 (Bcl-2) expression, an apoptosis regulator, were detected in samples from COPD patients. Bisulfite sequencing PCR (BSP) was conducted to observe the alterations in the methylation of the Bcl-2 promoter in specimens. The dysregulation of DNA methyltransferase enzyme 1 (DNMT1), a vital DNA methyltransferase enzyme, in the lungs of patients was confirmed through western blotting. To find out interactions between oxidative stress and DNA methylation in emphysema, mouse models were built with antioxidant treatment and DNMT1 silencing, and were examined with the pulmonary apoptosis, Bcl-2 and DNMT1 expression, and epigenetic alterations of Bcl-2.Results: Higher reactive oxygen species (ROS) levels and pulmonary apoptosis were observed in COPD patients than in healthy controls. Downregulated Bcl-2 expression with increased promoter methylation and DNMT1 protein expression was found in COPD patients. Antioxidant treatment reduced the level of ROS and dysregulation of DNMT1 expression and emphysematous progression in the smoking models. Following DNMT1 blockage, smoking models showed improved lung function, pulmonary apoptosis, emphysematous progression, and increased Bcl-2 protein expression with less promoter methylation than emphysema mice.Conclusion: Cigarette-induced oxidative stress mediates pulmonary apoptosis and hypermethylation of the Bcl-2 promoter in emphysema models through DNMT1.
What is the impact of rural-to-urban migration on exclusive breastfeeding: a population-based cross-sectional study
Authors: Yin Xiaohan , Zhao Chen , Yang YuMei , Shi HuiFeng , Wu TianChen , Xie JiaLei , Niu JieQiong , Wang XiaoLi , Fang Jin
Published: August 2020

Background: Breastfeeding is a well-established and recommended intervention for better development of infants. In China, less than one third of infants are exclusive breastfed at 6 months of age. Maternal rural-to-urban migration contributes to these low rates of breastfeeding practices. Therefore, the aim of this study was to assess the prevalence of breastfeeding practices and associated factors among rural-to-urban migrant children and local children with infants aged 0-12 months in China, 2018.Methods: Data were collected from a population-based cross-sectional survey in 2018 that included 6995 infants from 8 urban areas in China with available measures of breastfeeding. The prevalence of breastfeeding practices was calculated by maternal floating status and logistic regression was conducted to examine the association between them, after adjusting for social-demographic characteristics, mother-infant health information and supportive information. For exclusive breastfeeding, we calculated the prevalence and its association with maternal rural-to-urban migration, stratified by maternal education level, maternal resident place and maternal ethnicity, respectively. Results: The overall prevalence of ever breastfeeding, predominant breastfeeding, exclusive breastfeeding and age-appropriate breastfeeding was 97.51%, 29.84%, 59.89% and 45.07%, respectively. Rural-to-urban migrant children were less likely to be exclusively breastfed compared to local children (AOR=0.81, 95% CI 0.68, 0.95). Stratified by different social-demographic variables, a negative association between exclusive breastfeeding and rural-to-urban migration was only found in the group with high education level, in the group living in metropolis and in the group of minorities, respectively. Conclusion: The overall prevalence of breastfeeding practices was low in both rural-to-urban migrant children and local children. Besides common strategies, special approaches should be provided for migrants with high education, living in metropolis and being minorities.
Dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG)
Authors: Taday Roman , Grüneberg Marianne , DuChesne Ingrid , Reunert Janine , Marquardt Thorsten
Published: August 2020

Background
PMM2-CDG (CDG-Ia) is the most frequent N-glycosylation disorder. While supplying mannose to PMM2-deficient fibroblasts corrects the altered N-glycosylation in vitro, short term therapeutic approaches with mannose supplementation in PMM2-CDG patients have been unsuccessful. Mannose found no further mention in the design of a potential therapy for PMM2-CDG in the past years, as it applies as ineffective. This retrospective study analyzes the first long term mannose supplementation in 20 PMM2-CDG patients. Mannose was given at a total of 1-2 g mannose/kg b.w./d divided into 5 single doses over a mean time of 60,7 months. Protein glycosylation, blood mannose concentration and clinical presentation were monitored in everyday clinical practice.

Results
After a mean time period of more than 1 year the majority of patients showed significant improvements in protein glycosylation.

Conclusion
Long-term dietary D-mannose supplementation shows biological effects in PMM2-CDG, an inherited disorder of mannose metabolism. It improves glycosylation in the majority of patients and could become the first cornerstone in the treatment of this disease.
Utility of ultra-sensitive qPCR to detect Plasmodium falciparum and Plasmodium vivax infections under different transmission intensities
Authors: Gruenberg Maria , Moniz Clara Antunes , Hofmann Natalie E. , Koepfli Cristian , Robinson Leanne J. , Nate ELma , Monteiro Wuelton Marcelo , Melo Gisely Cardoso , Kuehn Andrea , Siqueira Andre M. , Nguitragool Wang , Bassat Quique , Lacerda Marcus , Sattabongkot Jetsumon Prachumsri , Mueller Ivo , Felger Ingrid
Published: August 2020

Background The use of molecular diagnostics has revealed an unexpectedly large number of asymptomatic low-density malaria infections in many malaria endemic areas. This study compared the gains in parasite prevalence obtained by the use of ultra-sensitive (us)-qPCR as compared to standard qPCR in cross sectional surveys conducted in Thailand, Brazil and Papua New Guinea (PNG). The compared assays differed in the copy number of qPCR targets in the parasite genome. Methods Plasmodium falciparum ( Pf ) and Plasmodium vivax ( Pv ) parasites were quantified by qPCR amplifying the low-copy Pf_ and Pv _18S rRNA genes or the multi-copy targets Pf _varATS and Pv _mtCOX1. Cross-sectional surveys at the three study sites included 2252 participants of all ages and represented different transmission intensities. Results In the two low-transmission areas, P. falciparum positivity was 1.3% (10/773) (Thailand) and 0.8% (5/651) (Brazil) using standard Pf _18S rRNA qPCR. In these two countries, P. falciparum positivity by Pf_ varATS us-qPCR increased to 1.9% (15/773) and 1.7% (11/651). In PNG, an area with moderate transmission intensity, P. falciparum positivity significantly increased from 8.6% (71/828) by standard qPCR to 12.2% (101/828) by us-qPCR. The proportions of P. falciparum infections not detected by standard qPCR were 33%, 55% and 30% in Thailand, Brazil and PNG. Plasmodium vivax was the predominating species in Thailand and Brazil, with 3.9% (30/773) and 4.9% (32/651) positivity by Pv _18S rRNA qPCR. In PNG, P. vivax positivity was similar to P. falciparum , at 8.0% (66/828). Use of Pv _mtCOX1 us-qPCR led to a significant increase in positivity to 5.1% (39/773), 6.4% (42/651) and 11.5% (95/828) in Thailand, Brazil, and PNG. The proportions of P. vivax infections missed by standard qPCR were similar at all three sites, with 23%, 24% and 31% in Thailand, Brazil and PNG. Conclusion The proportional gains in the detection of P. falciparum and P. vivax infections by ultra-sensitive diagnostic assays were substantial at all three study sites. Thus, us-qPCR yields more precise prevalence estimates for both P. falciparum and P. vivax at all studied levels of endemicity and represents a significant diagnostic improvement. Improving sensitivity in P. vivax surveillance by us-qPCR is of particular benefit, because the additionally detected P. vivax infections signal the potential presence of hypnozoites and subsequent risk of relapse and further transmission.
Peritumoral ductular reaction can be a prognostic factor for intrahepatic cholangiocarcinoma
Authors: Shen Zhenyang , Xiao Jingbo , Wang Junjun , Lu Lungen , Wan Xinjian , Cai Xiaobo
Published: August 2020

Background: Peritumoral ductular reaction (DR) was reported to be related to the prognosis of combined hepatocellular-cholangiocarcinoma and hepatocellular carcinoma. Non-mucin-producing intrahepatic cholangiocarcinoma (ICC) which may be derived from small bile duct cells or liver progenitor cells (LPCs) was known to us. However, whether peritumoral DR is also related to non-mucin-producing ICCs remains to be investigated. Methods: Forty-seven patients with non-mucin-producing ICC were eventually included in the study and clinicopathological variables were collected. Immunohistochemical analysis and immunofluorescence staining for cytokeratin 19, proliferating cell nuclear antigen, and α-smooth muscle actin were performed in tumor and peritumor liver tissues.Results: A significant correlation existed between peritumoral DR and local inflammation and fibrosis. (r = 0.357, 95% CI, 0.037-0.557; P = 0.008 and r = 0.742, 95% CI, 0.580-0.849; P < 0.001, respectively). Patients with obvious peritumoral DR had high recurrence rate (81.8% vs 56.0%, P = 0.058) and poor overall and disease-free survival time (P = 0.01 and P = 0.03, respectively) comparing with mild peritumoral DR. Compared with the mild peritumoral DR group, the proliferation activity of LPCs/ cholangiocytes was higher in obvious peritumoral DR, which, however, was not statistically significant. (0.43±0.29 vs 0.28±0.31, P = 0.172). Furthermore, the correlation analysis showed that the DR grade was positively related to the portal/septalα-SMA level (r = 0.359, P = 0.001).Conclusions: Peritumoral DR was associated with local inflammation and fibrosis. Patients with non-mucin-producing ICC having obvious peritumoral DR had a poor prognosis. Peritumoral DR could be a prognostic factor for ICC. However, the mechanism should be further investigated.
 A Urine-Based Exosomal Gene Expression Test Stratifies Risk of High-Grade Prostate Cancer in Men with Prior Negative Prostate Biopsy Undergoing Repeat Biopsy
Authors: McKiernan James , Noerholm Mikkel , Tadigotla Vasisht , Kumar Sonia , Torkler Phillipp , Sant Grannum , Alter Jason , Donovan Michael J , Skog Johan
Published: August 2020

BACKGROUND: Initial prostate biopsy often fails to identify prostate cancer resulting in patient anxiety, especially when clinical features such as prostate specific antigen (PSA) remain elevated, leading to the need for repeat biopsies. Prostate biomarker tests, such as the ExoDx™ Prostate(IntelliScore), or EPI test, have been shown to provide individualized risk assessment of clinically significant prostate cancer at initial biopsy; however, the performance in the repeat biopsy setting is not well established. Methods: As part of a previous prospective clinical validation study evaluating the performance of the EPI test, we collected first-catch, non-DRE urine samples across 22 sites from men with at least one prior negative biopsy scheduled to undergo a repeat prostate biopsy to rule out prostate cancer. All men were 50 years or older with a PSA 2-10ng/mL. Exosomal mRNA was extracted and expression of three genomic markers, PCA3, ERG and SPDEF was measured. The resulting EPI score was correlated with biopsy results. Results: 229 men with a prior negative biopsy underwent repeat biopsies. ExoDx Prostate demonstrated good performance ruling out high-grade (Grade group 2, GG2, or higher) prostate cancer (HGPCa) using the previously validated 15.6 cut point in the initial biopsy setting. The EPI test yielded an NPV of 92% independent of other clinical features and would have avoided 26% of unnecessary biopsies while missing only five patients with HGPCa (2.1%). Furthermore, the EPI test provided additional information at a cut-point of 20 and 29.6 with an NPV of 94%, potentially delaying 35% and 61% of unnecessary biopsies, respectively. AUC curves and Net Health Benefit Analyses demonstrated superior performance of ExoDx Prostate over PSA and clinical only risk calculators, i.e. ERSPC.Conclusions: The EPI test provided good performance using the 15.6 cut-point for ruling out HGPCa / GG2 or higher in men undergoing a repeat prostate biopsy with a PSA of 2-10ng/ml. Furthermore, the test utilizes gene expression data independent of clinical features to predict the likelihood of HGPCa / GG2 on a subsequent needle biopsy.
Outpatient Management of Oligosymptomatic Patients with Respiratory Infection in the Era of SARS-CoV-2. Experience from Rural German General Practitioners 
Authors: Wernhart Simon , Förster Tim Henning , Weihe Eberhard
Published: August 2020

Background: Covid-19 is causing a pandemic and forces physicians to restructure their daily work. We want to share our experience in the outpatient management of potentially infected patients with colleagues from other countries with special consideration of altered national test strategies during the crisis.Methods: We analysed all patients with respiratory symptoms reporting to our three rural general practioner (GP) offices in North Rhine Westphalia, Germany, from 27.01-20.04.2020 (n=489 from a total of 6090 patients). Patients with respiratory symptoms were examined in a separated isolation area, while the others were allowed to enter the office. We applied the first recommended algorithm of the German Robert Koch Institute (RKI) to test suspected patients and compared our results to an adapted, more liberal version of the RKI, which is currently applied in Germany.Results: Eighty patients (16.36%, mean age: 47.03years+-18.08) were sent to a nasopharyngeal smear. five patients (6.25%) turned out to be positive, four of which had established risk factors for COVID-19. Overall, the most common symptoms were cough (83.75%), sore throat (71.25%), as well as myalgia and fatigue (66.25%). The most common diagnoses were rhinopharyngitis (37.22%) and acute bronchitis (30.27%). A sore throat was more common in positively tested patients (80% vs. 12%). Applying the first RKI test strategy yielded 6.25% of positive tests (n=80), while the more liberal later RKI recommendation would have achieved 1.36% of positive tests from 369 patients. No positive test was missed by applying the conservative strategy. None of our employees called in sick during this period, which emphasizes the efficacy and safety of our screening methods. Conclusion: A clinical distinction between ordinary respiratory infections and COVID-19 is not possible in a low-prevalence population. Our model to prevent unprotected physical contact, screen patients in front of the office with protective equipment, and to examine respiratory infections in separated areas works in the GP setting without overt health risks for employees. Thus, this approach should be used as a GP standard to uphold patient care without major health risks for the personnel. Large multicenter studies are necessary to work out the most suitable test strategy.
Targeting high risk forest goers for malaria elimination: A novel approach for investigating forest malaria to inform program intervention in Vietnam
Authors: Canavati Sara E. , Kelly Gerard C. , Quintero Cesia E. , Vo Thuan Huu , Tran Long Khanh , Ngo Thang Duc , Tran Duong Thanh , Edgel Kimberly A. , Martin Nicholas J.
Published: August 2020

Background Individuals that work and sleep in remote forest and farm locations in the Greater Mekong Subregion continue to remain at high risk of both acquiring and transmitting malaria. These difficult-to-access population groups largely fall outside the reach of traditional village-centered interventions, presenting operational challenges for malaria programs. In Vietnam, over 60% of malaria cases are thought to be individuals who sleep in forests or on farms. New malaria elimination strategies are needed in countries where mobile and migrant workers frequently sleep outside of their homes. Aims of this study were to apply targeted surveillance-response based investigative approaches to gather location-specific data on confirmed malaria cases and identify associated malaria prevention, treatment and risk behaviors of individuals sleeping in remote forest and farms sites in Vietnam. Methods A cross-sectional study using novel targeted reactive investigative approaches at remote area sleeping sites was conducted in three mountainous communes in Phu Yen province in 2016. Index cases were defined as individuals routinely sleeping in forests or farms who had tested positive for malaria. Index cases and non-infected neighbors from forest and farm huts within 500m of the established sleeping locations of index cases were interviewed in person at their remote-area sleeping sites. Results A total of 307 participants, 110 index cases and 197 neighbors, were enrolled. Among 93 participants who slept in the forest, index cases were more likely to make >5 trips to the forest per year (prevalence odds ratio (POR) 7.41, 95% confidence interval (CI) 2.66–20.63), sleep in huts without walls (POR 44.00, 95% CI 13.05–148.33), sleep without mosquito nets (POR 2.95, 95% CI 1.26–6.92), and work after dark (POR 5.48, 95% CI 1.84–16.35). Of the 204 farm-based respondents, a significantly higher proportion of index cases were involved in non-farming activities (logging) (POR 2.74, 95% CI 1.27–5.91). Conclusion Investigative approaches employed in this study allowed for the effective recruitment and characterization of high-priority individuals frequently sleeping in remote forest and farm locations, providing relevant population and site specific data that decision makers can use to design and implement targeted interventions to support malaria elimination.
The Universal Sample Holders of Microanalytical Instruments of FIB, TEM, NanoSIMS, and STXM-NEXAFS for the Coordinated Analysis of Extraterrestrial Materials
Authors: Ito Motoo , Tomioka Naotaka , Uesugi Kentaro , Uesugi Masayuki , Kodama Yu , Sakurai Ikuya , Okada Ikuo , Ohigashi Takuji , Yuzawa Hayato , Yamaguchi Akira , Imae Naoya , Karouji Yuzuru , Shirai Naoki , Yada Toru , Abe Masanao
Published: August 2020

We developed universal sample holders (the Kochi grid, Kochi clamp, and Okazaki cell) and a transfer vessel (facility-to-facility transfer container (FFTC)) to analyze sensitive and fragile samples, such as extremely small extraterrestrial materials. The holders and container prevent degradation, contamination due to the terrestrial atmosphere (water vapor and oxygen gas) and small particles, as well as mechanical sample damage. The FFTC can isolate the samples from the effects of the atmosphere for more than a week. The Kochi grid and clamp were made for a coordinated micro/nano-analysis that utilizes a focused-ion beam apparatus, transmission electron microscope, and nanoscale secondary ion mass spectrometry. The Okazaki cell was developed as an additional attachment for a scanning transmission X-ray microscope that uses near-edge X-ray absorption fine structure (NEXAFS). These new apparatuses help to minimize possible alterations from the exposure of the samples to air. The coordinated analysis involving these holders was successfully carried out without any sample damage or loss, thereby enabling us to obtain sufficient analytical datasets of textures, crystallography, elemental/isotopic abundances, and molecular functional groups for µm-sized minerals and organics in both the Antarctic micrometeorite and a carbonaceous chondrite. We will apply the coordinated analysis to acquire the complex characteristics in samples obtained by the future spacecraft sample return mission.
Protein cysteine S-nitrosylation provides reducing power by enhancing lactate dehydrogenase activity in Trichomonas vaginalis under iron deficiency
Authors: Cheng Wei-Hung , Huang Kuo-Yang , Ong Seow-Chin , Ku Fu-Man , Huang Po-Jung , Lee Chi-Ching , Yeh Yuan-Ming , Lin Rose , Chiu Cheng-Hsun , Tang Petrus
Published: August 2020

Background: Iron plays essential roles in the pathogenesis and proliferation of Trichomonas vaginalis, the causative agent of the most prevalent nonviral human sexually transmitted infection. We previously demonstrated that under iron deficiency, the endogenous nitric oxide (NO) is accumulated and capable of regulating the survival of T. vaginalis. Herein, we aim to explore the influence of NO on the activity of the pyruvate-reducing enzyme lactate dehydrogenase in T. vaginalis (TvLDH).Methods : Levels of lactate and pyruvate were detected for determining glycolysis activity in T. vaginalis under iron deficiency. Quantitative PCR was performed to determine the expression of TvLDH. S-nitrosylated (SNO) proteomics was conducted to identify the NO-modified proteins. The activities of glyceraldehyde-3-phosphate dehydrogenase (TvGAPDH) and TvLDH were measured after sodium nitrate treatment. The effects of protein nitrosylation on the production of cellular reducing power were examined by measuring the amount of nicotinamide adenine dinucleotide (NAD) and the ratio of the NAD redox pair (NAD+/NADH).Results: We found that although the glycolytic pathway was activated in cells under iron depletion, the level of pyruvate was decreased due to the increased level of TvLDH. By analyzing the SNO proteome of T. vaginalis upon iron deficiency, we found that TvLDH is one of the glycolytic enzymes modified by SNO. The production of pyruvate was significantly reduced after nitrate treatment, indicating that protein nitrosylation accelerated the consumption of pyruvate by increasing TvLDH activity. Nitrate treatment also induced NAD oxidation, suggesting that protein nitrosylation was the key posttranslational modification controlling cellular redox status. Conclusion: We demonstrated that NO-mediated protein nitrosylation plays pivotal roles in the regulation of glycolysis, pyruvate metabolism, and the activity of TvLDH. The recycling of oxidized NAD catalyzed by TvLDH provided the reducing power that allowed T. vaginalis to adapt to the iron-deficient environment.
Short-duration, submaximal intensity exercise stress combined with adenosine triphosphate decreases artifacts in myocardial perfusion single-photon emission computed tomography
Authors: Shinoda Yukinori , Tachibana Koichi , Minamisaka Tomoko , Fukuoka Hidetada , Inui Hirooki , Ueno Keisuke , Inoue Soki , Mine Kentaro , Ueda Kumpei , Hoshida Shiro
Published: August 2020

Background: Myocardial perfusion single-photon emission computed tomography (SPECT) imaging with stress is a useful examination for detecting coronary artery disease. Since the presence of artifacts is remaining challenges, we aimed to define the minimum intensity of low-grade exercise stress levels combined with drug stress to reduce undesired artifacts and their related factors. Methods: We divided patients with suspicious coronary artery disease into 4 groups as follows: group A, adenosine triphosphate (ATP) for 6 min; group A+25 W, ATP+25 W exercise for 6 min; group A+35 W, ATP+35 W exercise for 6 min; group A+45 W, ATP+45 W exercise for 6 min) and enrolled only those whose summed stress scores were <3. Undesired artifacts were evaluated on the basis of heart-to-liver activity ( H/L ) ratio and heart-to-10 pixels below the heart ( H /below the H ) ratio. Results: The logarithmic values of H/L and H /below the H ratios were significantly higher in groups A+35 W and A+45 W than in group A (p<0.05, each). In all the patients, the logarithmic values of H/L and H /below the H ratios positively correlated with the increment of rate pressure product (RPP, p=0.002 and p=0.005, respectively) after stress in the univariate analysis. The left ventricular end-diastolic volume (LVEDV) after stress (p=0.002) negatively correlated with the logarithmic value of H /below the H ratio, but not H/L ratio. Although the increment of RPP was independently associated with the logarithmic values of both H/L (p=0.001) and H /below the H ratios (p=0.005), LVEDV was also independently associated with the logarithmic value of H /below the H ratio (p<0.001) in multivariate regression analysis under adjusting with age and sex. Conclusion: ATP plus ≥35 W exercise stress for 6 min was useful for reducing undesired artifacts after stress in myocardial perfusion SPECT. LVEDV after stress in addition to the increment of RPP was independently associated with the H /below the H ratio, but not the H/L ratio.
Boosting toxic protein expressionbiosynthesis: transient in vivo inactivation of engineered bacterial alkaline phosphatase
Authors: Krawczun Natalia , Bielawa Marta , Szemiako Kasjan , Lubkowska Beata , Sobolewski Ireneusz , Zylicz-Stachula Agnieszka , Skowron Piotr M
Published: August 2020

Background The biotechnology production of enzymes is often troubled by the toxicity of the recombinant products of cloned and expressed genes, which interferes with the recombinant hosts’ metabolism. Various approaches have been taken to overcome these limitations, exemplified by tight control of recombinant genes or secretion of recombinant proteins. An industrial approach to protein production demands maximum possible yields of biosynthesized proteins, balanced with the recombinant host’s viability. Bacterial alkaline phosphatase (BAP) from Escherichia coli (E. coli) is a key enzyme used in protein/antibody detection and molecular cloning. As it removes terminal phosphate from DNA, RNA and deoxyribonucleoside triphosphates, it is used to lower self-ligated vectors’ background. The precursor enzyme contains a signal peptide at the N-terminus and is secreted to the E. coli periplasm. Then, the leader is clipped off and dimers are formed upon oxidation.Results We present a novel approach to phoA gene cloning, engineering, expression, purification and reactivation of the transiently inactivated enzyme. The recombinant bap gene was modified by replacing a secretion leader coding section with a N-terminal his6-tag, cloned and expressed in E. coli in a PBAD promoter expression vector. The gene expression was robust, resulting in accumulation of His6-BAP in the cytoplasm, exceeding 50% of total cellular proteins. The His6-BAP protein was harmless to the cells, as its natural toxicity was inhibited by the reducing environment within the E. coli cytoplasm, preventing formation of the active enzyme. A simple protocol based on precipitation and immobilized metal affinity chromatography (IMAC) purification yielded homogeneous protein, which was reactivated by dialysis into a redox buffer containing reduced and oxidized sulfhydryl group compounds, as well as the protein structure stabilizing cofactors Zn2+, Mg2+ and phosphate. The reconstituted His6-BAP exhibited high activity and was used to develop an efficient protocol for all types of DNA termini, including problematic ones (blunt, 3’-protruding).Conclusions The developed method appears well suited for the industrial production of ultrapure BAP. Further, the method of transient inactivation of secreted toxic enzymes by conducting their biosynthesis in an inactive state in the cytoplasm, followed by in vitro reactivation, can be generally applied to other problematic proteins.
New Onset Diabetes Mellitus and Cardiovascular Events in Korean Patients with Acute Myocardial Infarction Receiving High-Intensity Statins
Authors: Choi Jah Yeon , Choi Cheol Ung , Choi Byoung Geol , Park Yoonjee , Kang Dong Oh , Jang Won Young , Kim Woohyeun , Na Jin Oh , Kim Jin Won , Kim Eung Ju , Rha Seung-Woon , Park Chang Gyu , Seo Hong Seog , Jeong Myung Ho , Chae Sung-Chull , Seong In-Whan , Yoon Chang-Hwan , Cha Kwang Soo , Oh Seok Kyu
Published: August 2020

Background: High-intensity statin therapy is typically used in patients with acute myocardial infarction (AMI) for secondary prevention. However, there have been consistent concerns regarding its association with diabetes mellitus. We investigated the effect of high-intensity atorvastatin and rosuvastatin on new-onset diabetes mellitus (NODM) and cardiovascular outcomes over a 3-year follow-up period.

Methods: Data from the Korea Acute Myocardial Infarction Registry were collected from November 2011 to October 2015, and 13,104 patients with AMI were enrolled from major cardiovascular centers. Among them, 2,221 patients without diabetes who had been administered with high-intensity atorvastatin (40–80 mg) and rosuvastatin (20 mg) were investigated. The atorvastatin and rosuvastatin groups were evaluated for the incidence of NODM and major adverse cardiac events (MACE) including death, myocardial infarction, and revascularization cases in the following 3 years.

Results: Baseline characteristics were comparable between the two groups. Event-free survival rate of NODM and MACE was not significantly different between the atorvastatin and rosuvastatin groups (92.5% vs. 90.8%, respectively; Log-rank P-value = 0.550). The event-free survival rate of MACE was also not significantly different between atorvastatin and rosuvastatin groups (89.0% vs. 89.6%, respectively; Log rank P-value = 0.662). Multivariate Cox analysis revealed that statin type was not a prognostic factor in the development of NODM and MACE.

Conclusions: Administering high-intensity atorvastatin and rosuvastatin in patients with AMI produced comparable effects on NODM and clinical outcomes, suggesting their clinical equivalence in secondary prevention.
Comparison of BSGI , MRI, mammography, and ultrasound for the diagnosis of breast lesions and their correlations with specific molecular subtypes in Chinese women
Authors: liu hongbiao , Zhan Hongwei , Sun Da , Zhang Ying
Published: August 2020

Background: Breast cancer is a leading cause of cancer in females, and is the second leading cancer-related cause of death in this group. Early diagnosis is essential to breast cancer to be effectively treated, and ultrasound, mammography, and magnetic resonance imaging (MRI) represent three key technologies that are utilized for the diagnosis of breast lesions. Breast-specific gamma imaging (BSGI) is an approach to molecular breast imaging that allows for high-resolution radio-imaging that is not adversely impacted by breast tissue density. This study was therefore designed to assess the relative diagnostic efficacy of BSGI, MRI, mammography, and ultrasound in different molecular subtypes of breast cancer among Chinese women. Methods: Diagnostic findings from 390 patients that had undergone diagnosis and treatment in our breast surgery department were retrospectively reviewed. Patients had been diagnosed via BSGI, mammography, ultrasound, and MRI. The diagnostic efficacy of these different imaging modalities and their associated biological characteristics were compared in the present study. Results: A total of 229 of these 390 patients (58.7%) were diagnosed with malignant breast cancer, with the remaining 161 (41.3%) cases having been found to be benign. BSGI, MRI, mammography, and ultrasound yielded respective sensitivity values of 91.7%, 92.5%, 77.3%, and 82.1%, while the respective specificity values for these imaging modalities were 80.7%, 69.7%, 74.5%, and 70.8%. For lesions > 1 cm, BSGI offered a sensitivity of 92.5%. For mammographic breast density A, B, C, and D, BSGI offered a sensitivity of 93.3%, 94.0%, 91.5%, and 89.3%, respectively. BSGI also yielded a significantly higher lesion-to-normal lesion ratio (LNR) for malignant lesions relative to benign lesions (2.76±1.32 vs 1.46±0.49). Conclusions: These findings confirm that BSGI is highly sensitive and is superior to mammography in the detection and diagnosis of ductal carcinomas in situ (DCIS). Such diagnostic efficacy can be further improved by using BSGI as an auxiliary modality to mammography and ultrasound, potentially improving the reliability of breast lesion diagnosis, thereby ensuring that patients receive rapid and effective treatment without the risk of misdiagnosis or unnecessary surgical treatment.