bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of monoclonal antibodies and simplified sandwich ELISA for canine neutrophil gelatinase-associated lipocalin A detection
Authors: Cao Jun , Tang Bo , Zhang Xinyu , Xia Xiaoli , Sun Huaichang
Published: February 2020

Background Acute kidney injury (AKI) is one of the most common canine diseases with a high mortality rate. Neutrophil gelatinase-associated lipocalin (NGAL) is the novel biomarker for early diagnosis of renal injury. Only few sandwich ELISA kits are commercially available, all of which require the use of expensive enzyme-conjugated secondary or biotinylated antibody. The aims of this study were to develop high affinity monoclonal antibodies (mAbs) and simplified sandwich ELISA for canine NGAL detection. Results Recombinant canine NGAL was expressed in E. coli and purified to a high purity. Six hybridoma cell lines were generated by immunization of mice with the purified protein, all of which secreted high titers of specific mAbs. By screening 36 different antibody combinations, a pair of mAbs with high additivity and P/N ratio was selected as the capture and detection antibodies. By conjugation of the detection mAb with horse radish peroxidase, a simplified sandwich ELISA was developed with a correlation coefficient of 0.9939, detection limit of 8.28 ng/mL. The parallel test of 42 samples from healthy and AKI dogs showed the good agreement in NGAL concentrations detected by the simplified sandwich ELISA and commercial ELISA kit. Conclusions We developed canine NGAL-specific monoclonal antibodies and simplified sandwich ELISA. The simplified sandwich ELISA could replace the commercial ELISA kits for canine NGAL detection with the advantages of reduced cost and detection time.
“You don't know my story. You don't know what I've been going through.” A qualitative exploration of HIV survivorship over decades through the lens of symbolic violence
Authors: Freeman Robert , Gwadz Marya , Wilton Leo , Silverman Elizabeth , Cluesman Sabrina , Martinez Belkis Y. , Collins Linda M. , Leonard Noelle R. , Dorsen Caroline
Published: February 2020

Background Persons living with HIV (PLWH) are living longer, although racial/ethnic and socioeconomic status (SES) disparities persist. Yet, little is known about successful HIV management over decades. To address this gap, the present study took a qualitative approach and used the lens of symbolic violence, a type of internalized, non-physical violence manifested in the power differential between social groups. We focused on adult African American/Black and Hispanic/Latinx (AABHL) PLWH from low SES-backgrounds. Methods Data were drawn from two studies with AABHL PLWH in New York City ( N =59). After providing signed informed consent, participants engaged in in-depth semi-structured interviews on aspects of HIV management. Interviews were audio-recorded and professionally transcribed verbatim, and data were analyzed using a systematic content analysis approach. Results Participants in the two studies were comparable on sociodemographic and HIV history characteristics. They had lived with HIV for 20 years, on average (range 3-33 years). All were from low-SES backgrounds and most were African American/Black and men. Participants experienced a convergence of multiple intersecting social exclusions, harms, and stigmas, consistent with symbolic violence, which contributed to disengagement from HIV care and medications. We found five specific sub-themes: (1) material, social, and emotional challenges combined to “grind down” participants over time and diminish self-worth and even, at times, the will to live, (2) social isolation and self-isolation, based in part on feeling devalued and dehumanized, served as both a stigma-avoidance strategy and a mechanism of social exclusion, (3) stigmatizing aspects of patient-provider interactions, both experienced and anticipated, and (4) perceived restricted autonomy in HIV care reduced engagement, and (5) poor HIV management was internalized as a personal failure. Importantly, resilience was also evident throughout the five sub-themes. Conclusions Symbolic violence is a useful framework for understanding the experiences of long-term HIV management/survivorship among AABHL PLWH from low-SES backgrounds. Aspects of symbolic violence are internalized over time (e.g., experiencing devaluation, dehumanization, loss of self-worth, and anticipated stigma), thereby impeding successful HIV management, including because avoiding HIV care and stopping HIV medications are primary coping strategies. Study findings have implications for interventions in community and health care settings.
Population-level investigation of the knowledge of ocular chemical injuries and proper immediate action
Authors: Seraj Hadeel , Khawandanh Shahad , Fatani Arwa , Saeed Afnan , Alotaibi Ghadeer , Basheikh Ahmed
Published: February 2020

Objective: Although the eyes occupy 0.1% of the total body surface, eye injuries are serious because vision is arguably the most important sense. We aimed to assess knowledge of Saudi Arabian residents regarding steps to be taken in cases of chemical eye injury, in order to promote awareness of such procedures. Results: A cross-sectional design was done. A random sampling method was utilized to select 888 individuals in the Saudi community. Participants completed an electronic closed ended, validated, anonymous, self-administered questionnaire. Two experts assessed content and face validity. Respondents were 18–29 years of age. 74 (8.3%) had a history of chemical eye injury. Regarding the first step taken in case of chemical eye injury, 697 (78.5%) respondents indicated washing with water, 164 (18.5%) indicated visiting the emergency department, 11 (1.2%) indicated using eye drops, and 5 (0.6%) indicated covering the eye immediately. Seventy-five (8.4%) respondents agreed that an eye injured with an acidic material should be washed with an alkaline solution. These results should be confirmed by health authorities and appropriate interventions should be developed for improving knowledge among masses, thereby promoting a healthier society. Keywords: Eye damage, Saudi Arabia, corrective steps, alkaline, acidic
Misconceptions about transmission, symptoms and prevention of HIV/AIDS among adolescents in Ebonyi state, South-east Nigeria
Authors: Agu Ifunanya Clara , Mbachu Chinyere Ojiugo , Okeke Chinyere , Eze Irene , Agu Chibuike , Ezenwaka Uchenna , Ezumah Nkoli , Onwujekwe Obinna
Published: February 2020

Objectives: Nigeria has the second largest number of adolescents and young people living with HIV/AIDS in the world. Misconceptions about HIV/AIDS contribute to spread of HIV, and constrain uptake of preventive services. This paper explored misconceptions about HIV/AIDS among adolescents in south-east Nigeria. A qualitative study was conducted in six urban and rural local government areas of Ebonyi state. Data were collected through twelve focus group discussions (FGD) with unmarried adolescents aged 13-18 who were either attending school or out-of-school. The FGDs were conducted using a pre-tested topic guide. Data were coded manually and analyzed using a thematic framework approach. Results : There are persistent misconceptions about transmission of HIV/AIDS through mosquito bites and sharing of personal belongings. Some adolescents had inaccurate notions that a HIV infected person could be identified through changes in physical features such as abdominal swelling and longer fingernails. A few of them also reported that HIV could be treated with antibiotics. These misconceptions were expressed by both male and female adolescents. Adolescents have some mistaken beliefs about HIV/AIDS which constrain them from taking necessary preventive measures. Hence, the need to target adolescents with health education interventions on HIV/AIDS.
Compbdt: an R program to compare two binary diagnostic tests subject to a paired design
Authors: Roldán-Nofuentes Jose Antonio
Published: February 2020

Background: The comparison of the effectiveness of two binary diagnostic tests is an important topic in Clinical Medicine. The most frequent type of sample design to compare two binary diagnostic tests is the paired design. This design consists of applying the two binary diagnostic tests to all of the individuals in a random sample, where the disease status of each individual is known through the application of a gold standard . This article presents an R program to compare parameters of two binary tests subject to a paired design. Results: The “compbdt” program estimates the sensitivity and the specificity, the likelihood ratios and the predictive values of each diagnostic test applying the confidence intervals with the best asymptotic performance. The program compares the sensitivities and specificities of the two diagnostic tests simultaneously, as well as the likelihood ratios and the predictive values, applying the global hypothesis tests with the best performance in terms of Type I error and power. When the global hypothesis test is significant, the causes of the significance are investigated solving the individual hypothesis tests and applying the multiple comparison method of Holm. The most optimal confidence intervals are also calculated for the difference or ratio between the respective parameters. Based on the data observed in the sample, the program also estimates the probability of making a Type II error if the null hypothesis is not rejected, or estimates the power if the if the alternative hypothesis is accepted. The “compbdt” program provides all the necessary results so that the researcher can easily interpret them. The estimation of the probability of making a Type II error allows the researcher to decide about the reliability of the null hypothesis when this hypothesis is not rejected. The “compbdt” program has been applied to a real example on the diagnosis of coronary artery disease. Conclusions: The “compbdt” program is one which is easy to use and allows the researcher to compare the most important parameters of two binary tests subject to a paired design. The “compbdt” program is available as supplementary material.
SARFIMA model prediction for infectious diseases: application to hemorrhagic fever with renal syndrome and comparing with SARIMA
Authors: Qi Chang , Zhang Dandan , Zhu Yuchen , Liu Lili , Li Chunyu , Wang Zhiqiang , Li Xiujun
Published: February 2020

Background The early warning model of infectious diseases plays a key role in prevention and control. Our study aims to using seasonal autoregressive fractionally integrated moving average (SARFIMA) model to predict the incidence of hemorrhagic fever with renal syndrome (HFRS) and comparing with seasonal autoregressive integrated moving average (SARIMA) model to evaluate its prediction effect. Methods Data on notified HFRS cases in Weifang city, Shandong Province were supplied by the Disease Reporting Information System of the Shandong Center for Disease Control and Prevention from January 1, 2005 to December 31, 2018. The SARFIMA model considering both the short-memory and long-memory were performed to fit and predict the HFRS series. Besides, we compared accuracy of fitting and prediction between SARFIMA and SARIMA which were used widely in infectious diseases. Results Both SARFIMA and SARIMA models show good fit of data. Model assessments indicated that the SARFIMA model has better goodness of fit (SARFIMA(2, 0.15, 2)(1, 0, 0) 12 : Akaike information criterion (AIC): -630.61; SARIMA(2, 0, 2)(1, 1, 0) 12 : AIC: -196.04) and better predictive ability than the SARIMA model (SARFIMA: root mean square error (RMSE): 0.067; SARIMA: RMSE: 0.111). Conclusions The SARFIMA model produces superior forecast performance than the SARIMA model for HFRS. Hence, the SARFIMA model may help us to improve the forecast of HFRS incidence.
Association of plasma chromium with metabolic syndrome among Chinese adults: a case-control study
Authors: Chen Sijing , Zhou Li , Guo Qianqian , Fang Can , Wang Mengke , Peng Xiaobo , Yin Jiawei , Li Shuzhen , Zhu Yalun , Yang Wei , Zhang Yan , Shan Zhilei , Chen Xiaoyi , Liu Liegang
Published: February 2020

Backgroud Chromium has been suggested playing a role in alleviating diabetes, insulin resistance and lipid anomalies, but the effect on MetS in humans remains controversial. Methods We conducted a matched case-control study in a Chinese population, involving 2,141 MetS cases and 2,141 healthy controls, which were 1:1 matched by age (±2 years) and sex. Plasma chromium was measured by inductively coupled plasma mass spectrometry. Results Plasma chromium levels were lower in MetS group than in control group (median: 4.23 μg/L and 4.46 μg/L, respectively, P < 0.001), and progressively decreased with the number of MetS components ( P for trend <0.001). After adjustment for potential confounding factors, the odds ratios (95% confidence intervals) for MetS across increasing quartiles of plasma chromium levels were 1 (reference), 0.84 (0.67-1.05), 0.76 (0.61-0.95), and 0.62 (0.49-0.78), respectively ( P for trend < 0.001). For the components of MetS (high waist circumference, high triglycerides and high blood glucose), the odds ratios (95% confidence intervals) of the highest quartiles were 0.77 (0.61-0.95), 0.67 (0.55-0.80), and 0.53 (0.44-0.64), respectively ( P for trend < 0.05). Conclusions Our results indicated that plasma chromium levels were inversely associated with MetS in Chinese adults. The association may be explained by the relations between plasma chromium levels and high waist circumference, and the triglycerides and blood glucose levels.
A policy Analysis of Phenylketonuria Screening National Program in Iran
Authors: Heidari Alireza , Arab Mohammad , Damari Behzad
Published: February 2020

Background Phenylketonuria (PKU) Screening is a public health measure aimed at identifying the early cases and managing the affected infants and trying to reduce infant morbidity and mortality. The aim of this study was to analyze the policies of the PKU national screening program in Iran. Methods PKU screening program policies were analyzed according to the policy triangle model. Document review and 38 semi-structured interviews were used for data collection. Document review data were analyzed using content analysis and interview data were analyzed using framework analysis. Results The findings of the study were categorized according to the content (structure and organization, rules, bylaws and guidelines), process (agenda setting, formation, implementation, and evaluation of screening policies and programs), the policy context (political and executive factors, economic and financial factors, social and cultural factors), and the stakeholders(Genetics office, Network Development Bureau, Population and Family Health Bureau, Health Reference Laboratory, Pediatric Health Department, Health Vice-Chancellor of Medical Sciences, Health Ministry Deputy of Health, PKU Selected Hospitals, Pastor Institute, Food and Drug Administration and Research Centers. Welfare Organization, the Health Insurance Agency, the PKU Patient Support Association, the Post Company, and the Registry). Conclusions The policy triangle framework helped to explain the different components of the PKU screening program.
"Once the child is delivered, he is no more your baby," Exclusive Breastfeeding experiences of first-time mothers in Kassena-Nankana Municipality, Ghana - a qualitative study
Authors: Adda Louisa , Opoku-Mensah Kwabena , Dako-Gyeke Phyllis
Published: February 2020

Background

Exclusive Breastfeeding (EBF) is globally accepted as the preferred method for infant feeding. In Ghana, an estimated 84% of children < 2 months old are exclusively breastfed. But by age 4 to 5 months, only 49% continue to receive EBF. This situation continues to deteriorate. Thus, the need to explore perceptions, practices as well as factors that influence EBF in Ghana.

Method

Using a qualitative design, four focus group discussions were conducted among first-time mothers and eight in-depth interviews with health workers and traditional birth attendants. The study was conducted in four communities in the Kassena-Nankana municipality of Ghana. Discussions and interviews were recorded and later transcribed verbatim to English language. The transcribed data was then coded with the aid of analysis computer software (Nvivo version 10.0) and later analyzed for the generation of themes.

Result

Exclusive breastfeeding is practiced among first-time mothers due to its perceived benefits; which include nutritional advantage, ability to enhance growth whilst boosting immunity and its economic value. However misconceptions as well as, certain cultural practices (e.g. giving herbal concoctions, breastmilk purification rites), and relational influences, may threaten a mother’s intention to exclusively breastfeed. Relational influences are mainly from mother in-laws, traditional birth attendants, grandmothers, herbalists and other older adults in the community.

Conclusion

Although first time mothers attempt EBF, external influences make it practically challenging. The availabilty and utilization of information on EBF was found to positively influence perceptions towards EBF, leading to change in attitude towards the act.

Recommendations

The provision of education on EBF should be targeted to mothers during antenatal and postnatal clinics in order to help address misconceptions of EBF. Again, the practice of community based health services should be strengthened to provide support to first-time mothers as well as continuous education to the family and community leaders who influence decision making on breastfeeding of infants.
Quality of Life of Patients with Metastatic Pancreatic Adenocarcinoma Initiating First‐Line Chemotherapy in Routine Practice
Authors: Laquente Berta , Macarulla Teresa , Bugés Cristina , Martín Marta , García Carlos , Pericay Carles , Merino Sandra , Visa Laura , Martín Teresa , Pedraza Manuela , Carnero Beatriz , Guardeño Raquel , Verdaguer Helena , Mut Alejandro , Vilanova David , García Adelaida
Published: February 2020

Background Considering the physical decline of patients with metastatic pancreatic adenocarcinoma, assessing their health-related quality of life becomes a matter of major concern. Methods Observational, prospective, multicenter study including patients with metastatic pancreatic adenocarcinoma who started first‐line chemotherapy in 12 Spanish centers. Treatment and clinical characteristics were recorded at baseline. Patients’ health-related quality of life, ECOG, and Karnofsky index were measured at baseline, at Days 15 and 30, and every four weeks up to 6 months of chemotherapy. Health-related quality of life was measured using the EORTC-QLQ‐C30 and EQ-5D questionnaires. Other endpoints included overall survival and progression‐free survival. Results The study sample included 116 patients (median age of 65 years). Mean (SD) scores for the QLQ-C30 global health status scale showed a significant increasing trend throughout the treatment (p=0.005). Patients with either a Karnofsky index of 70-80 or ECOG 2 showed greater improvement in the QLQ-C30 global health status score than the corresponding groups with better performance status (p≤0.010). Pain, appetite, sleep disturbance, nausea, and constipation significantly improved throughout the treatment (p<0.005). Patients with QLQ-C30 global health status scores ≥50 at baseline had significantly greater overall survival and progression-free survival (p=0.005 and p=0.021, respectively). No significant associations were observed regarding the EQ-5D score. Conclusions Most metastatic pancreatic adenocarcinoma patients receiving first-line chemotherapy improved their health-related quality of life throughout the treatment. Patients with lower performance status and health-related quality of life at baseline tended to greater improvement. The EORTC QLQ-C30 scale is suitable for measuring the health-related quality of life of metastatic pancreatic adenocarcinoma patients receiving first-line chemotherapy.
Feasibility of an integrated multidisciplinary geriatric rehabilitation programme for older stroke patients: a process evaluation
Authors: Vluggen Tom , Haastregt Jolanda van , Verbunt Jeanine , Heugten Caroline van , Schols Jos
Published: February 2020

Background

Almost half of the stroke patients admitted to geriatric rehabilitation has persisting problems after discharge. Currently, there is no evidence based geriatric rehabilitation programme available for older stroke patients, combining inpatient rehabilitation with adequate aftercare aimed at reducing the impact of persisting problems after discharge from a geriatric rehabilitation unit. Therefore, we developed an integrated multidisciplinary rehabilitation programme consisting of inpatient neurorehabilitation treatment using goal attainment scaling, home based self-management training, and group based stroke education for patients and informal caregivers. We performed a process evaluation to assess to what extent this programme was performed according to protocol. Furthermore, we assessed the participation of the patients in the programme, and the opinion of patients, informal caregivers and care professionals on the programme.

Methods

In this multimethod study, process data were collected by means of interviews, questionnaires, and registration forms among 97 older stroke patients, 89 informal caregivers, and 103 care professionals involved in the programme.

Results

A substantial part of patients and informal caregivers did not receive all key elements of the programme. Almost all patients formulated rehabilitation goals, but only among two thirds of the patients the goal attainment scaling method was used. Furthermore, the self-management training was considered rather complex and difficult to apply for frail elderly persons with stroke, and the percentage of therapy sessions performed in the patients’ home environment was lower than planned. In addition, only about a quarter of the patients and informal caregivers attended the education sessions. However, a large majority of patients, informal caregivers and care professionals indicated the beneficial aspects of the programme.

Conclusion

This study revealed that although the programme in general is perceived to be beneficial by patients, and informal and formal caregivers, the feasibility of the programme needs further attention. Because of persisting cognitive deficits and specific care needs in our frail and multimorbid target population, some widely used methods such as goal attainment scaling, and self-management training seemed not feasible in their current form. To optimize feasibility of the programme, it is recommended to tailor these elements more optimally to the population of frail older patients.
Application of Real-Time Simultaneous Amplification and Testing Method to Accurately and Rapidly Detect Extra-pulmonary Tuberculosis
Authors: Li Tongxin , Shi Tao , Sun Ying , Zhou Kan , Huang Zhenggu , Wang Pengsen , Luo Ming , Nie Xiaoping , Yang Guoqing , Chen Yu , Chen Yaokai
Published: February 2020

Background: This study aimed to establish and evaluate a simultaneous amplification and testing method for detection of extra-pulmonary tuberculosis. Methods: From January 2016 and December 2017 the pus or surgical excision from the lesions of inpatients admitted from Chongqing Public Health Treatment Center were collected. According to the clinical diagnosis, the samples were divided into two groups including extra-pulmonary tuberculosis (Group A) and other diseases excluded from tuberculosis diseases (Group B). Simultaneous detection of Mycobacterium tuberculosis (MTB) used Roche culture method, liquid culture method and simultaneous amplification and testing method (SAT). The sensitivity and specificity of the SAT method were compared with culture methods and clinical diagnosis of extra-pulmonary tuberculosis. Results: For 433 extra-pulmonary tuberculosis (EPTB) specimens and 49 non-TB specimens, the SAT-TB results correlated with 80.5% (388/482 specimens) of the culture assay results. The sensitivity, specificity, and positive and negative predictive values of the SAT-TB test for the diagnosis of EPTB were 83.6%, 79.4%, 59.4%, and 93.0%, respectively, compared to culture methods. Compared with the clinical diagnosis of patients, the sensitivity and specificity of the SAT-TB test were 41.6% and 100%, respectively, the cultures test were 29.3% and 98.0%. Conclusions: SAT test is a simple and rapid test with high specificity which may enhance the detection of EPTB. SAT-TB is a higher clinical diagnosis value for EPTB in clinical microbiology laboratories.
Gene network in pulmonary tuberculosis based on bioinformatic analysis
Authors: Li Lili , Lv Jian , He Yuan , Wang Zhihua
Published: February 2020

Background: Pulmonary tuberculosis (PTB) is one of the serious infectious diseases worldwide; however, the gene network involved in the host response remain largely unclear. Methods: This study integrated two cohorts profile datasets GSE34608 and GSE83456 to elucidate the potential gene network and signaling pathways in PTB. Differentially expressed genes (DEGs) were obtained for Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using Metascape database. Protein-Protein Interaction (PPI) network of DEGs was constructed by the online database the Search Tool for the Retrieval of Interacting Genes (STRING). Modules were identified by the plug-in APP Molecular Complex Detection (MCODE) in Cytoscape. GO and KEGG pathway of Module 1 were further analyzed by STRING. Hub genes were selected for further expression validation in dataset GSE19439. The gene expression level was also investigated in the dataset GSE31348 to display the change pattern during the PTB treatment. Results: Totally, 180 shared DEGs were identified from two datasets. Gene function and KEGG pathway enrichment revealed that DEGs mainly enriched in defense response to other organism, response to bacterium, myeloid leukocyte activation, cytokine production, etc. Seven modules were clustered based on PPI network. Module 1 contained 35 genes related to cytokine associated functions, among which 14 genes, including chemokine receptors, interferon-induced proteins and Toll-like receptors, were identified as hub genes. Expression levels of the hub genes were validated with a third dataset GSE19439. The signature of this core gene network showed significant response to Mycobacterium tuberculosis (Mtb) infection, and correlated with the gene network pattern during anti-PTB therapy. Conclusions: Our study unveils the coordination of causal genes during PTB infection, and provides a promising gene panel for PTB diagnosis. As major regulators of the host immune response to Mtb infection, the 14 hub genes are also potential molecular targets for developing PTB drugs.
Molecular epidemiology and clinical characteristics of hepatitis delta virus (HDV) infected patients with elevated transaminases in Shanghai, China
Authors: Wu Shanshan , Zhang Yi , Tang Yuyan , Yao Ting , Lv Mengjiao , Tang Zhenghao , Zang Guoqing , Yu Yongsheng , Chen Xiaohua
Published: February 2020

Background: Patients coinfected with HBV and hepatitis D virus (HDV) have a greater risk of HCC and cirrhosis. The current study was undertaken to assess HDV genotype distribution and determine clinical characteristics of hepatitis delta virus (HDV) among HBsAg positive individuals in Shanghai.Method: This retrospective study involved 225 serum samples from HBsAg positive hospitalized patients from October 2010 to April 2013. HDV-specific RT-nested PCR was used to amplify HDV RNA. HDV genotypes were characterized by Next-generation sequencing (NGS), followed by phylogenetic analyses. HDV/HBV co-infected patients and HBV mono-infected patients were compared clinically and virologically.Results: Out of the 225 HBsAg-positive serum samples with elevated transaminases, HDV-RNA was identified in 11 (4.9%) HBsAg positive patients. The HBV loads in the HDV positive group were significantly lower than the HDV negative HBV-infected patients. The aminotransferase enzymes were significantly higher in HDV/HBV co-infected compared to HDV negative patients (P<0.05). Phylogenetic analyses indicated that HDV-2 genotype being the predominant genotype, other HDV genotypes were not observed. HDV/HBV patients were significantly associated with a rather unfavourable clinical outcomeConclusion： In summary, our study showed that the prevalence of HDV infection in patients with elevated transaminases is not low and the predominance of HDV genotype 2 infection in Shanghai. This finding helps us to better understand the correlation of HDV/HBV co-infection. Moreover, Next-generation sequencing (NGS) technologies provide a rapid, precise method for generating HDV genomes to define infecting genotypes.
Do I Lose Cognitive Function as Fast as my Twin Partner? Analyses Based on Classes of MMSE Trajectories of Twins Aged 80 and older
Authors: Muniz-Terrera Graciela , Robitaille Annie , Goerdten Jantje , Massa Fernando , Johansson Boo
Published: February 2020

Background: Aging is associated with an increasing risk of decline in cognitive abilities. The decline is, however, not a homogeneous process. There are substantial differences across individuals although previous investigations have identified individuals with distinct cognitive trajectories. Evidence is accumulating that lifestyle contributes significantly to the classification of individuals into various clusters. How and whether genetically related individuals, like twins, change in a more similar manner is yet not fully understood. Methods: In this study, we fitted growth mixture models to Mini Mental State Exam scores (MMSE) from participants of the Swedish OCTO Twin study of oldest old monozygotic (MZ) and same-sex dizygotic (DZ) twins with the purpose of investigating whether twin pairs can be assigned to the same class of cognitive change. Results: We identified 4 distinct groups (latent classes) whose MMSE trajectories followed various patterns of change over time: a class of stable and high performing individuals, two groups of high performers who declined at different annual rates, and a small group of impaired individuals who declined more rapidly. Notably, our analyses show that few individuals in fact could be assigned to the same class as their co-twin. Conclusions: Our study provides evidence for more substantial impact of environmental, rather than genetic, influences on cognitive change trajectories in later life.
Predictors of physical activity in older adults experiencing an emergency hospital admission: a prospective cohort study
Authors: Hartley Peter , Dewitt Amanda L , Forsyth Faye , Romero-Ortuno Roman , Deaton Christi
Published: February 2020

BackgroundReduced mobility may be responsible for functional decline and acute sarcopenia in older hospitalised patients. The drivers of reduced in-hospital mobility are poorly understood, especially during the early phase of acute hospitalisation. We investigated predictors of in-hospital activity during the first 24 hours of hospital admission in older adults. MethodsThis was a secondary analysis of a prospective repeated measures cohort study. Participants aged 75 years or older were recruited within the first 24 hours of admission. At recruitment, patients underwent a baseline assessment including measurements of pre-morbid functional mobility, cognition, frailty, falls efficacy, co-morbidity, acute illness severity, knee extension strength and grip strength, and consented to wear accelerometers to measure physical activity during the first 7 days (or until discharge if earlier). In-hospital physical activity was defined as the amount of upright time (standing or walking). To examine the predictors of physical activity, we used a best subset analysis including all baseline measures. The optimal model was defined by having the lowest Bayesian information criterion in the best-subset analyses. The model specified a maximum of 5 covariates and used an exhaustive search.ResultsSeventy participants were recruited but eight were excluded from the final analysis due to lack of accelerometer data within the first 24 hours after recruitment. Patients spent a median of 0.50 hours (IQR: 0.21; 1.43) standing or walking. The optimal model selected the following covariates: functional mobility as measured by the de Morton Mobility Index and two measures of illness severity, the National Early Warning Score, and serum C-reactive protein.ConclusionsPhysical activity, particularly in the acute phase of hospitalisation, is very low in older adults. The association between illness severity and physical activity may be explained by symptoms of acute illness being barriers to activity. Interdisciplinary approaches are required to identify early mobilisation opportunities.
Cardiovascular and all-cause mortality attributable to loneliness in older Swedish men and women
Authors: Novak Masuma , waern Margda , Johansson Lena , Zettergren Anna , Ryden Lina , Wetterberg Hanna , Gudmundsson Pia , Skoog Ingmar
Published: February 2020

Background. This study examined whether loneliness predicts cardiovascular- and all-cause mortality in older men and women. Methods. Baseline data from the Gothenburg H70 Birth Cohort Studies, collected during 2000 on 70-year-olds born 1930 and living in Gothenburg were used for analysis (n=524). Mortality data was analyzed until 2012 through Swedish national registers. Results. Perceived loneliness was reported by 17.1% of the men and 30.9% of the women in a face-to-face interview with mental health professional. A total of 142 participants died during the 12-year follow-up period, with 5 334 person-years at risk, corresponding to 26.6 deaths/1000 person-years. Cardiovascular disease accounted for 59.2% of all deaths. The cumulative rates/1000 person-years for cardiovascular mortality were 20.8 (men) and 11.5 (women), and for all-cause mortality 33.8 (men) and 20.5 (women), respectively. In Cox regression models, no significant increased risk of mortality was seen for men with loneliness compared to men without loneliness (cardiovascular mortality HR 1.52, 95% CI 0.78 - 2.96; all-cause HR 1.32, 95% CI 0.77 - 2.28). Increased risk of cardiovascular mortality was observed in women with loneliness compared to those without (HR 2.25 95% CI 1.14 - 4.45), and the risk remained significant in a multivariable-adjusted model (HR 2.42 95% CI 1.04 - 5.65). Conclusions. Loneliness was shown to be an independent predictor of cardiovascular mortality in women. We found no evidence to indicate that loneliness was associated with an increased risk of either cardiovascular- or all-cause mortality in men.
What Lies Beneath: Clinical and Resource-use Characteristics of Institutionalized Older People. A Retrospective, Population-based Cohort Study in Catalonia
Authors: Amblàs-Novellas Jordi , Gonzàlez Sebastià J. Santaeugènia , Vela Emili , Clèries Montse , Contel Joan C.
Published: February 2020

BackgroundPlanning population care in a specific health care setting requires deep knowledge of the clinical characteristics of the target care recipients, which tend to be country specific. Our area virtually lacks any descriptive, far-reaching publications about institutionalized older people (IOP). We aimed to investigate the demographic and clinical characteristics of institutionalized older people (IOP) ≥65 years old and compare them with those of the rest of the population of the same age.MethodsRetrospective analysis (total cohort approach) of clinical and resource-use characteristics of IOP and non-IOP older than 65 years in Catalonia (North-East Spain). Variables analysed included age and sex, diagnoses, morbidity burden—using Adjusted Morbidity Groups (GMA)—, mortality, use of resources, and medications taken. All data were obtained from the administrative database of the local healthcare system.ResultsThis study included 93,038, 78,458, 68,545 and 67,456 IOP from 2011, 2013, 2015 and 2017, respectively. In this interval, an increase in mean age (82.02 vs. 85.95 years), in women (68.64% vs. 72.11%) and in annual mortality (11.74% vs. 20.46%) was observed. Compared with non-IOP (p<0.001 in all comparisons), IOP showed a higher annual mortality (20.46% vs. 3.13%), a larger number of chronic diseases (specially dementia: 46.47% vs. 4.58%), higher multimorbidity (15.2% vs. 4.2% with GMA of maximum complexity), and annual admissions to acute care (47.6% vs. 27.7%) and skilled nursing facilities (27.8% vs. 7.4%), mean length of hospital stay (10.0 vs. 7.2 days) and mean of medications taken (11.7 vs. 8.0). ConclusionsThere is a growing gap between the clinical and demographic characteristics of age-matched IOP and non-IOP, which overlaps with a higher mortality rate of IOP. The profile of resources utilization of IOP compared with non-IOP strongly suggests a deficiency of preventive actions and stresses the need to rethink the care model for IOP from a social and health care perspective.
Efficacy and biomarker analysis of nivolumab plus gemcitabine and cisplatin in patients with unresectable or metastatic biliary tract cancers: results from a phase II study
Authors: Feng Kaichao , Liu Yang , Zhao Yongtian , Yang Qingming , Dong Liang , Liu Jiejie , Li Xiang , Zhao Zhikun , Mei Qian , Han Weidong
Published: February 2020

Background: The prognosis of patients with unresectable or metastatic biliary tract cancer (BTC) is unacceptable low. This study aimed to determine the efficacy, safety and predicting biomarkers of immune checkpoint inhibitor nivolumab in combination with chemotherapy in advanced BTCs.Methods: In this open-label, single-arm, phase Ⅱ trial, chemo-immunology combination therapy consisting of gemcitabine 1000mg/m2, cisplatin 75mg/m2 plus nivolumab 3mg/kg was administered every 3 weeks for up to 6 cycles. Maintenance treatment with gemcitabine plus nivolumab was administered to patients achieving disease control following the combination therapy. The primary outcome was objective response rate (ORR). Secondary outcomes included safety, disease control rate (DCR), progression free survival (PFS) and overall survival (OS). The exploratory objectives were to assess biomarkers for predicting clinical response and prognosis.Results: 32 patients with a median age of 60 (range 27-69) years were enrolled. As of September 31, 2019, the median follow-up was 12.8 (95% CI, 10.8-14.8) months. 27 response-evaluable patients received a median of 4 (IQR, 3-6) cycles combination therapy, of which 15 (55.6%) patients achieved objective response, including 5 (18.6%)with complete response (CR), and the DCR was 92.6%. 2 of 6 patients in cohort A who were refractory to gemcitabine or cisplatin-based chemotherapy achieved 1 CR and 1 partial response. 13 of 21 chemotherapy-naive patients (61.9%) in cohort B achieved objective response. The median PFS of all patients in cohort A+B was 6.1 months. The median OS was 8.5 months with 33.3% 12-month OS rate. The most frequent grade 3 or higher adverse events were thrombocytopenia (56%), and neutropenia (22%). Fitness might be a biomarker for predicting clinical response. On-therapy change of serum sFASL, MCP-1 and IFN-γ were correlated with prognosis.Conclusions: Nivolumab in combination with gemcitabine and cisplatin offer promising efficacy and manageable safety profile for patients with advanced BTCs.
Tobacco exposure as a major modifier of oncologic outcomes in Human PapillomaVirus (HPV) associated oropharyngeal squamous cell carcinoma
Authors: Elhalawani Hesham , Mo Abdallah S.R. , Elgohari Baher , Lin Timothy A. , Sikora Andrew G. , Lai Stephen Y. , Phan Jack , Morrison William H. , Gunn G. Brandon , Rosenthal David I. , Garden Adam S. , Fuller Clifton D. , Sandulache Vlad C.
Published: February 2020

Background

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) in the US is rapidly increasing, driven largely by the epidemic of human papillomavirus (HPV)-mediated OPSCC. Although survival for patients with HPV mediated OPSCC (HPV+ OPSCC) is generally better than that of patients with non-viral HPV+ OPSCC, the improvement is not uniform. We hypothesized that tobacco exposure remains a critical modifier of survival for HPV+ OPSCC patients.

Methods

We conducted a retrospective analysis of 611 OPSCC patients with concordant p16 and HPV testing treated at a single institute (2002-2013). Survival analysis was performed using Kaplan-Meier analysis and Cox regression. Recursive partitioning analysis (RPA) was used to define tobacco exposure associated with survival (p<0.05).

Results

Tobacco exposure impacted overall survival (OS) for HPV+ patients on univariate and multivariate analysis (p=0.002, p=0.003 respectively). RPA identified 30 pack-years (PY) as a threshold at which survival became significantly worse in HPV+ patients. OS and disease-free survival (DFS) for HPV+ >30 PY patients didn’t differ significantly from HPV- group (p= 0.72, p= 0.27, respectively). HPV+ >30 PY patients had substantially lower 5-year OS when compared to their ≤30 PYs counterparts: 78.4% vs 91.6%; p= 0.03, 76% vs 88.3%; p= 0.07, and 52.3% vs 74%; p= 0.05, for stages I, II, and III (AJCC 8th Edition Manual), respectively.

Conclusions

Tobacco exposure can eliminate the survival benefit associated with HPV+ status in OPSCC patients. Until this effect can be clearly quantified using prospective datasets, de-escalation of treatment for HPV+OPSCC smokers should be avoided.
Diagnostic and prognostic performance of circulating levels of the Epstein-Barr virus microRNAs BART 7-3p and BART 13-3p in nasopharyngeal carcinoma
Authors: Lu Tianzhu , Guo Qiaojuan , Lin Keyu , Chen Honglin , Chen Yixin , Xu Yuanji , Lin Cheng , Su Ying , Chen Yan , Chen Mengyuan , Zheng Yuhong , Ye Yunbin , Lin Shaojun , Zong Jingfeng , Pan Jianji
Published: February 2020

Background Nasopharyngeal carcinoma (NPC) is closely associated with Epstein-Barr virus (EBV) infection. EBV BamHI A rightward transcripts (BART) encode microRNAs (EBV-miR-BARTs) abnormally highly expressed and play an essential role in NPC. Our previous study indicated that circulating EBV-miR-BARTs was potentially severed as a biomarker of NPC. This study aims to investigate the diagnostic and prognostic performance of miR-BART7-3p and miR-BART13-3p. Methods Plasma levels of EBV DNA, miR-BART7-3p, and miR-BART13-3p were examined by quantitative PCR in 483 treatment-naïve NPC patients and 243 controls without NPC. The prognostic performance was examined by comparing plasma levels with rates of distant metastasis during follow-up. Results Plasma EBV DNA was detected in 93.7% of NPC subjects vs. 8.6% of controls. The microRNAs BART7-3p and miR-BART13-3p were detected in 96.1% and 97.9% of NPC subjects vs. 3.39% and 3.3% of controls. The area under the receiver operating characteristic curve for diagnosing NPC was 0.926 for EBV DNA, 0.964 for miR-BART7-3p, 0.973 for miR-BART13-3p, and 0.997 for all three indices. Among 465 NPC patients without distant metastasis, the above-median miR-BART7-3p and EBV-DNA were independent risk for shorter distant metastasis-free survival (DMFS) (HR=2.94, 95%CI: 1.44-5.97, p=0.003; HR=2.27, 95%CI:1.26-4.10, p=0.006) in multivariate Cox regression. In the 245 patients who received radiotherapy, EBV DNA, miR-BART7-3p, and miR-BART13-3p were detectable immediately afterward in, respectively, 28.6%, 17.6%, and 54.7% of patients. Four-year DMFS rate was lower in patients with detectable miR-BART7-3p (73.0% vs. 89.7%, p<0.001), miR-BART13-3p (61.4% vs. 90.0%, p<0.001), and EBV-DNA (82.7% vs. 89.5%, p=0.035) after radiotherapy. In multivariate Cox regression, detectable miR-BART7-3p and EBV-DNA were independent risks for shorter DMFS (HR=4.13, 95%CI: 1.89-9.01, p<0.001; HR = 2.14, 95%CI: 1.04-4.42, p=0.039). Four-years DMFS rate was 92.0% in subjects (n=156) with neither detectable miR-BART7-3p nor EBV-DNA after radiotherapy, 80.0% in subjects (n=65) with either detectable miR-BART7-3p or EBV-DNA after radiotherapy, and 52.9% in subjects (n=24) with both detectable miR-BART7-3p and EBV-DNA after radiotherapy (p<0.001). Conclusions Circulating levels of miR-BART7-3p and miR-BART13-3p show excellent diagnostic performance for NPC. The combination of plasma levels of miR-BART7-3p and EBV DNA at diagnosis and after radiotherapy may help stratify patients by risk of poor DMFS.
Molecular Determinant s Elucidate the Selectivity in Abscisic acid Receptor and HAB1 Protein Interactions
Authors: Yang Jing-Fang , Yin Chun-Yan , Wang Di , Jia Chen-Yang , Hao Ge-Fei , Yang Guang-Fu
Published: February 2020

The abscisic acid (ABA), as a pivotal plant hormone, plays a key role in controlling the life cycle and adapting to the environmental stresses. The receptors of ABA are the Pyrabactin Resistance /Pyrabactin Resistance -Like/Regulatory Component of ABA Receptors (PYR/PYL/RCAR, PYLs for simplicity), which regulate the Protein Phosphatase 2Cs (PP2Cs) in the signal pathway. As an important ABA mimicking ligand, Pyrabactin shows the activation function to parts of members of PYLs, such as PYR1 and PYL1. Due to the antagonism of Pyrabactin to PYL2, it was used as a probe to discover a part of ABA receptors. Since then, many researchers have been trying to find out the determinants of the selective regulation of PYLs and PP2Cs interaction. However, the roles of residues on the selective regulation of PYR1/PYL2 and PP2Cs interaction induced by Pyrabactin are still ambiguous. This research investigated the selective activation mechanism of Pyrabactin through the sequence alignment, molecular docking, molecular dynamics simulation, and binding free energy calculation. Furthermore, the electrostatic and hydrophobic interaction differences induced by Pyrabactin and agonists were compared. The results indicate that Leu137/Val114, Ser85/Ser89, and Gly86/Gly90 from the pocket and gate of PYR1/PYL2 are the vital residues for the selective activation of Pyrabactin. Meanwhile, the electrostatic interaction between PP2Cs and PYLs complexed with agonists was improved. This mechanism provides strong support for the design of selective agonists and antagonists.
SYBA: Bayesian estimation of synthetic accessibility of organic compounds
Authors: Voršilák Milan , Kolář Michal , Čmelo Ivan , Svozil Daniel
Published: February 2020

SYBA (SYnthetic Bayesian Accessibility) is a fragment based method for the rapid classification of organic compounds as easy- (ES) or hard-to-synthesize (HS). SYBA is based on the Bayesian analysis of the frequency of molecular fragments in the database of ES and HS molecules. It was trained on ES molecules available in the ZINC15 database and on HS molecules generated by the Nonpher methodology. SYBA was compared with a random forest, that was utilized as a baseline method, as well as with other two methods for synthetic accessibility assessment: SAScore and SCScore. When used with their suggested thresholds, SYBA improves over random forest classification, albeit marginally, and outperforms SAScore and SCScore. However, with thresholds optimized by the analysis of ROC curves, SAScore improves considerably and yields similar results as SYBA. Because SYBA is based merely on fragment contributions, it can be used for the analysis of the contribution of individual molecular parts to compound synthetic accessibility. Though SYBA was developed to quickly assess compound synthetic accessibility, its underlying Bayesian framework is a general approach that can be applied to any binary classification problem. Therefore, SYBA can be easily re-trained to classify compounds by other physico-chemical or biological properties. SYBA is publicly available at https://github.com/lich-uct/syba under the GNU General Public License.