bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of the Atopic Dermatitis Control Tool (ADCT©) using a longitudinal survey of biologic-treated patients with atopic dermatitis
Authors: Simpson Eric , Eckert Laurent , Gadkari Abhijit , Mallya Usha G. , Yang Min , Nelson Lauren , Brown Michelle , Reaney Matt , Mahajan Puneet , Guillemin Isabelle , Boguniewicz Mark , Pariser David
Published: November 2019

Background

The Atopic Dermatitis Control Tool (ADCT©) is a brief patient self-administered instrument designed and validated to assess atopic dermatitis (AD) control; six AD symptoms and impacts are evaluated over the past week, including overall severity of symptoms, days with intense episodes of itching, intensity of bother, problem with sleep, impact on daily activities, and impact on mood or emotions. This study assessed the reliability, validity, and responsiveness of the ADCT in a longitudinal context, and provided thresholds to identify meaningful within-person change.

Methods

Data were from a prospective, longitudinal patient survey study of real-world effectiveness of dupilumab in patients with AD. Eligible patients completed a baseline survey before starting dupilumab and were followed at Months 1, 2, 3, and 6 post-initiation as they became eligible.

Results

Psychometric analyses confirmed internal consistency; Cronbach’s α coefficients were consistently above the threshold of 0.70 across each follow-up; item-to-total correlations were above the threshold of r ≥ 0.50. High correlations between the ADCT and the Dermatology Life Quality Index (DLQI) and skin pain supported construct validity, while known-group validity was shown on Patient Global Assessment of Disease (PGAD) overall well-being subgroups with worse AD-related overall well-being having higher mean ADCT total scores at all time points. The ability of the ADCT to detect change was confirmed; the threshold for meaningful within-person change was estimated to be 5 points. Finally, test–retest reliability was confirmed in subgroups of patients with stable PGAD responses.

Conclusions

Our findings confirm that the ADCT is a valid and reliable tool for assessing AD control.
Dental care during pregnancy based on the pregnancy risk assessment monitoring system in Utah
Authors: Muralidharan Chandni , Merrill Ray M.
Published: November 2019

Background

Although receiving dental care is recommended for women during pregnancy, getting such care remains low. This study will identify the level of dental care received during pregnancy and factors associated with care for a group of pregnant women in Utah.

Methods

Analyses were based on 2793 pregnant women completing the 2014–2015 Utah PRAMS survey. Descriptive and bivariate techniques were used.

Results

Approximately 91.2% knew it was important to care for their teeth and gums during pregnancy, yet only 58.8% had their teeth cleaned during pregnancy. Those who knew such care was important were 1.4 (95% CI 1.1–2.0) times more likely to have their teeth cleaned during pregnancy. Although 18.8% needed to see a dentist for a problem, only 74.5% of them received treatment for the problem during pregnancy. Approximately 76.0% had dental insurance during pregnancy. Those with dental insurance were 1.9 (95% CI 1.5–2.4) times more likely to have their teeth cleaned and 1.6 (95% CI 1.2–2.2) times more likely to go to a dentist for needed treatment during pregnancy. Approximately 51.4% had a dental/health care worker talk with them about how to care for their teeth and gums. These women were more likely to know it was important to care for their teeth and gums during pregnancy (97.4% vs 87.6%, p < 0.0001). For women who received care for a problem during pregnancy, 70.0% had a dental/health care worker talk with them about how to care for their teeth and gums. These women were more likely to know it was important to care for their teeth and gums during pregnancy (95.2% vs 82.8%, p < 0.0001). Women who had their teeth cleaned the year prior to pregnancy were more likely to have their teeth cleaned during pregnancy (78.5% vs 21.5%, p < 0.0001).

Conclusions

A large proportion of women knowing of the importance of dental care during pregnancy did not receive care. Knowledge of its importance during pregnancy, having a dental/health care worker talk with them about how to care for their teeth and gums, and having dental insurance during pregnancy are positively associated with dental care during pregnancy.
Child marriage in Ghana: evidence from a multi-method study
Authors: Ahonsi Babatunde , Fuseini Kamil , Nai Dela , Goldson Erika , Owusu Selina , Ndifuna Ismail , Humes Icilda , Tapsoba Placide L.
Published: November 2019

Background

Child marriage remains a challenge in Ghana. Over the years, government and development partners have made various commitments and efforts to curb the phenomenon of child marriage. However, there is little empirical evidence on the predictors, norms and practices surrounding the practice to support their efforts, a gap this study sought to fill.

Methods

The study employed a multiple-method approach to achieve the set objectives. Data from the women’s file of the 2014 Ghana Demographic and Health Survey (GDHS) was used to examine the predictors of child marriage using frequencies and logistic regression methods. Data from Key Informant Interviews (KIIs) and Focus Group Discussions (FGDs) collected in Central and Northern regions of Ghana were used to examine norms and practices surrounding child marriage using thematic analysis.

Results

Two in ten (20.68%) girls in the quantitative sample married as children. The results revealed that girls who had never attended school compared to those who had ever attended school were more likely to marry as children (OR, 3.01). Compared with girls in the lowest wealth quintile, girls in the middle (OR, 0.59), fourth (OR, 0.37) and highest (OR, 0.32) wealth quintiles were less likely to marry as children. From the qualitative data, the study identified poverty, teenage pregnancy, and cultural norms such as betrothal marriage, exchange of girls for marriage and pressure from significant others as the drivers of child marriage.

Conclusions

The findings show that various socio-economic and cultural factors such as education, teenage pregnancy and poverty influence child marriage. Hence, efforts to curb child marriage should be geared towards retention of girls in school, curbing teenage pregnancy, empowering girls economically, enforcing laws on child marriage in Ghana, as well as designing tailored advocacy programs to educate key stakeholders and adolescent girls on the consequences of child marriage. Additionally, there is the need to address socio-cultural norms/practices to help end child marriage.
Treatment satisfaction in Chinese medicine outpatient care: a comparison of patients’ and doctors’ views
Authors: Zhang Yanhong , Fang Jiqian , Gao Wei , Han Ying , Zhang Runshun , He Liyun , Liu Baoyan
Published: November 2019

Background

Both doctors’ and patients’ opinions are important in the process of treatment and healthcare of Chinese medicine. This study is to compare patients’ and doctors’ treatment satisfaction over the course of two visits in a Chinese medicine outpatient setting, and to explain their respective views.

Methods

Patients’ chief complaints were collected prior to the outpatient encounter. The doctor was then asked (through a questionnaire) to state what complaints he or she was prioritizing during the process of diagnosing disease and making a prescription for herbal medicine or acupuncture treatment. On the next visit, both the patient and the doctor completed a questionnaire assessing satisfaction with the treatment of Chinese medicine prescribed in the first visit and administered by the patient at home. A 5-point Likert scales was used to assess the patients’ and doctors’ satisfaction with treatment. The timing of the follow-up appointment was determined by the doctor. One chief specialist, one associate chief specialist and one attending practitioner in Chinese medicine, and 60 patients having a follow-up appointment with one of the doctors, participated in the study.

Results

For 11 patients, their most urgent complaint was different from what the doctor’s choose to focus on in his or her treatment. And only one patient refused to comply due to his or her dissatisfaction with the treatment focus of the doctor. Overall, 59 patients completed the satisfaction assessment, and 53 patients visited their doctors for a follow-up appointment. Patients’ total satisfaction was higher than their doctors’ (mean 3.55 vs. 3.45), and correlation of patients’ and doctors’ treatment satisfaction was moderate (r = 0.63, P < 0.01). Both of the patients’ and doctors’ satisfaction ratings were correlated with treatment adherence (P < 0.001). The predictors of their treatment satisfaction were different. Doctors’ satisfaction with treatment was a significant factor in the process of making further clinical decisions.

Conclusion

Patients and doctors form their opinion about the treatment effects in different ways. When evaluating treatment satisfaction, doctor’s opinions are also an important indicator of positive or negative clinical effects and affect the subsequent decisions-making.
Mastery learning in a bachelor’s of nursing program: the Roseman University of Health Sciences experience
Authors: Lipsky Martin S. , Cone Catherine J. , Watson Susan , Lawrence Phillip T. , Lutfiyya May Nawal
Published: November 2019

Background

Roseman University of Health Sciences (RUHS) developed and delivers a mastery learning curriculum designed for students to acquire the knowledge and skills to become competent nurses. Despite a trend in nursing education to adopt competency-based education (CBE) models, there is little in the nursing literature about programs based on a mastery model. The aim of this study is to describe an undergraduate nursing program built on a mastery learning model and to report on program outcome measures.

Methods

The 18-month BSN nursing program is divided into blocks, varying in length and focusing on a single subject. Students must demonstrate mastery, defined as ≥90% on an assessment, to pass a block. Recognizing the critical nature of health care, educators seek methods to assure that practitioners become competent to perform the services they provide.

Program outcomes reported include comparisons to national standards and RUHS student exit survey data.

Results

From 2013 to 2017 the RUHS College of Nursing students’ pass rates ranged from 82 to 97% for the National Council Licensure Examination exam compared to national pass rates between 81.8–84.5% during the same time frame. The program completion rate ranged from 86 to 100% and employment rates exceeded accreditation standards. Students reported overall satisfaction with their education as 4.38 and with the block system as 4.74 (5 point Likert scale).

Conclusions

Roseman University’s mastery learning model appears successful as measured by high levels of student satisfaction, outcomes on exams, and degree completion when compared to national averages. The results suggest that other nursing and health profession’s programs can develop a successful mastery based learning model.
Efficiency of blood utilization in elective surgical patients
Authors: Zewdie Kibruyisfaw , Genetu Abraham , Mekonnen Yeabsera , Worku Tewodros , Sahlu Abat , Gulilalt Dereje
Published: November 2019

Background

Requesting blood prior to a surgical procedure for perioperative transfusion is a common practice in surgical patients. More unit of blood is requested than used by anticipating the patient will be transfused to provide a safety margin in an event of unexpected haemorrhage. Over requesting with minimal utilization results in significant wastage of blood, reagents and human resource. This study was conducted to assess blood utilization practice of the largest tertiary hospital in Ethiopia.

Methods

A cross-sectional prospective study method was used. Data was collected using a Proforma questionnaire by perusal of each individual patient’s records from December 1, 2017 to February 28, 2018.patient age, sex, department requesting the blood, level of operating surgeon, hemodynamic status, number of unit requested, number of unit crossed matched and number of unit transfused were collected. Efficiency of blood utilization was calculated with three indices: Crossmatch to transfusion ratio, transfusion probability, and transfusion index indices.

Results

Blood was requested for 406 patients and a total of 898 units were crossmatched for this patients. Overall Crossmatch to transfusion ration, transfusion probability and transfusion index were 7.6, 15.3% and 0.29 respectively. Results showed insignificant blood usage. Among different departments and units, better blood utilization was seen in neurosurgical unit with C/T ratio, TP and TI of 4.9, 24.4 and 0.6% respectively, while worst indices were from obstetrics unit with C/T ratio, TP and TI of 31.0, 6.5% and 0.06.

Conclusion

Using all the three parameters for evaluation of efficiency of blood utilization, the practice in our hospital shows ineffective blood utilization in elective surgical procedure. Blood requesting physician should order the minimum blood anticipated to be used as much as possible.
Effectiveness of health care workers and peer engagement in promoting access to health services among population at higher risk for HIV in Tanzania (KPHEALTH): study protocol for a quasi experimental trial
Authors: Mmbaga Elia John , Leyna Germana Henry , Leshabari Melkizedeck Thomas , Tersbøl Britt , Lange Theis , Makyao Neema , Moen Kåre , Meyrowitsch Dan Wolf
Published: November 2019

Background

While there are indications of declining HIV infection rates in the general population globally, Tanzania included, men who have sex with men (MSM), female sex workers (FSW) and people who inject drugs (PWID), now called Key Populations (KP) for HIV epidemic have 2–20 times higher infections rates and contributes up to 30% of new HIV infection. Tanzania have developed a Comprehensive Guideline for HIV prevention among key population (CHIP) to address the epidemic among KPs. However, these populations are stigmatized and discriminated calling for innovative approaches to improve access to CHIP. This project seeks to test the effectiveness of healthcare workers and peer-to-peer engagement in promoting access to CHIP among HIV at risk populations in Tanzania.

Methods

A quasi-experimental design involving Dar es Salaam City as an intervention region and Tanga as a control region will be done. Using respondent driven sampling, 1800 at risk population (900 from Intervention site and 900 from control site) will be recruited at baseline to identify pull and push factors for health services access. Stakeholder’s consultation will be done to improve training contents for CHIP among health care workers and peers. Effectiveness of healthcare workers training and peer engagement will be tested using a quasi-experimental design.

Discussion

The results are expected to co-create service provision and improve access to services among KPs as a human right, reverse HIV infection rates among KPs and the general population, and improve social and economic wellbeing of Tanzanian.

Trial registration

Retrospectively registered on 28th August, 2019 with International Standard Randomized Clinical Trial Number (ISRCTN11126469).
A guideline for the prevention and management of Fetal Alcohol Spectrum Disorder in South Africa
Authors: Adebiyi Babatope O. , Mukumbang Ferdinand C. , Beytell Anna-Marie
Published: November 2019

Background

Fetal Alcohol Spectrum Disorder (FASD) is a public health problem globally, with South Africa having the highest recorded prevalence of all countries. Government programmes to prevent and manage FASD remain limited because of the lack of a specific policy. Herein, we developed a guideline to inform policy on the prevention and management of FASD in South Africa.

Methods

We applied a modified version of the World Health Organization’s approach to guideline development in three phases. In the first phase, we designed the initial guideline prototype. To do this, we conducted an in-depth interview with policymakers and a focus group with relevant service providers on policy requirements for FASD, a document review of policies on FASD and a scoping review of various interventions for FASD. In phase 2, we refined the initially formulated guideline prototype through a discursive approach with seven local and international experts on FASD. Phase 3 involved refining the prototype using a modified Delphi approach. Forty-three and forty-one experts participated in rounds 1 and 2 of the Delphi approach, respectively. The acceptable consensus for each included policy statement was 85%.

Results

We identified three aspects of the proposed guideline, which are the approaches and guiding principles, the prevention measures and the management measures. The guideline proposes that a FASD policy should consider lifespan needs, be culturally diverse, collaborative, evidence-based, multi-sectoral and address social determinants of health contributing to FASD. The essential components of FASD prevention policy consist of awareness and education of the dangers of drinking alcohol, access to treatment for alcohol problems and training of service providers. The management components include capacity building related to diagnosis, educating parents regarding the needs and management, appropriate referral pathways, training of teachers regarding classroom management and support for parents and individuals with FASD.

Conclusion

FASD in South Africa deserves urgent attention. Developing a specific policy to guide programmes could enhance and coordinate the efforts towards preventing and managing FASD. The guideline has the potential to assist policymakers in the development of a comprehensive and multi-sectoral policy for prevention and management of FASD, considering the consensus obtained from the experts.
Sexual and gender minorities rights in Latin America and the Caribbean: a multi-country evaluation
Authors: Malta Monica , Cardoso Reynaldo , Montenegro Luiz , de Jesus Jaqueline Gomes , Seixas Michele , Benevides Bruna , das Dores Silva Maria , LeGrand Sara , Whetten Kathryn
Published: November 2019

Background

Although the extent of legal inequities experienced by sexual and gender minorities (SGM) has declined during recent decades, this population still enjoys fewer legal protections and benefits than the non-gender-variant, heterosexual population. Herein we analyze the current scenario of SGM rights in Latin America and the Caribbean (LAC).

Methods

Policy documents and governmental strategies addressing SGM rights were analyzed within a timeline framework by three major LAC sub-regions: the Caribbean, Mesoamerica and South America.

Results

Our search identified 88 eligible documents addressing the following categories: (1) legal protections towards same-sex couples (decriminalization of same-sex acts among consenting adults, legal recognition of same-sex unions, same-sex marriage, adoption by same-sex couples), and (2) anti-discrimination laws (SGM allowed to serve openly in the military and anti-discrimination laws related to sexual orientation, gender identity and/or expression). The majority of Caribbean countries prohibit same-sex acts between consenting adults, while in Mesoamerica same-sex couples do not have equal marriage rights and are not allowed to adopt as a couple. In the Caribbean and Mesoamerica transgender people lack proper legal protection. Legislation to protect SGM rights in South America is the most inclusive and progressive in LAC. Several countries recognize same-sex marriage and the right of transgender people to legally change their name and gender. The majority of South American countries have some kind of anti-discrimination law, but no effective mechanisms to enforce these laws. In spite of those progresses, the LAC region registers the highest rate of violence and hate crimes against SGM in the world.

Conclusion

In the Caribbean and Mesoamerica the overall discriminatory legislation exacerbates violence against SGM within a social and cultural context of strong sexist, gender stereotypes and widespread violence. This scenario is driving hundreds of SGM to leave their home countries. In spite of progressive legislations, several South American countries are currently controlled either by highly conservative leaders (e.g. Brazil and Chile) or by repressive dictators (Venezuela). The near future of the LAC region is unknown, but if such trends continue, severe human rights problems, including setbacks in SGM legal protections, are likely.
Tick-borne pathogens in ticks collected from dogs, Latvia, 2011–2016
Authors: Namina Agne , Capligina Valentina , Seleznova Maija , Krumins Rudolfs , Aleinikova Darja , Kivrane Agnija , Akopjana Sarmite , Lazovska Marija , Berzina Inese , Ranka Renate
Published: November 2019

Background

Different tick species are able to transmit different pathogens, and tick-borne diseases are of substantial concern worldwide for both humans and animals. Environmental changes and changes in the range of tick species, including Dermacentor reticulatus in Europe, can affect the spread of zoonotic pathogens. The aim of this study was to investigate the prevalence of the tick-borne pathogens in ticks removed from dogs in Latvia, and to explore possible changes between years 2011 and 2016.

Results

In 2011, only Ixodes ticks (221 Ixodes ricinus and 22 Ixodes persulcatus) were collected from dogs, while in 2016 tick samples belonged to Ixodes ricinus (360), Ixodes persulcatus (2) and Dermacentor reticulatus (27) species. In total, 35.8 and 40.0% of adult ticks were pathogen-positive in 2011 and 2016, respectively; the difference was not statistically significant (P > 0.05). The molecular analysis indicated the presence of 13 tick-borne microorganisms; the most prevalent pathogen was Rickettsia, followed by Borrelia burgdorferi sensu lato group spirochetes, Anaplasma phagocytophilum and Babesia species. Borrelia miyamotoi was also present. A co-infection with two and three tick-borne pathogens was detected in 7.9 and 7.4% of Ixodes ricinus and Dermacentor reticulatus, respectively. The results of this study confirmed that the spread of novel vectors could bring additional risk of exposure to novel emerging pathogens to pets and their owners, as both Babesia canis and Rickettsia raoultii were shown to be highly associated with Dermacentor reticulatus ticks in Latvia.

Conclusions

This study demonstrates the potential danger from the inadvertent introduction of novel disease pathogens and vectors. Awareness of co-infections and Dermacentor reticulatus-related pathogens needs to be increased.
Spontaneous regression of extradural intraspinal cysts in a dog: a case report
Authors: Bonelli Marília de Albuquerque , da Costa Ronaldo Casimiro
Published: November 2019

Background

Extradural intraspinal cysts are fluid accumulations that appear to be associated with increased motion at vertebral joints.

Case presentation

We report the spontaneous regression of lumbar and lumbosacral cysts (presumably synovial cysts) and the unusual occurrence of an S1–2 extradural intraspinal cyst in a dog. The dog presented with lumbosacral pain. Six extradural intraspinal cysts were observed on high-field magnetic resonance imaging from L5–6 to S1-S2. The cysts between L5–6 and L7-S1 ranged from 0.12 to 0.44cm2at their largest area. The largest cyst was located at S1–2 (left), measuring 0.84 cm2at its largest view. The dog was medically managed. A follow-up magnetic resonance imaging scan was obtained 3.5 years after the first imaging. All cysts except the one at S1–2 had reduced in size. Mean reduction in size was 59.6% (35–81%).

Conclusions

In summary, we report a case with multiple extradural intraspinal cysts that underwent spontaneous regression of all but one cyst during a 3.5-year follow-up period. Whether this is a single occurrence, or is part of the natural history of these cysts in the lumbosacral region of dogs, remains to be established. Spontaneous regression of intraspinal cysts had not been described in dogs.
Linkage and exome analysis implicate multiple genes in non-syndromic intellectual disability in a large Swedish family
Authors: Lindholm Carlström Eva , Halvardson Jonatan , Etemadikhah Mitra , Wetterberg Lennart , Gustavson Karl-Henrik , Feuk Lars
Published: November 2019

Background

Non-syndromic intellectual disability is genetically heterogeneous with dominant, recessive and complex forms of inheritance. We have performed detailed genetic studies in a large multi-generational Swedish family, including several members diagnosed with non-syndromic intellectual disability. Linkage analysis was performed on 22 family members, nine affected with mild to moderate intellectual disability and 13 unaffected family members.

Methods

Family members were analyzed with Affymetrix Genome-Wide Human SNP Array 6.0 and the genetic data was used to detect copy number variation and to perform genome wide linkage analysis with the SNP High Throughput Linkage analysis system and the Merlin software. For the exome sequencing, the samples were prepared using the Sure Select Human All Exon Kit (Agilent Technologies, Santa Clara, CA, USA) and sequenced using the Ion Proton™ System. Validation of identified variants was performed with Sanger sequencing.

Results

The linkage analysis results indicate that intellectual disability in this family is genetically heterogeneous, with suggestive linkage found on chromosomes 1q31-q41, 4q32-q35, 6p25 and 14q24-q31 (LOD scores of 2.4, simulated p-value of 0.000003 and a simulated genome-wide p-value of 0.06). Exome sequencing was then performed in 14 family members and 7 unrelated individuals from the same region. The analysis of coding variation revealed a pathogenic and candidate variants in different branches of the family. In three patients we find a known homozygous pathogenic mutation in the Homo sapiens solute carrier family 17 member 5 (SLC17A5), causing Salla disease. We also identify a deletion overlapping KDM3B and a duplication overlapping MAP3K4 and AGPAT4, both overlapping variants previously reported in developmental disorders.

Conclusions

DNA samples from the large family analyzed in this study were initially collected based on a hypothesis that affected members shared a major genetic risk factor. Our results show that a complex phenotype such as mild intellectual disability in large families from genetically isolated populations may show considerable genetic heterogeneity.
Evaluating the role of RAD52 and its interactors as novel potential molecular targets for hepatocellular carcinoma
Authors: Li Ping , Xu YanZhen , Zhang Qinle , Li Yu , Jia Wenxian , Wang Xiao , Xie Zhibin , Liu Jiayi , Zhao Dong , Shao Mengnan , Chen Suixia , Mo Nanfang , Jiang Zhiwen , Li Liuyan , Liu Run , Huang Wanying , Chang Li , Chen Siyu , Li Hongtao , Zuo Wenpu , Li Jiaquan , Zhang Ruoheng , Yang Xiaoli
Published: November 2019

Background

Radiation sensitive 52 (RAD52) is an important protein that mediates DNA repair in tumors. However, little is known about the impact of RAD52 on hepatocellular carcinoma (HCC). We investigated the expression of RAD52 and its values in HCC. Some proteins that might be coordinated with RAD52 in HCC were also analyzed.

Methods

Global RAD52 mRNA levels in HCC were assessed using The Cancer Genome Atlas (TCGA) database. RAD52 expression was analyzed in 70 HCC tissues and adjacent tissues by quantitative real-time PCR (qRT-PCR), Western blotting and immunohistochemistry. The effect of over-expressed RAD52 in Huh7 HCC cells was investigated. The String database was then used to perform enrichment and functional analysis of RAD52 and its interactome. Cytoscape software was used to create a protein–protein interaction network. Molecular interaction studies with RAD52 and its interactome were performed using the molecular docking tools in Hex8.0.0. Finally, these DNA repair proteins, which interact with RAD52, were also analyzed using the TCGA dataset and were detected by qRT-PCR. Based on the TCGA database, algorithms combining ROC between RAD52 and RAD52 interactors were used to diagnose HCC by binary logistic regression.

Results

In TCGA, upregulated RAD52 related to gender was obtained in HCC. The area under the receiver operating characteristic curve (AUC) of RAD52 was 0.704. The results of overall survival (OS) and recurrence-free survival (RFS) indicated no difference in the prognosis between patients with high and low RAD52 gene expression. We validated that RAD52 expression was increased at the mRNA and protein levels in Chinese HCC tissues compared with adjacent tissues. Higher RAD52 was associated with older age, without correlation with other clinicopathological factors. In vitro, over-expressed RAD52 significantly promoted the proliferation and migration of Huh7 cells. Furthermore, RAD52 interactors (radiation sensitive 51, RAD51; X-ray repair cross complementing 6, XRCC6; Cofilin, CFL1) were also increased in HCC and participated in some biological processes with RAD52. Protein structure analysis showed that RAD52–RAD51 had the firmest binding structure with the lowest E-total energy (− 1120.5 kcal/mol) among the RAD52–RAD51, RAD52–CFL1, and RAD52–XRCC6 complexes. An algorithm combining ROC between RAD52 and its interactome indicated a greater specificity and sensitivity for HCC screening.

Conclusions

Overall, our study suggested that RAD52 plays a vital role in HCC pathogenesis and serves as a potential molecular target for HCC diagnosis and treatment. This study’s findings regarding the multigene prediction and diagnosis of HCC are valuable.
p62 acts as an oncogene and is targeted by miR-124-3p in glioma
Authors: Deng Danni , Luo Kaiming , Liu Hongmei , Nie Xichen , Xue Lian , Wang Rong , Xu Yuan , Cui Jun , Shao Naiyuan , Zhi Feng
Published: November 2019

Background

Glioma is the most common central nervous system (CNS) tumour. p62, an important autophagy adaptor, plays a crucial role in cancer. However, the role of p62 in the progression of glioma is poorly characterized.

Methods

We examined the expression of p62 in glioma tissues and cell lines. Then we investigated the function of p62 in vitro, and clarified the mechanism underlying the regulation of p62 expression.

Results

We revealed that p62 was upregulated at both the mRNA and protein levels in human glioma tissues irrelevant to isocitrate dehydrogenase (IDH) status. Then, we found that overexpression of p62 promoted glioma progression by promoting proliferation, migration, glycolysis, temozolomide (TMZ) resistance and nuclear factor κB (NF-κB) signalling pathway, and repressing autophagic flux and reactive oxygen species (ROS) in vitro. In accordance with p62 overexpression, knockdown of p62 exerted anti-tumour effects in glioma cells. Subsequently, we demonstrated that miR-124-3p directly targeted the 3′-UTR of p62 mRNA, leading to the downregulation of p62. Finally, we found that p62 function could be partially reversed by miR-124-3p overexpression.

Conclusions

Our results demonstrate that p62 can be targeted by miR-124-3p and acts as an oncogene in glioma, suggesting the potential value of p62 as a novel therapeutic target for glioma.
Time trends in nutrient intake and dietary patterns among five birth cohorts of 70-year-olds examined 1971–2016: results from the Gothenburg H70 birth cohort studies, Sweden
Authors: Samuelsson Jessica , Rothenberg Elisabet , Lissner Lauren , Eiben Gabriele , Zettergren Anna , Skoog Ingmar
Published: November 2019

Background

Nutrition is a key factor in healthy ageing but there are still gaps in knowledge about risk- and protective factors linking diet and healthy ageing. The aim of this study was to investigate time trends in dietary patterns and nutrient intake in an older population, in order to increase the understanding of whether dietary recommendations are followed and if nutrient needs are met.

Methods

Cross-sectional data was derived from five samples of 70-year-olds examined 1971–72, 1981–83, 1992–93, 2000–02 and 2014–16 from the Gothenburg H70 birth cohort studies in Sweden. A total of 2246 individuals (56% women) participated. Dietary intake was determined by the diet history method, which is an interview including questions on usual frequencies and portion sizes of food intake during the preceding three months. Recommended values of nutrient intake and determinants of healthful dietary patterns were based on the Nordic Nutrition Recommendations 2012. Statistical analyses were performed using general linear models, student’s t-test and chi-square test, stratified by sex.

Results

The intake of fruits and vegetables, fish and seafood, whole grain products and nuts and seeds increased during the study period (p < 0.0001), among both sexes. However, there was also an increase in alcohol intake (p < 0.0001), especially from wine and beer, and in 2014–16 more than 30% had an alcohol intake above recommendations. Protein intake increased (p < 0.0001 for women andp = 0.0004 for men), and 48% of the women and 37% of the men had a protein intake above recommended 1.2 g/kg body weight and day in 2014–16. The proportion of participants at risk of inadequate intake of vitamins C, D and folate decreased during the study period, among both sexes (p < 0.0001). However, vitamin D intake from diet was still below average requirement level of 7.5 μg/day for 49% of the women and 32% of the men in 2014–16.

Conclusions

Dietary patterns have changed among 70-year-olds during the past five decades, with an increase in healthful foods and a higher nutrient density in later born birth cohorts. However, the intake of alcohol increased, especially among women. Results from this study can be useful as a basis for dietary guidelines and used for prevention strategies involving older adults in population-based and health care settings.
Managing pollution from antibiotics manufacturing: charting actors, incentives and disincentives
Authors: Nijsingh Niels , Munthe Christian , Larsson D. G. Joakim
Published: November 2019

Background

Emissions of high concentrations of antibiotics from manufacturing sites select for resistant bacteria and may contribute to the emergence of new forms of resistance in pathogens. Many scientists, industry, policy makers and other stakeholders recognize such pollution as an unnecessary and unacceptable risk to global public health. An attempt to assess and reduce such discharges, however, quickly meets with complex realities that need to be understood to identify effective ways to move forward. This paper charts relevant key actor-types, their main stakes and interests, incentives that can motivate them to act to improve the situation, as well as disincentives that may undermine such motivation.

Methods

The actor types and their respective interests have been identified using research literature, publicly available documents, websites, and the knowledge of the authors.

Results

Thirty-three different actor-types were identified, representing e.g. commercial actors, public agencies, states and international institutions. These are in complex ways connected by interests that sometimes may conflict and sometimes pull in the same direction. Some actor types can act to create incentives and disincentives for others in this area.

Conclusions

The analysis demonstrates and clarifies the challenges in addressing industrial emissions of antibiotics, notably the complexity of the relations between different types of actors, their international dependency and the need for transparency. The analysis however also suggests possible ways of initiating incentive-chains to eventually improve the prospects of motivating industry to reduce emissions. High-resource consumer states, especially in multinational cooperation, hold a key position to initiate such chains.
Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4
Authors: Qin Shuang , Xu Linping , Yi Ming , Yu Shengnan , Wu Kongming , Luo Suxia
Published: November 2019

The emergence of immune checkpoint inhibitors (ICIs), mainly including anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) and anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) monoclonal antibodies (mAbs), has shaped therapeutic landscape of some type of cancers. Despite some ICIs have manifested compelling clinical effectiveness in certain tumor types, the majority of patients still showed de novo or adaptive resistance. At present, the overall efficiency of immune checkpoint therapy remains unsatisfactory. Exploring additional immune checkpoint molecules is a hot research topic. Recent studies have identified several new immune checkpoint targets, like lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), T cell immunoglobulin and ITIM domain (TIGIT), V-domain Ig suppressor of T cell activation (VISTA), and so on. The investigations about these molecules have generated promising results in preclinical studies and/or clinical trials. In this review, we discussed the structure and expression of these newly-characterized immune checkpoints molecules, presented the current progress and understanding of them. Moreover, we summarized the clinical data pertinent to these recent immune checkpoint molecules as well as their application prospects.
Correction to: protease-activated receptors (PARs): mechanisms of action and potential therapeutic modulators in PAR-driven inflammatory diseases
Authors: Heuberger Dorothea M. , Schuepbach Reto A.
Published: November 2019

Following the publication of this article [1], the authors reported an incorrect citation in the following sentence in the “Metalloproteases” sub-section:
Leap motion controlled video game-based therapy for upper limb rehabilitation in patients with Parkinson’s disease: a feasibility study
Authors: Fernández-González Pilar , Carratalá-Tejada María , Monge-Pereira Esther , Collado-Vázquez Susana , Sánchez-Herrera Baeza Patricia , Cuesta-Gómez Alicia , Oña-Simbaña Edwin Daniel , Jardón-Huete Alberto , Molina-Rueda Francisco , Balaguer-Bernaldo de Quirós Carlos , Miangolarra-Page Juan Carlos , Cano-de la Cuerda Roberto
Published: November 2019

Background

Non-immersive video games are currently being used as technological rehabilitation tools for individuals with Parkinson’s disease (PD). The aim of this feasibility study was to evaluate the effectiveness of the Leap Motion Controller® (LMC) system used with serious games designed for the upper limb (UL), as well as the levels of satisfaction and compliance among patients in mild-to-moderate stages of the disease.

Methods

A non-probabilistic sampling of non-consecutive cases was performed. 23 PD patients, in stages II-IV of the Hoehn & Yahr scale, were randomized into two groups: an experimental group (n = 12) who received treatment based on serious games designed by the research team using the LMC system for the UL, and a control group (n = 11) who received a specific intervention for the UL. Grip muscle strength, coordination, speed of movements, fine and gross UL dexterity, as well as satisfaction and compliance, were assessed in both groups pre-treatment and post-treatment.

Results

Within the experimental group, significant improvements were observed in all post-treatment assessments, except for Box and Blocks test for the less affected side. Clinical improvements were observed for all assessments in the control group. Statistical intergroup analysis showed significant improvements in coordination, speed of movements and fine motor dexterity scores on the more affected side of patients in the experimental group.

Conclusions

The LMC system and the serious games designed may be a feasible rehabilitation tool for the improvement of coordination, speed of movements and fine UL dexterity in PD patients. Further studies are needed to confirm these preliminary findings.
Important roles of C-terminal residues in degradation of capsid protein of classical swine fever virus
Authors: Chen Yuming , Zhu Erpeng , Fan Shuangqi , Ding Hongxing , Ma Shengming , Zhu Mengjiao , Deng Shaofeng , Chen Jinding , Zhao Mingqiu
Published: November 2019

Background

Capsid (C) protein plays an important role in the replication of classical swine fever virus (CSFV). The ubiquitin proteasome system (UPS) involves in replication of many viruses via modulation of viral proteins. The relationship of CSFV with UPS is poorly understood and the impact of 26S proteasome on C protein has never been reported before.

Methods

In this study, fused C protein with an EGFP tag is expressed in PK-15 and 3D4/2 cells. MG132 and 3-methyladenine (3-MA) are used to detect the roles of 26S proteasome and autophagolysosome in expression levels of C protein. Truncated and mutant C proteins are used to find the exact residues responsible for the degradation of C protein. Immunoprecipitaion is performed to find whether C protein is ubiquitinated or not.

Results

C-EGFP protein expresses in a cleaved form at a low level and is degraded by 26S proteasome which could be partly inhibited by MG132. C-terminal residues play more important roles in the degradation of C protein than N-terminal residues. Residues 260 to 267, especially M260 and L261, are crucial for the degradation. In addition, C-terminal residues 262 to 267 determine cleavage efficiency of C protein.

Conclusions

CSFV C protein is degraded by 26S proteasome in a ubiquitin-independent manner. Last 8 residues at C-terminus of immature C protein play a major role in proteasomal degradation of CSFV C protein and determine the cleavage efficiency of C protein by signal peptide peptidase (SPP). Our findings provide valuable help for fully understanding degradation process of C protein and contribute to fully understanding the role of C protein in CSFV replication.
A newly isolated roseophage represents a distinct member of Siphoviridae family
Authors: Cai Lanlan , Ma Ruijie , Chen Hong , Yang Yunlan , Jiao Nianzhi , Zhang Rui
Published: November 2019

Background

Members of theRoseobacterlineage are a major group of marine heterotrophic bacteria because of their wide distribution, versatile lifestyles and important biogeochemical roles. Bacteriophages, the most abundant biological entities in the ocean, play important roles in shaping their hosts’ population structures and mediating genetic exchange between hosts. However, our knowledge of roseophages (bacteriophages that infectRoseobacter) is far behind that of their host counterparts, partly reflecting the need to isolate and analyze the phages associated with this ecologically important bacterial clade.

Methods

vB_DshS-R4C (R4C), a novel virulent roseophage that infectsDinoroseobacter shibaeDFL12T, was isolated with the double-layer agar method. The phage morphology was visualized with transmission electron microscopy. We characterized R4C in-depth with a genomic analysis and investigated the distribution of the R4C genome in different environments with a metagenomic recruitment analysis.

Results

The double-stranded DNA genome of R4C consists of 36,291 bp with a high GC content of 66.75%. It has 49 genes with low DNA and protein homologies to those of other known phages. Morphological and phylogenetic analyses suggested that R4C is a novel member of the familySiphoviridaeand is most closely related to phages in the genusCronusvirus. However, unlike theCronusvirusphages, R4C encodes an integrase, implying its ability to establish a lysogenic life cycle. A terminal analysis shows that, like that of λ phage, the R4C genome utilize the ‘cohesive ends’ DNA-packaging mechanism. Significantly, homologues of the R4C genes are more prevalent in coastal areas than in the open ocean.

Conclusions

Information about this newly discovered phage extends our understanding of bacteriophage diversity, evolution, and their roles in different environments.
Correction to: Are industry-funded charities promoting “advocacy-led studies” or “evidence-based science”?: a case study of the International Life Sciences Institute
Authors: Steele Sarah , Ruskin Gary , Sarcevic Lejla , McKee Martin , Stuckler David
Published: November 2019

Since the publication of this article [1], the journal and the authors have received further context about the position of ILSI on the issue with the ILSI Mexico branch.
Sexual risky behavior, cocaine and alcohol use among substance users in an outpatient facility: a cross section study
Authors: Dallelucci Claudia Chaves , Bragiato Emi Carneiro , Areco Kelsy Catherina Nema , Fidalgo Thiago Marques , da Silveira Dartiu Xavier
Published: November 2019

Background

Substance dependence is considered an international health issue and studies that access the characteristic of this population are required to develop public health programs for harm reduction. To this aim, we purpose to to identify, in a population undergo addiction treatment, if the use of substances leads to sexual risky behavior and also check if another variables influences in this behavior.

Method

Observational study of clinical sample collected of adult patients seeking treatment to dependence of alcohol and cocaine. The data collected were: socio-demographic, substance use, sexual behavior and childhood abuse. Risky sexual behaviors were considered: inconsistent use of condoms and presence of multiple sexual partners in the past six months. An exploratory analysis of the association between the variable “risky sexual behavior” and the other variables was performed using Pearson’s chi-square, followed by a multivariate logistic regression analysis.

Results

After analyzing the variables with the presence or absence of risky sexual behavior, were included in the logistic regression the data that presented association with sexual risk behavior, and age appears as an independent factor for risky sexual behaviors. Other factors, such as schooling and unemployment, influence as much as the use of substances in risky sexual behaviors.

Conclusion

Attributing just to the substance use this risky sexual behavior seems too simplistic. Other structural factors such as schooling, work, age and sexual abuse in childhood can influence decision making for safe sex.
Cost-effectiveness analysis (CEA) of IMRT plus C12 boost vs IMRT only in adenoid cystic carcinoma (ACC) of the head and neck
Authors: Jensen A D , Debus Jürgen
Published: November 2019

Background

Particle therapy provides steep dose gradients to facilitate dose escalation in challenging anatomical sites which has been shown not only to improve local control but also overall survival in patients with ACC. Cost-effectiveness of intensity-modulated radiotherapy (IMRT) plus carbon ion (C12) boost vs IMRT alone was performed in order to objectivise and substantiate more widespread use of this technology in ACC.

Methods

Patients with pathologically confirmed ACC received a combination regimen of IMRT plus C12 boost. Patients presenting outside C12 treatment slots received IMRT only. Clinical results were published; economic analysis on patient-level data was carried out from a healthcare purchaser’s perspective based on costs of healthcare utilization. Cost histories were generated from resource use recorded in individual patient charts and adjusted for censoring using the Lin I method. Cost-effectiveness was measured as incremental cost-effectiveness ratio (ICER). Sensitivity analysis was performed regarding potentially differing management of recurrent disease.

Results

The experimental treatment increased overall costs by € 18,076 (€13,416 – €22,922) at a mean survival benefit of 0.86 years. Despite improved local control, following costs were also increased in the experimental treatment. The ICER was estimated to 26,863 €/LY. After accounting for different management of recurrent disease in the two cohorts, the ICER was calculated to 20,638 €/LY.

Conclusion

The combined treatment (IMRT+C12 boost) substantially increased initial and overall treatment cost. In view of limited treatment options in ACC, costs may be acceptable though. Investigations into quality of life measures may support further decisions in the future.