bluuebunny/crossref_metadata_2025 huggingface dataset:
Endoscopic resection techniques for squamous premalignant lesions and early carcinoma of the esophagus: ER-Cap, MBM, and ESD, how do we choose? A multicenter experience
Authors: Yu Xinying , Chen Jian , Yuan Zhiqiang , Liu Hui , Liu Fugang , Liu Yong , Xue Liyan , He Shun , Zhang Yueming , Dou Lizhou , Liu Xiao , Zhao Deli , Li Jun , Wang Shaofeng , Zhang Ping , Lu Ning , Wang Guiqi
Published: March 2020

Background:

Endoscopic resection cap technique (ER-Cap), multiband mucosectomy (MBM), and endoscopic submucosal dissection (ESD) have been widely applied in the treatment of esophageal squamous neoplasia and cancer. However, little is known with regards to the comparison of these methods. This study aimed to compare the feasibility, safety, effectiveness, and costs of these three techniques.

Methods:

A retrospective analysis of patients with squamous premalignant or early malignant lesions of the esophagus undergoing ER-Cap, MBM, or ESD from January 2009 to December 2015 in one of the centers in China was performed. The procedural data and follow-up data for all patients were recorded.

Results:

A total of 672 patients with 733 lesions were included; 148 lesions (133 patients) were treated with ER-Cap, 427 lesions (388 patients) with MBM, and 158 lesions (151 patients) with ESD. The mean age was 61.59 years and the male-to-female ratio was 2.78:1. The operation time was significantly shorter for ER-Cap (29.26 ± 16.73 mins, p < 0.001) group, and the hospitalization costs were significantly lower in the MBM group (20,942.03 ± 8435.56￥, p = 0.003). The resection sample size of ESD was significantly larger (4.40 ± 1.20 cm, p < 0.001) and the en bloc resection rate of ESD was significantly higher ( p < 0.001) than that of the other two groups. The frequencies of perforation, bleeding, and cicatricial stenosis were significantly lower in the MBM group ( p < 0.001, p = 0.011, p = 0.009). Three local recurrences were observed in the ER-Cap group, while no recurrence was observed in MBM and ESD groups. There were three and two metastatic patients observed in the MBM and ESD groups, respectively.

Conclusions:

ER-Cap, MBM, and ESD are all minimally invasive, safe, and effective methods for treating early esophageal squamous cell carcinoma. MBM could be considered as a good alternative when performed by a less-experienced endoscopist in high-incidence areas with limited resources.
Participation of Patients With Type 2 Diabetes in Online Support Groups is Correlated to Lower Levels of Diabetes Self-Management
Authors: Herrero Noelia , Guerrero-Solé Frederic , Mas-Manchón Lluís
Published: March 2020

Background:

Support groups play an important role in diabetes understanding and education. This study aims to find connections between participating in diabetes-related online communities (groups and forums) and the self-reported degree of self-care management and health problems associated with type 1 and 2 diabetes.

Methods:

A cross-sectional study using an online survey was conducted and 307 participants were recruited. Participants were asked about diabetes self-care management (glucose management, healthcare, dietary restrictions, and physical activity) and complications related to the disease, as well as their participation in online social groups and forums (duration, time, and intensity).

Results:

Belonging to diabetes-related online support groups (OSGs) was associated with lower scores in healthcare and self-management of diabetes ( M = 2.98, SD = 1.07, n = 207, for belonging to OSGs; and M = 4.22, SD = 0.59, n = 97, for not belonging to OSGs). These differences were not statistically significant for type 1 diabetes individuals ( M = 4.33, SD = 0.47, n = 28, for belonging to OSGs, and M = 4.29, SD = 0.48, n = 52, for not belonging to OSGs), but were highly significant for type 2 diabetes (T2D) individuals ( M = 2.41, SD = 0.68, n = 144, for belonging to OSGs; and M = 4.14, SD = 0.64, n = 61, for not belonging to OSGs). People with both type 1 and 2 diabetes reported to have suffered more complications derived from diabetes when they belonged to an OSG, but greater statistically significant differences were found in type 2 individuals.

Conclusion:

Patients with T2D who participate in OSGs show a higher correlation with having lower levels of diabetes self-care management as well as health complications related to the disease.
Ectopic transient overexpression of OCT-4 facilitates BMP4-induced osteogenic transdifferentiation of human umbilical vein endothelial cells
Authors: Kim Seung Hyun L , Lee Seunghun S , Kim Inseon , Kwon Janet , Kwon Song , Bae Taegeun , Hur Junho , Lee Hwajin , Hwang Nathaniel S
Published: March 2020

Limitation in cell sources for autologous cell therapy has been a recent focus in stem cell therapy and tissue engineering. Among various research advances, direct conversion, or transdifferentiation, is a notable and feasible strategy for the generation and acquirement of wanted cell source. So far, utilizing cell transdifferentiation technology in tissue engineering was mainly restricted at achieving single wanted cell type from diverse cell types with high efficiency. However, regeneration of a complete tissue always requires multiple cell types which poses an intrinsic complexity. In this study, enhanced osteogenic differentiation was achieved by transient ectopic expression of octamer-binding transcription factor 4 ( OCT-4) gene followed by bone morphogenetic protein 4 treatment on human umbilical vein endothelial cells. OCT-4 transfection and bone morphogenetic protein 4 treatment resulted in enhanced expression of osteogenic markers such as core-binding factor alpha 1, alkaline phosphatase, and collagen 1 compared with bone morphogenetic protein 4 treatment alone. Furthermore, we employed gelatin-heparin cryogel in cranial defect model for in vivo bone formation. Micro-computed tomography and histological analysis of in vivo samples showed that OCT-4 transfection followed by bone morphogenetic protein 4 treatment resulted in efficient transdifferentiation of endothelial cells to osteogenic cells. These results suggest that the combination of OCT-4 and bone morphogenetic protein 4 on endothelial cells would be a reliable multicellular transdifferentiation model which could be applied for bone tissue engineering.
Should musicians play in pain?
Authors: Stanhope Jessica , Weinstein Philip
Published: March 2020

Musculoskeletal symptoms, including pain, are often experienced by musicians at all levels. These symptoms may have a detrimental impact on musicians’ personal and work lives, and may also impact upon the ensembles they work within. Providing musicians with appropriate, evidence-based advice regarding pain management is therefore paramount. In this review, we aim to improve the advice given to musicians regarding playing when in pain, by answering the question ‘should musicians play in pain?’. This multidisciplinary narrative review draws upon contemporary pain science, including factors associated with poorer prognoses for those in pain, as well as the reported experiences of musicians with pain (including those who have taken time off from playing). Our current understanding of pain science provides further support for the potential for consequences related to avoiding activities due to pain. Pain is modulated by a number of neuro-immunological processes and is influenced by a range of psychosocial factors. Taking time off from playing might therefore not have any benefit. Importantly, one of the leading causes of a transition from acute to chronic pain is fear-avoidance behaviour (e.g. not playing when in pain); hence, encouraging such behaviour cannot be supported. Musicians who have taken time off from playing due to pain have experienced a range of consequences, including emotional and financial consequences. These experiences indicate that there are potential negative consequences related to taking time off from playing which need to be weighed against any benefits. We conclude that musicians should not necessarily be advised to take time off from playing to manage their pain, in keeping with current best practice for pain management. Instead, we recommend that musicians be educated on contemporary pain science and when to seek treatment from a health professional for individualised advice to reduce the burden of musicians’ pain.
Bending properties of dimension lumber produced from Siberian larch (Larix sibirica) in Mongolia
Authors: Tumenjargal Bayasaa , Ishiguri Futoshi , Takahashi Yusuke , Nezu Ikumi , Baasan Bayartsetseg , Chultem Ganbaatar , Aiso-Sanada Haruna , Ohshima Jyunichi , Yokota Shinso
Published: March 2020

The modulus of elasticity (MOE) and modulus of rupture (MOR) were evaluated for 190 pieces of dimension lumber (2 by 4 lumber, 38 by 89 mm in cross-section) produced fromLarix sibiricatrees grown in Mongolia. The 5% tolerance limits of the MOE and MOR were 5.70 GPa and 15.1 MPa, respectively. The value of the 5% tolerance limit of the MOR exceeded the characteristic value of 2 by 4 lumber in visual grading class No. 3 of the Japanese Agricultural Standard for the D. fir-L, Hem-Tam, JS-III and S-P-F softwood species groups. A significant positive correlation was found between the MOE and MOR, although air-dry density was weakly correlated with bending properties inL. sibirica.
Detection and visualization of encoded local features as anatomical predictors in cross-sectional images of Lauraceae
Authors: Hwang Sung-Wook , Kobayashi Kayoko , Sugiyama Junji
Published: March 2020

This paper describes computer vision-based quantitative microscopy and its application toward better understanding species specificity. An image dataset of the Lauraceae family that consists of nine species across six genera was investigated, and structural features were quantified using encoded local features implemented in a bag-of-features framework. Of the algorithms used for feature detection, the scale-invariant feature transform (SIFT) achieved the best performance in species discrimination. In the bag-of-features framework with the SIFT features, each image is represented by a histogram of codewords. The codewords were further analyzed by mapping them to each image to visualize the corresponding anatomical elements. From this analysis, we were able to classify and quantify the modes of aggregation of different combinations of cell elements based on clustered codewords. An analysis of the term frequency–inverse document frequency weights revealed that blob-based codewords are generally shared by all species, whereas corner-based codewords are more species specific.
Sensor-based systems for early detection of dementia (SENDA): a study protocol for a prospective cohort sequential study
Authors: Müller Katrin , Fröhlich Stephanie , Germano Andresa M. C. , Kondragunta Jyothsna , Agoitia Hurtado Maria Fernanda del Carmen , Rudisch Julian , Schmidt Daniel , Hirtz Gangolf , Stollmann Peter , Voelcker-Rehage Claudia
Published: March 2020

Background

Dementia and cognitive decline are serious social and economic burdens. An increase in the population of older people, as well as longer lifespans mean that numbers of dementia cases are exponentially rising. Neuropathological changes associated with dementia are thought to appear before the clinical manifestation of cognitive symptoms, i.e., memory impairments. Further, some older adults (OA) experience cognitive decline before it can be objectively diagnosed. For optimal care of these patients, it is necessary to detect cognitive decline and dementia at an early stage. In this vein, motor, sensory, and neurophysiological declines could be promising factors if found to be present before the onset of cognitive impairment. Hence, the objective of the SENDA study is to develop a multi-dimensional sensor-based instrument that allows early detection of cognitive decline or dementia in OA with the help of cognitive, sensory, motor, and neurophysiological parameters before its clinical manifestation.

Methods/design

In the cohort sequential study, participants are assigned to one of three study groups depending on their cognitive status: 1. cognitively healthy individuals (CHI), 2. subjectively cognitively impaired persons (SCI), or 3. (possible) mildly cognitively impaired persons (pMCI, MCI). All groups take part in the same cognitive (e.g., executive function tests), motor (e.g., gait analyses, balance tests), sensory (e.g., vibration perception threshold test, proprioception tests), and neurophysiological (e.g., electroencephalograms) measurements. Depending on the time at which participants are included into the study, all measurements are repeated up to four times in intervals of 8 months within 3 years to identify associations with cognitive changes over time.

Discussion

This study aims to detect possible motor, sensory, neurophysiological, and cognitive predictors to develop an early screening tool for dementia and its pre-stages in OA. Thus, affected persons could receive optimal health care at an earlier time point to maintain their health resources.

Trial status

The study is ongoing. The recruitment of participants will be continued until May 2020.
Nutritional status of school age children in Abakaliki metropolis, Ebonyi State, Nigeria
Authors: Umeokonkwo Adanna Anthonia , Ibekwe Maryann Ugochi , Umeokonkwo Chukwuma David , Okike Clifford Onuorah , Ezeanosike Obumneme Benaiah , Ibe Bede Chidozie
Published: March 2020

Background

Malnutrition is a major public health problem with short and long-term adverse effects on children particularly in middle and low-income countries. Three out of every ten under-five children are said to be stunted and 19.4% underweight in Nigeria. In Ebonyi State, between 2013 and 2015, the proportion of preschool children with chronic undernutrition rose from 16.2 to 20.6%. Little is documented about the nutritional status of school-age children in Ebonyi State and Nigeria.

Methods

We conducted a descriptive cross-sectional study among 780 children aged 6 to 12 years from 10 primary schools in Abakaliki metropolis. A multistage sampling method was used to select the participants. A pre-tested interviewer-administered structured questionnaire was used to collect information from the children and their parents. Body Mass Index (BMI), Z scores of the weight for age, BMI for age and height for age were obtained using the WHO AnthroPlus software. We estimated the prevalence of undernutrition, over-nutrition, underweight, thinness, stunting, overweight and obesity.

Result

Out of 751 pupils that participated, 397 (52.9%) were females and 595 (79.2%) were in public schools. The overall prevalence of undernutrition was 15.7% and that of over-nutrition was 2.1%. The prevalence of underweight, thinness and stunting, overweight and obesity were 8, 7.2, 9.9, 1.4 and 0.7% respectively. The proportion of pupils who were thin was higher among males (8.7%), those attending public schools (8.6%) and those dwelling in rural parts of the metropolis (14.3%) compared to females (5.8%) private school attendees (1.9%) and urban dwellers (4.6%). Stunting was found to be higher among pupils attending public schools (11.8%) compared to those attending private schools (2.5%). The prevalence of stunting was 19.3% among the pupils residing in rural areas and 5% among the pupils living in urban areas of the metropolis. No pupil in private schools was underweight. Over-nutrition was not found among the pupils in rural areas.

Conclusion

Both under and over nutrition exist in Abakaliki metropolis. Undernutrition is the more prevalent form of malnutrition among school age children in the metropolis.
Adolescent Interventions to Manage Self-Regulation in Type 1 Diabetes (AIMS-T1D): randomized control trial study protocol
Authors: Miller Alison L. , Lo Sharon L. , Albright Dana , Lee Joyce M. , Hunter Christine M. , Bauer Katherine W. , King Rosalind , Clark Katy M. , Chaudhry Kiren , Kaciroti Niko , Katz Benjamin , Fredericks Emily M.
Published: March 2020

Background

Self-regulation (SR), or the capacity to control one’s thoughts, emotions, and behaviors in order to achieve a desired goal, shapes health outcomes through many pathways, including supporting adherence to medical treatment regimens. Type 1 Diabetes (T1D) is one specific condition that requires SR to ensure adherence to daily treatment regimens that can be arduous and effortful (e.g., monitoring blood glucose). Adolescents, in particular, have poor adherence to T1D treatment regimens, yet it is essential that they assume increased responsibility for managing their T1D as they approach young adulthood. Adolescence is also a time of rapid changes in SR capacity and thus a compelling period for intervention. Promoting SR among adolescents with T1D may thus be a novel method to improve treatment regimen adherence. The current study tests a behavioral intervention to enhance SR among adolescents with T1D. SR and T1D medical regimen adherence will be examined as primary and secondary outcomes, respectively.

Methods

We will use a randomized control trial design to test the impact of a behavioral intervention on three SR targets: Executive Functioning (EF), Emotion Regulation (ER), and Future Orientation (FO); and T1D medical regimen adherence. Adolescents with T1D (n = 94) will be recruited from pediatric endocrinology clinics and randomly assigned to treatment or control group. The behavioral intervention consists of working memory training (to enhance EF), biofeedback and relaxation training (to enhance ER), and episodic future thinking training (to enhance FO) across an 8-week period. SR and treatment regimen adherence will be assessed at pre- and post-test using multiple methods (behavioral tasks, diabetes device downloads, self- and parent-report). We will use an intent-to-treat framework using generalized linear mixed models to test our hypotheses that: 1) the treatment group will demonstrate greater improvements in SR than the control group, and 2) the treatment group will demonstrate better treatment regimen adherence outcomes than the control group.

Discussion

If successful, SR-focused behavioral interventions could improve health outcomes among adolescents with T1D and have transdiagnostic implications across multiple chronic conditions requiring treatment regimen adherence.

Trial registration

ClinicalTrials.gov: NCT03688919; registered September 28, 2018.
Cross-cultural adaptation and validation of the Romanian knee disability and osteoarthritis outcome score for joint replacement (KOOSJR)
Authors: Florescu Sorin , Vermesan Dinu , Haragus Horia , Patrascu Jenel M. , Timar Bogdan , Todor Adrian
Published: March 2020

Aim

To perform validation of the Romanian Knee disability and Osteoarthritis Outcome Score for Joint Replacement (KOOSJR).

Method

Ninety-six patients (101 knees) with advanced osteoarthritis (OA) scheduled for total knee replacement completed Romanian translations of KOOSJR and IKDC (International Knee Documentation Committee – subjective knee form) and Euroqol EQ-5D-5 L, and the treating physician completed the original knee society score (KSS).

Results

Average age was 66.4 (range 50–83) years and male to female ratio 1:3.76. There was moderate correlation between the test-retest (average 4 days) KOOSJR (r = 0.618, n = 45) and IKDC (r = − 0.671, n = 99), weak between KOOSJR and EQ-5D-5 L Index (r = − 0.431, n = 100) and VAS (r = − 0.364, n = 99) and very weak to KSS score (r = − 0.133, n = 98) and function (r = − 0.072, n = 97) For the first KOOSJR, Cronbach’s alpha was 0.816 and intraclass correlation coefficient (ICC) 0.816 (95% CI 0.755–0.866) for average measures. For the retest, Cronbach’s alpha was 0.841 (95% CI 0.760–0.903) for averages.

Conclusion

The Romanian Knee disability and Osteoarthritis Outcome Score for Joint Replacement (KOOSJR) is a valid, reliable, consistent and reproducible clinical score for patients with OA requiring arthroplasty.
Acute and chronic diabetes complications associated with self-reported oral health: a retrospective cohort study
Authors: Kaura Parbhakar Kamini , Rosella Laura C. , Singhal Sonica , Quiñonez Carlos R.
Published: March 2020

Background

Oral health is associated with diabetes, but the chances of experiencing acute or chronic diabetes complications as per this association is unknown in Canada’s most populous province, Ontario. This study assesses the impact of self-reported oral health on the likelihood of experiencing acute and chronic complications among a cohort of previously diagnosed diabetics.

Methods

A retrospective cohort study was conducted of diabetics (n = 5183) who participated in the Canadian Community Health Survey 2003 and 2007–08. Self-reported oral health status was linked to health encounters in electronic medical records until March 31, 2016. Multinomial regression models determined the odds of the first acute or chronic complication after self-report of oral health status.

Results

Thirty-eight percent of diabetics reporting “poor to fair” oral health experienced a diabetes complication, in comparison to 34% of those reporting “good to excellent” oral health. The odds of an acute or chronic complication among participants reporting “poor to fair” oral health status was 10% (OR 1.10; 95% CI 0.81, 1.51) and 34% (OR 1.34; 95% CI 1.11, 1.61) greater respectively, than among participants experiencing no complications and reporting “good to excellent” oral health.

Conclusion

Self-reporting “poor to fair” oral health status is associated with a greater likelihood of chronic complications than acute complications. Further research regarding the underlying causal mechanisms linking oral health and diabetes complications is needed.
Germacrone protects against oxygen-glucose deprivation/reperfusion injury by inhibiting autophagy processes in PC12 cells
Authors: Zhang Jianxing , Yuan Li , Wang Sujie , Liu Jiang , Bi Huiqin , Chen Guojuan , Li Jingjing , Chen Lili
Published: March 2020

Background

Germacrone is an anti-inflammatory ingredient in the Chinese medicine zedoary turmeric. The purpose of this study was to explore the protective mechanism of germacrone against PC12 cells injury caused by oxygen-glucose deprivation/reperfusion (OGD/R).

Methods

OGD/R injury model of PC12 cells was established by using OGD/R (2 h/24 h). The cell viability was assessed by MTT assay and LDH release. The ultrastructure of cells was observed by transmission electron microscopy (TEM). The expression of autophagy related proteins in cells was determined by Western Blot.

Results

The results of ultrastructural observation showed that PC12 cells damaged by OGD/R showed typical autophagy characteristics. In addition, OGD/R observably up-regulated the expression of autophagy related proteins: the class III type phosphoinositide 3-kinase (PI3K III), light chain 3(LC3), and Beclin-1 in PC12 cells, and inhibited the expression of the class I type phosphoinositide 3-kinase (PI3K I), Protein kinase B (Akt), the mammalian target of rapamycin (mTOR), and B-cell lymphoma 2(Bcl-2) proteins. Furthermore, germacrone increased the cell viability of OGD/R-damaged PC12 cells by down-regulating the expression of LC3 protein in cells in a concentration-dependent manner. More importantly, germacrone significantly inhibited the expression of PI3K III, LC3, and Beclin-1 in OGD/R-injured PC12 cells, and up-regulated the expressionof PI3K I, Akt, mTOR, and Bcl-2 proteins in cells, and this inhibited or up-regulated effect was reversed by PI3K I inhibitor (ZSTK474).

Conclusion

The above results indicated that germacrone could inhibit the autophagy effect in OGD/R injury model of PC12 cells, the mechanism of inhibition was regulated by PI3K III/Beclin-1/Bcl-2 and PI3K I/Akt/mTOR pathways, thereby improving the cell viability of PC12 cells and playing a neuroprotective role, which provided a new drug for the treatment of OGD/R.
Acceptability and appropriateness of a perinatal depression preventive group intervention: a qualitative analysis
Authors: Diebold Alicia , Segovia Melissa , Johnson Jessica K. , Degillio Aria , Zakieh Dana , Park Hee Jin , Lim Kenneth , Tandon S. Darius
Published: March 2020

Background

Perinatal depression is a prevalent public health concern. Although preventive interventions exist, there is limited literature on the acceptability and appropriateness of these interventions, especially those delivered by paraprofessionals. The Mothers and Babies Program (MB) is a group-based perinatal depression preventive intervention delivered prenatally. A cluster-randomized controlled trial examined the acceptability, appropriateness, and effectiveness of MB delivered by mental health professionals compared to paraprofessional staff from home visiting programs.

Methods

The full study enrolled 874 pregnant women. Fifty-three facilitators were trained and delivered the MB intervention to women in one of seven states in the United States. Semi-structured interviews were attempted with a randomly-selected subset of the full sample of pregnant women who received the MB intervention and with all facilitators. Specifically, interviews were conducted with 88 women who received the MB group intervention (45 in the paraprofessional-led arm and 43 in the mental health professional-led arm) and 46 women who facilitated the groups (27 home visiting staff and 19 mental health professionals). Interviews were conducted over the phone in English or Spanish and audio recorded. The recordings were translated into English, as needed, and transcribed. Thematic analysis was conducted using NVIVO to identify key themes related to intervention acceptability and appropriateness. Similarities and differences between study arms were explored.

Results

Clients and facilitators found the MB content and group format acceptable. Challenges included maintaining group attendance, transportation issues, and managing group discussion. Overall, facilitators found the intervention appropriate for pregnant clients with some challenges presented for clients in crisis situations, experiencing housing instability, and with literacy and learning challenges. Participants provided suggestions for improvement, both for the course content and implementation. There were no significant differences found between study arms.

Conclusions

Overall, clients and facilitators enjoyed MB irrespective of study arm, and facilitators found the intervention appropriate for the population. These findings add to the qualitative literature on perinatal depression preventive interventions, specifically those delivered by paraprofessionals.

Trial registration

This trial is registered onClinicalTrials.gov(Initial post: December 1, 2016; identifier:NCT02979444).
PAN RNA: transcriptional exhaust from a viral engine
Authors: Campbell Mel , Izumiya Yoshihiro
Published: March 2020

Kaposi’s sarcoma-associated herpesvirus (KSHV), also designated human herpesvirus 8 (HHV-8), has been linked to Kaposi’s sarcoma, as well as to primary effusion lymphoma (PEL), and a subset of multicentric Castleman’s disease. KSHV genomes are maintained as episomes within infected cells and the virus exhibits a biphasic life cycle consisting of a life-long latent phase during which only a few viral genes are expressed and no viral progeny are produced and a transient lytic reactivation phase, in which a full repertoire of ~ 80 lytic genes are activated in a temporally regulated manner culminating in the release of new virions. Lytic replication is initiated by a single viral protein, K-Rta (ORF50), which activates more than 80 viral genes from multiple resident viral episomes (i.e., viral chromosomes). One of the major targets of K-Rta is a long non-coding nuclear RNA, PAN RNA (polyadenylated nuclear RNA), a lncRNA that accumulates to exceedingly high levels in the nucleus during viral reactivation. K-Rta directly binds to the PAN RNA promoter and robustly activates PAN RNA expression. Although PAN RNA has been known for over 20 years, its role in viral replication is still incompletely understood. In this perspective, we will briefly review the current understanding of PAN RNA and then describe our current working model of this RNA. The model is based on our observations concerning events that occur during KSHV lytic reactivation including (i) a marked accumulation of RNA Pol II at the PAN promoter, (ii) genomic looping emanating from the PAN locus, (iii) interaction of a second viral lytic protein (ORF57) with K-Rta, PAN RNA and RNA Pol II, (iv) the essential requirement for PAN RNA expression in cis for optimal transcriptional execution needed for the entire lytic program, and (v) ORF57 recruitment of RNA Pol II to the PAN genomic locus. Together our results generate a model in which the PAN locus serves as a hub for sequestration/trapping of the cellular transcriptional machinery proximal to viral episomes. Sequestration at the PAN locus facilitates high levels of viral transcription throughout the viral genome during lytic replication. ORF57 acts as a transcription-dependent transactivator at the PAN locus by binding to both Rta and PAN to locally trap RNA Pol II. The resulting accumulation of high levels of nuclear PAN RNA created by this process is an inducible enhancer-derived (eRNA) by-product that litters the infected cell nucleus.
Human sperm vitrification: the state of the art
Authors: Tao Yong , Sanger Erika , Saewu Arpornrad , Leveille Marie-Claude
Published: March 2020

Sperm cryopreservation has been widely used in assisted reproductive technology (ART) and has resulted in millions of live births. Two principal approaches have been adopted: conventional (slow) freezing and vitrification. As a traditional technique, slow freezing has been successfully employed and widely used at ART clinics whereas the latter, a process to solidify liquid into an amorphous or glassy state, may become a faster alternative method of sperm cryopreservation with significant benefits in regard to simple equipment and applicability to fertility centers. Sperm vitrification has its own limitations. Firstly, small volume of load is usually plunged to liquid nitrogen to achieve high cooling rate, which makes large volume sample cryopreservation less feasible. Secondly, direct contact with liquid nitrogen increases the potential risk of contamination. Recently, new carriers have been developed to facilitate improved control over the volume and speed, and new strategies have been implemented to minimize the contamination risk. In summary, although sperm vitrification has not yet been applied in routine sperm cryopreservation, its potential as a standard procedure is growing.
Data-driven translational prostate cancer research: from biomarker discovery to clinical decision
Authors: Lin Yuxin , Zhao Xiaojun , Miao Zhijun , Ling Zhixin , Wei Xuedong , Pu Jinxian , Hou Jianquan , Shen Bairong
Published: March 2020

Prostate cancer (PCa) is a common malignant tumor with increasing incidence and high heterogeneity among males worldwide. In the era of big data and artificial intelligence, the paradigm of biomarker discovery is shifting from traditional experimental and small data-based identification toward big data-driven and systems-level screening. Complex interactions between genetic factors and environmental effects provide opportunities for systems modeling of PCa genesis and evolution. We hereby review the current research frontiers in informatics for PCa clinical translation. First, the heterogeneity and complexity in PCa development and clinical theranostics are introduced to raise the concern for PCa systems biology studies. Then biomarkers and risk factors ranging from molecular alternations to clinical phenotype and lifestyle changes are explicated for PCa personalized management. Methodologies and applications for multi-dimensional data integration and computational modeling are discussed. The future perspectives and challenges for PCa systems medicine and holistic healthcare are finally provided.
Factor analysis and evaluation of each item of the tinnitus handicap inventory
Authors: Wakabayashi Satoko , Oishi Naoki , Shinden Seiichi , Ogawa Kaoru
Published: March 2020

Purpose

This study aims to examine the availability of subscales in the Tinnitus Handicap Inventory (THI) originally proposed by Newman and the possibility of other useful subscales. We also examine whether each item of the THI could be used to better understand the status of patients with tinnitus.

Methods

This study included 1332 patients who answered the THI on their first visit. Confirmatory factor analysis was conducted to the 25 items of the THI to confirm the usefulness of the emotional, functional, and catastrophic subscales. Exploratory factor analysis was performed to discover the availability of other suitable subscales in addition to the proposed subscales. The proportion of patients who chose “yes” in each item of the THI was also examined to understand the status of patients with tinnitus.

Results

In the confirmatory factor analysis, the emotional, functional, and catastrophic subscales did not fit the model. In the exploratory factor analysis, data were extremely biased to one factor. Examination of each item of the THI showed the tendency of worsening of comorbid symptoms when tinnitus handicap became worse.

Conclusions

As a result of the factor analysis, only the total score, not any subscale, would be clinically useful in the THI. Examination of each item of the THI was helpful to understand the status of patients with tinnitus and comorbid symptoms of tinnitus. It is necessary to consider treatment by taking these comorbid symptoms into account.
“Phantom akathisia” in an amputated leg of a sarcoma patient: a case report
Authors: Ishida Mayumi , Imanishi Jungo , Yazawa Yasuo , Sunakawa Yu , Torigoe Tomoaki , Onishi Hideki
Published: March 2020

Background

Akathisia is a rather common extrapyramidal side effect of antipsychotic drugs and antidepressants, often resulting in severe discomfort for patients. However, due to the diversity of symptoms, it is often overlooked. We hereby report a case with akathisia that mainly appeared in an amputated leg.

Case presentations

A 60-year-old woman, who had undergone external hemipelvectomy for a recurrent soft tissue sarcoma, was referred to the Department of Psycho-Oncology due to worsening anxiety and restlessness. She was not unconscious or disoriented. Her chief complains included restlessness, an itching sensation in the area corresponding to the amputated left leg, and a feeling as if the lost left leg were raising itself. Detailed examination revealed that she had been administered 10 mg per day of oral prochlorperazine maleate for nausea induced by the oxycodone that had been prescribed to control post-operative pain. Akathisia was suspected and prochlorperazine maleate treatment was discontinued. All the symptoms were alleviated on the next day, and disappeared in 3 days. Eventually, she was diagnosed with akathisia.

Conclusions

This case indicates that the symptoms associated with akathisia can occur in an amputated extremity. Considering two previous reports of “phantom dyskinesia”, extrapyramidal syndromes may result in unusual presentations if occurring in an amputated extremity. Not only should the use of antipsychotic drugs and antidepressants be carefully considered, but also closer observation of psychological symptoms is required after prescription of these drugs because the clinical presentation of akathisia can be various and confusing due to modifications caused by other factors as in this case.
Healthcare professionals’ perspectives on mental health service provision: a pilot focus group study in six European countries
Authors: Triliva Sofia , Ntani Spyridoula , Giovazolias Theodoros , Kafetsios Konstantinos , Axelsson Malin , Bockting Claudi , Buysse Ann , Desmet Mattias , Dewaele Alexis , Hannon Dewi , Haukenes Inger , Hensing Gunnel , Meganck Reitske , Rutten Kris , Schønning Viktor , Van Beveren Laura , Vandamme Joke , Øverland Simon
Published: March 2020

Background

The mental healthcare treatment gap (mhcGAP) in adult populations has been substantiated across Europe. This study formed part of MentALLY, a research project funded by the European Commission, which aimed to gather qualitative empirical evidence to support the provision of European mental healthcare that provides effective treatment to all adults who need it.

Methods

Seven focus groups were conducted with 49 health professionals (HPs), including psychologists, psychiatrists, social workers, general practitioners, and psychiatric nurses who worked in health services in Belgium, Cyprus, Greece, the Netherlands, Norway and Sweden. The focus group discussions centered on the barriers and facilitators to providing quality care to people with mild, medium, and severe mental health problems. Analyses included deductively and inductively driven coding procedures. Cross-country consensus was obtained by summarizing findings in the form of a fact sheet which was shared for triangulation by all the MentALLY partners.

Results

The results converged into two overarching themes: (1) Minding the treatment gap: the availability and accessibility of Mental Health Services (MHS). The mhcGAP gap identified is composed of different elements that constitute the barriers to care, including bridging divides in care provision, obstacles in facilitating access via referrals and creating a collaborative ‘chain of care’. (2) Making therapeutic practice relevant by providing a broad-spectrum of integrated and comprehensive services that value person-centered care comprised of authenticity, flexibility and congruence.

Conclusions

The mhcGAP is comprised of the following barriers: a lack of funding, insufficient capacity of human resources, inaccessibility to comprehensive services and a lack of availability of relevant treatments. The facilitators to the provision of MHC include using collaborative models of primary, secondary and prevention-oriented mental healthcare. Teamwork in providing care was considered to be a more effective and efficient use of resources. HPs believe that the use of e-mental health and emerging digital technologies can enhance care provision. Facilitating access to a relevant continuum of community-based care that is responsive coordinated and in line with people’s needs throughout their lives is an essential aspect of optimal care provision.
Implementing civic engagement within mental health services in South East Asia: a systematic review and realist synthesis of current evidence
Authors: James Karen , Brooks Helen , Susanti Herni , Waddingham Jessica , Irmansyah Irman , Keliat Budi-Anna , Utomo Bagus , Rose Diana , Colucci Erminia , Lovell Karina
Published: March 2020

Introduction

Civic engagement (CE) has the potential to transform mental health services and could be particularly important for low and middle-income countries (LMICs), which are rapidly developing to respond to the burden of poor mental health. Research from high income countries has found many challenges associated with the meaningful implementation of CE in practice, but this has been underexplored in LIMCS and in South East Asia (SEA) in particular.

Methods

We completed a realist synthesis and systematic review of peer reviewed publications and grey literature to identify the context and actions which promote successful implementation of CE approaches in SEA. We used a theory-driven approach—realist synthesis—to analyse data and develop context-mechanism-outcome configurations that can be used to explain how civic engagement approaches operate in South East Asian contexts. We worked closely with patient and public representatives to guide the review from the outset.

Results

Fifty-seven published and unpublished articles were included, 24 were evaluations of CE, including two Randomized Controlled Trials. The majority of CE interventions featured uptake or adaptation of Western models of care. We identified important cultural differences in the enactment of civic engagement in SEA contexts and four mechanisms which, alongside their contextual barriers and facilitators, can be used to explain how civic engagement produces a range of outcomes for people experiencing mental health problems, their families and communities. Our review illustrates how CE interventions can be successfully implemented in SEA, however Western models should be adapted to fit with local cultures and values to promote successful implementation. Barriers to implementation included distrust of services/outside agencies, stigma, paternalistic cultures, limited resource and infrastructure.

Conclusion

Our findings provide guidance for the implementation of CE approaches within SEA contexts and identify areas for further research. Due to the collectivist nature of many SEA cultures, and the impact of shared traumas on community mental health, CE might best be implemented at community level, with a focus on relational decision making.

RegistrationThis review is registered on PROSPERO: CRD42018087841.
Medications for sleep disturbance in children and adolescents with depression: a survey of Canadian child and adolescent psychiatrists
Authors: Boafo Addo , Greenham Stephanie , Sullivan Marla , Bazaid Khalid , Suntharalingam Sinthuja , Silbernagel Lana , Magner Katherine , Robillard Rébecca
Published: March 2020

Background

Primary care physicians and child and adolescent psychiatrists often treat sleep disturbances in children and adolescents with mood disorders using medications off-label, in the absence of clear evidence for efficacy, tolerability and short or long-term safety. This study is the first to report Canadian data about prescribing preferences and perceived effectiveness reported by child and adolescent psychiatrists regarding medications used to manage sleep disturbances in children and adolescents with depression.

Methods

Canadian child and adolescent psychiatrists were surveyed on their perception of effectiveness of a range of medications commonly prescribed for sleep disturbances, their ranked preferences for these medications, reasons for avoiding certain medications, and perceived side effects.

Results

Sixty-seven active child and adolescent psychiatrists completed the survey. Respondents reported noting significant sleep issues in 40% of all their patients. Melatonin and trazodone were identified as the first treatment of choice by 83% and 10% of respondents respectively, and trazodone was identified as the second treatment of choice by 56% of respondents for treating sleep disturbances in children and adolescents with depression. Melatonin (97%), trazodone (81%), and quetiapine (73%) were rated by a majority of respondents as effective. Doxepin, zaleplon, tricyclic antidepressants, zolpidem, or lorazepam were rarely prescribed due to lack of evidence and/or concerns about adverse effects, long-term safety, suitability for youth, suicidality, and dependence/tolerance.

Conclusions

Melatonin and certain off-label psychotropic drugs are perceived as being more effective and appropriate to address sleep disturbances in children and adolescents with depression. More empirical evidence on the efficacy, tolerability and indications for using these medications and newer group of sleep medications in this population is needed.
Ovarian cancer subtypes and survival in relation to three comprehensive imaging parameters
Authors: Sartor Hanna , Bjurberg Maria , Asp Mihaela , Kahn Anna , Brändstedt Jenny , Kannisto Päivi , Jirström Karin
Published: March 2020

Background

Ovarian cancer (OC) is usually detected in late clinical stages, and imaging at diagnosis is crucial. Peritoneal carcinomatosis (PC) and cardio phrenic lymph nodes (CPLN) are pathological findings of computed tomography (CT) and are relevant for surgical planning. Furthermore, mammographic breast density (BD) has shown an association with OC risk and might be prognostically relevant. However, it is not known if PC, CPLN, and BD are associated with aggressive OC subtypes and impaired OC survival. Herein, we investigated associations between three comprehensive image parameters and OC subtypes and survival.

Methods

The Malmö Diet and Cancer Study is a prospective study that included 17,035 women (1991–1996). Tumor information on 159 OC and information on OC specific survival (last follow-up, 2017-12-31) was registered. The CT and mammography closest to diagnosis were evaluated (Peritoneal Carcinomatosis Index PCI, CPLN, and BD). Associations between CT-PCI, CPLN, and BD vs. clinical stage [stage I vs. advanced stage (II-IV), histological type/grade (high grade serous and endometrioid vs. other subtypes], and OC-specific survival were analyzed by logistic and Cox regression.

Results

There was a significant association between higher CT-PCI score and advanced clinical stage (adjusted OR 1.26 (1.07–1.49)), adjusted for age at diagnosis and histological type/grade. Increasing CT-PCI was significantly associated with impaired OC specific survival (adjusted HR 1.04 (1.01–1.07)), adjusted for age at diagnosis, histological type/grade, and clinical stage. There was no significant association between PCI and histological type/grade, nor between BD or CPLN vs. the studied outcomes.

Conclusions

Image PCI score was significantly associated with advanced clinical stages and impaired OC survival. An objective approach (based on imaging) to scoring peritoneal carcinomatosis in ovarian cancer could help surgeons and oncologists to optimize surgical planning, treatment, and care.
Diet, weight management, physical activity and Ovarian & Breast Cancer Risk in women with BRCA1/2 pathogenic Germline gene variants: systematic review
Authors: Coletta Adriana M. , Peterson Susan K. , Gatus Leticia A. , Krause Kate J. , Schembre Susan M. , Gilchrist Susan C. , Arun Banu , You Y. Nancy , Rodriguez-Bigas Miguel A. , Strong Larkin L. , Lu Karen H. , Basen-Engquist Karen
Published: March 2020

Introduction

Women with pathogenic germline gene variants in BRCA1 and/or BRCA2 are at increased risk of developing ovarian and breast cancer. While surgical and pharmacological approaches are effective for risk-reduction, it is unknown whether lifestyle approaches such as healthful dietary habits, weight management, and physical activity may also contribute to risk-reduction. We conducted a systematic review of evidence related to dietary habits, weight status/change, and physical activity on ovarian and breast cancer risk among women with BRCA1/2 pathogenic variants.

Methods

We searched Medline, EMBASE, CENTRAL, PubMed, and clinicaltrials.gov up to October 3, 2019. We identified 2775 records and included 21.

Results

There is limited evidence related to these factors and ovarian cancer risk. For breast cancer risk, evidence suggests higher diet quality, adulthood weight-loss of ≥10 pounds, and activity during adolescence and young-adulthood may be linked with decreased risk. Higher meat intake and higher daily energy intake may be linked with increased risk.

Conclusions

There is not enough evidence to suggest tailored recommendations for dietary habits or weight management among women with BRCA1/2 pathogenic variants compared to the general population for ovarian and breast cancer risk-reduction, and physical activity recommendations should remain the same.