bluuebunny/crossref_metadata_2025 huggingface dataset:
1.5 T MR-guided and daily adapted SBRT for prostate cancer: feasibility, preliminary clinical tolerability, quality of life and patient-reported outcomes during treatment
Authors: Alongi Filippo , Rigo Michele , Figlia Vanessa , Cuccia Francesco , Giaj-Levra Niccolò , Nicosia Luca , Ricchetti Francesco , Sicignano Gianluisa , De Simone Antonio , Naccarato Stefania , Ruggieri Ruggero , Mazzola Rosario
Published: March 2020

Background

Unity Elekta is a unique magnetic resonance (MR)-linac that conjugates a 1.5 Tesla MR unit with a 7 MV flattening filter free accelerator.A prospective observational study for the clinical use of Elekta Unity is currently ongoing in our department. Herein, we present our preliminary report on the feasibility, quality of life, and patient-reported outcomes measures (PROMs) for localized prostate cancer (PC) treated with stereotactic body radiotherapy (SBRT).

Methods

The SBRT protocol consisted of a 35 Gy schedule delivered in 5 fractions within 2 weeks. Toxicity and quality of life (QoL) were assessed at baseline and after treatment using the Common Terminology Criteria for Adverse Events v5.0, International Prostatic Symptoms Score (IPSS), ICIQ-SF, IIEF-5, and EORTC-QLQ-C30 and PR-25 questionnaires.

Results

Between October 2019 and January 2020, 25 patients with localized PC were recruited. The median age was 68 years (range, 54–82); 4 were low risk, 11 favorable intermediate risk (IR) and 10 unfavorable IR. Median iPSA was 6.8 ng/ml (range, 1–19), and 9 of these patients (36%) received concurrent androgen deprivation therapy. Median prostate volume was 36 cc (range, 20–61); median baseline IPSS was 5 (range, 0–10). Median time for fraction was 53 min (range, 34–86); adaptive strategy with daily critical structure and target re-contouring and daily replanning (adapt to shape) was performed in all cases. No grade ≥ 3 adverse event was observed, three patients (12%) reported grade 2 acute genitourinary toxicity (urinary frequency, urinary tract pain and urinary retention), while only one patient reported mild rectal pain. No relevant deteriorations were reported in PROMs.

Conclusion

To the best of our knowledge, this is the first experience reporting feasibility, clinician-reported outcome measurements, and PROMs for 1.5 T MR-guided adaptive SBRT for localized prostate cancer. The preliminary data collected here report optimal safety and excellent tolerability, as also confirmed by PROMs questionnaires. Moreover, the data on technical feasibility and timing of online daily adapted planning and delivery are promising. More mature data are warranted.

Trial registration

Date of approval April 2019 and numbered MRI/LINAC n°23,748.
Correction to: Serum exosomal-annexin A2 is associated with African-American triple-negative breast cancer and promotes angiogenesis
Authors: Chaudhary Pankaj , Gibbs Lee D. , Maji Sayantan , Lewis Cheryl M. , Suzuki Sumihiro , Vishwanatha Jamboor K.
Published: March 2020

After publication of the original article [1], we were notified that the wrong version of Fig. 2b has been published
Postoperative complications and mobilisation following major abdominal surgery with vs. without fitness tracker-based feedback (EXPELLIARMUS): study protocol for a student-led multicentre randomised controlled trial (CHIR-Net SIGMA study group)
Authors: Schwab Marius , Brindl Niall , Studier-Fischer Alexander , Tu Thomas , Gsenger Julia , Pilgrim Max , Friedrich Mirco , Frey Pia-Elena , Achilles Christina , Leuck Alexander , Bürgel Thore , Feisst Manuel , Klose Christina , Tenckhoff Solveig , Dörr-Harim Colette , Mihaljevic André L.
Published: March 2020

Background

Postoperative complications following major abdominal surgery are frequent despite progress in surgical technique and perioperative care. Early and enhanced postoperative mobilisation has been advocated to reduce postoperative complications, but it is still unknown whether it can independently improve outcomes after major surgery. Fitness trackers (FTs) are a promising tool to improve postoperative mobilisation, but their effect on postoperative complications and recovery has not been investigated in clinical trials.

Methods

This is a multicentre randomised controlled trial with two parallel study groups evaluating the efficacy of an enhanced and early mobilisation protocol in combination with FT-based feedback in patients undergoing elective major abdominal surgery. Participants are randomly assigned (1:1) to either the experimental group, which receives daily step goals and a FT giving feedback about daily steps, or the control group, which is mobilised according to hospital standards. The control group also receives a FT, however with a blackened screen; thus no FT-based feedback is possible. Randomisation will be stratified by type of surgery (laparoscopic vs. open). The primary endpoint of the study is postoperative morbidity within 30 days measured via the Comprehensive Complication Index. Secondary endpoints include number of steps as well as a set of functional, morbidity and safety parameters. A total of 348 patients will be recruited in 15 German centres. The study will be conducted and organised by the student-led German Clinical Trial Network SIGMA.

Discussion

Our study aims at investigating whether the implementation of a simple mobilisation protocol in combination with FT-based feedback can reduce postoperative morbidity in patients undergoing major abdominal surgery. If so, FTs would offer a cost-effective intervention to enhance postoperative mobilisation and improve patient outcomes.

Trial registration

Deutsches Register Klinischer Studien (DRKS, German Clinical Trials Register): DRKS00016755, UTN U1111-1228-3320. Registered on 06.03.2019.
Associations between sport participation and knee symptoms: a cross-sectional study involving 3053 undergraduate students
Authors: Chan Lloyd L. Y. , Wong Arnold Y. L. , Wang Maggie H.
Published: March 2020

Background

While a number of studies have investigated knee symptoms among elite athletes, few have directly compared the association between engagement in different sports and knee symptoms among young adults in the general population. The current study aimed to investigate the relation between sports participation hours, type/ number of sports engaged, self-rated competitiveness and knee symptoms among undergraduates.

Methods

Undergraduates were invited to participate in a self-administered online survey through invitation emails. Respondents were instructed to provide demographic information (e.g., age, gender, sports participation hours, types of engaged sports, self-rated competitiveness in sports and anxiety level etc.) and to report knee symptoms (current, the last 7 days, the last 12 months, and lifetime). Multiple logistic regressions were conducted to investigate the association between sports participation and current knee symptoms.

Results

Of 17,552 invitees, 3744 responded to the survey. Valid data from 3053 respondents was used for analysis. Forty-four percent of the respondents engaged in sports regularly (≥once per week). Running, cross-training and swimming were the most frequently participated sports among the respondents. The current prevalence rate of knee symptoms was 6.4%. Hours spent participating in combat sports, soccer, yoga, and basketball participation hours were significantly associated with current knee symptoms. Respondents who rated themselves as “competitive” demonstrated a higher risk of having current knee symptoms than “recreational” players. Number of engaged sports was not associated with current knee symptoms among undergraduates.

Conclusions

Certain sports types were associated with current knee symptoms. Compared to self-rated “recreational” players, self-rated “competitive” players were more likely to have current knee symptoms. Students should take preventive measures to minimize their risk of developing knee symptoms, especially when participating in combat sports, soccer, yoga, and basketball, or engaging in sports at a highly competitive level.
Development of microsatellite markers for three at risk tiger beetles Cicindela dorsalis dorsalis, C. d. media, and C. puritana
Authors: Aunins Aaron W. , Eackles Michael S. , Kazyak David C. , Drummond Michael R. , King Timothy L.
Published: March 2020

Objective

Tiger beetles inhabiting sandy beaches and cliffs along the east coast of the United States are facing increasing habitat loss due to erosion, urbanization, and sea level rise. The northeastern beach tiger beetle Cicindela dorsalis dorsalis and Puritan tiger beetle Cicindela puritana are both listed as threatened under the Endangered Species Act of 1973, while the white beach tiger beetle Cicindela dorsalis media is not listed but has been declining. Extirpation of these beetles, in some cases from entire states, has isolated many populations reducing gene flow and elevating the risk for the loss of genetic variation. To facilitate investigations of population genetic structure, we developed suites of microsatellite loci for conservation genetic studies.

Results

Shotgun genomic sequencing of all species identified thousands of candidate microsatellite loci, among which 17 loci were optimized and verified to cross-amplify within C. d. media and C. d. dorsalis, and eight separate loci were optimized for C. puritana. Most loci conformed to Hardy–Weinberg equilibrium, showed no evidence of linkage disequilibrium or null alleles, and revealed population genetic characteristics informative for natural resource managers among the populations tested.
Correction to: Predictors of survival of very preterm births (born between 23 and 29 weeks’ gestation) at a tertiary care center in Karachi, Pakistan: additional multivariate analyses on data from primary cohort
Authors: Yakoob Mohammad Yawar
Published: March 2020

For better clarity, the author would like to amend the title of the original article [1].
High-throughput proteomics fiber typing (ProFiT) for comprehensive characterization of single skeletal muscle fibers
Authors: Kallabis Sebastian , Abraham Lena , Müller Stefan , Dzialas Verena , Türk Clara , Wiederstein Janica Lea , Bock Theresa , Nolte Hendrik , Nogara Leonardo , Blaauw Bert , Braun Thomas , Krüger Marcus
Published: March 2020

Background

Skeletal muscles are composed of a heterogeneous collection of fiber types with different physiological adaption in response to a stimulus and disease-related conditions. Each fiber has a specific molecular expression of myosin heavy chain molecules (MyHC). So far, MyHCs are currently the best marker proteins for characterization of individual fiber types, and several proteome profiling studies have helped to dissect the molecular signature of whole muscles and individual fibers.

Methods

Herein, we describe a mass spectrometric workflow to measure skeletal muscle fiber type-specific proteomes. To bypass the limited quantities of protein in single fibers, we developed a Proteomics high-throughput fiber typing (ProFiT) approach enabling profiling of MyHC in single fibers. Aliquots of protein extracts from separated muscle fibers were subjected to capillary LC-MS gradients to profile MyHC isoforms in a 96-well format. Muscle fibers with the same MyHC protein expression were pooled and subjected to proteomic, pulsed-SILAC, and phosphoproteomic analysis.

Results

Our fiber type-specific quantitative proteome analysis confirmed the distribution of fiber types in the soleus muscle, substantiates metabolic adaptions in oxidative and glycolytic fibers, and highlighted significant differences between the proteomes of type IIb fibers from different muscle groups, including a differential expression of desmin and actinin-3. A detailed map of the Lys-6 incorporation rates in muscle fibers showed an increased turnover of slow fibers compared to fast fibers. In addition, labeling of mitochondrial respiratory chain complexes revealed a broad range of Lys-6 incorporation rates, depending on the localization of the subunits within distinct complexes.

Conclusion

Overall, the ProFiT approach provides a versatile tool to rapidly characterize muscle fibers and obtain fiber-specific proteomes for different muscle groups.
Botulinum toxin type A promotes microglial M2 polarization and suppresses chronic constriction injury-induced neuropathic pain through the P2X7 receptor
Authors: Gui Xianwei , Wang Hansen , Wu Lanxiang , Tian Sheng , Wang Xuan , Zheng Heqing , Wu Wei
Published: March 2020

Background

Switching microglial polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype represents a novel therapeutic strategy for neuropathic pain (NP). This study aims to investigate whether botulinum toxin type A (BTX-A) regulates microglial M1/M2 polarization by inhibiting P2X7 expression in a rat model of NP.

Results

The BTX-A administration elevated pain threshold, induced microglial polarization toward the M2 phenotype, and decreased P2X7 protein level in a rat model of NP induced by chronic compression injury (CCI). Lipopolysaccharide (LPS) was used to activate HAPI rat microglial cells as an in vitro inflammatory model and we demonstrated that BTX-A promoted microglial M2 polarization in LPS-stimulated HAPI microglial cells through suppressing P2X7.

Conclusions

Our results indicate that BTX-A promotes microglial M2 polarization and suppresses CCI-induced NP through inhibiting P2X7 receptor. These findings provide new insights into the mechanism of BTX-A in relieving NP.
Robust head pose estimation based on key frames for human-machine interaction
Authors: Madrigal Francisco , Lerasle Frederic
Published: March 2020

Humans can interact with several kinds of machine (motor vehicle, robots, among others) in different ways. One way is through his/her head pose. In this work, we propose a head pose estimation framework that combines 2D and 3D cues using the concept of key frames (KFs). KFs are a set of frames learned automatically offline that consist the following: 2D features, encoded through Speeded Up Robust Feature (SURF) descriptors; 3D information, captured by Fast Point Feature Histogram (FPFH) descriptors; and target’s head orientation (pose) in real-world coordinates, which is represented through a 3D facial model. Then, the KF information is re-enforced through a global optimization process that minimizes error in a way similar to bundle adjustment. The KF allows to formulate, in an online process, a hypothesis of the head pose in new images that is then refined through an optimization process, performed by the iterative closest point (ICP) algorithm. This KF-based framework can handle partial occlusions and extreme rotations even with noisy depth data, improving the accuracy of pose estimation and detection rate. We evaluate the proposal using two public benchmarks in the state of the art: (1) BIWI Kinect Head Pose Database and (2) ICT 3D HeadPose Database. In addition, we evaluate this framework with a small but challenging dataset of our own authorship where the targets perform more complex behaviors than those in the aforementioned public datasets. We show how our approach outperforms relevant state-of-the-art proposals on all these datasets.
Temporal trend of research related to gun violence from 1981 to 2018 in the United States: a bibliometric analysis
Authors: Chien Lung-Chang , Gakh Maxim , Coughenour Courtney , Lin Ro-Ting
Published: March 2020

Background

We aimed to evaluate the variation in gun violence-related research in the US over time to determine if there are meaningful changes in frequency of research at certain time points. Related publications were searched from the Web of Science.

Methods

We searched articles from Web of Science to collect publication data of gun violence research in three disciplines (clinical sciences, life sciences, and social behavior sciences) from 1981 to 2018. The joinpoint regression approach was applied to evaluate the trend of publication ratio. We also adopted the generalized additive mixed model to compare the publication ratio among the three research disciplines.

Results

During the study period, each research discipline had a significant decrease in publication ratios, especially social behavioral sciences from 2001 to 2011, with an annual percentage change = − 9.77% (95% CI = − 13.45, − 5.93; p-value < .0001). After combining the three research disciplines, the average change of the publication ratio was significantly increased 9.18% (95% CI = 6.42, 12.01; p-value < .0001) per year from 1981 to 2018. Compared to social behavioral sciences, both clinical sciences and life sciences had a significantly smaller publication ratio.

Conclusions

Gun violence research exhibited a significant downward trend in publications in the early 2000s, which may be attributed at least in part to limited federal funding, but the publication ratio increased since the 2010s. To enhance the amount of peer-reviewed gun violence research so that research-informed gun violence interventions are more likely to succeed, decision-makers should keep supporting quality research.
Comparison of estimators of variance for forest inventories with systematic sampling - results from artificial populations
Authors: Magnussen Steen , McRoberts Ronald E. , Breidenbach Johannes , Nord-Larsen Thomas , Ståhl Göran , Fehrmann Lutz , Schnell Sebastian
Published: March 2020

Background

Large area forest inventories often use regular grids (with a single random start) of sample locations to ensure a uniform sampling intensity across the space of the surveyed populations. A design-unbiased estimator of variance does not exist for this design. Oftentimes, a quasi-default estimator applicable to simple random sampling (SRS) is used, even if it carries with it the likely risk of overestimating the variance by a practically important margin. To better exploit the precision of systematic sampling we assess the performance of five estimators of variance, including the quasi default. In this study, simulated systematic sampling was applied to artificial populations with contrasting covariance structures and with or without linear trends. We compared the results obtained with theSRS, Matérn’s, successive difference replication, Ripley’s, and D’Orazio’s variance estimators.

Results

The variances obtained with the four alternatives to theSRSestimator of variance were strongly correlated, and in all study settings consistently closer to the target design variance than the estimator forSRS. The latter always produced the greatest overestimation. In populations with a near zero spatial autocorrelation, all estimators, performed equally, and delivered estimates close to the actual design variance.

Conclusion

Without a linear trend, theSDRandDORestimators were best with variance estimates more narrowly distributed around the benchmark; yet in terms of the least average absolute deviation, Matérn’s estimator held a narrow lead. With a strong or moderate linear trend, Matérn’s estimator is choice. In large populations, and a low sampling intensity, the performance of the investigated estimators becomes more similar.
Promoter tools for further development of Aspergillus oryzae as a platform for fungal secondary metabolite production
Authors: Umemura Maiko , Kuriiwa Kaoru , Dao Linh Viet , Okuda Tetsuya , Terai Goro
Published: March 2020

Background

The filamentous fungusAspergillus oryzaeis widely used for secondary metabolite production by heterologous expression; thus, a wide variety of promoter tools is necessary to broaden the application of this species. Here we built a procedure to surveyA. flavusgenes constitutively highly expressed in 83 transcriptome datasets obtained under various conditions affecting secondary metabolite production, to find promoters useful for heterologous expression of genes inA. oryzae.

Results

To test the ability of the promoters of the top 6 genes to induce production of a fungal secondary metabolite, ustiloxin B, we inserted the promoters before the start codon ofustR, which encodes the transcription factor of the gene cluster responsible for ustiloxin B biosynthesis, inA. oryzae. Four of the 6 promoters induced ustiloxin B production in all tested media (solid maize, liquid V8 and PDB media), and alsoustRexpression. Two of the 4 promoters were those oftef1andgpdA, which are well characterized inA. oryzaeandA. nidulans, respectively, whereas the other two, those of AFLA_030930 and AFLA_113120, are newly reported here and show activities comparable to that of thegpdApromoter with respect to induction of gene expression and ustiloxin B production.

Conclusion

We newly reported two sequences as promoter tools for secondary metabolite production inA. oryzae. Our results demonstrate that our simple strategy of surveying for constitutively highly expressed genes in large-scale transcriptome datasets is useful for finding promoter sequences that can be used as heterologous expression tools inA. oryzae.
Bringing technology to the mature classroom: age differences in use and attitudes
Authors: Staddon Rachel V.
Published: March 2020

Mature students are anecdotally thought to be more anxious about technology than younger students, to the extent that they avoid using technology. This is a problem in today’s higher education classrooms which often use a range of learning technologies, particularly as cohorts are becoming more and more likely to contain mature students. Previous work examining the attitudes of mature students to technology no longer reflects contemporary student age profiles or the current technological landscape. This study asks whether modern mature students in a UK university have more negative attitudes towards technology than younger students, and whether their usage of technology is different. A new diagnostic instrument, the Technology Attitudes Questionnaire, was developed to determine how students use technology for course activities and personal use, and their attitudes towards technology more generally. It was found that mature students use fewer technologies than younger students and use them less frequently, but have used them for a longer period over their lives. No difference was found for attitudes towards technology between the mature and younger groups. This research aims to contribute to the wider field of technology attitudes and use, particularly for the modern mature student cohort. These findings can be used to inform how educators design learning resources and use technology on their courses, working towards an age-inclusive programme.
Autologous cell-free serum preparations in the management of knee osteoarthritis: what is the current clinical evidence?
Authors: Angadi Darshan S. , Macdonald Hamish , Atwal Navraj
Published: March 2020

Background

There is paucity in the current literature regarding clinical outcomes of autologous cell-free serum preparations. The objective of this paper is to collate the clinical evidence and review the results of intraarticular injections of autologous cell-free serum preparations in the management of knee osteoarthritis (OA).

Methods

A comprehensive English literature search was undertaken using the healthcare database website (https://hdas.nice.org.uk/). The PubMed, Medline, CINAHL, Embase and the Cochrane library databases were searched to identify all studies of autologous protein solution/autologous conditioned serum (ACS/APS) in the management of knee OA. We evaluated the reported clinical outcomes with respect to pain, function, morbidity, adverse effects and complications.

Results

Fifteen relevant articles were identified in the current literature. Outcomes following injection of ACS/APS have been reported in patients with age range (34–87 years) and unilateral or bilateral knee OA. Seven studies reported improvement in visual analog scale (VAS) whereas the Western Ontario and McMaster Universities osteoarthritis instrument (WOMAC) score improved in nine studies. Considerable variation was noted in the injection technique and duration of post-procedure assessment with only one study reporting long-term follow-up beyond 24 months. Joint swelling and injection-site pain were reported to be the most common complications; only one study reported a case of septic arthritis. However, no evidence is available to clearly identify factors that may predict the outcomes following this procedure.

Conclusion

Current data from the clinical studies would suggest that the intraarticular administration of autologous cell-free serum preparations, such as ACS/APS, in patients with knee OA may improve pain and function, with limited morbidity. High-quality clinical trials with stratified patient cohorts, longer follow-up duration and robust reporting of outcome measures are essential to improve the understanding of the indications and clinical effectiveness of these novel products.
Acute appendicitis within incisional hernia sac: a unique case report
Authors: Issa Mohamed G.
Published: March 2020

Background

Incisional hernia appendicitis is a rare form in which the vermiform appendix is located within the hernial sac. It is seen in less than 1% of inguinal hernia. Most often, the cases are misdiagnosed as incarcerated or strangulated hernia.

Case presentation

A 59-year-old female with history of hysterectomy 10 days ago for fibroid, came to the emergency department with diffuse abdominal pain and severe vomiting and absolute constipation for 3 days. Abdominal U/S was done and revealed inflamed fat within the hernia sac along with minimal collection. A defect was seen at the anterior abdominal wall measuring about 2.4 cm passing bowel loops and collection. CT scan with IV contrast revealed an inflamed appendix passing through the incisional hernia.

Conclusions

Appendicitis within a hernia sac is unusual with the incidence being 0.13% of all acute appendicitis. Acute hernia appendicitis is almost never been diagnosed prior to surgery. Most often, the diagnosis is incarcerated or strangulated hernia. The differential diagnosis should include hernia sac appendicitis for patients with signs of inflammatory process ongoing at the hernia sac.
Deterioration mechanism of steam-cured concrete subjected to coupled environmental acid and drying action
Authors: Long Guangcheng , Xie Youjun , Luo Zhiyu , Qu Lu , Zhou John L. , Li Wengui
Published: March 2020

In order to investigate the deterioration mechanism of steam-cured concrete under severe environmental actions such as acid rain corrosion, salt corrosion, and cyclic thermal loading, accelerated corrosion tests were conducted in this study. Surface damage as well as deteriorative kinetics of steam-cured concrete and cement paste suffering from coupled acid-thermal actions was investigated by soaking-drying cycle experiments. The effects of mineral admixture, curing regime and corrosion condition on the durability were all comparatively studied, and the X-ray diffractograms and nanoindentation were applied to analyse the mechanism of corrosion deterioration. The results revealed that compared with the cementitious materials under standard curing, larger depth and faster corrosion were observed for steam-cured concrete and cement paste, which might be partly attributed to the lower content of hydrated production presented in steam-cured specimens. Besides, under acid solution soaking-drying cycle regime, there was significant higher corrosion depth compared to only soaking in acid solution. The corrosion depth under steam curing and soaking-drying condition increased by 156.68% and 44.17%, respectively, compared with those under standard curing and only soaking treatment. In addition, fly ash effectively decreased the corrosion depth of steam-cured cement paste and concrete by 64.98% and 16.33%, respectively.
Keeping the brain in mind: why neuroscience matters to 21st-century psychiatrists
Authors: Tracy Derek K.
Published: March 2020

Psychiatry intertwines mind and brain, sometimes in a strained marriage. Psychiatrists feel the criticism of a ‘narrow’ biological or medical (and medication) focus, and we are very aware of the limitations of all treatments and diagnostic systems. Many understandably move towards a more social approach, seeing individuals in their wider lives. But there are dangers in losing the brain, something unique to our specialty in the world of mental health. This reflective piece calls for us to rediscover the joy of the science of the brain, which augments, not conflicts with, psychosocial approaches.
The link between formal thought disorder and social functioning in schizophrenia: A meta-analysis
Authors: Marggraf Matthew P. , Lysaker Paul H. , Salyers Michelle P. , Minor Kyle S.
Published: March 2020

Background.

Formal thought disorder (FTD) and social functioning impairments are core symptoms of schizophrenia. Although both have been observed for over a century, the strength of the relationship between FTD and social functioning remains unclear. Furthermore, a variety of methodological approaches have been used to assess these constructs—which may contribute to inconsistency in reported associations. This meta-analysis aimed to: (a) systematically test the relationship between FTD and social functioning and (b) determine if the methodology used to assess FTD and/or social functioning moderates this relationship.

Methods.

Following Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines, a targeted literature search was conducted on studies examining the relationship between FTD and social functioning. Correlations were extracted and used to calculate weighted mean effect sizes using a random effects model.

Results.

A total of 1,478 participants across 13 unique studies were included in this meta-analysis. A small-medium inverse association (r = −0.23, p < 0.001) was observed between FTD and social functioning. Although heterogeneity analyses produced a significant Q-statistic (Q = 52.77, p = <0.001), the relationship between FTD and social functioning was not moderated by methodology, study quality, demographic variables, or clinical factors.

Conclusions.

Findings illustrate a negative association between FTD and social functioning. Despite differences in the methodological approach used and type of information assessed, measurement type and clinical factors did not moderate the relationship between FTD and social functioning. Future studies should explore whether other variables, such as cognitive processes (e.g., social cognition), may account for variability in associations between these constructs.
Abnormal expression of GABAA receptor sub-units and hypomotility upon loss of gabra1 in zebrafish
Authors: Reyes-Nava Nayeli , Yu Hung-Chun , Coughlin Curtis R. , Shaikh Tamim H. , Quintana Anita M.
Published: March 2020

We used whole exome sequencing (WES) to determine the genetic etiology of a patient with a multi-system disorder characterized by a seizure phenotype. WES identified a heterozygous de novo missense mutation in the GABRA1 gene (c.875C>T). GABRA1 encodes the alpha subunit of the Gamma-Aminobutyric Acid receptor A (GABAAR). The GABAAR is a ligand gated ion channel that mediates the fast inhibitory signals of the nervous system and mutations in the sub-units that compose the GABAAR have been previously associated with human disease. To understand the mechanisms by which GABRA1 regulates brain development, we developed a zebrafish model of gabra1 deficiency. gabra1 expression is restricted to the nervous system and behavioral analysis of morpholino injected larvae suggests that the knockdown of gabra1 results in hypoactivity and defects in the expression of other sub-units of the GABAAR. Expression the human GABRA1 protein in morphants partially restored the hypomotility phenotype. In contrast, the expression of the c.875C>T variant did not restore these behavioral deficits. Collectively, these results represent a functional approach to understand the mechanisms by which loss of function alleles cause disease.
β1 integrin-mediated signaling regulates MT1-MMP phosphorylation to promote tumor cell invasion
Authors: Grafinger Olivia R. , Gorshtein Genya , Stirling Tyler , Brasher Megan I. , Coppolino Marc G.
Published: March 2020

Malignant cancer cells can invade extracellular matrix (ECM) through the formation of F-actin-rich subcellular structures termed invadopodia. ECM degradation at invadopodia is mediated by matrix metalloproteinases (MMPs), and recent findings indicate that membrane-anchored membrane type 1-matrix metalloproteinase (MT1-MMP, also known as MMP14) has a primary role in this process. Maintenance of an invasive phenotype is dependent on internalization of MT1-MMP from the plasma membrane and its recycling to sites of ECM remodeling. Internalization of MT1-MMP is dependent on its phosphorylation, and here we examine the role of β1 integrin-mediated signaling in this process. Activation of β1 integrin using the antibody P4G11 induced phosphorylation and internalization of MT1-MMP and resulted in increased cellular invasiveness and invadopodium formation in vitro. We also observed phosphorylation of Src and epidermal growth factor receptor (EGFR) and an increase in their association in response to β1 integrin activation, and determined that Src and EGFR promote phosphorylation of MT1-MMP on Thr567. These results suggest that MT1-MMP phosphorylation is regulated by a β1 integrin-Src-EGFR signaling pathway that promotes recycling of MT1-MMP to sites of invadopodia formation during cancer cell invasion.

This article has an associated First Person interview with the first author of the paper.
The variable presence of apoptosis in the testes of diploid and sterile allotetraploid Cobitis (Teleostei, Cobitidae) males during reproductive cycle
Authors: Jablonska Olga , Juchno Dorota , Leska Anna , Kowalewska Karolina , Boroń Alicja
Published: March 2020

Cobitis species exist in diploid populations, but mostly they occur in diploid-polyploid (d-p) ones. They are considered an important model organism to study biology and physiology of natural hybrid and polyploid vertebrates. Indeed, polyploidization causes a huge stress for the cell physiology and alter spermatogenesis in polyploid fish. The most extensively studied modes of germ cell death during spermatogenesis in vertebrates is apoptosis. The aim of the study was to examine the caspase-3 immunoexpression in the testes of Cobitis taenia from diploid population as well as C. taenia and sterile tetraploid Cobitis from d-p population before, during and after spawning. The obtained results suggest a different performance of apoptosis in testes of C. taenia from both studied populations and seems to be conditioned by their role as the only sperm donors in d-p populations. Moreover, apoptosis was active cell death process in the testes of tetraploid Cobitis.
The role of stationary intraoral tomosynthesis in reducing proximal overlap in bitewing radiography
Authors: Mauriello Sally M , Broome Angela M , Platin Enrique , Mol André , Inscoe Christina , Lu Jianping , Zhou Otto , Moss Kevin
Published: March 2020

Objectives:

This study examined the utility of stationary intraoral tomosynthesis (s-IOT) in opening proximal contacts in bitewing radiography.

Methods:

11 DENTSPLY Rinn Dental X-ray Teaching and Training Replica mannequins (Model #546002, Elgin, Ill) were imaged with a prototype s-IOT device (Surround Medical Systems, Morrisville, NC) and standard bitewing (SBW) technique. Premolar and molar bitewings were acquired with each system. Image receptor holders were used to position receptors and aid in the alignment of the position indicating devices. An expert operator (having more than 5 years of experience in intraoral radiography) acquired the images with the s-IOT prototype and standard intraoral X-ray devices. Images were assessed to analyze percentage overlap of the proximal surfaces using the tools available in ImageJ (NIH, Bethesda Maryland).

Results:

253-paired surfaces were included in the analysis. The difference in overlap was statistically significant with standard bitewing (SBW) images resulting in a median overlap of 13%, a minimum of 0%, a maximum of 100% and an interquartile range of 40%. s-IOT resulted in a median overlap of 1%, a minimum of 0%, a maximum of 37% and an interquartile range of 0%. The s-IOT prototype substantially reduced proximal surface overlap compared to conventional bitewing radiography.

Conclusions:

The use of s-IOT reduced proximal contact overlap compared to standard bitewing radiography for an experienced radiographer. Stationary intraoral tomosynthesis may be a potential alternative to SBW radiography, reducing the number of retakes due to closed contacts.
Medical applications based on nanotechnology
Authors: Manaj L. , Johnson L. , Punz E. , Joubert I.A. , Geppert M. , Geppert M. , Himly M.
Published: March 2020

Poly-lactic-co-glycolic acid can form nanoparticles whic can be applied in nanomedicine as delivery vehicle for therapeutic agents. Gere the aim is to reduce negative side-effects and to pbtain higher local concentration at the site of action. This work is about determining the biding-capacity of PLGA nanoparticles to several substances, applying a small set of model proteins. Our aim was to find out, whether PLGA nanoparticles can transport drygs in order to make drug targeting in medicine easier. This would show us a new scetion of medicine with new ways of therapy methods.
Medical applications based on nanotechnology
Authors: Manaj L. , Johnson L. , Punz E. , Joubert I.A. , Geppert M. , Himly M.
Published: March 2020

Poly-lactic-co-glycolic acid can form nanoparticles which can be applied in nanomedicine as delivery vehicle for therapeutic agents. Here the aim is to reduce negative side-effects and to obtain higher local concentrations at the site of action. This work is about determining the binding-capacity of PLGA nanoparticles to several substances, applying a small set of model proteins. Our aim was to find out, whether PLGA nanoparticles can transport drugs in order to make drug targeting in medicine easier. This would show us a new section of medicine with new ways of therapy methods.
Nanomedicine
Authors: Winkler L. , Woess I. , Joubert I.A. , Geppert M. , Himly M.
Published: March 2020

Important and life-sustaining processes such as teh uptake, transport and metabolism of biologicla substances take place on cellular level in the human body. Diseases and disorders happening on this level can now be targeted with diagnostic and threapeutic tools in the nano-scaled size range.
Controlled administration of cannabis to mitigate cannabis-attributable harm among recreational users: a quasi-experimental study in Germany
Authors: Manthey Jakob , Kalke Jens , Rehm Jürgen , Rosenkranz Moritz , Verthein Uwe
Published: March 2020

Background:New approaches are required to slow down or reverse increasing trends of levels of delta-9-tetrahydrocannabinol (THC) and cannabis-attributable hospitalizations in Germany. Legal access to cannabis may constitute one viable effective policy response; however, available evidence does not suffice to inform a regulation model for Germany. The proposed study aims to reduce harm for cannabis users through legal access to herbal cannabis through pharmacies.

Protocol:A quasi-experimental study comparing cannabis users with legal access to herbal cannabis (Berlin, intervention group) to those without legal access (Hamburg, control group) (total N=698). As the primary outcome, we hypothesize that: 1) illegal THC consumption will reduce by at least 50% in the intervention group and 2) total THC exposure in the intervention group will be reduced by at least 10% lower than that of the control group, taking into account baseline values. Secondary outcomes comprise measures of frequency of use, THC-impaired driving, and mode of administration. Paired t-tests and multilevel regression models will be performed for statistical analyses.

Discussion:This study proposal is currently being reviewed by the ‘Federal Institute for Drugs and Medical Devices’ – the body responsible for approving research studies on classified substances, including cannabis. Upon approval and prior to the start of the study, a full ethical review will be undertaken. Results may inform a regulation model for Germany and other jurisdictions and are expected to deepen the understanding of the effects of legal access to cannabis.

Pre-registration:German Clinical Trials Register (DRKS), DRKS00020829
Accuracy of short tandem repeats genotyping tools in whole exome sequencing data
Authors: Halman Andreas , Oshlack Alicia
Published: March 2020

Background: Short tandem repeats are an important source of genetic variation. They are highly mutable and repeat expansions are associated dozens of human disorders, such as Huntington's disease and spinocerebellar ataxias. Technical advantages in sequencing technology have made it possible to analyse these repeats at large scale; however, accurate genotyping is still a challenging task. We compared four different short tandem repeats genotyping tools on whole exome sequencing data to determine their genotyping performance and limits, which will aid other researchers in choosing a suitable tool and parameters for analysis.

Methods: The analysis was performed on the Simons Simplex Collection dataset, where we used a novel method of evaluation with accuracy determined by the rate of homozygous calls on the X chromosome of male samples. In total we analysed 433 samples and around a million genotypes for evaluating tools on whole exome sequencing data.

Results: We determined a relatively good performance of all tools when genotyping repeats of 3-6 bp in length, which could be improved with coverage and quality score filtering. However, genotyping homopolymers was challenging for all tools and a high error rate was present across different thresholds of coverage and quality scores. Interestingly, dinucleotide repeats displayed a high error rate as well, which was found to be mainly caused by the AC/TG repeats. Overall, LobSTR was able to make the most calls and was also the fastest tool, while RepeatSeq and HipSTR exhibited the lowest heterozygous error rate at low coverage.

Conclusions: All tools have different strengths and weaknesses and the choice may depend on the application. In this analysis we demonstrated the effect of using different filtering parameters and offered recommendations based on the trade-off between the best accuracy of genotyping and the highest number of calls.
Determinan Keputusan Pekerja Mandiri menjadi Peserta Jaminan Kesehatan Nasional
Authors: Laila Jumatra , Ainy Asmaripa , Safriantini Dian
Published: March 2020

Background: National health insurance is mandatory for all Indonesians. In Ogan Ilir Regency, the lowest percentage (24,14%) of its participants in December 2016 was found in Indralaya Utara Sub-district, and self-employed participants in this sub-district were only 6,99%. This study aimed to analyze the determinants of the self-employed’s decision to become national health insurance participants in Indralaya Utara Sub-district. Method: This was a cross-sectional study. The population was self-employed in Indralaya Utara Sub-district. The sample was 108 respondents who were selected using cluster sampling and consecutive sampling techniques. Data analysis was conducted by univariate and bivariate with chi-square statistical test. Results: The results illustrated that 18,52% of respondents decided to become national health insurance participants. Variables with p-value<0,005 were: knowledge about national health insurance (p-value=0,011), trust (p-value=0.000), perception about national health insurance (p-value=0,000), attitude (p-value=0,000), income (p-value=0,002), family support (p-value=0,005). Variables with p-value≥0,005 were: education (p-value=0,234), perception about health facilities (p-value=0,162), distance to health facilities (p-value=0,355), health workers support (p-value=0,112). Conclusion:  In conclusion, percentage of self-employed who decided become national health insurance participants was still small. Associated factors to the decision of self-employed as participants were: knowledge about national health insurance, trust, perception about national health insurance, attitude, income and family support. It is suggested that the Social Security Administrative Body for Health should routinely conduct socialization on national health insurance to improve the percentage of its participation for self-employed and the benefits of national health insurance could be felt by the entire community.
Efektivitas Media Leaflet dan Film dalam Peningkatan Pengetahuan Pubertas di SMP N 226 Pondok Labu
Authors: Hadiwiardjo Yanti Harjiono , Asiyanto Mila Citrawati , Aprilia Citra Ayu
Published: March 2020

Background: Adolescent is a trantition phase from childhood to adulthood. Knowledge about puberty is important during this phase. If there is no sufficient information about it, it could cause several problems such as adolescence growth and development failure and healt problems. Health promotion to increase awareness of puberty is definitely needed by junior high students aged around 8 to 14 years old. Puberty health promotion could be delivered through visual media such as leaflet or audiovisual media such as animation film. The aim of this study was to discover effectivity of leaflet and animation film in increasing puberty awareness in students of Public Junior High School 226, Pondok Labu, South Jakarta. Method: This study was a quasi experiment with one group pre test-posttest design. Population of this study was whole students of 7th grade Public Junior High School 226. Sampling technique used was total sampling as many as 256 students. Data was analyzed by Wilcoxon test to find out effectivity of leaflet and animation film, meanwhile Mann Whitney test was used to discover effectivity between leaflet and animation film. Results: Both leaflet and animation film were effective to improving knowledge for adolescent (p-value<0,001). Conclusion: Either leaflet or animation film increased puberty awareness of students. There was no effectivity difference between both media in increasing puberty awareness of students at Public Junior High School 226.
Surgical treatment of symptomatic post-slipped capital femoral epiphysis deformity: A comparative study between hip arthroscopy and surgical hip dislocation with or without intertrochanteric osteotomy
Authors: Wylie James D. , McClincy Michael P. , Uppal Nishant , Miller Patricia E. , Kim Young-Jo , Millis Michael B. , Yen Yi-Meng , Novais Eduardo N.
Published: March 2020

Purpose

Our primary research question was to investigate the severity of deformity and articular damage as well as outcomes in patients undergoing hip arthroscopy compared with open surgery for the treatment of symptomatic slipped capital femoral epiphysis (SCFE) deformity.

Methods

Retrospective review of surgical treatment of symptomatic SCFE deformity with a minimum one-year follow-up. Patients were divided into three groups: the arthroscopic group, surgical hip dislocation(SHD) group and SHD with femoral osteotomy (SHD+ITO) group. Deformity severity was quantified. Hip outcome was assessed by the modified Merle d'Aubigné Postel (MDP) scores.

Results

There were more severe slips treated by SHD and SHD+ITO. There was more severe deformity in the SHD+ITO group than the arthroscopy group (p < 0.001). There were more full thickness acetabular cartilage defects in the SHD and the SHD+ITO groups (> 40%) compared with the arthroscopy group (11%; p = 0.03). The SHD+ITO and SHD group had lower MDP scores compared with the arthroscopy group both before and after surgery but no difference was detected in the amount of improvement from surgery across groups (p > 0.05). Moderate and severe SCFEs had worse preoperative scores but improvement was not different compared with mild SCFEs (p > 0.05).

Conclusion

Patients undergoing open treatment had more severe SCFE deformity with more extensive articular damage at reconstructive surgery compared with patients undergoing arthroscopy. All groups with SCFE deformity had improved pain and hip function postoperatively.

Level of Evidence

III