bluuebunny/crossref_metadata_2025 huggingface dataset:
Trajectories of physical activity, from young adulthood to older adulthood, and pancreatic cancer risk; a population-based case-control study in Ontario, Canada
Authors: Sandhu Jaspreet , De Rubeis Vanessa , Cotterchio Michelle , Smith Brendan T. , Griffith Lauren E. , Brenner Darren R. , Borgida Ayelet , Gallinger Steven , Cleary Sean , Anderson Laura N.
Published: February 2020

Background

There is inconsistent evidence on the association between physical activity and pancreatic cancer risk and few studies have investigated early life or life-course physical activity. The objective of this study was to evaluate the association between trajectories of physical activity across the life-course and pancreatic cancer risk.

Methods

A population-based case-control study was conducted (2011–2013) using cases (n = 315) from the Ontario Pancreas Cancer Study and controls (n = 1254) from the Ontario Cancer Risk Factor Study. Self-reported recall of moderate and vigorous physical activity was measured at three time points: young adulthood (20s–30s), mid-adulthood (40s–50s) and older-adulthood (1 year prior to questionnaire completion). Physical activity trajectories were identified using latent class analysis. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from multivariable logistic regression adjusted for covariates: age, sex, race, alcohol, smoking, vegetable, fruit and meat consumption, and family history of pancreatic cancer.

Results

Six life-course physical activity trajectories were identified: inactive at all ages (41.2%), low activity at all ages (31.9%), increasingly active (3.6%), high activity in young adulthood with substantial decrease (13.0%), high activity in young adulthood with slight decrease (5.0%), and persistent high activity (5.3%). Compared to the inactive at all ages trajectory, the associations between each trajectory and pancreatic cancer after confounder adjustment were: low activity at all ages (OR: 1.11; 95% CI: 0.75, 1.66), increasingly active (OR: 1.11; 95% CI: 0.56, 2.21), high activity in young adulthood with substantial decrease in older adulthood (OR: 0.76; 95% CI: 0.47, 1.23), high activity in young adulthood with slight decrease in older adulthood (OR: 0.98; 95% CI: 0.62, 1.53), and persistently high activity (OR: 1.50; 95% CI: 0.86, 2.62). When time periods were evaluated separately, the OR for the association between high moderate activity in the 20s–30s and pancreatic cancer was 0.89 (95% CI: 0.64, 1.25) and some sex differences were observed.

Conclusion

Distinct life-course physical activity trajectories were identified, but there was no evidence that any of the trajectories were associated with pancreatic cancer. Future studies with larger sample sizes are needed to understand the associations between physical activity trajectories over the life-course and pancreatic cancer risk.
Temporal association between serious bleeding and immunization: vitamin K deficiency as main causative factor
Authors: Susanah Susi , Fadlyana Eddy , Dhamayanti Meita , Tarigan Rodman , Ariyanto Eko Fuji , Pamela Yunisa , Ismoetoto Yuzar I. B. , Sri Rita Verita , Hasna Monika , Rusmil Kusnandi
Published: February 2020

Background

Bleeding as an adverse event following immunization (AEFI) that is rarely reported in children, although it can be a parental concern. Bleeding episodes ranging in severity from mild to severe and defined as any external and/or internal bleeding can be caused by acquired or hereditary disorders. This study analyzes whether bleeding episodes in children that were recorded as AEFIs are causally associated with immunization and elaborates their etiology.

Methods

A cross-sectional study of 388 AEFI cases in children from West Java Provincial Committee in Indonesia confirmed by case findings from 2000 until 2017.

Results

Of the total number of cases studied, 55 (14%) involved children aged 5 days to 12 years who presented with bleeding and were referred to a provincial hospital. Analysis revealed that 32 cases were most likely caused by acquired prothrombin complex deficiency (APCD) and 30 of these APCD cases were strongly suspected to be manifestations of vitamin K deficiency bleeding (VKDB). All VKDB subjects were aged 5 days to 3 months without a history of administration of prophylactic vitamin K. When a World Health Organization classification was used, most bleeding cases in this study became coincidental events with a temporal association with immunization. A causality assessment suggested that these cases were causally unrelated.

Conclusion

Most cases of bleeding reported as an AEFI were found to be VKDB, which is considered a coincidental event following immunization with a temporal association, and an unrelated category based on the results of a causality assessment. Vitamin K should be administered to all newborns as a prophylactic and AEFI surveillance should be improved based on the low numbers of AEFI reported in Indonesia.
Different domains of self-reported physical activity and risk of type 2 diabetes in a population-based Swedish cohort: the Malmö diet and Cancer study
Authors: Mutie Pascal M. , Drake Isabel , Ericson Ulrika , Teleka Stanley , Schulz Christina-Alexandra , Stocks Tanja , Sonestedt Emily
Published: February 2020

Background

While a dose-response relationship between physical activity and risk of diabetes has been demonstrated, few studies have assessed the relative importance of different measures of physical activity on diabetes risk. The aim was to examine the association between different self-reported measures of physical activity and risk of type 2 diabetes in a prospective cohort study.

Methods

Out of 26,615 adults (45–74 years, 60% women) in the population-based Swedish Malmö Diet and Cancer Study cohort, 3791 type 2 diabetes cases were identified from registers during 17 years of follow-up. Leisure-time (17 activities), occupational and domestic physical activity were assessed through a questionnaire, and these and total physical activity were investigated in relation to type 2 diabetes risk.

Results

All physical activity measures showed weak to modest associations with type 2 diabetes risk. The strongest association was found in the lower end of leisure-time physical activity in dose-response analysis at levels approximately below 22 MET-hrs/week (300 min/week) representing around 40% of the population. Compared with the lowest quintile, the moderate leisure-time physical activity category had a 28% (95% CI: 0.71, 0.87) decreased risk of type 2 diabetes. Total physical activity showed a similar, but weaker, association with diabetes risk as to that of leisure-time physical activity. Domestic physical activity was positively and linearly related to diabetes risk, HR = 1.11 (95% CI: 0.99, 1.25) comparing highest to lowest quintile. There was no association between occupational physical activity and diabetes risk.

Conclusion

A curvilinear association was observed between leisure-time physical activity and risk of diabetes. Beyond a threshold level of approximately 22 MET-hrs/week or 300 min/week, no additional risk reduction was observed with increase in physical activity.
Biomechanical evaluation of strategies for adjacent segment disease after lateral lumbar interbody fusion: is the extension of pedicle screws necessary?
Authors: Liang Ziyang , Cui Jianchao , Zhang Jiarui , He Jiahui , Tang Jingjing , Ren Hui , Ye Linqiang , Liang De , Jiang Xiaobing
Published: February 2020

Background

Adjacent segment disease (ASD) is a well-known complication after interbody fusion. Pedicle screw-rod revision possesses sufficient strength and rigidity. However, is a surgical segment with rigid fixation necessary for ASD reoperation? This study aimed to investigate the biomechanical effect of different instrumentation on lateral lumbar interbody fusion (LLIF) for ASD treatment.

Methods

A validated L2~5 finite element (FE) model was modified for simulation. ASD was considered the level cranial to the upper-instrumented segment (L3/4). Bone graft fusion in LLIF with bilateral pedicle screw (BPS) fixation occurred at L4/5. The ASD segment for each group underwent a) LLIF + posterior extension of BPS, b) PLIF + posterior extension of BPS, c) LLIF + lateral screw, and d) stand-alone LLIF. The L3/4 range of motion (ROM), interbody cage stress and strain, screw-bone interface stress, cage-endplate interface stress, and L2/3 nucleus pulposus of intradiscal pressure (NP-IDP) analysis were calculated for comparisons among the four models.

Results

All reconstructive models displayed decreased motion at L3/4. Under each loading condition, the difference was not significant between models a and b, which provided the maximum ROM reduction (73.8 to 97.7% and 68.3 to 98.4%, respectively). Model c also provided a significant ROM reduction (64.9 to 77.5%). Model d provided a minimal restriction of the ROM (18.3 to 90.1%), which exceeded that of model a by 13.1 times for flexion-extension, 10.3 times for lateral bending and 4.8 times for rotation. Model b generated greater cage stress than other models, particularly for flexion. The maximum displacement of the cage and the peak stress of the cage-endplate interface were found to be the highest in model d under all loading conditions. For the screw-bone interface, the stress was much greater with lateral instrumentation than with posterior instrumentation.

Conclusions

Stand-alone LLIF is likely to have limited stability, particularly for lateral bending and axial rotation. Posterior extension of BPS can provide reliable stability and excellent protective effects on instrumentation and endplates. However, LLIF with the use of an in situ screw may be an alternative for ASD reoperation.
Comprehensive assessment of knee joint synovitis at 7 T MRI using contrast-enhanced and non-enhanced sequences
Authors: Treutlein Christoph , Bäuerle Tobias , Nagel Armin M. , Guermazi Ali , Kleyer Arnd , Simon David , Schett Georg , Hepp Tobias , Uder Michael , Roemer Frank W.
Published: February 2020

Background

Seven T ultra-high field MRI systems have recently been approved for clinical use by the U.S. and European regulatory agencies. These systems are now being used clinically and will likely be more widely available in the near future. One of the applications of 7 T systems is musculoskeletal disease and particularly peripheral arthritis imaging. Since the introduction of potent anti-rheumatic therapies over the last two decades MRI has gained increasing importance particularly for assessment of disease activity in early stages of several rheumatic disorders. Commonly gadolinium-based contrast agents are used for assessment of synovitis. Due to potential side-effects of gadolinium non-enhanced techniques are desirable that enable visualization of inflammatory disease manifestations. The feasibility of 7 T MRI for evaluation of peripheral arthritis has not been shown up to now. Aim of our study was to evaluate the feasibility of contrast-enhanced (CE) and non-enhanced MRI at 7 T for the assessment of knee joint synovitis.

Method

Seven T MRI was acquired for 10 patients with an established diagnosis of psoriatic or rheumatoid arthritis. The study pulse sequence protocol was comprised of a sagittal intermediate-weighted fat-suppressed (FS), axial fluid-attenuated inversion recovery (FLAIR) FS, sagittal 3D T1-weighted dynamic contrast enhanced (DCE) and an axial static 2D T1-weighted FS contrast-enhanced sequence (T1-FS CE). Ordinal scoring on non-enhanced (Hoffa- and effusion-synovitis) and enhanced MRI (11-point synovitis score), and comparison of FLAIR-FS with static T1-FS CE MRI using semiquantitative (SQ) grading and volume assessment was performed. For inter- and intra-reader reliability assessment weighted kappa statistics for ordinal scores and intraclass correlation coefficients (ICC) for continuous variables were used.

Results

The total length of study protocol was 15 min 38 s. Different amounts of synovitis were observed in all patients (mild: n = 3; moderate: n = 5; severe: n = 2). Consistently, SQ assessment yielded significantly lower peripatellar summed synovitis scores for the FLAIR-FS sequence compared to the CE T1-FS sequence (p < 0.01). FLAIR-FS showed significantly lower peripatellar synovial volumes (p < 0.01) compared to CE T1-FS imaging with an average percentage difference of 18.6 ± 9.5%. Inter- and intra-reader reliability for ordinal SQ scoring ranged from 0.21 (inter-reader Hoffa-synovitis) to 1.00 (inter-reader effusion-synovitis). Inter- and intra-observer reliability of SQ 3D-DCE parameters ranged from 0.86 to 0.99.

Conclusions

Seven T FLAIR-FS ultra-high field MRI is a potential non-enhanced imaging method able to visualize synovial inflammation with high conspicuity and holds promise for further application in research endeavors and clinical routine by trained readers.
Does group cohesion foster self-directed learning for medical students? A longitudinal study
Authors: Kim Soyun , Yang Eunbae B.
Published: February 2020

Background

The importance of self-directed learning (SDL) and collaborative learning has been emphasized in medical education. This study examined if there were changes in the pattern of SDL and group cohesion from the time of admission to medical school under the criterion-referenced grading system, increased group activities, and interaction of medical education curriculum. Second, it was examined whether group cohesion influences self-directed learning.

Methods

The participants were 106 medical students (71 males, 35 females) who enrolled in Yonsei University College of Medicine in Seoul, South Korea in March 2014. They were asked to complete a Korean version of the self-directed learning readiness scale (SDLRS) and group cohesion scale (GCS) at the end of each semester for three years. A repeated measures ANOVA and a correlation and regression analysis were conducted.

Results

All the participants completed the questionnaires. There were differences in the SDLRS scores over the three years. A significant increase was observed one year after admission followed by stable scores until the third year. There was a significant increase in GCS scores as students progressed through medical school years. Positive relationships were found between SDLRS and GCS scores, and the regression model predicted 32% variance.

Conclusions

SDLRS and GCS increased as medical school years progressed. In addition, GCS is a significant factor in fostering SDLRS. Medical schools should develop various curriculum activities that enhance group cohesion among medical students, which would in turn promote SDL.
Pattern of antibody responses to Plasmodium falciparum antigens in individuals differentially exposed to Anopheles bites
Authors: Aka Kakou G. , Traoré Dipomin F. , Sagna André B. , Zoh Dounin D. , Assi Serge B. , Tchiekoi Bertin N’cho , Adja Akré M. , Remoue Franck , Poinsignon Anne
Published: February 2020

Background

In malaria-endemic areas, human populations are frequently exposed to immunomodulatory salivary components injected during mosquito blood feeding. The consequences on pathogen-specific immune responses are not well known. This study evaluated and compared the humoral responses specific to merozoite stage vaccine candidates of Plasmodium falciparum, in children differentially exposed to Anopheles bites in a natural setting.

Methods

The cross-sectional study was carried out in Bouaké (Côte d’Ivoire) where entomological data and blood samples from children (0–14 years) were collected in two sites with similar malaria prevalence. Antibody (IgG, IgG1, IgG3) responses to PfAMA1 and PfMSP1 were evaluated by ELISA. Univariate and multivariate analysis were performed to assess the relationship between the immune responses to P. falciparum antigens and exposure to Anopheles bites in the total cohort and in each site, separately. The individual level of exposure to Anopheles bites was evaluated by quantifying specific IgG response to the Anopheles gSG6-P1 salivary peptide, which represents a proxy of Anopheles exposure.

Results

The anti-Plasmodium humoral responses were different according to the level of exposure of children, with those highly exposed to Anopheles presenting significantly lower antibody responses to PfMSP1 in total population (IgG and IgG3) and in Petessou village (IgG, IgG1, IgG3). No significant difference was seen for PfAMA1 antigen between children differently exposed to Anopheles. In Dar-es-Salam, a neighbourhood where a high Culex density was reported, children presented very low antibody levels specific to both antigens, and no difference according to the exposure to Anopheles bites was found.

Conclusion

These findings may suggest that immunomodulatory components of Anopheles saliva, in addition to other factors, may participate to the modulation of the humoral response specific to Plasmodium merozoite stage antigens. This epidemiological observation may form a starting point for additional work to decipher the role of mosquito saliva on the modulation of the anti-Plasmodium acquired immunity and clinical protection in combining both field and ex vivo immunological studies.
Predictors of primary and secondary sexual abstinence among never-married youth in urban poor Accra, Ghana
Authors: Alhassan Nurudeen , Dodoo F. Nii-Amoo
Published: February 2020

Background

Sexual abstinence is a key component of the strategy to address unwanted pregnancies, sexually transmitted infections and HIV among youth in sub-Sahara Africa. But contextual pressures make abstaining from sex a formidable task for urban poor youth in the sub-region. Nevertheless, some youth in these settings still manage to resist the pressure to initiate sex early, while others choose abstinence after an initial sexual debut. Few studies in the sub-region have examined sexual abstinence among urban poor youth. We therefore examined the factors that predict primary and secondary sexual abstinence among youth in urban poor Accra. The findings highlight the protective factors associated with sexual intercourse and should help to address the needs of youth at risk of unprotected sex.

Methods

The study analysed pooled data from two rounds of the Urban Health and Poverty Survey. The surveys analysed were conducted in 2011 and 2013. The analysis was restricted to unmarried youth between age 20 and 24 years. The total sample comprised 235 female and male youth. We conducted multinomial logistic regression analysis to examine the predictors of primary and secondary abstinence relative to current sexual intercourse.

Results

The results showed that being female, sexual communication with only fathers, sexual communication with only friends and slum residence were negatively associated with primary sexual abstinence. Contrarily, being in school, attaching importance to religion, residing in a household that received social support and sexual communication with both parents were positively associated with primary abstinence. Regarding secondary abstinence, only the sexual communication variables had significant effects. Sexual communication with both parents positively predicted secondary abstinence while communication with fathers-only and friends-only had a negative effect.

Conclusion

Sexual abstinence is predicted by factors which range from individual through household factors to the locality of residence. Despite the importance of all the predictors, the study found that sexual communication with both parents was the only factor that predicted a higher likelihood of both primary and secondary sexual abstinence. We therefore recommend sexual communication between parents and youth as a key strategy for promoting sexual abstinence among urban poor youth in Accra, Ghana.
Ethnography, ethnobiology and natural history: narratives on hunting and ecology of mammals among quilombolas from Southeast Brazil
Authors: Prado Helbert Medeiros , da Silva Raquel Costa , Schlindwein Marcelo Nivert , Murrieta Rui Sérgio Sereni
Published: February 2020

Background

As a leading practice of Homo sapiens’ environmental experience for hundreds of millennia, hunting continues to evoke key research inquiries in the fields of archaeology, human ecology, and conservation biology. Broadly speaking, hunting has been mainly a subject of qualitative-symbolic and quantitative-materialistic schemata of analyze, among anthropologists and biologists, respectively. However, the phenomenological dimension of the hunting experience, in the course of individuals` everyday life, received little academic attention until this century. This study analyzes the daily praxis of hunting among quilombolas (descendants from runaway African slaves) in Southeast Brazil, making use of an ethnographic approach of phenomenological orientation, which dialogue with central ethnobiological issues. The authors also report the local ecological knowledge about mammals hunted in the area, and its relationship to the scientific literature on this subject.

Methods

Between 2016 and 2019, the authors made use of participant observation and informal interviews among eight key local participants, in three quilombola communities in the Ribeira Valley (São Paulo, Brazil). Fragments of authors’ field notes and parts of interviewers’ speeches make up the core results obtained.

Results

Articulating local knowledge to scientific literature, this study yielded a hybrid and comprehensive narrative about natural history of the mammals in the area. The authors also accessed elementary aspects of research participants’ experience in hunting, such as strategies, tactics, motivations, and feelings. They reveal a set of human behavior dispositions that seems to emerge only in the context of the action, modulating the praxis of hunting on the course of individuals’ everyday life.

Conclusion

Ethnography, ethnobiology, and natural sciences backgrounds were systematically articulated in this research. This made possible to get a contextualized and multifaceted understanding of hunting praxis in the Ribeira Valley, an important socioenvironmental context of Atlantic Forest in Brazil. The role of an ethnographic approach applied to ethnoecological and biological conservation issues is especially considered here.
Trends in fracture development of the upper extremity in Germany—a population-based description of the past 15 years
Authors: Hemmann P. , Ziegler P. , Konrads C. , Ellmerer A. , Klopfer T. , Schreiner A. J. , Bahrs C.
Published: February 2020

Background

Recent studies investigating fracture development in Germany are not available especially with regard to demographic change. The primary aim of this study was to report trends in fracture development of the upper extremity in Germany between 2002 and 2017 and to evaluate changes over time.

Methods

Evaluating inpatient data from the German National Hospital Discharge Registry (International Classification of Diseases, ICD-10) between 2002 and 2017. Total count, incidences and percentage changes of the following fracture localizations were analysed: proximal humerus, distal humerus, proximal ulna, proximal radius, ulna diaphysis (including Monteggia lesion) and distal radius. Ten age groups for men and women were formed: 35–44, 45–54, 55–64, 65–74; 75–84; 85–90, and > 90 (years).

Results

The total count of proximal humeral fractures increased from 40,839 (2002, men/women 9967/30,872) to 59,545 (2017, men/women 14,484/45,061). Distal humeral fractures increased from 5912 (2002, men/women 1559/4353) to 6493 (2017, men/women1840/4653). The total count of forearm fractures increased from 68,636 (2002, men/women 17,186/51,450) to 89,040 (2017, men/women 20,185/68,855). Women were affected in 70–75% of all cases with rising incidences among nearly every age group in female patients.

Conclusion

Total count of nearly every evaluated fracture increased. Also, incidences increased especially in the older female age groups. Fracture development already seems to reflect demographic changes in Germany.
Repurposing the serotonin agonist Tegaserod as an anticancer agent in melanoma: molecular mechanisms and clinical implications
Authors: Liu Wei , Stachura Paweł , Xu Haifeng C. , Umesh Ganesh Nikkitha , Cox Fiona , Wang Ruifeng , Lang Karl S. , Gopalakrishnan Jay , Häussinger Dieter , Homey Bernhard , Lang Philipp A. , Pandyra Aleksandra A.
Published: February 2020

Background

New therapies are urgently needed in melanoma particularly in late-stage patients not responsive to immunotherapies and kinase inhibitors.

Methods

Drug screening, IC50 determinations as well as synergy assays were detected by the MTT assay. Apoptosis using Annexin V and 7AAD staining was assessed using flow cytometry. TUNEL staining was performed using immunocytochemistry. Changes in phosphorylation of key molecules in PI3K/Akt/mTOR and other relevant pathways were detected by western blot as well as immunocytochemistry. To assess in vivo anti-tumor activity of Tegaserod, syngeneic intravenous and subcutaneous melanoma xenografts were used. Immunocytochemical staining was performed to detect expression of active Caspase-3, cleaved Caspase 8 and p-S6 in tumors. Evaluation of immune infiltrates was carried out by flow cytometry.

Results

Using a screen of 770 pharmacologically active and/or FDA approved drugs, we identified Tegaserod (Zelnorm, Zelmac) as a compound with novel anti-cancer activity which induced apoptosis in murine and human malignant melanoma cell lines. Tegaserod (TM) is a serotonin receptor 4 agonist (HTR4) used in the treatment of irritable bowel syndrome (IBS). TM’s anti-melanoma apoptosis-inducing effects were uncoupled from serotonin signaling and attributed to PI3K/Akt/mTOR signaling inhibition. Specifically, TM blunted S6 phosphorylation in both BRAFV600E and BRAF wildtype (WT) melanoma cell lines. TM decreased tumor growth and metastases as well as increased survival in an in vivo syngeneic immune-competent model. In vivo, TM also caused tumor cell apoptosis, blunted PI3K/Akt/mTOR signaling and decreased S6 phosphorylation. Furthermore TM decreased the infiltration of immune suppressive regulatory CD4+CD25+ T cells and FOXP3 and ROR-γt positive CD4+ T cells. Importantly, TM synergized with Vemurafenib, the standard of care drug used in patients with late stage disease harboring the BRAFV600E mutation and could be additively or synergistically combined with Cobimetinib in both BRAFV600E and BRAF WT melanoma cell lines in inducing anti-cancer effects.

Conclusion

Taken together, we have identified a drug with anti-melanoma activity in vitro and in vivo that has the potential to be combined with the standard of care agent Vemurafenib and Cobimetinib in both BRAFV600E and BRAF WT melanoma.
Histone H3K27 acetylation is dispensable for enhancer activity in mouse embryonic stem cells
Authors: Zhang Tiantian , Zhang Zhuqiang , Dong Qiang , Xiong Jun , Zhu Bing
Published: February 2020

H3K27ac is well recognized as a marker for active enhancers and a great indicator of enhancer activity. However, its functional impact on transcription has not been characterized. By substituting lysine 27 in histone variant H3.3 with arginine in mouse embryonic stem cells, we diminish the vast majority of H3K27ac at enhancers. However, the transcriptome is largely undisturbed in these mutant cells, likely because the other enhancer features remain largely unchanged, including chromatin accessibility, H3K4me1, and histone acetylation at other lysine residues. Our results clearly reveal that H3K27ac alone is not capable of functionally determining enhancer activity.
Mesenteric excision surgery or conservative limited resection in Crohn’s disease: study protocol for an international, multicenter, randomized controlled trial
Authors: Li Yi , Mohan Helen , Lan Nan , Wu Xiaojian , Zhou Wei , Gong Jianfeng , Shen Bo , Stocchi Luca , Coffey J. Calvin , Zhu Weiming
Published: February 2020

Background

The structures of the mesentery including adipose tissue, nerves, and lymphatics play an important role in the pathogenesis and disease progression of Crohn’s disease (CD). Conventional surgical resection for CD usually does not involve resecting the mesentery en bloc with the specimen. This contrasts with complete mesocolic excision (CME) in colorectal cancer, which involves radical resection of the mesentery. Preliminary evidence from smaller studies suggests that applying the principle of mesocolic excision to CD surgery may reduce the risk of postoperative recurrence. This randomized controlled trial is designed to test whether applying the principles of mesocolic excision to CD results in reduced postoperative recurrence. It also aims to evaluate intra- and postoperative morbidity between the two approaches.

Methods

This international, multicenter, randomized controlled trial will randomize patients (n = 116) scheduled to undergo primary ileocolic resection to either receive extensive mesenteric excision (EME) or conventional ileocolic resection with limited mesenteric excision (LME). Five sites will recruit patients in three countries. In the EME group, the mesentery is resected following CME, while avoiding the root region, i.e., 1 cm from the root of the ileocolic artery and vein. In the LME group, the mesentery is retained, i.e., “close shave” or < 3 cm from the border of bowel. The primary end point will be surgical recurrence after surgery. The secondary end points will be the postoperative endoscopic and clinical recurrence, and intra- and postoperative morbidity. Demographics, risk factors, laboratory investigations, endoscopy, postoperative prophylaxis and imaging examination will be assessed. Analysis of the primary outcome will be on an intention-to-treat basis.

Discussion

If mesocolic excision in CD reduces postoperative disease recurrence and does not increase morbidity, this trial has the potential to change practice and reduce recurrence of CD after surgical resection.

Trial registration

Clinical Trials.gov, ID: NCT03769922. Registered on February 27, 2019.
Detecting gastrointestinal manifestations in patients with systemic sclerosis using anti-gAChR antibodies
Authors: Nakane Shunya , Umeda Masataka , Kawashiri Shin-ya , Mukaino Akihiro , Ichinose Kunihiro , Higuchi Osamu , Maeda Yasuhiro , Nakamura Hideki , Matsuo Hidenori , Kawakami Atsushi
Published: February 2020

Background

Patients with systemic sclerosis (SSc) complicated by gastrointestinal dysmotility are difficult to treat and have high mortality. To clarify the pathogenesis of gastrointestinal manifestations, we aimed to demonstrate the association among the clinical features of SSc, the serological markers, the autoantibodies against nicotinic acetylcholine receptor at autonomic ganglia (gAChR).

Methods

Fifty patients were enrolled and divided into two groups according to the presence or absence of gastrointestinal manifestations, and the characteristics were analyzed between these two groups. We measured biomarkers and the autoantibodies against two gAChRα3 and β4 subunits to test sera samples. Furthermore, patients were classified based on the presence or absence of anti-gAChR autoantibodies, and their clinical features were compared.

Results

In patients with SSc and gastrointestinal manifestations, digital ulcers were more frequent (p = 0.050) and VEGF expression was significantly higher (p = 0.038). Seven subjects with SSc were seropositive for α3 subunit, whereas one patient was seropositive for β4 subunit. The mean level of anti-gAChRα3 autoantibodies in SSc patients with gastrointestinal manifestations was significantly higher than that in SSc patients without gastrointestinal manifestations (p = 0.001). The group of patients with SSc and gAChR autoantibodies had significantly higher endostatin levels (p = 0.046).

Conclusions

This study is the first to demonstrate that clinical characteristics of SSc patients with seropositivity for gAChR autoantibodies. Patients with SSc have circulating autoantibodies against gAChR, which may contribute to gastrointestinal manifestations associated with this disease, suggesting that gAChR-mediated autonomic neurotransmission may provide a pathomechanism for gastrointestinal dysmotility in SSc.
A brief survey on replica consistency in cloud environments
Authors: Campêlo Robson A. , Casanova Marco A. , Guedes Dorgival O. , Laender Alberto H. F.
Published: February 2020

Cloud computing is a general term that involves delivering hosted services over the Internet. With the accelerated growth of the volume of data used by applications, many organizations have moved their data into cloud servers to provide scalable, reliable and highly available services. A particularly challenging issue that arises in the context of cloud storage systems with geographically-distributed data replication is how to reach a consistent state for all replicas. This survey reviews major aspects related to consistency issues in cloud data storage systems, categorizing recently proposed methods into three categories: (1) fixed consistency methods, (2) configurable consistency methods and (3) consistency monitoring methods.
Gastrointestinal perforation: clinical and MDCT clues for identification of aetiology
Authors: Pouli Styliani , Kozana Androniki , Papakitsou Ioanna , Daskalogiannaki Maria , Raissaki Maria
Published: February 2020

Gastrointestinal tract (GIT) perforation is a common medical emergency associated with considerable mortality, ranging from 30 to 50%. Clinical presentation varies: oesophageal perforations can present with acute chest pain, odynophagia and vomiting, gastroduodenal perforations with acute severe abdominal pain, while colonic perforations tend to follow a slower progression course with secondary bacterial peritonitis or localised abscesses. A subset of patients may present with delayed symptoms, abscess mimicking an abdominal mass, or with sepsis.

Direct multidetector computed tomography (MDCT) findings support the diagnosis and localise the perforation site while ancillary findings may suggest underlying conditions that need further investigation following primary repair of ruptured bowel. MDCT findings include extraluminal gas, visible bowel wall discontinuity, extraluminal contrast, bowel wall thickening, abnormal mural enhancement, localised fat stranding and/or free fluid, as well as localised phlegmon or abscess in contained perforations.

The purpose of this article is to review the spectrum of MDCT findings encountered in GIT perforation and emphasise the MDCT and clinical clues suggestive of the underlying aetiology and localisation of perforation site.
Keystroke biometrics in the encrypted domain: a first study on search suggestion functions of web search engines
Authors: Whiskerd Nicholas , Körtge Nicklas , Jürgens Kris , Lamshöft Kevin , Ezennaya-Gomez Salatiel , Vielhauer Claus , Dittmann Jana , Hildebrandt Mario
Published: February 2020

A feature of search engines is prediction and suggestion to complete or extend input query phrases, i.e. search suggestion functions (SSF). Given the immediate temporal nature of this functionality, alongside the character submitted to trigger each suggestion, adequate data is provided to derive keystroke features. The potential of such biometric features to be used in identification and tracking poses risks to user privacy.For our initial experiment, we evaluate SSF traffic with different browsers and search engines on a Linux PC and an Android mobile phone. The keystroke network traffic is captured and decrypted using mitmproxy to verify if expected keystroke information is contained, which we call quality assurance (QA). In our second experiment, we present first results for identification of five subjects searching for up to three different phrases on both PC and phone using naive Bayesian and nearest neighbour classifiers. The third experiment investigates potential for identification and verification by an external observer based purely on the encrypted traffic, thus without QA, using the Euclidean distance. Here, ten subjects search for two phrases across several sessions on a Linux virtual machine, and statistical features are derived for classification. All three test cases show positive tendencies towards the feasibility of distinguishing users within a small group. The results yield lowest equal error rates of 5.11% for the single PC and 11.37% for the mobile device with QA and 23.61% for various PCs without QA. These first tendencies motivate further research in feature analysis of encrypted network traffic and prevention approaches to ensure protection and privacy.
Six-month retention and changes in quality of life and substance use from a low-threshold methadone maintenance therapy programme in Durban, South Africa
Authors: Scheibe Andrew , Shelly Shaun , Gerardy Tara , von Homeyer Zara , Schneider Andrea , Padayachee Kalvanya , Naidoo Shalon Balaguru , Mtshweni Klaas , Matau Ayanda , Hausler Harry , Marks Monique
Published: February 2020

Background

Emerging data points to a potential heroin use epidemic in South Africa. Despite this, access to methadone maintenance therapy and other evidence-based treatment options remains negligible. We aimed to assess retention, changes in substance use and quality of life after 6 months on methadone maintenance therapy provided through a low-threshold service in Durban, South Africa.

Methods

We enrolled a cohort of 54 people with an opioid use disorder into the study. We reviewed and described baseline socio-demographic characteristics. Baseline and 6-month substance use was assessed using the World Health Organization’s Alcohol Smoking and Substance Use Involvement Screening Test (ASSIST) and quality of life, using the SF-12. We compared changes at 6 months on methadone to baseline using the Wilcoxon signed rank test and paired-tests for the ASSIST and SF-12 scores, respectively. McNemar’s test was used for comparisons between paired results of categorical variables relating to injecting frequency.

Results

The majority of the participants were young, Black African males, with a history of drug use spanning over 10 years. Retention after 6 months was 81%. After 6 months, the median heroin ASSIST score decreased from 37 to 9 (p < 0.0001) and the cannabis ASSIST score increased from 12.5 to 21 (p = 0.0003). The median mental health composite score of the SF-12 increased from 41.4 to 48.7 (p = 0.0254).

Conclusions

Interim findings suggest high retention, significant reductions in heroin use and improvements in mental health among participants retained on methadone maintenance therapy for 6 months. Further research into longer term outcomes and the reasons contributing to these changes would strengthen recommendations for the scale-up of methadone maintenance therapy in South Africa.
Substance use disorders and risk of suicide in a general US population: a case control study
Authors: Lynch Frances L. , Peterson Edward L. , Lu Christine Y. , Hu Yong , Rossom Rebecca C. , Waitzfelder Beth E. , Owen-Smith Ashli A. , Hubley Samuel , Prabhakar Deepak , Keoki Williams L. , Beck Arne , Simon Gregory E. , Ahmedani Brian K.
Published: February 2020

Background

Prior research suggests that substance use disorders (SUDs) are associated with risk of suicide mortality, but most previous work has been conducted among Veterans Health Administration patients. Few studies have examined the relationship between SUDs and suicide mortality in general populations. Our study estimates the association of SUDs with suicide mortality in a general US population of men and women who receive care across eight integrated health systems.

Methods

We conducted a case–control study using electronic health records and claims data from eight integrated health systems of the Mental Health Research Network. Participants were 2674 men and women who died by suicide between 2000–2013 and 267,400 matched controls. The main outcome was suicide mortality, assessed using data from the health systems and confirmed by state death data systems. Demographic and diagnostic data on substance use disorders and other health conditions were obtained from each health system. First, we compared descriptive statistics for cases and controls, including age, gender, income, and education. Next, we compared the rate of each substance use disorder category for cases and controls. Finally, we used conditional logistic regression models to estimate unadjusted and adjusted odds of suicide associated with each substance use disorder category.

Results

All categories of substance use disorders were associated with increased risk of suicide mortality. Adjusted odds ratios ranged from 2.0 (CI 1.7, 2.3) for patients with tobacco use disorder only to 11.2 (CI 8.0, 15.6) for patients with multiple alcohol, drug, and tobacco use disorders. Substance use disorders were associated with increased relative risk of suicide for both women and men across all categories, but the relative risk was more pronounced in women.

Conclusions

Substance use disorders are associated with significant risk of suicide mortality, especially for women, even after controlling for other important risk factors. Experiencing multiple substance use disorders is particularly risky. These findings suggest increased suicide risk screening and prevention efforts for individuals with substance use disorders are needed.
Differences in pulse rate variability with measurement site
Authors: Yuda Emi , Yamamoto Kento , Yoshida Yutaka , Hayano Junichiro
Published: February 2020

Background

Recently, attempts have been made to use the pulse rate variability (PRV) as a surrogate for heart rate variability (HRV). PRV, however, may be caused by the fluctuations of left ventricular pre-ejection period and pulse transit time besides HRV. We examined whether PRV differs not only from HRV but also depending on the measurement site.

Results

In five healthy subjects, pulse waves were measured simultaneously on both wrists and both forearms together with single-lead electrocardiogram (ECG) in the supine and sitting positions. Although average pulse interval showed no significant difference from average R-R interval in either positions, PRV showed greater power for the low-frequency (LF) and high-frequency (HF) components and lower LF/HF than HRV. The deviations of PRV from HRV in the supine and sitting positions were 13.2% and 7.9% for LF power, 24.5% and 18.3% for HF power, and − 15.0% and − 30.2% for LF/HF, respectively. While the average pulse interval showed 0.8% and 0.5% inter-site variations among the four sites in the supine and sitting positions, respectively, the inter-site variations in PRV were 4.0% and 3.6% for LF power, 3.8% and 4.7% for HF power, and 18.0% and 17.5% for LF/HF, respectively.

Conclusions

These suggest that PRV shows not only systemic differences from HRV but also considerable inter-site variations.
Cognitive functioning and lifetime major depressive disorder in UK Biobank
Authors: de Nooij Laura , Harris Mathew A. , Adams Mark J. , Clarke Toni-Kim , Shen Xueyi , Cox Simon R. , McIntosh Andrew M. , Whalley Heather C.
Published: February 2020

Background.

Cognitive impairment associated with lifetime major depressive disorder (MDD) is well-supported by meta-analytic studies, but population-based estimates remain scarce. Previous UK Biobank studies have only shown limited evidence of cognitive differences related to probable MDD. Using updated cognitive and clinical assessments in UK Biobank, this study investigated population-level differences in cognitive functioning associated with lifetime MDD.

Methods.

Associations between lifetime MDD and cognition (performance on six tasks and general cognitive functioning [g-factor]) were investigated in UK Biobank (N-range 7,457–14,836, age 45–81 years, 52% female), adjusting for demographics, education, and lifestyle. Lifetime MDD classifications were based on the Composite International Diagnostic Interview. Within the lifetime MDD group, we additionally investigated relationships between cognition and (a) recurrence, (b) current symptoms, (c) severity of psychosocial impairment (while symptomatic), and (d) concurrent psychotropic medication use.

Results.

Lifetime MDD was robustly associated with a lower g-factor (β = −0.10, PFDR = 4.7 × 10−5), with impairments in attention, processing speed, and executive functioning (β ≥ 0.06). Clinical characteristics revealed differential profiles of cognitive impairment among case individuals; those who reported severe psychosocial impairment and use of psychotropic medication performed worse on cognitive tests. Severe psychosocial impairment and reasoning showed the strongest association (β = −0.18, PFDR = 7.5 × 10−5).

Conclusions.

Findings describe small but robust associations between lifetime MDD and lower cognitive performance within a population-based sample. Overall effects were of modest effect size, suggesting limited clinical relevance. However, deficits within specific cognitive domains were more pronounced in relation to clinical characteristics, particularly severe psychosocial impairment.
Liberal Versus Restrictive Red Blood Cell Transfusion Thresholds in Hematopoietic Cell Transplantation: A Randomized, Open Label, Phase III, Noninferiority Trial
Authors: Tay Jason , Allan David S. , Chatelain Elizabeth , Coyle Doug , Elemary Mohamed , Fulford Adrienne , Petrcich William , Ramsay Timothy , Walker Irwin , Xenocostas Anargyros , Tinmouth Alan , Fergusson Dean
Published: February 2020

PURPOSE

Evidence regarding red blood cell (RBC) transfusion practices and their impact on hematopoietic cell transplantation (HCT) outcomes are poorly understood.

PATIENTS AND METHODS

We performed a noninferiority randomized controlled trial in four different centers that evaluated patients with hematologic malignancies requiring HCT who were randomly assigned to either a restrictive (hemoglobin [Hb] threshold < 70 g/L) or liberal (Hb threshold < 90 g/L) RBC transfusion strategy between day 0 and day 100. The noninferiority margin corresponds to a 12% absolute difference between groups in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) score relative to baseline. The primary outcome was health-related quality of life (HRQOL) measured by FACT-BMT score at day 100. Additional end points were collected: HRQOL by FACT-BMT score at baseline and at days 7, 14, 28, 60, and 100; transplantation-related mortality; length of hospital stay; intensive care unit admissions; acute graft-versus-host disease; Bearman toxicity score; sinusoidal obstruction syndrome; serious infections; WHO Bleeding Scale; transfusion requirements; and reactions to therapy.

RESULTS

A total of 300 patients were randomly assigned to either restrictive-strategy or liberal-strategy treatment groups between 2011 and 2016 at four Canadian adult HCT centers. After HCT, mean pre-transfusion Hb levels were 70.9 g/L in the restrictive-strategy group and 84.6 g/L in the liberal-strategy group ( P < .0001). The number of RBC units transfused was lower in the restrictive-strategy group than in the liberal-strategy group (mean, 2.73 units [standard deviation, 4.81 units] v 5.02 units [standard deviation, 6.13 units]; P = .0004). After adjusting for transfusion type and baseline FACT-BMT score, the restrictive-strategy group had a higher FACT-BMT score at day 100 (difference of 1.6 points; 95% CI, −2.5 to 5.6 points), which was noninferior compared with that of the liberal-strategy group. There were no significant differences in clinical outcomes between the transfusion strategies.

CONCLUSION

In patients undergoing HCT, the use of a restrictive RBC transfusion strategy threshold of 70 g/L was as effective as a threshold of 90 g/L and resulted in similar HRQOL and HCT outcomes with fewer transfusions.