bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomarker roles identification of miR-106 family for predicting the risk and poor survival of colorectal cancer
Authors: Peng Qiliang , Shen Yi , Zhao Peifeng , Cheng Ming , Zhu Yaqun , Xu Bo
Published: June 2020

Background

Recent studies have extensively investigated the roles of miR-106 in colorectal cancer (CRC). However, the associations and molecular mechanism underlying the roles of miR-106 in CRC remain unclear. We aimed to thoroughly investigate the biomarker roles of miR-106 for predicting the risk and survival outcome in CRC.

Methods

We first conducted a comprehensive meta-analysis to quantitatively evaluate the roles of miR-106 in the diagnosis and prognosis of CRC. Then, we qualitatively explored the biomarker roles of miR-106 in CRC through an integrative bioinformatics analysis.

Results

The results indicated that miR-106 yielded a combined AUC of 0.79 (95% CI: 0.76–0.83), with a pooled sensitivity of 0.50 (95% CI: 0.32–0.68) and a pooled specificity of 0.93 (95% CI: 0.79–0.98) for discriminating CRC cases from normal controls. Moreover, patients with higher expression of miR-106 were significantly associated with shorter disease-free survival (HR: 1.73; 95%CI: 1.23–2.44) and overall survival (HR: 1.39; 95%CI: 1.09–1.77). Finally, gene ontology and pathway analysis demonstrated that miR-106 family was highly involved in the initiation and progression of CRC and indicated the potential molecular mechanism for miR-106 in CRC.

Conclusions

Our results indicated that miR-106 showed promising potential as diagnostic and prognostic biomarker for CRC. Nevertheless, the underlying molecular mechanism of miR-106 family involved in CRC requires further investigation.
SCDb: an integrated database of stomach cancer
Authors: Gu Erli , Song Wei , Liu Ajing , Wang Hong
Published: June 2020

Background

Stomach cancer (SC) is a type of cancer, which is derived from the stomach mucous membrane. As there are non-specific symptoms or no noticeable symptoms observed at the early stage, newly diagnosed SC cases usually reach an advanced stage and are thus difficult to cure. Therefore, in this study, we aimed to develop an integrated database of SC.

Methods

SC-related genes were identified through literature mining and by analyzing the publicly available microarray datasets. Using the RNA-seq, miRNA-seq and clinical data downloaded from The Cancer Genome Atlas (TCGA), the Kaplan-Meier (KM) survival curves for all the SC-related genes were generated and analyzed. The miRNAs (miRanda, miRTarget2, PicTar, PITA and TargetScan databases), SC-related miRNAs (HMDD and miR2Disease databases), single nucleotide polymorphisms (SNPs, dbSNP database), and SC-related SNPs (ClinVar database) were also retrieved from the indicated databases. Moreover, gene_disease (OMIM and GAD databases), copy number variation (CNV, DGV database), methylation (PubMeth database), drug (WebGestalt database), and transcription factor (TF, TRANSFAC database) analyses were performed for the differentially expressed genes (DEGs).

Results

In total, 9990 SC-related genes (including 8347 up-regulated genes and 1643 down-regulated genes) were identified, among which, 65 genes were further confirmed as SC-related genes by performing enrichment analysis. Besides this, 457 miRNAs, 20 SC-related miRNAs, 1570 SNPs, 108 SC-related SNPs, 419 TFs, 44,605 CNVs, 3404 drug-associated genes, 63 genes with methylation, and KM survival curves of 20,264 genes were obtained. By integrating these datasets, an integrated database of stomach cancer, designated as SCDb, (available athttp://www.stomachcancerdb.org/) was established.

Conclusions

As a comprehensive resource for human SC, SCDb database will be very useful for performing SC-related research in future, and will thus promote the understanding of the pathogenesis of SC.
Network pharmacology to dissect the mechanisms of Yinlai Decoction for pneumonia
Authors: Xu Jingnan , Bai Chen , Huang Ling , Liu Tiegang , Wan Yuxiang , Zheng Zian , Ma Xueyan , Gao Fei , Yu He , Gu Xiaohong
Published: June 2020

Background

Pneumonia is a common respiratory disorder, which brings an enormous financial burden to the medical system. However, the current treatment options for pneumonia are limited because of drug resistance and side effects. Our previous study preliminarily confirmed that Yinlai Decoction (YD), a common prescription for pneumonia in clinical practice, can regulate the expression of inflammatory factors, but the mechanisms are unknown yet.

Methods

In our work, a method named network pharmacology was applied, which investigated the underlying mechanisms of herbs based on a variety of databases. We obtained bioactive ingredients of YD on TCMSP database and collected potential targets of these ingredients by target fishing. Then the pneumonia-related targets database was built by TTD, Drugbank, HPO, OMIM, and CTD. Based on the matching targets between YD and pneumonia, the PPI network was built by STRING to analyze the interactions among these targets and then input into Cytoscape for further topological analysis. DAVID and KEGG were utilized for GO and pathway enrichment analysis. Then rat model based on LPS stimulated pneumonia was used to verify the possible mechanism of YD in treating pneumonia.

Results

Sixty-eight active ingredients, 103 potential targets and 8 related pathways, which likely exert a number of effects, were identified. Three networks were constructed using Cytoscape, which were herb-component-network, YD-pneumonia target network, and herb-component-YD target-pneumonia network. YD was verified to treat LPS-induced pneumonia by regulating the inflammatory factor IL-6, which was a predicted target.

Conclusion

Network analysis indicated that YD could alleviate the symptoms and signs of pneumonia through regulating host immune inflammatory response, angiogenesis and vascular permeability, the barrier function of the airway epithelial cells, hormone releasing and cell growth, proliferation, and apoptosis.
Gangrenous mastitis in dromedary camels in UAE caused by Streptococcus agalactiae
Authors: El Tigani-Asil El Tigani Ahmed , Abdelwahab Ghada Elderdiri , Veedu Jayamohanan Thikkal Veedu Payyan , Khalafalla Abdelmalik Ibrahim , Mohamed Zayed Saud Abdullah , Ishag Hassan Zackaria Ali , Shah Asma Abdi Mohamed , Alhosani Mohamed Ali Abdulla , Al Muhairi Salama Suhail Mohammed
Published: June 2020

Background

Mastitis is a disease of economic concern that affects dairy industry worldwide. This study aimed to investigate and identify possible etiologies encountered in an episode of acute gangrenous mastitis in lactating she-camels in Al Dhafra region, Abu Dhabi Emirate, United Arab Emirates (UAE).

Beside the routine clinical examination, conventional bacteriological methods were used to isolate and identify possible aerobic/anaerobic bacterial or fungal pathogens from cultured milk samples collected from the mastitic she-camels. Moreover, quantitative real-time polymerase chain reaction (qPCR) was used for the detection of Mycoplasma agalactiae and Mycoplasma bovis strains, and the 16S rRNA gene was sequenced to confirm the isolation. The isolates were also tested for their susceptibility to antimicrobials.

Results

Acute gangrenous mastitis is reported in the dromedary camel herd with about 80% morbidity rate among lactating she-camels exhibited acute, painful hard swelling of affected teat, quarter or entire udder. About 41.7% of the infected animals were stamped out for culling due to complete or partial amputation of udder quarters. Streptococcus agalactiae was the sole isolated organism (6 isolates). The antimicrobial susceptibility testing revealed that, the Streptococcus agalactiae isolates were sensitive to both penicillin and ampicillin. Comparison of the 16S rRNA gene sequencing results by BLASTN confirmed the presence of Streptococcus agalactiae with high confidence (100% identity). Phylogenetic analysis indicated clustering of one isolate (CMAUAE accession number; MN267805.1) with Streptococcus agalactiae that infects multi-hosts including humans, while strains (CMBUAE to CMFUAE with accession numbers; MN267806.1 to MN267810.1 respectively) clustered with Streptococcus agalactiae that infects humans. No Mycoplasma spp was detected by qPCR analysis.

Conclusions

In the present study, the Streptococcus agalactiae was found to be the main cause of acute gangrenous mastitis in dromedary camels in UAE. More research should be done to investigate other possible causes of clinical or subclinical mastitis in dromedary camels in UAE.
Fatigue following radiotherapy of low-risk early breast cancer – a randomized controlled trial of intraoperative electron radiotherapy versus standard hypofractionated whole-breast radiotherapy: the COSMOPOLITAN trial (NCT03838419)
Authors: Forster Tobias , Jäkel Cornelia , Akbaba Sati , Krug David , Krempien Robert , Uhl Matthias , Häfner Matthias Felix , König Laila , Koerber Stefan Alexander , Harrabi Semi , Bernhardt Denise , Behnisch Rouven , Krisam Johannes , Hennigs Andre , Sohn Christof , Heil Jörg , Debus Jürgen , Hörner-Rieber Juliane
Published: June 2020

Background

Fatigue is one of the most common and distressing side-effects of breast cancer radiotherapy. According to current guidelines, accelerated partial breast irradiation (APBI) may be considered as an alternative treatment option for women with early-stage low-risk breast cancer. One method for APBI is single-dose intraoperative radiotherapy (IORT) applied directly to the tumor bed during breast conserving surgery (BCS). The COSMOPOLITAN trial therefore aims to analyze the intensity of fatigue following single-shot IORT with electrons (IOERT) compared to conventional hypofractionated whole breast irradiation (WBI) in low risk early breast cancer patients.

Methods

This trial is conducted as a multicenter, prospective, randomized, two-arm phase II study comparing the intensity of fatigue in early-stage breast cancer (cT1cN0cM0, tumor size < 2,5 cm, ER pos. Her2neu neg., age > 50 years) treated either with WBI or APBI after BCS. Secondary outcomes investigated are tumor control, overall survival (OS), disease-free survival (DFS), acute and chronic toxicity, quality of life (QoL) and cosmesis. A total of 202 patients will be randomized into two arms: Patients in arm A will receive WBI (40.05 Gy, 15 fractions) after surgical resection, while patients in arm B will receive IOERT (21 Gy to the 90%-isodose) during BCS. Fatigue will be assessed 12 weeks post surgery with the help of the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale.

Discussion

The present trial aims to evaluate treatment response to compare single-shot intraoperative electron APBI to conventional WBI following BCS in early-stage low risk breast cancer patients. Fatigue is selected as the primary, patient-reported endpoint due its major clinical relevance.

Trial registration

The study is prospectively registered on February 12th, 2019: Clinicaltrials.gov, NCT03838419. “Intraoperative Electron Radiotherapy for Low-risk Early Breast Cancer (COSMOPOLITAN)”.

Study status

Ongoing study. Start of recruitment was December 2019.
Natural outcome of hemoglobin and functional recovery after the direct anterior versus the posterolateral approach for total hip arthroplasty: a randomized study
Authors: Cao Jia , Zhou Yiqin , Xin Wei , Zhu Jun , Chen Yi , Wang Bo , Qian Qirong
Published: June 2020

Background

Total hip arthroplasty (THA) is one of the most successful orthopedic surgeries. There are many common surgical approaches for THA. The direct anterior approach (DAA) and posterolateral approach (PLA) were compared, leading to controversial results.

Methods

We report on a prospective randomized study which compared the changes of perioperative hemoglobin (Hb), the Harris hip score (HHS) and a visual analog scale (VAS) pain score following THA using DAA or PLA. A total of 130 participants were randomly divided into two groups (65 DAA versus 65 PLA). Perioperative ΔHb and other clinical outcomes were recorded.

Results

A total of 130 participants completed follow-up, while 14 patients were not recorded in blood outcomes due to blood transfusions and complications. The average Hb decrease immediately after surgery in the DAA group was greater than that in the PLA group (21.1 versus 15.8 g/L,P< .001). However, post-operative Hb descent velocity was slower in the DAA group, and the lowest point was reached earlier. No significant differences in ΔHb levels could be observed after 1 month in the two groups. When compared with the PLA group, the DAA group had a shorter incision (9.1 versus 13.5 cm,P< .001) and shorter hospital stay (4.2 versus 4.7 days,P= .004). However, the operation time of the DAA group was longer (88.0 versus 66.8 min,P< .001). The DAA group had a better HHS and VAS pain score at 6 weeks post-surgery. However, no significant differences were observed at later time points.

Conclusion

We concluded that DAA performed better on enhanced recovery after surgery (ERAS) than PLA in THA, while both DAA and PLA could result in a positive, similar result after 3 months.

Trial registration

The study was registered by the Chinese Clinical Trial Registry (ChiCTR1900020770, 19 January 2019).
Modulation of inflammatory factors predicts the outcome following spinal cord injury
Authors: Yu Zepeng , Sun Xingwei , Xia Rui , Chen Qian , Wu Qin , Zheng Weiwei
Published: June 2020

Background

The correlation between inflammatory responses caused by spinal cord injury (SCI) and the prognosis of patients with SCI still remains controversial.

Methods

In the present study, we preliminary investigated the serum levels of interleukin (IL)-4, IL-10, major histocompatibility complex (MHC)-I, and inducible nitric oxide synthase (iNOS) and compared the serum IL-4 and IL-10 expression in rats of high Basso-Beattie-Bresnahan (BBB) scores with these of low BBB scores. Besides, the infiltration of macrophage and the axonal regeneration of the injured spinal cord were observed from day 10 to day 30.

Results

We found that higher serum levels of IL-4 and IL-10 can reflect the restorability degree of SCI and could be potential biomarkers for the prognosis of SCI. The infiltration of the M2 subtype of macrophage and the axons regrowth might contribute to a better prognosis.

Conclusions

The current study demonstrates that the serum levels of IL-4 and IL-10 are preliminarily adopted as serologic markers to forecast SCI, and high serum levels of IL-4 and IL-10 may indicate a better prognosis. Moreover, the way to promote macrophage polarization from M1 to M2 may contribute to better axonal regeneration.
H1-antihistamines as antischistosomal drugs: in vitro and in vivo studies
Authors: Xavier Rogério P. , Mengarda Ana C. , Silva Marcos P. , Roquini Daniel B. , Salvadori Maria C. , Teixeira Fernanda S. , Pinto Pedro L. , Morais Thiago R. , Ferreira Leonardo L. G. , Andricopulo Adriano D. , de Moraes Josué
Published: June 2020

Background

Schistosomiasis is a socioeconomically devastating parasitic infection afflicting hundreds of millions of people and animals worldwide. It is the most important helminth infection, and its treatment relies solely on the drug praziquantel. Oral H1-antihistamines are available worldwide, and these agents are among the most widely used of all medications in children and adults. Given the importance of the drug repositioning strategy, we evaluated the antischistosomal properties of the H1-antihistamine drugs commonly used in clinical practices.

Methods

Twenty-one antihistamine drugs were initially screened against adult schistosomesex vivo. Subsequently, we investigated the anthelmintic properties of these antihistamines in a murine model of schistosomiasis for both early and chronicS. mansoniinfections at oral dosages of 400 mg/kg single dose or 100 mg/kg daily for five consecutive days. We also demonstrated and described the ability of three antihistamines to induce tegumental damage in schistosomes through the use of scanning electron microscopy.

Results

From phenotypic screening, we found that desloratadine, rupatadine, promethazine, and cinnarizine kill adultS. mansoni in vitroat low concentrations (5–15 µM). These results were further supported by scanning electron microscopy analysis. In an animal model, rupatadine and cinnarizine revealed moderate worm burden reductions in mice harboring either early or chronicS. mansoniinfection. Egg production, a key mechanism for both transmission and pathogenesis, was also markedly inhibited by rupatadine and cinnarizine, and a significant reduction in hepatomegaly and splenomegaly was recorded. Although less effective, desloratadine also revealed significant activity against the adult and juvenile parasites.

Conclusions

Although the worm burden reductions achieved are all only moderate, comparatively, treatment with any of the three antihistamines is more effective in early infection than praziquantel. On the other hand, the clinical use of H1-antihistamines for the treatment of schistosomiasis is highly unlikely.
Detection of gastrointestinal parasitism at recreational canine sites in the USA: the DOGPARCS study
Authors: Stafford Kristina , Kollasch Todd M. , Duncan Kathryn T. , Horr Stephanie , Goddu Troy , Heinz-Loomer Christine , Rumschlag Anthony J. , Ryan William G. , Sweet Sarah , Little Susan E.
Published: June 2020

Background

The rapid growth in off-leash dog parks provides opportunity for canine socialization activities but carries risk of exposure to intestinal parasites. This study assessed the prevalence of these infections in dogs visiting off-leash dog parks.

Methods

Fresh defecations were collected from dogs visiting parks in 30 metropolitan areas across the USA. Samples were analyzed by coproantigen immunoassay (CAI) (Fecal Dx® andGiardiaTest, IDEXX Laboratories, Inc.) and zinc sulfate centrifugal flotation (CF). Owners responded to a questionnaire on their dog’s signalment and use of heartworm/intestinal parasite control medications (HWCM).

Results

Samples were examined from 3006 dogs, 87.9% aged at least 12 months, visiting 288 parks. At least one intestinal parasite was detected in 622 (20.7%) samples, nematodes in 263 (8.8%), with hookworms, whipworms and ascarids in 7.1, 1.9 and 0.6% of samples, respectively. A sample positive for one or more intestinal parasites was found in 245 (85.1%) parks, with nematodes found in 143 (49.7%). Combined, CAI and CF detected 78.4% more intestinal nematode infections than CF alone. Hookworm and whipworm infections were detected in all age groups, but ascarids were only detected in dogs less than 4 years-old. Approximately 42% of dogs aged less than 1 year were positive for nematodes orGiardia. Based on owner reports, HWCM was current for 68.8% of dogs, dogs previously diagnosed with intestinal parasitism were more likely to be receiving a HWCM than those without such history, and a significantly lower (P = 0.0003) proportion of dogs receiving a HWCM were positive for intestinal nematodes compared with those not on such medication.

Conclusions

Intestinal parasites, the most common of which wereGiardia,Ancylostoma caninumandTrichuris vulpis, were found in 20% of dogs and 85% of dog parks across the USA. Enhanced detection of canine intestinal parasitism was achieved by combining CF and CAI. Canine intestinal parasites are common across the USA and dog health can be improved by regular testing of fecal samples and routine administration of medications effective against the most common infections.
Effect of high-intensity interval training in young heart transplant recipients: results from two randomized controlled trials
Authors: Nytrøen Kari , Rolid Katrine , Yardley Marianne , Gullestad Lars
Published: June 2020

Background

Little is known about the effect of exercise in young heart transplant recipients, and results on group level is lacking. This study summarizes the findings of the youngest participants in two previous randomized controlled trials.

Method

This is a hypothesis-generating study reporting the main results from the youngest participants in two larger randomized controlled trials investigating the effect of high-intensity interval training (HIT). The article summarizes the main results from 28 young participants (< 40 year of age) who have participated in two previous studies which evaluated the effect of HIT vs. controls in adult heart transplant recipients. One of the studies included de novo heart transplant recipients and the other included maintenance heart transplant recipients.

All study tests were performed in-hospital, in the specialist health care setting, but the exercise intervention was carried out locally, in cooperation with the primary health care. In both studies the exercise intervention lasted for 9–12 months. In one study, HIT (85–95% of peak effort) was compared to controls (no specific intervention), and in the other study HIT was compared to moderate, continuous exercise (MICT, 60–80% of peak effort). The main outcome measure was peak oxygen uptake (VO2peak) and a secondary endpoint was muscle strength.

Results

The summarized findings from the youngest heart transplant recipients in these two studies demonstrated mainly that the improvement in peak oxygen uptake among the younger recipients (< 40 years) was much larger (4.7 vs. 1.2 ml/kg/min and 7.0 vs. 2.2 ml/kg/min) compared to the improvement among the older recipients (≥ 40 years), and in accordance with results from adult heart transplant populations: HIT, compared to MICT, induced the largest improvement in peak oxygen consumption, also in the younger heart transplant recipients.

Conclusions

These results suggest that young heart transplant recipients have a greater effect of HIT than of MICT and may also suggest that younger recipients benefit more from high-intensity interval training than their older co-patients. However, larger randomized studies focusing on the young heart transplant population is strongly needed to confirm this hypothesis.

Trial registration

Clinical trial registrations: NCT01796379 and NCT01091194.
Mathematical modeling of vaporization during laser-induced thermotherapy in liver tissue
Authors: Blauth Sebastian , Hübner Frank , Leithäuser Christian , Siedow Norbert , Vogl Thomas J.
Published: June 2020

Laser-induced thermotherapy (LITT) is a minimally invasive method causing tumor destruction due to heat ablation and coagulative effects. Computer simulations can play an important role to assist physicians with the planning and monitoring of the treatment. Our recent study with ex-vivo porcine livers has shown that the vaporization of the water in the tissue must be taken into account when modeling LITT. We extend the model used for simulating LITT to account for vaporization using two different approaches. Results obtained with these new models are then compared with the measurements from the original study.
Genome sequencing and analysis of fungus Hirsutella sinensis isolated from Ophiocordyceps sinensis
Authors: Jin Li-Qun , Xu Zhe-Wen , Zhang Bo , Yi Ming , Weng Chun-Yue , Lin Shan , Wu Hui , Qin Xiang-Tian , Xu Feng , Teng Yi , Yuan Shui-Jin , Liu Zhi-Qiang , Zheng Yu-Guo
Published: June 2020

Ophiocordyceps sinensishas been used as a traditional medicine or healthy food in China for thousands of years.Hirsutella sinensiswas reported as the only correct anamorph ofO. sinensis. It is reported that the laboratory-grownH. sinensismycelium has similar clinical efficacy and less associated toxicity compared to the wildO. sinensis. The research of theH. sinensisis becoming more and more important and urgent. To gain deeper insight into the biological and pharmacological mechanisms, we sequenced the genome ofH. sinensis. The genome ofH. sinensis(102.72 Mb) was obtained for the first time, with > 99% coverage. 10,200 protein-encoding genes were predicted based on the genome sequence. A detailed secondary metabolism analysis and structure verification of the main ingredients were performed, and the biosynthesis pathways of seven ingredients (mannitol, cordycepin, purine nucleotides, pyrimidine nucleotides, unsaturated fatty acid, cordyceps polysaccharide and sphingolipid) were predicted and drawn. Furthermore, infection process and mechanism ofH. sinensiswere studied and elaborated in this article. The enzymes involved in the infection mechanism were also predicted, cloned and expressed to verify the mechanism. The genes and proteins were predicted and annotated based on the genome sequence. The pathways of several active components inH. sinensiswere predicted and key enzymes were confirmed. The work presented here would improve the understanding of the genetic basis of this organism, and contribute to further research, production and application ofH. sinensis.
The role of autophagy in the cytotoxicity induced by trastuzumab emtansine (T-DM1) in HER2-positive breast cancer cells
Authors: Liu Peipei , Fan Jiajun , Wang Ziyu , Zai Wenjing , Song Ping , Li Yongping , Ju Dianwen
Published: June 2020

Trastuzumab emtansine (T-DM1), an antibody–drug conjugate (ADC) of trastuzumab and cytotoxic agent emtansine (DM1), has been approved for the therapy of metastatic HER2-positive breast cancer after prior treatment of trastuzumab and taxane. The impressive efficacy exhibited by T-DM1 has heightened the need for more further studies on the underlying mechanisms of T-DM1 cytotoxicity. Previous research suggested that autophagy was crucial for cancer therapy, but the role of autophagy in T-DM1 treatment has not been investigated. Here, we demonstrated for the first time that T-DM1 triggered obvious autophagy in HER2-positive SK-BR-3 and BT-474 breast cancer cells. Blocking autophagy with pharmacological inhibitors chloroquine (CQ) or LY294002 partly reduced T-DM1-induced apoptosis and Caspase-3/7 activation, suggesting that autophagy played an essential role in the cytotoxicity induced by T-DM1 in HER2-positive breast cancer cells. Further investigation demonstrated that Akt/mTOR signaling pathway was involved in T-DM1-induced autophagy in a time-dependent manner. Altogether, our results highlighted the important role of autophagy as a novel mechanism for T-DM1-induced cytotoxicity and elucidated the critical relationships between T-DM1-induced autophagy and apoptosis in human HER2-positive breast cancer cells, which provides novel insight into the underlying anti-tumor mechanism of T-DM1.
Machine learning through cryptographic glasses: combating adversarial attacks by key-based diversified aggregation
Authors: Taran Olga , Rezaeifar Shideh , Holotyak Taras , Voloshynovskiy Slava
Published: June 2020

In recent years, classification techniques based on deep neural networks (DNN) were widely used in many fields such as computer vision, natural language processing, and self-driving cars. However, the vulnerability of the DNN-based classification systems to adversarial attacks questions their usage in many critical applications. Therefore, the development of robust DNN-based classifiers is a critical point for the future deployment of these methods. Not less important issue is understanding of the mechanisms behind this vulnerability. Additionally, it is not completely clear how to link machine learning with cryptography to create an information advantage of the defender over the attacker. In this paper, we propose a key-based diversified aggregation (KDA) mechanism as a defense strategy in a gray- and black-box scenario. KDA assumes that the attacker (i) knows the architecture of classifier and the used defense strategy, (ii) has an access to the training data set, but (iii) does not know a secret key and does not have access to the internal states of the system. The robustness of the system is achieved by a specially designed key-based randomization. The proposed randomization prevents the gradients’ back propagation and restricts the attacker to create a “bypass” system. The randomization is performed simultaneously in several channels. Each channel introduces its own randomization in a special transform domain. The sharing of a secret key between the training and test stages creates an information advantage to the defender. Finally, the aggregation of soft outputs from each channel stabilizes the results and increases the reliability of the final score. The performed experimental evaluation demonstrates a high robustness and universality of the KDA against state-of-the-art gradient-based gray-box transferability attacks and the non-gradient-based black-box attacks (The results reported in this paper have been partially presented in CVPR 2019 (Taran et al., Defending against adversarial attacks by randomized diversification, 2019) & ICIP 2019 (Taran et al., Robustification of deep net classifiers by key-based diversified aggregation with pre-filtering, 2019)).
e-Health interventions for healthy aging: a systematic review
Authors: Buyl Ronald , Beogo Idrissa , Fobelets Maaike , Deletroz Carole , Van Landuyt Philip , Dequanter Samantha , Gorus Ellen , Bourbonnais Anne , Giguère Anik , Lechasseur Kathleen , Gagnon Marie-Pierre
Published: June 2020

Background

Healthy aging (HA) is a contemporary challenge for population health worldwide. Electronic health (e-Health) interventions have the potential to support empowerment and education of adults aged 50 and over.

Objectives

To summarize evidence on the effectiveness of e-Health interventions on HA and explore how specific e-Health interventions and their characteristics effectively impact HA.

Methods

A systematic review was conducted based on the Cochrane Collaboration methods including any experimental study design published in French, Dutch, Spanish, and English from 2000 to 2018.

Results

Fourteen studies comparing various e-Health interventions to multiple components controls were included. The target population, type of interventions, and outcomes measured were very heterogeneous across studies; thus, a meta-analysis was not possible. However, effect estimates indicate that e-Health interventions could improve physical activity. Positive effects were also found for other healthy behaviors (e.g., healthy eating), psychological outcomes (e.g., memory), and clinical parameters (e.g., blood pressure). Given the low certainty of the evidence related to most outcomes, these results should be interpreted cautiously.

Conclusions

This systematic review found limited evidence supporting the effectiveness of e-Health interventions, although the majority of studies show positive effects of these interventions for improving physical activity in older adults. Thus, better quality evidence is needed regarding the effects of e-Health on the physiological, psychological, and social dimensions of HA.

Systematic review registration

The review protocol was registered in PROSPERO (registration number: CRD42016033163)
Derivation of computational formulas for Changhee polynomials and their functional and differential equations
Authors: So Ji Suk , Simsek Yilmaz
Published: June 2020

The goal of this paper is to demonstrate many explicit computational formulas and relations involving the Changhee polynomials and numbers and their differential equations with the help of functional equations and partial derivative equations for generating functions of these polynomials and numbers. These formulas also include the Euler polynomials, the Stirling numbers, the Bernoulli numbers and polynomials of the second kind, the Changhee polynomials of higher order, and the Daehee polynomials of higher order, which are among the well known polynomial families. By using PDEs of these generating functions, not only some recurrence relations for derivative formulas of the Changhee polynomials of higher order, but also two open problems for partial derivative equations for generating functions are given. Moreover, by using functional equations of the generating functions, two inequalities including combinatorial sums, the Changhee numbers of negative order, and the Stirling numbers of the second kind are provided. Finally, further remarks and observations for the results of this paper are given.
Prevalence, indications and neonatal complications of caesarean deliveries in Cameroon: a systematic review and meta-analysis
Authors: Njim Tsi , Tanyitiku Bayee Swiri , Mbanga Clarence
Published: June 2020

Background

The trend of increasing caesarean deliveries in developed countries over the past three decades is now being observed in sub-Saharan African. This rise might be associated with an increase in the complications that could arise from this surgical intervention. We therefore sought to assess the prevalence, indications and complications of caesarean deliveries in Cameroon.

Methods

We systematically searched online databases: Medline; Global Health and the CINAHL from 01st January 1966 to 25th July 2019. We reviewed published cohort studies, retrospective register analysis and cross-sectional studies that described cohorts of pregnant women presenting at delivery facilities in Cameroon; and included those that had an estimate of the proportion of women who delivered by caesarean sections.

Results

There were 126 articles initially identified by the search and 88 articles were retained after removal of duplicates. After screening of the titles and abstracts, and full text review, we identified 16 articles describing 22 cohorts of women presenting for delivery in health facilities in Cameroon. The overall estimate for the prevalence of caesarean deliveries was 9.9% (95% CI: 7.4, 12.8%, I2 = 99.68%, χ2 = 315.9, p < 0.001). The prevalence of caesarean deliveries increased progressively from 3.4% (95% CI: 2.2, 4.8%) before the year 2000, to 9.8% (95% CI: 7.4, 12.8%) between 2000 and 2009 and 14.7% (95% CI: 8.8, 21.7%) from 2010 to 2019. The three commonest indications for caesarean deliveries were: cephalopelvic disproportion (27.5%; 95% CI: 17.5, 38.7%); previous caesarean deliveries (13.2%; 95% CI: 7.4, 20.3%) and foetal distress (11.2%; 95% CI: 4.8, 19.5%). Neonates who were born by caesarean delivery were more likely to have neonatal asphyxia when compared with neonates born from vaginal deliveries (OR: 6.5; 95% CI: 2.5, 16.5).

Conclusion

The rates of caesarean deliveries in Cameroon falls just within the recommended 10–15% range proposed by the World Health Organisation but have however been increasing progressively in the past decades. There is a strong need to assess the various indications of caesarean deliveries in Cameroon in order to curb its associated complications.
Engineering CRISPR/Cas9 to mitigate abundant host contamination for 16S rRNA gene-based amplicon sequencing
Authors: Song Luyang , Xie Kabin
Published: June 2020

Background

High-throughput sequencing of bacterial 16S rRNA gene (16S-seq) is a useful and common method for studying bacterial community structures. However, contamination of the 16S rRNA genes from the mitochondrion and plastid hinders the sensitive bacterial 16S-seq in plant microbiota profiling, especially for some plant species such as rice. To date, efficiently mitigating such host contamination without a bias is challenging in 16S rRNA gene-based amplicon sequencing.

Results

We developed Cas-16S-seq method to reduce abundant host contamination for plant microbiota profiling. This method utilizes the Cas9 nuclease and specific guide RNA (gRNA) to cut 16S rRNA targets during library construction, thereby removing host contamination in 16S-seq. We used rice as an example to validate the feasibility and effectiveness of Cas-16S-seq. We established a bioinformatics pipeline to design gRNAs that specifically target rice 16S rRNA genes without bacterial 16S rRNA off-targets. We compared the effectiveness of Cas-16S-seq with that of the commonly used 16S-seq method for artificially mixed 16S rRNA gene communities, paddy soil, rice root, and phyllosphere samples. The results showed that Cas-16S-seq substantially reduces the fraction of rice 16S rRNA gene sequences from 63.2 to 2.9% in root samples and from 99.4 to 11.6% in phyllosphere samples on average. Consequently, Cas-16S-seq detected more bacterial species than the 16S-seq in plant samples. Importantly, when analyzing soil samples, Cas-16S-seq and 16S-seq showed almost identical bacterial communities, suggesting that Cas-16S-seq with host-specific gRNAs that we designed has no off-target in rice microbiota profiling.

Conclusion

Our Cas-16S-seq can efficiently remove abundant host contamination without a bias for 16S rRNA gene-based amplicon sequencing, thereby enabling deeper bacterial community profiling with a low cost and high flexibility. Thus, we anticipate that this method would be a useful tool for plant microbiomics.
Transcriptional profiling of multiple system atrophy cerebellar tissue highlights differences between the parkinsonian and cerebellar sub-types of the disease
Authors: Piras Ignazio S. , Bleul Christiane , Schrauwen Isabelle , Talboom Joshua , Llaci Lorida , De Both Matthew D. , Naymik Marcus A. , Halliday Glenda , Bettencourt Conceicao , Holton Janice L. , Serrano Geidy E. , Sue Lucia I. , Beach Thomas G. , Stefanova Nadia , Huentelman Matthew J.
Published: June 2020

Multiple system atrophy (MSA) is a rare adult-onset neurodegenerative disease of unknown cause, with no effective therapeutic options, and no cure. Limited work to date has attempted to characterize the transcriptional changes associated with the disease, which presents as either predominating parkinsonian (MSA-P) or cerebellar (MSC-C) symptoms. We report here the results of RNA expression profiling of cerebellar white matter (CWM) tissue from two independent cohorts of MSA patients (n = 66) and healthy controls (HC; n = 66). RNA samples from bulk brain tissue and from oligodendrocytes obtained by laser capture microdissection (LCM) were sequenced. Differentially expressed genes (DEGs) were obtained and were examined before and after stratifying by MSA clinical sub-type.

We detected the highest number of DEGs in the MSA-C group (n = 747) while only one gene was noted in MSA-P, highlighting the larger dysregulation of the transcriptome in the MSA-C CWM. Results from both bulk tissue and LCM analysis showed a downregulation of oligodendrocyte genes and an enrichment for myelination processes with a key role noted for the QKI gene. Additionally, we observed a significant upregulation of neuron-specific gene expression in MSA-C and enrichment for synaptic processes. A third cluster of genes was associated with the upregulation of astrocyte and endothelial genes, two cell types with a key role in inflammation processes. Finally, network analysis in MSA-C showed enrichment for β-amyloid related functional classes, including the known Alzheimer’s disease (AD) genes, APP and PSEN1.

This is the largest RNA profiling study ever conducted on post-mortem brain tissue from MSA patients. We were able to define specific gene expression signatures for MSA-C highlighting the different stages of the complex neurodegenerative cascade of the disease that included alterations in several cell-specific transcriptional programs. Finally, several results suggest a common transcriptional dysregulation between MSA and AD-related genes despite the clinical and neuropathological distinctions between the two diseases.
The lipid phosphatase Synaptojanin 1 undergoes a significant alteration in expression and solubility and is associated with brain lesions in Alzheimer’s disease
Authors: Ando Kunie , Ndjim Marième , Turbant Sabrina , Fontaine Gaëlle , Pregoni Gustavo , Dauphinot Luce , Yilmaz Zehra , Suain Valérie , Mansour Salwa , Authelet Michèle , De Dekker Robert , Leroy Karelle , Delatour Benoît ,   Brain Bank NeuroCEB Neuropathology Network, Letournel Franck , Martin-Négrier Marie-Laure , Chapon Françoise , Godfraind Catherine , Maurage Claude-Alain , Deramecourt Vincent , Meyronnet David , Streichenberger Nathalie , de Paula André Maues , Rigau Valérie , Vandenbos-Burel Fanny , Duyckaerts Charles , Seilhean Danielle , Boluda Susana , Plu Isabelle , Milin Serge , Chiforeanu Dan Christian , Laquerrière Annie , Lannes Béatrice , Duyckaerts Charles , Potier Marie-Claude , Brion Jean-Pierre
Published: June 2020

Synaptojanin 1 (SYNJ1) is a brain-enriched lipid phosphatase critically involved in autophagosomal/endosomal trafficking, synaptic vesicle recycling and metabolism of phosphoinositides. Previous studies suggest that SYNJ1 polymorphisms have significant impact on the age of onset of Alzheimer’s disease (AD) and that SYNJ1 is involved in amyloid-induced toxicity. Yet SYNJ1 protein level and cellular localization in post-mortem human AD brain tissues have remained elusive. This study aimed to examine whether SYNJ1 localization and expression are altered in post-mortem AD brains. We found that SYNJ1 is accumulated in Hirano bodies, plaque-associated dystrophic neurites and some neurofibrillary tangles (NFTs). SYNJ1 immunoreactivity was higher in neurons and in the senile plaques in AD patients carrying one or two ApolipoproteinE (APOE) ε4 allele(s). In two large cohorts of APOE-genotyped controls and AD patients, SYNJ1 transcripts were significantly increased in AD temporal isocortex compared to control. There was a significant increase in SYNJ1 transcript in APOEε4 carriers compared to non-carriers in AD cohort. SYNJ1 was systematically co-enriched with PHF-tau in the sarkosyl-insoluble fraction of AD brain. In the RIPA-insoluble fraction containing protein aggregates, SYNJ1 proteins were significantly increased and observed as a smear containing full-length and cleaved fragments in AD brains. In vitro cleavage assay showed that SYNJ1 is a substrate of calpain, which is highly activated in AD brains. Our study provides evidence of alterations in SYNJ1 mRNA level and SYNJ1 protein degradation, solubility and localization in AD brains.
Modeling of gonioscopic anterior chamber angle grades based on anterior segment optical coherence tomography
Authors: Dai Yingying , Zhang Shaodan , Shen Meixiao , Zhou Yuheng , Wang Mengyi , Ye Jie , Zhu Dexi
Published: June 2020

Background

To quantitatively assess anterior chamber angle (ACA) structure by anterior segment optical coherence tomography (AS-OCT) and develop a model to evaluate angle width as defined by gonioscopy.

Methods

The ACAs of each quadrant were evaluated by gonioscopy, classified by the Scheie grading system, and assigned into one of the three grades: small angle (SA), moderate angle (MA), and large angle (LA). The eyes were imaged by AS-OCT, and ACA structural parameters including angle opening distance at the scleral spur (AODSS) and at 750 μm anterior to the scleral spur (AOD750), trabecular-iris space area at 750 μm anterior to the scleral spur (TISA750), and a newly defined parameter “light intersection distance” (LID), were measured. The ACA structural data were used to construct an ordered logistic regression model for assignment of ACAs to one of the three angle grades. The validity of the model was then tested.

Results

A total of 169 quadrants from 53 subjects were included in the analysis, of which 111 quadrants were included in the modeling data and 58 in the testing data. In pairwise comparisons of SA, MA, and LA by ANOVA, the measured parameters were as follows: AOD750 (0.174 ± 0.060 vs. 0.249 ± 0.068 vs. 0.376 ± 0.114 mm;P < 0.001), TISA750 (0.075 ± 0.035 vs. 0.117 ± 0.036 vs. 0.181 ± 0.062 mm2;P < 0.001), and LID (− 0.300 ± 0.187 vs. -0.085 ± 0.170 vs. 0.122 ± 0.156 mm;P < 0.001). The ACA grading model based on LID showed a relatively high correction rate of 72.4%, and the model efficiency, calculated using the receiver operating characteristic, showed an area under the curve of 0.740. Weighted kappa statistics showed a good agreement for multiple ACA grades (0.772).

Conclusions

The AS-OCT-based multiple ACA grades model was demonstrated as a non-contact approach for ACA assessment with high speed and high spatial resolution, providing guidance for diagnosis of angle closure.
Right trisectionectomy for liver metastasis of granulosa cell tumor: a case report and literature review
Authors: Koganezawa Itsuki , Tomita Koichi , Nakagawa Masashi , Ozawa Yosuke , Kobayashi Toshimichi , Sano Toru , Tsutsui Rina , Chiba Naokazu , Okimura Akira , Nakatsugawa Munehide , Hirano Hiroshi , Kawachi Shigeyuki
Published: June 2020

Background

Granulosa cell tumor (GCT) is a type of ovarian sex cord-stromal tumor with low-grade malignancy, which can recur long after primary resection. All reports on GCTs in the liver describe cases of metastases, while there are no previous reports of primary GCTs originating from the liver. We report a case of GCT, with recurrence of liver metastasis long after ovariectomy, which was subsequently resected by a right trisectionectomy.

Case presentation

A 76-year-old woman presented with a history of surgical resection of an ovarian tumor performed 30 years previously; no details of the tumor were available. When she was 68 years old, an abdominal ultrasound revealed a small liver mass, which was diagnosed as a hepatic hemangioma with slow growth. Outpatient follow-up was discontinued for 5 years, and the patient was not examined again until the age of 76 years. At this point, the tumor had substantially increased in size, and surgical resection was required owing to suspicion of malignancy. The patient was then referred to our hospital. Contrast-enhanced computed tomography (CT) showed a large tumor, approximately 18 cm in size, occupying the right lobe and medial section of the liver. After percutaneous transhepatic portal vein embolization, a right trisectionectomy was performed. The histopathological findings of the resected specimen showed that the tumor cells had “coffee bean-like” nuclear grooves, which are characteristic of a GCT. Acidophilic non-structural Call-Exner bodies were also observed. Inhibin-α, CD99, and CD56 markers of sex cord-stromal tumors were detected on immunohistological examination; all pathology suggested a GCT. We considered the tumor to be a liver metastasis of a previous ovarian GCT that was resected 30 years prior by ovariectomy. There was no recurrence for > 15 months after the hepatectomy.

Conclusions

We report a case of a GCT in the liver, which was identified to be a liver metastasis. Right trisectionectomy was subsequently performed for tumor resection. Clinicians should be aware that ovarian GCTs may recur in the liver, and that GCT recurrence may occur long after ovariectomy of the primary ovarian GCT.
Internal hernia of the stomach associated with colostomy after laparoscopic surgery for rectal cancer: a case report
Authors: Hashida Hiroki , Kita Ryosuke , Kondo Masato , Mizuno Ryosuke , Kobayashi Hiroyuki , Kaihara Satoshi
Published: June 2020

Background

Colostomy via the intraperitoneal route is often performed during laparoscopic Hartmann’s operation or abdominoperineal resection. Internal hernia of the small intestine often occurs after colostomy. This report shows a rare case of internal hernia of the stomach associated with sigmoid colostomy after laparoscopic abdominoperineal resection for rectal cancer.

Case presentation

The patient was a 79-year-old woman with a sigmoid colostomy. Computed tomography scan showed a markedly distended stomach in the space between the lifted sigmoid colon and the lateral abdominal wall. Laparoscopy revealed that the body of the stomach had passed through a hernia orifice located between the lifted sigmoid colon and the left lateral abdominal wall. The dislocated stomach was restored to its normal position, and the lateral defect was closed with the lateral peritoneum and the lifted sigmoid colon laparoscopically.

Conclusions

Internal hernia associated with colostomy can lead to not only obstruction of the small intestine, but also obstruction of the stomach. We reported a successful case of the suture repair for the internal hernia of the stomach associated with colostomy.