bluuebunny/crossref_metadata_2025 huggingface dataset:
K-D Balance: An objective measure of balance in tandem and double leg stances
Authors: Zhang Chelsea , Talaber Alexandra , Truong Melanie , Vargas Bert B
Published: November 2019

Background and objective

Subjective grade-based scoring balance assessments tend to be lengthy and have demonstrated poor repeatability and reliability. This study examined the reliability of a mobile balance assessment tool and differences in balance measurements between individuals at risk for a balance deficit secondary to a diagnosed neurological or musculoskeletal condition and a control group of healthy individuals.

Methods

Objective balance testing was measured using K-D Balance on a compatible iPhone. Seventy-seven participants were enrolled (control group, n =  44; group at risk for balance deficits, n =  33). Mean and standard deviation of K-D Balance were recorded for each stance. Intra-rater reliability was calculated by repeating the trial.

Results

Overall balance scores were superior for the control group compared with the group at risk for balance deficits in double leg stance (mean (SD): 0.15 (0.12) versus 0.18 (0.13), p =  0.260), tandem stance right leg (mean (SD): 0.27 (0.17) versus 0.45 (0.49), p =  0.028), and tandem stance left leg (mean (SD): 0.26 (0.17) versus 0.35 (0.35), p =  0.136). Intra-rater reliability was good to excellent for K-D Balance double leg stance (intra-class correlation coefficient (ICC) = 0.80, 95% confidence interval (CI) 0.58–1.03), tandem stance right leg (ICC = 0.96, 95% CI 0.86–1.06) and tandem stance left leg (ICC = 0.98, 95% CI 0.95–1.0).

Conclusions

K-D Balance revealed differences in balance performance between healthy individuals compared with individuals with neurological or musculoskeletal impairment. Objective balance measures may improve the accuracy and reliability of clinical balance assessment by detecting subtle differences in balance and aid in early detection of diseases that impair balance.
Serum hepcidin levels in multiple sclerosis
Authors: Bsteh Gabriel , Haschka David , Tymoszuk Piotr , Berek Klaus , Petzer Verena , Hegen Harald , Wurth Sebastian , Auer Michael , Zinganell Anne , Pauli Franziska Di , Deisenhammer Florian , Weiss Guenter , Berger Thomas
Published: November 2019

Background

Brain iron accumulation is associated with multiple sclerosis (MS). Hepcidin is the master regulator of iron homeostasis and distribution. Dysregulation of hepcidin is a feature of different chronic inflammatory diseases but has not been investigated in MS so far.

Objective

The aim of this study was to determine serum hepcidin levels of MS patients and healthy volunteers serving as controls and to investigate possible relations between hepcidin levels, disease activity and disease course.

Methods

In a cross-sectional design, we measured serum hepcidin levels in 71 MS patients and 16 healthy controls (HC). MS patients were sub-grouped in active relapsing–remitting MS (aRRMS), inactive (i)RRMS, active progressive MS (aPMS) and inactive (i)PMS. Blood parameters were measured by standard laboratory methods.

Results

Median hepcidin levels were 26.9 ng/ml (confidence interval (CI) 22.8; 30.9) in MS and 17.3 ng/ml (CI 12.8; 23.4) in HC with significant age and sex effects. Hepcidin correlates were in line with hepcidin as an indicator of iron stores. After correction for age and sex, hepcidin was neither associated with MS subgroups nor degree of disability and occurrence of relapses.

Conclusions

Serum hepcidin levels are not associated with disease activity and disease course in MS.
When Context Is Hard to Come By: External Comparators and How to Use Them
Authors: Mack Christina , Christian Jennifer , Brinkley Emma , Warren Edward J. , Hall Marni , Dreyer Nancy
Published: November 2019

External comparators, also referred to as historical or synthetic controls, present transformational opportunities for broad context and insights alongside clinical research results. The recent confluence of access to quality real-world data (RWD), advanced epidemiologic methods, and legislative directives to regulators for expanded use of RWD is increasing interest in real-world external comparators, opening the door to achieve broader generalizability and learn more, faster. In this less standardized area of research, tailored scientific methodology must be applied for external comparators to accomplish clinical development objectives. Here, we describe methodological considerations for design and illustrate how RWD comparators have been used for regulatory and reimbursement decisions.
More on Van Leur’s ‘Pedlar’ Thesis
Authors: Chaudhury Sushil
Published: November 2019

Van Leur, a Dutch official in Indonesia, developed a theory about the pre-colonial nature of seaborne Asian trade. According to him it was large in volume but with minuscule units (pedlars). In contrast, the European companies, because of the advantage secured by them through economies of scale, were able to carry on oceanic trade far more successfully and so prevailed over the Asian pedlars. This thesis, along with its later versions, is examined in the following article, with evidence to show that (a) Asian merchants’ establishments could also be very large and (b) could successfully stand up to Europe Companies in fair competition. Moreover, van Leur was further wrong in imagining that pre-colonial Asian maritime commerce was confined to high-priced goods only.
‘In Search of Mammon’s Treasure Trove’: Hemendrakumar Roy’s Use of Travel in Children’s Adventure Literature
Authors: Mazumder Rajashree
Published: November 2019

Travel plays a critical role in twentieth-century Bengali adventure literature for adolescent males. Armchair journeys through the Empire and beyond let that audience discover the world: a panoply of high- to low-ranking cultures, utterly strange geographical spaces and, often, their ‘barbarous’, ‘uncivilized’ inhabitants. Exemplified by Hemendrakumar Roy’s works, the genre encourages boys to draw correlations between race, ethnicity and territory in a way that elevates Hindu elites within a civilizational hierarchy that borrows, but will not follow wholesale, the Western schema.

The literary trope of travel imaginatively transports the colonized protagonists and audience across their country’s borders. Yet the destinations, distanced from their experience by perilous voyages, are clearly chosen to spark reflection on their own domestic spaces. The adventures, in turn, fuel their individual and, ideally, national self-transformation. For Roy’s travel narratives promote such changes by featuring Bengali heroes defeating horrific hazards with courage, strength, intelligence, self-sacrifice and perseverance—‘masculine’ qualities the author hopes a new generation will imbibe and use to serve the nation. Doing so, he also hopes, will disprove in reality what he demolished in writing: colonizers’ stereotype of Bengalis as effeminate cowards, and their dismissal of Indian culture as beneath their own.
Mobilizing a fast policy fix: Exploring the translation of 10-year plans to end homelessness in Alberta, Canada
Authors: Evans Joshua , R Masuda Jeffrey
Published: November 2019

The management of homelessness has taken various forms over time. In 2003, the U.S. federal government significantly shifted its approach, ambitiously committing to end homelessness within 10 years by targeting the chronically homeless using the Housing First model. This approach to homelessness has rapidly spread across North America and beyond. This article is concerned with how the mobility of these 10-year plans has been realized. Drawing on Peck and Theodore’s concept of “fast policy,” and borrowing perspectives developed in actor-network theory, the article develops a case study of Alberta, Canada, to chronicle how 10-year plans were translated through a dense network of political alignments, socio-technical expertise, and statistical inscriptions. A close examination of these translations invites us to problematize this socio-technical infrastructure as a powerful mode of adaptive governance closely associated with the dynamism of neoliberalism itself.
A Glycine max sodium/hydrogen exchanger enhances salt tolerance through maintaining higher Na+ efflux rate and K+/Na+ ratio in Arabidopsis
Authors: Sun Tian-Jie , Fan Long , Yang Jun , Cao Ren-Zhi , Yang Chun-Yan , Zhang Jie , Wang Dong-Mei
Published: November 2019

Background

Soybean (Glycine max (L.)) is one the most important oil-yielding cash crops. However, the soybean production has been seriously restricted by salinization. It is therefore crucial to identify salt tolerance-related genes and reveal molecular mechanisms underlying salt tolerance in soybean crops. A better understanding of how plants resist salt stress provides insights in improving existing soybean varieties as well as cultivating novel salt tolerant varieties. In this study, the biological function of GmNHX1, a NHX-like gene, and the molecular basis underlying GmNHX1-mediated salt stress resistance have been revealed.

Results

We found that the transcription level of GmNHX1 was up-regulated under salt stress condition in soybean, reaching its peak at 24 h after salt treatment. By employing the virus-induced gene silencing technique (VIGS), we also found that soybean plants became more susceptible to salt stress after silencing GmNHX1 than wild-type and more silenced plants wilted than wild-type under salt treatment. Furthermore, Arabidopsis thaliana expressing GmNHX1 grew taller and generated more rosette leaves under salt stress condition compared to wild-type. Exogenous expression of GmNHX1 resulted in an increase of Na+ transportation to leaves along with a reduction of Na+ absorption in roots, and the consequent maintenance of a high K+/Na+ ratio under salt stress condition. GmNHX1-GFP-transformed onion bulb endothelium cells showed fluorescent pattern in which GFP fluorescence signals enriched in vacuolar membranes. Using the non-invasive micro-test technique (NMT), we found that the Na+ efflux rate of both wild-type and transformed plants after salt treatment were significantly higher than that of before salt treatment. Additionally, the Na+ efflux rate of transformed plants after salt treatment were significantly higher than that of wild-type. Meanwhile, the transcription levels of three osmotic stress-related genes, SKOR, SOS1 and AKT1 were all up-regulated in GmNHX1-expressing plants under salt stress condition.

Conclusion

Vacuolar membrane-localized GmNHX1 enhances plant salt tolerance through maintaining a high K+/Na+ ratio along with inducing the expression of SKOR, SOS1 and AKT1. Our findings provide molecular insights on the roles of GmNHX1 and similar sodium/hydrogen exchangers in regulating salt tolerance.
Unique characteristics of CpG island methylator phenotype (CIMP) in a Chinese population with colorectal cancer
Authors: Liu Jiang , Tang Li , Yi Jinhua , Li Guimei , Lu Youwang , Xu Yu , Zhao Shuhua , Mao Rui , Li Xiaolu , Ren Li , Wang Kunhua
Published: November 2019

Background

Molecular characteristics of CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) have been well documented in Western, but not in Chinese, populations.

Methods

We investigated the incidence of CIMP, BRAF/KRAS mutation, and microsatellite instability (MSI) in a Chinese population with CRC (n = 401) and analysed associations between CIMP status and clinicopathological and molecular features.

Results

A total of 41 cases, 310 cases, and 40 cases were classified as CIMP-high, CIMP-low, and CIMP-negative, respectively. We detected a significantly low incidence of BRAF mutation in adenomas (2%) and CRC (0.7%), and a relatively low incidence of KRAS mutation (24.9%) compared with that in other populations. We also detected a relatively low incidence of CIMP-high (10.2%), which was significantly associated with younger age (≤49 years of age), female sex, and proximal tumour location.

Conclusions

This study revealed unique characteristics of CIMP in a Chinese population with colorectal cancer. Developing specific CIMP markers based on unique populations or ethnic groups will further help to fully elucidate CIMP pathogenesis.
A multiepitope peptide vaccine against HCV stimulates neutralizing humoral and persistent cellular responses in mice
Authors: Dawood Reham M. , Moustafa Rehab I. , Abdelhafez Tawfeek H. , El-Shenawy Reem , El-Abd Yasmine , Bader El Din Noha G. , Dubuisson Jean , El Awady Mostafa K.
Published: November 2019

Background

Although DAAs hold promise to significantly reduce rates of chronic HCV infections, its eradication still requires development of an effective vaccine. Prolonged T cell responses and cross neutralizing antibodies are ideal for vaccination against the infection. We aimed to design and synthesize a 6 multi epitope peptide vaccine candidate and provide evidence for production of extended cellular and neutralizing Abs in mice.

Methods

Six peptides derived from conserved epitopes in E1, E2 (n = 2),NS4B, NS5A and NS5B were designed, synthesized in a multiple antigenic peptide (MAP) form and administered w/o adjuvant to BALB/c mice as HCVp6-MAP at doses ranging from 800 ng to 16 μg. Humoral responses to structural epitopes were assayed by ELISA at different times after injection. ELISpot assay was used to evaluate IFN ɣ producing CD4+/ CD8+ T- lymphocytes at extended durations i.e. > 20 weeks. Viral neutralization by mice sera was tested for genotypes 2a (JFH1) and a chimeric 2a/4a virus (ED43/JFH1) in HCVcc culture.

Results

HCVp6-MAP confers potent viral neutralization and specific cellular responses at > 1600 ng/ animal for at least 20 weeks.

Conclusion

We report on a promising anti HCV vaccine for future studies on permissive hosts and in clinical trials.
Transmission and serotype features of hand foot mouth disease in household contacts in Dong Thap, Vietnam
Authors: Hoang Cuong Quoc , Nguyen Thao Thanh Thi , Ho Nguyen Xuan , Nguyen Hai Duc , Nguyen An Binh , Nguyen Tham Hong Thi , Phan Hung Cong , Phan Lan Trong
Published: November 2019

Background

Hand, foot and mouth disease (HFMD) has emerged as a major public health issue in Vietnam since 2003. We aimed to investigate the household transmission of HFMD and its causative viruses from 150 households in a high incidence province in Vietnam.

Methods

A longitudinal study was conducted in patients presenting to the provincial hospital with a HFMD-like syndrome, along with their household members between April and August 2014 in Dong Thap Province. Each participant was followed up for 2 weeks. We enrolled 150 patients aged under 15 who were clinically diagnosed with HFMD in Dong Thap Hospital, 600 household members, and 581/600 household members completed the study. All participants were interviewed using a standard questionnaire. Throat swabs and blood samples were taken for molecular detection of viruses and assessment of neutralizing antibodies, respectively. Index cases were defined using a clinical case definition, household contact cases were defined using a similar definition applied to the 2 weeks before admission and 2 weeks after discharge of the index case. Characteristics of index cases, household contacts, the attack rate, serotype features and related factors of HFMD were reported.

Result

Among 150 index cases, 113 were laboratory confirmed: 90/150 were RT-PCR-positive, 101/142 had a ≥ 4-fold increase of neutralizing antibody against Enterovirus A71 (EV-A71), Coxsackievirus (CV) A6 or CV-A16 across the two samples collected. 80/150 (53%) were males, and 45/150 (30%) were under the age of 1. The predominant serotype was CV-A6, identified in 57/87 (65.5%) of the specimens. No deaths were reported. Among 581 household contacts, 148 were laboratory confirmed: 12/581 were RT-PCR-positive, 142/545 had a ≥ 4-fold increase of neutralizing antibodies against EV-A71, CV-A6 or CV-A16; 4 cases experienced HFMD in the past 4 weeks. Attack rate among household contacts was 148/581 (25.5%). In 7/12 (58%) instances, the index and secondary cases were infected with the same serotype. Having a relationship to index case was significantly associated with EV infection.

Conclusion

The attack rate among household contacts was relatively high (25.5%) in this study and it seems justified to also consider the household setting as an additional target for intervention programs.
Radiological appearance of hepatocellular carcinoma predicts the response to trans-arterial chemoembolization in patients undergoing liver transplantation
Authors: Zhang Wei , Xu An-Hui , Wang Wei , Wu Yan-Hui , Sun Qian-Ling , Shu Chang
Published: November 2019

Background

The ultimate goal of locoregional therapy (LRT) to the liver is to induce total tumor necrosis. Trans-arterial chemoembolization (TACE) is the mainstay bridging therapy for patients with hepatocellular carcinoma (HCC) waiting for liver transplantation (LT). However, tumor response rate is variable. The purpose of this study was to correlate HCC radiological appearance with level of tumor necrosis during explant analysis from patients undergoing LT who received pre-LT TACE.

Methods

From January 2000 to December 2018, a total of 66 patients with HCC who had been treated prior to LT by means of TACE were analyzed. Diagnosis of HCC was made based on AASLD guidelines and confirmed via histopathology explant analysis. Radiologic tumor response after TACE was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Degree of tumor necrosis was determined by histopathology analysis of liver explants. HCC radiological appearances on CT before TACE were assessed and correlated with histological findings after LT.

Results

Eighty nine TACE procedures (1.35 ± 0.67; 1–4) were performed, of which 18 were repeated TACE (27.3%) procedures. In 56.1% of the patients, ≥90% (near-complete) tumor necrosis was achieved. Concordance between mRECIST criteria and pathology was observed in 63% of the patients, with an underestimation of tumor response in 18 (27%) patients and an overestimation in 6 (9.1%). Near-complete tumor necrosis upon pathological analysis was associated with tumor hyper-enhancement in the arterial phase (P = 0.002), “typical tumor enhancement” (P = 0.010) and smooth tumor margins (p = 0.011). The multivariate analysis showed that well circumscribed HCCs with smooth margins and arterial hyper-enhancement independently correlated with post-TACE near-complete histological tumor necrosis.

Conclusions

The well circumscribed HCC lesions with arterial hyper-enhancement are more susceptible to TACE than lesions with arterial phase iso or hypo-enhancement and lesions with infiltrative appearance. Pre-TACE CT imaging may ease the selection of an optimal treatment strategy for bridging patients with HCC to liver transplantation.
Apparent diffusion coefficient cannot predict molecular subtype and lymph node metastases in invasive breast cancer: a multicenter analysis
Authors: Surov Alexey , Chang Yun-Woo , Li Lihua , Martincich Laura , Partridge Savannah C. , Kim Jin You , Wienke Andreas
Published: November 2019

Background

Radiological imaging plays a central role in the diagnosis of breast cancer (BC). Some studies suggest MRI techniques like diffusion weighted imaging (DWI) may provide further prognostic value by discriminating between tumors with different biologic characteristics including receptor status and molecular subtype. However, there is much contradictory reported data regarding such associations in the literature. The purpose of the present study was to provide evident data regarding relationships between quantitative apparent diffusion coefficient (ADC) values on DWI and pathologic prognostic factors in BC.

Methods

Data from 5 centers (661 female patients, mean age, 51.4 ± 10.5 years) were acquired. Invasive ductal carcinoma (IDC) was diagnosed in 625 patients (94.6%) and invasive lobular carcinoma in 36 cases (5.4%). Luminal A carcinomas were diagnosed in 177 patients (28.0%), luminal B carcinomas in 279 patients (44.1%), HER 2+ carcinomas in 66 cases (10.4%), and triple negative carcinomas in 111 patients (17.5%). The identified lesions were staged as T1 in 51.3%, T2 in 43.0%, T3 in 4.2%, and as T4 in 1.5% of the cases. N0 was found in 61.3%, N1 in 33.1%, N2 in 2.9%, and N3 in 2.7%. ADC values between different groups were compared using the Mann–Whitney U test and by the Kruskal-Wallis H test. The association between ADC and Ki 67 values was calculated by Spearman’s rank correlation coefficient.

Results

ADC values of different tumor subtypes overlapped significantly. Luminal B carcinomas had statistically significant lower ADC values compared with luminal A (p = 0.003) and HER 2+ (p = 0.007) lesions. No significant differences of ADC values were observed between luminal A, HER 2+ and triple negative tumors. There were no statistically significant differences of ADC values between different T or N stages of the tumors. Weak statistically significant correlation between ADC and Ki 67 was observed in luminal B carcinoma (r = − 0.130, p = 0.03). In luminal A, HER 2+ and triple negative tumors there were no significant correlations between ADC and Ki 67.

Conclusion

ADC was not able to discriminate molecular subtypes of BC, and cannot be used as a surrogate marker for disease stage or proliferation activity.
Sociodemographic determinants of knowledge and attitude in the primary prevention of cervical cancer among University Tunku Abdul Rahman (UTAR) students in Malaysia: preliminary study of HPV vaccination
Authors: Tusimin Maiza , Yee Chek Lo , Razak Nur Zarifah Syahmi Abdul , Zainol Mohamad Izwan , Minhat Halimatus Sakdiah , Rejali Zulida
Published: November 2019

Background

Cervical cancer is the third most common cancer affecting women around the world in which the Human Papillomavirus (HPV) is the one of the recognized causative agent affecting women health. In response to this health issue, the Malaysian government had officially implemented the HPV immunisation programme for secondary schoolchildren in 2010 at the age of 13 years old and above. The purpose of this study is to investigate the sociodemographic determinants of knowledge and attitude among students of Universiti Tunku Abdul Rahman (UTAR) towards the HPV vaccination programme.

Methods

A cross-sectional study was conducted using self-administered questionnaires, recruiting 374 UTAR’s students as the respondents by using convenience sampling method. Respondents were categorized as having good/poor level of knowledge and positive/negative attitude towards HPV vaccination.

Results

Over half of the respondents were females (64.5%) and the majority were aged 20 years old and below (55.8%). Generally, 54.7% of the total respondents had a high level of knowledge towards HPV vaccine while 57.5% of the total respondents showed a negative attitude towards HPV vaccine. Female respondents aged 20 years old and below showed good knowledge (56.4%) and a more positive attitude (55.8%) towards HPV vaccine. Students from the Faculty of Medicine and Health Sciences (FMHS) exhibited higher knowledge (67.3%) and positive attitude (62.4%) as compared to the Faculty of Accountancy and Management (FAM) which showed only 32.7% of knowledge and 37.6% of positive attitude towards the HPV vaccination.

Conclusion

The majority of UTAR students possess good knowledge regarding HPV vaccination. Nonetheless, they demonstrated a negative attitude towards HPV vaccination, depicting the necessity to impart and further intensify the sense of health awareness among all students, especially among male students. The judicious use of social media apart from the conventional mass media should be an advantage as to enhance the practice of HPV vaccination among them and thereafter minimize the health and economic burdens of cervical cancer.
Omentopexy with Glubran®2 for reducing complications after laparoscopic sleeve gastrectomy: results of a randomized controlled study
Authors: Pilone Vincenzo , Tramontano Salvatore , Renzulli Michele , Romano Mafalda , Monda Angela , Albanese Alice , Foletto Mirto
Published: November 2019

Background

Gastric fistulas, bleeding, and strictures are commonly reported after laparoscopic sleeve gastrectomy (LSG), that increase morbidity and hospital stay and may put the patient’s life at risk. We report our prospective evaluation of application of synthetic sealant, a modified cyanoacrylate (Glubran®2), on suture rime, associated with omentopexy, to identify results on LSG-related complications.

Methods

Patients were enrolled for LSG by two Bariatric Centers, with high-level activity volume. Intraoperative recorded parameters were: operative time, estimated intraoperative bleeding, conversion rate. We prospectively evaluated the presence of early complications after LSG during the follow up period. Overall complications were analyzed. Perioperative data and weight loss were also evaluated. A control group was identified for the study.

Results

Group A (treated with omentopexy with Glubran®2) included 96 cases. Control group included 90 consecutive patients. There were no differences among group in terms of age, sex and Body Mass Index (BMI). No patient was lost to follow-up for both groups. Overall complication rate was significantly reduced in Group A. Mean operative time and estimated bleeding did not differ from control group. We observed three postoperative leaks in Group B, while no case in Group A (not statistical significancy). We did not observe any mortality, neither reoperation. Weight loss of the cohort was similar among groups. In our series, no leaks occurred applying omentopexy with Glubran®2.

Conclusion

Our experience of omentopexy with a modified cyanoacrylate sealant may lead to a standardized and reproducible approach that can be safeguard for long LSG-suture rime.

Trial registration

Retrospective registration on clinicaltrials.gov PRS, with TRN NCT03833232 (14/02/2019).
Safety and effectiveness of a novel generator algorithm for bipolar vessel sealing: a randomised controlled chronic animal study
Authors: Kraemer Bernhard , Tsaousidis Christos , Kruck Stephan , Schenk Martin , Scharpf Marcus , Kommoss Stefan , Brucker Sara , Nuessle Daniela , Enderle Markus D. , Biber Ulrich
Published: November 2019

Background

Electrosurgical vessel sealers are gradually replacing conventional techniques such as ligation and clipping. Algorithms that control electrosurgical units (ESU), known as modes, are important for applications in different surgical disciplines. This chronic porcine animal study aimed to evaluate the safety and effectiveness of the novel thermoSEAL electrosurgical vessel sealing mode (TSM). The BiClamp® mode (BCM) of the renowned VIO® 300 D ESU served as control. BCM has been widely available since 2002 and has since been successfully used in many surgical disciplines. The TSM, for the novel VIO® 3 ESU, was developed to reduce sealing time and/or thermal lateral spread adjacent to the seal while maintaining clinical success rates. The primary aim of this study was to investigate the long-term and intraoperative seal quality of TSM.

Methods

The BiCision® device was used for vessel sealing with TSM and BCM in ten German Landrace pigs which underwent splenectomy and unilateral nephrectomy during the first intervention of the study. The seals were cut with the BiCision® knife. Ninety-nine arteries, veins and vascular bundles were chronically sealed for 5 or 21 days. Thereafter, during the second and terminal intervention of the study, 97 additional arteries and veins were sealed. The carotid arteries were used for histological evaluation of thermal spread.

Results

After each survival period, no long-term complications occurred with either mode. The intraoperative seal failure rates, i.e. vessel leaking or residual blood flow after the first sealing activation, were 2% with TSM versus 6% with BCM (p = 0.28). The sealing time was significantly shorter with TSM (3.5 ± 0.69 s vs. 7.3 ± 1.3 s, p < 0.0001). The thermal spread and burst pressure of arteries sealed with both modes were similar (p = 0.18 and p = 0.61) and corresponded to the histological evaluation. The measured tissue sticking parameter was rare with both modes (p = 0.33). Tissue charring did not occur. Regarding the cut quality, 97% of the seals were severed in the first and 3% in the second attempt (both with TSM and BCM).

Conclusions

The novel TSM seals blood vessels twice as fast as the BCM while maintaining excellent tissue effect and clinical success rates.

Trial registration

Not applicable.
Clinical and morphological effects of hyperbaric oxygen therapy in patients with interstitial cystitis associated with fibromyalgia
Authors: Bosco Gerardo , Ostardo Edoardo , Rizzato Alex , Garetto Giacomo , Paganini Matteo , Melloni Giorgio , Giron Giampiero , Pietrosanti Lodovico , Martinelli Ivo , Camporesi Enrico
Published: November 2019

Background

Interstitial Cystitis (IC) is a debilitating disorder of the bladder, with a multifactorial and poorly understood origin dealing with microcirculation repeated damages. Also Fibromyalgia (FM) is a persistent disorder whose etiology is not completely explained, and its theorized alteration of pain processing can compromise the quality of life. Both these conditions have a high incidence of conventional therapeutic failure, but recent literature suggests a significant beneficial response to Hyperbaric Oxygen Therapy (HBOT). With this study, this study we evaluated the effects of HBOT on quality of life, symptoms, urodynamic parameters, and cystoscopic examination of patients suffering from both IC and FM.

Methods

We structured an observational clinical trial design with repeated measures (questionnaires, urodynamic test, and cystoscopy) conducted before and 6 months after a therapeutic protocol with hyperbaric oxygen for the treatment of patients suffering from both IC and FM. Patients were exposed to breathing 100% oxygen at 2 atm absolute (ATA) in a multiplace pressure chamber for 90 min using an oro-nasal mask. Patients undertook a cycle of 20 sessions for 5 days per week, and a second cycle of 20 sessions after 1 week of suspension.

Results

Twelve patients completed the protocol. Changes after HBOT were not significant, except for hydrodistension tolerance (mean pre-treatment: 409.2 ml; mean post-treatment: 489.2 ml; p < 0.05). A regression of petechiae and Hunner’s ulcers was also noted 6 months after the completion of HBOT.

Conclusions

Our study showed no improvement of symptoms, quality of life, and urodynamic parameters, except for hydrodistension, and a slight improvement in cystoscopic pattern. However, to date, we could not demonstrate the significance of overall results to justify the use of HBOT alone in patients with IC and FM. This observation suggests that additional studies are needed to better understand if HBOT could treat this subset of patients.

Trial registration

NCT03693001; October 2, 2018. Retrospectively registered.
Predicting skilled delivery service use in Ethiopia: dual application of logistic regression and machine learning algorithms
Authors: Tesfaye Brook , Atique Suleman , Azim Tariq , Kebede Mihiretu M.
Published: November 2019

Background

Skilled assistance during childbirth is essential to reduce maternal deaths. However, in Ethiopia, which is among the six countries contributing to more than half of the global maternal deaths, the coverage of births attended by skilled health personnel remains very low. The aim of this study was to identify determinants and develop a predictive model for skilled delivery service use in Ethiopia by applying logistic regression and machine-learning techniques.

Methods

Data from the 2016 Ethiopian Demographic and Health Survey (EDHS) was used for this study. Statistical Package for Social Sciences (SPSS) and Waikato Environment for Knowledge Analysis (WEKA) tools were used for logistic regression and model building respectively. Classification algorithms namely J48, Naïve Bayes, Support Vector Machine (SVM), and Artificial Neural Network (ANN) were used for model development. The validation of the predictive models was assessed using accuracy, sensitivity, specificity, and area under Receiver Operating Characteristics (ROC) curve.

Results

Only 27.7% women received skilled delivery assistance in Ethiopia. First antenatal care (ANC) [AOR = 1.83, 95% CI (1.24–2.69)], birth order [AOR = 0.22, 95% CI (0.11–0.46)], television ownership [AOR = 6.83, 95% CI (2.52–18.52)], contraceptive use [AOR = 1.92, 95% CI (1.26–2.97)], cost needed for healthcare [AOR = 2.17, 95% CI (1.47–3.21)], age at first birth [AOR = 1.96, 95% CI (1.31–2.94)], and age at first sex [AOR = 2.72, 95% CI (1.55–4.76)] were determinants for utilizing skilled delivery services during the childbirth. Predictive models were developed and the J48 model had superior predictive accuracy (98%), sensitivity (96%), specificity (99%) and, the area under ROC (98%).

Conclusions

First ANC and contraceptive uses were among the determinants of utilization of skilled delivery services. A predictive model was developed to forecast the likelihood of a pregnant woman seeking skilled delivery assistance; therefore, the predictive model can help to decide targeted interventions for a pregnant woman to ensure skilled assistance at childbirth. The model developed through the J48 algorithm has better predictive accuracy. Web-based application can be build based on results of this study.
Investigation of the methylerythritol 4-phosphate pathway for microbial terpenoid production through metabolic control analysis
Authors: Volke Daniel Christoph , Rohwer Johann , Fischer Rainer , Jennewein Stefan
Published: November 2019

Background

Terpenoids are of high interest as chemical building blocks and pharmaceuticals. In microbes, terpenoids can be synthesized via the methylerythritol phosphate (MEP) or mevalonate (MVA) pathways. Although the MEP pathway has a higher theoretical yield, metabolic engineering has met with little success because the regulation of the pathway is poorly understood.

Results

We applied metabolic control analysis to the MEP pathway in Escherichia coli expressing a heterologous isoprene synthase gene (ispS). The expression of ispS led to the accumulation of isopentenyl pyrophosphate (IPP)/dimethylallyl pyrophosphate (DMAPP) and severely impaired bacterial growth, but the coexpression of ispS and isopentenyl diphosphate isomerase (idi) restored normal growth and wild-type IPP/DMAPP levels. Targeted proteomics and metabolomics analysis provided a quantitative description of the pathway, which was perturbed by randomizing the ribosome binding site in the gene encoding 1-deoxyxylulose 5-phosphate synthase (Dxs). Dxs has a flux control coefficient of 0.35 (i.e., a 1% increase in Dxs activity resulted in a 0.35% increase in pathway flux) in the isoprene-producing strain and therefore exerted significant control over the flux though the MEP pathway. At higher dxs expression levels, the intracellular concentration of 2-C-methyl-d-erythritol-2,4-cyclopyrophosphate (MEcPP) increased substantially in contrast to the other MEP pathway intermediates, which were linearly dependent on the abundance of Dxs. This indicates that 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (IspG), which consumes MEcPP, became saturated and therefore limited the flux towards isoprene. The higher intracellular concentrations of MEcPP led to the efflux of this intermediate into the growth medium.

Discussion

These findings show the importance of Dxs, Idi and IspG and metabolite export for metabolic engineering of the MEP pathway and will facilitate further approaches for the microbial production of valuable isoprenoids.
Diagnostic performance of CareStart™ malaria HRP2/pLDH test in comparison with standard microscopy for detection of uncomplicated malaria infection among symptomatic patients, Eastern Coast of Tanzania
Authors: Bwire George M. , Ngasala Billy , Kilonzi Manase , Mikomangwa Wigilya P. , Felician Fatuma F. , Kamuhabwa Appolinary A. R.
Published: November 2019

Background

CareStart™ malaria HRP2/pLDH (Pf/pan) combo test is one of the several rapid diagnostic tests (RDT) approved for diagnosis of malaria at the point of care in Tanzania. However, there are limited studies on the diagnostic performance of RDT after wide scale use in primary health care facilities in Tanzania. Therefore, this study was carried out to determine the diagnostic performance of RDT when compared with blood smear (BS) microscopy as a reference standard.

Methods

A cross-sectional study was conducted between March and August 2019 at Kibiti Health Centre, Pwani region, Tanzania. Blood samples for malaria tests were collected from patients with malaria symptoms. Diagnostic performance parameters of RDT, i.e. sensitivity, specificity, positive and negative likelihood ratios (LR+/−), diagnostic accuracy and predictive values were determined using contingency table. An agreement between RDT and microscopy was statistically determined by Cohen’s kappa test.

Results

Of 980 patients screened, 567 (57.9%) were found to be malaria positive by RDT, whereas 510 patients (52%) were positive by microscopy. Of the 510 microscopy-positive patients, 487 (95.5%) were infected with Plasmodium falciparum. The geometric mean parasite density was 2921parasites/µl, whereas majority (68.6%) of patients had parasite density greater than 10,000/µl. The sensitivity, specificity, positive and negative predictive values of CareStart™ were 99.8%, 87.6%, 89.8%, and 99.8%, respectively. The LR+ and LR− were 8.0 and 0.002, respectively. The diagnostic accuracy was 0.5. There was a strong agreement between the results obtained using CareStart™ and BS microscopy (kappa = 0.863, P < 0.0001).

Conclusion

CareStart™ malaria HRP2/pLDH (Pf/pan) had high sensitivity and strong agreement with microscopy results. However, moderate specificity of RDT resulted in a substantial number of patients with false positive malaria test. Wherever available, microscopy should be used to confirm RDT test results.
Barriers and facilitators to the implementation of brief interventions targeting smoking, nutrition, and physical activity for indigenous populations: a narrative review
Authors: Fazelipour Mojan , Cunningham Frances
Published: November 2019

Objective

This narrative review aimed to identify and categorize the barriers and facilitators to the provision of brief intervention and behavioral change programs that target several risk behaviors among the Indigenous populations of Australia, Canada, and New Zealand.

Methods

A systematic database search was conducted of six databases including PubMeD, Embase, CINAHL, HealthStar, PsycINFO, and Web of Science. Thematic analysis was utilized to analyze qualitative data extracted from the included studies, and a narrative approach was employed to synthesize the common themes that emerged. The quality of studies was assessed in accordance with the Joanna Briggs Institute’s guidelines and using the software SUMARI – The System for the Unified Management, Assessment and Review of Information.

Results

Nine studies were included. The studies were classified at three intervention levels: (1) individual-based brief interventions, (2) family-based interventions, and (3) community-based-interventions. Across the studies, selection of the intervention level was associated with Indigenous priorities and preferences, and approaches with Indigenous collaboration were supported. Barriers and facilitators were grouped under four major categories representing the common themes: (1) characteristics of design, development, and delivery, (2) patient/provider relationship, (3) environmental factors, and (4) organizational capacity and workplace-related factors. Several sub-themes also emerged under the above-mentioned categories including level of intervention, Indigenous leadership and participation, cultural appropriateness, social and economic barriers, and design elements.

Conclusion

To improve the effectiveness of multiple health behavior change interventions among Indigenous populations, collaborative approaches that target different intervention levels are beneficial. Further research to bridge the knowledge gap in this topic will help to improve the quality of preventive health strategies to achieve better outcomes at all levels, and will improve intervention implementation from development and delivery fidelity, to acceptability and sustainability.
A prospective study of acute kidney injury in the intensive care unit: development and validation of a risk prediction model
Authors: Wang Qi , Tang Yi , Zhou Jiaojiao , Qin Wei
Published: November 2019

Background

Acute kidney injury (AKI) has high morbidity and mortality in intensive care units (ICU). It can also lead to chronic kidney disease (CKD), more costs and longer hospital stay. Early identification of AKI is important.

Methods

We conducted this monocenter prospective observational study at West China Hospital, Sichuan University, China. We recorded information of each patient in the ICU within 24 h after admission and updated every two days. Patients who reached the primary outcome were accepted into the AKI group. Of all patients, we randomly drew 70% as the development cohort and the remaining 30% as the validation cohort. Using binary logistic regression we got a risk prediction model of the development cohort. In the validation cohort, we validated its discrimination by the area under the receiver operator curve (AUROC) and calibration by a calibration curve.

Results

There were 656 patients in the development cohorts and 280 in the validation cohort. Independent predictors of AKI in the risk prediction model including hypertension, chronic kidney disease, acute pancreatitis, cardiac failure, shock, pH ≤ 7.30, CK > 1000 U/L, hypoproteinemia, nephrotoxin exposure, and male. In the validation cohort, the AUROC is 0.783 (95% CI 0.730–0.836) and the calibration curve shows good calibration of this prediction model. The optimal cut-off value to distinguish high-risk and low-risk patients is 4.5 points (sensitivity is 78.4%, specificity is 73.2% and Youden’s index is 0.516).

Conclusions

This risk prediction model can help to identify high-risk patients of AKI in ICU to prevent the development of AKI and treat it at the early stages.

Trial registration TCTR, TCTR20170531001. Registered 30 May 2017, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=2573
Super short operations on both gene order and intergenic sizes
Authors: Oliveira Andre R. , Jean Géraldine , Fertin Guillaume , Dias Ulisses , Dias Zanoni
Published: November 2019

Background

The evolutionary distance between two genomes can be estimated by computing a minimum length sequence of operations, called genome rearrangements, that transform one genome into another. Usually, a genome is modeled as an ordered sequence of genes, and most of the studies in the genome rearrangement literature consist in shaping biological scenarios into mathematical models. For instance, allowing different genome rearrangements operations at the same time, adding constraints to these rearrangements (e.g., each rearrangement can affect at most a given number of genes), considering that a rearrangement implies a cost depending on its length rather than a unit cost, etc. Most of the works, however, have overlooked some important features inside genomes, such as the presence of sequences of nucleotides between genes, called intergenic regions.

Results and conclusions

In this work, we investigate the problem of computing the distance between two genomes, taking into account both gene order and intergenic sizes. The genome rearrangement operations we consider here are constrained types of reversals and transpositions, called super short reversals (SSRs) and super short transpositions (SSTs), which affect up to two (consecutive) genes. We denote by super short operations (SSOs) any SSR or SST. We show 3-approximation algorithms when the orientation of the genes is not considered when we allow SSRs, SSTs, or SSOs, and 5-approximation algorithms when considering the orientation for either SSRs or SSOs. We also show that these algorithms improve their approximation factors when the input permutation has a higher number of inversions, where the approximation factor decreases from 3 to either 2 or 1.5, and from 5 to either 3 or 2.
Development of molecular and pharmacological switches for chimeric antigen receptor T cells
Authors: Wu Bill X. , Song No-Joon , Riesenberg Brian P. , Li Zihai
Published: November 2019

The use of chimeric antigen receptor (CAR) T cell technology as a therapeutic strategy for the treatment blood-born human cancers has delivered outstanding clinical efficacy. However, this treatment modality can also be associated with serious adverse events in the form of cytokine release syndrome. While several avenues are being pursued to limit the off-target effects, it is critically important that any intervention strategy has minimal consequences on long term efficacy. A recent study published in Science Translational Medicine by Dr. Hudecek’s group proved that dasatinib, a tyrosine kinase inhibitor, can serve as an on/off switch for CD19-CAR-T cells in preclinical models by limiting toxicities while maintaining therapeutic efficacy. In this editorial, we discuss the recent strategies for generating safer CAR-T cells, and also important questions surrounding the use of dasatinib for emergency intervention of CAR-T cell mediated cytokine release syndrome.
Identification of key microRNAs in the carotid arteries of ApoE−/− mice exposed to disturbed flow
Authors: Wang Xinzhou , Gao Shuibo , Dai Liping , Wang Zhentao , Wu Hong
Published: November 2019

Background

Atherosclerosis (AS) is one of the main causes of cardiovascular disease. AS plaques often occur in blood vessels with oscillatory blood flow and their formation can be regulated by microRNAs (miRNAs). The aim of this study is to identify the key miRNAs and molecular pathways involved in this pathological process.

Methods

In this study, gene chip data obtained from the GEO database was analyzed using the LIMMA package to find differentially expressed miRNAs (DE miRNAs) in the carotid arteries of ApoE−/− mice exposed to different blood flow rates. Predicted targets of the DE miRNAs were identified using the TargetScan, miRDB, and DIANA databases respectively, and the potential target genes (PTGs) were found by analyzing the common results of three databases. The DAVID database was used to enrich the PTGs based on gene ontology (GO) and pathway (Kyoto Encyclopedia of Genes and Genomes, KEGG), and the STRING database was used to uncover any protein-protein interactions (PPI) of the PTGs.

Results

The networks of the DE miRNAs-PTGs, Pathway-PTGs-DE miRNAs, and PTGs PPI, were constructed using Cytoscape, and 11 up-regulated and 13 down-regulated DE miRNAs and 1479 PTGs were found. GO results showed that PTGs were significantly enriched in functions such as transcriptional regulation and DNA binding. KEGG results showed that PTGs were significantly enriched in inflammation-related mitogen-activated protein kinase (MAPK) and AS-related FOXO pathways. The PPI network revealed some key target genes in the PTGs.

Conclusions

The analysis of key miRNAs and molecular pathways that regulate the formation of AS plaques induced by oscillatory blood flow will provide new ideas for AS treatment.