bluuebunny/crossref_metadata_2025 huggingface dataset:
Progestins counteract estrogens to shift breast cancer cell metabolism
Authors: Ward Ashley V. , Matthews Shawna B. , Fettig Lynsey M. , Finlay-Schultz Jessica , Kabos Peter , Jackman Matthew , MacLean Paul S. , Sartorius Carol A.
Published: October 2020

Progesterone receptors (PR) profoundly influence breast cancer biology by modifying estrogen receptor (ER) gene regulation, and, under some contexts, increasing populations of cancer stem cells. Abnormal metabolism is a cancer hallmark that has largely been understudied in relation to hormones in ER+PR+ breast disease. In this study, we investigated how progestins, in the absence or presence of estrogens, affect breast cancer cell metabolism. We measured metabolites using ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) in three ER+PR+ breast cancer cell lines (T47D, UCD4, and UCD65) treated with vehicle, estrogen only, progestin only, or the combination. Progestins, in the absence or presence of estrogens, largely downregulated metabolites, particularly those involved in tricarboxylic acid (TCA) cycle and amino acid metabolism. Seahorse metabolic analysis found progestins (alone or plus estrogens) generally shifted cells towards glycolysis with reduced ATP production. Transmission electron microscopy in cell lines and patient-derived xenograft tumors found that estrogens produced an elongated mitochondrial morphology, while estrogen plus progestin treatment reversed this trend. Using the photoconvertible MitoTimer reporter, progestins reduced both baseline and estrogen-induced mitochondrial turnover. Progestins blocked the estrogen-induced expression of mitochondrial biogenesis regulators PGC1α and PGC1β and their downstream targets. These findings indicate that progestins dominantly affect cell metabolism to shift cells to a more glycolytic phenotype with reduced mitochondrial function and amino acid pools; this transition is indicative of less proliferative, but also more dedifferentiated cells. Our results highlight potential benefits and detriments of current clinical studies testing selective PR modulators in ER+ breast cancers.
Key stakeholder experiences of an integrated healthcare pilot in Australia: A thematic analysis
Authors: Trankle Steven , Usherwood Tim , Abbott Penelope , Roberts Mary , Crampton Michael , Girgis Christian M , Riskallah John , Chang Yashu , Saini Jaspreet , Reath Jennifer
Published: October 2020

Background In Australia and other developed countries, chronic illness prevalence is increasing, as are costs of healthcare, particularly hospital-based care. Integrating healthcare and supporting illness management in the community can be a means of preventing illness, improving outcomes and reducing unnecessary hospitalisation. Western Sydney has high rates of diabetes, heart and respiratory diseases and the NSW State Ministry of Health funded a range of key strategies through the Western Sydney Integrated Care Program (WSICP) to integrate care across hospital and community settings for patients with these illnesses. Complementing our previously reported analysis related to specific WSICP strategies, this research provided information concerning overall experiences and perspectives of WSICP implementation and integrated care generally.Methods We administered 125 in-depth interviews in two rounds over 12 months with 83 participants including patients and their carers, care facilitators, hospital specialists and nurses, allied health professionals, general practitioners and primary care nurses, and program managers. Half of the participants (n=42) were interviewed twice. We conducted an inductive, thematic analysis on the interview transcripts.Results Key themes related to the set-up and operationalising of WSICP; challenges encountered; and the added value of the program. Implementing WSICP was a large and time consuming undertaking but challenges including those with staffing and information technology were being addressed. The WSICP was considered valuable in reducing hospital admissions due to improved patient self-management and a focus on prevention, greater communication and collaboration between healthcare providers across health sectors and an increased capacity to manage chronic illness in the primary care setting.Conclusions Patients, carers and health providers experienced the WSICP as an innovative integrated care model and valued its patient-centred approach which was perceived to improve access to care, increase patient self-management and illness prevention, and reduce hospital admissions. Long-term sustainability of the WSICP will depend on retaining key staff, more effectively sharing information including across health sectors to support enhanced collaboration, and expanding the suite of activities into other illness areas and locations. Enhanced support for general practices to manage chronic illness in the community, in collaboration with hospital specialists is critical. Timely evaluation informs ongoing program implementation.
Genome-wide Identification of ATP Binding Cassette (ABC) Transporter and Heavy Metal Associated (HMA) Gene Families in Flax (Linum usitatissimum L.)
Authors: Khan Nadeem , You Frank , Datla Raju , Ravichandhran Sridhar , Jia Bosen , Cloutier Sylvie
Published: October 2020

Background The recent release of the reference genome sequence assembly of flax, a self-pollinated crop with 15 chromosome pairs, into chromosome-scale pseudomolecules enables the characterization of gene families. The ABC transporter and HMA gene families are important in the control of cadmium (Cd) accumulation in crops. To date, the genome-wide analysis of these two gene families has been successfully conducted in some plant species, but no systematic evolutionary analysis is available for the flax genome. Results Here we describe the ABC transporter and HMA gene families in flax to provide a comprehensive overview of its evolution and some support towards the functional annotation of its members. The 198 ABC transporter and 12 HMA genes identified in the flax genome were classified into eight ABC transporter and four HMA subfamilies based on their phylogenetic analysis and domains’ composition. Nine of these genes, i.e., LuABCC9, LuABCC10, LuABCG58, LuABCG59, LuABCG71, LuABCG72, LuABCG73, LuHMA3, and LuHMA4, were orthologous with the Cd associated genes in Arabidopsis, rice and maize. Ten motifs were identified from all ABC transporter and HMA genes. Also, several motifs were conserved among genes of similar length, but subfamilies each had their own motif structures. Both the ABC transporter and HMA gene families were highly conserved among subfamilies of flax and with those of Arabidopsis. While four types of gene duplication were observed at different frequencies, whole-genome or segmental duplications were the most frequent with 162 genes, followed by 29 dispersed, 14 tandem and 4 proximal duplications, suggesting that segmental duplications contributed the most to the expansion of both gene families in flax. The rates of non-synonymous to synonymous (Ka/Ks) mutations of paired duplicated genes were for the most part lower than one, indicative of a predominant purifying selection. Only five pairs of genes clearly exhibited positive selection with a Ka/Ks ratio greater than one. Gene ontology analyses suggested that most flax ABC transporter and HMA genes had a role in ATP binding, transport, catalytic activity, ATPase activity, and metal ion binding. The RNA-Seq analysis of eight different organs demonstrated diversified expression profiling patterns of the genes and revealed their functional or sub-functional conservation and neo-functionalization. Conclusion Characterization of the ABC transporter and HMA gene families will help in the functional analysis of candidate genes in flax and other crop species.
Healthcare utilisation and out-of-pocket expenditure of type 2 diabetes patients with and without comorbidity: A study in primary care in Bhubaneswar, India.
Authors: Pati Sandipana , Swain Subhashisa , Akker Marjan van den , Schellevis F. (François) G. , Burgers Jako S.
Published: October 2020

Background: Globally, non-communicable diseases (NCD) demand a higher healthcare expenditure. Amongst the NCDs, diabetes mellitus, is often associated with multiple, co-existing chronic conditions. In low- and middle-income countries where most of the healthcare expenditure is borne out of pocket, diabetes management may pose a significant financial stress.Methods: A cross-sectional study was conducted in 17 urban primary healthcare facilities of Bhubaneswar to assess the healthcare utilisation and out-of-pocket expenditure among type 2 diabetes patients attending these facilities. Healthcare utilisation was determined by the number of visits to healthcare facilities in the last six months, and out-of-pocket expenditure was assessed by outpatient consultation fees, medicines, travels to health care facilities and diagnostic tests. Total out-of-pocket expenditure was defined as the sum of these costs.Results: The median number of visits in 6 months for diabetes patients with any comorbidity was 4 and 5 for diabetes patients with more than 4 comorbidities. Among the comorbid conditions, depression, stroke, auditory impairment and acid peptic disease were associated with higher healthcare utilisation. The total out-of-pocket expense was 2.3 times higher among diabetes patients with any comorbid condition compared to patients with diabetes only. The total median expenditure was higher for diabetes patients having stroke, heart diseases, kidney diseases and cancer compared to other comorbid conditions. The association of comorbidity in diabetes patients with health care utilization and out-of-pocket expenditure is statistically significant after adjustment for sociodemographic characteristics and diabetes duration.Conclusion: Considerable expenditure is incurred by diabetes patients attending primary healthcare facilities for the management of diabetes and other chronic conditions. This is a significant burden for diabetes patients below the poverty line and with limited or no insurance cover. There is a need to increase the coverage of insurance schemes to address the chronic conditions management expenditure of outpatients.
Short-Term Changes in the Anterior Segment and Retina after Small Incision Lenticule Extraction
Authors: Chen Yanwei , Liao Huaping , Sun Yue , Shen Xi
Published: October 2020

Background: To analyse short-term changes in the anterior segment and retina after small incision lenticule extraction (SMILE).Methods: Patients with myopia scheduled for SMILE were recruited from Ruijin Hospital, Shanghai, China. Basic patient information such as age, sex, and refractive errors was recorded. Ocular measurements were taken before surgery, and 1 day and 1 week after surgery; they included axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), white to white (WTW), pupil diameter (PD), macular thickness (MT), ganglion cell layer thickness (GCL), retinal nerve fiber layer thickness (RNFL), choroidal thickness (CT), macular vessel density, and optic disc vessel density.Results: Sixty-one eyes of 31 patients were selected for this study. AL, CCT, ACD, and postoperative PD were significantly reduced (p<0.05), while LT was thickened after surgery (p<0.05). MT at the fovea decreased 1 day and 1 week after surgery (p<0.05). GCL showed no significant changes after surgery. RNFL was unchanged 1 day after surgery, but the inferior sector was thickened 1 week after surgery. CT was thicker at the fovea 1 day after surgery and 1.0 mm from the fovea in the nasal sector 1 week after surgery. Macular vessel density was significantly decreased 1 day after surgery and most recovered in 1 week. Optic disc vessel density decreased at the peripapillary part 1 day after surgery and recovered after 1 week. 𝜟ACD and 𝜟LT showed no significant correlation 1 day after surgery. 𝜟ACD was negatively correlated with 𝜟LT and sphere 1 week after surgery (r=-0.847, p<0.000; r=-0.398, p=0.002). 𝜟LT was positively correlated with the sphere 1 week after surgery (r=0.256, p=0.048).Conclusion: The anterior segment was the most affected, while the retina also underwent changes with regard to MT, RNFL, CT, macular vessel density, and peripapillary vessel density.
Atomistic insight into novel co-delivery of doxorubicin and paclitaxel using fullerene modified by dimethyl acrylamide trimethyl chitosan: A computational study
Authors: Alimohammadi Ehsan , Maleki Reza , Akbarialiabad Hossein , Dahri Mohammad
Published: October 2020

Background: The distribution of drugs could not be controlled in the conventional drug delivery system. This has led to the development of a smart nanoparticle-based drug delivery system, known as smart drug delivery systems. In cancer research, novel biocompatible nanocarriers have received much attention for various ranges of anticancer drugs.In the current study, the effect of a novel co-polymer "dimethyl acrylamide-trimethyl chitosan" was investigated on drug delivery of doxorubicin and paclitaxel utilizing modified fullerene nanocarrier. This study was performed via molecular dynamics simulation based on acidic pH sensitivity of the cancer microenvironment. Furthermore, hydrogen bonds, diffusion coefficient, gyration radius, and drug-carrier interaction energies were investigated here. Interestingly, a simultaneous pH and temperature-sensitive system was proposed for paclitaxel and doxorubicin for a co-polymer. A pH-sensitive and temperature-sensitive copolymer was used based on trimethyl chitosan and dimethyl acrylamide, respectively. In such a dualistic approach, co-polymer makes an excellent option to have two properties in one bio-polymer. Results: The results suggest the dramatic and indisputable role of the co-polymer in the release of doxorubicin and paclitaxel in cancerous tissues, as well as an increased biocompatibility and drug uptake in a neutral state. The validation test was performed by repeated simulations of a similar article. The results are very close to those of the reference paper .Conclusions: Overall, conjugated fullerene and dimethyl acrylamide-trimethyl chitosan (DMAA-TMC) as carriers can be a good proposition for loading, delivery, and release of anti-cancer drugs based on a pH/temperature-sensitive smart drug delivery system.
Protocol for a systematic review and network meta-analysis of randomised controlled trials examining the effectiveness of early parenting interventions in preventing internalising problems in children and adolescents.
Authors: Costantini Ilaria , Paul Elise , Caldwell Deborah M , López-López José A , Pearson Rebecca M
Published: October 2020

Background: Internalising problems, such as depression and anxiety, are common and represent an important economical and societal burden. The effectiveness of parenting interventions in reducing risk of internalising problems in children and adolescents has not yet been summarised. The aims of this review are to assess the effectiveness of parenting interventions in the primary, secondary and tertiary prevention of internalising problems in children and adolescents and to determine which intervention components and which intervention aspects are most effective for reducing risk of internalising problems in children and adolescents. Methods: Electronic searches in OVID SP versions of Medline, EMBASE and PsycINFO; Cochrane Central Register of Controlled Trials; EBSCO version of ERIC and clinicaltrials.gov have been performed to identify randomised controlled trials or quasi-randomised controlled trials of parenting interventions. At least two independent researchers will assess studies for inclusion and extract data from each paper. The risk of bias assessment will be conducted independently by two reviewers using the Cochrane Collaboration’s Risk of Bias Assessment Tool. Statistical heterogeneity is anticipated given potential variation in participant characteristics, intervention type and mode of delivery, and outcome measures. Random effects models, assuming a common between-study variability, will be used to account for statistical heterogeneity. Results will be analysed using a network meta-analysis (NMA). If appropriate, we will also conduct a component-level NMA, where the ‘active ingredients’ of interventions are modelled using a network meta-regression approach.Discussion: Preventing and reducing internalising problems could have major beneficial effects at the economic and societal level. Informing policy makers on the effectiveness of parenting interventions and on which intervention’s component is driving the effect is important for the development of treatment strategies. Systematic review registration: International Prospective Register for Systematic Reviews (PROSPERO) number CRD42020172251
The Association Between Alcohol Consumption and Dysmenorrhea in University Students in North China
Authors: Yang Zhuo , Guo Jia , Sun Ming-li , He Qin-cheng , Ma Ya-Nan
Published: October 2020

Background: Dysmenorrhea is common gynecological disease in the whole world. Unfortunately, only a few studies have estimated the relationship between alcohol consumption and dysmenorrhea among women. In particular, there are fewer studies to explore the association between alcohol consumption, dysmenorrhea, and age at menarche.Objective: This study aimed to evaluate whether and what extent alcohol consumption is related to dysmenorrhea and age at menarche.Methods: This is a cross-sectional, observational study conducted among college students. A total of 3,837 participants (age ≥18 years) volunteered to participate in the study and completed the questionnaire. Moreover, 145 were excluded from the study owing to exclusion criteria. Finally, a total of 3692 female college students were enrolled in this study using the following criteria. We divided female college students into two groups stratified by age at menarche 13 years. The logical regression model was performed to evaluate the association between alcohol use and primary dysmenorrhea. The model adjusted for confounding factors and estimated the odds ratio and 95% confidence interval.Results: A total of 3692 female college students completed the survey, including 409(11.08%) students with alcohol use and 3283 (88.92%) participants without alcohol use. We founded that alcohol use and alcohol consumption were not related to dysmenorrhea. However, stratified by age at menarche, we found that there was a negative association between alcohol consumption and dysmenorrhea among participants with AAM ≥13 years (OR,1.41; 95% CI, 1.06, 1.88). Compared with participants without alcohol consumption, participants with alcohol consumption at least once a month (OR,1.29; 95% CI, 0.94, 1.78) and alcohol consumption at least once a week (OR,1.92; 95% CI, 1.07, 3.45) were more likely to have dysmenorrhea adjusted for other confounding factors.Conclusion: Our findings showed there was a negative association between alcohol consumption and dysmenorrhea stratified by age at menarche (13 years).
Portable neuromodulation induces neuroplasticity to re-activate motor function recovery from brain injury: A high-density MEG case study
Authors: D'Arcy Ryan C.N. , Greene Trevor , Greene Debbie , Frehlick Zack , Fickling Shaun D. , Campbell Natasha KJ , Etheridge Tori , Smith Christopher , Bollinger Fabio , Danilov Yuri , Livingstone Ashley , Tannouri Pamela , Martin Pauline , Lakhani Bimal
Published: October 2020

Background: In a recent high-profile case study, we used functional magnetic resonance imaging (fMRI) to monitor improvements in motor function related to neuroplasticity following rehabilitation for severe traumatic brain injury (TBI). The findings demonstrated that motor function improvements can occur years beyond current established limits. The current study extends the functional imaging investigation to characterize neuromodulation effects on neuroplasticity to further push the limits.Methods: Canadian Soldier Captain (retired) Trevor Greene (TG) survived a severe open-TBI when attacked with an axe during a 2006 combat tour in Afghanistan. TG has since continued intensive daily rehabilitation to recover motor function, experiencing an extended plateau using conventional physical therapy. To overcome this plateau, we paired translingual neurostimulation (TLNS) with the continuing rehabilitation program.Results: Combining TLNS with rehabilitation resulted in demonstrable clinical improvements along with corresponding changes in movement evoked electro-encephalography (EEG) activity. High-density magneto-encephalography (MEG) characterized cortical activation changes in corresponding beta frequency range (27Hz). MEG activation changes corresponded with reduced interhemispheric inhibition in the post-central gyri regions together with increased right superior/middle frontal activation suggesting large scale network level changes.Conclusions: The findings provide valuable insight into the potential importance of non-invasive neuromodulation to enhance neuroplasticity mechanisms for recovery beyond the perceived limits of rehabilitation.
Pharmacokinetic herb-drug interactions between Aidi injection and Doxorubicin in rats with diethylnitrosamine-induced hepatocellular carcinoma
Authors: Lu Yuan , Pan Jie , Zhu Xiaoqing , Zhang Shuai , Chunhua Liu , Sun Jia , Li Yueting , Chen Siying , Huang Jing , Cao Chuang , Wang Yonglin , Li Yongjun , Liu Ting
Published: October 2020

Background: Aidi Injection (ADI), a Chinese herbal preparation with anti-cancer activity, is used for the treatment of hepatocellular carcinoma (HCC). Several clinical studies have shown that co-administration of ADI with doxorubicin (DOX) is associated with reduced toxicity of chemotherapy, enhanced clinical efficacy and improved quality of life for patients. However, limited information is available about the herb-drug interactions between ADI and DOX. The study aimed to investigate the pharmacokinetic mechanism of herb-drug interactions between ADI and DOX in a rat model of HCC. Methods: Experimental HCC was induced in rats by oral administration of diethylnitrosamine. The HCC rats were pretreated with ADI (10 mL/kg, intraperitoneal injection) for 14 consecutive days prior to administration of DOX (7 mg/kg, intravenous injection) to investigate pharmacokinetic interactions. Plasma concentrations of DOX and its major metabolite, doxorubicinol (DOXol), were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Results: Preadministration of ADI significantly altered the pharmacokinetics of DOX in HCC rats, leading to increased plasma concentrations of both DOX and DOXol. The area under the plasma drug concentration-time curve (AUCs) of DOX and DOXol in rats pretreated with ADI were 3.79-fold and 2.92-fold higher, respectively, than those in control rats that did not receive ADI. Conclusions: Increased levels of DOX and DOXol were found in the plasma of HCC rats pretreated with ADI.
Extensively drug-resistant Alcaligenes faecalis infection
Authors: Huang Chienhsiu
Published: October 2020

Background: Alcaligenes faecalis is usually causes opportunistic infections in humans. Alcaligenes faecalis infection is often difficult to treat due to its increased resistance to several antibiotics. The results from a clinical study of patients with Alcaligenes faecalis infection may help improve patients’ clinical care. Methods: We conducted a retrospective analysis of all patients presenting with Alcaligenes faecalis infection from January 2014 to December 2019. The medical records of all patients were reviewed for demographic information, clinical symptoms and signs, comorbidities, use of intravenous antibiotics within the past three months, bacterial culture, antibiotics sensitivity test, and clinical outcomes. Results: Sixty-one cases of Alcaligenes faecalis infection were seen during the study period, including 25 cases of cystitis, nine cases of diabetic foot infection, eight cases of pneumonia, seven cases of acute pyelonephritis, three cases of bacteremia, and nine cases of infection at specific sites. Thirty-seven patients (60.7%) had a history of receiving intravenous antibiotics within three months of the diagnosis. Fifty-one (83.6%) cases were mixed with other bacterial infections. Extensively drug-resistant infections have been reported since 2018. The best sensitivity rate to A. faecalis was 66.7% for three antibiotics (imipenem, meropenem, and ceftazidime) in 2019. Two antibiotics (ciprofloxacin and piperacillin/tazobactam) sensitivity rates to A. faecalis were less than 50%. Conclusions: The most frequent Alcaligenes faecalis infection sites, in order, are the bloodstream, urinary tract, skin and soft tissue, and middle ear. The susceptibility rate of Alcaligenes faecalis to commonly used antibiotics is decreasing. Extensively drug-resistant Alcaligenes faecalis infections have emerged.
Advancing integrated care evaluation in shifting contexts: Blending implementation research with case study design in Project SUSTAIN.
Authors: Billings Jenny , de Bruin Simone R. , Baan Caroline , Nijpels Giel
Published: October 2020

BackgroundDespite many studies evaluating the effectiveness of integrated care, evidence remains inconsistent. There is increasing commentary pointing out the mismatch between the ability to capture the somewhat ‘illusive’ impact of integrated care initiatives and programmes, and the most appropriate way to do this. Focusing on methodology, this paper describes and critically reviews the experiences of SUSTAIN, a Horizon 2020 funded project (2015-2019) with the purpose of advancing knowledge and understanding of cross-European integrated care evaluation. SUSTAIN sought to improve integrated care initiatives for older people in seven countries, and to maximise the potential for knowledge transfer and application across Europe. The methods approach drew from implementation research, employing the participative Evidence Integration Triangle (EIT) and incorporating a mixed method, multiple embedded case study design. A core set of qualitative and quantitative indicators, alongside context and process data, were created and tested within four key project domains (person-centredness, prevention-orientation, safety and efficiency). The paper critically discusses the overall approach, highlighting the value of the EIT and case study design, and signalling the challenges of data collection with frail older people and stakeholder involvement at the sites, as well as difficulties developing the core set of indicators.ConclusionsLessons learned and recommendations for advancing integrated care evaluation are put forward that focus on the status of integrated care as a complex intervention and a process. The use of implementation research methods and case study design are recommended as an additional evaluation approach for researchers to consider, alongside suggested ways of improving methods of data collection with frail populations and cost analysis.
Partograph utilization as a decision making tool and associated factors among obstetric care providers in Ethiopia: A systematic review and Meta-analysis
Authors: Ayenew Asteray , Zewdu Biruk Ferede
Published: October 2020

Background Globally, a total of 13.6 million women have died due to maternal causes from 1990 to 2015. Majority of these deaths occurred in resource-limited countries. Among the causes of these deaths, obstructed and prolonged labor covers the highest percentage, which could be prevented by cost-effective and affordable health interventions like partograph use. Therefore, this systematic review and meta-analysis aimed to assess the level of partograph utilization among obstetric care providers and its associated factors in Ethiopia. Method for this review, we used the standard PRISMA checklist guideline. Different online databases were used for the review: PubMed/Medline, Google Scholar, EMBASE, Cochrane Library, HINARI, WHO Afro Library Databases, and African Online Journals. Based on the adapted PICO principles, different search terms were applied to achieve and access all the essential articles. Microsoft Excel was used for data entrance and Stata version 11.0 (Stata Corporation, College Station, Texas, USA) for data analysis.Result Nineteen studies were included in this systematic review and meta-analysis with a total of 6237 obstetric care providers. The overall pooled prevalence of partograph utilization was 59.95% (95%CI: 46.8–73.09, I2 =99.4%, P <0.001). Being midwifery profession (adjusted odds ratio (AOR):3.97; 95% confidence interval (CI):95%CI:2.63–5.99, I2 =28.8%, P=0.198), presence of supervision (AOR = 3.21; 95%CI: 2.22–4.66, I2=0.0%, p=0.742), Basic Emergency Obstetric and Newborn Care (BEmONC) training (AOR  = 2.90; 95% CI: 2.19–3.84, I2=36.9%, P=0.13), Knowledge of partograph (AOR=2.5; 95%CI: 1.6–3.8, I2=64.58%, P=0.024), on-the-job refresher training on partograph (AOR =5.7; 95%CI:2.5–12.9, I2=87.8%, P<0.001), favorable attitude (AOR=2.12; 95%CI: 1.48–3.04, I2=0.0%, P=0.58), and working at health center (AOR=3.50; 95%CI: 2.49–4.92, I2=49.1%, P=0.08) were the determinant factors for partograph use among obstetric acre providers in Ethiopia.Conclusion The overall pooled prevalence of partograph utilization among obstetric care providers was low. Therefore, supportive supervision, providing Basic Emergency Obstetric and Newborn Care training, on-the-job refresher training on partograph, and promoting midwifery profession are strongly recommended to increase the use of partograph.
Evaluation of successfulness of a capacity building workshop on smokeless tobacco and areca nut cessation conducted among Dental Surgeons of Sri Lanka: A cross sectional study
Authors: Jayasinghe Ruwan Duminda , Jayasooriya PR , Amarasinghe H , Hettiarachchi PVKS , Siriwardena BSMS. , Wijerathne UKYGDM , Kithalawarachchi SK. , Tilakaratne WM
Published: October 2020

Background- Prevalence of smoking in Sri Lanka shows a gradual reduction whilst the use of smokeless tobacco and areca nut shows an increasing trend. At present, to the best of our knowledge only a few well-structured smokeless tobacco (SLT)/areca nut (AN) cessation programmes are conducted in Sri Lanka, which is a gross underachievement considering that betel chewing related oral squamous cell carcinoma being the commonest cancer in Sri Lankan males. As General Dental Practitioners (GDP) do not contribute significantly to SLT/AN cessation activities at present, capacity building programmes on SLT/AN control were carried out. The study evaluated the knowledge, attitude and practices related to SLT/AN control among dental surgeonsMethods: Following an one day educational programme on smokeless tobacco / areca nut control, two self-administered questionnaires were used to assess the improvement of knowledge and change of attitudes among 663 GDPs . Results - 27.1% of the participants had received formal tobacco cessation training in the past. Majority had a good knowledge on harmful effects of SLT but not on areca nut. Their knowledge on the current legislation on SLT control in Sri Lanka and carcinogenicity of areca nut was not satisfactory. Almost all agreed that proper counseling leads to patient quitting the habit, a formal training is necessary to conduct tobacco control activities and it should be the part of the regular treatment modalities. More than 80% of the participants believed that they should support strict legislation. Almost 50% agreed on tobacco and areca nut free environment in their dental clinics. Most important factors leading to poor involvement in tobacco cessation activities were lack of expertise and inadequate educational material, not breach of patient privacy and lack of financial incentives. Surprisingly, 20.1% of the dental surgeons had consumed smokeless tobacco / areca nut products in the past and only a few were current users of tobacco and/or areca nut. Conclusions - Well planned workshops are efficient in improving knowledge, practices and attitudes of dental surgeons towards SLT/AN cessation.
TRAPPC11-related muscular dystrophy with hypoglycosylation of alpha-dystroglycan in skeletal muscle and brain.
Authors: Munot Pinki , McCrea Nadine , Torelli Silvia , Manzur Adnan , Sewry Caroline , Chambers Darren , Feng Lucy , Ala Pierpaolo , Zaharieva Irina , Ragge Nicola , Roper Helen , Marton Tamas , Cox Phil , Milev Miroslav , Sacher Michael , Liang Wen-Chen , Maruyama Shinsuke , Nishino Ichizo , Phadke Rahul , Muntoni Francesco
Published: October 2020

Background: TRAPPC11, a subunit of the transport protein particle (TRAPP) complex is important for complex integrity and anterograde membrane transport from the endoplasmic reticulum (ER) to the ER-Golgi intermediate compartment. Several individuals with TRAPPC11 mutations have been reported with muscle weakness and other features including brain, liver, skeletal and eye involvement. A detailed analysis of brain and muscle biopsies will further our understanding of the presentation and etiology of TRAPPC11-disease. Methods: We describe five cases of early-onset TRAPPC11–related muscular dystrophy with a systematic review of muscle pathology in all five individuals, post-mortem brain pathology findings in one individual, and membrane trafficking assays in another. Results: All affected individuals presented in infancy with muscle weakness, motor delay and elevated serum creatine kinase (CK). Additional features included cataracts, liver disease, intellectual disability, cardiomyopathy, movement disorder, and structural brain abnormalities. Muscle pathology in all five revealed dystrophic changes, universal hypoglycosylation of alpha-dystroglycan and variably reduced dystrophin-associated complex proteins. Membrane trafficking assays showed defective Golgi trafficking in one individual. Neuropathological examination of one individual revealed cerebellar atrophy, granule cell hypoplasia, Purkinje cell (PC) loss and dendritic neurodegeneration, reduced alpha-dystroglycan (IIH6) expression in PC and dentate neurons, and absence of neuronal migration defects. Conclusions: This report suggests that recessive mutations in TRAPPC11 are linked to muscular dystrophies with hypoglycosylation of alpha-dystroglycan. The structural brain involvement that we document for the first time resembles the pathology previously reported in N-linked congenital disorders of glycosylation (CDG) such as PMM2-CDG, suggesting defects in multiple glycosylation pathways in this condition.
Distribution of cervical lesions in high-risk HPV (hr-HPV) positive women with ASC-US: A retrospective single-center study in China
Authors: Wang Zhiling , Gu Ying , Wang Hui , Chen Junyu , Zheng Yawen , Cui Baoxia , yang xingsheng
Published: October 2020

Background: To investigate distributions of cervical lesions and factors associated with the severity of the cervical lesions in high-risk HPV (hr-HPV) positive women with atypical squamous cells of undetermined significance (ASC-US) cytology.Methods: Clinical information of 250,000 women who underwent HPV and cytological test was collected from January 2012 to January 2019. The association between the severity of the cervical lesions and hr-HPV genotypes, hr-HPV viral load, and ages, were analyzed in hr-HPV-positive/ASC-US women.Results: 3459 hr-HPV-positive/ASC-US women were enrolled in this study. Overall, 43.51% of women with ASC-US had normal histological results, 34.35% had high-grade squamous intraepithelial lesion (HSIL), and 1.30% had cervical cancer. The rate of HSIL or worse (HSIL+) in women with single HPV16 infection (63.09%) was the highest, followed by HPV33 (57.50%), HPV51 (36.11%), HPV58 (36.11%), HPV52 (28.28%), HPV18(26.37%), HPV66 (19.35%), HPV39 (18.92%), HPV53 (15.00%), and HPV56 (8.51%). Detection rate of HSIL+ in low, intermediate and high viral-load groups were 15.87% (n=30), 34.91% (n=74) and 40.68% (n=214) (Cochran-Armitage Trend test χ2=35.03, P<0.0001). Compared with the 51-60-year-old group (21.65%), the women in ≤30 (40.52%), 31-40 (39.67%), and 41-50 (34.22%) year-old groups had significantly higher risk of HSIL+. The women in ≤51-60 (2.68%) and >60 (3.41%) year-old groups were at increased risk for cervical cancer, compared with the ≤30-year-old group (0.61%).Conclusions: ASC-US women with HPV 16/18/33/51/52/58 single infection and multiple infections, as well as high HPV viral loads, have high risk of HSIL+.
Survey on neutralizing antibodies against Zika virus eighteen months post-outbreak in two southern Thailand communities
Authors: Densathaporn Theerut , Sangthong Rassamee , Sakolnapa Monvaris , Surasombatpattana Smonrapat , Kemapunmanus Marisa , Masrinoul Promsin , Yoksan Sutee , McNeil Edward B , Chongsuvivatwong Virasakdi
Published: October 2020

Background: In 2016 and 2017, Zika virus (ZIKV) infection outbreaks occurred in two communities in southern Thailand. This re-immerging infection can widely spread by mosquito bites and cause serious complications in a central nervous system among children born to infected mothers. Thus, they should be protected. This study aims to (1) To determine the prevalence of neutralizing ZIKV antibodies in the post-outbreak areas among the general population and pregnancy women residing at various distances from the houses of the nearest index patients; (2) To examine the cross-neutralizing capacity of antibodies against ZIKV on other flaviviruses commonly found in the study areas; (3) To identify factors associated with the presence of neutralizing ZIKV antibodies.Methods: The two post-outbreak communities were visited at 18 months after the outbreaks. We enrolled (1) 18 confirmed ZIKV infected (index) cases, (2) sample of 554 neighbors in the outbreak areas who lived at various distances from the index patients’ houses, (3) 190 residents of non-outbreak areas, and (4) all pregnant women regardless of gestational age residing in the study areas (n = 805). All serum specimens underwent the plaque reduction neutralization test (PRNT). Ten randomly selected ZIKV seropositive and ten randomly selected seronegative specimens were tested for dengue virus serotypes 1-4 (DENV1-4) and Japanese encephalitis virus (JEV) antibodies using PRNT90. Serum titer above 1:10 was considered positive. Multiple logistic regression was used to assess factors associated with seropositivity.Results: Out of all 18 index cases, 9 remained seropositive. The seroprevalence (95% CI) in the two outbreak areas were 43.7% (35.9-51.6%) and 29.7% (23.3-36.0%) in general population, and 24.3% (20.1-28.8%) and 12.8% (9.7-16.5%) in pregnant women. Multivariate analysis showed that seropositivity was independent of the distance gradient from the index’s houses. However, being elderly was associated with seropositivity. DENV1-4 and JEV neutralizing antibodies were present in most ZIKV-positive and negative subsamples.Conclusion: Protective herd immunity for ZIKV infection is inadequate, especially among pregnant women in the two post-outbreak areas in southern Thailand.
Local delivery of USC-derived exosomes harboring ANGPTL3 enhances spinal cord functional recovery after injury by promoting angiogenesis
Authors: Cao Yong , Yan Xu , Chen Chunyuan , Xie Hui , Lu Hongbin , Hu Jianzhong
Published: October 2020

Background: Spinal cord injury is a devastating clinical condition for which there are currently no effective therapeutic options. In the present study, we aim to investigate the effect of an administered injection of exosomes derived human urine stem cell (USC-Exo) embedded in hydrogel could improve the spinal cord functional recovery after injury and the underlying mechanism.Methods: Exosome were isolate from USC and identified by transmission electron Microscopy (TEM) and western blot. Functional assays in vitro were performed to assess the effects of USC-Exo on tube formation and migration, as well as their regulatory role in the PI3K/AKT signaling pathway activation. A locally administered injection of exosome embedded in hydrogel was used for SCI treatment. The effects of USC-Exo on functional recovery and the role of the candidate protein ANGPTL3 harboring in USC-Exo for promoting angiogenesis in SCI model was assessed.Results: In the current study, we demonstrate that a locally administered injection of USC-Exo embedded in hydrogel can pass the spinal cord blood brain barrier and deliver ANGPTL3 to the injured spinal cord region. In addition, the administration of human USC-Exo could enhance spinal cord neurological functional recovery by promoting angiogenesis. The results of mechanistic studies revealed that ANGPTL3 is enriched in (USC-Exo) and is required for their ability to promote angiogenesis. Functional studies further confirmed that the effects of USC-Exo on angiogenesis are mediated by the PI3K/AKT signaling pathway. Conclusion: Collectively, our results indicate that USC-Exo serve as a crucial regulator of angiogenesis by delivering ANGPTL3 and may represent a promising novel therapeutic agent for SCI repair.
The cost ‑effectiveness of hypertonic saline inhalations for infant bronchiolitis.
Authors: buendia jefferson , Acuña-Cordero Ranniery
Published: October 2020

Background Pharmacological treatment for bronchiolitis is primarily supportive because bronchodilators, steroids, and antibiotics, show little benefit. Clinical studies have suggested that nebulized 3% hypertonic solution is useful for infants with bronchiolitis. This study aims to evaluate the cost-effectiveness of the HS inhalations in infant bronchiolitis in a tropical country Methods Decision tree analysis was used to calculate the expected costs and QALYs. All cost and use of resources were collected directly from medical invoices of 193 patient hospitalized with diagnosis of bronchiolitis in tertiary centers, of Rionegro, Colombia. The utility values applied to QALYs calculations were collected from the literature. The economic analysis was carried out from a societal perspective.Results The model showed that nebulized 3% hypertonic solution, was associated with lower total cost than controls (US $200vs US $240 average cost per patient), and higher QALYs ( 0.92 vs 0.91 average per patient); showing dominance. A position of dominance negates the need to calculate an incremental cost-effectiveness ratio.Conclusion The nebulized 3% hypertonic solution was cost-effective in the inpatient treatment of infant bronchiolitis. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines and should be replicated to validate their results in other tropical countries.
Serum CA242: a biomarker for diagnosis, progression, and metastasis in multiple tumors
Authors: Shen Kaicheng , Qin Xiangquan , Su Xingxing , Yang Yishi , Wang Hongqian , Dai Haisu , Jiang Yan , Bai Jie , Chen Zhiyu
Published: October 2020

BackgroundCA242 is a classic biomarker used for diagnosing digestive tract tumors, especially pancreatic cancer. However, CA242 serum levels in some tumor patients and what might influence these levels remain unknown or uncertain. This study aimed to reveal the pancancer landscape of serum CA242 levels and identify some influencing factors.MethodsIn the current study, serum CA242 levels and clinical information, including clinical stage and metastatic status, were collected from 37,493 patients with 35 different types of neoplastic disease, and CA242 values were also obtained for 880 healthy controls.ResultsSerum CA242 levels in patients with one of 21 different cancers were significantly higher than those in healthy controls and had diagnostic value in 9 tumors (AUC>0.7, P<0.05); serum CA242 levels were increased across all malignant digestive tract tumors. Compared to patients without metastasis, cancer patients with one of 15 kinds of cancer with lymph node metastasis and distant metastasis showed elevated CA242 levels. Moreover, CA242 was helpful in distinguishing the clinical stage and metastatic status in 6 cancers. In addition, the presence of multiple metastases and liver metastasis might result in increased CA242 levels.ConclusionsOverall, CA242 can not only serve as a diagnostic biomarker for malignant tumors in the digestive system but also predict the progression, stage, and metastasis of many other tumors that have not received clinical attention.
A Reconstructed Discontinuous Galerkin Method for Compressible Flows on Moving Curved Grids
Authors: Luo Hong , Wang Chuanjin
Published: October 2020

A high-order accurate reconstructed discontinuous Galerkin (rDG) method is developed for compressible inviscid and viscous flows in arbitrary Lagrangian-Eulerian (ALE) formulation on moving and deforming unstructured curved meshes. Taylor basis functions in the rDG method are defined on the time-dependent domain, where the integration and computations are performed. The Geometric Conservation Law (GCL) is satisfied by modifying the grid velocity terms on the right-hand side of the discretized equations at Gauss quadrature points. A radial basis function (RBF) interpolation method is used for propagating the mesh motion of the boundary nodes to the interior of the mesh. A third order Explicit first stage, Single Diagonal coefficient, diagonally Implicit Runge-Kutta scheme (ESDIRK3) is employed for the temporal integration. A number of benchmark test cases are conducted to assess the accuracy and robustness of the rDG-ALE method for moving and deforming boundary problems. The numerical experiments indicate that the developed rDG method can attain the designed spatial and temporal orders of accuracy, and the RBF method is effective and robust to avoid excessive distortion and elements near moving boundaries.
Automated computed tomography quantification of fibrosis predicts prognosis in combined pulmonary fibrosis and emphysema in a real-world setting-A single-centre, retrospective study
Authors: Nemoto Masahiro , Nei Yuichiro , Bartholmai Brian , Yoshida Kazuki , Matsui Hiroki , Nakashita Tamao , Motojima Shinji , Aoshima Masahiro , Ryu Jay H.
Published: October 2020

Background: Combined pulmonary fibrosis and emphysema (CPFE) is a heterogeneous clinico-radiological syndrome without a consensus definition. There are limited data on the relation between the amount of parenchymal fibrosis and prognosis. In this study, we assessed the prognostic implications of the extent of fibrosis assessed by an automated quantitative computed tomography (CT) technique and the radiological and functional change over time in patients with a broad spectrum of fibrotic interstitial lung diseases (ILDs) encountered in a real-world setting.Methods: We conducted a single-centre, retrospective study of 228 consecutive patients with CPFE, encountered from 2007 to 2015 at Kameda Medical Center, Chiba, Japan. We investigated the prognostic value of automated CT fibrosis quantification and the subsequent course of CPFE. Results: Among 228 patients with CPFE, 89 had fibrosis affecting <5% of their lungs, 54 had 5 to <10% fibrosis, and 85 had ≥10% fibrosis at the time of diagnosis. Lower volume of fibrosis correlated with lower rates of mortality and acute exacerbation (p<0.001). In particular, among those with <5% fibrosis, only 4.5% died and none experienced acute exacerbation during follow-up, whereas 57.6% and 29.4% of those with ≥10% fibrosis experienced death and acute exacerbation, respectively. Although, the ≥10% fibrosis group had the poorest overall survival as well as the highest incidence of acute exacerbation, the incidence of decline in pulmonary function tests, change per year in total lung volume, and progression of fibrosis on chest CT was highest in the 5 to <10% fibrosis group. The Cox proportional hazard model for CPFE progression (defined by composite criteria of death, acute exacerbation, and decline in forced vital capacity or diffusing capacity) showed fibrosis proportion was a risk factor independent of age, sex, smoking pack-years, the Charlson Comorbidity Index, lung cancer, connective tissue disease, and idiopathic pulmonary fibrosis.Conclusions: Less severe (<5%) fibrosis at baseline was associated with disease stability and better prognosis compared to more severe fibrosis in CPFE occurring with fibrotic ILDs. Further studies including a validation cohort will be needed.Trial Registration: retrospectively registered