bluuebunny/crossref_metadata_2025 huggingface dataset:
Volcanic imprint in the North Atlantic climate variability as recorded by stable water isotopes of Greenland ice cores
Authors: Guðlaugsdóttir Hera , Sjolte Jesper , Sveinbjörnsdóttir Árný Erla , Steen-Larsen Hans Christian
Published: September 2020

Volcanic eruptions are important drivers of climate variability on both seasonal and multi-decadal time scales as a result of atmosphere-ocean coupling. While the direct response after equatorial eruptions emerges as the positive phase of the North Atlantic Oscillation in the first two years after an eruption, less is known about high latitude northern hemisphere eruptions. In this study we assess the difference between equatorial and high latitude volcanic eruptions through the reconstructed atmospheric circulation and stable water isotope records of Greenland ice cores for the last millennia (1241-1979 CE), where the coupling mechanism behind the long-term response is addressed. The atmospheric circulation is studied through the four main modes of climate variability in the North Atlantic, the Atlantic Ridge, Scandinavian Blocking and the positive and negative phase of the North Atlantic Oscillation. We report a difference in the atmospheric circulation response after high latitude eruptions compared to the response after equatorial eruptions, where the positive phase of the North Atlantic Oscillation and the Atlantic Ridge seem to be more associated with equatorial eruptions while the negative phase of the North Atlantic Oscillation seems to follow high latitude eruptions. This response is present during the first five years and then again in years 8-12 after both equatorial and high latitude eruptions. Such a prolonged response is evidence of an ocean-atmosphere coupling that is initiated through different mechanisms, where we suspect sea ice to play a key role.
Tracing the fate of wastewater viruses reveals catchment-scale virome diversity and connectivity
Authors: Adriaenssens Evelien , Farkas Kata , McDonald James , Jones David , Allison Heather , McCarthy Alan
Published: September 2020

The discharge of wastewater-derived viruses in aquatic environments impacts catchment-scale virome composition and is a potential hazard to human health. Here, we used viromic analysis of RNA and DNA virus-like particle preparations to track virus communities entering and leaving wastewater treatment plants and the connecting river catchment system and estuary. We found substantial viral diversity and geographically distinct virus communities associated with different wastewater treatment plants. River and estuarine water bodies harboured more diverse viral communities in downstream locations, influenced by tidal movement and proximity to wastewater treatment plants. Shellfish and beach sand were enriched in viral communities when compared with the surrounding water, acting as entrapment matrices for virus particles. We reconstructed >40,000 partial viral genomes into 10,149 species-level groups, dominated by dsDNA and (+)ssRNA bacteriophages (Caudovirales and Leviviridae). We identified 73 (partial) genomes comprising six families that could pose a risk to human health; Astroviridae, Caliciviridae (sapovirus), Picornaviridae (cocksackievirus), Reoviridae (rotavirus), Parvoviridae and Circoviridae. Based on the pattern of viral incidence, we observe that wastewater-derived viral genetic material is commonly deposited in the environment, but due to fragemented nature of these viral genomes, the risk to human health is low, and is more likely driven by community transmission, with wastewater-derived viruses subject to cycles of dilution, enrichment and virion degradation influenced by local geography, weather events and tidal effects. Our data illustrate the utility of viromic analyses for wastewater- and environment-based epidemiology, and we present a conceptual model for the circulation of viruses in a freshwater catchment.
Implementation of a fetal ultrasound telemedicine service: an evaluation of outcomes, women’s views and family costs.
Authors: Marshall Alison , Lie Mabel , Bidmead Elaine , Beckwith Bob , Oudgaarden Elisabeth Van , Robson Stephen C , Smith Vikki J.
Published: September 2020

Background
The complexity of fetal medicine (FM) referrals that can be managed within obstetric units is dependent on the availability of specialist ultrasound expertise. Telemedicine can effectively transfer real-time ultrasound images via video‐conferencing. We report the successful introduction of a fetal ultrasound telemedicine service linking a specialist fetal medicine (FM) centre and a remote obstetric unit.
Methods
All women referred for FM consultation from the obstetric unit were seen via telemedicine, excluding cases where invasive testing or cardiac anomalies were anticipated. The image quality was rated following each consultation. Women's experiences and family costs were evaluated by a questionnaire completed following the first telemedicine appointment during the first phase of the project.
Results
Overall, 297 women had a telemedicine consultation during Phase 1 (pilot and evaluation) and Phase 2 (embedding and adoption) of the project, which covered a four year period. There were 154 new and 143 follow-up consultations. Thirty-four women completed questionnaires during the Phase 1 of the study. Travel to the telemedicine consultation took a median time of 20 minutes (4,150), in comparison to an estimated journey of 229.8 minutes (120,450) to the FM centre. Women were generally satisfied with the service and valued the opportunity to have a FM consultation locally.
Conclusions
We have demonstrated that a fetal ultrasound telemedicine service can be successfully introduced to provide FM ultrasound of sufficient quality to allow fetal diagnosis and specialist consultation with parents. Furthermore, the service is acceptable to parents, has shown a reduction in family costs and journey times.
Vertebrobasilar Artery Geometry and Basilar Artery Plaques: A High-Resolution Magnetic Resonance Imaging Study
Authors: Zheng Jinmei , Sun Bin , Lin Ruolan , Teng Yongqi , Zhao Xihai , Xue Yunjing
Published: September 2020

Background

Atherosclerotic plaques are often present in regions with complicated flow patterns. Vascular morphology plays a role in hemodynamics. In this study, we investigate the relationship between the geometry of the vertebrobasilar artery system and the basilar artery (BA) plaque prevalence.
Methods

We enrolled 290 patients with posterior circulation ischemic stroke. We distinguished four configurations of the vertebrobasilar artery: Walking, Tuning Fork, Lambda, and No Confluence. The diameter of the vertebral artery (VA) and the number of bends in the intracranial VA segment was assessed using three-dimensional time-of-flight magnetic resonance angiography. We differentiated between multi-bending (≥ 3 bends) and oligo-bending (< 3 bends) VAs. High-resolution magnetic resonance imaging was used to evaluate BA plaques. Logistic regression models examined the relationship between the geometry type and BA plaque prevalence.
Results

After adjusting for sex, age, body mass index ≥ 28, hypertension, and diabetes mellitus, the Walking, Lambda, and No Confluence geometries were associated with the presence of BA plaque. Patients with multi-bending VAs in both the Walking (71.43%, P = 0.003) and Lambda group (40.43%, P = 0.018) had more plaques compared to patients with oligo-bending VAs in these groups. In the Lambda group, the diameter difference between the VAs was larger in patients with BA plaques than that in patients without BA plaques (1.4 mm vs. 0.9 mm, P < 0.001).
Conclusions

The Walking, Lambda, and No Confluence geometry, ≥ 3 bends in the VAs, and a large diameter difference between the VAs were associated with the presence of BA plaque.
Effect of Speed and Gradient on Plantar Force When Running on an AlterG® Treadmill.
Authors: Thomson Athol , Whiteley Rodney , Hansen Clint , Welzel Julius , Racinais Sebastien , Wilson Mathew
Published: September 2020

Background
Anti-gravity treadmills are used to decrease musculoskeletal loading during treadmill running often in return to play rehabilitation programs. The effect different gradients (uphill/downhill running) have on kinetics and spatiotemporal parameters when using an AlterG® treadmill is unclear with previous research focused on level running only.
Methods
Ten well-trained healthy male running athletes ran on the AlterG® treadmill at varying combinations of bodyweight support (60%, 80%, and 100% BW), speed (12 km/hr, 15 km/hr, 18 km/hr, 21 km/hr, and 24 km/hr), and gradients (-15% decline, -10, -5, 0, + 5, +10 + 15% incline), representing a total of 78 conditions performed in random order. Maximum plantar force and contact time were recorded using a wireless in-shoe force sensor insole system.
Results
Regression analysis showed a linear relationship for maximum plantar force with bodyweight support and running speeds for level running (p < 0.0001, adj. R² = 0.604). The linear relationship, however, does not hold for negative gradients at speeds 12 & 15 km/h, with a relative ‘dip’ in maximum plantar force across all assisted bodyweight settings.
Conclusions
Maximum plantar force peaks are larger with faster running and smaller with more AlterG® assisted bodyweight support (athlete unweighing). Gradient made little difference except for a downhill grade of -5% decreasing force peaks as compared to level or uphill running.
Diagnostic Value of Mid-regional Pro-adrenomedullin (MR-proADM) as a Biomarker of Invasive Bacterial Infection in Children: A Systematic Review.
Authors: Corr Michael , Fairley Derek , McKenna James , Shields Michael , Waterfield Thomas
Published: September 2020

BackgroundIn children differentiating between the early stages of an invasive bacterial infection (IBI) and a benign self-limiting viral infection remains clinically challenging. This often leads to an over-use of antimicrobial drugs with resultant antimicrobial resistance due to the concern of not detecting a deteriorating child. Hence research into novel biomarkers for the early identification of IBI in children is of increasing interest. A more timely diagnosis through more accurate biomarkers may lead to improved clinical outcomes for children and reduced antimicrobial resistance. Mid-regional pro-adrenomedullin (MR-proADM) is a biomarker that is found at elevated levels in patients with IBI compared with those with viral infections. The aim of this systematic review was to determine the diagnostic accuracy of MR-proADM at identifying children with IBI. MethodsWe searched MEDLINE, Embase, Web of Science and Scopus from 1980 to the present day for all human clinical trials involving children that report the test accuracy of MR-proADM. Eligibility was assessed by screening titles and abstracts of articles found during the search process. This was then followed by full-text assessment and data extraction. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was used to assess the methodological quality of identified studies. The following test characteristics were extracted into 2 × 2 tables for all included studies: true positives, false positives, true negatives, and false negatives. ResultsA total of 501 articles were initially identified. After the removal of duplicates and abstract screening 11 texts were fully reviewed. 4 studies (totaling 1404 patients) were able to be included in the systematic analysis. Only one study was of a high quality and that study accounted for the vast majority of patients. A single study reported the diagnostic accuracy of MR-proADM for invasive bacterial infection reporting an Area under the Curve of 0.69. The paucity of available studies made meta-analysis and studies of heterogeneity impossible.ConclusionThere is a paucity of research regarding the diagnostic accuracy of MR-proADM in the diagnosis of invasive bacterial infections in children. Initial results would suggest that MR-proADM testing alone is poor at identifying IBI in young children. It remains unclear if MR-proADM performs differently in older children or in children with signs and symptoms of IBI. Trial registrationPROSPERO CRD42018096295
Comparison of the in-vivo Effect of Two Tranexamic Acid Doses on Fibrinolysis Parameters in Adults Undergoing Valvular Cardiac Surgery with Cardiopulmonary Bypass - A Pilot Investigation
Authors: ZHOU Zhen-feng , Zhai Wen , YU Li-na , SUN Kai , SUN Li-hong , XING Xiu-fang , YAN Min
Published: September 2020

Background: The blood saving efficacy of TXA in cardiac surgery has been proved in several studies, but TXA dosing regimens were varied in those studies. Therefore, we performed this study to investigate if there is a dose dependent in-vivo effect of TXA on fibrinolysis parameters by measurement of fibrinolysis markers in adults undergoing cardiac surgery with CPB, which has not been systematically elucidated.Methods: A double-blind, randomized, controlled prospective trial was conducted from February 11, 2017 to May 05, 2017. Thirty patients undergoing cardiac valve surgery were identified and randomly divided into a placebo group, low-dose group and high-dose group by 1: 1: 1. Fibrinolysis parameters were measured by plasma levels of D-Dimers, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), plasmin-antiplasmin complex (PAP), tissue plasminogen activator (tPA) and thrombomodulin (TM). Those proteins were measured at five different sample times: preoperatively before the TXA injection (T1), 5 min after the TXA bolus (T2), 5 min after the initiation of CPB (T3), 5 min before the end of CPB (T4) and 5 min after the protamine administration (T5). A Thrombelastography (TEG) and standard coagulation test were also performed.Results: Compared with the control group, the level of the D-Dimers decreased in the low-dose and high-dose groups when the patients arrived at the ICU and on the first postoperative morning. Over time, the concentrations of PAI-1, TAFI, and TM, but not PAP and tPA, showed significant differences between the three groups (p <0.05). Compared with the placebo group, the plasma concentrations of PAI-1 and TAFI decreased significantly at the T3 and T4 (p <0.05); TAFI concentrations also decreased at the T5 in low-dose group (p <0.05). Compared with the low-dose group, the concentration of TM increased significantly at the T4 in high-dose group. No significant differences were observed in the levels of the coagulation proteins at any points between the groups.Conclusions: The vivo effect of low dose TXA is equivalent to high dose TXA on fibrinolysis parameters in adults undergoing valvular cardiac surgery with cardiopulmonary bypass, and we recommend a low dose TXA regimen for those patients.Clinical trial number and registry URL: ChiCTR-IPR-17010303; http://www.chictr.org.cn, Principal investigator: Zhen-feng ZHOU, Date of registration: January 1, 2017.
Diseases Registered Among Integrated Textile Factory Workers in Ethiopia: A Retrospective Cross-Sectional Study
Authors: Tefera Yifokire , Kumie Abera , Deressa Wakgari , Bråtveit Magne , Moen Bente E.
Published: September 2020

Background: Textile and garment factories are growing in low and middle-income countries; integrated textile and garment production factories are developing, where workers are exposed to dust and dangerous, noisy machines in the work environment. Hence, workers' health might be affected negatively due to exposure to different occupational hazards. However, the health condition of workers in this sector is not adequately investigated. The aim of this study is to describe the registered diagnoses of health problems and their association to work-related and personal factors among workers in integrated textile factories in Ethiopia. Methods: A one year recording of worker’s clinical diagnoses (between March 2016 and February 2017) was gathered from the respective factory clinics in three integrated textile factories. Sociodemographic characteristics and work-related information is obtained from the factory’s human resource departments. The association between the registered diagnoses and work-related factors (work in textile production, garment production and support department) and personal factors (age, gender and educational status) were studied using logistic regression analyses.Results: The socio-demographic and clinical diagnosis statuses of 7992 workers are analyzed. The average of workers' age and years of service is 40 years and 11 years, respectively. Majority 4778(60%) of workers are females; a total of 5276 (66%) of workers had 27320 clinical diagnoses; in total this causes 16993 working days lost due to sick leave. Respiratory diseases (34%) and musculoskeletal disorders (29%) were the most prevalent diagnoses, while injuries cause most of the days of work absence. Work department, gender and educational status are the variables that are significantly associated with several disease groups.Conclusions: About two-thirds of the integrated textile factory workers were diagnosed with different types of diseases. The textile and garment production department workers were more affected than the support department workers, indicating that some of the diseases are related to work in these departments. Further study should investigate the occurrence of rare chronic diseases such as cancer, heart diseases, renal diseases and diabetics in relation with workers exposure profile.
Chidamide combined with doxorubicin induced p53-driven cell cycle arrest and cell apoptosis reverse multidrug resistance of breast cancer
Authors: CAO Lixia , Zhao Shaorong , Yang Qianxi , Shi Zhendong , Liu Jingjing , Pan Teng , Zhou Dongdong , Zhang Jin
Published: September 2020

Background: The multidrug-resistant (MDR) phenotype is usually accompanied by an abnormal expression of histone deacetylase (HDAC). Given that HDAC is vital in chromatin remodeling and epigenetics, inhibiting the role of HDAC has become an important approach for tumor treatment. However, the effect of HDAC inhibitors on MDR breast cancer has not been elucidated. This study aimed to evaluate the resistance of two MDR breast cancer cell lines to the HDAC-selective inhibitor chidamide (CHI).Methods: Cell viability, cell cycle and apoptosis were detected by CCK8, crystal violet staining, EDU staining, TUNEL assay, flow cytometry. The expression of HDAC1, H3K9, H3K18, p53, p21, caspase3/7/9 and the Bcl family was analyzed by western blotting and Quantitative real-time PCR. MDR breast cancer growth suppression by CHI and/or doxorubicin (DOX) in vivo was investigated in a tumor xenograft mouse model.Results: The results showed that, CHI combined with DOX showed significant cytotoxicity to MDR breast cancer cells in vitro and in vivo compared with the CHI monotherapy. The cell cycle distribution results showed that CHI caused G0/G1 cell cycle arrest and inhibited cell growth regardless of the addition of DOX. At the same time, Annexin V staining and TUNEL staining results showed that CHI enhanced the number of cell apoptosis in drug-resistant cells. The western blot analysis found that p53 as a tumor suppressor was in a silent state in drug-resistant cells. However, p53 was activated in the CHI-treated and combined treatment groups, which, in turn, activated the p53 up-regulated apoptosis regulator recombinant protein (Puma) and pro-apoptotic protein Bax, downregulated the apoptotic proteins Bcl-xL and Bcl-2, and activated the caspase cascade to induce apoptosis. ﻿Conclusion: The irreversible cell stress induced by CHI combined with DOX reduced the expression of HDAC1 and activated caspase-dependent apoptosis and p21-mediated growth arrest pathway, which might have been driven by the activation of p53. This provided a strong theoretical basis for exploring the treatment strategy of the combined use of CHI in patients with breast cancer who did not respond to chemotherapy or had cancer progression.
A New Surgical Technique of Laparoscopic Retrograde Inguinal Lymph Node Dissection: Our Initial Experience
Authors: Zhao Qinxin , Han Hu , Lei Hongen , Li Yajian , Tian Long , Xing Nianzeng
Published: September 2020

Background To explore the clinical efficacy of a new laparoscopic inguinal retrograde lymph node dissection (LND) in treating penile cancer and scrotal Paget’s disease. Methods 12 patients with penile cancer and 1 with scrotal Paget’s disease admitted and treated with laparoscopic retrograde inguinal LND in two medical centers from July 2018 to September 2020 were retrospectively analyzed. Thereafter, the basic clinical data, operation time, intraoperative blood loss, number of harvested lymph nodes and postoperative complications were evaluated. Results 13 patients were performed laparoscopic retrograde inguinal LND successfully under general anesthesia. Among them, 4 cases received pelvic lymph node dissection (PLND) simultaneously through the same incision. The operation time was (220.00±33.73) min, and the intraoperative blood loss was (15.38±13.76) ml. (8.92士4.00) lymph nodes were harvested in the left groin, (8.54士5.04) lymph nodes were dissected in the right groin. Meanwhile, (5.00士1.00) lymph nodes were harvested in the left pelvic cavity, and (8.50± 6.46) lymph nodes were dissected in the right pelvic cavity. All the 13 cases were successfully operated without conversions to open surgery. One case developed mild blister in subcutaneous skin, two had mild lower limb swelling, and one had lymph leakage; all these patients recovered favorably after symptomatic treatment, with no other surgery-related complications. The drainage tube removal time lasted for (13.23士3.83) days. The postoperative follow-up time ranged from 2.5 to 19.5 months, and no primary lesion, inguinal or pelvic lymph node relapse or metastasis was reported. Conclusion Laparoscopic retrograde inguinal LND can be applied to treat penile cancer and scrotal Paget’s disease, and it is safe and effective. Moreover, inguinal LND and PLND can be performed through the same incision, which is worthy of being promoted in clinic.
Clinical Characteristics of Severe Covid Pneumonia: Exploring New Trends in ICU
Authors: Akhtar Aftab , Bano Sheher , Iqbal Ahtesham , Ramzan Moazma , Qadeer Aayesha , Hussain Syed Waqar , Saleem Anam , Lodhi Omair-ul-Haq , Zubair Sana , kiani Abdul Hameed
Published: September 2020

Background: In late December 2019, Covid-19 emerged as clusters of pneumonia of unknown cause in a province of china, Wuhan. Etiological agent was identified as novel coronavirus that resembles severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East Respiratory syndrome coronavirus (MERS-CoV) and has zoonotic transmission. Covid pneumonia can remain asymptomatic, present as mild infection, severe pneumonia or respiratory failure. Diagnosis is based on rRT-PCR carried out on respiratory secretions. Covid related mortality exceeds 50% once patient requires ICU admission. Objective: To study the characteristics of ICU population admitted to ICU of Shifa International hospital.Results: we prospectively analysed 74 patients which included 43.3% females and 56.7% males. Commonest symptoms were shortness of breath (94.5%), fever (74.3%) and cough (74.3%). Most of our study population consisted of non-smokers (79.7%) and had hypertension (59.4%) followed by diabetes (47.2%). Hydroxychloroquine (HCQ) and azithromycin combination is superior to hydroxychloroquine and doxycycline in reducing mortality (p=0.023) whereas Doxycycline alone resulted in increased mortality (p=0.009). Those who did not require antibiotics or required only narrow spectrum antibiotics had increased survival and reduced requirement of invasive mechanical ventilation (p=< 0.0001). in our study population, (44.9%) developed acute kidney injury, 2.7% needed re-intubations 10.8% developed surgical emphysema and 2.7 % thromboembolic events despite full anticoagulation. ICU mortality was 41.8% and was higher in females (59.4%, p=0.008), those who had SOFA score > 3.5 at time of admission, raised D-Dimers > 931 ng/ml, NLR > 9.2. It was further high in those who required invasive mechanical ventilation and vasopressor support (58.1% mortality p=< 0.001). ICU stay was more prolonged in those requiring invasive mechanical ventilation as compared to those who did not. (23 days vs 6 days, p=0.001). Mean plateau pressure was 19.6 ± 7.6; mean Driving pressures 14.4 ± 4.6; mean PaO2/FiO2 150.7 ± 73.9; mean SPO2/FiO2 173.9 ± 106.9; mean PEEP was 8.2 ±4.33.Conclusion: We concluded that severe covid pneumonia is common amongst males, non-smokers those who had comorbid. HCQ and azithromycin combination is superior to combination of HCQ and doxycycline or doxycycline alone and QT prolongation is a rare complication. Baseline NLR, APACHI II, SOFA, SAPS II, NUTRIC scores, D-Dimers, invasive ventilation and vasopressor support are important tools to predict ICU mortality. Invasive mechanical ventilation carries higher mortality and associated with more prolonged ICU stay. AKI is most common complication followed by shock and surgical emphysema. CRP, Ferritin levels has no impact on outcome.
Usefulness of Cardiac Magnetic Resonance Images for Prediction of Sudden Cardiac Arrest in Patients with Mitral Valve Prolapse: A Multicenter Retrospective Cohort Study
Authors: Lee Jae-Hyuk , Uhm Jae-Sun , Suh Young Joo , Kim Min , Kim In-Soo , Jin Moo-Nyun , Cho Min Soo , Yu Hee Tae , Kim Tae-Hoon , Hong Yoo Jin , Lee Hye-Jeong , Shim Chi Young , Kim Young Jin , Kim Jun , Kim Jong-Youn , Joung Boyoung , Hong Geu-Ru , Pak Hui-Nam , Nam Gi-Byoung , Choi Kee-Joon , Kim You-Ho , Lee Moon-Hyoung
Published: September 2020

Background: An association has been identified between mitral valve prolapse (MVP) and sudden cardiac arrest (SCA), and ventricular arrhythmias (VA). This study aimed to elucidate risk factors for SCA or VA in MVP patients.Methods: MVP patients who had undergone cardiac magnetic resonance (CMR) were retrospectively included. Patients with other structural heart disease or causes of aborted SCA were excluded. Clinical characteristics (sex, age, body mass index, histories of diabetes, hypertension, coronary artery disease, and dyslipidemia), electrocardiographic (PR interval, QRS duration, corrected QT interval, bundle branch block, and atrial fibrillation), echocardiographic [mitral regurgitation grade, prolapsing mitral leaflet, and right ventricular systolic pressure (RVSP)] and CMR [both ventricular ejection fractions, both ventricular end-diastolic and systolic volume indexes, presence of late gadolinium enhancement (LGE), LGE volume and proportion] parameters were analyzed.Results: Of the 85 patients [age, 55.0 (41.0–65.0) years; 46 men] included, 7 experienced SCA or VA. Significantly young age and wide QRS complex were observed in the SCA/VA group compared to the no-SCA/VA group. The patients in the SCA/VA group had significantly lower RVSP, more presence of LGE, greater LGE volume, and higher LGE proportion than those in the no-SCA/VA group. A high risk for SCA or VA was observed in patients with LGE (odds ratio, 45.525; 95% confidence interval, 2.558–810.140; P = .009).Conclusions: Presence of LGE on CMR is a risk factor for SCA or VA in MVP patients. High LGE volume and LGE proportion may provide additional information for prediction of SCA or VA.
CONSENSUS: A Shiny application of Dementia evaluation and reporting for the KU ADC Longitudinal Clinical Cohort Database.
Authors: Sharma Palash , Montgomery Robert N. , Graves Rasinio S. , Meyer Kayla , Hunt Suzanne L , Vidoni Eric D. , Mahnken Jonathan D. , Swerdlow Russell H. , Burns Jeffrey M. , Mudaranthakam Dinesh Pal
Published: September 2020

Background: The University of Kansas Alzheimer’s Disease Center (KU ADC) maintains several large databases to track participant recruitment, enrollment, and capture various research related activities. It is challenging to manage and coordinate all the research related activities. One of the crucial activities involves capturing the data and maintaining high data quality, which ensures data reusability and reproducibility.Methods: To effectively manage the cohort, the KU ADC utilizes a combination of open source Electronic Data Capture (EDC) (i.e. REDCap), along with other homegrown data management and visualization systems developed using R-studio and Shiny.Results: In this manuscript, we describe the method and utility of the user-friendly dashboard that was developed for the rapid reporting of dementia evaluations along with data visualization, which allows clinical researchers to summarize recruitment metrics, automatically generate letters to both participants and health care providers, and depict other key metrics, which ultimately help optimize workflows. Conclusions: We believe this general framework would be beneficial to any institution for capturing and maintaining similar longitudinal databases for reporting and summarizing key metrics pertaining to their research.
Lipopolysaccharide-Induced Chorioamnionitis Induces Fetal Intestinal Injury and Affects Gut Colonization in Rats
Authors: Qingmei Huang , Siliang Lu , Yunlei Zhu , Bingmei Wei , Chen Yujun , Faming Bai
Published: September 2020

Background: Chorioamnionitis is associated with an increased risk of multiple adverse outcomes in offspring, especially neonatal necrotizing enterocolitis (NEC), which is one of the serious gastrointestinal diseases in neonates. However, the underlying mechanism remains undefined. We hypothesize that lipopolysaccharide (LPS)-induced chorioamnionitis causes intestinal injury in offspring, thereby affecting the composition of the intestinal microbiome.Methods: Pregnant Sprague Dawley rats were received intraperitoneal injections with 700 μg/kg Lipopolysaccharide (LPS) or saline at 15 days of gestation. Pups were allowed to deliver naturally, and euthanized at days 0,3 and 7 after birth. Intestinal tissue and faeces samples from offspring were collected to evaluate the effects of intrauterine infection on intestinal flora colonization and intestinal mucosal development. Results: Significant intestinal injury of the offspring induced by prenatal LPS exposure was observed at day 0 and 3 after birth.. In addition, prenatal LPS exposure also induced significant changes in the intestinal microbiome of the offspring with a significant increase in Proteobacteria (Escherichia-Shigella) and a decrease in Firmicutes at 7 days after birth . Conclusions: Thus, our findings suggest that LPS-induced chorioamnionitis induces intestinal injury in offspring and subsequently leads to NEC-like changes in the composition of the intestinal microbiome.
Harm reduction via online platforms for people who use drugs in Russia: A qualitative analysis of web outreach work
Authors: Davitadze Arsen , Meylakhs Peter , Lakhov Aleksey , King Elizabeth J.
Published: September 2020

Background
Harm reduction services to people who use drugs (PWUD) in Russia are insufficient in terms of quantity, government endorsement, and accessibility. The situation has recently deteriorated even further because of social distancing measures of the COVID-19 pandemic. Recently several harm reduction organizations have started to provide some harm reduction services via online platforms by web outreach. However, little is known on how online outreach services are organized and implemented. Drawing on the example of St. Petersburg-based NGO “Humanitarian Action” we explored web outreach work in Telegram instant messenger.
Methods
4 semi-structured interviews with the NGO staff and 301 cases of web outreach work with PWUD comprised the dataset. The process of web outreach, service provision to PWUD, and PWUD’s needs were thematically analyzed.
Results
Three stages of the process of web outreach work were determined: clients initiating communication, NGO workers addressing clients’ needs, and NGO workers receiving clients’ feedback. Communication proceeded either in group chat or in direct messages. Challenges in addressing clients’ needs happened when clients turned for help in nighttime, sent recorded voice messages, sent unclear messages, and/or were unwilling to transition to telephone communication. All web outreach workers reported receiving only positive feedback on their work. PWUD’s needs were categorized into two major themes, depending on whether they can be addressed fully or partially online. In cases of online only provision of services, web outreach workers helped PWUD treat minor injection drug use complications, obtain verified harm reduction information and receive general psychological support. In instances of partial online services provision, PWUD were assisted in getting treatment of severe injection drug use complications, overdoses, and in accessing offline medical, psychological, social, legal and harm reduction services.
Conclusions
Our research demonstrated that web outreach work is a convenient tool for delivering some harm reduction services to PWUD either partially or completely online and recruiting new clients (including hard-to-reach PWUD that avoid attending brick-and-mortar facilities). It indicates that harm reduction organizations should consider incorporating online harm reduction services into their activities. However, more research is needed to explore relative advantages and disadvantages of online harm reduction services delivery.
Meal frequency and associated factors among children 6-23 months in Tahtay michew district, northern Ethiopia, 2018
Authors: Brhane Ermyas , Grum Teklit , Abraha Teklehaymanot Huluf , Aregawi Gebrekiros
Published: September 2020

BackgroundThe term meal frequency is used to describe the adequacy of complementary feedings among children. In the absence of adequate meal frequency young children are susceptible to malnutrition like stunting, wasting, micronutrient deficiencies and associated morbidity and mortality. More half of Ethiopian children did not receive age appropriate minimum meal frequency. Therefore, the aim of this study is to determine minimum meal frequency and associated factors among children 6–23 months in Tahtay Michew district, Northern Ethiopia.MethodsA community based cross sectional study was conducted among systematically selected 981 mothers with index children 6–23 month. An interviewer- administered structured questionnaire was used to collect data. 24 hours dietary recalls was used to determine minimum meal frequency. Crude and Adjusted Odds Ratio with the corresponding 95% confidence interval were computed. In the multivariable analysis, variables with less than 0.05 P-value were considered statistically significant.ResultsMinimum meal frequency was 68% [95% CI: 64.9, 70.9%]. Wealth index (AOR = 1.69, 95% CI = 1.09, 2.61), growth monitoring follow up (AOR = 1.98, 95% CI = 1.41, 2.79) and mothers knowledge (AOR = 2.15, 95% CI = 1.51, 3.04) were factors significantly associated with minimum meal frequency.Conclusion and recommendationThe proportion of children who received the minimum meal frequency was found low. Improving the wealth status of families and encouraging all mothers to attend growth monitoring follow ups are important for improving meal frequency and dietary diversity.
Evaluation of demographic, clinical characteristics, and the prescribing practice of guideline-directed medical therapy among chronic heart failure outpatients in multidisciplinary clinics in a large tertiary hospital: a retrospective audit of 1186 patients from 12 years
Authors: Parajuli Daya Ram , Shakib Sepehr , Eng-Frost Joanne , McKinnon Ross , Caughey Gillian , Whitedhead Dean
Published: September 2020

BackgroundAdherence to guideline-directed medical therapy (GDMT) remains low particularly in elderly despite several approaches. Previous studies showed that heart failure (HF) patients who receive pharmacist-involved multidisciplinary care may have better clinical outcomes. We evaluated patient characteristics and the practice of receiving individual GDMT in chronic HF patients who attended multidisciplinary clinics.MethodsA retrospective audit of data of chronic HF patients presenting to two multidisciplinary outpatient clinics at a tertiary hospital between March 2005 and January 2017 was performed. Data were obtained from two clinics, a Multidisciplinary Ambulatory Consulting Service (MACS) clinic which uses a pharmacist-involved model of multidisciplinary care, and a General Cardiology Heart Failure Service (GCHFS) clinic which does not have the active involvement of a pharmacist.ResultsHF with mid-range ejection fraction (HFmrEF) subjects resembled the HF with preserved ejection fraction (HFpEF) patients in terms of age, heart rate (HR), systolic blood pressure (SBP) and having higher prevalence of polypharmacy whereas resembled with the HF with reduced ejection fraction (HFrEF) for the proportion of male distribution and prevalence of ischemic heart disease (IHD). Both the clinics had similar prescribing rates of GDMT and achieved maximal tolerated doses of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARB) in HFrEF, but significantly higher prescription of ACEIs/ARBs (70.5% v. 56.2%) was found in HFpEF patients in the MACS clinic. There was significantly lower rates of β-blockers and mineralocorticoid receptor antagonists (MRAs) prescription in HFrEF and HFpEF patients in both clinics. Use of digoxin in chronic atrial fibrillation (AF) was significantly higher in HFrEF patients (82.5% v. 58.5%), but number of people anticoagulated in presence of AF and prescription of diuretics were significantly lowered in MACS clinic in HFpEF patients. Age, anemia, chronic renal failure, SBP, HR and comorbidities were the significant predictors in a multivariate binary logistic regression for the utilization of GDMT.ConclusionsOur study concludes that pharmacist is an important member of a multidisciplinary team in the management of chronic heart failure. The other roles of the pharmacist within a multidisciplinary team, including continuity of care, medication compliance and prevention of adverse reactions need further research.
Treatment of Metformin Decreases the Risk of Varicose Vein: A Mendelian Randomization Study
Authors: Chen Qinchang , Li Lingling , Wu Ridong , Wang Shenming , Yao Chen
Published: September 2020

Background Varicose vein is a common illness of the vascular system which affects life quality and social function of patients. We aimed to assess the causality between metformin and varicose vein using a two-sample Mendelian randomization（MR）analysis based on genome-wide association study (GWAS) summary data.Methods Twenty-five single nucleotide polymorphisms (SNPs) were selected from the GWAS summary data from Neale Lab and MRC-IEU Consortium available on the MR-base platform. Inverse variance weighted (IVW), MR-egger method, weighted median method and weighted mode were adopted. Results were evaluated by pleiotropy test using an Egger regression method and sensitivity analysis preforming a leaving-one-out (LOO) method. Analyses were performed using R package “TwoSampleMR”.Results The result of IVW method showed that one SD increased treatment of metformin was linked with approximately 10% lower risk of varicose vein (OR,0.90; 95%CI, 0.85-0.96; P, 6.99e-04). It was similar to that measured by other methods in the aspect of effect size and direction. There is no evidence to supporting genetic pleiotropy in the MR-Egger regression method (intercept=2.5e-04, P=0.33). No single SNP was detected to be strongly driving the overall causal effect in a LOO sensitivity analysis. The genetically predicted treatment of metformin was negatively casually associated with varicose veins.Conclusions This study suggested that treatment of metformin was a casual protective factor of varicose vein. Further researches are required to confirm our findings and explore the potential mechanisms of metformin on varicose vein.
Disturbed temporal dynamics of episodic retrieval activity with preserved spatial activity pattern in amnestic mild cognitive impairment: A simultaneous EEG-fMRI study
Authors: Shu Hao , Gu Lihua , Yang Ping , Lucas Molly V. , Gao Lijuan , Zhang Hongxing , Zhang Haisan , Xu Zhan , Wu Wei , Li Ling , Zhang Zhijun
Published: September 2020

Background
Episodic memory (EM) deficit is the core cognitive dysfunction of amnestic mild cognitive impairment (aMCI). However, the episodic retrieval circuit detected by functional MRI (fMRI) appears preserved in aMCI subjects. To address this discrepancy, this study employed simultaneous electroencephalography (EEG)-fMRI recording to determine whether temporal dynamics of brain episodic retrieval activity were disturbed in patients with aMCI.
Methods
Twenty-six aMCI and 29 healthy control (HC) subjects completed a word-list memory retrieval task during simultaneous EEG-fMRI. The retrieval success activation pattern was detected with fMRI analysis, and the familiarity- and recollection-related components of episodic retrieval activity were identified using event-related potential (ERP) analysis. The fMRI-constrained ERP analysis explored the temporal dynamics of brain activity in the retrieval success pattern, and the ERP-informed fMRI analysis detected fMRI correlates of the ERP components related to familiarity and recollection processes.
Results
The two groups exhibited similar retrieval success patterns in the bilateral posteromedial parietal cortex, the left inferior parietal lobule (IPL), and the left lateral prefrontal cortex (LPFC). The fMRI-constrained ERP analysis showed that the aMCI group did not exhibit old/new effects in the IPL and LPFC that were observed in the HC group. In addition, the aMCI group showed decreased fMRI activity in the precuneus and left hippocampus related to ERP familiarity and recollection components, respectively.
Conclusions
This study identified disturbed temporal dynamics in episodic retrieval activity with a preserved spatial activity pattern in aMCI. Taken together, the simultaneous EEG-fMRI technique demonstrated the potential to identify individuals with a high risk of cognitive deterioration.
Single Cell Analysis of Regions of Interest (SCARI) using a Novel Photoswitchable Tag
Authors: Leun Anne van der , Hoekstra Mirjam , Reinalda Luuk , Scheele Colinda , Toebes Mireille , de Graaff Michel van , Li Hanjie , Bercovich Akhiad , Lubling Yaniv , David Eyal , Thommen Daniela , Tanay Amos , Rheenen Jacco van , Amit Ido , Kasteren Sander van , Schumacher Ton
Published: September 2020

The functional activity and differentiation potential of cells is determined by their interaction with surrounding cells. Approaches that allow the unbiased characterization of cell states while at the same time providing spatial information are of major value to assess this environmental influence. However, most current techniques are hampered by a trade-off between spatial resolution and cell profiling depth. Here, we developed a photoswitch-based technology that allows the isolation and in-depth analysis of live cells from regions of interest in complex ex vivo systems, including human tissues. The use of a highly sensitive 4-nitrophenyl(benzofuran)-cage coupled to nanobodies allowed photoswitching of cells in areas of interest with low-intensity violet light and without detectable phototoxicity. Single cell RNA sequencing of spatially defined CD8+ T cells was used to exemplify the feasibility of identifying location-dependent cell states at the single cell level. Finally, we demonstrate the efficient labeling and photoswitching of cells in live primary human tumor tissue. The technology described here provides a valuable tool for the analysis of spatially defined cells in diverse biological systems, including clinical samples.
Capsid Assembly is Regulated by Amino Acid Residues Asparagine 47 and 48 in The VP2 Protein of Porcine Parvovirus
Authors: Wang Jucai , Liu Yunchao , Chen Yumei , Zhang Teng , Wang Aiping , Wei Qiang , Liu Dongmin , Wang Fangyu , Zhang Gaiping
Published: September 2020

Background: Porcine parvovirus (PPV) is a major cause of reproductive failure in swine, and has caused huge losses throughout the world. Viral protein 2 (VP2) of PPV is a major structural protein that can self-assemble into virus-like particles (VLP) with hemagglutination (HA) activity. In order to identify the essential residues involved in the mechanism of capsid assembly and to further understand the function of HA, we analyzed a series of deletion mutants and site-directed mutations within the N-terminal of VP2 in the Escherichia coli (E. coli) system. Results: Our results showed that deletion of first 47 amino acids from the N-terminal of VP2 protein did not affect capsid assembly, and further truncation to residue 48 Asparagine (Asn, N) caused detrimental effects. Site-directed mutagenesis experiments demonstrated that residue 47Asn reduced the assembly efficiency of PPV VLP, while residue 48Asn destroyed the stability, hemagglutination, and self-assembly characteristics of the PPV VP2 protein. These findings indicated that the residues 47Asn and 48Asn are important amino acid sites to capsid assembly and HA activity. Results from Native PAGE inferred that macromolecular polymers were critical intermediates of the VP2 protein during the capsid assembly process. Site-directed mutation at 48Asn did not affect the association of monomers to form into oligomers, but destroyed the ability of oligomers to assemble into macromolecular particles, influencing both capsid assembly and HA activity. Conclusions: These results demonstrated that PPV capsid assembly is a complex process that is regulated by amino acids 47Asn and 48Asn, which are located at the N-terminal of VP2 and closely related to the association of macromolecular particles. Our findings provide valuable information on the mechanisms of PPV capsid assembly and the possibility of chimeric VLP vaccine development by replacing as much as 47 amino acids at the N-terminal of VP2 protein.
Validation of The Patient-Reported Experience Measure for Care in Chinese Hospitals (PREM-CCH)
Authors: Wang Xuanxuan , Chen Jiaying , Yang Yaling , Burström Bo , Burström Kristina
Published: September 2020

Background: A psychometrically validated instrument to measure patient experience in Chinese public hospitals would be useful and is currently lacking. Our research team developed the Patient-Reported Experience Measure for Care in Chinese Hospitals (PREM-CCH). We aimed to validate this PREM-CCH in the present study.Methods: Data were drawn from a cross-sectional patient survey in 2016. Complete responses from 2,293 outpatients and 1,510 inpatients were included. Separate psychometric evaluation was carried out on outpatient and inpatient PREM-CCHs in terms of exploratory factor analysis, internal consistency, construct validity and criterion validity.Results: The validated outpatient PREM-CCH contained 22 items and five Factors, i.e. Communication and information, Professional competence, Medical costs, Efficiency, and Hospital recommendation. The validated inpatient PREM-CCH contained 19 items and six Factors, i.e. Communication and information, Professional competence, Medical costs, Efficiency, Health outcomes, and Hospital recommendation. The PREM-CCH showed satisfactory internal consistency, construct validity and criterion validity.Conclusions: The PREM-CCH is one of the first validated instruments capturing patient experience of care in the context of Chinese public hospitals. It performed well in the psychometric evaluation. It consists of a basic set of items important to patients that could be applicable to public hospitals in China and actionable to inform quality improvement initiatives.