bluuebunny/crossref_metadata_2025 huggingface dataset:
Community perspectives on the benefits and risks of technologically enhanced communicable disease surveillance systems: a report on four community juries
Authors: Degeling Chris , Carter Stacy M. , van Oijen Antoine M. , McAnulty Jeremy , Sintchenko Vitali , Braunack-Mayer Annette , Yarwood Trent , Johnson Jane , Gilbert Gwendolyn L.
Published: April 2020

Background

Outbreaks of infectious disease cause serious and costly health and social problems. Two new technologies – pathogen whole genome sequencing (WGS) and Big Data analytics – promise to improve our capacity to detect and control outbreaks earlier, saving lives and resources. However, routinely using these technologies to capture more detailed and specific personal information could be perceived as intrusive and a threat to privacy.

Method

Four community juries were convened in two demographically different Sydney municipalities and two regional cities in New South Wales, Australia (western Sydney, Wollongong, Tamworth, eastern Sydney) to elicit the views of well-informed community members on the acceptability and legitimacy of:

making pathogen WGS and linked administrative data available for public health research

using this information in concert with data linkage and machine learning to enhance communicable disease surveillance systems

Fifty participants of diverse backgrounds, mixed genders and ages were recruited by random-digit-dialling and topic-blinded social-media advertising. Each jury was presented with balanced factual evidence supporting different expert perspectives on the potential benefits and costs of technologically enhanced public health research and communicable disease surveillance and given the opportunity to question experts.

Results

Almost all jurors supported data linkage and WGS on routinely collected patient isolates for the purposes of public health research, provided standard de-identification practices were applied. However, allowing this information to be operationalised as a syndromic surveillance system was highly contentious with three juries voting in favour, and one against by narrow margins. For those in favour, support depended on several conditions related to system oversight and security being met. Those against were concerned about loss of privacy and did not trust Australian governments to run secure and effective systems.

Conclusions

Participants across all four events strongly supported the introduction of data linkage and pathogenomics to public health research under current research governance structures. Combining pathogen WGS with event-based data surveillance systems, however, is likely to be controversial because of a lack of public trust, even when the potential public health benefits are clear. Any suggestion of private sector involvement or commercialisation of WGS or surveillance data was unanimously rejected.
Comparison of statistical and machine learning models for healthcare cost data: a simulation study motivated by Oncology Care Model (OCM) data
Authors: Mazumdar Madhu , Lin Jung-Yi Joyce , Zhang Wei , Li Lihua , Liu Mark , Dharmarajan Kavita , Sanderson Mark , Isola Luis , Hu Liangyuan
Published: April 2020

Background

The Oncology Care Model (OCM) was developed as a payment model to encourage participating practices to provide better-quality care for cancer patients at a lower cost. The risk-adjustment model used in OCM is a Gamma generalized linear model (Gamma GLM) with log-link. The predicted value of expense for the episodes identified for our academic medical center (AMC), based on the model fitted to the national data, did not correlate well with our observed expense. This motivated us to fit the Gamma GLM to our AMC data and compare it with two other flexible modeling methods: Random Forest (RF) and Partially Linear Additive Quantile Regression (PLAQR). We also performed a simulation study to assess comparative performance of these methods and examined the impact of non-linearity and interaction effects, two understudied aspects in the field of cost prediction.

Methods

The simulation was designed with an outcome of cost generated from four distributions: Gamma, Weibull, Log-normal with a heteroscedastic error term, and heavy-tailed. Simulation parameters both similar to and different from OCM data were considered. The performance metrics considered were the root mean square error (RMSE), mean absolute prediction error (MAPE), and cost accuracy (CA). Bootstrap resampling was utilized to estimate the operating characteristics of the performance metrics, which were described by boxplots.

Results

RF attained the best performance with lowest RMSE, MAPE, and highest CA for most of the scenarios. When the models were misspecified, their performance was further differentiated. Model performance differed more for non-exponential than exponential outcome distributions.

Conclusions

RF outperformed Gamma GLM and PLAQR in predicting overall and top decile costs. RF demonstrated improved prediction under various scenarios common in healthcare cost modeling. Additionally, RF did not require prespecification of outcome distribution, nonlinearity effect, or interaction terms. Therefore, RF appears to be the best tool to predict average cost. However, when the goal is to estimate extreme expenses, e.g., high cost episodes, the accuracy gained by RF versus its computational costs may need to be considered.
Integrating public preferences into national reimbursement decisions: a descriptive comparison of approaches in Belgium and New Zealand
Authors: Leopold Christine , Lu Christine Y. , Wagner Anita K.
Published: April 2020

Background

Public health care payer organizations face increasing pressures to make transparent and sustainable coverage decisions about ever more expensive prescription drugs, suggesting a need for public engagement in coverage decisions. However, little is known about countries’ approaches to integrating public preferences in existing funding decisions. The aim of this study was to describe how Belgium and New Zealand used deliberative processes to engage the public and to identify lessons learned from these countries’ approaches.

Methods

To describe two countries’ deliberative processes, we first reviewed key country policy documents and then conducted semi-structured interviews with five leaders of the processes from Belgium and New Zealand. We assessed each country’s rationales for and approaches to engaging the public in pharmaceutical coverage decisions and identified lessons learned. We used qualitative content analysis of the interviews to describe key themes and subthemes.

Results

In both countries, the national public payer organization initiated and led the process of integrating public preferences into national coverage decision making. Reimbursement criteria considered outdated and changing societal expectations prompted the change. Both countries chose a deliberative process of public engagement with a multi-year commitment of many stakeholders to develop new reimbursement processes. Both countries’ new reimbursement processes put a stronger emphasis on quality of life, the separation of individual versus societal perspectives, and the importance of final reimbursement decisions being taken in context rather than based largely on cost-effectiveness thresholds.

Conclusions

To face the growing financial pressure of sustainable funding of medicines, Belgium’s and New Zealand’s public payers have developed processes to engage the public in defining the reimbursement system’s priorities. Although these countries differ in context and geographic location, they came up with overlapping lessons learnt which include the need for 1) political commitment to initiate change, 2) broad involvement of all stakeholders, and 3) commitment of all to engage in a long-term process. To evaluate these changes, further research is required to understand how coverage decisions in systems with and without public engagement differ.
Dispensations of benzodiazepines, z-hypnotics, and gabapentinoids to patients receiving opioid agonist therapy; a prospective cohort study in Norway from 2013 to 2017
Authors: Vold Jørn Henrik , Skurtveit Svetlana , Aas Christer , Chalabianloo Fatemeh , Kloster Pia Synnøve , Johansson Kjell Arne , Fadnes Lars Thore
Published: April 2020

Background

Dispensations of benzodiazepines, z-hypnotics, and gabapentinoids to patients on opioid agonist therapy (OAT) are common and have pros and cons. The objectives of the current study are to define the dispensation rates of these potentially addictive drugs, and whether the number and the mean daily doses of dispensed OAT opioids and discontinuing OAT, are associated with being dispensed benzodiazepines, z-hypnotics and gabapentinoids among patients on OAT in Norway in the period 2013 to 2017.

Methods

Information about all dispensed opioids, benzodiazepines, z-hypnotics and gabapentinoids were recorded from the Norwegian Prescription Database (NorPD). A total of 10,371 OAT patients were included in the study period. The dispensation rates were defined as the number of patients who were dispensed at least one of the potentially addictive drugs divided among the number of patients who have dispensed an OAT opioid per calendar year. Mean daily doses were calculated, and for benzodiazepines and z-hypnotics, stated in diazepam equivalents. The association between dispensed potentially addictive drugs, and the number and the type of dispensed OAT opioids were calculated by using logistic regression models.

Results

Half of the OAT patients received at least one dispensation of a benzodiazepine or z-hypnotic, and 11% were dispensed at least a gabapentinoid in 2017. For dispensed benzodiazepines or z-hypnotics, the mean daily dose was reduced from 21 mg (95% confidence interval (CI): 20–23) diazepam equivalents in 2013 to 17 mg (95% CI: 16–17) in 2017. The mean daily dose of pregabalin increased from 365 mg (95% CI: 309–421) in 2013 to 386 mg (95% CI: 349–423) in 2017. Being dispensed a gabapentinoid (adjusted odds ratio (aOR) = 2.5, 95% CI: 2.1–3.0) or a non-OAT opioid (aOR = 3.0, 95% CI: 2.6–3.5) was associated with being dispensed a benzodiazepine or z-hypnotic. Discontinuing OAT did not affect the number of dispensations and the doses of potentially addictive drugs.

Conclusion

The dispensation rates of potentially addictive drugs are high in the OAT population. Treatment indications, as well as requirements for prescription authority, need to be debated and made explicit. Randomized controlled trials evaluating the benefits and risks of such co-prescription are required.
Understanding hand hygiene behaviour in the intensive care unit to inform interventions: an interview study
Authors: Lambe Kathryn , Lydon Sinéad , Madden Caoimhe , McSharry Jenny , Marshall Rebecca , Boylan Ruth , Hehir Aoife , Byrne Molly , Tujjar Omar , O’Connor Paul
Published: April 2020

Background

Improving hand hygiene (HH) compliance is one of the most important, but elusive, goals of infection control. The purpose of this study was to use the capability (C), opportunity (O), motivation (M), and behaviour (B; COM-B) model and the theoretical domains framework (TDF) to gain an understanding of the barriers and enablers of HH behaviours in an intensive care unit (ICU) in order to identify specific interventions to improve HH compliance.

Methods

A semi-structured interview schedule was developed based upon the COM-B model. This schedule was used to interview a total of 26 ICU staff: 12 ICU nurses, 11 anaesthetic specialist registrars, and three anaesthetic senior house officers.

Results

Participants were confident in their capabilities to carry out appropriate HH behaviours. The vast majority of participants reported having the necessary knowledge and skills, and believed they were capable of carrying out appropriate HH behaviours. Social influence was regarded as being important in encouraging HH compliance by the interviewees- particularly by nurses. The participants were motivated to carry out HH behaviours, and it was recognised that HH was an important part of their job and is important in preventing infection. It is recommended that staff are provided with targeted HH training, in which individuals receive direct and individualised feedback on actual performance and are provided guidance on how to address deficiencies in HH compliance at the bedside at the time at which the HH behaviour is performed. Modelling of appropriate HH behaviours by senior leaders is also suggested, particularly by senior doctors. Finally, appropriate levels of staffing are a factor that must be considered if HH compliance is to be improved.

Conclusions

This study has demonstrated that short interviews with ICU staff, founded on appropriate behavioural change frameworks, can provide an understanding of HH behaviour. This understanding can then be applied to design interventions appropriately tailored to the needs of a specific unit, which will have an increased likelihood of improving HH compliance.
Perilesional photobiomodulation therapy and physical rehabilitation in post-operative recovery of dogs surgically treated for thoracolumbar disk extrusion
Authors: Bruno Enrico , Canal Sara , Antonucci Michela , Bernardini Marco , Balducci Federica , Musella Vincenzo , Mussoni Matteo , Spinella Giuseppe
Published: April 2020

Background

Recent studies have reported contrasting results of the effects of laser therapy on post-operative intervertebral disk herniation, with a lack of evidence-based advantages of this modality within a rehabilitation protocol.

The aim of this study was to report the clinical effects of photobiomodulation therapy within a post-operative rehabilitation protocol in dogs submitted to surgery for thoracolumbar disk extrusion. Twenty-four dogs were included in the study (12 dogs treated with laser therapy and rehabilitation protocol and 12 dogs treated with same rehabilitation protocol but without laser therapy).

Results

All dogs treated with laser therapy showed improved neurological status (Modified Frankel Score more than 3 within 30 days of physiotherapy starting) if deep nociception on admission was maintained (P = 0.04). However, Kaplan-Meier analysis did not show any statistical difference in time to regain ambulatory ability, although there was a tendency for a shorter mean time of 14.2 ± 8.55 days in the laser group versus 24 ± 18.49 days in the no laser group.

Conclusions

The use of laser therapy in the post-operative rehabilitation of dogs affected by intervertebral disc extrusion and submitted to surgery for spinal decompression could help improve their neurological status.
CRISPR/Cas9-deaminase enables robust base editing in Rhodobacter sphaeroides 2.4.1
Authors: Luo Yufeng , Ge Mei , Wang Bolun , Sun Changhong , Wang Junyi , Dong Yuyang , Xi Jianzhong Jeff
Published: April 2020

Background

CRISPR/Cas9 systems have been repurposed as canonical genome editing tools in a variety of species, but no application for the model strain Rhodobacter sphaeroides 2.4.1 was unveiled.

Results

Here we showed two kinds of programmable base editing systems, cytosine base editors (CBEs) and adenine base editors (ABEs), generated by fusing endonuclease Cas9 variant to cytosine deaminase PmCDA1 or heterodimer adenine deaminase TadA–TadA*, respectively. Using CBEs, we were able to obtain C-to-T mutation of single and double targets following the first induction step, with the efficiency of up to 97% and 43%; while the second induction step was needed in the case of triple target, with the screening rate of 47%. Using ABEs, we were only able to gain A-to-G mutation of single target after the second induction step, with the screening rate of 30%. Additionally, we performed a knockout analysis to identify the genes responsible for coenzyme Q10 biosynthesis and found that ubiF, ubiA, ubiG, and ubiX to be the most crucial ones.

Conclusions

Together, CBEs and ABEs serve as alternative methods for genetic manipulation in Rhodobacter sphaeroides and will shed light on the fundamental research of other bacteria that are hard to be directly edited by Cas9-sgRNA.
Engineered butyrate-producing bacteria prevents high fat diet-induced obesity in mice
Authors: Bai Liang , Gao Mengxue , Cheng Xiaoming , Kang Guangbo , Cao Xiaocang , Huang He
Published: April 2020

Background

Obesity is a major problem worldwide and severely affects public safety. As a metabolite of gut microbiota, endogenous butyric acid participates in energy and material metabolism. Considering the serious side effects and weight regain associated with existing weight loss interventions, novel strategies are urgently needed for prevention and treatment of obesity.

Results

In the present study, we engineered Bacillus subtilis SCK6 to exhibited enhanced butyric acid production. Compared to the original Bacillus subtilis SCK6 strain, the genetically modified BsS-RS06550 strain had higher butyric acid production. The mice were randomly divided into four groups: a normal diet (C) group, a high-fat diet (HFD) group, an HFD + Bacillus subtilis SCK6 (HS) group and an HFD + BsS-RS06550 (HE) group. The results showed BsS-RS06550 decreased the body weight, body weight gain, and food intake of HFD mice. BsS-RS06550 had beneficial effects on blood glucose, insulin resistance and hepatic biochemistry. After the 14-week of experiment, fecal samples were collected for nontargeted liquid chromatography-mass spectrometry analysis to identify and quantify significant changes in metabolites. Sixteen potentially significant metabolites were screened, and BsS-RS06550 was shown to potentially regulate disorders in glutathione, methionine, tyrosine, phenylalanine, and purine metabolism and secondary bile acid biosynthesis.

Conclusions

In this study, we successfully engineered Bacillus subtilis SCK6 to have enhanced butyric acid production. The results of this work revealed that the genetically modified live bacterium BsS-RS06550 showed potential anti-obesity effects, which may have been related to regulating the levels of metabolites associated with obesity. These results indicate that the use of BsS-RS06550 may be a promising strategy to attenuate obesity.
Engineering of sugar transporters for improvement of xylose utilization during high-temperature alcoholic fermentation in Ogataea polymorpha yeast
Authors: Vasylyshyn Roksolana , Kurylenko Olena , Ruchala Justyna , Shevchuk Nadiya , Kuliesiene Neringa , Khroustalyova Galina , Rapoport Alexander , Daugelavicius Rimantas , Dmytruk Kostyantyn , Sibirny Andriy
Published: April 2020

Background

Xylose transport is one of the bottlenecks in the conversion of lignocellulosic biomass to ethanol. Xylose consumption by the wild-type strains of xylose-utilizing yeasts occurs once glucose is depleted resulting in a long fermentation process and overall slow and incomplete conversion of sugars liberated from lignocellulosic hydrolysates. Therefore, the engineering of endogenous transporters for the facilitation of glucose-xylose co-consumption is an important prerequisite for efficient ethanol production from lignocellulosic hydrolysates.

Results

In this study, several engineering approaches formerly used for the low-affinity glucose transporters in Saccharomyces cerevisiae, were successfully applied for earlier identified transporter Hxt1 in Ogataea polymorpha to improve xylose consumption (engineering involved asparagine substitution to alanine at position 358 and replacement of N-terminal lysine residues predicted to be the target of ubiquitination for arginine residues). Moreover, the modified versions of S. cerevisiae Hxt7 and Gal2 transporters also led to improved xylose fermentation when expressed in O. polymorpha.

Conclusions

The O. polymorpha strains with modified Hxt1 were characterized by simultaneous utilization of both glucose and xylose, in contrast to the wild-type and parental strain with elevated ethanol production from xylose. When the engineered Hxt1 transporter was introduced into constructed earlier advanced ethanol producer form xylose, the resulting strain showed further increase in ethanol accumulation during xylose fermentation. The overexpression of heterologous S. cerevisiae Gal2 had a less profound positive effects on sugars uptake rate, while overexpression of Hxt7 revealed the least impact on sugars consumption.
Long noncoding RNA BSN-AS2 induced by E2F1 promotes spinal osteosarcoma progression by targeting miR-654-3p/SYTL2 axis
Authors: Zhou Xianwei , Li Jitian , Teng Junyan , Liu Yufeng , Zhang Di , Liu Linyun , Zhang Wenming
Published: April 2020

Spinal osteosarcoma (OS) is a rare and aggressive malignancy. Long noncoding RNA (lncRNA) BSN-AS2 has been shown to be an oncogenic gene in several cancers. However, the role and function of BSN-AS2 in spinal OS were unfamiliar. Our study identified that BSN-AS2 expression was boosted in spinal OS tissues and cell lines. Transcription factor E2F1 induced the upregulation of BSN-AS2 expression in spinal OS cells. Afterwards, loss-of-function assays indicated that BSN-AS2 depletion reduced cell proliferation, migration and invasion as well as promoted cell apoptosis in spinal OS. Thereafter, RIP, RNA pull down and luciferase reporter assays manifested BSN-AS2 could sponge miR-654-3p in spinal OS. After that, the binding effect of between miR-654-3p and SYTL2 was proved. Finally, rescue experiments illustrated that miR-654-3p inhibition or SYTL2 overexpression could counteract the inhibitory effect caused by BSN-AS2 deficiency on spinal OS progression. In conclusion, the availability of miR-654-3p was antagonized by E2F1-induced BSN-AS2 for SYTL2-meidated spinal OS progression.
Role of cancer stem cells in the development of giant cell tumor of bone
Authors: War Abdul Rouf , Dang Kai , Jiang Shanfen , Xiao Zhongwei , Miao Zhiping , Yang Tuanmin , Li Yu , Qian Airong
Published: April 2020

The primary bone tumor is usually observed in adolescence age group which has been shown to be part of nearly 20% of the sarcomas known today. Giant cell tumor of bone (GCTB) can be benign as well as malignant tumor which exhibits localized dynamism and is usually associated with the end point of a long bone. Giant cell tumor (GCT) involves mononuclear stromal cells which proliferate at a high rate, multinucleated giant cells and stromal cells are equally present in this type of tumor. Cancer stem cells (CSCs) have been confirmed to play a potential role in the development of GCT. Cancer stem cell-based microRNAs have been shown to contribute to a greater extent in giant cell tumor of bone. CSCs and microRNAs present in the tumors specifically are a great concern today which need in-depth knowledge as well as advanced techniques to treat the bone cancer effectively. In this review, we attempted to summarize the role played by cancer stem cells involving certain important molecules/factors such as; Mesenchymal Stem Cells (MSCs), miRNAs and signaling mechanism such as; mTOR/PI3K-AKT, towards the formation of giant cell tumor of bone, in order to get an insight regarding various effective strategies and research advancements to obtain adequate knowledge related to CSCs which may help to focus on highly effective treatment procedures for bone tumors.
Sickle cell disease and malaria: decreased exposure and asplenia can modulate the risk from Plasmodium falciparum
Authors: Mwaiswelo Richard O. , Mawala William , Iversen Per O. , de Montalembert Mariane , Luzzatto Lucio , Makani Julie
Published: April 2020

Background

Patients with sickle cell disease (SCD), an inherited haemoglobinopathy, have increased risk of malaria, at least in part due to impaired splenic function. Infection with Plasmodium falciparum in SCD patients can trigger painful vaso-occlusive crisis, increase the severity of anaemia, and contribute to early childhood mortality.

Case presentation

A 17 year-old Tanzanian male with known SCD was admitted to Muhimbili National Hospital, a tertiary referral centre in Dar-es-Salaam, following an attack of malaria. From 2004 to 2007 the patient had lived in USA, and from 2010 to 2016 in France where, on account of hypersplenism and episodes of splenic sequestrations, in 2014 the spleen was removed. After appropriate clinical and laboratory assessment the patient was re-started on hydroxyurea; and anti-malarial-prophylaxis with proguanil was instituted. The patient has remained well and malaria-free for the following 15 months.

Conclusion

SCD patients are highly vulnerable to malaria infection, and impaired splenic function is a feature of SCD patients, even in those who still anatomically have a spleen. This patient had a surgical splenectomy and, in addition, had probably lost some of the acquired malaria-immunity by having lived for several years in malaria-free areas. This patient is a compelling reminder that long-term anti-malarial prophylaxis should be offered to all patients with SCD who live in malaria-endemic areas.
To connect between worlds, to bridge over gaps: learning about the complex role of cultural mediators in perinatal health promotion from a case in Israel
Authors: Peres Hagit , Sharaby Rachel
Published: April 2020

Background

Reduction of health gaps between ethno-cultural groups has become a major concern for health services, with a strong emphasis on eliminating social and cultural barriers and improving accessibility for diverse populations.

Methods

The study is based on a Participatory Action Research where an involved researcher accompanied the project for a decade, as well as on eleven in-depth interviews with Bedouin women-mediators working in a perinatal health promotion project in Israel.

Results

The research analyzes the work of Bedouin women health mediators who mediate between their Bedouin community and institutional health services and bridge over cultural gaps. The study presents the complex task of transferring messages across cultures, dealing with socio-cultural imperatives and the intricacy of multilayered power relations. The findings reveal an evolving process, beginning with a pragmatic mediation model in which the mediators are limited to instruction of pre-defined health materials, toward a transformative model of creating a ground for encouraging the mediators to act creatively according to socio-cultural circumstances.

Conclusion

The research elaborates on the adoption and implementation of the transformative approach in mediation and provides further understanding of the complexity of mediation role in sensitive issues such as pregnancy, birth and infant care.
Occupational exposure to ionizing radiation and risk of lymphoma subtypes: results of the Epilymph European case-control study
Authors: Satta Giannina , Loi Matteo , Becker Nickolaus , Benavente Yolanda , De Sanjose Silvia , Foretova Lenka , Staines Anthony , Maynadie Marc , Nieters Alexandra , Meloni Federico , Pilia Ilaria , Campagna Marcello , Pau Marco , Zablotska Lydia B. , Cocco Pierluigi
Published: April 2020

Background

Evidence linking risk of lymphoma and B-cell lymphoma subtypes to ionizing radiation is inconclusive, particularly at low exposure levels.

Methods

We investigated risk of lymphoma (all subtypes), B-cell lymphomas, and its major subtypes, associated with low-level occupational exposure to ionizing radiation, in 2346 lymphoma cases and 2463 controls, who participated in the multicenter EpiLymph case-control study. We developed a job-exposure matrix to estimate exposure to ionizing radiation, distinguishing between internal and external radiation, and we applied it to the lifetime occupational history of study subjects, We calculated the Odds Ratio (OR) and its 95% confidence interval (95% CI) for lymphoma (all subtypes combined), B-cell lymphoma, and its major subtypes using unconditional, polytomous logistic regression adjusting for age, gender, and education.

Results

We did not observe an association between exposure metrics of external and internal radiation and risk of lymphoma (all subtypes), nor with B-cell lymphoma, or its major subtypes, at the levels regularly experienced in occupational settings. An elevated risk of diffuse large B cell lymphoma was observed among the most likely exposed study subjects with relatively higher exposure intensity, which would be worth further investigation.

Conclusions

Further investigation is warranted on risk of B cell lymphoma subtypes associated with low-level occupational exposure to external ionizing radiation, and to clarify whether lymphoma should be included among the cancer outcomes related to ionizing radiation.
Left atrial reservoir strain combined with E/E' as a better single measure to predict elevated LV filling pressures in patients with coronary artery disease
Authors: Lin Jingru , Ma Hong , Gao Lijian , Wang Yang , Wang Jiangtao , Zhu Zhenhui , Pang Kunjing , Wang Hao , Wu Weichun
Published: April 2020

Background

The 2016 guidelines for left ventricular diastolic dysfunction diagnosis has been simplified from previous versions; however, multiparametric diagnosis approach still exists indeterminate left ventricular diastolic dysfunction category. Left atrial (LA) strain was recently found useful to predict elevated left ventricular (LV) filling pressures noninvasively. This study aimed to (1) analyze the diagnostic value of LA strain for noninvasive assessment of LV filling pressures in patients with stable coronary artery disease (CAD) with preserved LV ejection fraction (LVEF), using invasive hemodynamic assessment as the gold standard, and (2) explore whether LA strain combined with conventional diastolic parameters could detect elevated LV filling pressures alone.

Methods

Sixty-four patients with stable CAD having LVEF > 50% and 30 healthy controls were enrolled. Two-dimensional speckle-tracking echocardiography was used to measure LA strain during the reservoir (LASr), conduit, and contraction phases. LV end-diastolic pressure (LVEDP), as a surrogate for LV filling pressures, was invasively obtained by left heart catheterization. Logistic regression was used to calculate the odds ratio to predict LV filling pressures. Pearson’s correlation was used to analyze associations between echocardiographic parameters and LVEDP. The area under the receiver-operating characteristic curve was calculated to determine the capability of the echocardiographic parameters to detect elevated LVEDP. Inter-technique agreement was analyzed by contingency tables and tested by kappa statistics.

Results

LASr and the ratio of early-diastolic transmitral flow velocity (E) to tissue Doppler early-diastolic septal mitral annular velocity (E/E′septal) significantly predicted elevated LV filling pressures. LASr was combined with E/E′septal to generate a novel parameter (LASr/E/E′septal). LASr/E/E′septal had the best predictive ability of elevated LV filling pressures. LVEDP was negatively correlated with LASr and LASr/E/E′septal but positively correlated with E/E′septal. The area under the receiver-operating characteristic curve of LASr/E/E′septal was higher than that of LASr alone (0.83 vs. 0.75), better than all conventional LV diastolic parameters. Inter-technique agreement analysis showed that LASr/E/E′septal had good agreement with the invasive LVEDP measurement, better than the 2016 guideline (kappa = 0.63 vs. 0.25).

Conclusions

LASr provided additive diagnostic value for the noninvasive assessment of LV filling pressures. LASr/E/E′septal had the potential to be a better single noninvasive index to predict elevated LV filling pressures in patients with stable CAD and preserved LVEF.
Quality of life impact of refractive correction (QIRC) results three years after SMILE and FS-LASIK
Authors: Han Tian , Xu Ye , Han Xiao , Shang Jianmin , Zeng Li , Zhou Xingtao
Published: April 2020

Background

This study aimed to compare long-term postoperative quality of life and satisfaction differences between SMILE and FS-LASIK for myopia correction.

Methods

This cross-sectional study enrolled patients under the age of 39 years, who chose to undergo SMILE or FS-LASIK surgery to both eyes 3 years previously. Patients completed a common vision test and Quality of Life Impact of Refractive Correction (QIRC) questionnaire, together with the surgical satisfaction, adverse symptoms subjective survey. Patients with preoperative corrected distance visual acuity and postoperative uncorrected distance visual acuity of 20/20 or greater were included. Propensity score matching (PSM) was used to match the preoperative and postoperative spherical equivalent, age, and designed optical zones of the left and right eyes between the two groups.

Results

Forty-nine patients were included in each group after PSM from 188 patients. No significant difference in the total QIRC score was found between the SMILE and FS-LASIK groups (45.89 ± 5.91 vs 45.09 ± 5.65, p = 0.492). There were no differences in surgical satisfaction between the groups (p = 0.178). Compared to the SMILE group, the FS-LASIK group had more glare (2.12 ± 2.25 vs 3.22 ± 2.54, p = 0.026) and severe dryness (1.80 ± 1.98 vs 2.79 ± 2.19, p = 0.021).

Conclusion

Postoperative quality of life is similar after SMILE or FS-LASIK. Dry eye symptoms and glare were milder in the SMILE group than in the FS-LASIK group.
Do state insurance mandates alter ICSI utilization?
Authors: Zagadailov Pavel , Seifer David B. , Shan He , Zarek Shvetha M. , Hsu Albert L.
Published: April 2020

Background

Assisted reproductive technology (ART) insurance mandates resulted in improved access to infertility treatments like intracytoplasmic sperm injection (ICSI). Our objective was to examine whether ART insurance mandates demonstrate an increased association with ICSI use.

Methods

In this retrospective cohort study, clinic-specific data for 2000–2016 from the Centers for Disease Control (CDC) were grouped by state and subgrouped by the presence and extent of ART state insurance mandates. Mandated (n = 8) and non-mandated (n = 22) states were compared for ICSI use and male factor (MF) infertility in fresh non-donor ART cycles with a transfer in women < 35 years. Clinical pregnancy (CPR), live birth (LBR) rates, preimplantation genetic testing (PGT), elective single-embryo transfer (eSET) and twin birth rates per clinic were evaluated utilizing Welch’s t-test. Pearson correlation was used to measure the strength of association between MF and ICSI; ICSI and CPR, and ICSI and LBR over time. Results were considered statistically significant at a p-value of < 0.05, with Bonferroni correction used for multiple comparisons.

Results

From 2000 to 2016, ICSI use per clinic increased in both mandated and non-mandated states. ICSI use per clinic in non-mandated states was significantly greater from 2011 to 2016 (p < 0.05, all years) than in mandated states. Clinics in mandated states had less MF (30.5 ± 15% vs 36.7 ± 15%; p < 0.001), lower CPR (39.8 ± 4% vs 43.4 ± 4%; p = 0.02) and lower LBR (33.9 ± 3.5% vs 37.9 ± 3.5%; p < 0.05). PGT rates were not significantly different. ICSI use in non-mandated states correlated with MF rates (r = 0.524, p = 0.03). A significant correlation between ICSI and CPR (r = 0.8, p < 0.001) and LBR (r = 0.7, p < 0.001) was noted in mandated states only. eSET rates were greater and twin rates were lower in mandated compared with non-mandated states.

Conclusions

There was greater use of ICSI per clinic in non-mandated states, which correlated with an increased frequency of MF. In mandated states, lower ICSI rates per clinic were accompanied by a positive correlation with CPR and LBR, as well as a trend for greater eSET rates and lower twin rates, suggesting that state mandates for ART coverage may encourage more selective utilization of laboratory resources.
Decreased brain and muscle ARNT-like protein 1 expression mediated the contribution of hyperandrogenism to insulin resistance in polycystic ovary syndrome
Authors: Zhai Junyu , Li Shang , Hu Min , Di Fangfang , Liu Jiansheng , Du Yanzhi
Published: April 2020

Background

The interface between environmental risk factors and genetic factors could contribute to the pathogenesis of hyperandrogenism and insulin resistance in polycystic ovary syndrome (PCOS); however, the underlying complex mechanism remains to be elucidated.

Methods

We used dehydroepiandrosterone (DHEA)-induced PCOS-like rat model to measure circadian clock genes and insulin resistance-related genes. Additionally, we performed in vitro experiments in mature adipocytes to verify the molecular mechanisms.

Results

DHEA-induced PCOS-like rats exhibited insulin resistance and arrhythmic expression of circadian clock genes in the liver and adipose tissues, particularly showing decreased brain and muscle ARNT-like protein 1 (BMAL1) expression. In addition, hyperandrogenism gave rise to negative regulation of BMAL1 expression to nicotinamide phosphoribosyltransferase and sirtuin 1, which further inhibited downstream glucose transporter type 4, leading to insulin resistance in mature adipocytes, which was consistent with our previous results in HepG2 cells.

Conclusions

Decreased BMAL1 expression in the liver and adipose played a potentially novel role in the contribution of hyperandrogenism to insulin resistance, which might be a possible mechanism accounting for the pathogenesis of PCOS.
The effectiveness and complexity of interventions targeting sedentary behaviour across the lifespan: a systematic review and meta-analysis
Authors: Blackburn Nicole E. , Wilson Jason J. , McMullan Ilona I. , Caserotti Paolo , Giné-Garriga Maria , Wirth Katharina , Coll-Planas Laura , Alias Sergi Blancafort , Roqué Marta , Deidda Manuela , Kunzmann Andrew T. , Dallmeier Dhayana , Tully Mark A.
Published: April 2020

Background

Evidence suggests that sedentary behaviour (SB) is associated with poor health outcomes. SB at any age may have significant consequences for health and well-being and interventions targeting SB are accumulating. Therefore, the need to review the effects of multicomponent, complex interventions that incorporate effective strategies to reduce SB are essential.

Methods

A systematic review and meta-analysis were conducted investigating the impact of interventions targeting SB across the lifespan. Six databases were searched and two review authors independently screened studies for eligibility, completed data extraction and assessed the risk of bias and complexity of each of the included studies.

Results

A total of 77 adult studies (n=62, RCTs) and 84 studies (n=62, RCTs) in children were included. The findings demonstrated that interventions in adults when compared to active controls resulted in non-significant reductions in SB, although when compared to inactive controls significant reductions were found in both the short (MD -56.86; 95%CI -74.10, -39.63; n=4632; I283%) and medium-to-long term (MD -20.14; 95%CI -34.13, -6.16; n=4537; I265%). The findings demonstrated that interventions in children when compared to active controls may lead to relevant reductions in daily sedentary time in the short-term (MD -59.90; 95%CI -102.16, -17.65; n=267; I286%), while interventions in children when compared to inactive controls may lead to relevant reductions in the short-term (MD -25.86; 95%CI -40.77, -10.96; n=9480; I298%) and medium-to-long term (MD -14.02; 95%CI -19.49, -8.55; n=41,138; I298%). The assessment of complexity suggested that interventions may need to be suitably complex to address the challenges of a complex behaviour such as SB, but demonstrated that a higher complexity score is not necessarily associated with better outcomes in terms of sustained long-term changes.

Conclusions

Interventions targeting reductions in SB have been shown to be successful, especially environmental interventions in both children and adults. More needs to be known about how best to optimise intervention effects. Future intervention studies should apply more rigorous methods to improve research quality, considering larger sample sizes, randomised controlled designs and valid and reliable measures of SB.
Discovery of novel L-type voltage-gated calcium channel blockers and application for the prevention of inflammation and angiogenesis
Authors: Saddala Madhu Sudhana , Lennikov Anton , Mukwaya Anthony , Yang Yan , Hill Michael A. , Lagali Neil , Huang Hu
Published: April 2020

Background

The ways in which microglia activate and promote neovascularization (NV) are not fully understood. Recent in vivo evidence supports the theory that calcium is required for the transition of microglia from a surveillance state to an active one. The objectives of this study were to discover novel L-type voltage-gated channel (L-VGCC) blockers and investigate their application for the prevention of inflammation and angiogenesis.

Methods

Pharmacophore-based computational modeling methods were used to screen for novel calcium channel blockers (CCBs) from the ZINC compound library. The effects of CCBs on calcium blockade, microglial pro-inflammatory activation, and cell toxicity were validated in BV-2 microglial cell and freshly isolated smooth muscle cell (SMC) cultures. Laser-induced choroidal neovascularization (NV) and the suture-induced inflammatory corneal NV models of angiogenesis were used for in vivo validation of the novel CCBs. CX3CR1gfp/+mice were used to examine the infiltration of GFP-labeled microglial cells.

Results

We identified three compounds from the ZINC database (Zinc20267861, Zinc18204217, and Zinc33254827) as new blockers of L-type voltage-gated calcium channels (L-VGCC) using a structure-based pharmacophore approach. The effects of the three CCBs on Ca2+influx into cells were verified in BV-2 microglial cells using Fura-2 fluorescent dye and in freshly isolated SMCs using the voltage-patch clamp. All three CCBs reduced microglial cell migration, activation stimulated by lipopolysaccharide (LPS), and reduced the expression of the inflammatory markers NF-κB (phospho-IκBα) and cyclooxygenase-2 (COX-2) as well as reactive oxygen species. Of the three compounds, we further examined the in vivo activity of Zinc20267861. Topical treatment with Zinc20267861 in a rat model of suture-induced inflammatory cornea neovascularization demonstrated efficacy of the compound in reducing monocyte infiltration and overall corneal NV response. Subconjunctival administration of the compound in the choroidal NV mouse model effectively prevented CNV and microglial infiltration.

Conclusions

Our findings suggest that the novel CCBs identified here are effective anti-inflammatory agents that can be further evaluated for treating NV disorders and can be potentially applied in the treatment of ocular inflammatory and pathological angiogenetic disorders.
Exploring the effects of deep brain stimulation and vision on tremor in Parkinson’s disease - benefits from objective methods
Authors: Fransson Per-Anders , Nilsson Maria H. , Niehorster Diederick C. , Nyström Marcus , Rehncrona Stig , Tjernström Fredrik , Magnusson Måns , Johansson Rolf , Patel Mitesh
Published: April 2020

Background

Tremor is a cardinal symptom of Parkinson’s disease (PD) that may cause severe disability. As such, objective methods to determine the exact characteristics of the tremor may improve the evaluation of therapy. This methodology study aims to validate the utility of two objective technical methods of recording Parkinsonian tremor and evaluate their ability to determine the effects of Deep Brain Stimulation (DBS) of the subthalamic nucleus and of vision.

Methods

We studied 10 patients with idiopathic PD, who were responsive toL-Dopa and had more than 1 year use of bilateral subthalamic nucleus stimulation. The patients did not have to display visible tremor to be included in the study. Tremor was recorded with two objective methods, a force platform and a 3 dimensional (3D) motion capture system that tracked movements in four key proximal sections of the body (knee, hip, shoulder and head). They were assessed after an overnight withdrawal of anti-PD medications with DBS ON and OFF and with eyes open and closed during unperturbed and perturbed stance with randomized calf vibration, using a randomized test order design.

Results

Tremor was detected with the Unified Parkinson’s Disease Rating Scale (UPDRS) in 6 of 10 patients but only distally (hands and feet) with DBS OFF. With the force platform and the 3D motion capture system, tremor was detected in 6 of 10 and 7 of 10 patients respectively, mostly in DBS OFF but also with DBS ON in some patients. The 3D motion capture system revealed that more than one body section was usually affected by tremor and that the tremor amplitude was non-uniform, but the frequency almost identical, across sites. DBS reduced tremor amplitude non-uniformly across the body. Visual input mostly reduced tremor amplitude with DBS ON.

Conclusions

Technical recording methods offer objective and sensitive detection of tremor that provide detailed characteristics such as peak amplitude, frequency and distribution pattern, and thus, provide information that can guide the optimization of treatments. Both methods detected the effects of DBS and visual input but the 3D motion system was more versatile in that it could detail the presence and properties of tremor at individual body sections.
Immediate and long-term effects of BCI-based rehabilitation of the upper extremity after stroke: a systematic review and meta-analysis
Authors: Bai Zhongfei , Fong Kenneth N. K. , Zhang Jack Jiaqi , Chan Josephine , Ting K. H.
Published: April 2020

Background

A substantial number of clinical studies have demonstrated the functional recovery induced by the use of brain-computer interface (BCI) technology in patients after stroke. The objective of this review is to evaluate the effect sizes of clinical studies investigating the use of BCIs in restoring upper extremity function after stroke and the potentiating effect of transcranial direct current stimulation (tDCS) on BCI training for motor recovery.

Methods

The databases (PubMed, Medline, EMBASE, CINAHL, CENTRAL, PsycINFO, and PEDro) were systematically searched for eligible single-group or clinical controlled studies regarding the effects of BCIs in hemiparetic upper extremity recovery after stroke. Single-group studies were qualitatively described, but only controlled-trial studies were included in the meta-analysis. The PEDro scale was used to assess the methodological quality of the controlled studies. A meta-analysis of upper extremity function was performed by pooling the standardized mean difference (SMD). Subgroup meta-analyses regarding the use of external devices in combination with the application of BCIs were also carried out. We summarized the neural mechanism of the use of BCIs on stroke.

Results

A total of 1015 records were screened. Eighteen single-group studies and 15 controlled studies were included. The studies showed that BCIs seem to be safe for patients with stroke. The single-group studies consistently showed a trend that suggested BCIs were effective in improving upper extremity function. The meta-analysis (of 12 studies) showed a medium effect size favoring BCIs for improving upper extremity function after intervention (SMD = 0.42; 95% CI = 0.18–0.66; I2 = 48%; P < 0.001; fixed-effects model), while the long-term effect (five studies) was not significant (SMD = 0.12; 95% CI = − 0.28 – 0.52; I2 = 0%; P = 0.540; fixed-effects model). A subgroup meta-analysis indicated that using functional electrical stimulation as the external device in BCI training was more effective than using other devices (P = 0.010). Using movement attempts as the trigger task in BCI training appears to be more effective than using motor imagery (P = 0.070). The use of tDCS (two studies) could not further facilitate the effects of BCI training to restore upper extremity motor function (SMD = − 0.30; 95% CI = − 0.96 – 0.36; I2 = 0%; P = 0.370; fixed-effects model).

Conclusion

The use of BCIs has significant immediate effects on the improvement of hemiparetic upper extremity function in patients after stroke, but the limited number of studies does not support its long-term effects. BCIs combined with functional electrical stimulation may be a better combination for functional recovery than other kinds of neural feedback. The mechanism for functional recovery may be attributed to the activation of the ipsilesional premotor and sensorimotor cortical network.