bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of US Adults Delaying Dental Care Due to the COVID-19 Pandemic
Authors: Kranz A.M. , Gahlon G. , Dick A.W. , Stein B.D.
Published: September 2020

Background:

Coronavirus disease 2019 (COVID-19) has disrupted the delivery of health care services, including dental care. The objective of this study was to quantify and describe US adults who delayed dental care due to the COVID-19 pandemic.

Methods:

We analyzed cross-sectional responses collected from a nationally representative and long-running panel survey of US adults conducted in late May and early June 2020 (response rate = 70%). The survey included questions about dental care delayed due to the COVID-19 pandemic, purpose of the delayed dental visits, timing of future dental visits, and demographic information. Pearson’s chi-square tests were used to determine if rates of delayed dental care varied by subgroup. A multivariable regression model, adjusted for age, race, Hispanic ethnicity, census division, and rurality, was estimated to predict the odds of reporting delayed dental care.

Results:

Nearly half of respondents (46.7%) reported delaying going to the dentist or receiving dental care due to the COVID-19 pandemic. Among adults who reported delaying dental care due to the pandemic, 74.7% reported delaying a checkup, 12.4% reported delaying care to address something that was bothering them, and 10.5% reported delaying care to get planned treatment. About 44.4% of adults reported that they planned to visit the dentist within the next 3 mo. In the multivariable regression model, only living in an urban (vs. rural) area was associated with significantly higher odds of delayed dental care due to the pandemic (odds ratio: 1.5; 95% confidence interval: 1.1, 2.1).

Conclusions:

Nearly half of US adults reported delaying dental care due to the COVID-19 pandemic during the spring of 2020. Our results offer insight into the experiences of patients seeking dental care this spring and the economic challenges faced by dental providers due to the pandemic.

Knowledge Transfer Statement:

This article describes US adults who delayed dental care due to the COVID-19 pandemic. Results can be used by clinicians and policymakers to understand delayed care during the pandemic.
Using deep learning to examine the correlation between transportation planning and perceived safety of the built environment
Authors: Hollander Justin B , Nikolaishvili Giorgi , Adu-Bredu Alphonsus A , Situ Minyu , Bista Shabnam
Published: September 2020

In this study, we attempt to estimate the effects of various transportation policies on the perceived safety of the built environment. We train a convolutional neural network on a dataset of safety perception scores for Google Street View images taken in Boston, MA . We then apply the trained neural network to a large set of Google Street View images of coordinates in Montreal and Toronto to generate their respective safety perception scores. We estimate probit, logit, and ordinary least squares regression models using our cross-sectional dataset consisting of safety perception scores, as well as transportation policy variables and a set of control variables, by regressing the safety perception scores on the remaining set of variables. We answer our research question by observing the direction, magnitude, and statistical significance of the coefficient estimates associated with the policy variables across all regression models. We studied and cataloged transportation policies planned for over the past 10 years in both cities. We found that those census tracts with the poorest safety scores were the same places where planners focused their transportation investments. The study makes an important contribution to transportation planning methodologies by drawing on the novel data source of Google Street View images, to understand the safety of an area.
The combination of inspiratory muscle training and high-flow nasal cannula oxygen therapy for promoting weaning outcomes in difficult-to-wean patients: protocol for a randomised controlled trial
Authors: Patsaki Irini , Christakou Anna , Papadopoulos Emmanouel , Katartzi Martha , Kouvarakos Alexandros , Siempos Ilias , Tsimouris Dimitris , Skoura Anastasia , Xatzimina Antonina , Malachias Sotirios , Koulouris Νikolaos , Grammatopoulou Eirini , Zakinthinos Spiros , Ischaki Eleni
Published: September 2020

Background

According to the literature, 20–30% of intubated patients are difficult to wean off mechanical ventilation and have a prolonged intensive care unit (ICU) stay with detrimental effects on muscle strength, functional ability and quality of life. Inspiratory muscle training (IMT)viaa threshold device has been proposed as an effective exercise for minimising the effects of mechanical ventilation on respiratory muscles of critically ill patients with prolonged weaning. In addition, high-flow nasal cannula (HFNC) oxygen has been proved to provide efficient support for both high- and low-risk patients after extubation, thus preventing re-intubation.

Material and methods

A randomised controlled trial was designed to assess the efficacy of combining IMT and HFNC as therapeutic strategies for patients with high risk for weaning failure. Once patients with prognostic factors of difficult weaning are awake, ventilated with support settings and cooperative, they will be randomised to one of the two following study groups: intervention group (IMT and HFNC) and control group (IMT and Venturi mask). IMT will start as soon as possible. Each allocated oxygen delivery device will be applied immediately after extubation. IMT intervention will continue until patients' discharge from ICU. The primary outcome is the rate of weaning failure. Secondary outcomes are maximal inspiratory and expiratory strength, endurance of respiratory muscles, global muscle strength, functional ability and quality of life along with duration of ventilation (days) and ICU and hospital length of stay.

Conclusion

The present study could significantly contribute to knowledge of how best to treat patients with difficult weaning and high risk of re-intubation.
Are symptoms of obstructive sleep apnoea related to good continuous positive airway pressure compliance?
Authors: Kaewkes Chaiwat , Sawanyawisuth Kittisak , Sawunyavisuth Bundit
Published: September 2020

Obstructive sleep apnoea (OSA) is a common disease that can be treated with continuous positive airway pressure (CPAP). CPAP tolerance may be associated with its compliance. Even though there are several predictors for good CPAP compliance, there are limited data available on the correlation between CPAP compliance and OSA symptoms. This study aimed to evaluate this correlation. We conducted a cross-sectional study and enrolled adult patients diagnosed with OSA through polysomnography who had experience using a CPAP machine. A self-report questionnaire was used to evaluate CPAP compliance and study variables. Predictors of CPAP compliance were analysed using stepwise multivariate logistic regression analysis. There were 68 patients with OSA who completed the questionnaire during the study period. Of those, 14 (20.59%) exhibited good CPAP compliance. Only fatigue as a symptom was an independent factor associated with good CPAP compliance, with an adjusted odds ratio of 5.380 (95% CI 1.274–22.719). In conclusion, fatigue was the only symptom associated with good CPAP compliance in patients with OSA.
Exposure assessment in hypersensitivity pneumonitis: a comprehensive review and proposed screening questionnaire
Authors: Petnak Tananchai , Moua Teng
Published: September 2020

Hypersensitivity pneumonitis is an immune-mediated inflammatory lung disease characterised by the inhalation of environmental antigens leading to acute and chronic lung injury. Along with suggestive clinical and radiological findings, history and timing of suspected antigen exposure are important elements for diagnostic confidence. Unfortunately, many diagnoses remain tentative and based on vague and imprecise environmental or material exposure histories. To date, there has not been a comprehensive report highlighting the frequency and type of environmental exposure that might lead to or support a more systematic approach to antigen identification. We performed a comprehensive literature review to identify and classify causative antigens and their associated environmental contexts or source materials, with emphasis on the extent of the supportive literature for each exposure type. Eligible publications were those that reported unique inciting antigens and their respective environments or contexts. A clinical questionnaire was then proposed based on this review to better support diagnosis of hypersensitivity pneumonitis when antigen testing or other clinical and radiological variables are inconclusive or incomplete.
Deficits in skilled motor and auditory learning in a rat model of Rett syndrome
Authors: Adcock Katherine S. , Blount Abigail E. , Morrison Robert A. , Alvarez-Dieppa Amanda , Kilgard Michael P. , Engineer Crystal T. , Hays Seth A.
Published: September 2020

Background

Rett syndrome is an X-linked neurodevelopmental disorder caused by a mutation in the gene MECP2. Individuals with Rett syndrome display developmental regression at an early age, and develop a range of motor, auditory, cognitive, and social impairments. Several studies have successfully modeled some aspects of dysfunction and Rett syndrome-like phenotypes in transgenic mouse and rat models bearing mutations in the MECP2 gene. Here, we sought to extend these findings and characterize skilled learning, a more complex behavior known to be altered in Rett syndrome.

Methods

We evaluated the acquisition and performance of auditory and motor function on two complex tasks in heterozygous female Mecp2 rats. Animals were trained to perform a speech discrimination task or a skilled forelimb reaching task.

Results

Our results reveal that Mecp2 rats display slower acquisition and reduced performance on an auditory discrimination task than wild-type (WT) littermates. Similarly, Mecp2 rats exhibit impaired learning rates and worse performance on a skilled forelimb motor task compared to WT.

Conclusions

Together, these findings illustrate novel deficits in skilled learning consistent with clinical manifestation of Rett syndrome and provide a framework for development of therapeutic strategies to improve these complex behaviors.
Single-cell transcriptome analysis of tumor and stromal compartments of pancreatic ductal adenocarcinoma primary tumors and metastatic lesions
Authors: Lin Wei , Noel Pawan , Borazanci Erkut H. , Lee Jeeyun , Amini Albert , Han In Woong , Heo Jin Seok , Jameson Gayle S. , Fraser Cory , Steinbach Margaux , Woo Yanghee , Fong Yuman , Cridebring Derek , Von Hoff Daniel D. , Park Joon Oh , Han Haiyong
Published: September 2020

Background

Solid tumors such as pancreatic ductal adenocarcinoma (PDAC) comprise not just tumor cells but also a microenvironment with which the tumor cells constantly interact. Detailed characterization of the cellular composition of the tumor microenvironment is critical to the understanding of the disease and treatment of the patient. Single-cell transcriptomics has been used to study the cellular composition of different solid tumor types including PDAC. However, almost all of those studies used primary tumor tissues.

Methods

In this study, we employed a single-cell RNA sequencing technology to profile the transcriptomes of individual cells from dissociated primary tumors or metastatic biopsies obtained from patients with PDAC. Unsupervised clustering analysis as well as a new supervised classification algorithm, SuperCT, was used to identify the different cell types within the tumor tissues. The expression signatures of the different cell types were then compared between primary tumors and metastatic biopsies. The expressions of the cell type-specific signature genes were also correlated with patient survival using public datasets.

Results

Our single-cell RNA sequencing analysis revealed distinct cell types in primary and metastatic PDAC tissues including tumor cells, endothelial cells, cancer-associated fibroblasts (CAFs), and immune cells. The cancer cells showed high inter-patient heterogeneity, whereas the stromal cells were more homogenous across patients. Immune infiltration varies significantly from patient to patient with majority of the immune cells being macrophages and exhausted lymphocytes. We found that the tumor cellular composition was an important factor in defining the PDAC subtypes. Furthermore, the expression levels of cell type-specific markers for EMT+ cancer cells, activated CAFs, and endothelial cells significantly associated with patient survival.

Conclusions

Taken together, our work identifies significant heterogeneity in cellular compositions of PDAC tumors and between primary tumors and metastatic lesions. Furthermore, the cellular composition was an important factor in defining PDAC subtypes and significantly correlated with patient outcome. These findings provide valuable insights on the PDAC microenvironment and could potentially inform the management of PDAC patients.
Mitochondrial DNA copy number can influence mortality and cardiovascular disease via methylation of nuclear DNA CpGs
Authors: Castellani Christina A. , Longchamps Ryan J. , Sumpter Jason A. , Newcomb Charles E. , Lane John A. , Grove Megan L. , Bressler Jan , Brody Jennifer A. , Floyd James S. , Bartz Traci M. , Taylor Kent D. , Wang Penglong , Tin Adrienne , Coresh Josef , Pankow James S. , Fornage Myriam , Guallar Eliseo , O’Rourke Brian , Pankratz Nathan , Liu Chunyu , Levy Daniel , Sotoodehnia Nona , Boerwinkle Eric , Arking Dan E.
Published: September 2020

Background

Mitochondrial DNA copy number (mtDNA-CN) has been associated with a variety of aging-related diseases, including all-cause mortality. However, the mechanism by which mtDNA-CN influences disease is not currently understood. One such mechanism may be through regulation of nuclear gene expression via the modification of nuclear DNA (nDNA) methylation.

Methods

To investigate this hypothesis, we assessed the relationship between mtDNA-CN and nDNA methylation in 2507 African American (AA) and European American (EA) participants from the Atherosclerosis Risk in Communities (ARIC) study. To validate our findings, we assayed an additional 2528 participants from the Cardiovascular Health Study (CHS) (N = 533) and Framingham Heart Study (FHS) (N = 1995). We further assessed the effect of experimental modification of mtDNA-CN through knockout ofTFAM, a regulator of mtDNA replication, via CRISPR-Cas9.

Results

Thirty-four independent CpGs were associated with mtDNA-CN at genome-wide significance (P < 5 × 10− 8). Meta-analysis across all cohorts identified six mtDNA-CN-associated CpGs at genome-wide significance (P < 5 × 10− 8). Additionally, over half of these CpGs were associated with phenotypes known to be associated with mtDNA-CN, including coronary heart disease, cardiovascular disease, and mortality. Experimental modification of mtDNA-CN demonstrated that modulation of mtDNA-CN results in changes in nDNA methylation and gene expression of specific CpGs and nearby transcripts. Strikingly, the “neuroactive ligand receptor interaction” KEGG pathway was found to be highly overrepresented in the ARIC cohort (P = 5.24 × 10− 12), as well as theTFAMknockout methylation (P = 4.41 × 10− 4) and expression (P = 4.30 × 10− 4) studies.

Conclusions

These results demonstrate that changes in mtDNA-CN influence nDNA methylation at specific loci and result in differential expression of specific genes that may impact human health and disease via altered cell signaling.
Accelerated long-term forgetting in healthy older adults predicts cognitive decline over 1 year
Authors: Wearn Alfie R. , Saunders-Jennings Esther , Nurdal Volkan , Hadley Emma , Knight Michael J. , Newson Margaret , Kauppinen Risto A. , Coulthard Elizabeth J.
Published: September 2020

Background

Here, we address a pivotal factor in Alzheimer’s prevention—identifying those at risk early, when dementia can still be avoided. Recent research highlights an accelerated forgetting phenotype as a risk factor for Alzheimer’s disease. We hypothesized that delayed recall over 4 weeks would predict cognitive decline over 1 year better than 30-min delayed recall, the current gold standard for detecting episodic memory problems which could be an early clinical manifestation of incipient Alzheimer’s disease. We also expected hippocampal subfield volumes to improve predictive accuracy.

Methods

Forty-six cognitively healthy older people (mean age 70.7 ± 7.97, 21/46 female), recruited from databases such as Join Dementia Research, or a local database of volunteers, performed 3 memory tasks on which delayed recall was tested after 30 min and 4 weeks, as well as Addenbrooke’s Cognitive Examination III (ACE-III) and CANTAB Paired Associates Learning. Medial temporal lobe subregion volumes were automatically measured using high-resolution 3T MRI. The ACE-III was repeated after 12 months to assess the change in cognitive ability. We used univariate linear regressions and ROC curves to assess the ability of tests of delayed recall to predict cognitive decline on ACE-III over the 12 months.

Results

Fifteen of the 46 participants declined over the year (≥ 3 points lost on ACE-III). Four-week verbal memory predicted cognitive decline in healthy older people better than clinical gold standard memory tests and hippocampal MRI. The best single-test predictor of cognitive decline was the 4-week delayed recall on the world list (R2 = .123, p = .018, β = .418). Combined with hippocampal subfield volumetry, 4-week verbal recall identifies those at risk of cognitive decline with 93% sensitivity and 86% specificity (AUC = .918, p < .0001).

Conclusions

We show that a test of accelerated long-term forgetting over 4 weeks can predict cognitive decline in healthy older people where traditional tests of delayed recall cannot. Accelerated long-term forgetting is a sensitive, easy-to-test predictor of cognitive decline in healthy older people. Used alone or with hippocampal MRI, accelerated forgetting probes functionally relevant Alzheimer’s-related change. Accelerated forgetting will identify early-stage impairment, helping to target more invasive and expensive molecular biomarker testing.
Production of probiotic Mozzarella cheese by incorporating locally isolated Lactobacillus acidophilus
Authors: Mukhtar Hamid , Yaqub Saima , Haq Ikram ul
Published: September 2020

Purpose

The present study was conducted to isolate and screen the potential probiotic strains for incorporation in Mozzarella cheese.

Methods

Probiotic cultures were isolated from different randomly purchased yogurt samples and were identified as Lactobacillus sp., Bifidobacteria sp., and Pediococcus sp. after morphological and biochemical characterization. Heat tolerance of isolates was tested at 55 °C and 65 °C to determine the survival of isolates in conditions similar to commercial cheese production. Lactobacillus acidophilus (S2) showed remarkable heat tolerance among all strains and was therefore selected to assess the probiotic potential. It showed good survival at acidic pH values (2–3). Moreover, it also showed > 50% tolerance to bile salt and was resistant to antibiotics, chloramphenicol, tetracycline, gentamycin, and vancomycin and also exhibited anti-microbial activity against Salmonella typhimurium, Escherichia coli, and Staphylococcus aureus. Thus, heat-tolerant Lactobacillus acidophilus (S2) isolate was an ideal strain for incorporation in Mozzarella cheese as probiotics. Three types of cheeses viz., cheese A with free cells of Lactobacillus acidophilus (S2), cheese B with encapsulated cells of Lactobacillus acidophilus (S2), and control cheese having no probiotics, were made.

Result

Microbiological analysis of prepared cheese revealed lesser loss of Lactobacillus acidophilus (S2) from encapsulated form (3.41 × 108 CFU/mL) compared to free cells of Lactobacillus acidophilus (S2) (1.10 × 107 CFU/mL). Coliforms were observed in control cheese after 10 days of storage, whereas no coliforms were observed in cheese A and cheese B even after 15 days of storage. Organoleptic properties of cheese A and cheese B were almost the same with an acceptability score of 2.7 ± 0.1 and 2.65 ± 0.1, respectively. Control cheese got the lowest scores after 15 days of storage.

Conclusion

The addition of probiotics in cheese not only prolongs the shelf-life of cheese but also increases the organoleptic properties of the cheese, making cheese a good delivery system for probiotics.
Early experiences of radiographers in Ireland during the COVID-19 crisis
Authors: Foley Shane J. , O’Loughlin Anne , Creedon Jill
Published: September 2020

Background

Imaging is crucial for assessing the severity and progression of COVID-19. Radiographers are amongst the first-line health professionals that may be exposed to infected persons. This work describes the early experience of radiographers in Ireland to the impact of COVID-19 using two electronic surveys distributed 6 weeks apart. Results were analysed using descriptive statistics and thematic analysis.

Results

A total of 370 responded to the first survey and 276 the second, with all six Irish health regions represented. Three quarters of radiographers (77%) reported having adequate personal protective equipment (PPE) available to them. However, almost half of the radiographers were inadvertently exposed to COVID-19-positive patients without appropriate PPE, largely attributed to poor communication and testing. Anxiety levels while initially high, reduced substantially 6 weeks into the crisis period. However, obvious distress was noted amongst some respondents. Forty percent of radiographers reported burnout symptoms due to the COVID-19 crisis and 30% reported considering changing jobs or retiring since the COVID-19 outbreak.

Conclusion

Clear communication regarding changing protocols and importantly patients’ infectious status are essential to safeguard healthcare workers and to minimise unnecessary anxiety and distress. Attention is required to staff mental health including the identification of burnout symptoms to prevent long-term negative consequences of the pandemic on radiography services.
Time-dependent LPS exposure commands MSC immunoplasticity through TLR4 activation leading to opposite therapeutic outcome in EAE
Authors: Kurte Mónica , Vega-Letter Ana María , Luz-Crawford Patricia , Djouad Farida , Noël Danièle , Khoury Maroun , Carrión Flavio
Published: September 2020

Background

Mesenchymal stem cells (MSCs) have been recognized for their regenerative and anti-inflammatory capacity which makes them very attractive to cell therapy, especially those ones to treat inflammatory and autoimmune disease. Two different immune-phenotypes have been described for MSCs depending on which Toll-like receptor (TLR) is activated. MSC1 is endowed with a pro-inflammatory phenotype following TLR4 activation with LPS. On the other hand, anti-inflammatory MSC2 is induced by the activation of TLR3 with Poly(I:C). High immunoplasticity of MSCs is a matter of concern in cell-based therapies. In this study, we investigated whether a single stimulus can induce both types of MSCs through a differential activation of TLR4 with LPS.

Methods

MSCs were activated with LPS following a short exposure of 1-h (MSCs-LPS1h) or long-time exposure for 48 h (MSCs-LPS48h), and then, we evaluated the biological response in vitro, the immunosuppressive capacity of MSCs in vitro, and the therapeutic potential of MSCs in an experimental autoimmune encephalomyelitis (EAE) mouse model.

Results

Our results showed that 1-h LPS exposure induced a MSC1 phenotype. Indeed, MSCs-LPS1h expressed low levels of NO/iNOS and decreased immunosuppressive capacity in vitro without therapeutic effect in the EAE model. In contrast, MSCs-LPS48h achieved a MSC2-like phenotype with significant increase in the immunosuppressive capacity on T cell proliferation in vitro, together with an improved in the therapeutic effect and higher Treg, compared to unstimulated MSCs. Furthermore, we determine through the MSCs-TLR4KO that the expression of TLR4 receptor is essential for MSCs’ suppressive activity since TLR4 deletion was associated with a diminished suppressive effect in vitro and a loss of therapeutic effect in vivo.

Conclusions

We demonstrate that MSCs display a high immunoplasticity commanded by a single stimulus, where LPS exposure time regulated the MSC suppressive effect leading into either an enhanced or an impairment therapeutic activity. Our results underscore the importance of phenotype conversion probably related to the TLR4 expression and activation, in the design of future clinical protocols to treat patients with inflammatory and autoimmune diseases.
Molecular characterization of a Trichinella spiralis serine proteinase
Authors: Yue Xin , Sun Xiang Yuan , Liu Fang , Hu Chen Xi , Bai Ying , Da Yang Qi , Liu Ruo Dan , Zhang Xi , Cui Jing , Wang Zhong Quan
Published: September 2020

The aim of this study was to investigate the biological characteristics and functions of a Trichinella spiralis serine proteinase (TsSerp) during larval invasion and development in the host. The full-length TsSerp cDNA sequence was cloned and expressed in Escherichia coli BL21. The results of RT-PCR, IFA and western blotting analyses showed that TsSerp was a secretory protein that was highly expressed at the T. spiralis intestinal infective larva and muscle larva stages and primarily located at the cuticle, stichosome and intrauterine embryos of the parasite. rTsSerp promoted the larval invasion of intestinal epithelial cells (IECs) and the enteric mucosa, whereas an anti-rTsSerp antibody impeded larval invasion; the promotion and obstruction roles were dose-dependently related to rTsSerp and the anti-rTsSerp antibodies, respectively. Vaccination of mice with rTsSerp elicited a remarkable humoral immune response (high levels of serum IgG, IgG1/IgG2a, IgE and IgM), and it also triggered both systemic (spleen) and local intestinal mucosal mesenteric lymph node (MLN) cellular immune responses, as demonstrated by a significant elevation in Th1 cytokines (IFN-γ) and Th2 cytokines (IL-4) after the spleen and MLN cells from vaccinated mice were stimulated with rTsSerp. Anti-TsSerp antibodies participated in the killing and destruction of newborn larvae via ADCC. The mice vaccinated with rTsSerp exhibited a 48.7% reduction in intestinal adult worms and a 52.5% reduction in muscle larvae. These results indicated that TsSerp participates in T. spiralis invasion and development in the host and might be considered a potential candidate target antigen to develop oral polyvalent preventive vaccines against Trichinella infection.
Association of working conditions including digital technology use and systemic inflammation among employees: study protocol for a systematic review
Authors: Kaltenegger Helena C. , Becker Linda , Rohleder Nicolas , Nowak Dennis , Weigl Matthias
Published: September 2020

Background

With the dynamic advancement of digitalization, working environments are changing and risk for employee stress may be increasing. Work stress has been associated with a dysregulation of inflammatory processes as a component of immune function. Systemic low-grade inflammation is discussed as a key player in the relation between stress exposure and chronic illness, such as cardiovascular diseases. The objective of this investigation will be to evaluate the association of working conditions including digital technology use and systemic inflammation among employees.

Methods

We designed and registered a study protocol for a systematic review of randomized controlled trials and prospective non-randomized studies (e.g., cohort, interrupted time series, or before-after studies). We will include studies conducted among adult workers reporting associations of working conditions and inflammatory activity. The outcome will be biomarkers of systemic low-grade inflammation on cell, plasma molecule and intracellular level, such as C-reactive protein, or different types of leukocytes, cytokines, etc. Literature searches will be conducted in several electronic databases (from January 1982 onwards), including PubMed/MEDLINE, Embase, PsycINFO, Web of Science, and CENTRAL. Two reviewers will independently screen all retrieved records, full-text articles, and extract data. The study methodological quality (or bias) will be appraised using appropriate tools. Our results will be described qualitatively. Random effects meta-analysis will be conducted, if feasible and appropriate. Additional analyses will be performed to explore potential sources of heterogeneity.

Discussion

This systematic review and meta-analysis will provide a synthesis of studies evaluating the association of working conditions and systemic inflammation. We anticipate our findings to identify knowledge gaps in the literature that future research should address. Moreover, results of our review may provide implications for corporate and public policy action for employee health promotion and prevention of occupational stress.

Systematic review registration

PROSPERO ID:CRD42020166887
Hopf bifurcation in a diffusive predator–prey model with Smith growth rate and herd behavior
Authors: Jiang Heping , Fang Huiping , Wu Yongfeng
Published: September 2020

This paper mainly aims to consider the dynamical behaviors of a diffusive delayed predator–prey system with Smith growth and herd behavior subject to the homogeneous Neumann boundary condition. For the analysis of the predator–prey model, we have studied the existence of Hopf bifurcation by analyzing the distribution of the roots of associated characteristic equation. Then we have proved the stability of the periodic solution by calculating the normal form on the center of manifold which is associated to the Hopf bifurcation points. Some numerical simulations are also carried out in order to validate our analysis findings. The implications of our analytical and numerical findings are discussed critically.
Stability and solvability for a class of optimal control problems described by non-instantaneous impulsive differential equations
Authors: Chen Yi , Meng Kaixuan
Published: September 2020

In this paper, we investigate the existence and stability of solutions for a class of optimal control problems with 1-mean equicontinuous controls, and the corresponding state equation is described by non-instantaneous impulsive differential equations. The existence theorem is obtained by the method of minimizing sequence, and the stability results are established by using the related conclusions of set-valued mappings in a suitable metric space. An example with the measurable admissible control set, in which the controls are not continuous, is given in the end.
Assessing farmers' contribution to greenhouse gas emission and the impact of adopting climate-smart agriculture on mitigation
Authors: Israel Michael Ayeah , Amikuzuno Joseph , Danso-Abbeam Gideon
Published: September 2020

Background

The adoption of climate-smart agricultural (CSA) practices is expected to improve farmers’ adaptation to climate change and also increase yields while simultaneously curbing greenhouse gas (GHG) emissions. This paper explores the determinants of smallholder farmers’ participation in GHG-emitting activities. It also estimates the impact of CSA activities on reducing GHG emissions.

Methods

The findings are based on survey data obtained from 350 smallholder farmers in the East Gonja district of Northern Ghana. We adopted the generalized Poisson regression model in identifying factors influencing farmers’ participation in the GHG emission practices and inverse-probability-weighted regression adjustment (IPWRA) to estimate the impact of CSA adoption on GHG emissions.

Results

Most farming households engaged in at least one emission activity. The findings of the generalized Poisson model found that wealthier households, higher education, and households with access to extension services were less likely to participate in GHG emission activities. There was also evidence that CSA adoption significantly reduces GHG emissions.

Conclusion

Advocacy in CSA adoption could be a necessary condition for environmental protection through the reduction of GHG emissions.
Effectiveness of two-stage horizontal subsurface flow constructed wetland planted with Cyperus alternifolius and Typha latifolia in treating anaerobic reactor brewery effluent at different hydraulic residence times
Authors: Alayu Ermias , Leta Seyoum
Published: September 2020

Background

Agro-industrial wastewaters in Ethiopia cause severe environmental pollution problems. Research evidence showed that anaerobic reactors are good options for the treatment of these wastewaters. But, their final effluent does not meet the discharge standards. Conversely, a series stage horizontal subsurface flow constructed wetland (HSSFCW) system is encouraging for the polishing of anaerobic reactor effluents. However, its treatment efficiency is dependent on hydraulic residence time (HRT). Cyperus alternifolius and Typha latifolia-based wastewater treatment showed good removal efficiencies individually. However, data on their combined treatment effectiveness is negligible. Therefore, this study assesses HRT influences on the treatment effectiveness of a two-stage HSSFCW system planted with these two macrophytes for the polishing of anaerobic reactor brewery effluent. A series connected two-stage HSSFCW unit planted with Cyperus alternifolius and Typha latifolia was built to treat Kombolcha brewery anaerobic reactor effluent. Then, the macrophytes were endorsed to grow with continuous application of diluted brewery effluent from a reservoir tank using gravity force. After dense stand formation, the experiment was initiated to determine the influence of HRTs on the removal efficiency of a complete wetland system. The system was operated sequentially by supplying fixed influent inflow rates of 2791, 1395, 930, 698, and 558 L day−1, respectively, for 1, 2, 3, 4, and 5 days HRT. Both the influent and effluent of the two-stage HSSFCW system were analyzed following common procedures for main brewery pollutants.

Result

Results showed that as HRT increased from 1 to 5 days, the effluent pH and temperature were decreased along with enhanced pollutant removals ranging from 47.8–87.2%, 29.2–90.1%, 32.9–77.7%, 16.8–75.4%, and 18.4–76.8% with decreased influent mass loading rates ranging from 26.4–2.1, 64.5–7.3, 11.5–0.8, 5–0.6, and 3.8–0.4 gm−2 day−1, respectively, for total suspended solids, chemical oxygen demand, total nitrogen, total phosphorous and orthophosphate. However, better and steadier pollutant removals were achieved at higher HRTs.

Conclusion

For better nutrient removals, the 4 and 5 days HRT can serve as a good benchmark.
Radiotherapy Practice for Treatment of Bone Metastasis in Ethiopia
Authors: Rick Tara J. , Habtamu Biruk , Tigeneh Wondemagegnhu , Abreha Aynalem , Grover Surbhi , Assefa Mathewos , Heemsbergen Wilma , Incrocci Luca
Published: September 2020

PUROSE

Ethiopia has one cobalt radiotherapy (RT) machine to serve a population of more than 100 million. The purpose of this study was to report on patterns of palliative RT of bone metastasis in a severely low-capacity setting.

PATIENTS AND METHODS

Patient and treatment characteristics of patients irradiated for palliation of symptomatic bone metastasis were extracted from a retrospective database of patients treated between May 2015 and January 2018. This database included a random sample of 1,823 of the estimated 4,000 patients who were treated with RT within in the study period. Associations between the applied RT schedule and patient and tumor characteristics were evaluated with the χ2 test. Hypothetical savings of RT sessions and time were compared in the case of a single-fraction policy.

RESULTS

From the database, 234 patients (13%) were treated for bone metastasis. Most patients were ≤ 65 years of age (n = 189; 80%) and female (n = 125; 53%). The most common primary sites were breast (n = 82; 35%) and prostate (n = 36; 15%). Fractionated regimens were preferred over single fraction: 20 Gy in 5 fractions (n = 192; 82.1%), 30 Gy in 10 fractions (n = 7; 3%), and 8 Gy in 1 fraction (n = 28; 12%). Factors associated with single-fraction RT included nonaxial sites of bone metastasis ( P < .01) and an address outside Addis Ababa ( P ≤ .01). If single-fraction RT would have been given uniformly for bone metastasis, this would have resulted in a 78% reduction in the number of RT sessions and 76% reduction in total RT time.

CONCLUSION

The pattern of palliative RT for bone metastasis in Ethiopia favors fractionated regimens over single fraction. Efforts should be made to adopt evidence-based and cost-effective guidelines.
Venetoclax Plus Rituximab in Relapsed Chronic Lymphocytic Leukemia: 4-Year Results and Evaluation of Impact of Genomic Complexity and Gene Mutations From the MURANO Phase III Study
Authors: Kater Arnon P. , Wu Jenny Qun , Kipps Thomas , Eichhorst Barbara , Hillmen Peter , D’Rozario James , Assouline Sarit , Owen Carolyn , Robak Tadeusz , de la Serna Javier , Jaeger Ulrich , Cartron Guillaume , Montillo Marco , Dubois Julie , Eldering Eric , Mellink Clemens , Van Der Kevie-Kersemaekers Anne-Marie , Kim Su Young , Chyla Brenda , Punnoose Elizabeth , Bolen Christopher R. , Assaf Zoe June , Jiang Yanwen , Wang Jue , Lefebure Marcus , Boyer Michelle , Humphrey Kathryn , Seymour John F.
Published: September 2020

PURPOSE

In previous analyses of the MURANO study, fixed-duration venetoclax plus rituximab (VenR) resulted in improved progression-free survival (PFS) compared with bendamustine plus rituximab (BR) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). At the 4-year follow-up, we report long-term outcomes, response to subsequent therapies, and the predictive value of molecular and genetic characteristics.

PATIENTS AND METHODS

Patients with CLL were randomly assigned to 2 years of venetoclax (VenR for the first six cycles) or six cycles of BR. PFS, overall survival (OS), peripheral-blood minimal residual disease (MRD) status, genomic complexity (GC), and gene mutations were assessed.

RESULTS

Of 389 patients, 194 were assigned to VenR and 195 to BR. Four-year PFS and OS rates were higher with VenR than BR, at 57.3% and 4.6% (hazard ratio [HR], 0.19; 95% CI, 0.14 to 0.25), and 85.3% and 66.8% (HR, 0.41; 95% CI, 0.26 to 0.65), respectively. Undetectable MRD (uMRD) at end of combination therapy (EOCT) was associated with superior PFS compared with low MRD positivity (HR, 0.50) and high MRD positivity (HR, 0.15). Patients in the VenR arm who received ibrutinib as their first therapy after progression (n = 12) had a reported response rate of 100% (10 of 10 evaluable patients); patients subsequently treated with a venetoclax-based regimen (n = 14) had a reported response rate of 55% (six of 11 evaluable patients). With VenR, the uMRD rate at end of treatment (EOT) was lower in patients with GC than in those without GC ( P = .042); higher GC was associated with shorter PFS. Higher MRD positivity rates were seen with BIRC3 and BRAF mutations at EOCT and with TP53, NOTCH1, XPO1, and BRAF mutations at EOT.

CONCLUSION

Efficacy benefits with fixed-duration VenR are sustained and particularly durable in patients who achieve uMRD. Salvage therapy with ibrutinib after VenR achieved high response rates. Genetic mutations and GC affected MRD rates and PFS.
Enhanced Stromal Cell CBS-H2S Production Promotes Estrogen-Stimulated Human Endometrial Angiogenesis
Authors: Qi Qian-Rong , Lechuga Thomas J , Patel Basari , Nguyen Nicole A , Yang Yi-Hua , Li Yan , Sarnthiyakul Sassi , Zhang Quan-Wei , Bai Jin , Makhoul Josh , Chen Dong-Bao
Published: September 2020

Angiogenesis is a physiological process for endometrial regeneration in the menstrual cycle and remodeling during pregnancy. Endogenous hydrogen sulfide (H2S), produced by cystathionine-β synthase (CBS) and cystathionine-γ lyase (CSE), is a potent proangiogenic factor; yet, whether the H2S system is expressed in the endometrium and whether H2S plays a role in endometrial angiogenesis are unknown. This study was to test whether estrogens stimulate endometrial H2S biosynthesis to promote endometrial microvascular endothelial cell (EMEC) angiogenesis. CBS messenger RNA/protein and H2S production significantly differed among endometria from postmenopausal (POM), premenopausal secretory (sPRM), and proliferative (pPRM) nonpregnant (NP) and pregnant (Preg) women (P < .05) in a rank order of POM approximately equal to sPRM is less than pPRM is less than Preg, positively correlating with angiogenesis indices and endogenous estrogens and with no difference in CSE expression. CBS and CSE proteins were localized to stroma, glands, and vessels in endometrium, and greater stromal CBS protein was observed in the pPRM and Preg states. Estradiol-17β (E2) (but not progesterone) stimulated CBS (but not CSE) expression and H2S production in pPRM endometrial stromal cells (ESCs) in vitro, which were attenuated by ICI 182 780. The H2S donor sodium hydrosulfide promoted in vitro EMEC angiogenesis. Co-culture with sPRM, pPRM, and Preg ESCs all stimulated EMEC migration with a rank order of sPRM less than pPRM approximately equal to Preg. CBS (but not CSE) inhibition attenuated ESC-stimulated EMEC migration. E2 did not affect EMEC migration but potentiated ESC-stimulated EMEC migration. Altogether, estrogens stimulate specific receptor-dependent stromal CBS-H2S production to promote endometrial EMEC angiogenesis in women.
Empiric Determination of the Daily Glucocorticoid Replacement Dose in Adrenal Insufficiency
Authors: Caetano Celina M , Sliwinska Aleksandra , Madhavan Parvathy , Grady James , Malchoff Carl D
Published: September 2020

Background

For the treatment of adrenal insufficiency (AI) in adults, the Endocrine Society’s recommended daily glucocorticoid replacement dose (DGRD) is 15 to 25 mg hydrocortisone (HC), which is approximately 1.7 times the reported mean daily cortisol production rate. Prolonged glucocorticoid overtreatment causes multiple morbidities.

Hypothesis

We tested the hypotheses that the DGRD, empirically determined by individual patient titration, is lower than that of the Endocrine Society guidelines and tolerated without evidence of glucocorticoid under-replacement.

Methods

We empirically determined the DGRD in 25 otherwise healthy adults with AI by titrating the DGRD to the lowest dose tolerated as judged by body mass index, blood pressure, serum sodium concentration and AI symptoms. Patients received either HC or prednisone (PRED). The HC equivalent of PRED was assumed to be 4:1.

Results

The mean empirically determined DGRD, expressed as HC equivalent, was significantly less than the midpoint of the Endocrine Society’s recommended DGRD (7.6 ± 3.5 mg/m2 vs 11.8 mg/m2; P < 0.001). The DGRD in the adrenalectomy group was not significantly different than the DGRD of those with other AI causes (7.9 ± 4.0 mg/m2 vs 7.3 ± 3.1 mg/m2; P = ns), demonstrating that the empirically determined DGRD was not biased by residual cortisol secretion. There was no evidence of glucocorticoid under-replacement as determined by measured biometrics and AI symptoms.

Conclusions

We conclude that an empirically determined DGRD is significantly lower than that of the Endocrine Society guidelines and tolerated without evidence of glucocorticoid under-replacement.
Test Utilization and Value in the Evaluation of Peripheral Neuropathies
Authors: Callaghan Brian C.
Published: September 2020

Peripheral neuropathies can be classified as typical or atypical. Patients with atypical neuropathy have one or more of the following features: acute/subacute onset, non–length dependence, motor predominance, or asymmetry. This classification is important because it informs the appropriate diagnostic evaluation of this highly prevalent condition. The evaluation of a typical peripheral neuropathy, also known as distal symmetric polyneuropathy, requires a thorough history, neurologic examination, and focused laboratory testing. Electrodiagnostic testing and MRI account for the majority of costs but rarely lead to changes in diagnosis or management. These costs are increasingly being passed on to patients, especially those with high-deductible health plans. In contrast, patients with atypical neuropathy require more extensive testing, including electrodiagnostic tests. These tests are much more likely to lead to the use of disease-modifying therapies in these patients compared to in those with typical peripheral neuropathy. This article describes two cases to illustrate the appropriate diagnostic workup of those with typical or atypical neuropathy.
Charcot-Marie-Tooth Disease and Other Hereditary Neuropathies
Authors: Klein Christopher J.
Published: September 2020

PURPOSE OF REVIEW

This article provides an overview of Charcot-Marie-Tooth disease (CMT) and other inherited neuropathies. These disorders encompass a broad spectrum with variable motor, sensory, autonomic, and other organ system involvement. Considerable overlap exists, both phenotypically and genetically, among these separate categories, all eventually exhibiting axonal injury and neurologic impairment. Depending on the specific neural and non-neural localizations, patients experience varying morbidity and mortality. Neurologic evaluations, including neurophysiologic testing, can help diagnose and predict patient disabilities. Diagnosis is often complex, especially when genetic and acquired components overlap.

RECENT FINDINGS

Next-generation sequencing has greatly improved genetic diagnosis, with many third-party reimbursement parties now embracing phenotype-based panel evaluations. Through the advent of comprehensive gene panels, symptoms previously labeled as idiopathic or atypical now have a better chance to receive a specific diagnosis. A definitive molecular diagnosis affords patients improved care and counsel. The new classification scheme for inherited neuropathies emphasizes the causal gene names. A specific genetic diagnosis is important as considerable advances are being made in gene-specific therapeutics. Emerging therapeutic approaches include small molecule chaperones, antisense oligonucleotides, RNA interference, and viral gene delivery therapies. New therapies for hereditary transthyretin amyloidosis and Fabry disease are discussed.

Comprehensive genetic testing through a next-generation sequencing approach is simplifying diagnostic algorithms and affords significantly improved decision-making processes in neuropathy care. Genetic diagnosis is essential for pathogenic understanding and for gene therapy development. Gene-targeted therapies have begun entering the clinic. Currently, for most inherited neuropathy categories, specific symptomatic management and family counseling remain the mainstays of therapy.
Management of Neuropathic Pain in Polyneuropathy
Authors: Peltier Amanda C. , Wood Derek
Published: September 2020

PURPOSE OF REVIEW

Many polyneuropathies cause significant neuropathic pain, resulting in substantial morbidity and reduced quality of life. Appropriate management is crucial for maintaining quality of life for patients with painful polyneuropathies. The US Food and Drug Administration (FDA) has only approved one new drug for painful diabetic neuropathy in the past decade, a topical capsaicin patch that was initially approved for the treatment of postherpetic neuralgia in 2009. Gabapentinoids and serotonin norepinephrine reuptake inhibitors (SNRIs) continue to have an advantage in safety profiles and efficacy. Other antiepileptic medications remain second-line agents because of fewer studies documenting efficacy.

RECENT FINDINGS

This article reviews recent literature on complementary and pharmacologic therapies for the management of painful polyneuropathies. Exercise has emerged as an important therapeutic tool and may also improve the underlying polyneuropathy in the setting of obesity, metabolic syndrome, and diabetes.

The approach to management of painful polyneuropathies is multifactorial, using both pharmacologic and nonpharmacologic measures to improve pain severity and patient quality of life.