bluuebunny/crossref_metadata_2025 huggingface dataset:
Hot topics in the mechanisms of pulmonary arterial hypertension disease: cancer‐like pathobiology, the role of the adventitia, systemic involvement, and right ventricular failure
Authors: Spiekerkoetter Edda , Goncharova Elena A. , Guignabert Christophe , Stenmark Kurt , Kwapiszewska Grazyna , Rabinovitch Marlene , Voelkel Norbert , Bogaard Harm J. , Graham Brian , Pullamsetti Soni S. , Kuebler Wolfgang M.
Published: November 2019

In order to intervene appropriately and develop disease‐modifying therapeutics for pulmonary arterial hypertension, it is crucial to understand the mechanisms of disease pathogenesis and progression. We herein discuss four topics of disease mechanisms that are currently highly debated, yet still unsolved, in the field of pulmonary arterial hypertension. Is pulmonary arterial hypertension a cancer‐like disease? Does the adventitia play an important role in the initiation of pulmonary vascular remodeling? Is pulmonary arterial hypertension a systemic disease? Does capillary loss drive right ventricular failure? While pulmonary arterial hypertension does not replicate all features of cancer, anti‐proliferative cancer therapeutics might still be beneficial in pulmonary arterial hypertension if monitored for safety and tolerability. It was recognized that the adventitia as a cell‐rich compartment is important in the disease pathogenesis of pulmonary arterial hypertension and should be a therapeutic target, albeit the data are inconclusive as to whether the adventitia is involved in the initiation of neointima formation. There was agreement that systemic diseases can lead to pulmonary arterial hypertension and that pulmonary arterial hypertension can have systemic effects related to the advanced lung pathology, yet there was less agreement on whether idiopathic pulmonary arterial hypertension is a systemic disease per se. Despite acknowledging the limitations of exactly assessing vascular density in the right ventricle, it was recognized that the failing right ventricle may show inadequate vascular adaptation resulting in inadequate delivery of oxygen and other metabolites. Although the debate was not meant to result in a definite resolution of the specific arguments, it sparked ideas about how we might resolve the discrepancies by improving our disease modeling (rodent models, large‐animal studies, studies of human cells, tissues, and organs) as well as standardization of the models. Novel experimental approaches, such as lineage tracing and better three‐dimensional imaging of experimental as well as human lung and heart tissues, might unravel how different cells contribute to the disease pathology.
The Relationships Between Physical Health and Chronic Disease, Stress, and Resource Strain in Head Start Employees
Authors: Snyder Kristin , Hill Madelyn , Lee Miryoung , Crawford Timothy N. , Orlowski Marietta
Published: November 2019

Background: Emerging research indicates that Head Start employees often struggle with health issues and may not be able to model the healthy behaviors that they hope to instill in young children. The purpose of this study was to examine the relationships between perceived physical health and chronic disease, stress, financial-resource strain, and job type. Method: This study was conducted in a large, multi-site Head Start agency located across five counties in the American Midwest. Employees ( N = 550) were invited to complete a 58-item questionnaire that assessed overall health and health behaviors, demographics, workplace environment, and interest in well-being programs. Bivariate analysis and multinomial logistic regressions were used to analyze the relationships between variables of interest and physical health. Findings: More than half ( n = 295; 53.64%) responded, and one quarter of the employees (25.42%) reported poor or fair health. Poor and fair physical health was associated with the number of chronic conditions, difficulty paying for basic necessities, and perceived stress, but not job type. A high percentage of responding employees (83.34%) reported interest in well-being programs, yet interests varied significantly by health status. Employees with poor and fair health expressed interest in stress and emotional-coping programs, in contrast to the fitness interests of employees who reported good, very good, or excellent health. Conclusion/Application to Practice: To meet the needs of employees with poor or fair physical health, employers should offer health behavior modification programs that address the sources of employee stress, including financial-resource strain and mental health challenges.
Spinal Injury in Indian Children: Review of 204 Cases
Authors: Bansal M. L. , Sharawat Rajesh , Mahajan Rajat , Dawar Hitesh , Mohapatra Bibhudendu , Das Kalidutta , Chhabra Harvinder Singh
Published: November 2019

Study design:

Retrospective study.

Objective:

The purpose of the study was to analyze the epidemiological parameters and associated factors after spinal cord injury (SCI) in children, in the last 14 years admitted at a tertiary care center (Indian Spinal Injury Centre [ISIC], New Delhi, India).

Method:

The demographic and injury-related data was analyzed descriptively. The incidence, type, and level of injury were compared across the age groups using a χ2 test. Wherever appropriate, Fisher exact test was used.

Results:

There were 1660 pediatric trauma cases admitted at ISIC from 2002 to 2015, where 204 cases presented with spine injuries. The average age of children sustaining spine injury was 15.69 years (3-18 years of range). There were 15 patients in the age group 0 to 9 years, 27 patients in the age group 10 to 14 years, and 162 patients in the age group 15 to 18 years. This difference in spine injury incidence among the age groups was statistically significant. Fall from height was a common mode of injury. In our sample, boys were 3 times more likely to be injured than girls. Burst fractures were common among the type of injuries.

Conclusion:

Our study confirms the predominance of cervical spine injury and the high incidence of multilevel contiguous with a lesser percentage of noncontiguous multilevel spinal involvement. SCIWORA (spinal cord injury without radiological abnormality) incidences were in a similar context to the literature available. There was a very low incidence of death. Neurological improvement was seen in 8 operated cases and 4 conservatively treated cases.
Disruptive Innovation in Indian Aerospace and Defence Industry
Authors: Rao Shuktij Singh , Banik Arindam , Khanna Ashutosh , Philip Deepu
Published: November 2019

This article analyses disruptive innovation in Indian aerospace and defence industry using a theoretical model developed on the basis of Christensen’s framework for analysing disruptive innovation and by addressing the requirements of aerospace and defence industry. This framework is then used to collect data from key stakeholders and analyse the movements of Indian aerospace and defence industry. Analysis of a large sample of data reveals that there are forces of disruptive innovation that have been set in motion in the Indian aerospace and defence industry by recent events driven by the signals of changes in the industry and the steps taken by Government of India; however, they do not appear to be sufficient to be able to drive innovation and business activity that may amount to a scale of disruptive innovation due to lack of user participation and inadequate access to the global network of technology and management expertise.

JEL Classifications: O31, O32, O33, O38
Discrimination of Gain Increments in Speech
Authors: Caswell-Midwinter Benjamin , Whitmer William M.
Published: November 2019

During a hearing-aid fitting, the gain applied across frequencies is often adjusted from an initial prescription in order to meet individual needs and preferences. These gain adjustments in one or more frequency bands are commonly verified using speech in quiet (e.g., the clinician’s own voice). Such adjustments may be unreliable and inefficient if they are not discriminable. To examine what adjustments are discriminable when made to speech, this study measured the just-noticeable differences (JNDs) for gain increments in male, single-talker sentences. Sentences were presented with prescribed gains to the better ears of 41 hearing-impaired listeners. JNDs were measured at d’ of 1 for octave-band, dual-octave-band, and broadband increments using a fixed-level, same-different task. The JNDs and interquartile ranges for 0.25, 1, and 4 kHz octave-band increments were 6.3 [4.0–7.8], 6.7 [4.6–9.1], and 9.6 [7.3–12.4] dB, respectively. The JNDs and interquartile ranges for low-, mid-, and high-frequency dual-octave-band increments were 3.7 [2.5–4.6], 3.8 [2.9–4.7], and 6.8 [4.7–9.1] dB, respectively. The JND for broadband increments was 2.0 [1.5–2.7] dB. High-frequency dual-octave-band JNDs were positively correlated with high-frequency pure-tone thresholds and sensation levels, suggesting an effect of audibility for this condition. All other JNDs were independent of pure-tone threshold and sensation level. JNDs were independent of age and hearing-aid experience. These results suggest using large initial adjustments when using short sentences in a hearing-aid fitting to ensure patient focus, followed by smaller subsequent adjustments, if necessary, to ensure audibility, comfort, and stability.
Large-Scale Estimates of LGBQ-Heterosexual Disparities in the Presence of Potentially Mischievous Responders: A Preregistered Replication and Comparison of Methods
Authors: Cimpian Joseph R. , Timmer Jennifer D.
Published: November 2019

Although numerous survey-based studies have found that students who identify as lesbian, gay, bisexual, or questioning (LGBQ) have elevated risk for many negative academic, disciplinary, psychological, and health outcomes, the validity of the types of data on which these results rest have come under increased scrutiny. Over the past several years, a variety of data-validity screening techniques have been used in attempts to scrub data sets of “mischievous responders,” youth who systematically provide extreme and untrue responses to outcome items and who tend to falsely report being LGBQ. We conducted a preregistered replication of Cimpian et al. with the 2017 Youth Risk Behavior Survey to (1) estimate new LGBQ-heterosexual disparities on 20 outcomes; (2) test a broader, mechanistic theory relating mischievousness effects with a feature of items (i.e., item response-option extremity); and (3) compare four techniques used to address mischievous responders. Our results are consistent with Cimpian et al.’s findings that potentially mischievous responders inflate LGBQ-heterosexual disparities, do so more among boys than girls, and affect outcomes differentially. For example, we find that removing students suspected of being mischievous responders can cut male LGBQ-heterosexual disparities in half overall and can completely or mostly eliminate disparities in outcomes including fighting at school, driving drunk, and using cocaine, heroin, and ecstasy. Methodologically, we find that some methods are better than others at addressing the issue of data integrity, with boosted regressions coupled with data removal leading to potentially very large decreases in the estimates of LGBQ-heterosexual disparities, but regression adjustment having almost no effect. While the empirical focus of this article is on LGBQ youth, the issues discussed are relevant to research on other minority groups and youth generally, and speak to survey development, methodology, and the robustness and transparency of research.
Prevalence of the JAK2 V617F Mutation in Patients with Peripheral Arterial Disease
Authors: Kinz Elena , Gasser Klaus , Muendlein Axel , Leiherer Andreas , Steurer Michael , Fraunberger Peter , Lang Alois , Drexel Heinz
Published: November 2019

Introduction:

The acquired JAK2 V617F mutation is common in patients with myeloproliferative neoplasms and increases thrombotic risk. We previously showed that JAK2 V617F is also found in healthy subjects as well as in patients with coronary artery disease (0.6% and 1.3%, respectively). Peripheral arterial disease (PAD) is an important manifestation of diffuse atherosclerosis and PAD patients are at exceptionally high risk for cardiovascular events, showing a worse prognosis than that of patients with coronary artery disease Due to the close relation of the JAK2 V617F mutation to thrombotic events we hypothesized that this mutation may play an important role in the risk management of PAD patients. However, prevalence of JAK2 V617F or of occult myeloproliferative neoplasms is unknown in PAD patients.

Methods:

In the present study we determined the prevalence of JAK2 V617F in a cohort of 287 patients with sonographically proven PAD. JAK2 mutational status from 997 age-matched healthy people was available from a previous study. JAK2 V617F screening and quantification of allele burden in both cohorts was performed with allele-specific quantitative real-time PCR.

Results:

From a total of 287 PAD patients samples, 9 (3.1%) were tested positive for JAK2 V617F mutation corresponding to a 5-fold, highly significant increase compared with healthy people (p<0.001). Mutant allele burden of JAK2 V617F positive samples was ranging between 0.2% and 96.2% (median=0.75%). Generally, our study showed no significant association of the JAK2 V617F mutation with abnormal blood cell counts. However, the patient with the highest mutant allele burden showed elevated hemoglobin values (> 18.5 g/dL) indicating polycythemia vera (PV).

Conclusion:

We conclude that the prevalence of JAK2 V617F mutation is significantly increased in PAD patients compared to the general population. For this reason mutation analysis should be considered in PAD patients with abnormal blood cell counts to identify occult myeloproliferative neoplasms and to adjust therapeutic treatment, possibly reducing the risk of future vascular complications.

Disclosures

No relevant conflicts of interest to declare.
Psychological burden in family caregivers of patients with advanced cancer at initiation of specialist inpatient palliative care
Authors: Oechsle Karin , Ullrich Anneke , Marx Gabriella , Benze Gesine , Heine Julia , Dickel Lisa-Marie , Zhang Youyou , Wowretzko Feline , Wendt Kim Nikola , Nauck Friedemann , Bokemeyer Carsten , Bergelt Corinna
Published: November 2019

Background

This study prospectively evaluated distress, depressive and anxiety symptoms as well as associated factors in family caregivers (FC) of advanced cancer patients at initiation of specialist inpatient palliative care.

Methods

Within 72 h after the patient’s first admission, FCs were asked to complete German versions of the Distress Thermometer, Generalized Anxiety Disorder 7-item scale (GAD-7), Patient Health Questionnaire depression module 9-item scale (PHQ-9) for outcome measure. Multivariate logistic regression analyses were used to identify associated factors.

Results

In 232 FCs (62% spouses/partners), mean level of distress was 7.9 (SD 1.8; range, 2–10) with 95% presenting clinically relevant distress levels. Most frequent problems were sadness (91%), sorrows (90%), anxiety (78%), exhaustion (77%) and sleep disturbances (73%). Prevalence rates of moderate to severe anxiety and depressive symptoms were 47 and 39%, respectively. Only 25% of FCs had used at least one source of support previously. In multivariate regression analysis, being female (OR 2.525), spouse/partner (OR 2.714), exhaustion (OR 10.267), and worse palliative care outcome ratings (OR 1.084) increased the likelihood for moderate to severe anxiety symptom levels. Being female (OR 3.302), low socio-economic status (OR 6.772), prior patient care other than home-based care (OR 0.399), exhaustion (OR 3.068), sleep disturbances (OR 4.183), and worse palliative care outcome ratings (OR 1.100) were associated with moderate to severe depressive symptom levels.

Conclusions

FCs of patients presenting with indication for specialist palliative care suffer from high distress and relevant depressive and anxiety symptoms, indicating the high need of psychological support not only for patients, but also their FCs. Several socio-demographic and care-related risk-factors influence mental burden of FCs and should be in professional caregivers’ focus in daily clinical practice.
Correction to: Effects of workload, work complexity, and repeated alerts on alert fatigue in a clinical decision support system
Authors:   with the HITEC Investigators, Ancker Jessica S. , Edwards Alison , Nosal Sarah , Hauser Diane , Mauer Elizabeth , Kaushal Rainu
Published: November 2019

Following publication of the original article [1], the authors reported that the article erroneously stated that Dr. Ancker was affiliated with the Tehran University of Medical Sciences. Dr. Ancker is not affiliated with that institution.
Concurrent genome and epigenome editing by CRISPR-mediated sequence replacement
Authors: Alexander Jes , Findlay Gregory M. , Kircher Martin , Shendure Jay
Published: November 2019

Background

Recent advances in genome editing have facilitated the direct manipulation of not only the genome, but also the epigenome. Genome editing is typically performed by introducing a single CRISPR/Cas9-mediated double-strand break (DSB), followed by non-homologous end joining (NHEJ)- or homology-directed repair-mediated repair. Epigenome editing, and in particular methylation of CpG dinucleotides, can be performed using catalytically inactive Cas9 (dCas9) fused to a methyltransferase domain. However, for investigations of the role of methylation in gene silencing, studies based on dCas9-methyltransferase have limited resolution and are potentially confounded by the effects of binding of the fusion protein. As an alternative strategy for epigenome editing, we tested CRISPR/Cas9 dual cutting of the genome in the presence of in vitro methylated exogenous DNA, with the aim of driving replacement of the DNA sequence intervening the dual cuts via NHEJ.

Results

In a proof of concept at the HPRT1 promoter, successful replacement events with heavily methylated alleles of a CpG island resulted in functional silencing of the HPRT1 gene. Although still limited in efficiency, our study demonstrates concurrent epigenome and genome editing in a single event.

Conclusions

This study opens the door to investigations of the functional consequences of methylation patterns at single CpG dinucleotide resolution. Our results furthermore support the conclusion that promoter methylation is sufficient to functionally silence gene expression.
Parent–child cooking meal together may relate to parental concerns about the diets of their toddlers and preschoolers: a cross-sectional analysis in Japan
Authors: Ishikawa Midori , Eto Kumi , Miyoshi Miki , Yokoyama Tetsuji , Haraikawa Mayu , Yoshiike Nobuo
Published: November 2019

Background

Parents often have concerns about the food habits of their young children. Cooking is a frequent behavior related to dietary activities at home. We hypothesized that “a parent cooking meals together with young children might alleviate dietary concerns.” The aim of this study was to identify the relationship between parental cooking practices (e.g., cooking meals together with the child) and diet-related concerns.

Methods

Data were extracted from the “National nutrition survey on preschool children” conducted among nation-wide households with toddlers and preschoolers in 2015 by the Ministry of Health, Labour and Welfare of Japan. Parents were classified into two groups comprising those who cooked meals together with their children and those who did not. The following variables were compared: taking too much time to eat (slow eaters), “picky” eating (eating only certain foods), inconsistent food intake (eating too much or too little), playing with food/utensils while eating, preferring sweetened beverages and snacks over meals, eating too fast to chew well, not swallowing food, disinterested in eating, and spitting out food. The associations between parent–child cooking meals together and the concerns pertaining to the child’s dietary habits and food intake were analyzed and compared between the two groups.

Results

The concerns of “picky eating” and “playing with food/utensils while eating” were lower, while “eating too much” was higher in the parent-cooking together group. The intake frequency of fish, soybeans/soy products, vegetables, and milk among children were higher in the “cooking together” group than among those in the “not cooking together” group. Children in the “cooking together” group consumed a significantly greater variety of foods than those in the “not cooking together” group.

Conclusions

Cooking a meal together with a child may be related to the parent’s lower concerns about the dietary habits of the child, including “picky eating” and “playing with food/utensils while eating,” but may also be related to the higher concerns of “eating too much.”
Neuronal maturation reduces the type I IFN response to orthobunyavirus infection and leads to increased apoptosis of human neurons
Authors: Winkler Clayton W. , Woods Tyson A. , Groveman Bradley R. , Carmody Aaron B. , Speranza Emily E. , Martens Craig A. , Best Sonja M. , Haigh Cathryn L. , Peterson Karin E.
Published: November 2019

Background

La Crosse virus (LACV) is the leading cause of pediatric arboviral encephalitis in the USA. LACV encephalitis can result in learning and memory deficits, which may be due to infection and apoptosis of neurons in the brain. Despite neurons being the primary cell infected in the brain by LACV, little is known about neuronal responses to infection.

Methods

Human cerebral organoids (COs), which contain a spectrum of developing neurons, were used to examine neuronal responses to LACV. Plaque assay and quantitative reverse transcription (qRT) PCR were used to determine the susceptibility of COs to LACV infection. Immunohistochemistry, flow cytometry, and single-cell transcriptomics were used to determine specific neuronal subpopulation responses to the virus.

Results

Overall, LACV readily infected COs causing reduced cell viability and increased apoptosis. However, it was determined that neurons at different stages of development had distinct responses to LACV. Both neural progenitors and committed neurons were infected with LACV, however, committed neurons underwent apoptosis at a higher rate. Transcriptomic analysis showed that committed neurons expressed fewer interferon (IFN)-stimulated genes (ISGs) and genes involved IFN signaling in response to infection compared to neural progenitors. Furthermore, induction of interferon signaling in LACV-infected COs by application of recombinant IFN enhanced cell viability.

Conclusions

These findings indicate that neuronal maturation increases the susceptibility of neurons to LACV-induced apoptosis. This susceptibility is likely due, at least in part, to mature neurons being less responsive to virus-induced IFN as evidenced by their poor ISG response to LACV. Furthermore, exogenous administration of recombinant IFN to LACV COs rescued cellular viability suggesting that increased IFN signaling is overall protective in this complex neural tissue. Together these findings indicate that induction of IFN signaling in developing neurons is an important deciding factor in virus-induced cell death.
S100A10 silencing suppresses proliferation, migration and invasion of ovarian cancer cells and enhances sensitivity to carboplatin
Authors: Wang Lingzhi , Yan Wei , Li Xukun , Liu Zhihua , Tian Tian , Chen Tanxiu , Zou Liang , Cui Zhumei
Published: November 2019

Background

Ovarian cancer is the leading cause of gynecological cancer-related mortality. The novel oncogene S100A10 has been reported to be involved in cancer cell proliferation, invasion and metastasis. The role of S100A10 in ovarian cancer has not been well studied and the effect of S100A10 on chemotherapy remains unclear. The aims of the present study were to investigate the functional role of S100A10 in the progression and carboplatin sensitivity of ovarian cancer.

Methods

We examined the expression levels in tissues of S100A10 in 138 cases of ovarian cancer by IHC. To determine the functional roles of downregulated S100A10 in ovarian cancer, cell proliferation, colony formation, cell migration and invasion assays were performed. Chemoresistance was analyzed by apoptosis assay. A xenograft tumor model was established to confirm the role of S100A10 in carboplatin resistance in vivo. Using Western blot assays, we also explored the possible mechanisms of S100A10 in ovarian cancer.

Results

The results showed that increased expression of S100A10 was positively associated with carboplatin resistance (P < 0.001), tumor grade (P = 0.048) and a poorer prognosis (P = 0.0053). Functional analyses demonstrated that S100A10 suppression significantly suppressed ovarian cancer cell proliferation, colony formation, cell migration and invasion, remarkably increased carboplatin-induced apoptosis in SKOV3 and A2780 cells and inhibited tumor growth in vivo. Downregulation of S100A10 expression could inhibit cell proliferation and enhance ovarian cancer cell sensitivity to carboplatin, possibly involving the regulation of cleaved-Caspase3 and cleaved-PARP.

Conclusions

Together, the results of the present study reveal that S100A10 expression can be used as a predictive marker for the prognosis of ovarian cancer and chemosensitivity to carboplatin.
Potentiometric sensor for iron (III) quantitative determination: experimental and computational approaches
Authors: Badakhshan Somayeh , Ahmadzadeh Saeid , Mohseni-Bandpei Anoushiravan , Aghasi Majid , Basiri Amir
Published: November 2019

The current work deals with fabrication and validation of a new highly Fe3+ selective sensor based on benzo-18-crown-6 (b-18C6) using the potentiometric method. The proposed sensor revealed satisfactory performance for quantitative evaluation of Fe3+ trace amount in environmental samples. The ratio of membrane ingredients optimized and the membrane with the composition of 4:30:65.5:0.5 mg of b-18C6:PVC:o-NPOE:KTpClPB exhibited the desirable Nernstian slope of 19.51 ± 0.10 (mV per decade of activity) over the pH range from 2.5 to 5.7 with an acceptable dynamic concentration range of 1.0 × 10−6 M to 1.0 × 10−1 M and lower detection limit of 8.0 × 10−7 M. The proposed sensor demonstrated an appropriate reproducibility with a rapid response time of 12 s and the suitable lifetime of 10 weeks. To validate the accurate response of the proposed sensor, AAS technique applied for the determination of Fe3+ in real aqueous mediums such as drinking tap water and hospital wastewater sample after treatment by electrocoagulation process. Theoretical studies carried out using DFT/B3LYP computational level with 6-311G basis set to optimize the adsorption sites of Fe+3 cationic species by b-18C6. The obtained adsorption energy with large negative value confirmed the formation of a stable complex.
Eco-friendly consolidated process for co-production of xylooligosaccharides and fermentable sugars using self-providing xylonic acid as key pretreatment catalyst
Authors: Zhou Xin , Xu Yong
Published: November 2019

Background

Obtaining high-value products from lignocellulosic biomass is central for the realization of industrial biorefinery. Acid pretreatment has been reported to yield xylooligosaccharides (XOS) and improve enzymatic hydrolysis. Moreover, xylose, an inevitable byproduct, can be upgraded to xylonic acid (XA). The aim of this study was to valorize sugarcane bagasse (SB) by starting with XA pretreatment for XOS and glucose production within a multi-product biorefinery framework.

Results

SB was primarily subjected to XA pretreatment to maximize the XOS yield by the response surface method (RSM). A maximum XOS yield of 44.5% was achieved by acid pretreatment using 0.64 M XA for 42 min at 154 °C. Furthermore, XA pretreatment can efficiently improve enzymatic digestibility, and achieved a 90.8% cellulose conversion. In addition, xylose, the inevitable byproduct of the acid-hydrolysis of xylan, can be completely converted to XA via bio-oxidation of Gluconobacter oxydans (G. oxydans). Subsequently, XA and XOS can be simultaneously separated by electrodialysis.

Conclusions

XA pretreatment was explored and exhibited a promising ability to depolymerize xylan into XOS. Mass balance analysis showed that the maximum XOS and fermentable sugars yields reached 10.5 g and 30.9 g per 100 g raw SB, respectively. In summary, by concurrently producing XOS and fermentable sugars with high yields, SB was thus valorized as a promising feedstock of lignocellulosic biorefinery for value-added products.
Screening for thyroid dysfunction and treatment of screen-detected thyroid dysfunction in asymptomatic, community-dwelling adults: a systematic review
Authors: Reyes Domingo Francesca , Avey Marc T. , Doull Marion
Published: November 2019

Background

This systematic review was conducted to inform the Canadian Task Force on Preventive Health Care recommendations on screening for thyroid dysfunction (TD). The review sought to answer key questions on the benefits and harms of screening for TD, patients’ values and preferences for screening, and the benefits and harms of treating screen-detected TD.

Methods

This review followed Canadian Task Force on Preventive Health Care methods, which include the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The search strategy used for benefits and harms of screening and treatment was an update to the 2014 review by the US Preventive Services Task Force and searched MEDLINE and the Cochrane Library. MEDLINE, Embase, ProQuest Public Health, and SCOPUS were searched for patients’ values and preferences for screening. Outcomes of interest included all-cause mortality, deaths due to cardiovascular diseases, fatal and non-fatal cardiovascular events, atrial fibrillation, fractures, quality of life, cognitive function, and harms due to TD treatment. Two reviewers independently screened abstracts and full texts according to pre-determined inclusion criteria and assessed the risk of bias for each study included. Strength and quality of the evidence was assessed for each outcome. A narrative synthesis was conducted due to heterogeneity of the included studies.

Results

No studies were found on screening for TD, treatment of subclinical hyperthyroidism, or patients’ values and preferences for screening for TD. Twenty-two studies (from 24 publications) on the treatment of TD in patients with screen-detected subclinical hypothyroidism were included. Results from the included randomized controlled trials suggested no benefit of treatment for subclinical hypothyroidism for the large majority of outcomes. We found very low-quality evidence (from two cohort studies) for a small reduction in all-cause mortality among adults < 65 or 40–70 years who were treated for TD compared to those who were not.

Conclusions

This review found moderate to very low-quality evidence on the benefits and harms of treatment for subclinical hypothyroidism, with most of the evidence showing no benefit of treatment.
Projected climate changes in four different regions in Colombia
Authors: Molina Oscar D. , Bernhofer Christian
Published: November 2019

Background

Considering the lack of research over this region the Statistical Downscaling Model (SDSM) was used as a tool for downscaling meteorological data statistically over four representative regions in the eastern side of Colombia. Data from the two Global Climate Models CanESM2 and IPSL-CM5A-MR, which are part of the CMIP5-project have been used to project future maximum and minimum temperature, precipitation and relative humidity for the periods 2021–2050 and 2071–2100. For both models, the Representative Concentration Pathways RCP2.6 and RCP8.5 were considered, representing two different possible future emission trajectories and radiative forcings. Predictor variables from the National Centre for Environmental Prediction (NCEP-DOE 2) reanalysis dataset, together with analyzed correlation coefficient (R) and root mean square error (RMSE) were used as performance indicators during the calibration and validation process.

Results

Results indicate that Maximum and minimum temperature is projected to increase for both Global Climate Models and both Representative Concentration Pathways; relative humidity shows a decreasing trend for all scenarios and all regions; and precipitation shows a slight decrease over three regions and an increase over the warmest region. As expected, the results of the simulation for the period 2071–2100 show a more drastic change when compared to the baseline period of observations.

Conclusions

The SDSM model proves to be efficient in the downscaling of maximum/minimum temperature as well as relative humidity over the studied regions; while showing a lower performance for precipitation, agreeing with the results for other statistical downscaling studies. The results of the projections offer good information for the evaluation of possible future-case scenarios and decision-making management.
Correction to: The rumen microbiome as a reservoir of antimicrobial resistance and pathogenicity genes is directly affected by diet in beef cattle
Authors: Auffret Marc D. , Dewhurst Richard J. , Duthie Carol-Anne , Rooke John A. , Wallace R. John , Freeman Tom C. , Stewart Robert , Watson Mick , Roehe Rainer
Published: November 2019

Following publication of the original article [1], the authors reported an error in the Additional file 1.
Non-invasive identification of polymers in cultural heritage collections: evaluation, optimisation and application of portable FTIR (ATR and external reflectance) spectroscopy to three-dimensional polymer-based objects
Authors: Bell Julianne , Nel Petronella , Stuart Barbara
Published: November 2019

The conservation of polymer-based cultural heritage is a major concern for collecting institutions internationally. Collections include a range of different polymers, each with its own degradation processes and preservation needs, however, they are frequently unidentified in collection catalogues. Fourier transform infrared (FTIR) spectroscopy is a useful analytical tool for identifying polymers, which is vital for determining storage, exhibition, loan and treatment conditions. Attenuated Total Reflection (ATR), and External Reflection (ER) are proven effective FTIR sampling techniques for polymer identification and are beginning to appear in conservation labs. This paper evaluates and optimises the application of these two FTIR techniques to three-dimensional plastic objects in the museum context. Elements of the FTIR measurement process are investigated for 15 common polymers found in museum collections using both authentic reference sheets, and case study objects to model for surface characteristics. Including: use of the ATR and ER modules, the difference between clamping and manually holding objects in contact with the ATR crystal, use of the Kramers–Kronig Transformation, signal-to-noise ratios for increasing number of co-added scans, resultant time taken to collect each measurement, associated professional, health and safety considerations, and the use and availability of reference materials for polymer identify verification. Utilising this information, a flowchart for applying FTIR spectroscopy to three-dimensional historic plastic objects during museum collection surveys is proposed to guide the conservation profession.
Lost in translation: the valley of death across preclinical and clinical divide – identification of problems and overcoming obstacles
Authors: Seyhan Attila A.
Published: November 2019

A rift that has opened up between basic research (bench) and clinical research and patients (bed) who need their new treatments, diagnostics and prevention, and this rift is widening and getting deeper. The crisis involving the “translation” of basic scientific findings in a laboratory setting into human applications and potential treatments or biomarkers for a disease is widely recognized both in academia and industry. Despite the attempts that have been made both in academic and industry settings to mitigate this problem, the high attrition rates of drug development and the problem with reproducibility and translatability of preclinical findings to human applications remain a fact and the return on the investment has been limited in terms of clinical impact.

Here I provide an overview of the challenges facing the drug development, and translational discordance with specific focus on a number of “culprits” in translational research including poor hypothesis, irreproducible data, ambiguous preclinical models, statistical errors, the influence of organizational structures, lack of incentives in the academic setting, governmental funding mechanisms, the clinical relevance of basic research, insufficient transparency, and lack of data sharing in research. I further provide some suggestions and new strategies that include some new aspects on open innovation models, entrepreneurship, transparency, and decision making to overcome each of the many problems during the drug discovery and development process and to more dynamically adjust for innovation challenges with broader scientific feedback.
Pathogenicity of some commercial formulations of entomopathogenic fungi on the tomato leaf miner, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae)
Authors: Ndereyimana Assinapol , Nyalala Samuel , Murerwa Patrick , Gaidashova Svetlana
Published: November 2019

The tomato leaf miner, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), is a major threat to tomato production in Rwanda. Laboratory bioassays were conducted to evaluate some commercial entomopathogenic fungi (EPF) formulations on T. absoluta larvae. The larvae, inside the leaf galleries, were obtained from the established tomato field. Commercial EPF: Metatech® WP [Metarhizium anisopliae (Metschn.) Sorok, Strain FCM Ar 23B3], Beauvitech® WP [Beauveria bassiana (Bals.) Vuill., Strain J25], and Botanigard ES [B. bassiana (Bals.), Strain GHA] were tested in Petri dishes against T. absoluta larvae at a concentration of 108 spores/ml. A synthetic insecticide, imidacloprid was included for comparison as a positive control, while water was used as a negative control. All the tested commercial EPF formulations were pathogenic to T. absoluta larvae in all conducted bioassays. Mortality rates increased with an increase in time (days). However, the insignificant difference was observed in the mortality of T. absoluta larvae treated with the commercial EPF during the first 3 days in all bioassays. Highly significant differences (p < 0.01) in pathogenicity among treatments were observed from the 4th to 6th days after inoculation. Metatech® WP and Beauvitech® WP recorded the highest mortality rates (82.8 and 60.8%) with the LT50 values of 3.9 and 5.2 days, respectively, while imidacloprid caused the least larval mortality. Since the EPF demonstrated high virulence level against the target pest, the efficacy of Metatech® WP and Beauvitech® WP should be advanced to field evaluation to determine their potential as alternatives to the synthetic insecticides.
The roles of rice microRNAs in rice-Magnaporthe oryzae interaction
Authors: Li Yan , Jeyakumar John Martin Jerome , Feng Qin , Zhao Zhi-Xue , Fan Jing , Khaskheli Muhammad Ibrahim , Wang Wen-Ming
Published: November 2019

MicroRNAs (miRNAs) are a class of small (20–24 nucleotides (nt) long) non-coding RNAs. One mature miRNA can be transcribed from one or more gene loci known as miRNA genes (MIRs). The transcript of a MIR forms a stem-loop structure that is processed into a 20–24-nt miRNA-5p/−3p duplex by RNase III family endoribonucleases such as Dicer-like1 (DCL1). In turn, the overhang ends of the duplex are methylated by HUA ENHANCER 1 (HEN1), generating stabilized mature miRNAs. The mature miRNAs are loaded onto ARGONAUTE (AGO) proteins, forming a miRNA-induced gene silencing complex (miRISC). Then, the miRISC binds to target sites with sequences complementary to the miRNAs, leading to either cleavage or translational inhibition of the target mRNAs, or methylation of the target sequences, resulting in post-transcriptional and transcriptional gene silencing, respectively. In the past decade, more than 700 miRNAs have been identified in rice, a subset of which have been found to be responsive to the rice blast fungus, Magnaporthe oryzae, or its elicitors. Moreover, members of 10 miRNA families have been found to positively or negatively regulate rice defense against M. oryzae, namely miR160, miR164, miR166, miR167, miR169, miR319, miR396, miR398, miR444 and miR7695. This review summarizes the identification and functional characterization of the miRNAs, which respond to M. oryzae or its elicitors and describes the current understanding of the complicated but well-organized network in the context of rice-M. oryzae interaction.
The launch of BMC Materials
Authors: Manning Harriet E. , Barquinha Pedro , Cui Wenguo , Evans Drew , Kymakis Emmanuel , Wang Haiyan , Zschech Ehrenfried , Martins Rodrigo
Published: November 2019

BMC Materials is a new, community-focussed venue for all publishable research across the broad discipline of materials science. It joins the mature and reputable BMC Series of journals, adhering to the same standards of publishing and the ethos of open research set by the Series. Together with its sister journals BMC Chemical Engineering, BMC Biomedical Engineering, BMC Energy and BMC Chemistry, BMC Materials furthers the BMC Series’ expansion into the physical sciences and engineering.
Gene-environment and gene-gene interactions between CHRNA3 rs1051730, XRCC1 rs25487, and ERCC1 rs735482 variants highly elevate the risk of lung cancer
Authors: Ezzeldin Nada , El-Lebedy Dalia , Mohammed Asmaa
Published: November 2019

Background

Gene-gene and gene-environment interactions play an important role in cancer susceptibility. In this work, we studied the association of XRCC1 rs25487, ERCC1 rs735482, and CHRNA3 rs1051730 variants with lung cancer and assessed the modulatory effect of potential interaction between these variants on disease risk.

Results

In this study, 86 primary lung cancer patients and 64 control subjects were genotyped for CHRNA3 rs1051730, XRCC1 rs25487, and ERCC1 rs735482 by real-time PCR. The frequency of the three studied variants was higher among lung cancer patients than in control subjects, but with no statistical significance. ERCC1 rs735482 variant was associated with 6.9-fold increased risk to develop lung cancer among smokers (p = 0.03). Concomitant presence of CHRNA3 and ERCC1 wild alleles was associated with 2.7-fold elevated risk of lung cancer (p < 0.0001), while concomitant presence of CHRNA3 rs1051730 variant allele with ERCC1 wild allele was associated with 20-fold elevated risk (p < 0.000). Concomitant presence of both variants, ERCC1 rs735482 and CHRNA3 rs1051730, was associated with 9.9-fold elevated risk (p < 0.0001). Meanwhile, the concomitant presence of XRCC1 rs25487 with either ERCC1 rs735482 or CHRNA3 rs1051730 or both was not associated with increased risk of the disease.

Conclusion

Our results emphasize the role of gene-gene interaction in the pathogenesis of lung cancer. Large-scale further studies to clarify the underlying mechanisms are needed.
Role of diffusion MR imaging (DWI) and three-dimensional ultrasound (3DUS) in the assessment of placental insufficiency in the gestational hypertension
Authors: Mansour Sahar , Hamed Soha , Sayed Safia , Hosny Shreen
Published: November 2019

Background

DWI is a non-invasive MR modality that is not contrast-based. In the current study, we aimed to evaluate DWI in correlation with 3DUS in the detection of placental insufficiency in high-risk pregnancies complicated with hypertension.

This prospective analysis included 80 pregnancies; 40 hypertensive and 40 controls, gestational age ranged from 22 to 34 weeks. All cases had undergone 3DUS aided by power Doppler scanning and DWI. There is no given contrast. Data were correlated to histopathology.

Results

Doppler US showed a significant relation between RI of the right uterine artery of cases and control (P = 0.014). There was also a positive correlation between the presence of the diastolic notch and RI value. The mean ADC value in the controls was 1.87 ± 0.26 mm2/s, while in hypertensive was 1.36 ± 0.09 mm2/s. In DWI images, there was a significant difference between patients with normal and those with abnormal placental signals (P value = 0.047). Also, there was a significant difference between the measurement of placental volume by MRI and US among cases and controls (P values ≤0.001 and 0.017, respectively).

Conclusion

Diffusion-weighted imaging can detect early subtle findings and signs of placental dysfunction more than detected with 3DUS, so it can add to the diagnostic accuracy of US in imaging of pregnancies at high risk of placental insufficiency.
DNA Methylation Profiling Reveals Prognostically Significant Groups in Pediatric Adrenocortical Tumors: A Report From the International Pediatric Adrenocortical Tumor Registry
Authors: Clay Michael R. , Pinto Emilia M. , Cline Cynthia , Tran Quynh T. , Lin Tong , Dyer Michael A. , Shi Lei , Wu Huiyun , Pounds Stanley B. , Zambetti Gerard P. , Orr Brent A. , Ribeiro Raul C.
Published: November 2019

PURPOSE

Pediatric adrenocortical carcinomas (ACCs) are aggressive; the overall survival of patients with ACCs is 40%-50%. Appropriate staging and histologic classification are crucial because children with incomplete resections, metastases, or relapsed disease have a dismal prognosis. The clinical course of pediatric adrenocortical tumors (ACTs) is difficult to predict using the current classification schemas, which rely on subjective microscopic and gross macroscopic variables. Recent advances in adult ACT studies have revealed distinct DNA methylation patterns with prognostic significance that have not been systematically interrogated in the pediatric population.

PATIENTS AND METHODS

We performed DNA methylation analyses on 48 newly diagnosed ACTs from the International Pediatric Adrenocortical Tumor Registry and 12 pediatric adrenal controls to evaluate for distinct methylation groups. Pediatric methylation data were also compared systematically with the adult ACC cohort from The Cancer Genome Atlas (TCGA).

RESULTS

Two pediatric ACT methylation groups were identified and showed differences in selected clinicopathologic and outcome characteristics. The A1 group was enriched for CTNNB1 variants and unfavorable outcome. The A2 group was enriched for TP53 germline variants, younger age at onset, and favorable outcome. Pediatric ACT methylation groups were maintained when International Pediatric Adrenocortical Tumor Registry cohort data were combined with TCGA cohort data. The CpG-island hypermethylator phenotype characterizing the TCGA cohort was not identified in the pediatric patients. When methylome findings were combined with independent histopathologic review using the Wieneke criteria, a high-risk population was identified with uniform fatal outcome.

CONCLUSION

Our results indicate DNA methylation analysis can enhance current diagnostic algorithms. A combination of methylation and histologic classification produced the strongest prediction model and may prove useful in future risk-adapted therapeutic trials.