bluuebunny/crossref_metadata_2025_split huggingface dataset:
A monogenic autoinflammatory disease with fatal vasculitis: deficiency of adenosine deaminase 2
Authors: Sahin Sezgin , Adrovic Amra , Kasapcopur Ozgur 
Published: October 2019

Purpose of reviewTo recap the expanding clinical spectrum, genotype–phenotype associations and treatment options in the light of recently published articles regarding the deficiency of adenosine deaminase 2 (DADA2).Recent findingsWhole-exome sequencing enabled novel clinical phenotypes associated withADA2mutations. Since its discovery, the phenotypic spectrum of DADA2 has substantially expanded to cover Diamond–Blackfan anaemia, cytopenia and immunodeficiency syndromes. In addition to elevated TNF alpha levels, increased levels of interferon-stimulated genes were also detected in patients with DADA2. Given the absence of clinical trials until now, no standard treatment strategy exists for DADA2. Currently, anti-TNF alpha agents are the mainstay of treatment, based on the data both from the initial two reports and from subsequent studies. However, it is still unclear how to manage asymptomatic patients withADA2mutation and/or with absent ADA2 activity and what is the optimal duration of anti-TNF therapy.SummaryAmong a total of 206 DADA2 patients described so far, the overall mortality was found as 8.3%. Biallelic homozygous G47R mutations were mostly associated with a vascular phenotype, whereas patients with homozygous R169Q mutations seem to display a mixed clinical phenotype including vascular, haematological and immunological manifestations. HSCT should be reserved as a curative treatment option for DADA2 patients unresponsive to the anti-TNF therapy, as it carries a significant morbidity.
Novel therapeutic options for radioiodine-refractory thyroid cancer: redifferentiation and beyond
Authors: Bulotta Stefania , Celano Marilena , Costante Giuseppe , Russo Diego 
Published: October 2019

Purpose of review
Radioiodine-refractory thyroid cancers represent the main cause of thyroid cancer-related death. At present, targeted therapies with multikinase inhibitors represent a unique therapeutic tool, though they have limited benefit on patient survival and severe drug-associated adverse events. This review summarizes current treatment strategies for radioiodine-refractory thyroid cancer and focuses on novel approaches to redifferentiate thyroid cancer cells to restore responsiveness to radioiodine administration.

Recent findings
We summarize and discuss recent clinical trial findings and early data from real-life experiences with multikinase-inhibiting drugs. Possible alternative strategies to traditional redifferentiation are also discussed.

Summary
The current review focuses primarily on the major advancements in the knowledge of the pathophysiology of iodine transport and metabolism and the genetic and epigenetic alterations occurring in thyroid neoplasia as described using preclinical models. Results of clinical studies employing new compounds to induce thyroid cancer cell redifferentiation by acting against specific molecular targets are also discussed. Finally, we describe the current scenario emerging from such findings as well as future perspectives.
Is It the Surgery or the Block? Incidence, Risk Factors, and Outcome of Nerve Injury following Upper Extremity Surgery
Authors: Droog Wouter , Lin D-Yin , van Wijk Jan J. , Ho-Asjoe Raissah C. H. , Coert J. Henk , Stolker Robert Jan , Galvin Eilish M. 
Published: October 2019

Background:
Although numerous studies have addressed the topic of postoperative nerve injury, debate continues to exist on its exact incidence, risk factors, etiology, and functional outcome. The aim of this study is to investigate the incidence of nerve injury and to identify patient, anesthetic, and surgical factors pertaining to perioperative nerve injury. Also, long-term nerve injury outcomes were assessed in terms of functionality.

Methods:
A total of 297 patients, scheduled for elective distal upper extremity surgery, were prospectively included. At various time points, patients were screened for new onset nerve injury by means of clinical examination and questionnaires (including the Quick Disabilities of the Arm, Shoulder and Hand functionality measure).

Results:
New nerve injury was diagnosed in 14 patients [4.7% (95% CI, 2.8–7.8)], but no causative risk factors were identified. The exact origin of nerve injury is suspected to be surgical in 11 cases. At 4 years postoperatively, 5 of the 14 patients with nerve injury (36%) were still symptomatic and had reduced functionality relative to preoperative status.

Conclusions:
This study demonstrates an incidence of all cause nerve injury of 4.7%. No specific patient, anesthetic, or surgical risk factors are identified and, importantly, patients who received regional anesthesia are not at more risk of nerve injury than those who received general anesthesia. The exact origin of nerve injury is very difficult to determine, but is suspected to be caused by direct surgical trauma in most cases. Four years following the nerve injury, approximately 40% of the patients with new onset nerve injury have reduced functionality.
Aggregate health and economic burden of herpes zoster in the United States: illustrative example of a pain condition
Authors: Harvey Michael , Prosser Lisa A. , Rose Angela M. , Ortega-Sanchez Ismael R. , Harpaz Rafael 
Published: October 2019

Abstract
Our objective was to develop comprehensive national estimates of the total burden of herpes zoster (HZ) among U.S. adults, including direct (ie, medical costs) and indirect (ie, productivity losses) costs, as well as its psychosocial impact (ie, quality of life losses). Using a patient-level microsimulation model, we projected health and economic outcomes among U.S. adults aged 18 years and older using a 10-year time horizon. We conducted a comprehensive systematic literature review to generate parameter values and conducted simulation modeling to generate our outcomes, including numbers of cases of uncomplicated HZ, postherpetic neuralgia (PHN), and ocular complications, productivity losses, and losses in quality-adjusted life years (QALYs). We used a societal perspective for outcomes; the costing year was 2015. Projected outcomes for an unvaccinated population included 1.1 million HZ cases, 114,000 PHN cases, and 43,000 ocular complications annually, resulting in approximately 67,000 QALYs lost. HZ and its complications would incur costs of $2.4 billion in direct medical costs and productivity losses annually. Projected QALY losses were most sensitive to HZ and PHN health utility values in the model. Cost estimates were most sensitive to the probability of HZ and to the costs per episode of PHN. The national burden of direct, indirect, and psychosocial HZ costs is substantial. Our results can inform economic analyses for HZ vaccines. Comprehensive, national assessments of the total burden of other painful conditions would be very informative.
Does Aggressive Variant Histology Without Invasive Features Predict Overall Survival in Papillary Thyroid Cancer?
Authors: Limberg Jessica , Ullmann Timothy M. , Stefanova Dessislava , Buicko Jessica L. , Finnerty Brendan M. , Zarnegar Rasa , Fahey Thomas J. , Beninato Toni 
Published: October 2019

Objective:
We aimed to clarify whether aggressive histology of papillary thyroid cancer (PTC) impacts overall survival (OS).

Summary Background Data:
Aggressive variants of PTC (AVPTC) are associated with invasive features. However, their behavior in the absence of these features is not well characterized.

Methods:
Patients treated from 2004 to 2015 for classic PTC (cPTC) or AVPTCs were identified from the National Cancer Database. Patients were further stratified based on presence of at least 1 invasive feature—extrathyroidal extension, multifocality, lymphovascular invasion, nodal or distant metastasis. Demographics, treatments, and OS were compared.

Results:
A total of 170,778 patients were included—162,827 cPTC and 7951 AVPTC. Invasive features were more prevalent in AVPTC lesions compared to cPTC (70.7% vs 59.7%, P < 0.001). AVPTC included tall cell/columnar cell (89.5%) and diffuse sclerosing (10.5%) variants. Patients with invasive features had worse OS irrespective of histology. Furthermore, when controlling for demographics, tumor size, and treatment variables in patients with noninvasive lesions, AVPTC histology alone was not associated with worse OS compared to cPTC (P = 0.209). In contrast, among patients who had at least 1 invasive feature, AVPTC histology was independently predictive of worse OS (P < 0.05) {TCV/Columnar hazard ratio [HR] 1.2; [95% confidence interval (CI) 1.1–1.3] and diffuse sclerosing HR 1.3; 95% CI 1.0–1.7]}. All invasive features, except multifocality, were independently associated with worse OS, with metastasis being the most predictive [HR 2.9 (95% CI 2.6–3.2) P < 0.001].

Conclusions:
In the absence of invasive features, AVPTC histology has similar OS compared to cPTC. In contrast, diffuse sclerosing and tall cell/columnar variants are associated with worse OS when invasive features are present.
Reduction of Postoperative Wound Infections by Antiseptica (RECIPE)?
Authors: Strobel Rahel M. , Leonhardt Marja , Krochmann Anika , Neumann Konrad , Speichinger Fiona , Hartmann Lisa , Lee Lucas D. , Beyer Katharina , Daum Severin , Kreis Martin E. , Lauscher Johannes C. 
Published: October 2019

Objective:
To evaluate whether intraoperative subcutaneous wound irrigation with 0.04% polyhexanide can reduce surgical site infection (SSI) in elective laparotomies compared to saline.

Background:
SSI is a common complication after gastrointestinal surgery. To date, there is a lack of evidence whether subcutaneous wound irrigation is beneficial in terms of reduction of SSI.

Methods:
The RECIPE trial was an investigator initiated single-center, single-blind prospective, randomized controlled trial with 2 parallel treatment groups, comparing wound irrigation with 0.9% saline to antiseptic 0.04% polyhexanide solution in elective laparotomies. Primary endpoint was the rate of SSI within 30 days postoperatively according to Centers for Disease Control and Prevention criteria.

Results:
Between February 02, 2015, and May 23, 2018, 456 patients were randomly assigned to saline (n = 228) or polyhexanide (n = 228). Final cohort for analysis comprised 393 patients (202 in the saline and 191 in the polyhexanide group). Overall rate of SSI was 28.2%, n = 111. Simple analysis with cross tabulation revealed that significantly fewer SSIs occurred in the polyhexanide group: n = 70 (34.7%) versus n = 41 (21.5%); P = 0.004. In a multiple logistic regression model the factor wound irrigation with polyhexanide [odds ratio (OR) 0.44; 95% confidence interval (CI) 0.27–0.72; P = 0.001) was associated with risk reduction of SSI. Preoperative anemia (OR 2.08; 95% CI 1.27–3.40; P = 0.004) and more than 5 prior abdominal operations compared to none (OR 8.51; 95% CI 2.57–28.21; P < 0.001) were associated with SSI.

Conclusions:
Intraoperative subcutaneous wound irrigation with antiseptic 0.04% polyhexanide solution is effective in reducing SSI after elective laparotomies.
Isolated night cough in children: how does it differ from wheeze?
Authors: Jurca Maja , Goutaki Myrofora , Latzin Philipp , Gaillard Erol A. , Spycher Ben D. , Kuehni Claudia E. 
Published: October 2019

AbstractBackgroundChildren with night cough but no wheeze might have a mild form of asthma (cough variant asthma), sharing risk factors with children who wheeze, and possibly developing wheeze later.MethodsWe compared risk factors of children with isolated night cough and children with wheeze in the Leicester Respiratory Cohort study at ages 1, 4, 6, and 9 years. We also compared prognoses of children with isolated night cough, children with wheeze, and asymptomatic children.ResultsAmong 4,101 children at age 1 year, 2,854 at 4, 2,369 at 6, and 1,688 at 9 years, the prevalence of isolated night cough was 10% at age 1 and 18% in older children, while prevalence of wheeze decreased from 35% at 1 year to 13% at age 9. Although many risk factors were the same for cough and wheeze, day care, reflux, and family history of bronchitis were more strongly associated with cough, and male sex and family history of asthma with wheeze. Over one-third of pre-schoolers with cough continued to cough at school age, but their risk of developing wheeze was similar to that of children asymptomatic at earlier surveys. Wheeze tracked more strongly throughout childhood than cough.ConclusionsSome risk factors for cough and wheeze were shared and some were not; there was little evidence that children with isolated night cough have an increased risk of future wheeze. This suggests that only a fraction of children with isolated night cough might have a variant of asthma, if at all.
Quaternary Prevention: Is this Concept Relevant to Public Health? A Bibliometric and Descriptive Content Analysis
Authors: Depallens Miguel Andino , Guimarães Jane Mary de Medeiros , Filho Naomar Almeida 
Published: October 2019

AbstractObjectiveTo measure and map research output on Quaternary Prevention (P4) and outline research trends; to assess the papers content, mainly regarding methods and subjects approached in order to contribute to the improvement of global knowledge about P4 and to evaluate its relevance for public health.DesignBibliometric and descriptive content analysis.Articles reviewedScientific articles about P4 recorded in Pubmed, LILACS, Scielo or CINAHL published until August 2018, with correspondent full articles available in Portuguese, English, Spanish, German or French.Main outcome measuresYear of publication, first authors’ name and nationality, journals’ name, country and ranking, publication language, used methods and main reported subjects.Results65 articles were included, published in 33 journals of 16 countries between 2003 and 2018 with a peak of publications in 2015. The first authors came from 17 different countries, 23% of them were Brazilian and Uruguay was the leading nation according to the scientific production per capita. 40% of all the selected articles were in English, 32% in Portuguese, 26% in Spanish. 28% of the papers were published in Q1 or Q2 journals. The research outputs on P4 begun first in the South of Europe, went to South America and then expanded worldwide. 88% of the articles were bibliographic research and 38% of all focused on specific examples of medical overuse (including several screening tests).ConclusionsQuaternary prevention represents an ethical and valid approach to prevent occurence of iatrogenic events and to achieve equal and fair access to health services. Conceptual, geographical and linguistic elements, as well as WONCA conferences and type of healthcare systems in the authors’ country were fundamental factors that affected research output. The quality and quantity of available studies is still limited, therefore further investigations are recommended to assess the effective impact of P4 on public health.
Joint modelling of individual trajectories, within-individual variability and a later outcome: systolic blood pressure through childhood and left ventricular mass in early adulthood
Authors: Parker Richard M.A. , Leckie George , Goldstein Harvey , Howe Laura D. , Heron Jon , Hughes Alun D. , Phillippo David M. , Tilling Kate 
Published: October 2019

ABSTRACTWithin-individual variability of repeatedly-measured exposures may predict later outcomes: e.g. blood pressure (BP) variability (BPV) is an independent cardiovascular risk factor above and beyond mean BP. Since two-stage methods, known to introduce bias, are typically used to investigate such associations, we introduce a joint modelling approach, examining associations of both mean BP and BPV across childhood to left ventricular mass (indexed to height; LVMI) in early adulthood with data from the UK’s Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Using multilevel models, we allow BPV to vary between individuals (a “random effect”) as well as to depend on covariates (allowing for heteroscedasticity). We further distinguish within-clinic variability (“measurement error”) from visit-to-visit BPV. BPV was predicted to be greater at older ages, at higher bodyweights, and in females, and was positively correlated with mean BP. BPV had a positive association with LVMI (10% increase in SD(BP) was predicted to increase LVMI by mean = 0.42% (95% credible interval: −0.47%, 1.38%)), but this association became negative (mean = −1.56%, 95% credible interval: −5.01%, 0.44%)) once the effect of mean BP on LVMI was adjusted for. This joint modelling approach offers a flexible method of relating repeatedly-measured exposures to later outcomes.
Inconsistent Addiction Treatment for Patients Undergoing Cardiac Surgery for Injection Drug Use-Associated Infective endocarditis
Authors: Tiako Max Jordan Nguemeni , Hong Seong , Mahmood Syed Usman Bin , Mori Makoto , Mangi Abeel , Yun James , Juthani-Mehta Manisha , Geirsson Arnar 
Published: October 2019

AbstractIntroductionCases of injection drug use-related infective endocarditis (IDU-IE) requiring surgery are rising in the setting of the current U.S. opioid epidemic. We thus aimed to determine the nature of addiction interventions in the perioperative period.MethodsThis is a retrospective review of surgical IDU-IE from 2011 to 2016 at a tertiary care center in New Haven, Connecticut. The data collected included substances consumed recreationally, consultations by social work (SW), psychiatry, pharmacotherapy for addiction, and evidence of enrollment in a drug rehabilitation program upon discharge.Among patients with active drug use (ADU), we compared the 24-month survival of those who received at least one form of addiction intervention to that of those who did not.ResultsForty-two patients (75%) had active drug use. Among them, 22 used heroin. Forty-one patients (73.2%) saw SW, 17 (30.4%) saw psychiatry; 14 (25%) saw neither SW nor psychiatry.Twenty-one patients (37.5%) received methadone, 6 (10.7%) received buprenorphine, 1 (0.02%) received naltrexone; 26 (46.4%) did not receive any pharmacotherapy. Fifteen patients (26.8%) attended a drug rehabilitation program, 13 (86.7%) of whom had seen SW and 8 (53%) psychiatry. Among patients with ADU, there was no statistically significant difference in survival between those who received at least one intervention and those who did not (p=0.1 by log rank).ConclusionAddiction interventions are deployed inconsistently for patients with surgical IDU-IE. Untreated substance use disorder and recurrent endocarditis are the leading cause of death in this population. Studying best-practices for perioperative interventions in IDU-IE and establishing protocols are of the upmost importance.
Microbial signalling of Rhizobium bacteria as a method for cereal crop germination enhancement
Authors: Judge Ciara , Hickey Emer 
Published: October 2019

1.AbstractRhizobiumnitrogen-fixing bacteria are a well studied microorganism family in the scientific community and it’s effects have been investigated thoroughly since its initial identification. This study aimed to research further the interactions of this bacteria with members of non-legume plant families, i.e. thepoaceaegrass species. This multi-year experimental series focuses on the germination stage of these plants, with varying treatments being applied to the seeds pre-germination in order to first test for a quantifiable effect taking place, and later to characterise the mechanism due to which an effect was noted. The identifier used to establish the presence of an effect was the germination rate of the seeds, which was found by examining the testa of each seed for the emergence of a radicle or plumule. Approximately 15,000 samples were tested during this process, the results of which were subsequently statistically analysed at a 95% confidence level. A conclusive increase of 40% (p<0.0001) was noted in the germination of barley seeds when treated withR. leguminosarum. Following tests which confirmed increase enzymatic activity, tests using a different bacterium (A. tumefaciens) and further review of existing literature, it was deemed likely that this effect was due to the release of lipo-chitooligosaccharides (LCOs) by the bacteria. It has been established that synthetically isolated LCO’s can positively effect barley germination. It is believed that this is the first time it has been demonstrated that freeRhizobiumbacteria in suspension can stimulate faster germination in thepoaceaespecies due to the natural release of LCO’s by the bacteria.
Effects of mutations in pigeonMc1rimplicate an expanded plumage color patterning regulatory network
Authors: Krishnan Shreyas , Cryberg Richard L. 
Published: October 2019

AbstractStudies in mammals have shown that the Melanocortin 1 receptor occupies a pivotal role as a nexus for integrating paracrine and autocrine signals to regulate pigment production and type-switching between pheomelanin (red/yellow) and eumelanin (black/brown) pigment synthesis in melanocytes. Inactivating mutations in theMc1rgene are responsible for recessive pheomelanic reddening traits in several species, while mutations that increase activity cause dominant eumelanic darkening traits in mammals and birds. Previous efforts to associateMc1rcoding variants with color variation in pigeons (Columba livia) have yielded conflicting results. Applying a reverse genomic approach, we discovered a novel 500 base pair frameshifting deletion in pigeonMc1rthat likely inactivates the single-exon gene. Segregation analysis revealed complete cosegregation (LOD = 12.2) withsmoky(symbolsy), a recessive pigmentation trait reported in these pages by Willard F. Hollander 80 years ago. We coupled these findings with breeding tests to determine thatDirty(V), a dominant darkening trait, is allelic tosy, and identified two independentValleles, one of which is associated with melanic morphs of two other bird species. In contrast to observations thatMc1rinactivation results in uniform pheomelanic pelage in mammals, its loss in otherwise wild-type pigeons occurs without apparent pheomelanism, instead increasing plumage eumelanism while leaving black bar pattern elements of the tail and wing largely intact. These findings require reconsideration of Mc1r’s presumed role in pigment type-switching in birds, and suggest the existence of Mc1r-independent pathways for eumelanic pigmentation pattern regulation unknown in mammals.
Shared transcriptional responses to con- and heterospecific behavioral antagonists in a wild songbird
Authors: Louder Matthew I. M. , Lafayette Michael , Louder Amber A. , Uy Floria M. K. , Balakrishnan Christopher N. , Yasukawa Ken , Hauber Mark E. 
Published: October 2019

AbstractThe recognition of and differential responses to salient stimuli are among the main drivers of behavioral plasticity, yet, how animals evolve and modulate functional responses to novel classes of antagonistic stimuli remain poorly understood. We studied free-living male red-winged blackbirds (Agelaius phoeniceus) to test whether gene expression responses in blood are distinct or shared between patterns of aggressive behavioral responses directed at simulated conspecific versus heterospecific intruders. In this species, males defend territories against conspecific males and respond aggressively to female brown-headed cowbirds (Molothrus ater), a brood parasite that commonly lays eggs in blackbird nests. Both conspecific songs and parasitic calls elicited aggressive responses from focal subjects and caused a downregulation in genes associated with immune system response, relative to control calls of a second, harmless heterospecific species. In turn, only the conspecific song treatment elicited an increase in singing behavior and an upregulation of genes associated with metabolic processes relative to the two heterospecific calls. Our results suggest that aspects of antagonistic responses to both conspecifics and brood parasites can be based on similar physiological responses, suggestive of shared molecular and behavioral pathways involved in the recognition and reaction to both evolutionarily old and new enemies.