bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Indicator Derived From Reticulocyte Hemoglobin Content for Screening Iron Deficiency in an Area Prevalent for Thalassemia
Authors: Jamnok Jutatip , Sanchaisuriya Kanokwan , Chaitriphop Chaninthorn , Sanchaisuriya Pattara , Fucharoen Goonnapa , Fucharoen Supan 
Published: December 2019

Abstract

Objective
To establish a new indicator derived from reticulocyte hemoglobin (Ret-He) content and red blood cell (RBC) indices for screening for iron deficiency anemia (IDA) in an area in whch thalassemia is prevalent.

Methods
Blood specimens from 304 women aged between 18 and 30 years residing in northeast Thailand were collected and measured for RBC and reticulocyte parameters. Iron deficiency was diagnosed when a participant had a serum ferritin level of less than 15 ng per mL. Thalassemia genotypes were defined by hemoglobin (Hb) and DNA analyses.

Results
Of the total participants, 25% had iron deficiency (ID) and 50% carried the thalassemia gene. Various mathematical formulas were established and analyzed using the receiver operating characteristic (ROC) curve. The formula derived from Ret-He: (Ret-He/RDW-SD) × 10, was the best predictor for identifying ID among participants (area under the curve [AUC] = 0.812). Further testing of this indicator among individuals with positive thalassemia-screening results revealed stronger performance with an AUC of 0.874.

Conclusions
The findings indicate that the formula derived from Ret-He might be applicable for screening ID in areas in which thalassemia is prevalent.
Identification and characterization of occult human-specific LINE-1 insertions using long-read sequencing technology
Authors: Zhou Weichen , Emery Sarah B , Flasch Diane A , Wang Yifan , Kwan Kenneth Y , Kidd Jeffrey M , Moran John V , Mills Ryan E 
Published: December 2019

AbstractLong Interspersed Element-1 (LINE-1) retrotransposition contributes to inter- and intra-individual genetic variation and occasionally can lead to human genetic disorders. Various strategies have been developed to identify human-specific LINE-1 (L1Hs) insertions from short-read whole genome sequencing (WGS) data; however, they have limitations in detecting insertions in complex repetitive genomic regions. Here, we developed a computational tool (PALMER) and used it to identify 203 non-reference L1Hs insertions in the NA12878 benchmark genome. Using PacBio long-read sequencing data, we identified L1Hs insertions that were absent in previous short-read studies (90/203). Approximately 81% (73/90) of the L1Hs insertions reside within endogenous LINE-1 sequences in the reference assembly and the analysis of unique breakpoint junction sequences revealed 63% (57/90) of these L1Hs insertions could be genotyped in 1000 Genomes Project sequences. Moreover, we observed that amplification biases encountered in single-cell WGS experiments led to a wide variation in L1Hs insertion detection rates between four individual NA12878 cells; under-amplification limited detection to 32% (65/203) of insertions, whereas over-amplification increased false positive calls. In sum, these data indicate that L1Hs insertions are often missed using standard short-read sequencing approaches and long-read sequencing approaches can significantly improve the detection of L1Hs insertions present in individual genomes.
Assessing interobserver variability and accuracy in the histological diagnosis and classification of cutaneous neurofibromass
Authors: Ortonne Nicolas , Carroll Steven L , Rodriguez Fausto J , Miller Douglas C , Nazarian Rosalynn M , Blakeley Jaishri O , Madaj Zachary B , Verma Sharad K , Stemmer-Rachamimov Anat 
Published: December 2019

Abstract

Background
Cutaneous neurofibromas (cNFs) are the most common tumors in people with neurofibromatosis type 1 (NF1) and are associated with reduced quality of life. There is currently no widely accepted standardized language for describing cNFs clinically or histopathologically. The objective of this study was to evaluate interobserver agreement across pathologists in describing and reporting of neurofibromas involving the skin.

Methods
Twenty-eight (H&E)-stained slides of cNF were scanned using an Aperio XT scanner. The digital images were reviewed by 6 pathologists, who entered free text of up to a 200 word description for each case into a REDcap database. Responses were analyzed for the most commonly used terms based on frequency, as well as agreement (reported as concordance) between reviewers.

Results
A set of the terms most commonly used by pathologists for the histological classification of cNF along with areas of agreement and disagreement have been identified. The study shows that there was strong agreement across reviewers that not all neurofibromas involving the skin are cutaneous neurofibromas and regarding the presence or absence of atypical features and heterologous elements. Areas of less concordance were identified and include cNF subtypes, definition of extension and pattern of growth, as well as the distinction of a cNF from a plexiform without an intraneural component involving skin.

Conclusions
This work is the first step towards development of a robust classification system and devising “gold standard” histopathologic diagnostic criteria for cutaneous neurofibromas.
Organic photovoltaic cell with 17% efficiency and superior processability
Authors: Cui Yong , Yao Huifeng , Hong Ling , Zhang Tao , Tang Yabing , Lin Baojun , Xian Kaihu , Gao Bowei , An Cunbin , Bi Pengqing , Ma Wei , Hou Jianhui 
Published: December 2019

Abstract
The development of organic photoactive materials, especially the newly emerging non-fullerene electron acceptors (NFAs), has enabled rapid progress in organic photovoltaic (OPV) cells in recent years. Although the power conversion efficiencies (PCEs) of the top-performance OPV cells have surpassed 16%, the devices are usually fabricated via a spin-coating method and are not suitable for large-area production. Here, we demonstrate that the fine-modification of the flexible side chains of NFAs can yield 17% PCE for OPV cells. More crucially, as the optimal NFA has a suitable solubility and thus a desirable morphology, the high efficiencies of spin-coated devices can be maintained when using scalable blade-coating processing technology. Our results suggest that optimization of the chemical structures of the OPV materials can improve device performance. This has great significance in larger-area production technologies that provide important scientific insights for the commercialization of OPV cells.
Real-World Effectiveness of Smoking Cessation Strategies for Young and Older Adults: Findings From a Nationally Representative Cohort
Authors: Watkins Shannon Lea , Thrul Johannes , Max Wendy , Ling Pamela M 
Published: December 2019

Abstract

Introduction
Young adults have high combustible cigarette and e-cigarette use rates, and low utilization of evidence-based smoking cessation strategies compared to older adults. It is unknown whether young adults who try to quit smoking without assistance, with evidence-based strategies, or with e-cigarettes, are equally successful compared to older adults.

Aims and Methods
This analysis used a population-based sample from the Population Assessment of Tobacco and Health study of young adult (aged 18–24, n = 745) and older adult (aged 25–64, n = 2057) established cigarette smokers at Wave 1 (2013–2014) who reported having made a quit attempt at Wave 2 (2014–2015). Cessation strategies were: behavioral therapy, pharmacotherapy, product substitution, 2+ strategies, and unassisted. Logistic regression estimated associations between cessation strategy and short-term cessation status at Wave 2 (quit, no quit); multinomial logistic regression predicted long-term cessation patterns at Waves 2 and 3 (sustained quit, temporary quit, delayed quit, no quit).

Results
No cessation strategy (ref: unassisted) significantly predicted short-term cessation. No cessation strategy (ref: unassisted) significantly predicted long-term cessation patterns for young adults. Substitution with e-cigarettes predicted short-term cessation for older daily smokers of ≥5 cigarettes/day (adjusted odds ratio [AOR]: 1.70; 95% confidence interval: 1.08, 2.67) but did not predict long-term cessation patterns.

Conclusions
Despite differences in cessation strategy use between young and older adult smokers, strategy effectiveness largely did not differ by age group. No strategy examined, including e-cigarettes, was significantly associated with successful cessation for young adults. More work is needed to identify effective interventions that help young adult smokers quit.

Implications
(1) Neither behavioral support, pharmacotherapy, nor product substitution was associated with short-term cessation for young or older adults compared to quitting unassisted. (2) Neither behavioral support, pharmacotherapy, nor product substitution was associated with longer-term cessation for young or older adults compared to quitting unassisted. (3) Substitution with e-cigarettes predicted short-term cessation for older daily smokers of ≥5 cigarettes/day but was not associated with longer-term cessation.
A Phase-3 Study to Compare Delafloxacin to Moxifloxacin for the Treatment of Adults with Community-acquired Bacterial Pneumonia (DEFINE-CABP)
Authors: Horcajada Juan P , Salata Robert A , Álvarez-Sala Rodolfo , Nitu Floarea Mimi , Lawrence Laura , Quintas Megan , Cheng Chun-Yen , Cammarata Sue ,   DEFINE-CABP Study Group
Published: December 2019

Abstract

Background
The clinical and economic burden of community-acquired bacterial pneumonia (CABP) is significant and is anticipated to increase as the population ages and pathogens become more resistant. Delafloxacin is a fluoroquinolone antibiotic approved in the United States for the treatment of adults with acute bacterial skin and skin structure infections. Delafloxacin’s shape and charge profile uniquely impacts its spectrum of activity and side effect profile. This phase 3 study compared the efficacy and safety of delafloxacin to moxifloxacin for the treatment of CABP.

Methods
A randomized, double-blind, comparator-controlled, multicenter, global Phase 3 study compared the efficacy and safety of delafloxacin 300 mg BID or moxifloxacin 400 mg QD in adults with CABP. The primary endpoint was early clinical response (ECR) defined as improvement at 96 (± 24) hours after first dose of study drug. Clinical response at test of cure (TOC) and microbiologic response were also assessed.

Results
In the intent-to-treat analysis population (ITT), ECR rates were 88.9% in the delafloxacin group and 89.0% in the moxifloxacin group. Noninferiority of delafloxacin compared with moxifloxacin was demonstrated. At TOC in the ITT population, the success rates were similar between groups. Treatment-emergent adverse events considered at least possibly related to the study drug occurred in 65 subjects (15.2%) in the delafloxacin group and 54 (12.6%) in the moxifloxacin group.

Conclusions
IV/oral delafloxacin monotherapy is effective and well tolerated in the treatment of adults with CABP, providing coverage for grampositive, gramnegative, and atypical pathogens.
Telemedicine Infectious Diseases Consultations and Clinical Outcomes: A Systematic Review
Authors: Burnham Jason P , Fritz Stephanie A , Yaeger Lauren H , Colditz Graham A 
Published: December 2019

Abstract

Background
Telemedicine use is increasing in many specialties, but its impact on clinical outcomes in infectious diseases has not been systematically reviewed. We reviewed the current evidence for clinical effectiveness of telemedicine infectious diseases consultations, including outcomes of mortality, hospital readmission, antimicrobial use, cost, length of stay, adherence, and patient satisfaction.

Methods
We queried Ovid MEDLINE 1946-, Embase.com 1947-, Scopus 1823-, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov 1997- through August 5, 2019, for studies looking at clinical outcomes of infectious diseases in the setting of telemedicine use. We did not restrict by language or year of publication. Clinical outcomes searched included 30-day all-cause mortality, 30-day readmissions, patient compliance/adherence, patient satisfaction, cost or cost-effectiveness, length of hospital stay, antimicrobial use, and antimicrobial stewardship. Bias was assessed using standard methodologies. PROSPERO CRD42018105225.

Results
From a search pool of 1154 studies, only 18 involved telemedicine infectious diseases consultation and our selected clinical outcomes. The outcomes tracked were heterogeneous, precluding meta-analysis, and the majority of studies were of poor quality. Overall, clinical outcomes with telemedicine infectious diseases consultation seem comparable to in-person infectious diseases consultation.

Conclusions
Although in widespread use, the clinical effectiveness of telemedicine infectious diseases consultations has yet to be sufficiently studied. Further studies, or publication of previously collected and available data, are warranted to verify the cost-effectiveness of this widespread practice.

Systematic review registration
PROSPERO CRD42018105225.
Real-World Experience With Ceftazidime-Avibactam for Multidrug-Resistant Gram-Negative Bacterial Infections
Authors: Jorgensen Sarah C J , Trinh Trang D , Zasowski Evan J , Lagnf Abdalhamid M , Bhatia Sahil , Melvin Sarah M , Steed Molly E , Simon Samuel P , Estrada Sandra J , Morrisette Taylor , Claeys Kimberly C , Rosenberg Joshua R , Davis Susan L , Rybak Michael J 
Published: December 2019

Abstract

Background
We conducted this study to describe the clinical characteristics, microbiology, and outcomes of patients treated with ceftazidime-avibactam (CZA) for a range of multidrug-resistant Gram-negative (MDR-GN) infections.

Methods
This is a multicenter, retrospective cohort study conducted at 6 medical centers in the United States between 2015 and 2019. Adult patients who received CZA (≥72 hours) were eligible. The primary outcome was clinical failure defined as a composite of 30-day all-cause mortality, 30-day microbiological failure, and/or failure to resolve or improve signs or symptoms of infection on CZA.

Results
In total, data from 203 patients were evaluated. Carbapenem-resistant Enterobacteriaceae (CRE) and Pseudomonas spp were isolated from 117 (57.6%) and 63 (31.0%) culture specimens, respectively. The most common infection sources were respiratory (37.4%), urinary (19.7%), and intra-abdominal (18.7%). Blood cultures were positive in 22 (10.8%) patients. Clinical failure, 30-day mortality, and 30-day recurrence occurred in 59 (29.1%), 35 (17.2%), and 12 (5.9%) patients, respectively. On therapy, CZA resistance developed in 1 of 62 patients with repeat testing. Primary bacteremia or respiratory tract infection and higher SOFA score were positively associated with clinical failure (adjusted odds ratio [aOR] = 2.270, 95% confidence interval [CI] = 1.115–4.620 and aOR = 1.234, 95% CI = 1.118–1.362, respectively). Receipt of CZA within 48 hours of infection onset was protective (aOR, 0.409; 95% CI, 0.180–0.930). Seventeen (8.4%) patients experienced a potential drug-related adverse effect (10 acute kidney injury, 3 Clostridioides difficile infection, 2 rash, and 1 each gastrointestinal intolerance and neutropenia)

Conclusions
Ceftazidime-avibactam is being used to treat a range of MDR-GN infections including Pseudomonas spp as well as CRE.
Designing an improved T-cell mobilising CXCL10 mutant through enhanced GAG binding affinity
Authors: Gerlza Tanja , Nagele Michael , Gschwandtner Martha , Winkler Sophie , Kungl Andreas 
Published: December 2019

Abstract
The chemokine CXCL10 is released by a plethora of cells, including immune and metastatic cancer cells, following stimulation with interferon-gamma. It acts via its GPC receptor on T-cells attracting them to various target tissues. Glycosaminoglycans (GAGs) are regarded as co-receptors of chemokines, which enable the establishment of a chemotactic gradient for target cell migration. We have engineered human CXCL10 towards improved T-cell mobilisation by implementing a single site-directed mutation N20K into the protein, which leads to a higher GAG binding affinity compared to the wild type. Interestingly, this mutation not only increased T-cell migration in a transendothelial migration assay, the mutant intensified T-cell chemotaxis also in a Boyden chamber set-up thereby indicating a strong role of T-cell-localised GAGs on leukocyte migration. A CXCL10 mutant with increased GAG-binding affinity could therefore potentially serve as a T-cell mobiliser in pathological conditions where the immune surveillance of the target tissue is impaired, as is the case for most solid tumors.
Using hierarchical clustering to explore patterns of deprivation among English local authorities
Authors: Senior Steven L 
Published: December 2019

Abstract

Background
The English Indices of Multiple Deprivation (IMD) is widely used as a measure of deprivation. However, similarly ranked areas can differ substantially in the underlying domains of deprivation. These domains contain a richer set of data that might be useful for classifying local authorities. Clustering methods offer a set of techniques to identify groups of areas with similar patterns of deprivation.

Methods
Hierarchical agglomerative (i.e. bottom-up) clustering methods were applied to domain scores for 152 upper tier local authorities. Advances in statistical testing allow clusters to be identified that are unlikely to have arisen from random partitioning of a homogeneous group. The resulting clusters are described in terms of their subdomain scores and basic geographic and demographic characteristics.

Results
Five statistically significant clusters of local authorities were identified. These clusters only partially reflect different levels of overall deprivation. In particular, two clusters share similar overall IMD scores but have contrasting patterns of deprivation.

Conclusion
Hierarchical clustering methods identify five distinct clusters that do not correspond closely to quintiles of deprivation. This approach may help to distinguish between places that face similar underlying challenges, and places that appear similar in terms of overall deprivation scores, but that face different challenges.
Opioid prescriptions in patients with osteoarthritis: a population-based cohort study
Authors: van den Driest Jacoline J , Schiphof Dieuwke , de Wilde Marcel , Bindels Patrick J E , van der Lei Johan , Bierma-Zeinstra Sita M A 
Published: December 2019

Abstract

Objectives
To examine the incidence, prevalence and trends for opioid prescriptions in patients with OA. Furthermore, types of opioids prescribed and long-term prescription rates were examined. Finally, the patient characteristics associated with the prescription of opioids were assessed.

Methods
A population-based cohort study was conducted using the Integrated Primary Care Information database. Incidence and prevalence of opioid prescriptions were calculated for the period 2008–2017. Logistic regression was used to assess which patient characteristics were associated with opioid prescriptions.

Results
In total, 157 904 OA patients were included. The overall prescription rate remained fairly stable, at around 100 incident and 170 prevalent prescriptions per 1000 person years. However, the incident prescription rate for oxycodone increased from 7.1 to 40.7 per 1000 person years and for fentanyl from 4.2 to 7.4 per 1000 person years. The incident prescription rate for paracetamol/codeine decreased from 63.0 to 13.3 per 1000 person years. Per follow-up year, long-term use was found in 3% of the patients with incident OA. Finally, factors associated with more prescriptions were increasing age, OA in ≥2 joint groups [odds ratio (OR) 1.56; 95% CI: 1.51, 1.65] and the presence of other musculoskeletal disorders (OR 4.91; 95% CI: 4.76, 5.05). Men were less likely to be prescribed opioids (OR 0.78; 95% CI: 0.76, 0.80).

Conclusion
Prescription rates for opioids remained stable, but types of opioids prescribed changed. Oxycodone and fentanyl were increasingly prescribed, while prescriptions of paracetamol/codeine decreased. Since the benefit of opioids for OA pain is questionable and side effects are common, opioids should be prescribed with caution.
Cacna1c Hemizygosity Results in Aberrant Fear Conditioning to Neutral Stimuli
Authors: Moon Anna L , Brydges Nichola M , Wilkinson Lawrence S , Hall Jeremy , Thomas Kerrie L 
Published: December 2019

Abstract
CACNA1C, a gene that encodes an alpha-1 subunit of L-type voltage-gated calcium channels, has been strongly associated with psychiatric disorders including schizophrenia and bipolar disorder. An important objective is to understand how variation in this gene can lead to an increased risk of psychopathology. Altered associative learning has also been implicated in the pathology of psychiatric disorders, particularly in the manifestation of psychotic symptoms. In this study, we utilize auditory-cued fear memory paradigms in order to investigate whether associative learning is altered in rats hemizygous for the Cacna1c gene. Cacna1c hemizygous (Cacna1c+/−) rats and their wild-type littermates were exposed to either delay, trace, or unpaired auditory fear conditioning. All rats received a Context Recall (24 h post-conditioning) and a Cue Recall (48 h post-conditioning) to test their fear responses. In the delay condition, which results in strong conditioning to the cue in wild-type animals, Cacna1c+/− rats showed increased fear responses to the context. In the trace condition, which results in strong conditioning to the context in wild-type animals, Cacna1c+/− rats showed increased fear responses to the cue. Finally, in the unpaired condition, Cacna1c+/− rats showed increased fear responses to both context and cue. These results indicate that Cacna1c heterozygous rats show aberrantly enhanced fear responses to inappropriate cues, consistent with key models of psychosis.
Metabolic Basis for Nonlinearity in 1,3-Dichloropropene Toxicokinetics and Use in Setting a Kinetically-derived Maximum Inhalation Exposure Concentration in Mice
Authors: Bartels Michael J , Hackett Michael J , Himmelstein Matthew W , Green John W , Walker Carl , Terry Claire , Rasoulpour Reza , Challender Mary , Yan Zhongyu (June) 
Published: December 2019

Abstract
1,3-Dichloropropene (1,3-D) showed a statistically increased incidence of bronchioloalveolar adenomas in male B6C3F1 mice at 60 ppm air concentration during previous chronic inhalation testing. No tumors were observed in female mice, nor in either sex of F344 rats up to 60 ppm, the highest dose tested. Therefore, to understand if lung tumors observed in high dose male mice are due to saturation of metabolic clearance, the linearity of 1,3-D concentrations in mouse blood was investigated on day 15 of repeated nose-only inhalation exposure to 0, 10, 20, 40, 60, 90, and 120 ppm (6 h/d, 7 d/week). Additional groups were included at 20, 60, and 120 ppm for blood collection at 1.5 and 3 h of exposure and up to 25 or 40 min post-exposure to determine area-under-the-curve. The data provide multiple lines of evidence that systemic exposures to 1,3-D in the mouse become nonlinear at inhalation exposure levels of 30 ppm or above. A reduction in minute volume occurred at the highest exposure concentration. The glutathione (GSH)-dependent metabolism of 1,3-D results in significant depletion of GSH at repeated exposure levels of 30 ppm and above. This loss of GSH results in decreased metabolic clearance of this test material, with a concomitant increase of the 1,3-D isomers in circulating blood at exposure concentrations ≥30 ppm. Shifts in the ratio of cis- and trans-1,3-D also support nonlinear toxicokinetics well below 60 ppm. Based on this data, a kinetically derived maximum dose for 1,3-D in mice for repeated exposures should be at or below 30 ppm. These results support non-relevance of 1,3-D-induced benign pulmonary tumorigenicity in mice for human health risk assessment.