bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reducing Fatty Acid Oxidation Improves Cancer-free Survival in a Mouse Model of Li-Fraumeni Syndrome
Authors: Wang Ping-Yuan , Ma Jin , Li Jie , Starost Matthew F. , Wolfgang Michael J. , Singh Komudi , Pirooznia Mehdi , Kang Ju-Gyeong , Hwang Paul M. 
Published: September 2020

Abstract

Germline mutations of TP53, which cause the cancer predisposition disorder Li-Fraumeni syndrome (LFS), can increase mitochondrial activity as well as fatty acid β-oxidation (FAO) in mice. Increased fatty acid metabolism can promote cancer malignancy, but its specific contribution to tumorigenesis in LFS remains unclear. To investigate this, we crossed LFS mice carrying the p53 R172H knock-in mutation (p53172H/H, homolog of the human TP53 R175H LFS mutation) with myoglobin-knockout (MB−/−) mice known to have decreased FAO. MB−/− p53172H/H double-mutant mice also showed mildly reduced FAO in thymus, a common site of T lymphoma development in LFS mice, in association with an approximately 40% improvement in cancer-free survival time. RNA sequencing profiling revealed that the p53 R172H mutation promotes mitochondrial metabolism and ribosome biogenesis, both of which are suppressed by the disruption of MB. The activation of ribosomal protein S6, involved in protein translation and implicated in cancer promotion, was also inhibited in the absence of MB. To further confirm the role of FAO in lymphomagenesis, mitochondrial FAO enzyme, carnitine palmitoyltransferase 2 (CPT2), was specifically disrupted in T cells of p53172H/H mice using a Cre-loxP–mediated strategy. The heterozygous knockout of CPT2 resulted in thymus FAO haploinsufficiency and an approximately 30% improvement in survival time, paralleling the antiproliferative signaling observed with MB disruption. Thus, this study demonstrates that moderating FAO in LFS can suppress tumorigenesis and improve cancer-free survival with potential implications for cancer prevention.

Prevention Relevance:
Mildly inhibiting the increased fatty acid oxidation observed in a mouse model of Li-Fraumeni syndrome, a cancer predisposition disorder caused by inherited mutations of TP53, dampens aberrant pro-tumorigenic cell signaling and improves the survival time of these mice, thereby revealing a potential strategy for cancer prevention in patients.
Risk of Skin Cancer Associated with Metformin Use: A Meta-Analysis of Randomized Controlled Trials and Observational Studies
Authors: Chang Michael S. , Hartman Rebecca I. , Xue Junchao , Giovannucci Edward L. , Nan Hongmei , Yang Keming 
Published: September 2020

Abstract

Previous studies demonstrate mixed evidence regarding the association between metformin and skin cancer risk. To synthesize prior evidence and evaluate the association between metformin and skin cancer risk in patients with diabetes/prediabetes, we conducted a meta-analysis. A systematic literature search was performed up to March 23, 2020 to identify randomized controlled trials (RCT) and observational studies of metformin that reported any event of squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma. In a meta-analysis of 6 trials involving 8,541 patients (Peto method), compared with controls, metformin was not significantly associated with decreased risk of melanoma [OR, 0.82; 95% confidence interval (CI), 0.27–2.43], BCC (OR, 0.75; 95% CI, 0.36–1.57), SCC (OR, 0.98; 95% CI, 0.06–15.60), total nonmelanoma skin cancer (NMSC; OR, 0.69; 95% CI, 0.38–1.24), or total skin cancer (OR, 0.71; 95% CI, 0.42–1.20). This nonsignificant association pattern was consistent with the random-effects meta-analysis of 4 cohort studies with 354,746 patients (melanoma: RR, 0.91; 95% CI, 0.62–1.33; NMSC: RR, 0.65; 95% CI, 0.35–1.18; total skin cancer: RR, 0.83; 95% CI, 0.59–1.16). In conclusion, meta-analyses of both RCT and cohort studies showed no statistically significant association between metformin and skin cancer risks, although suggestive evidence of modestly reduced risks of skin cancer among metformin users was observed. Further studies are needed.

Prevention Relevance:
Meta-analyses of RCT and cohort studies showed no significant association between metformin and skin cancer, although suggestive evidence of modestly reduced skin cancer risks among metformin users was observed. These findings suggest metformin use should not influence current medical decision making for diabetes patients at risk of developing skin cancer.
COVID-19, Cancer Care and Prevention
Authors: DuBois Raymond N. 
Published: September 2020

Abstract
The COVID-19 pandemic has had an enormous impact on our society and healthcare delivery in the United States. Importantly, elective procedures and screening exams for cancer have been delayed or canceled over the past 4–5 months raising concerns over the future incidence and outcomes for those at risk or diagnosed with cancer. It is clear to everyone in the cancer field that the earlier we detect premalignant disease or cancer, the better the clinical outcome is for the patient. Most healthcare institutions have now put safety procedures and guidelines in place, which have dramatically reduced the risk of viral spread during encounters in their healthcare facilities. We must now encourage the public and those individuals at high risk for cancer to resume normal cancer screening.
Disparities in the Management of Newly Diagnosed Paroxysmal Supraventricular Tachycardia for Women Versus Men in the United States
Authors: Sacks Naomi C. , Everson Katie , Emden Maia R. , Cyr Phillip L. , Wood David R. , Raza Sajjad , Wood Kathryn A. , Pokorney Sean D. 
Published: September 2020

Background
Information on differences in paroxysmal supraventricular tachycardia (PSVT) diagnosis, healthcare resource use, expenditures, and treatment among women versus men is limited.

Methods and Results

Study participants identified in the IBM MarketScan Commercial Research Databases were aged 18 to 40 years with newly diagnosed PSVT (
International Classification of Diseases, Ninth Revision
[
ICD‐9
]: 427.0;
International Classification of Diseases, Tenth Revision
[
ICD‐10
]: I47.1) from October 1, 2012, through September 30, 2016, observable 1 year preindex and postindex diagnosis. Study outcomes were mean annual per‐patient healthcare resource use and expenditures before and after diagnosis. Among 5466 patients newly diagnosed with PSVT, most (66.9%) were women. Compared with men, women with PSVT tended to have higher rates of anxiety (13.9% versus 10.9%;
P
<0.01) and chronic pulmonary disease (10.9% versus 8.3%;
P
<0.01). Following diagnosis, mean annual per‐patient expenditures increased for all patients, but were significantly lower for women ($26 922 versus $33 112;
P
<0.05), reflecting lower spending for services billed as a result of a PSVT diagnosis ($8471 versus $11 405;
P
<0.05). After diagnosis, nearly half of all patients had at least 1 emergency department visit (women versus men, 49.6% versus 44.5%;
P
<0.01) and more had hospital admissions (women versus men, 24.7% versus 20.0%;
P
<0.01). Fewer women were treated with cardiac ablation (12.6% versus 15.3%;
P
<0.01), and more were treated with medical therapy, including β blockers or calcium channel blockers (odds ratio, 1.15; 95% CI, 1.02–1.31).

Conclusions
Among patients aged 18 to 40 years, ≈2 of 3 patients diagnosed with PSVT were women. After diagnosis, spending was significantly lower for women, reflecting lower ablation rates and less spending on services with a PSVT diagnosis.
Distributed Temperature Sensing for Oceanographic Applications
Authors: Sinnett Gregory , Davis Kristen A. , Lucas Andrew J. , Giddings Sarah N. , Reid Emma , Harvey Madeleine E. , Stokes Ian 
Published: September 2020

AbstractDistributed temperature sensing (DTS) uses Raman scatter from laser light pulsed through an optical fiber to observe temperature along a cable. Temperature resolution across broad scales (seconds to many months, and centimeters to kilometers) make DTS an attractive oceanographic tool. Although DTS is an established technology, oceanographic DTS observations are rare since significant deployment, calibration, and operational challenges exist in dynamic oceanographic environments. Here, results from an experiment designed to address likely oceanographic DTS configuration, calibration, and data processing challenges provide guidance for oceanographic DTS applications. Temperature error due to suboptimal calibration under difficult deployment conditions is quantified for several common scenarios. Alternative calibration, analysis, and deployment techniques that help mitigate this error and facilitate successful DTS application in dynamic ocean conditions are discussed.
The utility of kidney injury molecule-1 as an early biomarker of kidney injury in people living with HIV
Authors: Danjuma Mohammed I , Al Shokri Shaikha , Bakhsh Nadia , Alamin Mohammed A , Mohamedali Mohamed GH , Tamuno Igbiks 
Published: September 2020

There are increasing reports of antiretroviral therapy (ART) drug-related kidney dysfunction. Traditional markers of kidney dysfunction such as urine protein/creatinine ratio and estimated glomerular filtration rate (eGFR) have thus far proven ineffective at detecting some sub-clinical forms of ART-related kidney injury. This is a cross-sectional examination of 114 people living with HIV (PLWH), either naïve ( N =104) or treatment experienced ( N =10). Urinary kidney injury molecule-1 (KIM-1 ng/mg) thresholds were estimated using electrochemiluminescent assays from stored urine samples and normalised for urinary creatinine excretion (KIM-1/Cr). Correlation coefficients and predictors of kidney tubular injury were compared and derived for both adjusted and unadjusted urinary KIM-1/CR (ng/mg). In PLWH (both ART-naïve and treatment experienced) had a higher baseline unadjusted and adjusted median (≥3.7 ng/mg) and upper tertile (≥6.25 ng/mg) urinary KIM-1/Cr levels compared to either non-normal volunteers (0.39 ng/mg) or those with acute kidney injury in the general population (0.57 ng/mg). When upper tertile KIM-1/Cr (≥6.25 ng/mg) was utilised as a marker of kidney injury, eGFR (ml/min/1.73 m2), white Caucasian ethnicity, and protease inhibitor exposure were significantly associated with increased risk of kidney injury in multivariate analyses (odds ratio 0.91, confidence interval [CI] 0.68–0.98, P = 0.02; odds ratio 8.9, CI 1.6–48.6, p = 0.01; and odds ratio 0.05, CI 0.03–0.9, p =0.04, respectively). We found a significant degree of sub-clinical kidney injury (high unadjusted and adjusted KIM-1/Cr) in PLWH with normal kidney function (eGFR ≥60 ml/min/1.73 m2). We also found a higher baseline KIM-1/Cr (ng/mg) in our study cohort than reported both in normal volunteers and patients with kidney injury in the general population.
Benefits and Limitations of the Minimally Invasive Postmortem: A Review of an Innovative Service Development
Authors: Hyde Georgia , Rummery Rachel , Whitby Elspeth H , Bloor Jessica , Raghavan Ashok , Cohen Marta C 
Published: September 2020

Introduction Pediatric postmortem (PM) rates have significantly declined, creating a need for effective minimally invasive alternatives to correlate with parental wishes. We review the use of a minimally invasive fetal and neonatal PM service further to preliminary findings published in 2015. Materials and Methods Cases taken from the mortuary electronic database from 2012 to 2017 are analyzed. The minimally invasive service consisted primarily of external examination, magnetic resonance imaging (MRI), and placental examination. Any significant conditions found noted. All pathology reports include a Relevant Condition at Death (ReCoDe) obstetric classification. Reports analyzed to determine which aspects of the service provided positive information. Results Of 1498 perinatal postmortems, 105 (7%) were PM MRI, of which 75.24% were intrauterine fetal deaths. Relevant conditions were identified in 94 cases (89.52%), and ReCoDe categories in 80 cases (76.19%). Moreover, 90% of cases had a ReCoDe condition, with 10% unclassified. Seven cases had more than 1 ReCoDe. Main conditions related to placenta (32.5%) and umbilical cord (27.5%). The most informative elements were placental examination and MRI. Conclusion Minimally invasive PMs are a viable alternative to traditional autopsy when this option is refused. However, further case analysis is needed to determine potential bias toward certain classification codes.
Type 2 diabetes in older patients: an analysis of the DPV and DIVE databases
Authors: van Mark Gesine , Tittel Sascha R. , Sziegoleit Stefan , Putz Franz Josef , Durmaz Mesut , Bortscheller Michaela , Buschmann Ivo , Seufert Jochen , Holl Reinhard W. , Bramlage Peter 
Published: September 2020

Background: The clinical profile differs between old and young patients with type 2 diabetes mellitus (T2DM). We explored, based on a large real-world database, patient and disease characteristics and actual treatment patterns by age. Methods: The analysis was based on the DIVE and DPV registries of patients with T2DM. Patients were analyzed by age groups 50–59 (middle-young), 60–69 (young-old), 70–79 (middle-old), 80–89 (old), and 90 years or more (oldest-old). Results: A total of 396,719 patients were analyzed, of which 17.7% were 50–59 years, 27.7% 60–69 years, 34.3% 70–79 years, 18.3% 80–89 years and 2.0% at least 90 years. We found that (a) T2DM in old and oldest-old patients was characterized much less by the presence of metabolic risk factors such as hypertension, obesity, dyslipidemia and smoking than in younger patients; (b) the HbA1c was much lower in oldest-old than in middle-young patients (7.2 ± 1.6% versus 8.0 ± 2.2%; p < 0.001), but it was associated with higher proportions of patients with severe hypoglycemia (7.0 versus 1.6%; p < 0.001); (c) this was potentially associated with the higher and increasing rates of insulin use in older patients (from 17.6% to 37.6%, p < 0.001) and the particular comorbidity profile of these patients, for example, chronic kidney disease (CKD); (d) patients with late diabetes onset had lower HbA1c values, lower bodyweight and less cardiovascular risk factors; (e) patients with a longer diabetes duration had a considerable increase in macrovascular and even more microvascular complications. Conclusion: In very old patients there is a need for frequent careful routine assessment and a tailored pharmacotherapy in which patient safety is much more important than blood-glucose-lowering efficacy.
HRI depletion cooperates with pharmacologic inducers to elevate fetal hemoglobin and reduce sickle cell formation
Authors: Peslak Scott A. , Khandros Eugene , Huang Peng , Lan Xianjiang , Geronimo Carly L. , Grevet Jeremy D. , Abdulmalik Osheiza , Zhang Zhe , Giardine Belinda M. , Keller Cheryl A. , Shi Junwei , Hardison Ross C. , Blobel Gerd A. 
Published: September 2020

Abstract
Increasing fetal hemoglobin (HbF) provides clinical benefit in patients with sickle cell disease (SCD). We recently identified heme-regulated inhibitor (HRI, EIF2AK1), as a novel HbF regulator. Because HRI is an erythroid-specific protein kinase, it presents a potential target for pharmacologic intervention. We found that maximal HbF induction required &gt;80% to 85% HRI depletion. Because it remains unclear whether this degree of HRI inhibition can be achieved pharmacologically, we explored whether HRI knockdown can be combined with pharmacologic HbF inducers to achieve greater HbF production and minimize potential adverse effects associated with treatments. Strongly cooperative HbF induction was observed when HRI depletion was combined with exposure to pomalidomide or the EHMT1/2 inhibitor UNC0638, but not to hydroxyurea. Mechanistically, reduction in the levels of the HbF repressor BCL11A reflected the cooperativity of HRI loss and pomalidomide treatment, whereas UNC0638 did not modulate BCL11A levels. In conjunction with HRI loss, pomalidomide maintained its HbF-inducing activity at 10-fold lower concentrations, in which condition there were minimal observed detrimental effects on erythroid cell maturation and viability, as well as fewer alterations in the erythroid transcriptome. When tested in cells from patients with SCD, combining HRI depletion with pomalidomide or UNC0638 achieved up to 50% to 60% HbF and 45% to 50% HbF, respectively, as measured by high-performance liquid chromatography, and markedly counteracted cell sickling. In summary, this study provides a foundation for the exploration of combining future small-molecule HRI inhibitors with additional pharmacologic HbF inducers to maximize HbF production and preserve erythroid cell functionality for the treatment of SCD and other hemoglobinopathies.
Distributional effects of carbon taxation in passenger transport with lump-sum offset: low income households, retirees and families would benefit in Germany
Authors: Eisenmann Christine , Steck Felix , Hedemann Lars , Lenz Barbara , Koller Florian 
Published: September 2020

Abstract
Background
The introduction of a carbon tax on passenger transport is currently being discussed in Germany. Various stakeholders favour a consumption-based, revenue-neutral carbon tax with a uniform lump-sum offset for private households and a tax rate of 40 € per ton of CO2.

Objective
In this study, we examine the distributional effects of carbon taxation for the German passenger transport sector under the assumption of the proposed tax model. We discuss as to what extent which socioeconomic groups would be burdened and who might even benefit from carbon taxation. To answer these questions we use a uniquely modelled data set that encompasses all forms of passenger transport (i.e. in Germany and abroad) of the German resident population over 1 year. The national household travel survey Mobility in Germany 2017 is the basis of the microscopic data set. We derive annual CO2 emissions and carbon tax burdens for various population groups using the data on passenger transport, as well as specific emission factors.

Results
Results show that low income households, retirees, single parents and family households with two or more children would benefit from the proposed carbon taxation scheme due to below-average emissions per person; in contrast, working age households without children and car owners with heavy car use would be burdened. Our results are of particular relevance to transport researchers, transport politicians and decision makers as a basis for designing, developing and introducing a carbon taxation scheme.
PacBio genome sequencing reveals new insights into the genomic organisation of the multi-copy ToxB gene of the wheat fungal pathogen Pyrenophora tritici-repentis
Authors: Moolhuijzen Paula , See Pao Theen , Moffat Caroline S. 
Published: September 2020

Abstract
Background
Necrotrophic effector proteins secreted by fungal pathogens are important virulence factors that mediate the development of disease in wheat. Pyrenophora tritici-repentis (Ptr), the causal agent of wheat tan spot, has a race structure dependent on the combination of effectors. In Ptr, ToxA and ToxB are known proteinaceous effectors responsible for necrosis and chlorosis respectively. While Ptr ToxA is encoded by the single gene ToxA, ToxB has multiple loci in the Ptr genome, which is postulated to be directly related to the level of ToxB production and leaf chlorosis. Although previous analysis has indicated that the majority of the ToxB loci lie on a single chromosome, the exact number and chromosomal locations for all the ToxB loci have not been fully identified.

Results
In this study, we have sequenced the genome of a race 5 ToxB-producing isolate (DW5), using PacBio long read technology, and found that ToxB duplications are nested in the complex subtelomeric chromosomal regions. A total of ten identical ToxB gene copies were identified and based on flanking sequence identity, nine loci appeared associated with chromosome 11 and a single copy with chromosome 5. Chromosome 11 multiple ToxB gene loci were separated by large sequence regions between 31 and 66 kb within larger segmental duplications in an alternating pattern related to loci strand, and flanked by transposable elements.

Conclusion
This work provides for the first time the full accompaniment of ToxB loci and surrounding regions, and identifies the organization and distribution of ten ToxB loci to subtelomeric regions. To our knowledge, this is the first report of an interwoven strand-related duplication pattern event. This study further highlights the importance of resolving the highly complex distal chromosomal regions, that remain difficult to assemble, and can harbour important effectors and virulence factors.
Development of EST-SSR markers and association mapping with floral traits in Syringa oblata
Authors: Yang Yunyao , He Ruiqing , Zheng Jian , Hu Zenghui , Wu Jing , Leng Pingsheng 
Published: September 2020

AbstractBackgroundLilac (Syringa oblata) is an important woody plant with high ornamental value. However, very limited genetic marker resources are currently available, and little is known about the genetic architecture of important ornamental traits forS. oblata, which is hindering its genetic studies. Therefore, it is of great significance to develop effective molecular markers and understand the genetic architecture of complex floral traits for the genetic research ofS. oblata.ResultsIn this study, a total of 10,988 SSRs were obtained from 9864 unigene sequences with an average of one SSR per 8.13 kb, of which di-nucleotide repeats were the dominant type (32.86%, 3611). A set of 2042 primer pairs were validated, out of which 932 (45.7%) exhibited successful amplifications, and 248 (12.1%) were polymorphic in eightS. oblataindividuals. In addition, 30 polymorphic EST-SSR markers were further used to assess the genetic diversity and the population structure of 192 cultivatedS. oblataindividuals. Two hundred thirty-four alleles were detected, and the PIC values ranged from 0.23 to 0.88 with an average of 0.51, indicating a high level of genetic diversity within this cultivated population. The analysis of population structure showed two major subgroups in the association population. Finally, 20 significant associations were identified involving 17 markers with nine floral traits using the mixed linear model. Moreover, marker SO104, SO695 and SO790 had significant relationship with more than one trait.ConclusionThe results showed newly developed markers were valuable resource and provided powerful tools for genetic breeding of lilac. Beyond that, our study could serve an efficient foundation for further facilitate genetic improvement of floral traits for lilac.