bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diversity of stem rust resistance in modern Siberian bread wheat (Triticum aestivum) germplasm
Authors: Kelbin Vasiliy N. , Skolotneva Ekaterina S. , Shamanin Vladimir P. , Salina Elena A. 
Published: January 2022

AbstractStem rust disease caused by the obligate biotrophic fungus Puccinia graminis f. sp. tritici significantly reduces the yield and quality of wheat grain. A total of 92 entries of new Siberian agricultural wheat germplasm were studied with an integrated approach: phenotyping in the field and seedling stage reactions and using molecular markers to identify stem rust resistance genes. Among the tested germplasm, 38% were highly or moderately sensitive to stem rust, and 56% were resistant or moderately resistant. In total, 10 out of 16 molecular markers were positive in 92 entries of the new Siberian germplasm: specific or major genes Sr15, Sr22, Sr23, Sr24, Sr25, Sr31, Sr38 and Sr44 and nonspecific or minor genes Sr2 and Sr57, singly or combined. The Sr31 + Sr44, Sr31 + Sr24 and Sr31 + Sr25 gene pyramids provided effective resistance to natural infection. Since a substantial number of gene pyramids with various degrees of genetic resistance were identified, this wheat germplasm could be useful to pursue a strategy of durable resistance to stem rust in Western Siberia.
Anemic Women are More at Risk of Injectable Contraceptive Discontinuation due to Side Effects in Ethiopia
Authors: Stevens Rose , Malbos Blandine , Gurmu Eshetu , Riou Jérémie , Alvergne Alexandra 
Published: January 2022

AbstractThis paper investigates the importance of women's physiological condition, alongside sociocultural factors, for predicting the risk of discontinuation of the injectable contraceptive due to side effects in Ethiopia. Contraceptive calendar data from the 2016 Ethiopian Demographic and Health Survey were analyzed. Women aged 15–49 who had initiated the injectable contraceptive in the last two years were included in the analysis (n = 1,513). Physiological factors investigated were body mass, iron status, reproductive depletion, and physical strain. After checking for reverse causality, associations between physiological and sociocultural risk factors and discontinuation due to side effects (DSE) or discontinuation due to other reasons (DOR) were estimated using multivariate Cox proportional regression analyses. Anemia status was associated with DSE, but not DOR. Anemic women were two times more at risk of DSE compared with nonanemic women (adjusted hazard ratios [aHR] = 2.38, confidence interval [CI] = 1.41–4.00). DOR was predicted by religion, wealth, and relationship status. Accounting for diversity in physiological condition is key for understanding contraceptive discontinuation due to side effects. To reduce side effects, family planning programs might benefit from providing hormonal contraception within an integrated package addressing anemia.
Alternative splicing of an exitron determines the subnuclear localization of the Arabidopsis DNA glycosylase MBD4L under heat stress
Authors: Cecchini Nicolás Miguel , Torres José Roberto , López Ignacio Lescano , Cobo Santiago , Nota Florencia , Alvarez María Elena 
Published: January 2022

SUMMARYDNA glycosylases are critical enzymes that recognize small base lesions in DNA and trigger their repair to preserve genome integrity. The Arabidopsis MBD4‐like (MBD4L) DNA glycosylase improves tolerance to genotoxic stress. This enzyme is encoded by a single gene carrying an exonic intron (exitron) at its 5′ region. Although alternative splicing (AS) of exitrons (protein‐coding cryptic introns within exons) is suspected to increase protein diversity, phenotypes associated to exitron removal or retention are only known for a few genes. Here, we show that AS of the MBD4L exitron determines the generation of two enzyme isoforms with different subnuclear localization. Both isoforms conserve the catalytic domain but are directed to either the nucleoplasm or the nucleolus. Interestingly, heat stress regulates the AS of the MBD4L exitron and increases the relative abundance of the nucleolar variant. This process depends on the splicing factors NTR1 and RS31. Next, we generated transgenic plants expressing a mutated MBD4L‐GFP gene version that abolished exitron splicing and found that nucleolar protein targeting was impaired in these plants. Our findings suggest that AS of the MBD4L exitron can function as a mechanism to drive the enzyme to the nucleolus during heat stress. Several DNA repair enzymes reach the nucleolus under particular conditions although AS of exitrons has not been so far associated with this process. To our knowledge, this is the first example of an exitron mediating enzyme localization in eukaryotes.
Morphing of Reversible Axial Fan Blade: A FSI-FEM Study
Authors: Barnabei Valerio F. , Castorrini Alessio , Corsini Alessandro , Rispoli Franco 
Published: January 2022

Abstract
Reversible axial fans are widely used in industrial and tunnel ventilation systems, and a lot of research effort is spent in the design process of the blades shape and blades profile. The target is to achieve reasonable performances in both flow directions, but those are still below the levels of the corresponding nonreversible geometries. In this article, an alternative design solution for reversible axial fan is presented by adopting flexible blades instead of the rigid ones. Such design, inspired by the boat sails, could allow the blade to change its shape by passively adapting to the flow field, from a symmetrical blade profile to a not symmetric one, and thus adapting the curvature to the flow condition. In this article, a series of alternative materials and material distributions are analyzed and compared. The analysis is conducted by performing fluid–structure interaction simulations using stabilized finite elements formulations for both the fluid and the structure dynamics. Simulations are performed using the in-house built software fempar, which implements the Residual Based Variational MultiScale to model the Navier–Stokes equation, the total Lagrangian formulation for the nonlinear elastic solid, and the solid extension moving mesh technique to move the fluid mesh.
lncRNA ROR and miR-125b Predict the Prognosis in Heart Failure Combined Acute Renal Failure
Authors: Xue Qianlong , Yang Lipeng , Wang Jia , Li Linlin , Wang Hui , He Ying 
Published: January 2022

Objective. To elucidate the correlation between expression levels of long noncoding RNA (lncRNA) ROR and microRNA-125b (miR-125b) with the prognosis in heart failure (HF) patients combined acute renal failure (ARF). Methods. HF patients combined ARF (

n
=
90

) and healthy controls (

n
=
90

) in the same period were included in our hospital from April 2016 to December 2018. Every subject was followed up for 24 months. Serum levels of lncRNA ROR and miR-125b were detected, and their expression correlation was analyzed by Pearson correlation test. Receiver operating characteristic (ROC) curves were depicted for assessing the sensitivity and specificity of lncRNA ROR and miR-125b in diagnosing HF combined ARF. Results. lncRNA ROR was upregulated in serum of HF patients combined ARF, and its level was positively correlated to NYHA classification. miR-125b displayed an opposite trend. In serum samples of HF combined ARF, expression level of lncRNA ROR was negatively related to that of miR-125b. Diagnostic potentials of lncRNA ROR and miR-125b in HF combined ARF were confirmed by ROC curve analyses (lncRNA ROR:

AUC
=
0.9199

,

cutoff

value
=
5.595

,

sensitivity
=
92.22
%

, and

specificity
=
73.33
%

; miR-125b:

AUC
=
0.8509

,

cutoff

value
=
2.290

,

sensitivity
=
81.11
%

, and

specificity
=
74.44
%

). After 2-year follow-up, 16 cases were dead. Higher incidences of death and rehospitalization were observed in HF combined ARF cases expressing higher serum level of lncRNA ROR or lower level of miR-125b. Conclusions. Serum level of lncRNA ROR is upregulated, and miR-125b is downregulated in HF patients combined ARF. Their levels are linked to NYHA classification, which can be utilized as prognostic biomarkers in HF combined ARF.
Comparison of Approaches for Measuring Adherence and Persistence to Oral Oncologic Therapies in Patients Diagnosed with Metastatic Renal Cell Carcinoma
Authors: Chun Danielle S. , Hicks Blánaid , Hinton Sharon Peacock , Funk Michele Jonsson , Gooden Kyna , Keil Alexander P. , Tan Hung-Jui , Stürmer Til , Lund Jennifer L. 
Published: January 2022

AbstractBackground:Adherence and persistence studies face several methodologic difficulties, including short-term mortality. We compared approaches to quantify adherence and persistence to first line (1L) oral targeted therapy (TT) in patients diagnosed with metastatic renal cell carcinoma (mRCC).Methods:Patients with mRCC ages 66 years or more who initiated TTs within 4 months of diagnosis were identified in the Surveillance, Epidemiology, and End Results Medicare-linked database (2007–2015). Adherence [proportion of days covered (PDC) &gt;80%] was calculated using (i) PDC with a fixed 6-month denominator including then excluding patients who died within the 6 months and (ii) PDC with a denominator measuring time on treatment. Risk of nonpersistence was obtained by censoring death or treating death as a competing risk using cumulative incidence functions.Results:Among 485 patients with mRCC initiating a 1L oral TT (sunitinib, 64%; pazopanib, 25%; other, 11%), 40% died within 6 months. Adherence was higher after restricting to patients who survived (60%) compared with including those patients and assigning zero days covered after death (47%). Risk of nonpersistence was higher when censoring patients at death, 0.91 [95% confidence interval (CI), 0.88–0.94], compared with treating death as a competing risk, 0.75 (95% CI, 0.71–0.79).Conclusions:Different approaches to handling death resulted in different adherence and persistence estimates in the metastatic setting. Future studies should explicitly report the proportion of patient deaths over time and explore appropriate methods to account for death as competing risk.Impact:Use of several approaches can provide a more comprehensive picture of medication-taking behavior in the metastatic setting where death is a major competing risk.
Oncotype DX Risk Recurrence Score and Total Mortality for Early-Stage Breast Cancer by Race/Ethnicity
Authors: Moore Jaleesa , Wang Fei , Pal Tuya , Reid Sonya , Cai Hui , Bailey Christina E. , Zheng Wei , Lipworth Loren , Shu Xiao-Ou 
Published: January 2022

Abstract

Background:
Oncotype DX recurrence score (ODX RS) is a prognostic biomarker for early-stage, node-negative, estrogen receptor–positive (ER+) breast cancer. Whether test uptake, associated factors, and the test's prognostic values differ by race/ethnicity is unknown.

Methods:
From the National Cancer Database, 2010–2014, we identified 227,259 early-stage ER+, node-negative breast cancer cases. Logistic regression was used to examine ODX RS uptake and associated factors among non-Hispanic White (White), non-Hispanic Black (Black), Hispanic, and Asian American patients. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for overall mortality with ODX RS by race/ethnicity.

Results:
White patients were more likely to receive an ODX RS test compared with Black, Hispanic, and Asian American patients (36.7%, 32.8%, 31.6%, and 35.5%, respectively; P &lt; 0.001). Disparities persisted after adjustments for demographics, clinical characteristics, and access-to-care, with rate ratios of 0.87 (95% CI, 0.85–0.88), 0.82 (95% CI, 0.80–0.85), and 0.89 (95% CI, 0.87–0.92), respectively, for Black, Hispanic, and Asian American compared with White patients. Black patients had higher proportions of high-risk scores (≥26) compared with White, Hispanic, and Asian American patients (19.1%, 14.0%, 14.2%, and 15.6%, respectively; P &lt; 0.0001). ODX RS was predictive for total mortality across all races/ethnicities, particularly younger patients (&lt;50). No significant race/ethnicity interactions were observed.

Conclusions:
Although ODX RS uptake and risk distribution varied by race/ethnicity, ODX RS was prognostic for mortality across groups.

Impact:
These findings emphasize the importance of developing strategies to increase ODX RS uptake among racial/ethnic minorities and call for more investigations on potential racial/ethnic differences in breast cancer biology.
See related commentary by Wang et al., p. 704
Assessing the Coverage of US Cancer Center Primary Catchment Areas
Authors: Leader Amy E. , McNair Christopher , Yurick Christina , Huesser Matthew , Schade Elizabeth , Stimmel Emily E. , Lerman Caryn , Knudsen Karen E. 
Published: January 2022

Abstract

Background:
Cancer centers are expected to engage communities and reduce the burden of cancer in their catchment areas. However, the extent to which cancer centers adequately reach the entire US population is unknown.

Methods:
We surveyed all members of the Association of American Cancer Institutes (N = 102 cancer centers) to document and map each cancer center's primary catchment area. Catchment area descriptions were aggregated to the county level. Catchment area coverage scores were calculated for each county and choropleths generated representing coverage across the US. Similar analyses were used to overlay US population density, cancer incidence, and cancer-related mortality compared with each county's cancer center catchment area coverage.

Results:
Roughly 85% of US counties were included in at least one cancer center's primary catchment area. However, 15% of US counties, or roughly 25 million Americans, do not reside in a catchment area. When catchment area coverage was integrated with population density, cancer incidence, and cancer-related mortality metrics, geographical trends in both over- and undercoverage were apparent.

Conclusions:
Geographic gaps in cancer center catchment area coverage exist and may be propagating cancer disparities. Efforts to ensure coverage to all Americans should be a priority of cancer center leadership.

Impact:
This is the first known geographic analysis and interpretation of the primary catchment areas of all US-based cancer centers and identifies key geographic gaps important to target for disparities reduction.
See related commentary by Lieberman-Cribbin and Taioli, p. 949
Impact of F
LT3 Mutation on Outcomes after Venetoclax and Azacitidine for Patients with Treatment-Naïve Acute Myeloid Leukemia
Authors: Konopleva Marina , Thirman Michael J. , Pratz Keith W. , Garcia Jacqueline S. , Recher Christian , Pullarkat Vinod , Kantarjian Hagop M. , DiNardo Courtney D. , Dail Monique , Duan Yinghui , Chyla Brenda , Potluri Jalaja , Miller Catherine L. , Wei Andrew H. 
Published: January 2022

Abstract

Purpose:
To evaluate efficacy and safety of venetoclax + azacitidine among treatment-naïve patients with FLT3-mutant acute myeloid leukemia.

Patients and Methods:
Data were pooled from patients enrolled in a phase III study (NCT02993523) that compared patients treated with venetoclax + azacitidine or placebo + azacitidine and a prior phase Ib study (NCT02203773) where patients were treated with venetoclax + azacitidine. Enrolled patients were ineligible for intensive therapy due to age ≥75 years and/or comorbidities. Patients on venetoclax + azacitidine received venetoclax 400 mg orally (days 1–28) and azacitidine (75 mg/m2; days 1–7/28-day cycle). FLT3 mutation was analyzed centrally on pretreatment bone marrow aspirates.

Results:
In the biomarker evaluable population, FLT3 mutation was detected in 42 (15%) and 22 (19%) patients in the venetoclax + azacitidine and azacitidine groups. Composite complete remission [CRc; complete remission (CR) + CR with incomplete hematologic recovery (CRi)] rates (venetoclax + azacitidine/azacitidine) for FLT3-mutant patients were 67%/36%, median duration of remission (DoR) was 17.3/5.0 months, and median OS was 12.5/8.6 months. The CRc rates among FLT3 wild-type patients were 67%/25%, median DoR 18.4/13.4 months, and median OS 14.7/10.1 months. In patients treated with venetoclax + azacitidine, CRc in patients with FLT3-ITD and FLT3-TKD was 63% and 77% and median OS was 9.9 and 19.2 months, and in comutated FLT3-ITD + NPM1 patients, CRc was 70%, median DoR was not reached, and median OS was 9.1 months. There were no unexpected toxicities in the venetoclax + azacitidine group.

Conclusions:
When treated with venetoclax + azacitidine, patients with FLT3 mutations and FLT3 wild-type had similar outcomes. Future analyses in larger patient populations may further define the impact of venetoclax + azacitidine in patients harboring FLT3-ITD.
See related commentary by Perl and Vyas, p. 2719
Identity Frame as the Anchor of Interstate Conflicts: The Case of the United States–North Korea Denuclearization Negotiation
Authors: Park Doyoun , Seo Yongseok 
Published: January 2022

Abstract
This study examines the fundamental causes of intractable conflict and deadlocked negotiation by centering on identity. The cognitive variables of identity are derived, and the causal layered analysis framework is used to analyze the influencing mechanism among cognitive layers. This research assumes that conflicts are influenced by interactions among key variables of the identity frame in the cognitive layer: “ingroup definition,” “outgroup definition,” and “conflict narrative.” The United States–North Korea denuclearization negotiation case is examined using this framework, seeking to understand how these factors influenced the conflict, policy initiatives and negotiations.
A potential implication of UDP-glucuronosyltransferase 2B10 in the detoxification of drugs used in pediatric hematopoietic stem cell transplantation setting: an in silico investigation
Authors: Robin Shannon , Hassine Khalil Ben , Muthukumaran Jayaraman , Jurkovic Mlakar Simona , Krajinovic Maja , Nava Tiago , Uppugunduri Chakradhara Rao S. , Ansari Marc 
Published: January 2022

Abstract
Background
Sinusoidal occlusion syndrome (SOS) is a potentially severe complication following hematopoietic stem cell transplantation (HSCT) in pediatric patients. Treatment related risk factors such as intensity of conditioning, hepatotoxic co-medication and patient related factors such as genetic variants predispose individuals to develop SOS. The variant allele for SNP rs17146905 in UDP-glucuronosyl transferase 2B10 (UGT2B10) gene was correlated with the occurrence of SOS in an exome-wide association study. UGT2B10 is a phase II drug metabolizing enzyme involved in the N-glucuronidation of tertiary amine containing drugs.

Methods
To shed light on the functionality of UGT2B10 enzyme in the metabolism of drugs used in pediatric HSCT setting, we performed in silico screening against custom based library of putative ligands. First, a list of potential substrates for in silico analysis was prepared using a systematic consensus-based strategy. The list comprised of drugs and their metabolites used in pediatric HSCT setting. The three-dimensional structure of UGT2B10 was not available from the Research Collaboratory Structural Bioinformatics - Protein Data Bank (RCSB - PDB) repository and thus we predicted the first human UGT2B10 3D model by using multiple template homology modeling with MODELLER Version 9.2 and molecular docking calculations with AutoDock Vina Version 1.2 were implemented to quantify the estimated binding affinity between selected putative substrates or ligands and UGT2B10. Finally, we performed molecular dynamics simulations using GROMACS Version 5.1.4 to confirm the potential UGT2B10 ligands prioritized after molecular docking (exhibiting negative free binding energy).

Results
Four potential ligands for UGT2B10 namely acetaminophen, lorazepam, mycophenolic acid and voriconazole n-oxide intermediate were identified. Other metabolites of voriconazole satisfied the criteria of being possible ligands of UGT2B10. Except for bilirubin and 4-Hydroxy Voriconazole, all the ligands (particularly voriconazole and hydroxy voriconazole) are oriented in substrate binding site close to the co-factor UDP (mean ± SD; 0.72 ± 0.33 nm). Further in vitro screening of the putative ligands prioritized by in silico pipeline is warranted to understand the nature of the ligands either as inhibitors or substrates of UGT2B10.

Conclusions
These results may indicate the clinical and pharmacological relevance UGT2B10 in pediatric HSCT setting. With this systematic computational methodology, we provide a rational-, time-, and cost-effective way to identify and prioritize the interesting putative substrates or inhibitors of UGT2B10 for further testing in in vitro experiments.
Gene expression profiles in Malpighian tubules of the vector leafhopper Psammotettix striatus (L.) revealed regional functional diversity and heterogeneity
Authors: Yuan Feimin , Wei Cong 
Published: January 2022

AbstractBackgroundMany leafhoppers are known as pests and disease vectors of economically important plants. Previous studies of the physiological functions of vector leafhoppers have mainly focused on the salivary glands and the alimentary tract that are deemed to be associated with digestion, host defense and phytoplasma and/or virus transmission. By contrast, the significance of Malpighian tubules (MTs) is less studied. To clarify the physiological function of MTs of the vector leafhopperPsammotettix striatusthat transmits phytoplasma triggering the wheat blue dwarf disease, we performed a transcriptome study onP. striatusMTs and compared gene expression profiles among different anatomical regions in the tubules (i.e., MT1+2, the anterior segment together with the sub-anterior segment; MT3, the inflated segment; and MT4, the distal segment).ResultsTranscriptome ofP. striatusMTs generate a total of 42,815 high-quality unigenes, among which highly expressed unigenes are mainly involved in organic solute transport, detoxification and immunity in addition to osmoregulation. Region-specific comparative analyses reveal that all these MT regions have functions in osmoregulation, organic solute transport and detoxification, but each region targets different substrates. Differential expression and regional enrichment of immunity-related effector activities and molecules involved in phagocytosis and the biosynthesis of antimicrobial peptides among different regions indicate that MT1+2 and MT4 have the ability to eliminate the invading pathogens. However, in MT3 which secrets brochosomes to the integument and eggs as physical barriers, disulfide-isomerase, acidic ribosomal protein P and many other unigenes were highly expressed, which can be attractive candidate genes for future studies of the biosynthesis and the origin of brochosomes.ConclusionsPsammotettix striatusMTs perform multiple physiological functions as versatile organs than just excretory organs with osmoregulatory function. Heterogeneity of physiological functions among different MT regions is related to organic solute transport, detoxification, immunity and brochosome biosynthesis in addition to osmoregulation, and each region targets different substrates. These functions may be helpful forP. striatusto resist pathogens from habitats and to utilize a wider range of host plants, which may assist the transmission and spread of phytoplasmas. The results provide potential molecular targets for the exploit of chemical and/or gene-silencing insecticides.