bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lithium isotopic composition of soil pore water: Responses to evapotranspiration
Authors: Xu Zhewen , Li Tao , Li Gaojun , Hedding David W. , Wang Yunqiang , Gou Long-Fei , Zhao Liang , Chen Jun 
Published: November 2021

Abstract
Lithium isotopes show great potential to trace Earth surface processes due to the large mass discrimination between 6Li and 7Li associated with clay uptake. However, factors controlling the Li isotopic composition (δ7Li) of river water, especially those with a water-bedrock δ7Li difference higher than that of the equilibrium fractionation associated with clay formation (ΔW-C), have not yet been fully resolved. Traditional interpretation involves the Rayleigh distillation, but it unrealistically separates the stage of clay formation from that of silicate dissolution using fractionation factors that are much lower than laboratories can constrain. We propose an in situ mechanism that simulates high δ7Li by evapotranspiration. A model with coupled mineral dissolution and clay precipitation shows that evaporative enrichment of pore-water Li progressively increases the incorporation of Li into clays with light δ7Li, resulting in higher δ7Li values in the residual water than ΔW-C. We also provide evidence from the Chinese Loess Plateau, where an evaporative effect readily explains the observed δ7Li. The influence of evapotranspiration on riverine δ7Li implies that changes in aridity may partly explain the variations of seawater δ7Li. The same principle may also apply to other stable isotopic systems whereby incorporation into secondary precipitates controls the isotopic fractionation.
Giant meandering channel evolution, Campos deep-water salt basin, Brazil
Authors: Covault Jacob A. , Sylvester Zoltán , Ceyhan Can , Dunlap Dallas B. 
Published: November 2021

AbstractSubmarine channels are conduits for sediment delivery to continental margins, and channel deposits can be sandy components of the fill in tectonically active salt basins. Examples of salt-withdrawal basin fill commonly show successions of sandy channelized or sheet-like systems alternating with more mud-rich mass-transport complexes and hemipelagites. This alternation of depositional styles is controlled by subsidence and sediment-supply histories. Salt-basin fill comprising successions of largely uninterrupted meandering-channel deposition are less commonly recognized. This begs the questions: can sediment supply be large enough to overwhelm basin subsidence and result in a thick succession of channel deposits, and, if so, how would such a channel system evolve? Here, we use three-dimensional seismic-reflection data from a &gt;1500 km2 region with salt-influenced topography in the Campos Basin, offshore Brazil, to evaluate the influence of salt diapirs on an Upper Cretaceous–Paleogene giant meandering submarine-channel system (channel elements &gt;1 km wide; meander wavelengths several kilometers to &gt;10 km). The large scale of the channels in the Campos Basin suggests that sediment discharge was large enough to sustain the meandering channel system in spite of large variability in subsidence across the region. We interpreted 22 channel centerlines to reconstruct the detailed kinematic evolution of this depositional system; this level of detail is akin to that of recent studies of meandering fluvial channels in time-lapse Landsat satellite images. The oldest channel elements are farther from salt diapirs than many of the younger ones; the centerlines of the older channel elements exhibit a correlation between curvature and migration rate, and a spatial delay between locations of peak curvature and maximum migration distance, similar to that observed in rivers. As many of the younger channel centerlines expanded toward nearby salt diapirs, their migration pattern switched to downstream translation as a result of partial confinement. Channel segments that docked against salt diapirs became less mobile, and, as a result, they do not show a correlation between curvature and migration rate. The channel migration pattern in the Campos Basin is different compared to that of a tectonically quiescent continental rise where meander evolution is unobstructed. This style of channelized basin filling is different from that of many existing examples of salt-withdrawal minibasins that are dominated by overall less-channelized deposits. This difference might be a result of the delivery of voluminous coarse sediment and high discharge of channel-forming turbidity currents to the Campos Basin from rivers draining actively uplifting coastal mountains of southeastern Brazil. Detailed kinematic analysis of such well-preserved channels can be used to reconstruct the impact of structural deformation on basin fill.
Double exotic state productions in pion and kaon induced reactions
Authors: Liu Jing , Chen Dian-Yong , He Jun 
Published: November 2021

AbstractIn the present work, we investigate the pion/kaon induced $$P_c/P_{cs}$$

P
c

/

P

cs

productions with $$Z_c$$

Z
c

state off proton target with an effective Lagrangian approach. Our estimations indicate that the cross sections depend on the model parameters and beam energies, in particular, the cross sections for $$\pi p \rightarrow Z_c(3900) P_c(4312)$$

π
p
→

Z
c

(
3900
)

P
c

(
4312
)

and $$\pi p \rightarrow Z_c(3900) P_c(4440)$$

π
p
→

Z
c

(
3900
)

P
c

(
4440
)

are similar and can reach up to 10 nb, while those for $$\pi p \rightarrow Z_c(3900) P_c(4457)$$

π
p
→

Z
c

(
3900
)

P
c

(
4457
)

can be 30 nb. As for $$Kp \rightarrow Z_{cs}(3985)P_c$$

K
p
→

Z

cs

(
3985
)

P
c

, the cross sections are about 2.5 times smaller than those for $$\pi p \rightarrow Z_c(3900) P_c$$

π
p
→

Z
c

(
3900
)

P
c

. The discussed processes in the present work, especially $$\pi p \rightarrow Z_c(3900) P_c(4457)$$

π
p
→

Z
c

(
3900
)

P
c

(
4457
)

process, may be accessible by the high-energy pion and kaon beams in the facilities of J-PARC and COMPASS.
Evaluating the Impact of Social and Built Environments on Health-Related Quality of Life among Cancer Survivors
Authors: Chu Janet N. , Canchola Alison J. , Keegan Theresa H.M. , Nickell Alyssa , Oakley-Girvan Ingrid , Hamilton Ann S. , Yu Rosa L. , Gomez Scarlett Lin , Shariff-Marco Salma 
Published: November 2021

Abstract

Background:
With almost 17 million U.S. cancer survivors, understanding multilevel factors impacting health-related quality of life (HRQOL) is critical to improving survivorship outcomes. Few studies have evaluated neighborhood impact on HRQOL among cancer survivors.

Methods:
We combined sociodemographic, clinical, and behavioral data from three registry-based studies in California. Using a three-level mixed linear regression model (participants nested within block groups and study/regions), we examined associations of both independent neighborhood attributes and neighborhood archetypes, which capture interactions inherent among neighborhood attributes, with two HRQOL outcomes, physical (PCS) and mental (MCS) composite scores.

Results:
For the 2,477 survivors, 46% were 70+ years, 52% were non-Hispanic White, and 53% had localized disease. In models minimally adjusted for age, stage, and cancer recurrence, HRQOL was associated with neighborhood socioeconomic status (nSES), racial/ethnic composition, population density, street connectivity, restaurant environment index, traffic density, urbanicity, crowding, rental properties, and non–single family units. In fully adjusted models, higher nSES remained associated with better PCS, and restaurant environment index, specifically more unhealthy restaurants, associated with worse MCS. In multivariable-adjusted models of neighborhood archetype, compared with upper middle-class suburb, Hispanic small town and inner city had lower PCS, and high status had higher MCS.

Conclusions:
Among survivors, higher nSES was associated with better HRQOL; more unhealthy restaurants were associated with worse HQROL. As some neighborhood archetypes were associated with HRQOL, they provide an approach to capture how neighborhood attributes interact to impact HRQOL.

Impact:
Elucidating the pathways through which neighborhood attributes influence HRQOL is important in improving survivorship outcomes.
DNA Methylation Abnormalities and Altered Whole Transcriptome Profiles after Switching from Combustible Tobacco Smoking to Heated Tobacco Products
Authors: Ohmomo Hideki , Harada Sei , Komaki Shohei , Ono Kanako , Sutoh Yoichi , Otomo Ryo , Umekage So , Hachiya Tsuyoshi , Katanoda Kota , Takebayashi Toru , Shimizu Atsushi 
Published: November 2021

AbstractBackground:The use of heated tobacco products (HTP) has increased exponentially in Japan since 2016; however, their effects on health remain a major concern.Methods:Tsuruoka Metabolome Cohort Study participants (n = 11,002) were grouped on the basis of their smoking habits as never smokers (NS), past smokers (PS), combustible tobacco smokers (CS), and HTP users for &lt;2 years. Peripheral blood mononuclear cells were collected from 52 participants per group matched to HTP users using propensity scores, and DNA and RNA were purified from the samples. DNA methylation (DNAm) analysis of the 17 smoking-associated DNAm biomarker genes (such as AHRR, F2RL3, LRRN3, and GPR15), as well as whole transcriptome analysis, was performed.Results:Ten of the 17 genes were significantly hypomethylated in CS and HTP users compared with NS, among which AHRR, F2RL3, and RARA showed intermediate characteristics between CS and NS; nonetheless, AHRR expression was significantly higher in CS than in the other three groups. Conversely, LRRN3 and GPR15 were more hypomethylated in HTP users than in NS, and GPR15 expression was markedly upregulated in all the groups when compared with that in NS.Conclusions:HTP users (switched from CS &lt;2 years) display abnormal DNAm and transcriptome profiles, albeit to a lesser extent than the CS. However, because the molecular genetic effects of long-term HTP use are still unknown, long-term molecular epidemiologic studies are needed.Impact:This study provides new insights into the molecular genetic effects on DNAm and transcriptome profiles in HTP users who switched from CS.
Alcohol and Cancer: Existing Knowledge and Evidence Gaps across the Cancer Continuum
Authors: Gapstur Susan M. , Bandera Elisa V. , Jernigan David H. , LoConte Noelle K. , Southwell Brian G. , Vasiliou Vasilis , Brewster Abenaa M. , Naimi Timothy S. , Scherr Courtney L. , Shield Kevin D. 
Published: November 2021

Abstract
Alcoholic beverages are carcinogenic to humans. Globally, an estimated 4.1% of new cancer cases in 2020 were attributable to alcoholic beverages. However, the full cancer burden due to alcohol is uncertain because for many cancer (sub)types, associations remain inconclusive. Additionally, associations of consumption with therapeutic response, disease progression, and long-term cancer outcomes are not fully understood, public awareness of the alcohol–cancer link is low, and the interrelationships of alcohol control regulations and cancer risk are unclear. In December 2020, the U.S. NCI convened a workshop and public webinar that brought together a panel of scientific experts to review what is known about and identify knowledge gaps regarding alcohol and cancer. Examples of gaps identified include: (i) associations of alcohol consumption patterns across the life course with cancer risk; (ii) alcohol's systemic carcinogenic effects; (iii) alcohol's influence on treatment efficacy, patient-reported outcomes, and long-term prognosis; (iv) communication strategies to increase awareness of the alcohol–cancer link; and (v) the impact of alcohol control policies to reduce consumption on cancer incidence and mortality. Interdisciplinary research and implementation efforts are needed to increase relevant knowledge, and to develop effective interventions focused on improving awareness, and reducing harmful consumption to decrease the alcohol-related cancer burden.
Anti-apoptotic MCL1 Protein Represents Critical Survival Molecule for Most Burkitt Lymphomas and BCL2-negative Diffuse Large B-cell Lymphomas
Authors: Klanova Magdalena , Kazantsev Dmitry , Pokorna Eva , Zikmund Tomas , Karolova Jana , Behounek Matej , Renesova Nicol , Sovilj Dana , Kelemen Cristina D. , Helman Karel , Jaksa Radek , Havranek Ondrej , Andera Ladislav , Trneny Marek , Klener Pavel 
Published: November 2021

Abstract
The pro-survival MCL1 protein is overexpressed in many cancers, including B-cell non–Hodgkin lymphomas (B-NHL). S63845 is a highly specific inhibitor of MCL1. We analyzed mechanisms of sensitivity/resistance to S63845 in preclinical models of diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma. Annexin V-based cytotoxic assays, Western blot analysis, protein co-immunoprecipitation, and cell clones with manipulated expression of BCL2 family proteins were used to analyze mechanisms of sensitivity to S63845. Experimental in vivo therapy with S63845 and/or venetoclax was performed using patient-derived xenografts (PDX) of treatment-refractory B-NHL. A subset of DLBCL and majority of Burkitt lymphoma cell lines were sensitive to S63845. The level of BCL2 protein expression was the major determinant of resistance to S63845: BCL2 serves as a buffer for pro-apoptotic proteins released from MCL1 upon exposure to S63845. While BCL2-negative lymphomas were effectively eliminated by single-agent S63845, its combination with venetoclax was synthetically lethal in BCL2-positive PDX models. Concerning MCL1, both, the level of MCL1 protein expression, and its occupational status represent key factors mediating sensitivity to S63845. In contrast to MCL1-BIM/BAK1 complexes that prime lymphoma cells for S63845-mediated apoptosis, MCL1-NOXA complexes are associated with S63845 resistance. In conclusion, MCL1 represents a critical survival molecule for most Burkitt lymphomas and a subset of BCL2-negative DLBCLs. The level of BCL2 and MCL1 expression and occupational status of MCL1 belong to the key modulators of sensitivity/resistance to S63845. Co-treatment with venetoclax can overcome BCL2-mediated resistance to S63845, and enhance efficacy of MCL1 inhibitors in BCL2-positive aggressive B-NHL.
Targeting DNMTs to Overcome Enzalutamide Resistance in Prostate Cancer
Authors: Farah Elia , Zhang Zhuangzhuang , Utturkar Sagar M. , Liu Jinpeng , Ratliff Timothy L. , Liu Xiaoqi 
Published: November 2021

Abstract
Prostate cancer is the second leading cause of cancer death among men in the United States. The androgen receptor (AR) antagonist enzalutamide is an FDA-approved drug for treatment of patients with late-stage prostate cancer and is currently under clinical study for early-stage prostate cancer treatment. After a short positive response period to enzalutamide, tumors will develop drug resistance. In this study, we uncovered that DNA methylation was deregulated in enzalutamide-resistant cells. DNMT activity and DNMT3B expression were upregulated in resistant cell lines. Enzalutamide induced the expression of DNMT3A and DNMT3B in prostate cancer cells with a potential role of p53 and pRB in this process. The overexpression of DNMT3B3, a DNMT3B variant, promoted an enzalutamide-resistant phenotype in C4-2B cell lines. Inhibition of DNA methylation and DNMT3B knockdown induced a resensitization to enzalutamide. Decitabine treatment in enzalutamide-resistant cells induced a decrease of the expression of AR-V7 and changes of genes for apoptosis, DNA repair, and mRNA splicing. Combination treatment of decitabine and enzalutamide induced a decrease of tumor weight, Ki-67 and AR-V7 expression and an increase of cleaved-caspase3 levels in 22Rv1 xenografts. The collective results suggest that DNA methylation pathway is deregulated after enzalutamide resistance onset and that targeting DNA methyltransferases restores the sensitivity to enzalutamide in prostate cancer cells.
A Functional Precision Oncology Approach to Identify Treatment Strategies for Myxofibrosarcoma Patients
Authors: Pauli Chantal , De Boni Lamberto , Pauwels Jonathan E. , Chen Yanjiang , Planas-Paz Lara , Shaw Reid , Emerling Brooke M. , Grandori Carla , Hopkins Benjamin D. , Rubin Mark A. 
Published: November 2021

Abstract

In this era of precision medicine, numerous workflows for the targeting of high-recurrent mutations in common tumor types have been developed, leaving patients with rare diseases with few options. Here, we implement a functional precision oncology approach utilizing comprehensive genomic profiling in combination with high-throughput drug screening, to identify tumor-specific drug sensitivities for patients with rare tumor types such as myxofibrosarcoma. From a patient with a high-grade myxofibrosarcoma, who was enrolled in the Englander Institute for Precision Medicine (EIPM) program, we established patient-derived 3D sarco-spheres and xenograft models for functional testing. In the absence of a large cohort of clinically similar cases, high-throughput drug screening was performed on the patient-derived cells, and compared with two other myxofibrosarcoma lines and a benign fibroblast line to functionally identify tumor-specific drug sensitivities. The addition of functional drug sensitivity testing to complement genomic profiling identified multiple therapeutic options that were further validated in patient derived xenograft models. Genomic analyses detected the frequently known codeletion of the tumor suppressors CDKN2A/B together with the methylthioadenosine phosphorylase (MTAP) and a TP53 E286fs*50 mutation. High-throughput drug screening demonstrated tumor-specific sensitivity to compounds targeting the cell cycle. Based on genomic analysis and high-throughput drug screening, we show that targeting the cell cycle in these tumors is a powerful approach.

Implications:
This study demonstrates the potential of functional testing to aid clinical decision making for patients with rare or molecularly complex malignancies when combined with comprehensive genomic profiling.
PERK, Beyond an Unfolded Protein Response Sensor in Estrogen-Induced Apoptosis in Endocrine-Resistant Breast Cancer
Authors: Fan Ping , Jordan V. Craig 
Published: November 2021

Abstract
The discovery of 17β-estradiol (E2)–induced apoptosis has clinical relevance. Mechanistically, E2 over activates nuclear estrogen receptor α that results in stress responses. The unfolded protein response (UPR) is initiated by E2 in the endoplasmic reticulum after hours of treatment in endocrine-resistant breast cancer cells, thereby activating three UPR sensors—PRK-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1α (IRE1α), and activating transcription factor 6 (ATF6) with different functions. Specifically, PERK plays a critical role in induction of apoptosis whereas IRE1α and ATF6 are involved in the endoplasmic reticulum stress-associated degradation (ERAD) of PI3K/Akt/mTOR pathways. In addition to attenuating protein translation, PERK increases the DNA-binding activity of NF-κB and subsequent TNFα expression. In addition, PERK communicates with the mitochondria to regulate oxidative stress at mitochondria-associated endoplasmic reticulum membranes (MAM). Furthermore, PERK is a component enriched in MAMs that interacts with multifunctional MAM-tethering proteins and integrally modulates the exchange of metabolites such as lipids, reactive oxygen species (ROS), and Ca2+ at contact sites. MAMs are also critical sites for the initiation of autophagy to remove defective organelles and misfolded proteins through specific regulatory proteins. Thus, PERK conveys signals from nucleus to these membrane-structured organelles that form an interconnected network to regulate E2-induced apoptosis. Herein, we address the mechanistic progress on how PERK acts as a multifunctional molecule to commit E2 to inducing apoptosis in endocrine-resistant breast cancer.
ОСНОВНІ ТЕНДЕНЦІЇ І ПРОГНОЗНІ ОЦІНКИ СМЕРТНОСТІ ТА ЗАХВОРЮВАНОСТІ НА ОНКОГІНЕКОЛОГІЧНУ ПАТОЛОГІЮ У ЖІНОК РЕПРОДУКТИВНОГО ВІКУ В УКРАЇНІ Й ТЕРНОПІЛЬСЬКІЙ ОБЛАСТІ
Authors: Гандзюк Н. М. , Теренда Н. О. 
Published: November 2021

Мета: вивчити тенденцію захворюваності та смертності від злоякісних новоутворень жіночих репродуктивних органів до 2023 р.
Матеріали і методи. Проаналізовано дані Національного канцер-реєстру України за 2010–2020 рр. Використано бібліосемантичний, епідеміологічний, аналітичний методи дослідження.
Результати. У статті наведено дані щодо захворюваності та смертності від онкогінекологічних патологій репродуктивних органів – молочної залози, шийки матки та тіла матки за 2010–2020 рр. У результаті досліджень показано, що до 2023 р. в Україні може відбутися зростання захворюваності на рак жіночих репродуктивних органів, зокрема, на рак молочної залози з 60,3 до 69,4 на 100 тис. жіночого населення, рак тіла матки з 29,4 до 40,4 на 100 тис. жіночого населення і рак шийки матки з 16,2 до 20,1 на 100 тис. жіночого населення.
Смертність від раку молочної залози в Україні до 2023 р. в Україні може збільшитися на 17,5 % порівняно із 2020 р., у Тернопільській області – зменшитися на 7,7 % (25,4 на 100 тис. жіночого населення), що практично не зміниться порівняно з 2010 р. – 24,9 на 100 тис. жіночого населення. Смертність від раку тіла матки може зрости до 12,3 % в Україні та в Тернопільській області на 6,3 % відповідно, від раку шийки матки збільшитися на 14,7 % в Україні та зменшитися на 11,1 % в Тернопільській області.
Висновки. Серед жінок репродуктивного віку в Україні та в Тернопільській області до 2023 р. відслідковується тенденція до зростання захворюваності та смертності на рак молочної залози, рак тіла матки та рак шийки матки.
КОНЦЕПТУАЛЬНІ НАПРЯМИ ФОРМУВАННЯ УПРАВЛІННЯ РЕГІОНАЛЬНИМ МЕДИЧНИМ ЦЕНТРОМ НА ПРИНЦИПАХ ДЕРЖАВНО-ПРИВАТНОГО ПАРТНЕРСТВА
Authors: Іванюк А. В. 
Published: November 2021

Мета: обґрунтувати концептуальні напрями формування управління регіональним медичним центром на принципах державно-приватного партнерства.
Матеріали і методи. Для досягнення поставленої мети у роботі застосовували загальнонаукові методи аналізу, синтезу, узагальнення, інтерпретації наукових даних, а також системний і структурно-функціональний підходи.
Результати. Концептуальні напрями формування управління регіональним медичним центром спрямовані на вирішення практичного завдання – організації діяльності медичного закладу, який працює на принципах державно-приватного партнерства. Вони обґрунтовані з урахуванням системного підходу, Конституції України, законів та інших нормативно-правових актів України, загальновизнаних принципів і норм міжнародного права у галузі охорони здоровʼя, вітчизняного і зарубіжного досвіду. Концептуальні напрями формують нову систему управління медичним закладом на принципах державно-приватного партнерства, забезпечують стійкий економічний стан і можливість розвитку виробничої бази медичного закладу.
Висновки. Розробка концептуальних напрямів дозволила оптимізувати роботу регіонального медичного центру за рахунок визначення основних принципів формування управління з механізмами державно-приватного партнерства, організації інтегрованої системи управління, створення ефективної та результативної системи маркетингу і, як результат, забезпечити задоволеність пацієнтів послугами регіонального медичного центру.