bluuebunny/crossref_metadata_2025_split huggingface dataset:
Method for developing sustainable water resource plans
Authors: Pouya Sahar , Turkoglu Handan 
Published: September 2021

AbstractWith the economic expansion and population growth, water basins have encountered environmental issues, and water basin protection and sustainability have achieved more importance. This study aimed to provide a method to develop sustainable plans for water resources. Thus, it needs to determine the sustainability criteria of a water basin plan and then rank them in terms of their role in the basin sustainability. Using the Analytic Hierarchy Process, the criteria were prioritized by experts with relevant knowledge and experience. The results revealed that in weighting the sustainability factors of the water basin plan, judgments by academics were affected by their fields of interest, and practitioners' choices reflected their organization's scopes and responsibilities. Considering the differences that emerged over the prioritizations of sustainability dimensions, built environment and ecological sub‐factors, it suggests a flexible method for developing the basin plans which is open to future changes.
Post-Ore Processes of Uranium Migration in the Sandstone-Hosted Type Deposits: 234U/238U, 238U/235U and U–Pb Systematics of Ores of the Namaru Deposit, Vitim District, Northern Transbaikalia
Authors: Golubev V. N. , Tarasov N. N. , Chernyshev I. V. , Chugaev A. V. , Ochirova G. V. , Kochkin B. T. 
Published: September 2021

Abstract
To assess the nature of the post-ore behaviour of uranium in the Namaru deposit (Khiagda ore field), U–Pb isotope systems and the isotopic composition of uranium (234U/238U and 238U/235U) were studied. The studied samples represent different ore zones of the deposit and were collected along cross-sections both vertically and horizontally. Wide variations in the isotopic composition of uranium and U–Pb isotopic age have been established. Deviations of the 234U/238U ratio from equilibrium values, which for some samples exceed 50%, along with significant variations in the isotopic age, indicate that permafrost layer, which covered the catchment areas of paleovalleys with meteoric oxygen-containing waters ca. 2.5 Ma ago, did not lead to preserving uranium ores at the deposit. Uranium migration took place during the Quaternary period. The effective combining the U–Pb dating and 234U/238U data in assessing the post-ore redistribution of uranium made it possible to recognize: removal of uranium from some zones of the ore body and its accompanying redeposition in others. Wide variations in the 238U/235U (137.484–137.851) ratios throughout the entire studied cross-sections can be explained by the different locations of samples relatively to the ore deposition front and change in redox conditions as this front advanced. Depletion of the light isotope 235U in the lower zone of the ore body may be associated with the influence of ascending carbonic waters established in the regional basement. The effect of such waters on uranium-bearing rocks causes predominant leaching of light 235U.
Reflective Nested Simulations Supporting Optimizations within Sequential Railway Traffic Simulators
Authors: Diviš Roman , Kavička Antonín 
Published: September 2021

This article describes and discusses railway-traffic simulators that use reflective nested simulations. Such simulations support optimizations (decision-making) with a focus on the selection of the most suitable solution where selected types of traffic problems are present.
This approach allows suspension of the ongoing main simulation at a given moment and, by using supportive nested simulations (working with an appropriate lookahead), assessment of the different acceptable solution variants for the problem encountered—that is, a what-if analysis is carried out. The variant that provides the best predicted operational results (based on a specific criterion) is then selected for continuing the suspended main simulation. The proposed procedures are associated, in particular, with the use of sequential simulators specifically developed for railway traffic simulations. Special attention is paid to parallel computations of replications both of the main simulation and of supportive nested simulations.
The concept proposed, applicable to railway traffic modelling, has the following advantages. First, the solution variants for the existing traffic situation are analyzed with respect to the feasibility of direct monitoring and evaluation of the natural traffic indicators or the appropriate (multi-criterial) function. The indicator values compare the results obtained from the variants being tested. Second, the supporting nested simulations, which potentially use additional hierarchic nesting, can also include future occurrences of random effects (such as train delay), thereby enabling us to realistically assess future traffic in stochastic conditions.
The guidelines presented (for exploiting nested simulations within application projects with time constraints) are illustrated on a simulation case study focusing on traffic assessment related to the track infrastructure of a passenger railway station. Nested simulations support decisions linked with dynamic assignments of platform tracks to delayed trains.
The use of reflective nested simulations is appropriate particularly in situations in which a reasonable number of admissible variants are to be analyzed within decision-making problem solution. This method is applicable especially to the support of medium-term (tactical) and long-term (strategic) planning. Because of rather high computational and time demands, nested simulations are not recommended for solving short-term (operative) planning/control problems.
Biomimetic Rotary Tillage Blade Design for Reduced Torque and Energy Requirement
Authors: Yang Yuwan , Tong Jin , Huang Yuxiang , Li Jinguang , Jiang Xiaohu 
Published: September 2021

A rotary cultivator is a primary cultivating machine in many countries. However, it is always challenged by high operating torque and power requirement. To address this issue, biomimetic rotary tillage blades were designed in this study for reduced torque and energy requirement based on the geometric characteristics (GC) of five fore claws of mole rats, including the contour curves of the five claw tips (GC-1) and the structural characteristics of the multiclaw combination (GC-2). Herein, the optimal blade was selected by considering three factors: (1) the ratio (

r

) of claw width to lateral spacing, (2) the inclined angle (

θ

) of the multiclaw combination, and (3) the rotary speed (

n

) through the soil bin tests. The results showed that the order of influence of factors on torque was

n

,

r

, and

θ

; the optimal combination of factors with the minimal torque was

r
=
1.25

,

θ
=

60

°

, and

n
=
240

rpm

. Furthermore, the torque of the optimal blade (BB-1) was studied by comparing with a conventional (CB) and a reported optimal biomimetic blade (BB-2) in the soil bin at the rotary speed from 160 to 320 rpm. Results showed that BB-1 and BB-2 averagely reduced the torque by 13.99% and 3.74% compared with CB, respectively. The field experiment results also showed the excellent soil-cutting performance of BB-1 whose average torques were largely reduced by 17.00%, 16.88%, and 21.80% compared with CB at different rotary speeds, forward velocities, and tillage depths, respectively. It was found that the geometric structure of the five claws of mole rats could not only enhance the penetrating and sliding cutting performance of the cutting edge of BB-1 but also diminish the soil failure wedge for minimizing soil shear resistance of BB-1. Therefore, the GC of five fore claws of mole rats could inspire the development of efficient tillage or digging tools for reducing soil resistance and energy consumption.
Dietary Advanced Glycation End-Products and Mortality after Breast Cancer in the Women's Health Initiative
Authors: Omofuma Omonefe O. , Peterson Lindsay L. , Turner David P. , Merchant Anwar T. , Zhang Jiajia , Thomson Cynthia A. , Neuhouser Marian L. , Snetselaar Linda G. , Caan Bette J. , Shadyab Aladdin H. , Saquib Nazmus , Banack Hailey R. , Uribarri Jaime , Steck Susan E. 
Published: September 2021

AbstractBackground:Advanced glycation end-products (AGE) are formed through nonenzymatic glycation of free amino groups in proteins or lipid. They are associated with inflammation and oxidative stress, and their accumulation in the body is implicated in chronic disease morbidity and mortality. We examined the association between postdiagnosis dietary Nϵ-carboxymethyl-lysine (CML)–AGE intake and mortality among women diagnosed with breast cancer.Methods:Postmenopausal women aged 50 to 79 years were enrolled in the Women's Health Initiative (WHI) between 1993 and 1998 and followed up until death or censoring through March 2018. We included 2,023 women diagnosed with first primary invasive breast cancer during follow-up who completed a food frequency questionnaire (FFQ) after diagnosis. Cox proportional hazards (PH) regression models estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) of association between tertiles of postdiagnosis CML-AGE intake and mortality risk from all causes, breast cancer, and cardiovascular disease.Results:After a median 15.1 years of follow-up, 630 deaths from all causes were reported (193 were breast cancer–related, and 129 were cardiovascular disease–related). Postdiagnosis CML-AGE intake was associated with all-cause (HRT3vsT1, 1.37; 95% CI, 1.09–1.74), breast cancer (HRT3vsT1, 1.49; 95% CI, 0.98–2.24), and cardiovascular disease (HRT3vsT1, 1.91; 95% CI, 1.09–3.32) mortality.Conclusions:Higher intake of AGEs was associated with higher risk of major causes of mortality among postmenopausal women diagnosed with breast cancer.Impact:Our findings suggest that dietary AGEs may contribute to the risk of mortality after breast cancer diagnosis. Further prospective studies examining dietary AGEs in breast cancer outcomes and intervention studies targeting dietary AGE reduction are needed to confirm our findings.
Immunogenicity and Safety of COVID-19 Vaccine BNT162b2 for Patients with Solid Cancer: A Large Cohort Prospective Study from a Single Institution
Authors: Di Noia Vincenzo , Pimpinelli Fulvia , Renna Davide , Barberi Vittoria , Maccallini Maria Teresa , Gariazzo Ludovica , Pontone Martina , Monti Alessandro , Campo Flaminia , Taraborelli Emanuela , Di Santo Maria , Petrone Fabrizio , Mandoj Chiara , Ferraresi Virginia , Ferretti Gianluigi , Carlini Paolo , Di Bella Ornella , Conti Laura , La Malfa Antonia Marina , Pellini Raul , Bracco Domenico , Giannarelli Diana , Morrone Aldo , Cognetti Francesco 
Published: September 2021

Abstract

Purpose:
We assessed the immunogenicity and safety of the BNT162b2 vaccine in a large cohort of patients with cancer (CP).

Experimental Design:
From March 1, 2021 to March 20, 2021, this prospective cohort study included 816 CP afferent to our institution and eligible for the vaccination. A cohort of 274 health care workers (HCW) was used as age- and sex-matched control group. BNT162b2 was administered as a two-dose regimen given 21 days apart. Blood samples to analyze anti-Spike (S) IgG antibodies (Ab) were collected prevaccination [timepoint (TP) 0], and at 3 weeks (TP1) and 7 weeks (TP2) after the first dose.

Results:
Patients characteristics: median age 62 (range, 21–97); breast/lung cancer/others (31/21/48%); active treatment/follow-up (90/10%). In the whole CP cohort, the serologic response rate (RR) and the titre of anti-S IgG significantly increased across the TPs; at TP2, the responders (IgG &gt;15 AU/mL) were 94.2%. Active chemotherapy and chronic use of steroids were independent predictors of lower RR. Adverse events (AE) after the booster predicted higher likelihood of response (OR, 4.04; 95% confidence interval, 1.63–9.99; P = 0.003). Comparing the matched cohorts, the responders were significantly lower in CP than in HCW at TP1 (61.2% vs. 93.2%) and TP2 (93.3% vs. 100%), while the geometric mean concentration of IgG did not significantly differ at TP2 being significantly lower in CP (23.3) than in HCW (52.1) at TP1. BNT162b2 was well tolerated in CP; severe-grade AEs were 3.5% and 1.3% after the first and second doses, respectively.

Conclusions:
BNT162b2 assures serologic immunization without clinically significant toxicity in CP. The second dose is needed to reach a satisfactory humoral response.
Novel Mitochondria-Based Targeting Restores Responsiveness in Therapeutically Resistant Human Lung Cancer Cells
Authors: Yin Liyuan , Zhang Yi , Yin Lijuan , Ou Yan , Lewis Michael S. , Wang Ruoxiang , Zhau Haiyen E. , Zhou Qinghua , Chung Leland W.K. 
Published: September 2021

Abstract
Cisplatin and tyrosine kinase inhibitors (TKI) are recommended to treat non–small cell lung cancer (NSCLC). However, ubiquitously acquired drug resistance in patients with NSCLC diminishes their therapeutic efficacy. Strategies for overcoming cisplatin and TKI resistance are an unmet medical need. We previously described a group of near-infrared heptamethine carbocyanine fluorescent dyes, referred to as DZ, with tumor-homing properties via differentially expressed organic anion-transporting polypeptides on cancer cells. This group of organic dyes can deliver therapeutic payloads specifically to tumor cells in the form of a chemical conjugate. We synthesized DZ-simvastatin (DZ-SIM) initially to target cholesterol biosynthesis in lung cancer cells. DZ-SIM killed both cisplatin-sensitive and cisplatin-resistant as well as EGFR-TKI–sensitive and EGFR-TKI–resistant lung cancer cells. This conjugate specifically accumulated in and effectively inhibited the growth of xenograft tumors formed by NSCLC cells resistant to first-generation (H1650) and third-generation (PC9AR) EGFR TKIs. DZ-SIM induced cell death by targeting mitochondrial structure and function. We concluded that DZ-SIM could be a promising novel therapy for overcoming drug resistance in patients with NSCLC.
Paclitaxel Induces Micronucleation and Activates Pro-Inflammatory cGAS–STING Signaling in Triple-Negative Breast Cancer
Authors: Hu Yang , Manasrah Baraa K. , McGregor Stephanie M. , Lera Robert F. , Norman Roshan X. , Tucker John B. , Scribano Christina M. , Yan Rachel E. , Humayun Mouhita , Wisinski Kari B. , Tevaarwerk Amye J. , O'Regan Ruth M. , Wilke Lee G. , Weaver Beth A. , Beebe David J. , Jin Ning , Burkard Mark E. 
Published: September 2021

AbstractTaxanes remain one of the most effective medical treatments for breast cancer. Clinical trials have coupled taxanes with immune checkpoint inhibitors in patients with triple-negative breast cancer (TNBC) with promising results. However, the mechanism linking taxanes to immune activation is unclear. To determine if paclitaxel could elicit an antitumoral immune response, we sampled tumor tissues from patients with TNBC receiving weekly paclitaxel (80 mg/m2) and found increased stromal tumor-infiltrating lymphocytes and micronucleation over baseline in three of six samples. At clinically relevant concentrations, paclitaxel can induce chromosome missegregation on multipolar spindles during mitosis. Consequently, post-mitotic cells are multinucleated and contain micronuclei, which often activate cyclic GMP-AMP synthase (cGAS) and may induce a type I IFN response reliant on the stimulator of IFN genes (STING) pathway. Other microtubule-targeting agents, eribulin and vinorelbine, recapitulate this cGAS/STING response and increased the expression of immune checkpoint molecule, PD-L1, in TNBC cell lines. To test the possibility that microtubule-targeting agents sensitize tumors that express cGAS to immune checkpoint inhibitors, we identified 10 patients with TNBC treated with PD-L1 or PD-1, seven of whom also received microtubule-targeting agents. Elevated baseline cGAS expression significantly correlated with treatment response in patients receiving microtubule-targeting agents in combination with immune checkpoint inhibitors. Our study identifies a mechanism by which microtubule-targeting agents can potentiate an immune response in TNBC. Further, baseline cGAS expression may predict patient treatment response to therapies combining microtubule-targeting agents and immune checkpoint inhibitors.
Glypican-1 Is a Novel Target for Stroma and Tumor Cell Dual-Targeting Antibody–Drug Conjugates in Pancreatic Cancer
Authors: Tsujii Shigehiro , Serada Satoshi , Fujimoto Minoru , Uemura Sunao , Namikawa Tsutomu , Nomura Taisei , Murakami Ichiro , Hanazaki Kazuhiro , Naka Tetsuji 
Published: September 2021

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a stroma-rich cancer. Extracellular matrix proteins produced by cancer-associated fibroblasts (CAFs) found in tumor stroma that impedes effective delivery of chemotherapeutic agents results in poor response in patients with PDAC. Previously, our group reported that glypican-1 (GPC1) was overexpressed in human PDAC and negatively correlated with patient survival. Immunohistochemical analysis of 25 patients with PDAC tumor specimens revealed elevated expression of GPC1 in stromal cells and pancreatic cancer cells in 80% of patients. Interestingly, GPC1 was expressed on CAFs in PDAC. We generated a GPC1 antibody–drug conjugate conjugated with monomethyl auristatin E [GPC1-ADC(MMAE)] and evaluated its preclinical antitumor activity by targeting GPC1-positive CAF and cancer cells in PDAC. GPC1-ADC(MMAE) inhibited the growth of GPC1-positive PDAC cell lines in vitro. Furthermore, GPC1-ADC(MMAE) showed a potent antitumor effect in the PDAC patient-derived tumor xenograft (PDX) model against GPC1-positive CAF and heterogeneous GPC1-expressing cancer cells. Notably, GPC1-ADC(MMAE) showed robust preclinical efficacy against GPC1 in a stroma-positive/cancer-negative PDAC PDX model. GPC1-ADC(MMAE) was delivered and internalized to CAFs. Although apoptosis was not observed in CAFs, the released MMAE from CAFs via MDR-1 induced apoptosis of cancer cells neighboring CAFs and efficiently inhibited PDAC tumor growth. GPC1-ADC(MMAE) exhibited potent and unique antitumor activity in GPC1-positive PDAC PDX models, which suggests that GPC1 is a novel therapeutic target in PDAC and other stromal GPC1-positive solid tumors. These findings show that targeting GPC1 on CAF using GPC1-ADC(MMAE) is a useful approach in case of stroma-rich tumors such as PDAC.
Rational Combination of CRM1 Inhibitor Selinexor and Olaparib Shows Synergy in Ovarian Cancer Cell Lines and Mouse Models
Authors: Handley Katelyn F. , Rodriguez-Aguayo Cristian , Ma Shaolin , Stur Elaine , Joseph Robiya , Bayraktar Emine , Dasari Santosh K. , Nguyen Nghi , Powell Reid T. , Sobieski Mary , Ivan Cristina , Kim Mark , Umamaheswaran Sujanitha , Glassman Deanna , Wen Yunfei , Amero Paola , Stephan Clifford , Coleman Robert L. , Landesman Yosef , Westin Shannon N. , Ram Prahlad T. , Sood Anil K. 
Published: September 2021

Abstract
CRM1 inhibitors have demonstrated antitumor effects in ovarian and other cancers; however, rational combinations are largely unexplored. We performed a high-throughput drug library screen to identify drugs that might combine well with selinexor in ovarian cancer. Next, we tested the combination of selinexor with the top hit from the drug screen in vitro and in vivo. Finally, we assessed for mechanisms underlying the identified synergy using reverse phase protein arrays (RPPA). The drug library screen assessing 688 drugs identified olaparib (a PARP inhibitor) as the most synergistic combination with selinexor. Synergy was further demonstrated by MTT assays. In the A2780luc ip1 mouse model, the combination of selinexor and olaparib yielded significantly lower tumor weight and fewer tumor nodules compared with the control group (P &lt; 0.04 and P &lt; 0.03). In the OVCAR5 mouse model, the combination yielded significantly fewer nodules (P = 0.006) and markedly lower tumor weight compared with the control group (P = 0.059). RPPA analysis indicated decreased expression of DNA damage repair proteins and increased expression of tumor suppressor proteins in the combination treatment group. Collectively, our preclinical findings indicate that combination with selinexor to expand the utility and efficacy of PARP inhibitors in ovarian cancer warrants further exploration.
Identificação das unidades de paisagem em trecho do centro da cidade de Macaé, Rio de Janeiro, Brasil
Authors: Pereira Fernanda de Abreu , Aliprandi Danielly Cozer 
Published: September 2021

A cidade de Macaé, localizada no interior do estado do Rio de Janeiro, conhecida como a capital nacional do petróleo, recebeu este título por ser um polo importante para a gestão da atividade petrolífera brasileira. As interferências dessa atividade atingiram diversos aspectos da cidade, como a economia, o crescimento populacional, a expansão urbana e, consequentemente, a paisagem. Com o interesse em caracterizar a paisagem, foi utilizado o método de unidades de paisagem aplicado em um trecho da cidade. Este artigo possui mapas de análise elaborados para observar diferentes aspectos do trecho, com objetivo de auxiliar no diagnóstico das unidades de paisagem existentes. Como ferramenta de subsídio, foram estudados autores referência no tema de mapeamento temático, assim como observação do local. Por fim, foram identificadas as unidades de paisagem e apontadas suas características e potencialidades.
Fine structure of spermatogenesis in the spider crab Lissa chiragra (Fabricius, 1775) (Eubrachyura, Epialtidae)
Authors: Gaber Ibrahim , Al-Mahasneh Abdallah 
Published: September 2021

Abstract
This article uses the male spider crab Lissa chiragra, collected from Ras el Tin beach on the Mediterranean Sea at Alexandria, Egypt, between January and December 2017, as a model for a descriptive study of the functional morphology of the different structures of spermatogenesis with the aid of the transmission electron microscope. This study divides the seminiferous tubule into three zones, i.e., the germinal, transformation, and evacuation zone. The transformation or maturation zone occupies the central area. The evacuation zone lies at a pole opposite to the germinal zone. The anterior vas deferens is a tube where the formation of the spermatophore occurs by means of secretions from the epithelium. The ejaculatory duct is located between the muscles of the coxae of the fifth walking legs. This study concluded that the complex acrosome vesicle is formed during spermiogenesis and the cytoplasm includes the membrane system, constituted by the endoplasmic reticulum, Golgi apparatus, and vesicles associated with microtubules, and a few mitochondria. The Golgi apparatus is developed and is organized progressively to produce various vesicles. The cytoplasm forms a ring at the base of the nuclear extensions. The merger of the plasma and nuclear membranes, results in a pentalaminar membranous structure in some regions of the cell surface.