bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding commercial actors’ engagement in policy debates on proposed e-cigarette regulation in Scotland
Authors: Ikegwuonu Theresa , Hilton Shona , Smith Katherine E. , Buckton Christina H. , Wong Mark , Weishaar Heide B. 
Published: March 2021

IntroductionThere is growing concern about transnational tobacco corporations’ (TTCs) and other commercial actors’ involvement in e-cigarette policy development. Previous analyses suggest that TTCs used e-cigarette debates to demonstrate alignment with public health and re-gain policy influence. Less is known about the engagement of other types of commercial actors in e-cigarette policy debates.MethodsThis paper is the first to empirically analyse commercial actors’ engagement in an e-cigarette policy consultation process and to examine their views on proposed regulation. It applies mixed methods, drawing on policy consultation submissions (n=32), semi-structured interviews (n=9) and a social network analysis of website links among 32 commercial actors.ResultsThe results show that commercial actors’ positions on e-cigarette regulation aligned with business interests. TTCs, independent e-cigarette manufacturers and other non-licensed commercial actors were opposed to most aspects of potential e-cigarette regulation (except for age of sale restrictions), whereas licensed commercial actors, including pharmaceutical companies, supported more stringent regulation. While collaboration was viewed as strategically important to gain policy influence, distinct commercial interests and concerns about TTC credibility led to strategic distancing and to collaboration being largely confined to sector boundaries. In addition to reiterating arguments employed by TTCs in previous regulatory debates, commercial actors focused on highlighting the technical complexity and harm reduction potential of e-cigarettes.ConclusionAwareness of the various commercial interests and strategic positioning of commercial actors in e-cigarette policy should inform public health advocacy and policy development, including managing conflicts of interest in the context of Framework Convention on Tobacco Control Article 5.3.
Testing anomalous $$H-W$$ couplings and Higgs self-couplings via double and triple Higgs production at $$e^+e^-$$ colliders
Authors: Gonzalez-Lopez M. , Herrero M. J. , Martinez-Suarez P. 
Published: March 2021

AbstractIn the present work we study the implications at the future $$e^+e^-$$

e
+

e
-

colliders of the modified interaction vertices WWH, WWHH, HHH and HHHH within the context of the non-linear effective field theory given by the Electroweak Chiral Lagrangian. These vertices are given by four parameters, a, b, $$\kappa _3$$

κ
3

and $$\kappa _4$$

κ
4

, respectively, that are independent and without any constraint from symmetry considerations in this non-linear effective Lagrangian context, given the fact the Higgs field is a singlet. This is in contrast to the Standard Model, where the vertices are related by $$V_{WWH}^\mathrm{SM}=v V_{WWHH}^\mathrm{SM}$$

V

WWH

SM

=
v

V

WWHH

SM

and $$V_{HHH}^\mathrm{SM}=v V_{HHHH}^\mathrm{SM}$$

V

HHH

SM

=
v

V

HHHH

SM

, with $$v=246$$

v
=
246

GeV. We investigate the implications of the absence of these relations in the Electroweak Chiral Lagrangian case. We explore the sensitivity to these Higgs anomalous couplings in the two main channels at these colliders: double and triple Higgs production (plus neutrinos). Concretely, we study the access to a and b in $$e^+e^- \rightarrow HH \nu {\bar{\nu }}$$

e
+

e
-

→
H
H
ν

ν

¯

and the access to $$\kappa _3$$

κ
3

and $$\kappa _4$$

κ
4

in $$e^+e^- \rightarrow HHH \nu {\bar{\nu }}$$

e
+

e
-

→
H
H
H
ν

ν

¯

. Our study of the beyond the Standard Model couplings via triple Higgs boson production at $$e^+e^-$$

e
+

e
-

colliders is novel and shows for the first time the possible accessibility to the quartic Higgs self-coupling.
Impacts of vehicle-to-infrastructure communication on traffic flows with mixed connected vehicles and human-driven vehicles
Authors: Du Mengxiao , Yang Shiyao , Chen Qun 
Published: March 2021

This paper explored the impacts of vehicle-to-infrastructure (V2I) communication on the mixed traffic flow consisting of connected vehicles (CVs) and human-driven vehicles (HVs). We developed a cellular automaton model for mixed flow at the signalized intersection. In addition to considering the motion characteristics of CVs and the influence of HVs on the motion behavior of CVs, the model also considered the influence of signal lights. CVs determine their velocities via V2I communication in order to pass the signal light with less delay and avoid stopping. Through simulations, we found that the presence, frequency and range of V2I communication all make a difference in the mixed flow. Also, 1-Hz communication reduces the number of vehicles within 300 m before the red light from 36 to 26, and the 10-Hz communication reduces one more; 1-Hz communication increases the number of accelerations, but when the frequency increases to 10 Hz, the number of accelerations decreases to the same value as without V2I communication, but the value of number of accelerations increases monotonously with the frequency; traffic delay decreases and capacity increases as the frequency increases. However, as the communication range increases, except that the number of accelerations first decreases and then increases, other traffic characteristics remain unchanged. The number of accelerations reaches a minimum at about 500 m.
Design and implementation for the PWM closed-loop feedback interface circuit of a sandwich capacitive accelerometer based on ARM
Authors: Chen Haitao , Che Lufeng 
Published: March 2021

Owing to the advantages of small size and high integration that accelerometers made by MEMS technology, the Pulse Width Modulation (PWM) closed-loop feedback interface circuit of a sandwich capacitive accelerometer based on ARM is designed. Based on the design, a simulation by SIMULINK and a PCB board-level circuit are conducted. Simulation and measurement are provided to support the design. The realization of Proportion Integral Differential (PID) control algorithm and the generation of PWM are performed by STM32 microcontroller instead of the circuit in the design. The output form of the interface circuit is PWM with different duty cycle and filtered DC voltage. According to the measurement results, the output of the PWM duty cycle change is 16.9%/g, and the sensitivity is 1.045 V/g.
Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of Vardenafil and Its Application of Bioequivalence
Authors: Gan Kok Zheng , Widodo Riyanto Teguh , Chik Zamri , Teh Lay Kek , Rofiee Mohd Salleh , Mohamad Yusof Mohd Izwan 
Published: March 2021

A simple, rapid, and sensitive method of liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was developed and validated for the determination of vardenafil in rabbit plasma. A simple protein precipitation method with ice-cold acetonitrile was used for plasma extraction. The mass transitions m/z 489⟶151 and m/z 390⟶169 were used to measure vardenafil and tadalafil (internal standard), respectively, with a total assay run time of 6 min. The limit of detection was 0.2 ng/mL. The assay was reproducible with intra-assay and interassay precision ranging 1.17%–9.17% and 1.31%–5.86%, respectively. There was also good intra-assay and interassay accuracy between 89.3%–105.3% and 94%–102% of the expected value, respectively. The linearity range was 0.5–60 ng/mL in rabbit plasma (

r

2

≥ 0.99). The measured AUC from 0 to 24 h

AUC

0
−
24

t

for the test and reference formulations were 174.38 ± 95.91 and 176.45 ± 76.88, respectively. For the test,

C

max

and

T

max

were 75.36 ± 59.53 ng/mL and 1.42 ± 0.19 h, whereas, for the reference, these were 58.22 ± 36.11 ng/mL and 2.04 ± 0.33 h, respectively. The test formulation achieved a slightly lower

AUC

0
−
24

t

value (

p

> 0.05), higher

C

max

values (

p

> 0.05), faster

T

max

(

p

< 0.05), and almost equal bioavailability compared with the reference formulation.
Long Noncoding RNA VESTAR Regulates Lymphangiogenesis and Lymph Node Metastasis of Esophageal Squamous Cell Carcinoma by Enhancing VEGFC mRNA Stability
Authors: Wang Yali , Zhang Weimin , Liu Wenzhong , Huang Lijie , Wang Yan , Li Dan , Wang Guangchao , Zhao Zitong , Chi Xinming , Xue Yu , Song Yongmei , Liu Xuefeng , Zhan Qimin 
Published: March 2021

Abstract

Lymph node metastasis is one of the most malignant clinical features in patients with esophageal squamous cell carcinoma (ESCC). Understanding the mechanism of lymph node metastasis will provide treatment strategies for patients with ESCC. Long noncoding RNAs (lncRNA) play a critical role in the development and progression of human cancers. However, the role and mechanism of lncRNAs in lymph node metastasis remain largely unknown. Here we show that VEGFC mRNA stability–associated long noncoding RNA (VESTAR) is involved in lymph node metastasis of ESCC. VESTAR was overexpressed in ESCC tissues and was predictive of poor prognosis in patients with ESCC. In ESCC, NXF1 and SRSF3 facilitated nuclear export of VESTAR to the cytoplasm, which was associated with lymph node metastasis. Depletion of VESTAR inhibited ESCC-associated lymphangiogenesis and lymphatic metastasis. Mechanistically, VESTAR directly bound and stabilized VEGFC mRNA. VESTAR also interacted with HuR, a positive regulator of VEGFC mRNA stability, and increased HuR binding to VEGFC mRNA. Our study reveals a novel lncRNA-guided mechanism of lymph node metastasis in ESCC and may provide a potential target for treatment of ESCC lymphatic metastasis.

Significance:
These findings illustrate the lncRNA-guided regulation of VEGFC mRNA stability via direct RNA–RNA interactions, highlighting a therapeutic target for patients with ESCC with lymphatic metastasis.
Afatinib Exerts Immunomodulatory Effects by Targeting the Pyrimidine Biosynthesis Enzyme CAD
Authors: Tu Hsin-Fang , Ko Chun-Jung , Lee Ching-Tai , Lee Cheng-Fan , Lan Shao-Wei , Lin Hsin-Hsien , Lin Hsin-Ying , Ku Chia-Chi , Lee Der-Yen , Chen I-Chun , Chuang Ya-Hui , Del Caño-Ochoa Francisco , Ramón-Maiques Santiago , Ho Chao-Chi , Lee Ming-Shyue , Chang Geen-Dong 
Published: March 2021

Abstract

Current clinical trials of combined EGFR-tyrosine kinase inhibitors (TKI) and immune checkpoint blockade (ICB) therapies show no additional effect. This raises questions regarding whether EGFR-TKIs attenuate ICB-enhanced CD8+ T lymphocyte function. Here we show that the EGFR-TKI afatinib suppresses CD8+ T lymphocyte proliferation, and we identify CAD, a key enzyme of de novo pyrimidine biosynthesis, to be a novel afatinib target. Afatinib reduced tumor-infiltrating lymphocyte numbers in Lewis lung carcinoma (LLC)–bearing mice. Early afatinib treatment inhibited CD8+ T lymphocyte proliferation in patients with non–small cell lung cancer, but their proliferation unexpectedly rebounded following long-term treatment. This suggests a transient immunomodulatory effect of afatinib on CD8+ T lymphocytes. Sequential treatment of afatinib with anti-PD1 immunotherapy substantially enhanced therapeutic efficacy in MC38 and LLC-bearing mice, while simultaneous combination therapy showed only marginal improvement over each single treatment. These results suggest that afatinib can suppress CD8+ T lymphocyte proliferation by targeting CAD, proposing a timing window for combined therapy that may prevent the dampening of ICB efficacy by EGFR-TKIs.

Significance:
This study elucidates a mechanism of afatinib-mediated immunosuppression and provides new insights into treatment timing for combined targeted therapy and immunotherapy.
A Phase I Dose-Escalation Study to Evaluate the Safety and Tolerability of Evofosfamide in Combination with Ipilimumab in Advanced Solid Malignancies
Authors: Hegde Aparna , Jayaprakash Priyamvada , Couillault Coline A. , Piha-Paul Sarina , Karp Daniel , Rodon Jordi , Pant Shubham , Fu Siqing , Dumbrava Ecaterina E. , Yap Timothy A. , Subbiah Vivek , Bhosale Priya , Coarfa Cristian , Higgins Jack P. , Williams Eric T. , Wilson Thomas F. , Lim JoAnn , Meric-Bernstam Funda , Sumner Elizabeth , Zain Hira , Nguyen Di , Nguyen Ly M. , Rajapakshe Kimal , Curran Michael A. , Hong David S. 
Published: March 2021

Abstract

Purpose:
As hypoxia can mediate resistance to immunotherapy, we investigated the safety, tolerability, and efficacy of combining evofosfamide, a prodrug that alleviates hypoxia, with ipilimumab, an immune checkpoint inhibitor, in immunologically “cold” cancers, which are intrinsically insensitive to immunotherapy, as well as in “hot/warm” metastatic cancers that are, atypical of such cancers, resistant to immunotherapy.

Patients and Methods:
In a phase I, 3+3 dose-escalation trial (NCT03098160), evofosfamide (400–640 mg/m2) and ipilimumab (3 mg/kg) were administered in four 3-week cycles. The former was administered on days 1 and 8 of cycles 1–2, while the latter was administered on day 8 of cycles 1–4. Response was assessed using immune-related RECIST and retreatment was allowed, if deemed beneficial, after completion of cycle 4 or at progression.

Results:
Twenty-two patients were enrolled, of whom 21 were evaluable, encompassing castration-resistant prostate cancer (n = 11), pancreatic cancer (n = 7), immunotherapy-resistant melanoma (n = 2), and human papillomavirus–negative head and neck cancer (n = 1). Drug-related hematologic toxicities, rash, fever, nausea, vomiting, and elevation of liver enzymes were observed in &gt; 10% of patients. The most common drug-related grade 3 adverse event was alanine aminotransferase elevation (33.3%). Two patients discontinued ipilimumab and 4 required evofosfamide deescalation due to toxicity. Of 18 patients with measurable disease at baseline, 3 (16.7%) achieved partial response and 12 (66.7%) achieved stable disease. The best responses were observed at 560 mg/m2 evofosfamide. Preexisting immune gene signatures predicted response to therapy, while hypermetabolic tumors predicted progression. Responders also showed improved peripheral T-cell proliferation and increased intratumoral T-cell infiltration into hypoxia.

Conclusions:
No new or unexpected safety signals were observed from combining evofosfamide and ipilimumab, and evidence of therapeutic activity was noted.
Circulating Tumor Cell Genomic Evolution and Hormone Therapy Outcomes in Men with Metastatic Castration-Resistant Prostate Cancer
Authors: Gupta Santosh , Halabi Susan , Kemeny Gabor , Anand Monika , Giannakakou Paraskevi , Nanus David M. , George Daniel J. , Gregory Simon G. , Armstrong Andrew J. 
Published: March 2021

Abstract

Men with circulating tumor cell (CTC) AR-V7–positive metastatic castration-resistant prostate cancer (mCRPC) have worse outcomes when treated with enzalutamide/abiraterone. However, most men lack CTC AR-V7 detection, and additional predictive biomarkers are needed. We conducted a retrospective secondary analysis of the prospective PROPHECY trial (NCT02269982) of men with mCRPC undergoing treatment with enzalutamide/abiraterone, analyzing pooled CTC and germline DNA for whole-genome copy-number alterations (CNA) in 73 samples from 48 men over time along with pooled CTC and germline whole-exome sequencing on 22 paired samples before and following progression on androgen receptor (AR) inhibitor therapy to identify somatic genomic alterations associated with acquired resistance. We observed broad interpatient and longitudinal CTC genomic heterogeneity from AR-V7–negative men with mCRPC, including common gains of KDM6A, MYCN, and AR, and loss of ZFHX3, BRCA1, and PTEN. Men who had progression-free survival of ≤3 months despite enzalutamide/abiraterone treatment were more likely to have baseline CTC genomic loss of CHD1, PTEN, PHLPP1, and ZFHX3 and gains of BRCA2, KDM5D, MYCN, and SPARC. After progression on abiraterone/enzalutamide, we observed clonal evolution of CTCs harboring TP53 mutations and gain of ATM, KDM6A, and MYC, and loss of NCOR1, PTEN, RB1, and RUNX2. CTC genomic findings were independently confirmed in a separate cohort of mCRPC men who progressed despite prior treatment with abiraterone/enzalutamide (NCT02204943).

Implications:
We identified common and reproducible genomic alterations in CTCs from AR-V7–negative mCRPC men associated with poor outcomes during enzalutamide/abiraterone treatment, including CNAs in genes linked to lineage plasticity and epigenetic signaling, DNA repair, AR, TP53/RB1, PTEN, and WNT pathways.
Occurrence of mammalian small carnivores in Kalakad-Mundanthurai Tiger Reserve, Western Ghats, India
Authors: Venkatesh A. , Sridharan N. , Jeya Packiavathi S. Agnes , Selvan K. Muthamizh 
Published: March 2021

The small mammalian carnivores are important for maintaining healthy ecosystems. The present documentation is based on the camera trap survey in Kalakad-Mundanthurai Tiger Reserve, Tamil Nadu. Paired camera-traps were set in a grid of 1.413 × 1.413 km area of 180km² within an altitudinal range of 80–1,866 m. A total of 11 species were recorded in different habitat types. Brown Palm Civet Paradoxurus jerdoni and Leopard Cat Prionailurus bengalensis had the highest capture rates and the lowest was Rusty Spotted Cat Prionailurus rubiginosus.
Addition of four woodlice species (Crustacea: Isopoda) to the checklist of Iranian Oniscidea
Authors: Bakhshi Yaser , Sadeghi Saber , Darvishnia Hamid , Dashan Meysam 
Published: March 2021

Four new records of Oniscidea from Iran including Armadillidium azerbaidzhanum, A. nasatum, Platyarthrus schoeblii, and Armadillo alievi are provided. Important diagnostic characters of the recorded species are photographed.
Not all gone: the rediscovery of Jaguar (Carnivora: Felidae: Panthera onca) and records of threatened monkeys (Primates: Mammalia) in the Magdalena River Valley of Caldas Department in Colombia, a call for their conservation
Authors: Mendieta-Giraldo Leonardo , Escobar-Lasso Sergio , Grajales-Suaza Esteban , González-Maya José F. 
Published: March 2021

For decades, the middle Magdalena Valley of Colombia has been a scene of heavy social and civil conflict, which have resulted on a sustained and extensive expansion of the agricultural border, dedicating most lands to extensive cattle production activities. Such extensive disturbances have led to a progressive loss and isolation of natural forests of the region, severely threatening biodiversity. A group highly susceptible to local extinction in the middle Magdalena Valley are the large and medium mammals, because they usually require large extensions of habitat with a good degree of connectivity to be able to disperse between fragments. In this sense, it is especially important to identify the last remnants of habitat that still persist in the middle Magdalena and that still are occupied by endemic and threatened mammal species. Therefore, this work confirms the presence of Jaguar Panthera onca and four threatened monkeys, Ateles hybridus (Critically Endangered), Saguinus leucopus (Endangered), Cebus versicolor (Endangered), and Aotus griseimembra (Vulnerable) inside an isolated remnant of tropical rainforest called “Ciénaga de la Tortuga” in the Magdalena River Valley of the department of Caldas. After 21 years of not having reliable records of Jaguars in the Caldas department, this work renews the hope for conserving this iconic species in the territory and is perhaps the last opportunity to take conservation actions to prevent the total local extinction of Jaguar in the department. This work also represents the first confirmed records of C. versicolor for Caldas department and the second known records of P. onca and A. hybridus. The records of A. hybridus are also considered the southernmost locality for the species.
Begonia flaviflora Hara (Begoniaceae): a new record to the flora of Bhutan
Authors: Gyeltshen Phub , Jamtsho Sherab , Wangchuk Sangay , Subba Dhan Bahadur 
Published: March 2021

Begonia flaviflora Hara, a new record to Bhutan is proposed and described. The species belongs to section Platycentrum (Klotzsch) A. DC. and is very distinctive with yellow flowers, lobed leaves, stems and petioles with brownish pubescence. Geographical distribution along with ecology, notes and photographs of the species are provided.
“We Are Not Aliens in the Universe”
Authors: Tóth Sára 
Published: March 2021

Abstract
Marilynne Robinson, in her novels and essays, sets out to retrieve a foundational strain of religious experience, one that has been minimized or even repressed in most branches of the Protestant tradition. This is what, following Paul Ricœur, American theologian David Tracy calls “the manifestation orientation” in religious expression. Building on Tracy’s distinction between “manifestation and proclamation” within Christianity, I identify and analyze a shift of emphasis from the “proclamation orientation” of Robinson’s first novel, Housekeeping, with its presentation of human existence as radically homeless and alienated, to “manifestation” in Robinson’s later work. In the Gilead novels, while preserving the proclamation orientation of Protestantism through an indictment of social injustice, she corrects the one-sided Protestant emphasis on divine transcendence and human sin, affirming a fundamental “at-home-ness” (Tracy) in the universe. Through her fictional Protestant minister and a creative rereading of classical Protestant theologians, Robinson offers an imaginative alternative to Weberian accounts of Protestant spirituality.
The Prosperity Ethic
Authors: Medina Erron , Cornelio Jayeel 
Published: March 2021

Abstract
A new prosperity gospel is emerging in the Philippines. We call it the prosperity ethic. Its dimensions set it apart from the previous incarnation of the prosperity gospel, which emphasized tithing and confessing. Specifically, the prosperity ethic values upward mobility and uses biblical principles for the acquisition of practical skills to become rich. We make our case by drawing on the writings of Bo Sanchez and Chinkee Tan, two of the most influential prosperity-oriented preachers in the country. The prosperity ethic has three dimensions: the morality of wealth (believing right), the prescribed mindset (thinking right), and the practical skills to accumulate wealth (doing it right). In the latter part we explain the rise of the prosperity ethic by relating it to major shifts in the economy since the 1990s. For sanctifying individual hard work and desire, the new prosperity gospel is emblematic of neoliberal Christianity in the Philippines today.
Plague, Pentecostalism, and Pastoral Guidance
Authors: Butler Geoffrey 
Published: March 2021

Abstract
Plagues and pandemics are nothing new for the Christian church. Throughout its history, believers have been forced to grapple with outbreaks, the latest being the COVID-19 crisis of 2020. As a relatively young branch of the Christian faith, Pentecostalism itself does not have a great deal of experience with this subject compared to many older traditions. In addition, with its emphasis on divine healing, a triumphalist attitude has unfortunately hindered some segments of the movement from developing a robust response to sickness and suffering at all. Martin Luther’s sixteenth-century response to the Black Death outbreak in Germany, however, might offer a prime example for contemporary Pentecostals to emulate. His pastoral wisdom, approach to suffering, and distinctive theology of the cross together compose a prudent yet ultimately optimistic take on how Christians should behave in such instances, making his voice an invaluable one for the contemporary church to learn from.