bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tropical temperature in the Maastrichtian Danish Basin: Data from coccolith Δ47 and δ18O
Authors: Tagliavento Mattia , John Cédric M. , Stemmerik Lars 
Published: September 2019

AbstractThe Cretaceous Earth, with its greenhouse climate and absence of major ice caps in the polar regions, represents an extreme scenario for modeling future warming. Despite considerable efforts, we are just at the verge of fully understanding the conditions of a warm Earth, and better, more extensive proxy evidence is needed to solve existing discrepancies between the applied temperature proxies. In particular, the Maastrichtian temperature trends are controversial, since data indicate cooling in the South Atlantic and contemporary warming of the North Atlantic. The “heat piracy” hypothesis involves northward heat transport to midlatitudes via oceanic currents and is used to explain the contrasting polar cooling/warming patterns. Here, we present Δ47 and δ18O data from nine coccolith-enriched samples from a shallow core taken from the Danish Basin (Chalk Sea), representing a key location at the northern mid-latitudes. Based on Δ47 data of coccolith-enriched material, sea-surface temperatures for the late Campanian–Maastrichtian ranged from 24 °C to 30 °C, with an average of 25.9 °C ± 2 °C. This is 4–6 °C higher than estimates based on Δ47 of bulk samples and 8–10 °C higher than reported temperatures based on bulk δ18O data from the same core. However, these higher temperature estimates are lower, but overall in line with estimates of Late Cretaceous tropical sea-surface temperatures from TEX86 (tetraether index of 86 carbons), when considering latitudinal differences. The study highlights the potential of clumped isotope paleothermometry on coccoliths as a valid, reliable proxy with which to reconstruct sea-surface temperatures.
Health professionals’ experiences and views on obstetric ultrasound in Vietnam: a regional, cross-sectional study
Authors: Holmlund Sophia , Lan Pham Thi , Edvardsson Kristina , Phuc Ho Dang , Ntaganira Joseph , Small Rhonda , Kidanto Hussein , Ngarina Matilda , Mogren Ingrid 
Published: September 2019

ObjectivesObstetric ultrasound is an important part of antenatal care in Vietnam, although there are great differences in access to antenatal care and ultrasound services across the country. The aim of this study was to explore Vietnamese health professionals’ experiences and views of obstetric ultrasound in relation to clinical management, resources and skills.DesignA cross-sectional questionnaire study was performed as part of the CROss Country UltraSound study.SettingHealth facilities (n=29) in urban, semiurban and rural areas of Hanoi region in Vietnam.ParticipantsParticipants were 289 obstetricians/gynaecologists and 535 midwives.ResultsA majority (88%) of participants agreed that ‘every woman should undergo ultrasound examination’ during pregnancy to determine gestational age. Participants reported an average of six ultrasound examinations as medically indicated during an uncomplicated pregnancy. Access to ultrasound at participants’ workplaces was reported as always available regardless of health facility level. Most participants performing ultrasound reported high-level skills for fetal heart rate examination (70%), whereas few (23%) reported being skilled in examination of the anatomy of the fetal heart. Insufficient ultrasound training leading to suboptimal pregnancy management was reported by 37% of all participants. ‘Better quality of ultrasound machines’, ‘more physicians trained in ultrasound’ and ‘more training for health professionals currently performing ultrasound’ were reported as ways to improve the utilisation of ultrasound.ConclusionsObstetric ultrasound is used as an integral part of antenatal care at all selected health facility levels in the region of Hanoi, and access was reported as high. However, reports of insufficient ultrasound training resulting in suboptimal pregnancy management indicate a need for additional training of ultrasound operators to improve utilisation of ultrasound.
Direct thromboaspiration efficacy for mechanical thrombectomy is related to the angle of interaction between the aspiration catheter and the clot
Authors: Bernava Gianmarco , Rosi Andrea , Boto José , Brina Olivier , Kulcsar Zsolt , Czarnetzki Christoph , Carrera Emmanuel , Schaller Karl , Lovblad Karl-Olof , Machi Paolo 
Published: September 2019

BackgroundDirect thromboaspiration has been reported as an effective mechanical treatment for acute ischemic stroke. We aimed to determine whether the angle of interaction between the aspiration catheter and the clot affects the success of clot removal in ischemic stroke patients with large vessel occlusion in the anterior and posterior circulation.MethodsAll patients treated at our institution by direct thromboaspiration as a firstline technique between January 2016 and December 2017 were enrolled in the study. We retrospectively reviewed baseline and procedural characteristics, the angle of interaction formed between the aspiration catheter and the clot, the modified Thrombolysis in Cerebral Infarction score, and the 3 month modified Rankin Scale score.Results85 patients underwent direct thromboaspiration as the firstline treatment during the study period. 100 direct thromboaspiration passes were performed. An angle of interaction of ≥125.5° significantly influenced the success of clot removal (P<0.001) with good sensitivity and specificity, in particular for occlusion of the middle cerebral and basilar artery. The combination of aspiration with a stent retriever based thrombectomy was a valid rescue treatment in cases of standalone direct thromboaspiration failure.ConclusionsIn our series, an angle of interaction between the aspiration catheter and the clot of ≥125.5° was significantly associated with successful clot removal. The prediction of the angle of interaction on pretreatment imaging may help operators to select the most adequate mechanical thrombectomy technique on a case by case basis.
Avoiding instabilities in antisymmetric tensor field driven inflation
Authors: Aashish Sandeep , Padhy Abhilash , Panda Sukanta 
Published: September 2019

Abstract
Models of inflation with antisymmetric tensor studied in the past are plagued with ghost instability even in an unperturbed FRW background. We show that it is possible to avoid ghosts in an unperturbed FRW background by considering the most general kinetic term for antisymmetric tensor field. The kinetic part acquires a new gauge symmetry violating term whose effect on perturbed modes is to prevent the appearance of nondynamical modes, and thus avoid ghosts. For completeness, we perform a check for gradient instability and derive the conditions for perturbations to be free of gradient instability.
Comment on “Three-party quantum secret sharing based on d-dimensional Bell state”
Authors: Gao Gan , Song Hong-Ru 
Published: September 2019

In the paper [Mod. Phys. Lett. B 33 (2019) 1950023 ], Qin et al. proposed a three-party quantum secret sharing scheme based on [Formula: see text]-dimensional Bell states. We study the security of the proposed scheme and find that it is not secure, that is, one sharer can obtain Alice’s secret messages without the help of the other sharer.
NSAID-induced injury of gastric epithelial cells is reversible: roles of mitochondria, AMP kinase, NGF, and PGE2
Authors: Ahluwalia Amrita , Hoa Neil , Jones Michael K. , Tarnawski Andrzej S. 
Published: September 2019

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac (DFN) and indomethacin (INDO) are extensively used worldwide. Their main side effects are injury of the gastrointestinal tract, including erosions, ulcers, and bleeding. Since gastric epithelial cells (GEPCs) are crucial for mucosal defense and are the major target of injury, we examined the extent to which DFN- and INDO-induced GEPC injury can be reversed by nerve growth factor (NGF), 16,16 dimethyl prostaglandin E2 (dmPGE2), and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), the pharmacological activator of the metabolic sensor AMP kinase (AMPK). Cultured normal rat gastric mucosal epithelial (RGM1) cells were treated with PBS (control), NGF, dmPGE2, AICAR, and/or NSAID (DFN or INDO) for 1–4 h. We examined cell injury by confocal microscopy, cell death/survival using calcein AM, mitochondrial membrane potential using MitoTracker, and phosphorylation of AMPK by Western blotting. DFN and INDO treatment of RGM1 cells for 2 h decreased mitochondrial membrane potential and cell viability. NGF posttreatment (initiated 1 or 2 h after DFN or INDO) reversed the dissipation of mitochondrial membrane potential and cell injury caused by DFN and INDO and increased cell viability versus cells treated for 4 h with NSAID alone. Pretreatment with dmPGE2 and AICAR significantly protected these cells from DFN- and INDO-induced injury, whereas dmPGE2 and AICAR posttreatment (initiated 1 h after NSAID treatment) reversed cell injury and significantly increased cell viability and rescued the cells from NSAID-induced mitochondrial membrane potential reduction. DFN and INDO induce extensive mitochondrial injury and GEPC death, which can be significantly reversed by NGF, dmPGE2, and AICAR. NEW & NOTEWORTHY This study demonstrated that mitochondria are key targets of diclofenac- and indomethacin-induced injury of gastric epithelial cells and that diclofenac and indomethacin injury can be prevented and, importantly, also reversed by treatment with nerve growth factor, 16,16 dimethyl prostaglandin E2, and 5-aminoimidazole-4-carboxamide ribonucleotide.
Acid-sensing ion channels blockade attenuates pressor and sympathetic responses to skeletal muscle metaboreflex activation in humans
Authors: Campos Monique O. , Mansur Daniel E. , Mattos João D. , Paiva Adrielle C. S. , Videira Rogerio L. R. , Macefield Vaughan G. , da Nóbrega Antonio C. L. , Fernandes Igor A. 
Published: September 2019

In animals, the blockade of acid-sensing ion channels (ASICs), cation pore-forming membrane proteins located in the free nerve endings of group IV afferent fibers, attenuates increases in arterial pressure (AP) and sympathetic nerve activity (SNA) during muscle contraction. Therefore, ASICs play a role in mediating the metabolic component (skeletal muscle metaboreflex) of the exercise pressor reflex in animal models. Here we tested the hypothesis that ASICs also play a role in evoking the skeletal muscle metaboreflex in humans, quantifying beat-by-beat mean AP (MAP; finger photoplethysmography) and muscle SNA (MSNA; microneurography) in 11 men at rest and during static handgrip exercise (SHG; 35% of the maximal voluntary contraction) and postexercise muscle ischemia (PEMI) before (B) and after (A) local venous infusion of either saline or amiloride (AM), an ASIC antagonist, via the Bier block technique. MAP (BAM +30 ± 6 vs. AAM +25 ± 7 mmHg, P = 0.001) and MSNA (BAM +14 ± 9 vs. AAM +10 ± 6 bursts/min, P = 0.004) responses to SHG were attenuated under ASIC blockade. Amiloride also attenuated the PEMI-induced increases in MAP (BAM +25 ± 6 vs. AAM +16 ± 6 mmHg, P = 0.0001) and MSNA (BAM +16 ± 9 vs. AAM +8 ± 8 bursts/min, P = 0.0001). MAP and MSNA responses to SHG and PEMI were similar before and after saline infusion. We conclude that ASICs play a role in evoking pressor and sympathetic responses to SHG and the isolated activation of the skeletal muscle metaboreflex in humans. NEW & NOTEWORTHY We showed that regional blockade of the acid-sensing ion channels (ASICs), induced by venous infusion of the antagonist amiloride via the Bier block anesthetic technique, attenuated increases in arterial pressure and muscle sympathetic nerve activity during both static handgrip exercise and postexercise muscle ischemia. These findings indicate that ASICs contribute to both pressor and sympathetic responses to the activation of the skeletal muscle metaboreflex in humans.
Early Enrichment of ESR1 Mutations and the Impact on Gene Expression in Presurgical Primary Breast Cancer Treated with Aromatase Inhibitors
Authors: Leal Mariana Ferreira , Haynes Ben P. , Schuster Eugene , Yeo Belinda , Afentakis Maria , Zabaglo Lila , Martins Vera , Buus Richard , Dodson Andrew , Cheang Maggie C.U. , Smith Ian E. , Martin Lesley-Ann , Dowsett Mitch 
Published: September 2019

AbstractPurpose:To investigate the presence of ESR1 mutations in primary estrogen-receptor–positive (ER+) breast cancer treated with extended (&gt;4 weeks) neoadjuvant (presurgical) aromatase inhibitor (NAI) therapy and to identify patients who may gain less benefit from aromatase inhibition (AI) alone based upon on-treatment changes in gene expression.Experimental Design:We evaluated ER, progesterone receptor, and Ki67 by immunostaining, ESR1 mutations by droplet-digital PCR and expression of over 800 key breast cancer genes in paired pre- and post-NAI tumor samples from 87 ER+ breast cancer patients.Results:Cell proliferation and estrogen-regulated genes (ERG) remained suppressed in most tumors indicative of persistent response to NAI. Enrichment of ESR1 mutations was found in five tumors and predominantly in patients receiving therapy for &gt;6 months. ESR1-mutant tumors showed increased expression of ESR1 transcript and limited suppression of ERGs and proliferation-associated genes in response to NAI. ESR1 wild-type tumors with high residual proliferation (Ki67r ≥10%; 15/87 tumors) showed lower ESR1/ER expression pre- and post-therapy and lower ERGs. Tumors with ESR1 mutations or Ki67r ≥10% showed less inhibition of estrogen response, cell cycle, and E2F-target genes.Conclusions:Ligand-independent ER signaling, as a result of ESR1 mutation or reduced ER dependence, identified after extended NAI therapy, can guide early selection of patients who would benefit from combination therapy.
Multispecific Targeting with Synthetic Ankyrin Repeat Motif Chimeric Antigen Receptors
Authors: Balakrishnan Ashwini , Rajan Anusha , Salter Alexander I. , Kosasih Paula L. , Wu Qian , Voutsinas Jenna , Jensen Michael C. , Plückthun Andreas , Riddell Stanley R. 
Published: September 2019

Abstract

Purpose:
The outgrowth of antigen-negative variants is a significant challenge for adoptive therapy with T cells that target a single specificity. Chimeric antigen receptors (CAR) are typically designed with one or two scFvs that impart antigen specificity fused to activation and costimulation domains of T-cell signaling molecules. We designed and evaluated the function of CARs with up to three specificities for overcoming tumor escape using Designed Ankyrin Repeat Proteins (DARPins) rather than scFvs for tumor recognition.

Experimental Design:
A monospecific CAR was designed with a DARPin binder (E01) specific for EGFR and compared with a CAR designed using an anti-EGFR scFv. CAR constructs in which DARPins specific for EGFR, EpCAM, and HER2 were linked together in a single CAR were then designed and optimized to achieve multispecific tumor recognition. The efficacy of CAR-T cells bearing a multispecific DARPin CAR for treating tumors with heterogeneous antigen expression was evaluated in vivo.

Results:
The monospecific anti-EGFR E01 DARPin conferred potent tumor regression against EGFR+ targets that was comparable with an anti-EGFR scFv CAR. Linking three separate DARPins in tandem was feasible and in an optimized format generated a single tumor recognition domain that targeted a mixture of heterogeneous tumor cells, each expressing a single antigen, and displayed synergistic activity when tumor cells expressed more than one target antigen.

Conclusions:
DARPins can serve as high-affinity recognition motifs for CAR design, and their robust architecture enables linking of multiple binders against different antigens to achieve functional synergy and reduce antigen escape.
Impact of FDG PET Imaging for Expanding Patient Eligibility and Measuring Treatment Response in a Genome-Driven Basket Trial of the Pan-HER Kinase Inhibitor, Neratinib
Authors: Ulaner Gary A. , Saura Cristina , Piha-Paul Sarina A. , Mayer Ingrid , Quinn David , Jhaveri Komal , Stone Ben , Shahin Seta , Mann Grace , Dujka Melanie , Bryce Richard , Meric-Bernstam Funda , Solit David B. , Hyman David M. 
Published: September 2019

Abstract

Purpose:
To determine whether FDG PET can expand eligibility in biomarker-selected clinical trials by providing a means to quantitate response in patients with non-assessable disease by RECIST.

Experimental Design:
SUMMIT (NCT01953926) is a multicenter phase II “basket” trial of the Pan-HER kinase inhibitor, neratinib. Patients had advanced ERBB2 (HER2)-mutant solid tumors, ≥1 measurable lesion, preferably defined unidimensionally by RECIST v1.1, or alternatively metabolically by PET Response Criteria (PRC). The primary aim was to determine the proportion of additional breast cancer patients accrued using PRC who would have otherwise been ineligible based on RECIST criteria alone. The secondary aim was to determine the concordance of response versus non-response between RECIST and PRC.

Results:
Eighty-one patients with HER2-mutant metastatic breast cancer were accrued; 77 were evaluable for response by RECIST and/or PRC. 63 (82%) were RECIST-evaluable and 14 (18%) were accrued using PRC alone. Bone-only disease (n = 11; 79%) was the most common reason for classification as non-measurable by RECIST. Twenty-nine patients were accrued and followed using both criteria, of which 25 (86%; 95% confidence interval, 68%–96%) were concordant for response versus non-response as defined by RECIST and PRC.

Conclusions:
PRC allowed patients with non-RECIST measurable disease access to therapy and facilitated more rapid accrual of patients to this trial of a rare biomarker. PRC and RECIST both provided methods of response assessment and were generally concordant. Thus, PRC was useful as a supplement to RECIST criteria. This provides a rationale for including FDG PET measurements in future clinical trials involving rare tumors or rare genomically defined subpopulations of more common cancers.
Co-occurring Alterations in the RAS–MAPK Pathway Limit Response to MET Inhibitor Treatment in MET Exon 14 Skipping Mutation-Positive Lung Cancer
Authors: Rotow Julia K. , Gui Philippe , Wu Wei , Raymond Victoria M. , Lanman Richard B. , Kaye Frederic J. , Peled Nir , Fece de la Cruz Ferran , Nadres Brandon , Corcoran Ryan B. , Yeh Iwei , Bastian Boris C. , Starostik Petr , Newsom Kimberly , Olivas Victor R. , Wolff Alexander M. , Fraser James S. , Collisson Eric A. , McCoach Caroline E. , Camidge D. Ross , Pacheco Jose , Bazhenova Lyudmila , Li Tianhong , Bivona Trever G. , Blakely Collin M. 
Published: September 2019

Abstract

Purpose:
Although patients with advanced-stage non–small cell lung cancers (NSCLC) harboring MET exon 14 skipping mutations (METex14) often benefit from MET tyrosine kinase inhibitor (TKI) treatment, clinical benefit is limited by primary and acquired drug resistance. The molecular basis for this resistance remains incompletely understood.

Experimental Design:
Targeted sequencing analysis was performed on cell-free circulating tumor DNA obtained from 289 patients with advanced-stage METex14-mutated NSCLC.

Results:
Prominent co-occurring RAS–MAPK pathway gene alterations (e.g., in KRAS, NF1) were detected in NSCLCs with METex14 skipping alterations as compared with EGFR-mutated NSCLCs. There was an association between decreased MET TKI treatment response and RAS–MAPK pathway co-occurring alterations. In a preclinical model expressing a canonical METex14 mutation, KRAS overexpression or NF1 downregulation hyperactivated MAPK signaling to promote MET TKI resistance. This resistance was overcome by cotreatment with crizotinib and the MEK inhibitor trametinib.

Conclusions:
Our study provides a genomic landscape of co-occurring alterations in advanced-stage METex14-mutated NSCLC and suggests a potential combination therapy strategy targeting MAPK pathway signaling to enhance clinical outcomes.
Health-Related Quality of Life, Satisfaction with Care, and Cosmetic Results in Relation to Treatment among Patients with Keratinocyte Cancer in the Head and Neck Area: Results from the PROFILES Registry
Authors: Arts Lindy Paulina Johanna , Waalboer-Spuij Rick , de Roos Kees-Peter , Thissen Monique R.T.M. , Scheijmans Luc J. , Aarts Mieke J. , Oerlemans Simone , Lybeert Marnix L.M. , Louwman Marieke W.J. 
Published: September 2019

<b><i>Background:</i></b> Little is known about the impact of keratinocyte cancer (KC) and its treatment on health-related quality of life (HRQoL). <b><i>Objectives:</i></b> The objectives of the present study were (1) to evaluate HRQoL among patients with KC in a population-based setting and compare this with an age- end sex-matched normative population and (2) to compare HRQoL, satisfaction with care, and cosmetic results among patients who underwent conventional excision, Mohs’ micrographic surgery, or radiotherapy. <b><i>Method:</i></b> A random sample of 347 patients diagnosed with cutaneous basal cell or squamous cell carcinoma in the head and neck area between January 1, 2010, and December 31, 2014, were selected from the Netherlands Cancer Registry (NCR) and were invited to complete a questionnaire on HRQoL, satisfaction with care, and cosmetic results. Data were collected within Patient-Reported Outcomes Following Initial Treatment and Long-term Evaluation of Survivorship (PROFILES). Outcomes were compared to an age- and sex-matched normative population. <b><i>Results:</i></b> Two hundred fifteen patients with KC returned a completed questionnaire (62% response). Patients with KC reported better global quality of life (79.6 vs. 73.3, <i>p</i> &#x3c; 0.01) and less pain (<i>p</i> &#x3c; 0.01) compared to the normative population. No statistically significant differences in HRQoL, satisfaction with care, and cosmetic results were found between patients with KC who underwent conventional excision, Mohs’ micrographic surgery, or radiotherapy. <b><i>Conclusions:</i></b> The impact of KC and its treatment seems relatively low and more positive than negative as patients reported better HRQoL compared to an age- and sex-matched normative population, probably due to adaptation. No statistically significant differences between treatment types were found concerning HRQoL, patient satisfaction, and cosmetic results. This information could be used by healthcare professionals involved in KC care to improve patients’ knowledge about different aspects of the disease as patient’s preference is an important factor for treatment choice.