bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute cigarette smoke‐induced eQTL affects formyl peptide receptor expression and lung function
Authors: Pouwels Simon D. , Wiersma Valerie R. , Fokkema Immeke E. , Berg Marijn , ten Hacken Nick H.T. , van den Berge Maarten , Heijink Irene , Faiz Alen 
Published: October 2020

ABSTRACTBackground and objectiveCigarette smoking is one of the most prevalent causes of preventable deaths worldwide, leading to chronic diseases, including chronic obstructive pulmonary disease (COPD). Cigarette smoke is known to induce significant transcriptional modifications throughout the respiratory tract. However, it is largely unknown how genetic profiles influence the smoking‐related transcriptional changes and how changes in gene expression translate into altered alveolar epithelial repair responses.MethodsWe performed a candidate‐based acute cigarette smoke‐induced eQTL study, investigating the association between SNP and differential gene expression of FPR family members in bronchial epithelial cells isolated 24 h after smoking and after 48 h without smoking. The effects FPR1 on lung epithelial integrity and repair upon damage in the presence and absence of cigarette smoke were studied in CRISPR‐Cas9‐generated lung epithelial knockout cells.ResultsOne significant (FDR < 0.05) inducible eQTL (rs3212855) was identified that induced a >2‐fold change in gene expression. The minor allele of rs3212855 was associated with significantly higher gene expression of FPR1, FPR2 and FPR3 upon smoking. Importantly, the minor allele of rs3212855 was also associated with lower lung function. Alveolar epithelial FPR1 knockout cells were protected against CSE‐induced reduction in repair capacity upon wounding.ConclusionWe identified a novel smoking‐related inducible eQTL that is associated with a smoke‐induced increase in the expression of FPR1, FPR2 and FPR3, and with lowered lung function. in vitro FPR1 down‐regulation protects against smoke‐induced reduction in lung epithelial repair.
A case report of cleidocranial dysplasia: A noninvasive approach
Authors: Ayub Nur Aliya Filzah Mohd , Hamzah Siti Hajar , Hussein Alaa Sabah , Rajali Aimeeza , Ahmad Mas Suryalis 
Published: October 2020

AbstractCleidocranial dysplasia (CCD) is a rare bone disorder. The main dental features are the presence of multiple retained deciduous teeth and supernumerary teeth, as well as unerupted permanent teeth. To date, CCD is managed by a combination approach, which consists of the extraction of deciduous and supernumerary teeth, followed by orthodontic traction of unerupted permanent teeth. This case highlights the management of a girl with CCD, who refused the recommended protocol. A 15‐year‐old Malay female presented with a complaint of retained deciduous teeth. Intraoral examination revealed multiple retained deciduous teeth. Radiographs showed numerous impacted supernumerary and unerupted permanent teeth. The patient opted to improve her facial appearance with a less aggressive treatment option. A composite build‐up on all anterior maxillary deciduous teeth was carried out until the patient was ready to undergo surgical intervention.
Variscan ultra‐high‐pressure eclogite in the Upper Allochthon of the Rhodope Metamorphic Complex (Bulgaria)
Authors: Trapp Svenja , Janák Marian , Fassmer Kathrin , Froitzheim Nikolaus , Münker Carsten , Georgiev Neven 
Published: October 2020

AbstractThe Rhodope Metamorphic Complex (RMC) in Bulgaria has been established as a Mesozoic ultra‐high‐pressure metamorphic province by findings of microdiamond in gneisses. Additionally, Variscan ultra‐high‐pressure metamorphism has been proposed for the Ograzhden/Vertiskos Unit in the Upper Allochthon of the RMC, based on findings of coesite, graphite pseudomorphs after diamond and indirect age constraints. We confirm ultra‐high‐pressure metamorphism of eclogites in this unit using thermobarometry, phase‐equilibrium modelling and the Variscan age of metamorphism using Lu–Hf garnet–whole‐rock dating. In Belica (southern Rila Mountains), kyanite‐ and phengite‐bearing eclogite enclosed in high‐grade gneisses records P‐T conditions of 3.0–3.5 GPa and 700–750°C. Lu–Hf dating of eclogite samples from Belica and Gega (Ograzhden Mountain), where coesite was found, yielded ages of 334.1 ± 1.8 and 334.0 ± 2.2 Ma, respectively, interpreted as the age of garnet growth during post‐collisional subduction of continental crust after closure of the Rheic Ocean.
Eliciting Attribute-Level User Needs From Online Reviews With Deep Language Models and Information Extraction
Authors: Han Yi , Moghaddam Mohsen 
Published: October 2020

Abstract
Eliciting user needs for individual components and features of a product or a service on a large scale is a key requirement for innovative design. Synthesizing data as an initial discovery phase of a design process is usually accomplished with a small number of participants, employing qualitative research methods such as observations, focus groups, and interviews. This leaves an entire swath of pertinent user behavior, preferences, and opinions not captured. Sentiment analysis is a key enabler for large-scale need finding from online user reviews generated on a regular basis. A major limitation of current sentiment analysis approaches used in design sciences, however, is the need for laborious labeling and annotation of large review datasets for training, which in turn hinders their scalability and transferability across different domains. This article proposes an efficient and scalable methodology for automated and large-scale elicitation of attribute-level user needs. The methodology builds on the state-of-the-art pretrained deep language model, BERT (Bidirectional Encoder Representations from Transformers), with new convolutional net and named entity recognition (NER) layers for extracting attribute, description, and sentiment words from online user review corpora. The machine translation algorithm BLEU (BiLingual Evaluation Understudy) is utilized to extract need expressions in the form of predefined part-of-speech combinations (e.g., adjective–noun, verb–noun). Numerical experiments are conducted on a large dataset scraped from a major e-commerce retail store for apparel and footwear to demonstrate the performance, feasibility, and potentials of the developed methodology.
Vomiting-induced costal cartilage fracture: a case report
Authors: Drakonaki Eleni , Karageorgiou Ioannis , Kokkinakis Stamatios , Maliotis Neofytos , Spyridaki Rania , Symvoulakis Emmanouil K 
Published: October 2020

The use of ultrasonography as a first line imaging test in cases of possible costal cartilage fracture can be pivotal. In this case report, we present the case of a patient with a suspected atraumatic vomiting-induced costal cartilage fracture. The costal cartilage fracture was non-displaced and incomplete, thus not visible in a Computed Tomography scan. When Ultrasound imaging was employed at the area of tenderness, soft tissue edema and hematoma around the cartilage were visualized. High level of suspicion for a cartilage fracture in this case revealed a subtle osseous injury.
Assessing the value of human papillomavirus vaccination in Gavi-eligible low-income and middle-income countries
Authors: Ochalek Jessica , Abbas Kaja , Claxton Karl , Jit Mark , Lomas James 
Published: October 2020

IntroductionEstimating the value of providing effective healthcare interventions in a country requires an assessment of whether the improvement in health outcomes they offer exceeds the improvement in health that would have been possible if the resources required had, instead, been made available for other healthcare activities in that country. This potential alternative use of the same resources represents the health opportunity cost of providing the intervention. Without such assessments, there is a danger that blanket recommendations made by international organisations will lead to the adoption of healthcare interventions that are not cost effective in some countries, even given existing donor mechanisms intended to support their affordability.MethodsWe assessed the net health impact to 46 Gavi-eligible countries of achieving one of the WHO’s proposed 90-70-90 targets for cervical cancer elimination, which includes 90% coverage of human papillomavirus (HPV) vaccination among girls by 15 years of age, using published estimates of the expected additional benefits and costs in each country and estimates of the marginal productivity of each healthcare system. We calculated the maximum price each country could afford to pay for HPV vaccination to be cost effective by assessing the net health impact that would be expected to be generated at different potential prices.ResultsAt Gavi negotiated prices, HPV vaccination offers net health benefits across most Gavi-eligible countries included in this study. However, if Gavi-eligible countries faced the average price faced by non-Gavi eligible countries, providing HPV vaccination would result in reduced overall population health in most countries.ConclusionEstimates of the net health impact of providing a healthcare intervention can be used to assess the benefit (or lack of) to countries of adhering to global guidance, inform negotiations with donors, as well as pricing negotiations and the value of developing new healthcare interventions.
Vacuum Brans–Dicke theory in the Jordan and Einstein frames: Can they be distinguished by lensing?
Authors: Izmailov Ramil N. , Karimov Ramis Kh. , Potapov Alexander A. , Nandi Kamal K. 
Published: October 2020

Vacuum Brans-Dicke (BD) theory continues to receive widespread attention since it is consistent with solar and cosmological experiments. The theory can be self-consistently described in two frames, the Jordan frame (JF) and the conformally rescaled Einstein frame (EF), the transformations providing an easy passage from one frame to the other at the level of actions and solutions. While coordinate transformations do not change curvature properties, conformal transformations do change them leading to corresponding changes in the numerical values of observables. A previous article by Bhadra et al.[Formula: see text] did exemplify this change between JF and EF using the diagnostic of second-order light deflection. This important work leaves room for further improvements on two points, which we do here. First, the measurement of second-order effect faced technically unsurmountable difficulties even around the Sun, hence actually abandoned. Second, the comparison of quantitative values between JF and EF should be based on a common value of [Formula: see text] connecting the two frames. Keeping these in mind, we investigate a technically easier diagnostic, viz., the weak field lensing (WFL) and compare the quantitative changes at common [Formula: see text] to show that the two frames can indeed be distinguished by lensing experiments. Specifically, the predictions of light deflection, image position, total magnification and magnification factor are computed in the EF and compared with those recently obtained (by Gao et al.[Formula: see text]) directly in the JF BD class I solution. The use of the value of BD coupling constant [Formula: see text], suggested by the Cassini spacecraft solar experiment, reveals that an exceptionally high degree of accuracy is needed to experimentally rule out one or the other frame by means of WFL measurements.
A cohomological gravity in D = 11
Authors: Yu Feng 
Published: October 2020

A [Formula: see text] cohomological gravity is introduced. The central piece is a new BRST-like symmetry [Formula: see text] with [Formula: see text] up to a diffeomorphism and gauge symmetry. The only nontrivial observable of this symmetry is a Chern–Simons integral. The construction of the symmetry requires a spin 0 fermion [Formula: see text] and a spin [Formula: see text] boson [Formula: see text] at the minimum, in addition to the standard gravity and gauge fields, to close the algebra off-shell. The gravity action is uniquely determined by requiring a field redefinition type of global symmetry between bosonic and fermionic fields. It is of a simple form [Formula: see text] plus a Chern–Simons term, and appears as the [Formula: see text] supergravity action under a special combination of the fields without independent presence of [Formula: see text] and [Formula: see text]. The [Formula: see text]-invariant path-integral measure, which is also invariant under the global symmetry, is shown to exist for the theory to be valid at quantum level. It achieves only when the fields are redefined under certain combination that is different from the special combination, and the fields in this combination are interpreted as physical fields. At [Formula: see text] limit, where all field combinations converges, the theory reduces to [Formula: see text] supergravity and the global symmetry becomes the local supersymmetry with [Formula: see text] as the local variable. At a nonvanishing [Formula: see text] limit set by residue symmetries upon broken [Formula: see text]-symmetry, the theory admits a cosmological solution that has a wavy term to allow accelerated expansion of the universe while not violate null energy condition.
Assessing 10-Year Safety of a Single Negative HPV Test for Cervical Cancer Screening: Evidence from FOCAL-DECADE Cohort
Authors: Gottschlich Anna , van Niekerk Dirk , Smith Laurie W. , Gondara Lovedeep , Melnikow Joy , Cook Darrel A. , Lee Marette , Stuart Gavin , Martin Ruth E. , Peacock Stuart , Franco Eduardo L. , Coldman Andrew , Krajden Mel , Ogilvie Gina 
Published: October 2020

Abstract

Background:
Long-term safety of a single negative human papillomavirus (HPV) test for cervical cancer screening is unclear. The HPV FOr cerviCAL Cancer Trial (FOCAL) was a randomized trial comparing HPV testing with cytology. The FOCAL-DECADE cohort tracked women who received one HPV test during FOCAL, and were HPV negative, for up to 10 years to identify cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+) detected through a provincial screening program.

Methods:
FOCAL participants who received one HPV test, were negative, and had at least one post-FOCAL cervix screen were included (N = 5,537). We constructed cumulative incidence curves of CIN2+/CIN3+ detection, analyzed cumulative risk of detection at intervals post-HPV test, calculated average incidence rates for detection, and compared hazard across ages.

Results:
Ten years after one negative HPV test, the probability of CIN2+ detection was lower than 1%, with most lesions detected 7 years or later. Average incidence rates of CIN2+/CIN3+ lesions over follow-up were 0.50 [95% confidence interval (CI), 0.31–0.78] and 0.18 (95% CI, 0.07–0.36) per 1,000 person-years, respectively. Hazards were higher for younger ages (nonsignificant trend).

Conclusions:
Among women with a single negative HPV test, long-term risk of CIN2+ detection was low, particularly through 7 years of follow-up; thus, one negative HPV test appears to confer long-term protection from precancerous lesions. Even 10-year risk is sufficiently low to support extended testing intervals in average-risk populations.

Impact:
Our findings support the safety of screening policies using HPV testing alone at 5-year or longer intervals.
Overcoming MET-Dependent Resistance to Selective RET Inhibition in Patients with RET Fusion–Positive Lung Cancer by Combining Selpercatinib with Crizotinib
Authors: Rosen Ezra Y. , Johnson Melissa L. , Clifford Sarah E. , Somwar Romel , Kherani Jennifer F. , Son Jieun , Bertram Arrien A. , Davare Monika A. , Gladstone Eric , Ivanova Elena V. , Henry Dahlia N. , Kelley Elaine M. , Lin Mika , Milan Marina S.D. , Nair Binoj C. , Olek Elizabeth A. , Scanlon Jenna E. , Vojnic Morana , Ebata Kevin , Hechtman Jaclyn F. , Li Bob T. , Sholl Lynette M. , Taylor Barry S. , Ladanyi Marc , Jänne Pasi A. , Rothenberg S. Michael , Drilon Alexander , Oxnard Geoffrey R. 
Published: October 2020

Abstract

Purpose:
The RET proto-oncogene encodes a receptor tyrosine kinase that is activated by gene fusion in 1%–2% of non–small cell lung cancers (NSCLC) and rarely in other cancer types. Selpercatinib is a highly selective RET kinase inhibitor that has recently been approved by the FDA in lung and thyroid cancers with activating RET gene fusions and mutations. Molecular mechanisms of acquired resistance to selpercatinib are poorly understood.

Patients and Methods:
We studied patients treated on the first-in-human clinical trial of selpercatinib (NCT03157129) who were found to have MET amplification associated with resistance to selpercatinib. We validated MET activation as a targetable mediator of resistance to RET-directed therapy, and combined selpercatinib with the MET/ALK/ROS1 inhibitor crizotinib in a series of single patient protocols (SPP).

Results:
MET amplification was identified in posttreatment biopsies in 4 patients with RET fusion–positive NSCLC treated with selpercatinib. In at least one case, MET amplification was clearly evident prior to therapy with selpercatinib. We demonstrate that increased MET expression in RET fusion–positive tumor cells causes resistance to selpercatinib, and this can be overcome by combining selpercatinib with crizotinib. Using SPPs, selpercatinib with crizotinib were given together generating anecdotal evidence of clinical activity and tolerability, with one response lasting 10 months.

Conclusions:
Through the use of SPPs, we were able to offer combination therapy targeting MET-amplified resistance identified on the first-in-human study of selpercatinib. These data suggest that MET dependence is a recurring and potentially targetable mechanism of resistance to selective RET inhibition in advanced NSCLC.
T-cell–engaging Therapy for Solid Tumors
Authors: de Miguel Maria , Umana Pablo , Gomes de Morais Ana Luiza , Moreno Victor , Calvo Emiliano 
Published: October 2020

Abstract
T-cell engagers (TCE) are a rapidly evolving novel group of treatments that have in common the concurrent engagement of a T-cell surface molecule and a tumoral cell antigen. Bispecific antibodies and genetically engineered adoptive cell therapies, as chimeric antigen receptors or T-cell receptors, have similarities and differences among their mechanisms of action, toxicity profiles, and resistance pathways. Nevertheless, the success observed in the hematologic field has not been obtained with solid tumors yet, as they are biologically more complex and have few truly tumor-specific cell surface antigens that can be targeted with high avidity T cells. Different strategies are under study to improve their short-term perspective, such as new generations of more active TCEs, multi-target or combination of different treatments approaches, or to improve the manufacturing processes. A comprehensive review of TCEs as a grouped treatment class, their current status, and research directions in their application to solid tumors therapeutics are discussed here.
Hematopoietic Stem Cell Transplantation Positively Affects the Natural History of Cancer in Nijmegen Breakage Syndrome
Authors: Wolska-Kusnierz Beata , Pastorczak Agata , Fendler Wojciech , Wakulinska Anna , Dembowska-Baginska Bozena , Heropolitanska-Pliszka Edyta , Piątosa Barbara , Pietrucha Barbara , Kałwak Krzysztof , Ussowicz Marek , Pieczonka Anna , Drabko Katarzyna , Lejman Monika , Koltan Sylwia , Gozdzik Jolanta , Styczynski Jan , Fedorova Alina , Miakova Natalia , Deripapa Elena , Kostyuchenko Larysa , Krenova Zdenka , Hlavackova Eva , Gennery Andrew R. , Sykora Karl-Walter , Ghosh Sujal , Albert Michael H. , Balashov Dmitry , Eapen Mary , Svec Peter , Seidel Markus G. , Kilic Sara S. , Tomaszewska Agnieszka , Wiesik-Szewczyk Ewa , Kreins Alexandra , Greil Johann , Buechner Jochen , Lund Bendik , Gregorek Hanna , Chrzanowska Krystyna , Mlynarski Wojciech 
Published: October 2020

Abstract

Purpose:
Nijmegen breakage syndrome (NBS) is a DNA repair disorder with a high predisposition to hematologic malignancies.

Experimental Design:
We describe the natural history of NBS, including cancer incidence, risk of death, and the potential effectiveness of hematopoietic stem cell transplantation (HSCT) in preventing both pathologies: malignancy and immunodeficiency.

Results:
Among 241 patients with NBS enrolled in the study from 11 countries, 151 (63.0%) patients were diagnosed with cancer. Incidence rates for primary and secondary cancer, tumor characteristics, and risk factors affecting overall survival (OS) were estimated. The cumulative cancer incidence was 40.21% ± 3.5% and 77.78% ± 3.4% at 10 years and 20 years of follow-up, respectively. Most of the tumors n = 95 (62.9%) were non-Hodgkin lymphomas. Overall, 20 (13.2%) secondary malignancies occurred at a median age of 18 (interquartile range, 13.7–21.5) years. The probability of 20-year overall survival (OS) for the whole cohort was 44.6% ± 4.5%. Patients who developed cancer had a shorter 20-year OS than those without malignancy (29.6% vs. 86.2%; P &lt; 10−5). A total of 49 patients with NBS underwent HSCT, including 14 patients transplanted before malignancy. Patients with NBS with diagnosed cancer who received HSCT had higher 20-year OS than those who did not (42.7% vs. 30.3%; P = 0.038, respectively). In the group of patients who underwent preemptive transplantation, only 1 patient developed cancer, which is 6.7 times lower as compared with nontransplanted patients [incidence rate ratio 0.149 (95% confidence interval, 0.138–0.162); P &lt; 0.0001].

Conclusions:
There is a beneficial effect of HSCT on the long-term survival of patients with NBS transplanted in their first complete remission of cancer.
Therapy of Myeloid Leukemia using Novel Bispecific Fusion Proteins Targeting CD45 and 90Y-DOTA
Authors: Orozco Johnnie J. , Kenoyer Aimee L. , Lin Yukang , O'Steen Shyril , Guel Rosario , Nartea Margaret E. , Hernandez Alexandra H. , Hylarides Mark D. , Fisher Darrell R. , Balkin Ethan R. , Hamlin Donald K. , Wilbur D. Scott , Orcutt Kelly D. , Wittrup K. Dane , Green Damian J. , Gopal Ajay K. , Till Brian G. , Sandmaier Brenda , Press Oliver W. , Pagel John M. 
Published: October 2020

Abstract
Pretargeted radioimmunotherapy (PRIT) has been investigated as a multi-step approach to decrease relapse and toxicity for high-risk acute myeloid leukemia (AML). Relevant factors including endogenous biotin and immunogenicity, however, have limited the use of PRIT with an anti-CD45 antibody streptavidin conjugate and radiolabeled DOTA-biotin. To overcome these limitations we designed anti-murine and anti-human CD45 bispecific antibody constructs using 30F11 and BC8 antibodies, respectively, combined with an anti-yttrium (Y)-DOTA single-chain variable fragment (C825) to capture a radiolabeled ligand. The bispecific construct targeting human CD45 (BC8-Fc-C825) had high uptake in leukemia HEL xenografts [7.8 ± 0.02% percent injected dose/gram of tissue (% ID/g)]. Therapy studies showed that 70% of mice with HEL human xenografts treated with BC8-Fc-C825 followed by 44.4 MBq (1,200 μCi) of 90Y-DOTA-biotin survived at least 170 days after therapy, while all nontreated controls required euthanasia because of tumor progression by day 32. High uptake at sites of leukemia (spleen and bone marrow) was also seen with 30F11-IgG1-C825 in a syngeneic disseminated SJL murine leukemia model (spleen, 9.0 ± 1.5% ID/g and bone marrow, 8.1 ± 1.2% ID/g), with minimal uptake in all other normal organs (&lt;0.5% ID/g) at 24 hours after 90Y-DOTA injections. SJL leukemia mice treated with the bispecific 30F11-IgG1-C825 and 29.6 MBq (800 μCi) of 90Y-DOTA-biotin had a survival advantage compared with untreated leukemic mice (median, 43 vs. 30 days, respectively; P &lt; 0.0001). These data suggest bispecific antibody–mediated PRIT may be highly effective for leukemia therapy and translation to human studies.