bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Validation of a Novel Nomogram for Individualized Prediction of Survival in Cancer of Unknown Primary
Authors: Raghav Kanwal , Hwang Hyunsoo , Jácome Alexandre A. , Bhang Eric , Willett Anneleis , Huey Ryan W. , Dhillon Nishat P. , Modha Jignesh , Smaglo Brandon , Matamoros Aurelio , Estrella Jeannelyn S. , Jao Justin , Overman Michael J. , Wang Xuemei , Greco F. Anthony , Loree Jonathan M. , Varadhachary Gauri R.
Published: April 2021

Purpose:

Prognostic uncertainty is a major challenge for cancer of unknown primary (CUP). Current models limit a meaningful patient-provider dialogue. We aimed to establish a nomogram for predicting overall survival (OS) in CUP based on robust clinicopathologic prognostic factors.

Experimental Design:

We evaluated 521 patients with CUP at MD Anderson Cancer Center (MDACC; Houston, TX; 2012–2016). Baseline variables were analyzed using Cox regression and nomogram developed using significant predictors. Predictive accuracy and discriminatory performance were assessed by calibration curves, concordance probability estimate (CPE ± SE), and concordance statistic (C-index). The model was subjected to bootstrapping and multi-institutional external validations using two independent CUP cohorts: V1 [MDACC (2017), N = 103] and V2 (BC Cancer, Vancouver, Canada and Sarah Cannon Cancer Center/Tennessee Oncology, Nashville, TN; N = 302).

Results:

Baseline characteristics of entire cohort (N = 926) included: median age (63 years), women (51%), Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1 (64%), adenocarcinomas (52%), ≥3 sites of metastases (30%), and median follow-up duration and OS of 40.1 and 14.7 months, respectively. Five independent prognostic factors were identified: gender, ECOG PS, histology, number of metastatic sites, and neutrophil-lymphocyte ratio. The resulting model predicted OS with CPE of 0.69 [SE: ± 0.01; C-index: 0.71 (95% confidence interval: 0.68–0.74)] outperforming Culine/Seve prognostic models (CPE: 0.59 ± 0.01). CPE for external validation cohorts V1 and V2 were 0.67 (± 0.02) and 0.70 (± 0.01), respectively. Calibration curves for 1-year OS showed strong agreement between nomogram prediction and actual observations in all cohorts.

Conclusions:

Our user-friendly CUP nomogram integrating commonly available baseline factors provides robust personalized prognostication which can aid clinical decision making and selection/stratification for clinical trials.
Phase II Multicenter Study of Enzalutamide in Metastatic Castration-Resistant Prostate Cancer to Identify Mechanisms Driving Resistance
Authors: McKay Rana R. , Kwak Lucia , Crowdis Jett P. , Sperger Jamie M. , Zhao Shuang G. , Xie Wanling , Werner Lillian , Lis Rosina T. , Zhang Zhenwei , Wei Xiao X. , Lang Joshua M. , Van Allen Eliezer M. , Bhatt Rupal S. , Yu Evan Y. , Nelson Peter S. , Bubley Glenn J. , Montgomery R. Bruce , Taplin Mary-Ellen
Published: April 2021

Purpose:

Enzalutamide is a second-generation androgen receptor (AR) inhibitor that has improved overall survival (OS) in metastatic castration-resistant prostate cancer (CRPC). However, nearly all patients develop resistance. We designed a phase II multicenter study of enzalutamide in metastatic CRPC incorporating tissue and blood biomarkers to dissect mechanisms driving resistance.

Patients and Methods:

Eligible patients with metastatic CRPC underwent a baseline metastasis biopsy and then initiated enzalutamide 160 mg daily. A repeat metastasis biopsy was obtained at radiographic progression from the same site when possible. Blood for circulating tumor cell (CTC) analysis was collected at baseline and progression. The primary objective was to analyze mechanisms of resistance in serial biopsies. Whole-exome sequencing was performed on tissue biopsies. CTC samples underwent RNA sequencing.

Results:

A total of 65 patients initiated treatment, of whom 22 (33.8%) had received prior abiraterone. Baseline biopsies were enriched for alterations in AR (mutations, amplifications) and tumor suppression genes (PTEN, RB1, and TP53), which were observed in 73.1% and 92.3% of baseline biopsies, respectively. Progression biopsies revealed increased AR amplifications (64.7% at progression vs. 53.9% at baseline) and BRCA2 alterations (64.7% at progression vs. 38.5% at baseline). Genomic analysis of baseline and progression CTC samples demonstrated increased AR splice variants, AR-regulated genes, and neuroendocrine markers at progression.

Conclusions:

Our results demonstrate that a large proportion of enzalutamide-treated patients have baseline and progression alterations in the AR pathway and tumor suppressor genes. We demonstrate an increased number of BRCA2 alterations post-enzalutamide, highlighting the importance of serial tumor sampling in CRPC.
Small Molecule Inhibitors of TEAD Auto-palmitoylation Selectively Inhibit Proliferation and Tumor Growth of NF2-deficient Mesothelioma
Authors: Tang Tracy T. , Konradi Andrei W. , Feng Ying , Peng Xiao , Ma Mingyue , Li Jian , Yu Fa-Xing , Guan Kun-Liang , Post Leonard
Published: April 2021

Mutations in the neurofibromatosis type 2 (NF2) gene that limit or abrogate expression of functional Merlin are common in malignant mesothelioma. Merlin activates the Hippo pathway to suppress nuclear translocation of YAP and TAZ, the major effectors of the pathway that associate with the TEAD transcription factors in the nucleus and promote expression of genes involved in cell proliferation and survival. In this article, we describe the discovery of compounds that selectively inhibit YAP/TAZ-TEAD promoted gene transcription, block TEAD auto-palmitoylation, and disrupt interaction between YAP/TAZ and TEAD. Optimization led to potent analogs with excellent oral bioavailability and pharmacokinetics that selectively inhibit NF2-deficient mesothelioma cell proliferation in vitro and growth of subcutaneous tumor xenografts in vivo. These highly potent and selective TEAD inhibitors provide a way to target the Hippo-YAP pathway, which thus far has been undruggable and is dysregulated frequently in malignant mesothelioma and in other YAP-driven cancers and diseases.

Watch the interview with Tracy T. Tang, PhD, recipient of the 2023 Molecular Cancer Therapeutics Award for Outstanding Journal Article: https://vimeo.com/847434464
Abstract PO-046: Combining PARP inhibition with radiation to sensitize homologous recombination proficient pancreatic cancer to immunotherapy
Authors: Zhang Qiang , Jiang Long , Zheng Yawen , Lawrence Theodore , Sahai Vaibhav , Green Michael D. , Morgan Meredith
Published: April 2021

Pancreatic cancer is notoriously resistant to most cancer therapeutics including immunotherapy. We have previously shown that inhibition of the DNA damage response (DDR) enhances radiation-induced Type I interferon (T1IFN) and sensitizes pancreatic cancers to immunotherapy. In this study, we investigated the efficacy of radiation in combination with the poly (ADP-ribose) polymerase (PARP)inhibitor olaparib and programmed death ligand 1 (PD-L1) immune checkpoint blockade in otherwise resistant homologous recombination (HR) proficient pancreatic cancer. Initial studies demonstrated, in contrast to olaparib alone, that the combination of olaparib and radiation induced innate immune signaling in HR proficient pancreatic cancer cells marked by increases in pTBK1, T1IFN and pSTAT1. In animal tumor models, we found that the therapeutic efficacy of olaparib and radiation was greater in immune competent versus immune deficient hosts. In addition to the positive immune effects of olaparib and radiation, we also observed increased expression of PD-L1, a negative immune regulatory mechanism that likely restrains T1IFN-mediated innate immunity. We therefore went on to test the combined efficacy of PD-L1 blocking antibody with olaparib and radiation in syngeneic pancreatic tumor models. We found that monotherapy was ineffective in controlling tumor growth while doublet therapy with olaparib and radiation produced an intermediate tumor growth response. Importantly, maximal tumor growth inhibition was achieved following combined treatment with olaparib, radiation, and anti-PD-L1 which was significant relative to doublet therapy with olaparib-radiation or anti-PD-L1-radiation, and associated with a 20% complete response rate. Given that advances in therapy of pancreatic cancer require improvements in both local and systemic disease control, we examined the efficacy of combined therapy against tumors outside of the radiation field. In addition to the effects on tumors in the radiation field, we found that combined therapy with olaparib, radiation and anti-PD-L1 significantly delayed the growth of contralateral tumors outside of the radiation field, suggesting an adaptive immune response. Taken together, these studies illustrate the potential efficacy of combined therapy with olaparib, radiation, and anti-PD-L1 on both local and systemic pancreatic cancer and support our proposed clinical trial in patients with pancreatic cancer.

Citation Format: Qiang Zhang, Long Jiang, Yawen Zheng, Theodore Lawrence, Vaibhav Sahai, Michael D. Green, Meredith Morgan. Combining PARP inhibition with radiation to sensitize homologous recombination proficient pancreatic cancer to immunotherapy [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-046.
The “Flying Intervention Team”: A Novel Stroke Care Concept for Rural Areas
Authors: Hubert Gordian Jan , Kraus Frank , Maegerlein Christian , Platen Sabine , Friedrich Benjamin , Kain Hans-Ulrich , Witton-Davies Thomas , Hubert Nikolai Dominik , Zimmer Claus , Bath Philip M. , Audebert Heinrich J. , Haberl Roman L.
Published: April 2021

Background: Endovascular treatment of large vessel occlusion in acute ischemic stroke patients is difficult to establish in remote areas, and time dependency of treatment effect increases the urge to develop health care concepts for this population. Summary: Current strategies include direct transportation of patients to a comprehensive stroke center (CSC) (“mothership model”) or transportation to the nearest primary stroke center (PSC) and secondary transfer to the CSC (“drip-and-ship model”). Both have disadvantages. We propose the model “flying intervention team.” Patients will be transported to the nearest PSC; if telemedically identified as eligible for thrombectomy, an intervention team will be acutely transported via helicopter to the PSC and endovascular treatment will be performed on site. Patients stay at the PSC for further stroke unit care. This model was implemented at a telestroke network in Germany. Fifteen remote hospitals participated in the project, covering 14,000 km2 and a population of 2 million. All have well established telemedically supported stroke units, an angiography suite, and a helicopter pad. Processes were defined individually for each hospital and training sessions were implemented for all stroke teams. An exclusive project helicopter was installed to be available from 8 a.m. to 10 p.m. during 26 weeks per year. Key Messages: The model of the flying intervention team is likely to reduce time delays since processes will be performed in parallel, rather than consecutively, and since it is quicker to move a medical team rather than a patient. This project is currently under evaluation (clinicaltrials NCT04270513).
Interleukin 8 Elicits Rapid Physiological Changes in Neutrophils That Are Altered by Inflammatory Conditions
Authors: Bernhard Stefan , Hug Stefan , Stratmann Alexander Elias Paul , Erber Maike , Vidoni Laura , Knapp Christiane Leonie , Thomaß Bertram Dietrich , Fauler Michael , Nilsson Bo , Nilsson Ekdahl Kristina , Föhr Karl , Braun Christian Karl , Wohlgemuth Lisa , Huber-Lang Markus , Messerer David Alexander Christian
Published: April 2021

A sufficient response of neutrophil granulocytes stimulated by interleukin (IL)-8 is vital during systemic inflammation, for example, in sepsis or severe trauma. Moreover, IL-8 is clinically used as biomarker of inflammatory processes. However, the effects of IL-8 on cellular key regulators of neutrophil properties such as the intracellular pH (pHi) in dependence of ion transport proteins and during inflammation remain to be elucidated. Therefore, we investigated in detail the fundamental changes in pHi, cellular shape, and chemotactic activity elicited by IL-8. Using flow cytometric methods, we determined that the IL-8-induced cellular activity was largely dependent on specific ion channels and transporters, such as the sodium-proton exchanger 1 (NHE1) and non-NHE1-dependent sodium flux. Exposing neutrophils in vitro to a proinflammatory micromilieu with N-formyl-Met-Leu-Phe, LPS, or IL-8 resulted in a diminished response regarding the increase in cellular size and pH. The detailed kinetics of the reduced reactivity of the neutrophil granulocytes could be illustrated in a near-real-time flow cytometric measurement. Last, the LPS-mediated impairment of the IL-8-induced response in neutrophils was confirmed in a translational, animal-free human whole blood model. Overall, we provide novel mechanistic insights for the interaction of IL-8 with neutrophil granulocytes and report in detail about its alteration during systemic inflammation.
Fast Automated Stereo-EEG Electrode Contact Identification and Labeling Ensemble
Authors: Ervin Brian , Rozhkov Leonid , Buroker Jason , Leach James L. , Mangano Francesco T. , Greiner Hansel M. , Holland Katherine D. , Arya Ravindra
Published: April 2021

Introduction: Stereotactic electroencephalography (SEEG) has emerged as the preferred modality for intracranial monitoring in drug-resistant epilepsy (DRE) patients being evaluated for neurosurgery. After implantation of SEEG electrodes, it is important to determine the neuroanatomic locations of electrode contacts (ECs), to localize ictal onset and propagation, and integrate functional information to facilitate surgical decisions. Although there are tools for coregistration of preoperative MRI and postoperative CT scans, identification, sorting, and labeling of SEEG ECs is often performed manually, which is resource intensive. We report development and validation of a software named Fast Automated SEEG Electrode Contact Identification and Labeling Ensemble (FASCILE). Methods: FASCILE is written in Python 3.8.3 and employs a novel automated method for identifying ECs, assigning them to respected SEEG electrodes, and labeling. We compared FASCILE with our clinical process of identifying, sorting, and labeling ECs, by computing localization error in anteroposterior, superoinferior, and lateral dimensions. We also measured mean Euclidean distances between ECs identified by FASCILE and the clinical method. We compared time taken for EC identification, sorting, and labeling for the software developer using FASCILE, a first-time clinical user using FASCILE, and the conventional clinical process. Results: Validation in 35 consecutive DRE patients showed a mean overall localization error of 0.73 ± 0.15 mm. FASCILE required 10.7 ± 5.5 min/patient for identifying, sorting, and labeling ECs by a first-time clinical user, compared to 3.3 ± 0.7 h/patient required for the conventional clinical process. Conclusion: Given the accuracy, speed, and ease of use, we expect FASCILE to be used frequently for SEEG-driven epilepsy surgery. It is freely available for noncommercial use. FASCILE is specifically designed to expedite localization of ECs, assigning them to respective SEEG electrodes (sorting), and labeling them and not for coregistration of CT and MRI data as there are commercial software available for this purpose.
Public Perception and Attitude toward Community Pharmacists in Saudi Arabia
Authors: Almohammed Omar A. , Alsanea Sary
Published: April 2021

Background: The Saudi healthcare system is undergoing a major transformation, and pharmacists will assume more responsibilities in providing healthcare services. The current study aims to determine the current perception and attitude of the public toward pharmacists, as well as the public satisfaction with pharmacists’ practices and services in the community pharmacy setting. Methods: A cross-sectional, online questionnaire-based study was conducted between February and April 2019 and included adult participants (≥18 years) who could read and complete an Arabic online survey. χ2 and correlation tests were used to investigate differences in perception and attitude toward community pharmacists based on study population demographics and characteristics and assess the association between public perception and attitude. Statistical analysis was conducted using SAS software, version 9.4. Results: A total of 387 participants completed the survey. The overall Saudi public’s perception and attitude toward community pharmacists were positive in the study population, scoring 81.4% for perception and 69.8% for attitude, with female participants having a more favorable perception of community pharmacists than male participants (89.3 vs. 77.7%, p < 0.01). A strong and positive correlation between public perception and attitude was recognized in the study (r = 0.71, p < 0.01). The participants were found to be mostly satisfied with pharmacists’ commitment and communication skills, but not, however, with the level of pharmaceutical care services provided. Conclusion: The current positive perception and attitude toward community pharmacists among the Saudi public create an opportunity for pharmacists to assume expanded roles as healthcare providers. However, their pharmaceutical care skills should be improved in order to gain their patients’ trust and provide them with valuable services.
Etiology of Dementia in Thai Patients
Authors: Dharmasaroja Pornpatr A. , Assanasen Jintana , Pongpakdee Sunsanee , Jaisin Kankamol , Lolekha Praween , Phanasathit Muthita , Cheewakriengkrai Laksanun , Chotipanich Chanisa , Witoonpanich Pirada , Pitiyarn Sutisa , Lertwilaiwittaya Pongtawat , Dejthevaporn Charungthai , Limwongse Chanin , Phanthumchinda Kammant ,   The Collaborative Aging and Dementia Research Society Thailand (CART)
Published: April 2021

Introduction: Molecular imaging has been developed and validated in Thai patients, comprising a portion of patients in the dementia registry. This should provide a more accurate diagnosis of the etiology of dementia, which was the focus of this study. Methods: This was a multicenter dementia study. The baseline characteristics, main presenting symptoms, and results of investigations and cognitive tests of the patients were electronically collected in the registry. Functional imaging and/or molecular imaging were performed in patients with an equivocal diagnosis of the causes of dementia, especially in atypical dementia or young onset dementia (YOD). Results: There were 454 patients in the study. The mean age of the patients was 78 years, with 60% female. Functional imaging and/or molecular imaging were performed in 57 patients (57/454 patients, 13%). The most common cause of dementia was Alzheimer’s disease (AD; 50%), followed by vascular dementia (VAD; 24%), dementia with Lewy bodies (6%), Parkinson’s disease dementia (6%), frontotemporal dementia (FTD; 2.6%), progressive supranuclear palsy (2%), multiple system atrophy (0.8%), and corticobasal syndrome (0.4%). YOD accounted for 17% (77/454 patients), with a mean age of 58 years. The causes of YOD were early onset amnestic AD (44%), VAD (16%), behavioral variant FTD (8%), posterior cortical atrophy (6.5%), and logopenic variant primary progressive aphasia (5.2%). Conclusion: AD was the most common cause of dementia in Thai patients and the distribution of other types of dementia and main presenting symptoms were similar to previous reports in Western patients; however, the proportion of YOD was higher.
Donkey skin trade: is it sustainable to slaughter donkeys for their skin?
Authors: Tatemoto Patricia , Lima Yuri Fernandes , Santurtun Eduardo , Reeves Emily Kate , Raw Zoe
Published: April 2021

Donkeys (Equus asinus) face a global crisis. The health, welfare, and even survival of donkeys are being compromised as the demand for their skins increases. It is driven by the production of ejiao, a traditional Chinese remedy believed by some to have medicinal properties. It is estimated that the ejiao industry currently requires approximately 4.8 million donkey skins per year. Since there is no productive chain for donkey skin production outside of China, the activity is extractive and has resulted in the decimation of donkeys. Gestation is 12 months in donkeys, increasing the risk of extinction if such practices are not controlled. In this scenario, the donkeys are collected (purchased for low prices, stolen, and collected from the side of the roads) and are then often transported for long distances, usually without water, food, or rest. The trade, in Brazil, poses significant biosecurity risks, particularly because examinations are rarely conducted and therefore infectious diseases, such as glanders and infectious anemia, remain undetected. Furthermore, in chronic stress situations, the immune system is suppressed, increasing the biosecurity risk, especially because donkeys are a silent carrier of diseases. Rarely there is traceability with animals from different origins being put together in “fake farms”, before being delivered to slaughterhouses. The opportunistic strategy of collecting animals, or buying for low prices, keeping them without access to food and veterinary assistance, is what makes this trade profitable. Our experience in donkey welfare and the global skin trade suggest that it will be enormously challenging and cost-prohibitive to run a trade at the standards required to be considered humane, sustainable, and safe. Although donkeys are being blamed for the involvement in road accidents, it is not an ethical solution to maintain this trade as an alternative. Moreover, the ecological role of donkeys in native ecosystems has not been elucidated, and some studies indicate they could even have a positive effect. Regardless of the future the donkeys will have; we must guarantee a life with the least dignity to the animals under our responsibility.
The human-animal relationship and its influence in our culture: the case of donkeys
Authors: Lima Yuri Fernandes , Tatemoto Patricia , Santurtun Eduardo , Reeves Emily Kate , Raw Zoe
Published: April 2021

Donkeys (Equus asinus) face a global crisis. Their health, welfare, and even their local survival are compromised as the demand for their skins increases. Such demand for donkey skins aims to supply the ejiao industry. Ejiao is a traditional remedy made from the collagen of donkey skins. Some people believe it has medicinal properties. It is estimated that the ejiao industry currently requires approximately 4.8 million donkey skins per year. Although the future of the donkeys is still uncertain, we must guarantee a life free from suffering to the animals under our responsibility. The trade of donkey skins also undermines the cultural role of donkeys. Donkeys have developed an essential role in Brazil, especially in the Northeast region of the country, carrying on their backs construction materials, water, and food, and, as a consequence, helping people build cities in the deepest hinterland. The close relationship between people and donkeys affords donkeys a unique place in the local culture. This central importance has been recognized by Brazilian artists throughout history. We have many examples of songs, books, “cordeis” (typical Brazilian literature), poems, documentaries, movies, woodcuts, paintings, and sculptures, created to honor this important actor. Here we describe some examples of this human-donkey relationship, and its influence on our culture.
Loss of Transforming Growth Factor Beta Signaling in Aortic Smooth Muscle Cells Causes Endothelial Dysfunction and Aortic Hypercontractility
Authors: Zhu Jay , Angelov Stoyan , Alp Yildirim Ilkay , Wei Hao , Hu Jie Hong , Majesky Mark W. , Brozovich Frank V. , Kim Francis , Dichek David A.
Published: April 2021

Objective:

Humans and mice with loss-of-function variants of genes in the TGF-β (transforming growth factor beta) signaling pathway develop aortic aneurysms. These aneurysms could be caused by decreased aortic smooth muscle cell (SMC) contractile-protein levels and impaired aortic SMC contractile-unit function. Accordingly, we investigated whether loss of SMC TGF-β signaling in mice alters aortic contractile-protein levels and aortic contractility.

Approach and Results:

We used immunoblotting, wire myography, histological analyses, and measurements of aortic nitric oxide and superoxide levels to assess aortic contractile-protein levels and vasomotor function in mice with SMC-specific deletion of the type 2 TGF-β receptor (TBR2
SMΔ
mice). Aortic contractile-protein levels were not altered in TBR2
SMΔ
mice. Surprisingly, TBR2
SMΔ
mice had increased aortic contractility and severe endothelial dysfunction. Endothelial dysfunction was manifested as decreased relaxation to acetylcholine (Emax 37% versus 97%;
P
<0.0001), decreased aortic nitric oxide (50%;
P
=0.005), decreased endothelial nitric oxide synthase activation (31%;
P
=0.002), and lower aortic levels of phosphorylated vasodilator-stimulated phosphoprotein (an indicator of nitric oxide bioavailability: 65%;
P
<0.0001). Aortic hypercontractility was reduced by mechanical denudation of endothelium and was eliminated by pretreatment of TBR2
SMΔ
and control aortas with a nitric oxide synthase inhibitor, revealing a significant positive interaction between aortic hypercontractility and absence of endothelium-derived nitric oxide (
P
<0.05 for both denudation and nitric oxide inhibition).

Conclusions:

Aortic aneurysms that develop in TBR2
SMΔ
mice are not caused by decreased SMC contractility. Loss of physiological SMC TGF-β signaling causes endothelial dysfunction leading to aortic hypercontractility. Endothelial dysfunction may contribute to vascular pathologies associated with abnormal TGF-β signaling.
Nanoart and the Moving Image: Shifts in Perception from Optical Microscopy to Nanoscopy
Authors: Rassell Andrea
Published: April 2021

Artists engaging with the nanoscale have a particular problem of representation: Humans are unable to directly perceive nanoscale phenomena. Even without sensory or temporal experience of these phenomena, nanoartists are exploring technological, interactive and audiovisual mediation techniques. The author discusses this “problematic perception,” describes a key piece of nanoscientific instrumentation and finds diverse nanoart practices that exhibit a common concern for multisensoriality and embodied experience. This reflects our human desire to use our bodies to explore the world. Finally the author explores the question: How might nanoscientific and cinematic imaging systems work together with the perceiving body to further facilitate this multisensoriality?
The Grammar of PP-like Free Relatives: Evidence from Subordinatewo-Clauses in German
Authors: Bücking Sebastian
Published: April 2021

This article addresses the grammar of PP-like free relatives (= PP-FRs) such as the locative clause in Bello schläft, wo Grace schläft ‘Bello is sleeping where Grace is sleeping’. The most prominent compositional analysis of PP-FRs is developed by Caponigro (2004), Caponigro and Pearl (2009), and Hall and Caponigro (2010). They derive PP-FRs from a stacked CP-structure that is based on silent prepositions and a nominal treatment of wh-words such as where. I first argue against this analysis by means of a detailed discussion of subordinate clauses introduced by wo ‘where’ in German. Specifically, I show that wo-clauses do not involve silent prepositions, and that both wo and wo-clauses are prepositional instead of nominal in nature. Second, I sketch a surface-oriented alternative approach to PP-FRs that dispenses with silent prepositions and assigns the prepositional nature of PP-like wh-words a key role in the derivation. Specifically, I propose that the fronting of PP-like wh-words in free relatives licenses an abstraction over predicates (instead of entities) and a corresponding type shifting. I relate the new analysis to analyses of corresponding subordinate headed relative and interrogative clauses. Furthermore, I evaluate it against potential general constraints on higher-order abstraction as argued for, in particular, by Poole (2017).
EDITOR: An Edit-Based Transformer with Repositioning for Neural Machine Translation with Soft Lexical Constraints
Authors: Xu Weijia , Carpuat Marine
Published: April 2021

We introduce an Edit-Based TransfOrmer with Repositioning (EDITOR), which makes sequence generation flexible by seamlessly allowing users to specify preferences in output lexical choice. Building on recent models for non-autoregressive sequence generation (Gu et al., 2019), EDITOR generates new sequences by iteratively editing hypotheses. It relies on a novel reposition operation designed to disentangle lexical choice from word positioning decisions, while enabling efficient oracles for imitation learning and parallel edits at decoding time. Empirically, EDITOR uses soft lexical constraints more effectively than the Levenshtein Transformer (Gu et al., 2019) while speeding up decoding dramatically compared to constrained beam search (Post and Vilar, 2018). EDITOR also achieves comparable or better translation quality with faster decoding speed than the Levenshtein Transformer on standard Romanian-English, English-German, and English-Japanese machine translation tasks.
Fixed Forms of Behavior as Excessively Rigid Behavior in Normal and Pathological Individual and Group Systems
Authors: Zalevskii Genrikh V.
Published: April 2021

Background. !is article is devoted to the problem of excessively rigid behavior, which the author has named “"xed forms of behavior” (FFB). !is term was suggested to me by the concepts of P. Janet (idée !xe), S. Freud (Fixierung), and D. Uznadze (!ksirovanaya ustanovka — "xed set/attitude). By FFB, the author understands a broad spectrum of behaviors of a person or a group of people, which, according to the cultural norms of a given society for persons of a certain age, gender, and status, have become inappropriate, yet are repeated in situations objectively requiring that they change; the degree of realization and acceptance of the need for this change can vary. Results. !rough literature analysis and the collection of experimental data over many years of research, in which over 1,150 persons took part — 550 healthy subjects and 600 mental patients from a broad spectrum — and on the basis of a biopsychosocionoetic model of the nature of man and his health, and a system-network approach, it has become possible to distinguish the following models to explain the nature of "xed forms of behavior: neurodynamic, energy-economic, phylogenetic, personenvironment relationship, dispositional, stressogenic, pathogenic, psychodynamic, learning (behavioral-cognitive), system (an excessively rigid system and structural relations between levels of action).
Using Tree-Ring Research to Introduce Students to Geoscience Fieldwork
Authors: Tucker Clay S. , Trepanier Jill C. , Blanchard Pamela B. , Bush Ed , Jordan James W. , Schafer Mark J. , Nyman John Andrew
Published: April 2021

Environmental education is key in solving environmental problems and for producing a future workforce capable of solving issues of climate change. Over the last two decades, the Coastal Roots Program at Louisiana State University (LSU) has reached more than 26,676 K–12 students in Louisiana to teach them environmental science and has brought them to restoration sites to plant 194,336 school-grown trees and grasses. The codirectors of Coastal Roots are continually searching for opportunities to enrich the experience of teachers and students in connecting school subjects, Coastal Roots, and stewardship. In school year 2018/19, students in five local schools entered a pilot program to learn how tree-ring science informs environmental science broadly. During their scheduled restoration planting trips, students were asked to collect the following tree data: tree cores, tree height, tree diameter, tree species, and global positioning system location points. Data were given to scientists at LSU for preliminary analysis, and graphical representation of the data were shown to the students for their interpretation. Results from this program indicate that bringing students into the field and teaching them a new scientific skill improved their understanding of environmental science and their role in coastal restoration, and tree-ring data showed significant correlations to various climate parameters in Louisiana. Additionally, we find that bringing this knowledge to teachers allows the knowledge to spread for multiple generations of students. Here we present tree-ring data from this project, lessons learned during the pilot program, advantages to student-based citizen science, and recommendations for similar programs.
Implementation of a semi-Lagrangian fully-implicit time integration of the unified soundproof system of equations for numerical weather prediction
Authors: Qaddouri Abdessamad , Girard Claude , Husain Syed Zahid , Aider Rabah
Published: April 2021

An alternate dynamical core that employs the unified equations of A. Arakawa and C.S. Konor (2009) has been developed within Environment and Climate change Canada’s GEM (Global Environmental Multiscale) atmospheric model. As in the operational GEM dynamical core, the novel core utilizes the same fully-implicit two-time-level semi-Lagrangian scheme for time discretization while the log-pressure-based terrain-following vertical coordinate has been slightly adapted. Overall, the new dynamical core implementation required only minor changes to the existing informatics code of the GEM model and from a computational performance perspective, the new core does not incur any significant additional cost. A broad range of tests – that include both two-dimensional idealized theoretical cases and three-dimensional deterministic forecasts covering both hydrostatic and non-hydrostatic scales–have been carried out to evaluate the performance of the new dynamical core. For all the tested cases, when compared to the operational GEM model, the new dynamical core based on the unified equations has been found to produce statistically equivalent results. These results imply that the unified equations can be adopted for operational numerical weather prediction that would employ a single soundproof system of equations to produce reliable forecasts for all meteorological scales of interest with negligible changes for the computational overhead.
Physics-augmented Deep Learning to Improve Tropical Cyclone Intensity and Size Estimation from Satellite Imagery
Authors: Zhuo Jing-Yi , Tan Zhe-Min
Published: April 2021

A deep learning-based method augmented by prior knowledge of tropical cyclones (TCs), called DeepTCNet, is introduced to estimate TC intensity and wind radii from infrared (IR) imagery over the North Atlantic Ocean. While standard deep learning practices have many advantages over conventional analysis approaches and can produce reliable estimates of TCs, the data-driven models informed by machine-readable physical knowledge of TCs could achieve higher performance. To this end, two approaches are explored to develop the physics-augmented DeepTCNet: (i) infusing the auxiliary physical information of TCs into models for single-task learning; (ii) learning auxiliary physical tasks for multi-task learning. More specifically, augmented by auxiliary information of TC fullness (a measure of the radial decay of the TC wind field), the DeepTCNet yielded a 12% improvement in estimating TC intensity over the non-augmented one. By learning TC wind radii and auxiliary TC intensity task simultaneously, the model’s wind radii estimation skill is improved by 6% over only learning four wind radii tasks, and by 9% over separately learning a single wind radii task. The evaluation results showed that the DeepTCNet is in-line with the Satellite Consensus technique (SATCON) but systematically outperforms the Advanced Dvorak Technique (ADT) at all intensity scales with an averaged 39% enhancement in TC intensity estimation. The DeepTCNet also surpasses the Multi-platform Tropical Cyclone Surface Wind Analysis technique (MTCSWA) with an average improvement of 32% in wind radii estimation.
Cascading Crises: Society in the Age of COVID-19
Authors: Robinson Laura , Schulz Jeremy , Ball Christopher , Chiaraluce Cara , Dodel Matías , Francis Jessica , Huang Kuo-Ting , Johnston Elisha , Khilnani Aneka , Kleinmann Oliver , Kwon K. Hazel , McClain Noah , Ng Yee Man Margaret , Pait Heloisa , Ragnedda Massimo , Reisdorf Bianca C. , Ruiu Maria Laura , Xavier da Silva Cinthia , Trammel Juliana Maria , Wiborg Øyvind N. , Williams Apryl A.
Published: April 2021

The tsunami of change triggered by the COVID-19 pandemic has transformed society in a series of cascading crises. Unlike disasters that are more temporarily and spatially bounded, the pandemic has continued to expand across time and space for over a year, leaving an unusually broad range of second-order and third-order harms in its wake. Globally, the unusual conditions of the pandemic—unlike other crises—have impacted almost every facet of our lives. The pandemic has deepened existing inequalities and created new vulnerabilities related to social isolation, incarceration, involuntary exclusion from the labor market, diminished economic opportunity, life-and-death risk in the workplace, and a host of emergent digital, emotional, and economic divides. In tandem, many less advantaged individuals and groups have suffered disproportionate hardship related to the pandemic in the form of fear and anxiety, exposure to misinformation, and the effects of the politicization of the crisis. Many of these phenomena will have a long tail that we are only beginning to understand. Nonetheless, the research also offers evidence of resilience on several fronts including nimble organizational response, emergent communication practices, spontaneous solidarity, and the power of hope. While we do not know what the post COVID-19 world will look like, the scholarship here tells us that the virus has not exhausted society’s adaptive potential.
Performance characteristics of five SARS-CoV-2 serological assays: Clinical utility in health-care workers
Authors: Heffernan Emma , Kennedy Lisa , Hannan Margaret M , Ramlaul Navneet , Denieffe Stephanie , Courtney Garry , Watt Alison , Hurley John , Lynch Maureen , Fitzgibbon Maria
Published: April 2021

Study objective:

SARS-CoV-2, which causes coronavirus disease (COVID-19), continues to cause significant morbidity and mortality. The diagnosis of acute infection relies on reverse transcription-polymerase chain reaction (RT-PCR)-based viral detection. The objective of this study was to evaluate the optimal serological testing strategy for anti-SARS-CoV-2 antibodies which provides an important indicator of prior infection and potential short-term immunity.

Methods

The sensitivity and specificity of four different ELISA assays (Euroimmun IgG, Euroimmun NCP-IgG, Fortress and DIAsource) and one CLIA assay (Roche ELECSYS) were evaluated in 423 samples; 137 patients with confirmed RT-PCR COVID-19 infection (true positives), and 100 pre-pandemic samples collected prior to October 2019 (true negatives). A further 186 samples were collected from health-care staff and analysed by all five assays.

Results

The Fortress ELISA assay demonstrated the highest sensitivity and specificity followed by the Roche ECLIA assay. The highest overall sensitivity came from the assays that measured total antibody (IgM–IgG combined) and the three assays that performed the best (Fortress, Roche, Euroimmun IgG) all have different antigens as their target proteins which suggests that antigen target does not affect assay performance. In mildly symptomatic participants with either a negative RT-PCR or no RT-PCR performed, 16.76% had detectable antibodies suggesting previous infection.

Conclusions

We recommend a combined testing strategy utilizing assays with different antigenic targets using the fully automated Roche ECLIA assay and confirming discordant samples with the Fortress Total Antibody ELISA assay. This study provides an important indicator of prior infection in symptomatic and asymptomatic individuals.
Efficacy of CO-OP Approach With and Without Parental Coaching: RCT Study Protocol: Efficacité de l’approche CO-OP avec et sans coaching parental : protocole d’essai clinique randomisé
Authors: Araújo Clarice Ribeiro Soares , Cardoso Ana Amélia , Magalhães Lívia de Castro
Published: April 2021

Background.

Developmental coordination disorder (DCD) leads to decreased occupational performance and restricted participation. Cognitive Orientation to daily Occupational Performance Approach (CO-OP) is effective, and as parental support is a key element, it seems relevant to investigate.

Purpose.

To describe a study protocol that will compare CO-OP with and without Occupational Performance Coaching (OPC) on activity and participation of children with DCD.

Method.

Randomized controlled with seven to 12-year-olds, assigned to either experimental (CO-OP+OPC) or control (CO-OP) group, both receiving traditional CO-OP, with four additional parental group sessions for the experimental group.

Key Issues.

Actual and perceived occupational performance and satisfaction of children’s chosen goals and participation, motor performance and executive function. Measures will be obtained at baseline, post-intervention, and at 3-month follow-up.

Implications.

Detailed description of an intervention protocol may help further replication and may contribute to clarify if a boost on parents’ participation promotes better outcomes for children with DCD.

Trial registration.

Clinical Trials, NCT02893852. ( https://clinicaltrials.gov/ct2/show/NCT02893852 )
The weak frequency anomaly detection method of atomic clocks based on Kalman filter and extrapolation-accumulation
Authors: Yan Ran , Liu Junliang , Wu Jianfeng , Xu Chao , Hu Yonghui
Published: April 2021

A new method based on the innovation of Kalman filter and extrapolation-accumulation is proposed to detect weak frequency anomalies in atomic clocks with short detection time and high detection probability. In this method, the detection statistics of the innovation extrapolation method in several epochs are accumulated. It avoids the influence of outliers, increases the noncentrality parameter of chi-square distribution, and realizes more effective detection of weak frequency anomalies. The simulation results show that compared with the innovation method and the innovation extrapolation method, the new method has a higher detection probability for micro frequency anomalies, and the detection time is shortened. The new method is used to analyze the real data of the cesium atomic clock, and the results are consistent with the simulation results.
A modified genetic algorithm for task assignment of heterogeneous unmanned aerial vehicle system
Authors: Han Song , Fan Chenchen , Li Xinbin , Luo Xi , Liu Zhixin
Published: April 2021

This study deals with the task assignment problem of heterogeneous unmanned aerial vehicle (UAV) system with the limited resources and task priority constraints. The optimization model which comprehensively considers the resource consumption, task completion effect, and workload balance is formulated. Then, a concept of fuzzy elite degree is proposed to optimize and balance the transmission of good genes and the variation strength of population during the operations of algorithm. Based on the concept, we propose the fuzzy elite strategy genetic algorithm (FESGA) to efficiently solve the complex task assignment problem. In the proposed algorithm, two unlock methods are presented to solve the deadlock problem in the random optimization process; a sudden threat countermeasure (STC) mechanism is presented to help the algorithm quickly respond to the change of task environment caused by sudden threats. The simulation results demonstrate the superiority of the proposed algorithm. Meanwhile, the effectiveness and feasibility of the algorithm in workload balance and task priority constraints are verified.
Stigma towards schizophrenia in Cyprus: Does studying a mental health related programme make a difference?
Authors: Nikolaou Elena , Petkari Eleni
Published: April 2021

Background and aims:

Students from mental health related programmes may display stigmatising attitudes towards people of schizophrenia, however there are no data available on this population in Cyprus. The purpose of the present study was (a) to examine the levels of contact and stigma towards schizophrenia in Cypriot students of programmes related to mental health and students of other programmes and (b) to examine whether the successful recognition of a person with schizophrenia through a vignette and the estimation of severity levels was related to stigmatising attitudes.

Methods:

The participants were undergraduate students purposively selected across Cypriot universities ( N = 152). A vignette depicting a person with schizophrenia, followed by the OMI to examine stigma and the BAE to examine contact with mental illness were used to collect the data.

Results:

The results showed that studying a mental health related programme and being a man was associated with more positive views related to social integration. No further stigma dimensions were predicted by the included variables. Similarly, level of contact and being able to identify the mental condition and estimate its severity was not related to stigma.

Conclusion:

The results emphasise the need to develop educational interventions to tackle stigma across students independently of their study programme and enhance mental health related programmes with opportunities for structured contact with patients with mental illness.
Imaging, clinical, and pathologic findings of Sertoli-leydig cell tumors
Authors: Chen Jingya , Liu Yuting , Zhang Yu , Wang Yaohui , Chen Xiao , Wang Zhongqiu
Published: April 2021

To explore the clinical features, imaging findings, and pathological manifestations of ovarian Sertoli-Leydig cell tumors (SLCTs). The clinical and pathological manifestations, tumor location, size, morphology, vascularity, computed tomography (CT) density, magnetic resonance imaging (MRI) signal intensity, and contrast enhancement patterns in five cases with SLCTs were retrospectively reviewed. SLCTs most commonly occurred in young women. Virilization was observed in three cases (60%). All five tumors were unilateral and oval or round, with a clear boundary. The solid part of the tumor was isoattenuated on the conventional CT scan, and showed isoattenuation or slight hypoattenuation relative to adjacent myometrium on T1 weighted imaging (T1WI) and T2 weighted imaging (T2WI). On contrast-enhanced images, three tumors showed marked enhancement. DICER1 hotspot mutations were commonly seen in SLCTs. A highly vascularized mass with low signal intensity (SI) of the solid part on T2WI and androgen overproduction symptoms may suggest an SLCT.