bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of DNA-PK with AZD7648 Sensitizes Tumor Cells to Radiotherapy and Induces Type I IFN-Dependent Durable Tumor Control
Authors: Nakamura Kyoko , Karmokar Ankur , Farrington Paul M. , James Neil H. , Ramos-Montoya Antonio , Bickerton Susan J. , Hughes Gareth D. , Illidge Timothy M. , Cadogan Elaine B. , Davies Barry R. , Dovedi Simon J. , Valge-Archer Viia 
Published: May 2021

Abstract

Purpose:
Combining radiotherapy (RT) with DNA damage response inhibitors may lead to increased tumor cell death through radiosensitization. DNA-dependent protein kinase (DNA-PK) plays an important role in DNA double-strand break repair via the nonhomologous end joining (NHEJ) pathway. We hypothesized that in addition to a radiosensitizing effect from the combination of RT with AZD7648, a potent and specific inhibitor of DNA-PK, combination therapy may also lead to modulation of an anticancer immune response.

Experimental Design:
AZD7648 and RT efficacy, as monotherapy and in combination, was investigated in fully immunocompetent mice in MC38, CT26, and B16-F10 models. Immunologic consequences were analyzed by gene expression and flow-cytometric analysis.

Results:
AZD7648, when delivered in combination with RT, induced complete tumor regressions in a significant proportion of mice. The antitumor efficacy was dependent on the presence of CD8+ T cells but independent of NK cells. Analysis of the tumor microenvironment revealed a reduction in T-cell PD-1 expression, increased NK-cell granzyme B expression, and elevated type I IFN signaling in mice treated with the combination when compared with RT treatment alone. Blocking of the type I IFN receptor in vivo also demonstrated a critical role for type I IFN in tumor growth control following combined therapy. Finally, this combination was able to generate tumor antigen-specific immunologic memory capable of suppressing tumor growth following rechallenge.

Conclusions:
Blocking the NHEJ DNA repair pathway with AZD7648 in combination with RT leads to durable immune-mediated tumor control.
Preexisting and Post–COVID-19 Immune Responses to SARS-CoV-2 in Patients with Cancer
Authors: Bilich Tatjana , Roerden Malte , Maringer Yacine , Nelde Annika , Heitmann Jonas S. , Dubbelaar Marissa L. , Peter Andreas , Hörber Sebastian , Bauer Jens , Rieth Jonas , Wacker Marcel , Berner Fiamma , Flatz Lukas , Held Stefanie , Brossart Peter , Märklin Melanie , Wagner Philipp , Erne Eva , Klein Reinhild , Rammensee Hans-Georg , Salih Helmut R. , Walz Juliane S. 
Published: May 2021

Abstract

Patients with cancer, in particular patients with hematologic malignancies, are at increased risk for critical illness upon COVID-19. We here assessed antibody as well as CD4+ and CD8+ T-cell responses in unexposed and SARS-CoV-2–infected patients with cancer to characterize SARS-CoV-2 immunity and to identify immunologic parameters contributing to COVID-19 outcome. Unexposed patients with hematologic malignancies presented with reduced prevalence of preexisting SARS-CoV-2 cross-reactive CD4+ T-cell responses and signs of T-cell exhaustion compared with patients with solid tumors and healthy volunteers. Whereas SARS-CoV-2 antibody responses did not differ between patients with COVID-19 and cancer and healthy volunteers, intensity, expandability, and diversity of SARS-CoV-2 T-cell responses were profoundly reduced in patients with cancer, and the latter associated with a severe course of COVID-19. This identifies impaired SARS-CoV-2 T-cell immunity as a potential determinant for dismal outcome of COVID-19 in patients with cancer.

Significance:
This first comprehensive analysis of SARS-CoV-2 immune responses in patients with cancer reports on the potential implications of impaired SARS-CoV-2 T-cell responses for understanding pathophysiology and predicting severity of COVID-19, which in turn might allow for the development of therapeutic measures and vaccines for this vulnerable patient population.
See related commentary by Salomé and Horowitz, p. 1877.
This article is highlighted in the In This Issue feature, p. 1861
Late Outcomes of the RAPID-TnT Randomized Controlled Trial: 0/1-Hour High-Sensitivity Troponin T Protocol in Suspected ACS
Authors: Lambrakis Kristina , Papendick Cynthia , French John K. , Quinn Stephen , Blyth Andrew , Seshadri Anil , Edmonds Michael J.R. , Chuang Anthony , Khan Ehsan , Nelson Adam J. , Wright Deborah , Horsfall Matthew , Morton Erin , Karnon Jonathan , Briffa Tom , Cullen Louise A. , Chew Derek P. 
Published: May 2021

Background:
High-sensitivity troponin assays are increasingly being adopted to expedite evaluation of patients with suspected acute coronary syndromes. Few direct comparisons have examined whether the enhanced performance of these assays at low concentrations leads to changes in care that improves longer-term outcomes. This study evaluated late outcomes of participants managed under an unmasked 0/1-hour high-sensitivity cardiac troponin T (hs-cTnT) protocol compared with a 0/3-hour masked hs-cTnT protocol.

Methods:
We conducted a multicenter prospective patient-level randomized comparison of care informed by unmasked 0/1-hour hs-cTnT protocol (reported to <5 ng/L) versus standard practice masked hs-cTnT testing (reported to ≤29 ng/L) assessed at 0/3 hours and followed participants for 12 months. Participants included were those presenting to metropolitan emergency departments with suspected acute coronary syndromes, without ECG evidence of coronary ischemia. The primary end point was time to all-cause death or myocardial infarction using Cox proportional hazards models adjusted for clustering within hospitals.

Results:

Between August 2015 and April 2019, we randomized 3378 participants, of whom 108 withdrew, resulting in 12-month follow-up for 3270 participants (masked: 1632; unmasked: 1638). Among these, 2993 (91.5%) had an initial troponin concentration of ≤29 ng/L. Deployment of the 0/1-hour hs-cTnT protocol was associated with reductions in functional testing. Over 12-month follow-up, there was no difference in invasive coronary angiography (0/1-hour unmasked: 232/1638 [14.2%]; 0/3-hour masked: 202/1632 [12.4%];
P
=0.13), although an increase was seen among patients with hs-cTnT levels within the masked range (0/1-hour unmasked arm: 168/1507 [11.2%]; 0/3-hour masked arm: 124/1486 [8.3%];
P
=0.010). By 12 months, all-cause death and myocardial infarction did not differ between study arms overall (0/1-hour: 82/1638 [5.0%] versus 0/3-hour: 62/1632 [3.8%]; hazard ratio, 1.32 [95% CI, 0.95–1.83];
P
=0.10). Among participants with initial troponin T concentrations ≤29 ng/L, unmasked hs-cTnT reporting was associated with an increase in death or myocardial infarction (0/1-hour: 55/1507 [3.7%] versus 0/3-hour: 34/1486 [2.3%]; hazard ratio, 1.60 [95% CI, 1.05–2.46];
P
=0.030).

Conclusions:
Unmasked hs-cTnT reporting deployed within a 0/1-hour protocol did not reduce ischemic events over 12-month follow-up. Changes in practice associated with the implementation of this protocol may be associated with an increase in death and myocardial infarction among those with newly identified troponin elevations.

Registration:

URL:
https://www.anzctr.org.au
; Unique identifier: ACTRN12615001379505.
The response of rice varieties to Meloidogyne graminicola from the Mekong Delta, Vietnam
Authors: Nguyê˜n Phong V. , Trâ`n Thă´ng B. , Nguyê˜n Phong T. , Nguyê˜n Loan N.T. , Biện Thanh L.T. , Tôn Linh B. , Lê Tiên T.H. , Tôn Ánh T. , Nguyê˜n Quô´c B. , Huỳnh Biê´t V. , Lê Ðôn Ð. , Bellafiore Stéphane 
Published: May 2021

Summary
The rice root-knot nematode, Meloidogyne graminicola, is a serious pathogen of rice production worldwide. In Vietnam, scientific information on the rice root-knot nematode is limited. In this circumstance, our study aimed to investigate the characteristics of M. graminicola from rice fields in southern Vietnam and to evaluate the reaction of 20 rice varieties to this soil-borne pathogen in a glasshouse experiment. Ten populations of root-knot nematode collected from rice fields at different geographical regions in the Mekong Delta were identified as M. graminicola based on the perineal configuration of females and species-specific molecular markers. The morphological, morphometric and molecular characteristics of ten nematode isolates were defined, and the variations observed between these isolates were not significantly different. The pathogenicity of these isolates was examined in the susceptible Indica rice, Oryza sativa ‘IR64’, with a reproduction factor ranging from 18.1 to 37.8. Of the 20 Indica rice varieties tested in response to the nematode population MG-PN08, the ‘Tetep’ variety showed moderate resistance to the nematode (reproductive factor = 11.7; galling index = 2.4), while others were ranked at levels ranging from moderately susceptible to highly susceptible. The life cycle of M. graminicola in ‘Tetep’ root is 28 days compared to 21 in ‘IR64’. ‘Tetep’-nematode interaction at the histological and molecular levels needs further investigation to develop new rice varieties resistant to rice root-knot nematode.
Bursaphelenchus hibisci n. sp. (Nematoda: Aphelenchoididae) isolated from Ernoporus corpulentus (Scolytinae) emerged from dead Hibiscus tiliaceus (Malvaceae) twigs from Okinawa, Japan
Authors: Kanzaki Natsumi , Tsujimoto Satoshi , Kajimura Hisashi 
Published: May 2021

Summary
A Bursaphelenchus sp. belonging to the B. idius-group was isolated from a bark beetle, Ernoporus corpulentus, which had emerged from dead twigs of Hibiscus tiliaceus collected in Okinawa, in the subtropical region of Japan. In addition to its group-specific characters, i.e., four lateral lines in both male and female and less developed capitulum and relatively broad blade of the male spicules, the species is characterised by a relatively slender female tail with various tip shapes. Molecularly, the species is close to B. fagi and B. tiliae based on SSU and D2-D3 LSU sequences, but can be clearly distinguished from these two species. The species is described and illustrated herein as B. hibisci n. sp.
‘Goat Beautiful of Voice’: A Piyyut of Abraham ibn Ezra from Medinet el-Fayyūm, Egypt
Authors: Harris Alex , Zellmann-Rohrer Michael 
Published: May 2021

Abstract
This zuta provides an edition of a new copy of a known piyyut by Abraham ibn Ezra, ‘Goat beautiful of voice’ (יַעְלָה יְפַת קוֹל), with translation, full collation, and commentary. This copy, now in the collection of the University of Michigan (P.Mich. inv. 531), offers some valuable new readings as well as evidence for the readership of Ibn Ezra in a provincial setting in medieval Egypt, as its provenance can be traced to the city of Medinet el-Fayyūm; the text can be added to evidence for a Jewish presence there, of which an overview is also given.
The Naturalizing Program of Perceptions Defended
Authors: de Sá Pereira Roberto Horácio 
Published: May 2021

Abstract
The author defends the naturalizing program of the notion of representation against the primitivist view according to which the notion of representation as belonging to psychology as a mature science is irreducible. First, the author concedes that the original teleological project trivializes the concept of representation by applying it to bacteria, protozoa, amoeba, when the best available explanation is the assumption that primitive organisms and artifacts are merely indicating proximal stimulation rather than representing the distal causes of stimulation. Yet, the author does not believe that this presents an unsurmountable obstacle for the naturalizing program when what is in question is genuine sensory representation, namely perception. In the author’s view, what matters for the naturalizing program are not cases in which the concept of representation is misemployed, but rather cases in which the focus is genuine sensory representation, that is, genuine perceptions; or so he shall argue.
Double warm-core structure and potential vorticity diagnosis during the rapid intensification of Supertyphoon Lekima (2019)
Authors: Shi Donglei , Chen Guanghua 
Published: May 2021

AbstractThe rapid intensification (RI) of supertyphoon Lekima (2019) is investigated from the perspective of balanced potential vorticity (PV) dynamics using a high-resolution numerical simulation. The PV budget shows that the inner-core PV anomalies (PVAs) formed during the RI mainly comprise an eyewall PV tower generated by diabatic heating, a high-PV bridge extending into the eye resulting from the PV mixing, and an upper-tropospheric high-PV core induced by the PV intrusion from stratosphere. The inversion of the total PVA at the end of the RI captures about 90% of changes in pressure and wind fields, indicating that the storm is quasi-balanced. The piecewise PV inversion further demonstrates that the eyewall and mixed PVAs induce the upper-level and midlevel warm cores in the eye region, respectively. The two warm cores cause nearly all the balanced central pressure decrease and thus dominate the RI, with the contribution of the upper warm core being twice that of the midlevel one. In contrast, the upper-tropospheric PV core induces significant warming near the tropopause and deep-layer cooling beneath, reinforcing the upper-level warm core but causing little surface pressure drop.By comparing the diabatic PV generation due to the convective burst (CB) and non-CB precipitation, we found that the non-CB precipitation accounts for a larger portion for the eyewall PVA and thus the associated upper-level warming, distinct from previous studies that primarily attributed the upper-level warm-core formation to the CB. Nevertheless, CBs act to be more efficient PV generators due to their vigorous latent heat release and are thus favorable for RI.
Hand Posture and Force Estimation Using Surface Electromyography and an Artificial Neural Network
Authors: Wang Mengcheng , Zhao Chuan , Barr Alan , Fan Hao , Yu Suihuai , Kapellusch Jay , Harris Adamson Carisa 
Published: May 2021

Objective The purpose of this study was to develop an approach to predict hand posture (pinch versus grip) and grasp force using forearm surface electromyography (sEMG) and artificial neural networks (ANNs) during tasks that varied repetition rate and duty cycle. Background Prior studies have used electromyography with machine learning models to predict grip force but relatively few studies have assessed whether both hand posture and force can be predicted, particularly at varying levels of duty cycle and repetition rate. Method Fourteen individuals participated in this experiment. sEMG data for five forearm muscles and force output data were collected. Calibration data (25, 50, 75, 100% of maximum voluntary contraction (MVC)) were used to train ANN models to predict hand posture (pinch versus grip) and force magnitude while performing tasks that varied load, repetition rate, and duty cycle. Results Across all participants, overall hand posture prediction accuracy was 79% (0.79 ± .08), whereas overall hand force prediction accuracy was 73% (0.73 ± .09). Accuracy ranged between 0.65 and 0.93 based on varying repetition rate and duty cycle. Conclusion Hand posture and force prediction were possible using sEMG and ANNs, though there were important differences in the accuracy of predictions based on task characteristics including duty cycle and repetition rate. Application The results of this study could be applied to the development of a dosimeter used for distal upper extremity biomechanical exposure measurement, risk assessment, job (re)design, and return to work programs.
Status of Agricultural Credit and Indebtedness in India: An Analysis
Authors: Maurya Suresh Kumar , Vishwakarma Neha 
Published: May 2021

This article attempts to analyse status of agricultural credit and indebtedness in India. The objectives of the study are as follows: (a) to study a comparison of flow of total institutional agricultural credit among different land size groups at all India level; (b) to study a comparison of indebtedness of agricultural households between different size classes of land possessed at both states and all India level and (c) to analyse incidence of indebtedness in major Indian states. It is concluded that mostly, short- and medium-term loans of agricultural purposes are taken for marginal land size groups in India. The percentage of indebted agricultural households to total agricultural household increases as land size increases. The percentage of holdings is less than percentage of indebted agricultural households in Punjab, Uttar Pradesh, Andhra Pradesh, West Bengal, Karnataka, Odisha and Rajasthan. JEL Code: Q14
Achieving Testing Effects in an Authentic College Classroom
Authors: Shobe Elizabeth 
Published: May 2021

Background: Findings from the testing effect literature suggest several ways to achieve testing effects in an authentic classroom, but few consider instructor workload, equity, and resources that determine feasibility and sustainability of testing effect methods in practice. Objective: To determine elements and procedures from the testing effect literature for practical application, devise a method for feasibly and sustainably implementing testing effect methods in practice, and determine if a simple way to incorporate retrieval practice into an existing introduction to psychology course was sufficient to observe testing effects. Method: Quiz scores of Introductory Psychology sections with and without retrieval practice were compared. Sections with retrieval practice also compared the effects of repeated and new questions on quiz performance. Results: Students with retrieval practice performed significantly better on quizzes than those without. Repeated and new retrieval practice were equally superior. Conclusion: Retrieval practices can successfully be implemented, feasibly and sustainably, in an authentic classroom environment. Retrieval practice questions can be related to delayed practice questions, rather than exact repeats, to achieve a testing effect. Teaching Implications: Distributing low stakes multiple-choice questions throughout lectures is effective for increasing test performance. The current method was neither burdensome to workload, content, or resources.
Effects of Age on Recovery of Olfactory Function After Endoscopic Sinus Surgery and Related Risk Factors
Authors: Qi Weiping , Feng Liang , Yang Fengyan , Ma Weihuan 
Published: May 2021

Objectives: To study the effects of age on the olfactory function recovery of chronic rhinosinusitis patients after endoscopic sinus surgery and related risk factors. Methods: A total of 176 chronic rhinosinusitis (CRS) patients enrolled from February 2017 to October 2019 were divided into child, youth, middle-aged, and elderly groups. Their baseline data, T&T olfactory test score, visual analogue scale (VAS) olfactory score, sinus computed tomography (CT) Lund-Mackay score, and Lund-Kennedy score were compared. Based on postoperative olfactory function, they were divided into good and poor improvement groups. Results: Complication with nasal polyps, allergic rhinitis history, and sinus surgery history had significant differences among patients of different ages ( P < .05). Three months after surgery, T&T olfactory, VAS olfactory, Lund-Mackay, and Lund-Kennedy scores all rose with increasing age, with significant differences between any 2 groups ( P < .05). The improvement of postoperative olfactory function became poorer with aging ( P < .05). T&T and VAS olfactory scores had significant positive correlations with Lund-Mackay and Lund-Kennedy scores ( P < .001). Age, preoperative Lund-Mackay and Lund-Kennedy scores, complication with nasal polyps, allergic rhinitis history, sinus surgery history, and postoperative complications were risk factors for the poor improvement of postoperative olfactory function. Doctor-directed treatment was a protective factor for good improvement. Conclusions: The improvement of olfactory function of CRS patients after endoscopic sinus surgery declines with aging. Age, preoperative Lund-Mackay and Lund-Kennedy scores, complication with nasal polyps, allergic rhinitis history, sinus surgery history, and postoperative complications are risk factors for the poor improvement of postoperative olfactory function. Doctor-directed treatment is a protective factor for good improvement.
Cost Analysis of Open Surgical Bedside Tracheostomy in Intensive Care Unit Patients
Authors: Døving Mats , Anandan Steven , Rogne Kjetil Gudmundson , Utheim Tor Paaske , Brunborg Cathrine , Galteland Pål , Sunde Kjetil 
Published: May 2021

Objectives: Open surgical tracheostomy (OST) is a common procedure performed on intensive care unit (ICU) patients. The procedure can be performed bedside in the ICU (bedside open surgical tracheostomy, BeOST) or in the operating room (operating room open surgical tracheostomy, OROST), with comparable safety and long-term complication rates. We aimed to perform a cost analysis and evaluate the use of human resources and the total time used for both BeOSTs and OROSTs. Methods: All OSTs performed in 2017 at 5 different ICUs at Oslo University Hospital Ullevål were retrospectively evaluated. The salaries of the personnel involved in the 2 procedures were obtained from the hospital’s finance department. The time taken and the number of procedures performed were extracted from annual reports and from the electronic patient record system, and the annual expenditures were calculated. Results: Altogether, 142 OSTs were performed, of which 122 (86%) and 20 (14%) were BeOSTs and OROSTs, respectively. A BeOST cost 343 EUR (95% CI: 241.4-444.6) less than an OROST. Bedside open surgical tracheostomies resulted in an annual cost efficiency of 41.818 EUR. In addition, BeOSTs freed 279 hours of operating room occupancy during the study year. Choosing BeOST instead of OROST made 1 nurse, 2 surgical nurses, and 1 anesthetic nurse redundant. Conclusion: Bedside open surgical tracheostomy appears to be cost-, time-, and resource-effective than OROST. In the absence of contraindications, BeOSTs should be performed in ICU patients whenever possible.