bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concomitant or delayed anti-TNF differentially impact on immune-related adverse events and antitumor efficacy after anti-CD40 therapy
Authors: Jacoberger-Foissac Celia , Blake Stephen J , Liu Jing , McDonald Elizabeth , Triscott Hannah , Nakamura Kyohei , Smyth Mark J , Teng Michele WL 
Published: November 2020

BackgroundConcomitant tumor necrosis factor (TNF) neutralization in combination with immune checkpoint inhibitors (ICIs) reduces clinical immune-related adverse events (irAEs) and appears to improve antitumor efficacy in preclinical tumor models. Agonistic antibodies targeting costimulatory receptors such as CD40 represent an additional strategy to boost antitumor immune response and potentiate the activity of ICIs. However, the dose-limiting toxicities observed in anti-CD40-treated cancer patients have hindered its clinical development.MethodsWe previously described a mouse model to assess both antitumor activity and irAEs induced by various effective combination immunotherapies. Using the BALB/c and C57BL/6 strains of FoxP3-GFP-DTR (FoxP3DTR) mice, transient depletion of T regulatory cells (Tregs) prior to immunotherapy with additional immunomodulatory antibodies, lowered immune self-tolerance, resulting in the development of a spectrum of physical and biochemical irAEs similar to that reported clinically. In MC38 and 4T1.2 tumor models, following transient Treg depletion, we evaluated the impact of anti-CD40 on antitumor efficacy and the development of irAEs and the impact of concomitant or delayed TNF blockade on both these parameters. Physical irAEs were scored and biochemical irAEs were measured in the serum (ALT and cytokine levels). Histopathological liver and colon tissue analysis were performed to assess immune cell infiltration and tissue damage.ResultsSimilar to early clinical trials of CD40 agonists, in our tumor models we observed liver toxicities and rapid release of proinflammatory cytokines (TNF, interleukin 6, interferon-γ). In the BALB/c strain, anti-CD40 induced severe physical and biochemical irAEs. Concomitant anti-TNF treatment abrogated weight loss, liver damage and colitis, which consequently resulted in an improved clinical score. However, concomitant anti-TNF impaired antitumor response in a proportion of anti-CD40-treated C57BL/6 FoxP3DTR mice. Delaying TNF blockade in these mice reduced biochemical but not physical irAEs while preserving antitumor efficacy.ConclusionsOur results suggest concomitant rather than delayed anti-TNF is most effective in reducing biochemical and physical irAEs induced by anti-CD40, although it had the potential to negatively impact antitumor efficacy. Furthermore, our findings highlight the utility of our mouse model to assess the severity of irAEs induced by novel immunotherapeutic agents and evaluate whether their toxicity and antitumor efficacy can be uncoupled.
Creating a market for IQOS: analysis of Philip Morris’ strategy to introduce heated tobacco products to the Australian consumer market
Authors: Watts Christina , Burton Suzan , Freeman Becky 
Published: November 2020

BackgroundPhilip Morris International has made efforts to expand the sale of its heated tobacco product, IQOS, into new domestic markets globally. In Australia, where heated tobacco products are prohibited, the company recently attempted to overturn Australian legislation in order to permit their sale. In light of this recent move, this study presents a case study of the company’s strategies to legalise and distribute IQOS in the Australian market.MethodsTo assess Philip Morris’ lobbying activities and corporate strategies, a case study approach was used by triangulating data from three sources: interviews with former Philip Morris employees, news articles reporting Philip Morris’ lobbying activities or plans for IQOS in Australia, and submissions to relevant government inquiries and reviews from 2015 to 2020.ResultsPhilip Morris has actively lobbied Australian policy-makers to overturn bans on nicotine-containing products. Information obtained from key informants and Philip Morris’ government submissions indicates that the company’s goal is for heated tobacco products in Australia to be regulated in a new product category, exempt from tobacco control laws. Informants revealed that Philip Morris was also working to establish a network of upmarket pubs, clubs and bars where they could sell IQOS once legalisation was achieved.ConclusionsPhilip Morris has strongly lobbied the Australian government to legalise heated tobacco products, while simultaneously making plans to sell IQOS at young adult-friendly premises such as bars, clubs and pubs if its proposed legislative changes are made. This case study provides valuable insights for other countries where Philip Morris may be replicating similar strategies to weaken tobacco control legislation.
Extraluminal oesophageal stricture following traumatic diaphragmatic hernia repair in a cat
Authors: Maskell Kirsty Ann , Corzo‐Menendez Nuria , Henderson Elisabeth 
Published: November 2020

A one‐year six‐month‐old male neutered domestic shorthaired cat was presented for regurgitation of increasing severity, 10 days following surgical repair of a suspected traumatic diaphragmatic hernia. Diaphragmatic hernia repair had been carried out between the aortic and oesophageal hiatuses. Abdominal ultrasound and video fluoroscopy were performed, revealing an extraluminal oesophageal obstruction. Exploratory laparotomy performed at the referral centre revealed a large multifilament knot and associated adhesions causing a stricture of the oesophagus. Removal of previously placed suture material and revised hernia closure was performed. Closure involved using a simple interrupted suture pattern, ensuring no excessive tension was placed on the tissue. In addition, a left sided gastropexy was carried out. No further regurgitation was noted following revision surgery. Stricture of the oesophagus was not previously a recognised complication of diaphragmatic hernia repair and this case highlights the importance of suture material selection and placement.
Chapter 6 Jubaila–Arab–Hith sequences
Authors: Wilson A. O. 
Published: November 2020

Abstract
During deposition of the Jubaila-Arab-Hith sequences, the most important Arab-D reservoir, the Arab-C to A reservoirs and the Arab and Hith anhydrite seals were formed. The Kimmeridgian Jubaila-Arab-D transgression (MFS J70) restored and expanded the intrashelf basin geometry. The restored basin was filled by deeper subtidal Jubaila facies, which graded upwards to the Arab-D reservoir facies. In the late stages the Arab-D facies included both basin rim shoal facies and at least one large isolated shoal surrounded by ‘lagoonal’ intrashelf basin remnants interconnected by accessway channels. This differentiation was facilitated by local structural growth of a few metres. The Arab-D reservoir is overlain by the Arab-D anhydrite, deposited initially as gypsum in broad salinas, which blanketed the intrashelf basin region, forming the first major seal. By the end of Arab-D anhydrite deposition, the entire intrashelf basin area had been ﬁlled and transformed into a broad evaporite platform. Atop this platform, the Arab-C to -A (MFS J80-100) alternating shallow water carbonate and anhydrite (initially gypsum) intervals were deposited, ending regionally with the thick Hith Anhydrite Formation. The depositional setting for each of the main Jubaila-Arab-Hith sequences is reviewed and illustrated. The evolution of Jubaila-Arab-D reservoir models is discussed. Different interpretations of Jubaila-Arab-D-Hith sequences are compared, including the issue of whether the Arab carbonate-evaporite depositional sequence boundaries should be taken at the top of the carbonate intervals or the top of the anhydrites. Examples are included which illustrate how easterly palaeowind directions were an important factor controlling Arab-D facies variation. A scenario is presented to show how the Late Jurassic Tethys shelf uplift and low angle unconformity coupled with westward structural tilt were important. An alternating balance developed between the evolving land barrier and eustatic sea-level change during deposition of the Arab carbonate–evaporites and the Hith Anhydrite. Carbonates were deposited when the barrier was inundated and evaporites when the barrier was exposed and the area restricted and hypersaline. A major late Tithonian ﬂooding event (MFS J110) formed the top-Hith Manifa carbonate reservoir and brought open marine carbonate mud-rich deposition to the area, continuing without hiatus into the Early Cretaceous.
Chapter 8 Summary and conclusions
Authors: Wilson A. O. 
Published: November 2020

Abstract
This chapter summarizes the main conclusions in this Memoir. Included is a comparison of the Arabian Intrashelf Basin events to the Haq (2017) revision of the Jurassic sea level curve. One conclusion is that the Mid- to Late Jurassic Arabian Intrashelf Basin, with its stable tectonic setting during deposition, extensive present-day outcrops and subsurface well and seismic control, may be an ideal place to evaluate global changes during its time span. The last part of this chapter lists and discusses topics and questions raised within this Memoir which warrant further evaluation.
Perspectives on Policing: Cynthia Lum
Authors: Lum Cynthia 
Published: November 2020

The Editorial Committee of the Annual Review of Criminology has launched a new section within the journal in which we invite one or more authors to write a more personal and yet scholarly article that puts forth their perspective on an important and timely topic. For Volume 4, we asked Dr. Cynthia Lum and Dr. Phillip Atiba Goff to provide their perspectives on policing.We hope our readers enjoy this new and exciting series of “Perspectives.”
Impact of Body Mass Index on Presence of ctDNA and Disease Recurrence after Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer: Analysis from BRE12-158
Authors: Ballinger Tarah J. , Jiang Guanglong , Kassem Nawal , Radovich Milan , Schneider Bryan P. 
Published: November 2020

Abstract

Purpose:
This retrospective analysis aimed to determine the relationship between body mass index (BMI) and circulating tumor DNA (ctDNA) in triple-negative breast cancer (TNBC), and to evaluate the impact of BMI on disease recurrence and survival in the homogeneous, high-risk population of patients with residual TNBC after neoadjuvant chemotherapy.

Experimental Design:
BRE12-158 was a phase II trial of genomically directed therapy versus physician’s choice in residual TNBC after chemotherapy. ctDNA was isolated from plasma samples, and categorized as positive or negative. BMI (kg/m2) after surgery was analyzed as both a continuous and categorical variable: normal weight, &lt;25; overweight, 25–30; and obese, ≥30. We compared ctDNA category and BMI, and estimated probability of disease-free survival (DFS), distant DFS (DDFS), and overall survival (OS) by BMI.

Results:
Of 177 patients in BRE12-158, 172 had BMI and 140 had ctDNA data. There was no difference in mean BMI between those with ctDNA positivity versus negativity (P = 0.48). There was no relationship between BMI category and presence of ctDNA (P = 0.31). In multivariate analysis, continuous BMI was not prognostic of DDFS (P = 0.996), DFS (P = 0.41), or OS (P = 0.98). There was no association between BMI categories and survival (P = 0.92, 0.74, and 0.97 for DDFS, DFS, and OS, respectively).

Conclusions:
In patients with residual TNBC after neoadjuvant chemotherapy, BMI was not prognostic of DDFS, DFS, or OS. There was no signal of a relationship between BMI and presence of ctDNA. This suggests inherent aggressive tumor biology, in which host phenotype may have less influence and impact of weight loss interventions may be diminished.
CDK12 Deficiency and the Immune Microenvironment in Prostate Cancer
Authors: Lotan Tamara L. , Antonarakis Emmanuel S. 
Published: November 2020

Abstract
CDK12 inactivation in prostate cancer is associated with tandem genomic duplications that may generate fusion-associated neoantigens and elicit immune responses amenable to checkpoint blockade. In the first study to comprehensively characterize the T-cell immune microenvironment of CDK12-deficient prostate cancers, subsets of immunosuppressive CD4+FOXP3− T cells were increased compared with CDK12-proficient controls.
See related article by Rescigno et al., p. 566
Monoallelic Mutations in
CC2D1A
Suggest a Novel Role in Human Heterotaxy and Ciliary Dysfunction
Authors: Ma Alvin Chun Hang , Mak Christopher Chun Yu , Yeung Kit San , Pei Steven Lim Cho , Ying Dingge , Yu Mullin Ho Chung , Hasan Kazi Md Mahmudul , Chen Xiangke , Chow Pak Cheong , Cheung Yiu Fai , Chung Brian Hon Yin 
Published: November 2020

Background:
Human heterotaxy is a group of congenital disorders characterized by misplacement of one or more organs according to the left-right axis. The genetic causes of human heterotaxy are highly heterogeneous.

Methods:
We performed exome sequencing in a cohort of 26 probands with heterotaxy followed by gene burden analysis for the enrichment of novel rare damaging mutations. Transcription activator-like effector nuclease was used to generate somatic loss-of-function mutants in a zebrafish model. Ciliary defects were examined by whole-mount immunostaining of acetylated α-tubulin.

Results:

We identified a significant enrichment of novel rare damaging mutations in the
CC2D1A
gene. Seven occurrences of
CC2D1A
mutations were found to affect 4 highly conserved amino acid residues of the protein. Functional analyses in the transcription activator-like effector nuclease–mediated zebrafish knockout models were performed, and heterotaxy phenotypes of the cardiovascular and gastrointestinal systems in both somatic and germline mutants were observed. Defective cilia were demonstrated by whole-mount immunostaining of acetylated α-tubulin. These abnormalities were rescued by wild-type
cc2d1a
mRNA but not
cc2d1a
mutant mRNA, strongly suggesting a loss-of-function mechanism. On the other hand, overexpression of
cc2d1a
orthologous mutations
cc2d1a
P559L and
cc2d1a
G808V (orthologous to human
CC2D1A
P532L and
CC2D1A
G781V) did not affect embryonic development.

Conclusions:

Using a zebrafish model, we were able to establish a novel association of
CC2D1A
with heterotaxy and ciliary dysfunction in the F2 generation via a loss-of-function mechanism. Future mechanistic studies are needed for a better understanding of the role of
CC2D1A
in left-right patterning and ciliary dysfunction.
Penser l’ écart dans la copie du texte coranique à l’ époque ottomane
Authors: Garnier Sébastien 
Published: November 2020

Résumé
Sur le territoire français, les villes de province recèlent maints manuscrits en scripts orientaux encore assez peu exploités. Si ces documents n’ apportent guère de contenus nouveaux, ils peuvent nous renseigner sur les pratiques lettrées. La Bibliothèque municipale de Dijon conserve un exemplaire maghrébin du Coran d’ époque ottomane à plusieurs égards instructif. Notre communication fournit un certain nombre de traits codicologiques sur les irrégularités qui s’ y observent. Nous les classons selon les modalités suivantes : l’ organisation, l’ erreur et la personnalisation afin de penser le concept d’ écart.
Sufi Symbol as Gap, Metaphor as Clue
Authors: Binmayaba Mustafa Muhammad T. 
Published: November 2020

Abstract
This article introduces an approach to analyzing the way in which figurative language interfaces with cognitive, cultural, and spiritual experience in the symbols employed by the Sufis to express their love of God. It relies on the Cognitive Linguistic Approach to reveal the relationship between the Sufis’ thoughts about God, secular language of love, and the idea of divine love. Through a case study analysis of the symbols of love in Ibn ʿArabī’s poetry, the two chief undertakings here are: first, to argue that thoughts and feelings of human love inspired the Sufis to express their ideas about their experience of divine love through secular symbols that create gaps of indeterminacy in their poems, and second, to explain, using Conceptual Metaphor Theory, how these gaps can be closed through mappings of the Sufi symbols, as parts of the target domain of divine love, onto the source domain of secular love.
Deep-Learning-Based Gridded Downscaling of Surface Meteorological Variables in Complex Terrain. Part I: Daily Maximum and Minimum 2-m Temperature
Authors: Sha Yingkai , Gagne II David John , West Gregory , Stull Roland 
Published: November 2020

AbstractMany statistical downscaling methods require observational inputs and expert knowledge and thus cannot be generalized well across different regions. Convolutional neural networks (CNNs) are deep-learning models that have generalization abilities for various applications. In this research, we modify UNet, a semantic-segmentation CNN, and apply it to the downscaling of daily maximum/minimum 2-m temperature (TMAX/TMIN) over the western continental United States from 0.25° to 4-km grid spacings. We select high-resolution (HR) elevation, low-resolution (LR) elevation, and LR TMAX/TMIN as inputs; train UNet using Parameter–Elevation Regressions on Independent Slopes Model (PRISM) data over the south- and central-western United States from 2015 to 2018; and test it independently over both the training domains and the northwestern United States from 2018 to 2019. We found that the original UNet cannot generate enough fine-grained spatial details when transferred to the new northwestern U.S. domain. In response, we modified the original UNet by assigning an extra HR elevation output branch/loss function and training the modified UNet to reproduce both the supervised HR TMAX/TMIN and the unsupervised HR elevation. This improvement is named “UNet-Autoencoder (AE).” UNet-AE supports semisupervised model fine-tuning for unseen domains and showed better gridpoint-level performance with more than 10% mean absolute error (MAE) reduction relative to the original UNet. On the basis of its performance relative to the 4-km PRISM, UNet-AE is a good option to provide generalizable downscaling for regions that are underrepresented by observations.
Ascending Columns, WTG, and Convective Aggregation
Authors: Romps David M. 
Published: November 2020

AbstractAnalytic solutions are derived for a convecting atmosphere with mean ascent using a zero-buoyancy bulk-plume approximation for moist convection. It has been suggested that such solutions should serve as a model for the relationship between humidity, instability, and precipitation in the tropics, but it is shown here that this interpretation is incompatible with the observed weak temperature gradient (WTG). Instead, the solutions can be used to understand the atmospheric state averaged over all tropical convecting regions. Using the analytic solutions in this way, they predict the changes in humidity, instability, and precipitation as a function of the size of the moist patch in a convectively aggregated state.
A New Approach to Homogenize Global Subdaily Radiosonde Temperature Data from 1958 to 2018
Authors: Zhou Chunlüe , Wang Junhong , Dai Aiguo , Thorne Peter W. 
Published: November 2020

AbstractThis study develops an innovative approach to homogenize discontinuities in both mean and variance in global subdaily radiosonde temperature data from 1958 to 2018. First, temperature natural variations and changes are estimated using reanalyses and removed from the radiosonde data to construct monthly and daily difference series. A penalized maximal F test and an improved Kolmogorov–Smirnov test are then applied to the monthly and daily difference series to detect spurious shifts in the mean and variance, respectively. About 60% (40%) of the changepoints appear in the mean (variance), and ~56% of them are confirmed by available metadata. The changepoints display a country-dependent pattern likely due to changes in national radiosonde networks. Mean segment length is 7.2 (14.6) years for the mean (variance)-based detection. A mean (quantile)-matching method using up to 5 years of data from two adjacent mean (variance)-based segments is used to adjust the earlier segments relative to the latest segment. The homogenized series is obtained by adding the two homogenized difference series back to the subtracted reference series. The homogenized data exhibit more spatially coherent trends and temporally consistent variations than the raw data, and lack the spurious tropospheric cooling over North China and Mongolia seen in several reanalyses and raw datasets. The homogenized data clearly show a warming maximum around 300 hPa over 30°S–30°N, consistent with model simulations, in contrast to the raw data. The results suggest that spurious changes are numerous and significant in the radiosonde records and our method can greatly improve their homogeneity.
Free Senior High School Lunch Contributes to Dietary Quality of Nonresidential Students in Ghana
Authors: Abizari Abdul-Razak , Ali Zakari , Abdulai Seidu Alhassan , Issah Fauzia , Frimpomaa Nana Adwoa 
Published: November 2020

Background: School feeding offers an excellent opportunity for targeted intervention to students not only as means for improving educational outcomes but also enhancing nutritional outcomes. The Government of Ghana introduced the free lunch feeding policy for nonresidential students in senior high schools (SHS) in 2018. Objective: We assessed unintended benefits of the free lunch program to dietary improvement. Methods: This was an analytical cross-sectional study among 403 (202 beneficiary and 201 non-beneficiary) students in SHS. The Food and Agriculture Organization’s standard procedure for measuring dietary diversity score (DDS) was followed. A 3-day dietary recall was used to assess school day DDS, while a 24-hour recall was used to assess weekend DDS of students. Differences in DDS and food group consumption were determined using student t test and χ2 test, respectively. Results: Nearly all (98.5%) beneficiary students consumed the free school lunch and 7 (70%) in 10 of them consumed it on all school days. While the students did not differ in their weekend meal DDS (6.3 ± 1.4 vs 6.5 ± 1.4, P = .39), beneficiaries of the school lunch had higher lunch DDS (7.5 ± 0.5 vs 6.5 ± 1.4, P < .001) and whole day DDS (11.5 ± 1 vs 9.3 ± 2.0, P < .001) compared to non-beneficiary students on school days. Even though the school lunch increased food group intake, vitamin-A rich vegetables and tubers, fruits, flesh and organ meats, and dairy products were hardly provided as components of school lunch. Conclusion: Provision of free school lunch meal to nonresidential students in SHSs in Ghana could contribute to improved diet quality.