bluuebunny/crossref_metadata_2025 huggingface dataset:
BiTE secretion by adoptively transferred stem-like T cells improves FRα+ ovarian cancer control
Authors: McGray A J Robert , Chiello Jessie L , Tsuji Takemasa , Long Mark , Maraszek Kathryn , Gaulin Nicole , Rosario Spencer R , Hess Suzanne M , Abrams Scott I , Kozbor Danuta , Odunsi Kunle , Zsiros Emese
Published: July 2023

Background

Cancer immunotherapies can produce complete therapeutic responses, however, outcomes in ovarian cancer (OC) are modest. While adoptive T-cell transfer (ACT) has been evaluated in OC, durable effects are rare. Poor therapeutic efficacy is likely multifactorial, stemming from limited antigen recognition, insufficient tumor targeting due to a suppressive tumor microenvironment (TME), and limited intratumoral accumulation/persistence of infused T cells. Importantly, host T cells infiltrate tumors, and ACT approaches that leverage endogenous tumor-infiltrating T cells for antitumor immunity could effectively magnify therapeutic responses.

Methods

Using retroviral transduction, we have generated T cells that secrete a folate receptor alpha (FRα)-directed bispecific T-cell engager (FR-B T cells), a tumor antigen commonly overexpressed in OC and other tumor types. The antitumor activity and therapeutic efficacy of FR-B T cells was assessed using FRα+ cancer cell lines, OC patient samples, and preclinical tumor models with accompanying mechanistic studies. Different cytokine stimulation of T cells (interleukin (IL)-2+IL-7 vs IL-2+IL-15) during FR-B T cell production and the resulting impact on therapeutic outcome following ACT was also assessed.

Results

FR-B T cells efficiently lysed FRα+ cell lines, targeted FRα+ OC patient tumor cells, and were found to engage and activate patient T cells present in the TME through secretion of T cell engagers. Additionally, FR-B T cell therapy was effective in an immunocompetent in vivo OC model, with response duration dependent on both endogenous T cells and FR-B T cell persistence. IL-2/IL-15 preconditioning prior to ACT produced less differentiated FR-B T cells and enhanced therapeutic efficacy, with mechanistic studies revealing preferential accumulation of TCF-1+CD39−CD69− stem-like CD8+ FR B T cells in the peritoneal cavity over solid tumors.

Conclusions

These findings highlight the therapeutic potential of FR-B T cells in OC and suggest FR-B T cells can persist in extratumoral spaces while actively directing antitumor immunity. As the therapeutic activity of infused T cell therapies in solid tumor indications is often limited by poor intratumoral accumulation of transferred T cells, engager-secreting T cells that can effectively leverage endogenous immunity may have distinct mechanistic advantages for enhancing therapeutic responses rates.
Incivility in healthcare: the impact of poor communication
Authors: Guppy Joseph H , Widlund Hedda , Munro Ross , Price Jim
Published: July 2023

Incivility is a common issue within healthcare in the UK and internationally. Experienced by at least one-third of staff within the UK National Health Service, incivility has been demonstrated to have significant negative implications on both patient care and healthcare staff. These include contributing to direct medical errors, diagnostic inaccuracy and team communication, with a large associated cost burden, while for staff it has significant negative impacts on retention, productivity and morale. Proposed methods do already exist to both prevent and address incivility, and it is in the interest of healthcare institutions, for their patients and staff, to investigate incivility and adopt these methods. This review explores existing literature on the effects of incivility, researched strategies to address it, as well as the proposed ways of integrating these. Through raising awareness and exploring these issues, our aim is to increase recognition of incivility, as well as inspire healthcare managers and leaders to collectively take efforts to reduce the rates of incivility.
Validation of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in an academic tertiary care centre
Authors: Schmidtmann Irene , Kraus Daniel , Weinmann Arndt , Pütz Katharina , Claßen Paul , Schleicher Eva Maria , Boedecker-Lips Simone Cosima , Weinmann-Menke Julia
Published: July 2023

Objectives

To assess the sensitivity and specificity of the 2019 EULAR/American College of Rheumatology (ACR) classification criteria for systemic lupus erythematosus (SLE) in outpatients at an academic tertiary care centre and to compare them to the 1997 ACR and the 2012 Systemic Lupus International Collaborating Clinics criteria.

Methods

Prospective and retrospective observational cohort study.

Results

3377 patients were included: 606 with SLE, 1015 with non-SLE autoimmune-mediated rheumatic diseases (ARD) and 1756 with non-ARD diseases (hepatocellular carcinoma, primary biliary cirrhosis, autoimmune hepatitis). The 2019 criteria were more sensitive than the 1997 criteria (87.0% vs 81.8%), but less specific (98.1% vs 99.5% in the entire cohort and 96.5% vs 98.8% in patients with non-SLE ARD), resulting in Youden Indexes for patients with SLE/non-SLE ARD of 0.835 and 0.806, respectively. The most sensitive items were history of antinuclear antibody (ANA) positivity and detection of anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies. These were also the least specific items. The most specific items were class III/IV lupus nephritis and the combination of low C3 and low C4 complement levels, followed by class II/V lupus nephritis, either low C3 or low C4 complement levels, delirium and psychosis, when these were not attributable to non-SLE causes.

Conclusions

In this cohort from an independent academic medical centre, the sensitivity and specificity of the 2019 lupus classification criteria were confirmed. Overall agreement of the 1997 and the 2019 criteria was very good.
Decoherence effects in reactor and Gallium neutrino oscillation experiments: a QFT approach
Authors: Krueger Raphael , Schwetz Thomas
Published: July 2023

We adopt the quantum field theoretical method to calculate the amplitude and event rate for a neutrino oscillation experiment, considering neutrino production, propagation and detection as a single process. This method allows to take into account decoherence effects in the transition amplitude induced by the quantum mechanical uncertainties of all particles involved in the process. We extend the method to include coherence loss due to interactions with the environment, similar to collisional line broadening. In addition to generic decoherence induced at the amplitude level, the formalism allows to include, in a straightforward way, additional damping effects related to phase-space integrals over momenta of unobserved particles as well as other classical averaging effects. We apply this method to neutrino oscillation searches at reactor and Gallium experiments and confirm that quantum decoherence is many orders of magnitudes smaller than classical averaging effects and therefore unobservable. The method used here can be applied with minimal modifications also to other types of oscillation experiments, e.g., accelerator based beam experiments.
Design and analysis of tweet-based election models for the 2021 Mexican legislative election
Authors: Vigna-Gómez Alejandro , Murillo Javier , Ramirez Manelik , Borbolla Alberto , Márquez Ian , Ray Prasun K.
Published: July 2023

Modelling and forecasting real-life human behaviour using online social media is an active endeavour of interest in politics, government, academia, and industry. Since its creation in 2006, Twitter has been proposed as a potential laboratory that could be used to gauge and predict social behaviour. During the last decade, the user base of Twitter has been growing and becoming more representative of the general population. Here we analyse this user base in the context of the 2021 Mexican Legislative Election. To do so, we use a dataset of 15 million election-related tweets in the six months preceding election day. We explore different election models that assign political preference to either the ruling parties or the opposition. We find that models using data with geographical attributes determine the results of the election with better precision and accuracy than conventional polling methods. These results demonstrate that analysis of public online data can outperform conventional polling methods, and that political analysis and general forecasting would likely benefit from incorporating such data in the immediate future. Moreover, the same Twitter dataset with geographical attributes is positively correlated with results from official census data on population and internet usage in Mexico. These findings suggest that we have reached a period in time when online activity, appropriately curated, can provide an accurate representation of offline behaviour.
Deep Learning-based Sequence Labeling Tools for Nepali
Authors: Rai Pooja , Chatterji Sanjay , Kim Byung-Gyu
Published: July 2023

A Part-of-Speech (POS) tagger and Chunker (or shallow parser) are sequence labeling tools, crucial for improving the accuracy of Natural Language Processing (NLP) tasks like parsing, named entity recognition, sentiment analysis, information extraction, and so on. Developing such tools for a low-resource language is an arduous task. Nepali is a relatively resource-poor Indian language and has not been able to evolve from a computational perspective. Therefore, we present effective part-of-speech tagging and chunking tools for the Nepali text using sequential deep learning models—Bidirectional Long Short-Term Memory Network with a Conditional Random Field Layer (BI-LSTM-CRF) and other LSTM-based models exploring both character and word embeddings of the Nepali texts. Word Embedding has been used to capture syntactic as well as semantic information whereas character embedding has been applied to capture the morphological as well as shape information of words and also to handle the out-of-vocabulary problem. The developed chunker is the first statistical chunker for the Nepali language. A baseline model with a Conditional Random Field has also been developed to identify the optimum feature set for the aforementioned tasks. The BI-LSTM-CRF model produced an accuracy of 99.20% and 98.40%, for Nepali POS tagging and chunking, respectively. This is the highest-ever accuracy for Nepali. Thorough error analysis and observations have also been reported with examples. The developed tools can help advance research in Nepali language processing, improve the accuracy of language technology applications, and contribute to the preservation and promotion of the Nepali language.
An Automated Data-driven Machine Intelligence Framework for Mining Knowledge To Classify Fake News Using NLP
Authors: Mundra Shikha , Reddy Jaiwanth , Mundra Ankit , Mittal Namita , Vidyarthi Ankit , Gupta Deepak
Published: July 2023

The rapid spread of fake news has become a serious concern over the internet. In recent years, social media platforms are widely used for news consumption. These platforms are excellent for their low-cost accessibility and rapid dissemination of news. Contrariwise, it encourages the rapid propagation of ’fake news,’ or low-quality news containing intentionally misleading content. The quick dissemination of fake news has the potential to have devastating consequences for individuals and society as a whole. Therefore, to overcome this problem, this paper proposed an artificial intelligence framework that incorporates ensembles of deep learning features for the classification of fake news. Deep learning approaches such as Multilayer Perceptron (MLP), Convolutional Neural Networks (CNN), and Bidirectional Long Short Term Memory (BILSTM) have been used to extract local and sequential features. To obtain relevant features at the word level, these approaches are initialized using pretrained GLOVE word embedding, which results in, three base learners as GLOVE+MLP, GLOVE+CNN, and GLOVE+BiLSTM. Moreover, to extract features at the sentence level, Bidirectional Encoder Representations from Transformers (BERT) are adopted, which results in, three more base learners as BERT+MLP, BERT+CNN, BERT+BiLSTM. In total, six models are employed as base learners. Later, predictions from the best of these models are ensembled and performance is computed using ensembling techniques. Overall, we have investigated nine ensembling techniques, including weighted voting, bagging, boosting, stacked ensembles like SVC, and logistic regression. The performance is computed using four publicly available datasets regarding the macro average f1-score. We observed that soft weighted voting-based ensemble outperformed other models on three datasets achieving an f1-score of 92.99% (McIntyre), 95.22% (Kaggle), and 78.3% (Gossipcop).
The Market Stability Reserve in the EU Emissions Trading System: A Critical Review
Authors: Borghesi Simone , Pahle Michael , Perino Grischa , Quemin Simon , Willner Maximilian
Published: July 2023

Having experienced low prices for about a decade, the European Union Emissions Trading System has been supplemented with the market stability reserve (MSR) that adjusts the supply of allowances to market outcomes. We critically review the literature assessing the performance of the MSR against several policy objectives. In doing so, we cover both conceptual aspects and quantitative assessments. We conclude by pointing out important policy implications and open issues for further research.
Shear Behavior of Reinforced Concrete Beams with Different Arrangements of Externally Bonded Carbon Fiber-Reinforced Polymer
Authors: Jassim Majid Faissal , Lafta Yousif Jabbar , Malik Hawraa S.
Published: July 2023

Carbonfiber-reinforced polymer (CFRP) composites are frequently utilized in the repair and reinforcement of reinforced concrete members because they are more corrosion-resistant, durable, and flexible than commonly used materials like steel plates. Many studies have demonstrated that the use of CFRP as an internal strengthening material has a substantial impact on the shear capacity of RC beams. This research looks into the possibility of using FRP material as an externally bonded reinforcement to increase the shear strength of RC beams. Because shear improvement and mode of failure are based on the right configuration of the CFRP sheets, the experimental work consisted of eight RC beams with various types, orientations, and configurations of CFRP sheets. All beams were examined under two-point bending. The test results show that the CFRP sheet significantly improved the beam’s shear strength and ductility and that it is advantageous to orient the FRP at 45 degrees to the beam’s longitudinal axis.
Durable Flame-Retardant Cotton Fabric Modified by a Novel Reactive P-N Intumescent Flame Retardant
Authors: Wu Denghui , Li Xinhang , Zhao Peihua
Published: July 2023

A novel reactive P-N intumescent flame retardant tetroxo (3-triethylphosphine-5-chlorine-1-triazine) neopentane (TTCTN) was prepared, and its structure was determined by Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR). The flame retardance and physiological comfort properties of TTCTN-treated cotton fabrics (TTCTN-CF) was researched. The CF treated with 20 wt% TTCTN (TTCTN(20)-CF) showed the limiting oxygen index (LOI) was up to 28.6%, and the flame retardancy reached the class B1 of national standard of flame retardant fabrics, and its peak heat release rate and total heat release were reduced by 55.7% and 37.4% comparing with untreated CF, respectively. The FTIR proved the TTCTN was grafted on the CF matrix. Thermogravimetric (TG) showed TTCTN could reduce the decomposition speed of the cotton fabric and formed the stable char residue at high temperature to protect the remaining CF from complete dehydration. After 50 washing cycles, the LOI of TTCTN(20)-CF was 26.2%, still reaching class B1 of national standard of flame retardant fabrics. Scanning electron microscope showed the TTCTN was still bounded to the matrix of CF after 50 washing cycles which further proved TTCTN(20)-CF had excellent durable flame retardancy.
Stability Analysis of Support Anchor Bolt in the Process of Surrounding Rock Fracture Evolution
Authors: Cao Juncai , Zhang Nong , Pi Liming , An Tieliang , Li Shuchen , CHi Enan
Published: July 2023

Various diseases and failures inevitably appear on expressway roadways in water-rich strata under the long-term erosion of water. It is very difficult to support the surrounding rock of a water-rich roadway because water will corrode the anchorage bond and weaken the surrounding rock mass. In the process of supporting, damage and fracture of anchor bolt often appear in water-rich roadway. In order to study the stability analysis of a support anchor bolt in the process of surrounding rock fracture evolution and the relationship between the prestressed value and the length of the anchor bolt, this paper studied the fracture evolution law of surrounding rock and the progressive debonding law of the bolt are studied by RFPA3D numerical simulation and used MATLAB software to calculate and draw several graphs to reveal the mechanism by analytical method. The following main conclusions were drawn: (1) the change and attenuation of the surrounding rock stress have a certain influence on the stability of the supporting bolt. The existence of confining pressure (horizontal stress) has a significant impact on the ultimate pullout force of anchor bolts. (2) With the gradual destruction of the surrounding rock, the shear stress, horizontal stress, and vertical stress in the surrounding rock are gradually reduced to zero, and the change speed of the surrounding rock is fast at the shallow surface and slow at the deep. (3) The interface shear stress tends to a low stable value after debonding, which means the value of friction resistance is relatively stable in different positions. (4) The frictional resistance after interface debonding is an important condition to maintain the balance of higher anchorage force. If there is no friction resistance, when the axial force of the anchor bolt reaches the initial critical value, the interface debunking process will develop catastrophically and cannot be stabilized until complete failure, even if the axial force no longer increases.
Periodic Solution for a Kind of Third-Order Neutral-Type Differential Equation
Authors: Shu Axiu , Du Bo
Published: July 2023

In this paper, we investigate a class of a third-order neutral-type differential equation with time-varying delays. Some sufficient conditions on the existence of a periodic solution are established for the considered system. Different from the previously reported research results, by utilizing the properties of neutral operators and a special variable substitution, we transform a high-order neutral equation into a first-order three-dimensional nonneutral system. The existence of a periodic solution such as the high-order neutral equation has not been given much attention in past papers due to the difficulty of estimation of prior bounds of solutions. This paper is devoted to the use of properties of neutral-type operators with a variable parameter and Mawhin’s continuation theorem for overcoming the above difficulties. The neutral term in the third-order neutral differential equation in this paper contains a variable parameter which is different from third-order neutral-type equations that have been studied. The third-order neutral-type equation studied in this paper is more general, and similar equations studied in the past are special cases of the equations studied in this paper. Finally, an example is given to elucidate the effectiveness and values of the present results. Our results are new and complement the related results of third-order functional differential equations.
Catatonia, Pregnancy, and Electroconvulsive Therapy (ECT)
Authors: Gandhi Khushbu , Nguyen KieuHanh , Driscoll Maggie , Islam Zahid , Maru Siddhartha
Published: July 2023

Background. Catatonia is a neuropsychiatric syndrome, which typically occurs in the context of another psychiatric or medical condition, with a significant morbidity and mortality risk. Significant medical conditions resulting from catatonia include nutritional deficiencies, skin ulcerations, electrolyte disturbances, aspiration pneumonia, and venous thromboembolism. As a result, prompt treatment is required. Gold standard treatment consists of benzodiazepines, followed by electroconvulsive therapy (ECT) if pharmacotherapy alone is ineffective. With pregnancy and catatonia, there is a high risk of adverse maternal/fetal outcomes, and the risks/benefits of treatment must be carefully considered. Case. Here, we present a case of a young pregnant woman with schizoaffective disorder whose catatonic state was not successfully resolved with lorazepam, therefore requiring ECT. Patient presented to the emergency department at 20 weeks of pregnancy, displaying symptoms of catatonia and psychosis. She was admitted to the inpatient behavioral health unit, where she was treated with lorazepam for catatonia. Treatment occurred in close collaboration with the obstetrics team. While initially, the patient appeared to have a positive response to lorazepam, she became increasingly catatonic with minimal oral intake, mutism, and urinary retention. As a result, she was transferred to the medical floor, where ECT was initiated due to the ineffectiveness of lorazepam. Her catatonia was successfully resolved with 12 total treatments of ECT; there were no adverse effects to the fetus. Patient delivered her baby at 39 weeks with no complications. She continued to receive inpatient psychiatric care until she was stable for discharge to an extended acute care unit. Objectives. In this report, we will review relevant literature on catatonia in pregnancy, with focus on treatment with ECT. Conclusions. Though the literature on these topics is limited and typically presented in case reports format, there appears to be a favorable view toward the use of ECT for pregnant catatonic patients. This case could be considered a vital contribution to the literature, as it provides a successful example of treating catatonia in pregnancy with no known adverse effects to the mother or child.
Supplementary Fig. 11 from Disruption of the MYC Superenhancer Complex by Dual Targeting of FLT3 and LSD1 in Acute Myeloid Leukemia
Authors: Yashar William M. , Curtiss Brittany M. , Coleman Daniel J. , VanCampen Jake , Kong Garth , Macaraeg Jommel , Estabrook Joseph , Demir Emek , Long Nicola , Bottomly Daniel , McWeeney Shannon K. , Tyner Jeffrey W. , Druker Brian J. , Maxson Julia E. , Braun Theodore P.
Published: July 2023

Single cell ATAC-seq cell population dynamics in primary patient samples follow-ing treatment with dual FLT3/LSD1 inhibition.
Supplementary Table 3 from EIF4A3 Acts on the PI3K–AKT–ERK1/2–P70S6K Pathway through FLOT1 to Influence the Development of Lung Adenocarcinoma
Authors: Yu Wenhao , Liang Jinghui , Fang Tao , Jiang Jin , Zhao Renchang , Li Rongyang , Han Jingyi , Tian Hui
Published: July 2023

Correlation between EIF4A3 expression and clinicopathological characteristics in LUAD
Supplementary Figure S2 from Comutations and KRASG12C Inhibitor Efficacy in Advanced NSCLC
Authors: Negrao Marcelo V. , Araujo Haniel A. , Lamberti Giuseppe , Cooper Alissa J. , Akhave Neal S. , Zhou Teng , Delasos Lukas , Hicks J. Kevin , Aldea Mihaela , Minuti Gabriele , Hines Jacobi , Aredo Jacqueline V. , Dennis Michael J. , Chakrabarti Turja , Scott Susan C. , Bironzo Paolo , Scheffler Matthias , Christopoulos Petros , Stenzinger Albrecht , Riess Jonathan W. , Kim So Yeon , Goldberg Sarah B. , Li Mingjia , Wang Qi , Qing Yun , Ni Ying , Do Minh Truong , Lee Richard , Ricciuti Biagio , Alessi Joao Victor , Wang Jing , Resuli Blerina , Landi Lorenza , Tseng Shu-Chi , Nishino Mizuki , Digumarthy Subba R. , Rinsurongkawong Waree , Rinsurongkawong Vadeerat , Vaporciyan Ara A. , Blumenschein George R. , Zhang Jianjun , Owen Dwight H. , Blakely Collin M. , Mountzios Giannis , Shu Catherine A. , Bestvina Christine M. , Garassino Marina Chiara , Marrone Kristen A. , Gray Jhanelle E. , Patel Sandip Pravin , Cummings Amy L. , Wakelee Heather A. , Wolf Juergen , Scagliotti Giorgio Vittorio , Cappuzzo Federico , Barlesi Fabrice , Patil Pradnya D. , Drusbosky Leylah , Gibbons Don L. , Meric-Bernstam Funda , Lee J. Jack , Heymach John V. , Hong David S. , Heist Rebecca S. , Awad Mark M. , Skoulidis Ferdinandos
Published: July 2023

A) ORR (left), PFS (middle) and OS (right) in patients with ECOG-PS 0 or 1, at least 1 prior line of therapy for metastatic disease and without untreated brain metastases; B) Survival outcomes in patients with treated or untreated brain metastases prior to starting KRAS G12Ci; C) Survival outcomes according to PD-L1 status (TPS: tumor proportion score); D) survival outcomes in patients with or without prior immune checkpoint inhibitor therapy.
Data from Type I Interferon Signaling via the EGR2 Transcriptional Regulator Potentiates CAR T Cell–Intrinsic Dysfunction
Authors: Jung In-Young , Bartoszek Robert L. , Rech Andrew J. , Collins Sierra M. , Ooi Soon-Keat , Williams Erik F. , Hopkins Caitlin R. , Narayan Vivek , Haas Naomi B. , Frey Noelle V. , Hexner Elizabeth O. , Siegel Donald L. , Plesa Gabriela , Porter David L. , Cantu Adrian , Everett John K. , Guedan Sonia , Berger Shelley L. , Bushman Frederic D. , Herbst Friederike , Fraietta Joseph A.
Published: July 2023

Abstract
Chimeric antigen receptor (CAR) T cell therapy has shown promise in treating hematologic cancers, but resistance is common and efficacy is limited in solid tumors. We found that CAR T cells autonomously propagate epigenetically programmed type I interferon signaling through chronic stimulation, which hampers antitumor function. EGR2 transcriptional regulator knockout not only blocks this type I interferon–mediated inhibitory program but also independently expands early memory CAR T cells with improved efficacy against liquid and solid tumors. The protective effect of EGR2 deletion in CAR T cells against chronic antigen-induced exhaustion can be overridden by interferon-β exposure, suggesting that EGR2 ablation suppresses dysfunction by inhibiting type I interferon signaling. Finally, a refined EGR2 gene signature is a biomarker for type I interferon–associated CAR T cell failure and shorter patient survival. These findings connect prolonged CAR T cell activation with deleterious immunoinflammatory signaling and point to an EGR2–type I interferon axis as a therapeutically amenable biological system.
Significance:
To improve CAR T cell therapy outcomes, modulating molecular determinants of CAR T cell–intrinsic resistance is crucial. Editing the gene encoding the EGR2 transcriptional regulator renders CAR T cells impervious to type I interferon pathway–induced dysfunction and improves memory differentiation, thereby addressing major barriers to progress for this emerging class of cancer immunotherapies.

This article is highlighted in the In This Issue feature, p. 1501
Data from Early Infiltration of Innate Immune Cells to the Liver Depletes HNF4α and Promotes Extrahepatic Carcinogenesis
Authors: Goldman Omer , Adler Lital N. , Hajaj Emma , Croese Tommaso , Darzi Naama , Galai Sivan , Tishler Hila , Ariav Yarden , Lavie Dor , Fellus-Alyagor Liat , Oren Roni , Kuznetsov Yuri , David Eyal , Jaschek Rami , Stossel Chani , Singer Oded , Malitsky Sergey , Barak Renana , Seger Rony , Erez Neta , Amit Ido , Tanay Amos , Saada Ann , Golan Talia , Rubinek Tamar , Sang Lee Joo , Ben-Shachar Shay , Wolf Ido , Erez Ayelet
Published: July 2023

Abstract
Multiple studies have identified metabolic changes within the tumor and its microenvironment during carcinogenesis. Yet, the mechanisms by which tumors affect the host metabolism are unclear. We find that systemic inflammation induced by cancer leads to liver infiltration of myeloid cells at early extrahepatic carcinogenesis. The infiltrating immune cells via IL6–pSTAT3 immune–hepatocyte cross-talk cause the depletion of a master metabolic regulator, HNF4α, consequently leading to systemic metabolic changes that promote breast and pancreatic cancer proliferation and a worse outcome. Preserving HNF4α levels maintains liver metabolism and restricts carcinogenesis. Standard liver biochemical tests can identify early metabolic changes and predict patients’ outcomes and weight loss. Thus, the tumor induces early metabolic changes in its macroenvironment with diagnostic and potentially therapeutic implications for the host.
Significance:
Cancer growth requires a permanent nutrient supply starting from early disease stages. We find that the tumor extends its effect to the host's liver to obtain nutrients and rewires the systemic and tissue-specific metabolism early during carcinogenesis. Preserving liver metabolism restricts tumor growth and improves cancer outcomes.

This article is highlighted in the In This Issue feature, p. 1501
Data from Targeting N-linked Glycosylation for the Therapy of Aggressive Lymphomas
Authors: Scheich Sebastian , Chen Jiji , Liu Jiamin , Schnutgen Frank , Enssle Julius C. , Ceribelli Michele , Thomas Craig J. , Choi Jaewoo , Morris Vivian , Hsiao Tony , Nguyen Hang , Wang Boya , Bolomsky Arnold , Phelan James D. , Corcoran Sean , Urlaub Henning , Young Ryan M. , Haupl Bjorn , Wright George W. , Huang Da Wei , Ji Yanlong , Yu Xin , Xu Weihong , Yang Yandan , Zhao Hong , Muppidi Jagan , Pan Kuan-Ting , Oellerich Thomas , Staudt Louis M.
Published: July 2023

Abstract
Diffuse large B-cell lymphoma (DLBCL) can be subdivided into activated B-cell like (ABC) and germinal center B-cell-like (GCB) DLCBL. Self-antigen engagement of B-cell receptors (BCRs) in ABC tumors induces their clustering, thereby initiating chronic active signaling and activation of NF-kB and PI3 kinase. Constitutive BCR signaling is essential in some GCB tumors but primarily activates PI3 kinase. We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. Unexpectedly, inactivation of N-linked protein glycosylation by the oligosaccharyltransferase-B (OST-B) complex reduced IRF4 expression. OST-B inhibition of BCR glycosylation reduced BCR clustering and internalization while promoting its association with CD22, which attenuated PI3 kinase and NF-kB activation. By directly interfering with proximal BCR signaling, OST-B inactivation killed models of ABC and GCB DLBCL, supporting the development of selective OST-B inhibitors for the treatment of these aggressive cancers.
Table S8 from Characterizing the immune microenvironment and neoantigen landscape of Hürthle cell carcinoma to identify potential immunologic vulnerabilities
Authors: Ganly Ian , Kuo Fengshen , Makarov Vladimir , Dong Yiyu , Ghossein Ronald A. , Xu Bin , Morris Luc G.T. , Chan Timothy A.
Published: July 2023

Neopeptides (9mer) associated with INDELS in HCC
Supp Figure S1 from Inhibition of microsomal prostaglandin E2 synthase reduces collagen deposition in melanoma tumors and may improve immunotherapy efficacy by reducing T cell exhaustion
Authors: Fukuda Yasunari , Kim Sun-Hee , Bustos Matias A. , Cho Sung-Nam , Roszik Jason , Burks Jared K. , Kim Hong , Hoon Dave S.B. , Grimm Elizabeth A. , Ekmekcioglu Suhendan
Published: July 2023

Figure S1 shows the selection of ROIs in tumors
Análise da pisada e da marcha com o uso da órtese TheraTogs® em criança com paralisia cerebral atetóide: um relato de caso
Authors: Machado Francine Zillmer , Almeida Carla Skilhan de , Gerzson Laís Rodrigues
Published: July 2023

Para crianças com paralisia cerebral (PC), as órteses assumem papel importante em seu desempenho funcional. Objetivo: Analisar a pisada estática e a marcha de uma criança com PC do tipo atetóide após uso diário do TheraTogs®. Método: Estudo de caso de um menino com nove anos de idade, PC do tipo atetóide, já possuía a veste terapêutica, mas não aplicava diariamente. Foi possível verificar dados do sujeito por meio de uma entrevista com a família e, para caracterização motora inicial, utilizou-se o Gross Motor Function Measure – 88. Para o diagnóstico e avaliação plantar, executou-se o baropodômetro e, na aferição cinemática da marcha, empregou-se a câmera Gopro Hero 7. O sujeito passou a usar de seis a 10 horas ao dia por oito semanas de forma sistemática e foi reavaliado. Resultado: O mesmo apresentou melhora na passada, redução da rotação externa de quadril e no apoio do pé direito (D) no solo. Na pisada estática, o ponto máximo de pressão ocorreu em retropé D, o centro de gravidade sofreu uma lateralização para a esquerda (E). No arco longitudinal ocorreu uma diminuição da carga, principalmente no médio pé D, onde a pressão maior foi no calcanhar. No médio pé E a descarga no arco longitudinal reduziu, mas ainda permaneceu. Conclusão: Foram encontradas mudanças na pisada estática e na marcha de um paciente com PC do tipo atetóide com uso diário, por oito semanas. São necessárias mais pesquisas que investiguem esse tema.
Thermotherapy associated with flexibility training does not increase the knee range of movement of healthy adults: systematic review and meta-analysis of randomized clinical trials
Authors: Ferreira Luis Fernando , Oliveira Arielle Rosa de , Rosa Luis Henrique Telles da
Published: July 2023

The stretching with thermotherapies associated have been related in the literature as a way to increase the range of motion (ROM), but still are not consensus about this efficacy and cost-effectiveness. The muscle stretching is a useful technique in rehabilitation and in physical activities programs, either to gain or maintain the flexibility, as a recovery of musculoskeletal and joint injuries. Objective: To determine the effects of thermotherapies associated to flexibility training in ROM of knee extension in healthy adults. Method: The search strategy was conducted in main databases, as Cochrane Library, LILACS, PEDro, PUBMED/ Medline, Scopus and Web of Science. The searches were done in 2016, and renewed in 2023, in order to achieve new publications along this time. Were selected only randomized clinical trials that have executed a training of hamstrings stretching, associated or not with one or more thermotherapies in healthy young adults, as long as the outcome was knee extension ROM. Only papers in Portuguese or English were assessed. To evaluate risk of bias was used the Cochrane Collaboration’s Risk of Bias Tool, and the methodological quality assessment was rated following the PEDro Scale. Results: Eight articles were included, totalizing 260 participants. The papers showed low methodological quality, and uncertain risk of bias. Only chronic effect of local warming and cryotherapy plus stretching showed a statistically significant difference versus control group. However, the thermotherapy action associated with stretching is still unclear, once the results suggest that even without the thermotherapy there are ROM increases. Conclusion: The stretching is effective in knee extension ROM improvement in healthy adults, with or without thermotherapy. New studies with higher methodological rigor and standardized protocols are needed.
O valor em tempos de crise: uma entrevista com Anselm Jappe
Authors: Carvalheiro Adriano , Amaral Paulo
Published: July 2023

A presente entrevista foi realizada no primeiro semestre de 2022 parcialmente em forma escrita (e-mail) e parcialmente através de uma conversa por videochamada com o autor. Em ambas, os entrevistadores indagaram o filósofo sobre uma grande quantidade de temas, todos presentes em suas diversas obras. Ao mesmo tempo, deu-se particular atenção à questão que se aproxima de sua pesquisa mais recente, i. e., o vínculo entre desenvolvimento capitalista da forma-valor e as formas patológicas de narcisismo em sua acepção psicanalítica. Tal pesquisa encontra-se cristalizada amplamente em seu livro, recentemente publicado no Brasil, A sociedade autofágica: capitalismo, desmedida e autodestruição (2021). O objetivo da entrevista é, de modo geral, contribuir para a divulgação da crítica do valor e, em particular, do pensamento de Anselm Jappe. Consideramos que as respostas aqui apresentadas possam oferecer instrumentos conceituais, se não suficientes, ao menos necessários, para construir uma correta compreensão dos problemas que os tempos atuais de crise permanente põem.
A ilusão transcendental e o seu mecanismo em geral na Crítica da razão pura
Authors: Cruz Patrícia Fernandes da
Published: July 2023

Neste artigo, percorremos os principais momentos da análise kantiana na Dialética transcendental da Crítica da razão pura sobre a relação intrínseca entre a ilusão transcendental e os princípios racionais. Kant trata brevemente da passagem entre a máxima lógica e o princípio transcendental, que é de suma importância para a caracterização do mecanismo geral da ilusão transcendental. Depois de analisarmos detidamente essa passagem, traremos da interpretação de Grier (2001) sobre a ilusão transcendental e dos possíveis desdobramentos da crítica de Longuenesse (2003) acerca dessa interpretação.
Dedução transcendental e realismo na Crítica da razão pura
Authors: Hickmann Gabriel Cunha
Published: July 2023

O artigo aborda o mérito da Dedução Transcendental, argumento central para a Crítica da razão pura, no que concerne especificamente ao embate com o ceticismo epistemológico de Hume. Desenvolve-se a ideia de que o preço pago por Kant em seu projeto (em algum sentido) anti-humeano, a posição idealista transcendental, apesar de conceitualmente distinta do idealismo de Berkeley e aliás o desenvolvimento consequente de um antirrealismo comum aos dois autores, situa-se, ainda e exatamente por conta desse apego antirrealista, em território inapelavelmente vulnerável à crítica do conhecimento, de onde a presença de um fundamento dogmático implícito nesse ponto da obra de Kant.
Um convite a repensar, via Nietzsche, a importância e a originalidade de Horkheimer como filósofo
Authors: Mattos Fernando Costa
Published: July 2023

Resenha de: Fernandes, Simone. Subjetividade e dominação. A filosofia de Nietzsche na teoria crítica de Horkheimer nos anos 1930 e 1940. Santo André: EdUFABC, 2022.
Health and Economic Impacts of Implementing Produce Prescription Programs for Diabetes in the United States: A Microsimulation Study
Authors: Wang Lu , Lauren Brianna N. , Hager Kurt , Zhang Fang Fang , Wong John B. , Kim David D. , Mozaffarian Dariush
Published: July 2023

Background

Produce prescription programs, providing free or discounted produce and nutrition education to patients with diet‐related conditions within health care systems, have been shown to improve dietary quality and cardiometabolic risk factors. The potential impact of implementing produce prescription programs for patients with diabetes on long‐term health gains, costs, and cost‐effectiveness in the United States has not been established.

Methods and Results

We used a validated state‐transition microsimulation model (Diabetes, Obesity, Cardiovascular Disease Microsimulation model), populated with national data of eligible individuals from the National Health and Nutrition Examination Survey 2013 to 2018, further incorporating estimated intervention effects and diet‐disease effects from meta‐analyses, and policy‐ and health‐related costs from published literature. The model estimated that over a lifetime (mean=25 years), implementing produce prescriptions in 6.5 million US adults with both diabetes and food insecurity (lifetime treatment) would prevent 292 000 (95% uncertainty interval, 143 000–440 000) cardiovascular disease events, generate 260 000 (110000–411 000) quality‐adjusted life‐years, cost $44.3 billion in implementation costs, and save $39.6 billion ($20.5–58.6 billion) in health care costs and $4.8 billion ($1.84–$7.70 billion) in productivity costs. The program was highly cost effective from a health care perspective (incremental cost‐effectiveness ratio: $18 100/quality‐adjusted life‐years) and cost saving from a societal perspective (net savings: $−0.05 billion). The intervention remained cost effective at shorter time horizons of 5 and 10 years. Results were similar in population subgroups by age, race or ethnicity, education, and baseline insurance status.

Conclusions

Our model suggests that implementing produce prescriptions among US adults with diabetes and food insecurity would generate substantial health gains and be highly cost effective.
Number of Passes of Endovascular Therapy for Stroke With a Large Ischemic Core: Secondary Analysis of RESCUE-Japan LIMIT
Authors: Namitome Satoshi , Uchida Kazutaka , Shindo Seigo , Yoshimura Shinichi , Sakai Nobuyuki , Yamagami Hiroshi , Toyoda Kazunori , Matsumaru Yuji , Matsumoto Yasushi , Kimura Kazumi , Ishikura Reiichi , Inoue Manabu , Beppu Mikiya , Sakakibara Fumihiro , Shirakawa Manabu , Ueda Mitsuharu , Morimoto Takeshi ,   for the RESCUE-Japan LIMIT Investigators
Published: July 2023

BACKGROUND:

The increased risk of intracranial hemorrhage with multiple passes in endovascular therapy (EVT) for large vessel occlusion with a large ischemic core is a concern. We explored the effect of the number of EVT passes on patients in a randomized clinical trial.

METHODS:

This post hoc study was the secondary analysis of RESCUE-Japan LIMIT, which was a randomized clinical trial comparing EVT and medical treatment alone for large vessel occlusion with large ischemic core. We grouped patients according to the number of passes with successful reperfusion (modified Thrombolysis in Cerebral Infarction score, ≥2b) in 1, 2, and 3 to 7 passes and failed reperfusion (modified Thrombolysis in Cerebral Infarction score, 0–2a) after any pass in the EVT group, and these groups were compared with medical treatment group. The primary outcome was modified Rankin Scale score of 0 to 3 at 90 days. Secondary outcomes were improvement in National Institutes of Health Stroke Scale score of ≥8 at 48 hours, mortality at 90 days, symptomatic intracranial hemorrhage, and any intracranial hemorrhage within 48 hours.

RESULTS:

The number of patients who received EVT with successful reperfusion after 1, 2, and 3 to 7 passes and failed reperfusion were 44, 23, 19, and 14, respectively, and 102 received medical treatment alone. The adjusted odds ratios (95% CIs) for the primary outcome relative to medical treatment were 5.52 (2.23–14.28) after 1 pass, 6.45 (2.22–19.30) after 2 passes, 1.03 (0.15–4.48) after 3 to 7 passes, and 1.17 (0.16–5.37) if reperfusion failed. The adjusted odds ratios (95% CIs) for any intracranial hemorrhage within 48 hours relative to medical treatment were 1.88 (0.90–3.93) after 1 pass, 5.14 (1.97–14.72) after 2 passes, 3.00 (1.09–8.58) after 3 to 7 passes, and 6.16 (1.87–24.27) if reperfusion failed.

CONCLUSIONS:

The successful reperfusion within 2 passes was associated with better clinical outcomes.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03702413.
Collaborators of Justice: Consensual Procedural Forms Serving Probative Purposes Analysed Through Practitioners’ Experiences in Croatia
Authors: Ivičević Karas Elizabeta , Buric Zoran , Pajčić Matko
Published: July 2023

This paper presents the research results of Croatian practitioners’ experiences in applying consensual forms which serve probative purposes. The aim of the research was to find out, through the qualitative analysis of practical experiences obtained through semi-structured interviews with 60 practitioners in criminal justice system – 20 judges, 20 state attorneys and 20 defence attorneys, and then through discussions in four focus groups, how measures of rewarding collaborators of justice are applied in practice. The focus was on procedural tools which may be used to ensure respect of the principle of legality and the lawful application of the principle of discretionary prosecution, as well as on judicial control, which should efficiently prevent “mixing the procedural roles” of the accused and the witness. Particular attention was paid to the emergence of informal agreements, which puts into question the whole concept of regulated consensual forms serving probative purposes. An analysis of the practical experiences of different stakeholders reveals the existing deficiencies of normative regulation and applied practices.
The Global Wind Atlas: A High-Resolution Dataset of Climatologies and Associated Web-Based Application
Authors: Davis Neil N. , Badger Jake , Hahmann Andrea N. , Hansen Brian O. , Mortensen Niels G. , Kelly Mark , Larsén Xiaoli G. , Olsen Bjarke T. , Floors Rogier , Lizcano Gil , Casso Pau , Lacave Oriol , Bosch Albert , Bauwens Ides , Knight Oliver James , Potter van Loon Albertine , Fox Rachel , Parvanyan Tigran , Krohn Hansen Søren Bo , Heathfield Duncan , Onninen Marko , Drummond Ray
Published: July 2023

The Global Wind Atlas (GWA) provides high-resolution databases and maps of the wind resource for all land points and for water points within 200 km of the coastline, excluding Antarctica. The GWA is used to identify and understand the global, national, regional, and local potential for wind energy and to guide energy specialists, policymakers, and planners in the transition to a sustainable energy system. This information is vital to ensuring the growth of wind energy, helping to transition to a sustainable energy system, which will mitigate climate change and meet the world’s need for reliable, affordable, and clean energy. The GWA uses the established numerical wind atlas methodology to downscale coarse-resolution wind data to microscale, using linearized flow modeling and high-resolution topographic data. There have been three versions of the GWA, each using mesoscale model data at successively higher spatial resolution. A website and geographic information system (GIS) files support quick and in-depth analysis. Validation data and analysis, using measurements from tall masts located worldwide, are also provided through the web application. The development process of the GWA involves a dialogue between meteorological modelers, wind energy development experts, web designers, and representatives of the end users to provide accurate data in a dynamic and relevant way. This article outlines the general method, specific development, and application of the Global Wind Atlas.
Infrared Spectra in the 1000–100 cm−1 Region Combined with 4000–3000 cm−1 Region to Evaluate the States of Water
Authors: Ishikawa Daitaro , Shinohara Rin , Shichishima Natsumi , Fujii Tomoyuki
Published: July 2023

In this study, we evaluated the state of water by performing infrared (IR) spectroscopic analysis in the 4000–100 cm−1 region. The effects of ions on the structure of water molecules were investigated by analyzing specific IR bands of salt solutions in the 1000–100 cm−1 region. Chloride solutions of Li, Na, K, Cs, Ba, and Ca were prepared at different concentrations, and their IR spectra were recorded by the attenuated total reflection method. The isosbestic point was observed in the 1000–100 cm−1 region, and the position was related to the ratio of the Stokes radius and effective ionic radius of each ion. Two bands were identified at around 660 and 400 cm−1 by curve fitting, and the intensity ratio increased linearly with a decrease in water activity. Thus, this demonstrates the potential of the 1000–100 cm−1 region as a marker for the evaluation of water structure subjected to ions. Moreover, it is possible to evaluate different states of water simultaneously by combining this with the band in the 4000–3000 cm−1 region. These results successfully demonstrate the effectiveness of the spectra in the 1000–100 cm−1 region to evaluate the state of water in ionic solutions.