bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic Interrogation of Tumor Cell Resistance to Chimeric Antigen Receptor T-cell Therapy in Pancreatic Cancer
Authors: Hagel Kimberly R. , Arafeh Rand , Gang Sydney , Arnoff Taylor E. , Larson Rebecca C. , Doench John G. , Mathewson Nathan D. , Wucherpfennig Kai W. , Maus Marcela V. , Hahn William C. 
Published: December 2022

AbstractChimeric antigen receptor (CAR) T-cell therapy can lead to dramatic clinical responses in B-cell malignancies. However, early clinical trials with CAR T-cell therapy in non–B-cell malignancies have been disappointing to date, suggesting that tumor-intrinsic features contribute to resistance. To investigate tumor-intrinsic modes of resistance, we performed genome scale CRISPR-Cas9 screens in mesothelin (MSLN)-expressing pancreatic cancer cells. Co-culture with MSLN-targeting CAR T cells identified both antigen-dependent and antigen-independent modes of resistance. In particular, loss of the majority of the genes involved in the pathway responsible for GPI-anchor biosynthesis and attachment abrogated the ability of CAR T cells to target pancreatic cancer cells, suggesting that disruption of this pathway may permit MSLN CAR T-cell evasion in the clinic. Antigen-independent mediators of CAR T-cell response included members of the death receptor pathway as well as genes that regulate tumor transcriptional responses, including TFAP4 and INTS12. TFAP4-mediated CAR T resistance depended on the NFκB transcription factor p65, indicating that tumor resistance to CAR T-cell therapy likely involves alterations in tumor-intrinsic states. Overall, this study uncovers multiple antigen-dependent and -independent mechanisms of CAR T-cell evasion by pancreatic cancer, paving the way for overcoming resistance in this disease that is notoriously refractory to immunotherapy.Significance:The identification and validation of key determinants of CAR T-cell response in pancreatic cancer provide insights into the landscape of tumor cell intrinsic resistance mechanisms and into approaches to improve therapeutic efficacy.
Project Confirm: Accelerated Drug Approvals for Chronic Myeloid Leukemia
Authors: Sweet Kendra L. , Cortes Jorge E. , Apperley Jane F. , Mann Mel , Mauro Michael J. , Oehler Vivian G. , Ruiz Cristina , Schiffer Charles A. , Ehrlich Lori A. , Pamuk Gulsum E. , Wynne Joseph , Mehta Gautam U. , de Claro R. Angelo , Theoret Marc R. , Smith B. Douglas , Norsworthy Kelly J. 
Published: December 2022

Abstract
The FDA has an accelerated approval program for drugs that have been identified as promising treatments for serious conditions when the available data suggest that the benefits outweigh the foreseeable risks. All of the currently available treatment options for chronic myeloid leukemia (CML) initially went through the accelerated approval program. Here, a group of academic CML experts, patient panelists, and members from the FDA convened to discuss the utility of the accelerated approval program as it pertains to CML, and the utility of this program in future drug development in this disease. The results of that discussion are summarized here.
A Single-Arm Phase II Trial of Sitravatinib in Advanced Well-Differentiated/Dedifferentiated Liposarcoma
Authors: Ingham Matthew , Lee Shing , Van Tine Brian A. , Choy Edwin , Oza Jay , Doshi Sahil , Ge Liner , Oppelt Peter , Cote Gregory , Corgiat Brian , Sender Naomi , Sta Ana Sarah , Panchalingam Lavan , Petricoin Emmanuel , Schwartz Gary K. 
Published: December 2022

AbstractPurpose:To evaluate sitravatinib, an inhibitor of multiple receptor tyrosine kinases (RTK), for the treatment of well-differentiated/dedifferentiated liposarcoma (WD/DD LPS).Patients and Methods:This multicenter, open-label, Phase II trial enrolled patients with advanced WD/DD LPS who had received at least one prior systemic regimen and had progression within 12 weeks of enrollment. Patients received sitravatinib 150 mg (later amended to 120 mg) orally daily. A Simon two-stage design was used to evaluate for an improvement in the primary endpoint, progression-free rate at 12 weeks (PFR12), from 20% to 40%. Secondary endpoints included antitumor activity and safety. A subset of patients underwent paired biopsies analyzed using reverse-phase protein array.Results:Twenty-nine patients enrolled. Median age was 62 years and 31% had received 3 or more prior lines. Most patients (93%) had DDLPS or mixed WD/DD LPS. Overall, 12 of 29 patients (41%) were alive and progression-free at 12 weeks and the study met the primary endpoint. There were no confirmed responses. Median progression-free survival was 11.7 weeks [95% confidence interval (CI): 5.9–35.9] and median overall survival was 31.7 weeks (95% CI: 18.1–90.1). The most common treatment-related adverse events were diarrhea (59%), hypertension (52%), hoarseness (41%), mucositis (31%), and nausea (31%). Baseline expression of phospho-RTKs was not significantly different between patients with and without clinical benefit from sitravatinib, but the number of samples was small.Conclusions:Sitravatinib provided a PFR12 of 41% and meaningful disease control in a subset of patients with advanced, progressive WD/DD LPS.
Syntaphilin Regulates Neutrophil Migration in Cancer
Authors: Fu Shuyu , Deng Hui , Bertolini Irene , Perego Michela , Chen Eric S. , Sanseviero Emilio , Mostafa Ali , Alicea-Torres Kevin , Garcia-Gerique Laura , Stone Erica L. , Kossenkov Andrew V. , Schug Zachary T. , Nam Brian , Mulligan Charles , Altieri Dario C. , Nefedova Yulia , Gabrilovich Dmitry I. 
Published: December 2022

AbstractPathologically activated neutrophils (PMN) with immunosuppressive activity, which are termed myeloid-derived suppressor cells (PMN-MDSC), play a critical role in regulating tumor progression. These cells have been implicated in promoting tumor metastases by contributing to premetastatic niche formation. This effect was facilitated by enhanced spontaneous migration of PMN from bone marrow to the premetastatic niches during the early-stage of cancer development. The molecular mechanisms underpinning this phenomenon remained unclear. In this study, we found that syntaphilin (SNPH), a cytoskeletal protein previously known for anchoring mitochondria to the microtubule in neurons and tumor cells, could regulate migration of PMN. Expression of SNPH was decreased in PMN from tumor-bearing mice and patients with cancer as compared with PMN from tumor-free mice and healthy donors, respectively. In Snph-knockout (SNPH-KO) mice, spontaneous migration of PMN was increased and the mice showed increased metastasis. Mechanistically, in SNPH-KO mice, the speed and distance travelled by mitochondria in PMN was increased, rates of oxidative phosphorylation and glycolysis were elevated, and generation of adenosine was increased. Thus, our study reveals a molecular mechanism regulating increased migratory activity of PMN during cancer progression and suggests a novel therapeutic targeting opportunity.
Antigen-Loaded Extracellular Vesicles Induce Responsiveness to Anti–PD-1 and Anti–PD-L1 Treatment in a Checkpoint Refractory Melanoma Model
Authors: Veerman Rosanne E. , Akpinar Gözde Güclüler , Offens Annemarijn , Steiner Loïc , Larssen Pia , Lundqvist Andreas , Karlsson Mikael C.I. , Gabrielsson Susanne 
Published: December 2022

Abstract

Extracellular vesicles (EV) are important mediators of intercellular communication and are potential candidates for cancer immunotherapy. Immune checkpoint blockade, specifically targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis, mitigates T-cell exhaustion, but is only effective in a subset of patients with cancer. Reasons for therapy resistance include low primary T-cell activation to cancer antigens, poor antigen presentation, and reduced T-cell infiltration into the tumor. Therefore, combination strategies have been extensively explored. Here, we investigated whether EV therapy could induce susceptibility to anti–PD-1 or anti–PD-L1 therapy in a checkpoint-refractory B16 melanoma model. Injection of dendritic cell–derived EVs, but not checkpoint blockade, induced a potent antigen-specific T-cell response and reduced tumor growth in tumor-bearing mice. Combination therapy of EVs and anti–PD-1 or anti–PD-L1 potentiated immune responses to ovalbumin- and α-galactosylceramide–loaded EVs in the therapeutic model. Moreover, combination therapy resulted in increased survival in a prophylactic tumor model. This demonstrates that EVs can induce potent antitumor immune responses in checkpoint refractory cancer and induce anti–PD-1 or anti–PD-L1 responses in a previously nonresponsive tumor model.
Depression detection in social media comments data using machine learning algorithms
Authors: Vasha Zannatun Nayem , Sharma Bidyut , Esha Israt Jahan , Al Nahian Jabir , Polin Johora Akter 
Published: December 2022

Depression is the next level of negative emotions. When a person is in a sad mood or going through a difficult situation and it is not leaving him and giving him pain continuously and he is unable to bear it anymore, that situation is called depression. The last stage of depression occurs in suicide. According to the World Health Organization (WHO), Currently, 4.4% of people in the world are currently suffering from depression. In 2021, fourteen thousand people committed suicide all over the world and the rating of suicide is increasing day by day. So, our study is to find depressed people by their comments, posts, or texts on social media. We collected almost 10,000 data from Facebook posts, comments, and YouTube comments. Data mining and machine learning (ML) algorithms make our work easier and play a big role in easily detecting a person’s emotions. We applied six classifiers to predict depression non-depression and found the best accuracy on a support vector machine (SVM).
Phthalates exposure as environmental risk factor for type 2 diabetes mellitus
Authors: Fauziah Munaya , Suhartono Suhartono , Widjanarko Bagoes , Gasem Muhammad Hussein 
Published: December 2022

Phthalates exposure occurs in all areas, such as foods' plastic packaging, cosmetics, and others. Previous studies showed that phthalates are associated with the prevalence of T2DM. Type 2 Diabetes Mellitus (T2DM) is caused by a combination of defective insulin secretion by pancreatic β-cells and the insulin-resistance. This study aimed to investigate whether phthalate exposure is an environmental risk factor for T2DM. A case-control study was conducted among residents in the South Tangerang district from June 2020 to February 2021 using a purposive sampling technique. The cases were the patients diagnosed T2DM with HbA1c<span style="text-decoration: underline;">&gt;</span>6.5% random blood sugar<span style="text-decoration: underline;">&gt;</span>200 mg/dL, with history T2DM treatment. The respondents' urines were collected and evaluated using liquid chromatography/mass spectrometry (LC/MS). A total of 47 cases and 47 controls were recruited in the study. The lowest monomethyl phthalate (MEP) and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were 5.37 µg/L and 2.02 µg/L, respectively. On multivariable regression analysis, the high urinary MEP level (&gt;131.91 µg/L) was independently associated with T2DM (OR: 3.754, 95% CI: 1.559–8.811, p-value: 0.002). MEP is an environmental risk factor for T2DM and likely has a significant impact on human health than MEHHP.
Identifying and Localizing Multiple Objects Using Artificial Ventral and Dorsal Cortical Visual Pathways
Authors: Han Zhixian , Sereno Anne 
Published: December 2022

Abstract
In our previous study (Han & Sereno, 2022a), we found that two artificial cortical visual pathways trained for either identity or space actively retain information about both identity and space independently and differently. We also found that this independently and differently retained information about identity and space in two separate pathways may be necessary to accurately and optimally recognize and localize objects. One limitation of our previous study was that there was only one object in each visual image, whereas in reality, there may be multiple objects in a scene. In this study, we find we are able to generalize our findings to object recognition and localization tasks where multiple objects are present in each visual image. We constrain the binding problem by training the identity network pathway to report the identities of objects in a given order according to the relative spatial relationships between the objects, given that most visual cortical areas including high-level ventral steam areas retain spatial information. Under these conditions, we find that the artificial neural networks with two pathways for identity and space have better performance in multiple-objects recognition and localization tasks (higher average testing accuracy, lower testing accuracy variance, less training time) than the artificial neural networks with a single pathway. We also find that the required number of training samples and the required training time increase quickly, and potentially exponentially, when the number of objects in each image increases, and we suggest that binding information from multiple objects simultaneously within any network (cortical area) induces conflict or competition and may be part of the reason why our brain has limited attentional and visual working memory capacities.
L’‘allitterazione della solitudine’ in Virgilio
Authors: Dainotti Paolo 
Published: December 2022

Abstract
The article focusses on a particular type of ‘pathetic alliteration’ in Virgil’s poetry which links the adjective solus with words strictly related in meaning. By means of a detailed stylistic analysis of passages from Aeneid, Eclogues and Georgics the author demonstrates the stylistically motivated use of this kind of alliteration and shows how sound effects are usually combined with other stylistic figures charging the diction with expressiveness.
Il Περὶ τοῦ ἀνθρώπου: un inedito testo isagogico nel Vaticanus gr. 279
Authors: Ecca Giulia 
Published: December 2022

Abstract
In the folia 275r–276r of the MS. Vaticanus gr. 279 we find a so far unedited text, which shows some similarities with other late antique and Byzantine medical writings on the four humors. However, this new text reveals particular features, like, for example, manifest parallels with the pseudo-Galenic Introductio sive medicus, that emphasize its isagogical (i.e., introductive) function. In this article, I offer the first critical edition, with Italian translation and notes of commentary, of this new text from the Byzantine period.
Book Review: Tomasz Kamusella, "Words in Space and Time: A Historical Atlas of Language Politics in Modern Central Europe". Budapest: Central European University Press, 2022, 289 pp. ISBN: 978-963-386-417-3
Authors: Olszewska Izabela 
Published: December 2022

The paper is a presentation of Tomasz Kamusella’s latest book on language policy in Central Europe. The volume in question provides the reader with substantial information on the mechanisms of the creation and use of Central European languages for political action.
Future Changes in Tropical and Extratropical Cyclones Affecting Hokkaido and Their Related Precipitation Based on Large-Ensemble Climate Simulations
Authors: Kawazoe Sho , Inatsu Masaru , Yamada Tomohito J. , Hoshino Tsuyoshi 
Published: December 2022

Abstract
This study investigates the impact of future climate warming on tropical cyclones (TC) and extratropical cyclones (ETC) using the database for Policy Decision-Making for Future Climate Change (d4PDF) large ensemble simulations. Cyclone tracking was performed using the neighbor enclosed area tracking algorithm (NEAT), and TC and ETCs were identified over the western North Pacific Ocean (WNP). For cyclone frequency, it was revealed that, although a slight underestimation of the total number of TCs and ETCs in both the WNP and near Hokkaido, Japan, exists, the d4PDF reproduced the spatial distribution of both TC and ETC tracks well when compared with observations/reanalysis. The 4-K warming scenarios derived from six different sea surface temperature warming patterns showed robust decreases in TC frequency in the tropical WNP and a slight reduction in ETCs near Japan. Next, precipitation characteristics for TCs or ETCs in the vicinity of Hokkaido were examined using 5-km-mesh regional climate ensemble simulations. Four representative cyclone locations near Hokkaido are identified using K-means clustering and revealed distinct precipitation characteristics between clusters, with higher TC-associated precipitation than ETC-associated precipitation and the heaviest precipitation in the southern portion of the prefecture. The 4-K warming scenarios revealed increased precipitation for all cyclone placements for both TCs and ETCs. Last, average cyclone intensity, translation speed, and size were examined. It was shown that TCs in future climates are more intense, propagate more slowly, and are smaller in terms of enclosed vorticity area as they approach Hokkaido. For ETCs, mean intensity does not change much; they travel slightly faster, and become smaller.
Impacts of Methods for Estimating the Observation Error Variance for the Frequent Assimilation of Thermodynamic Profilers on Convective-Scale Forecasts
Authors: Degelia Samuel K. , Wang Xuguang 
Published: December 2022

Abstract
The observation error covariance partially controls the weight assigned to an observation during data assimilation (DA). True observation error statistics are rarely known and likely vary depending on the meteorological state. However, operational DA systems often apply static methods that assign constant observation errors across a dataset. Previous studies show that these methods can degrade forecast quality when assimilating ground-based remote sensing datasets. To improve the impact of assimilating such observations, we propose two novel methods for estimating the observation error variance for high-frequency thermodynamic profilers. These methods include an adaptive observation error inflation technique and the Desroziers method that directly estimates the observation error variances using paired innovation and analysis residuals. Each method is compared for a nocturnal mesoscale convective system (MCS) observed during the Plains Elevated Convection at Night (PECAN) experiment. In general, we find that these novel methods better represent the large variability of observation error statistics for high-frequency profiles collected by Atmospheric Emitted Radiance Interferometers (AERIs). When assimilating AERIs by statically inflating retrieval error variances, the trailing stratiform region of the MCS is degraded compared to a baseline simulation with no AERI data assimilated. Assimilating the AERIs using the adaptive inflation or Desroziers method results in better maintenance of the trailing stratiform region and additional suppression of spurious convection. The forecast improvements from these novel methods are primarily linked to increased error variances for some moisture retrievals. These results indicate the importance of accurately estimating observation error statistics for convective-scale DA and suggest that accounting for flow dependence can improve the impacts from assimilating remote sensing datasets.
Direct Measurement of Chocolate Components Using Dispersive Raman Spectroscopy at 1000 nm Excitation
Authors: Esmonde-White Karen , Lewis Mary , Lewis Ian R. 
Published: December 2022

Chocolate is a popular food around the world. Making chocolate-based confectionaries involve multiple processing steps including cocoa bean fermentation, cocoa bean roasting, grinding, and then a controlled crystallization, where the processing conditions yields the desirable polymorph V to give chocolate its characteristic snap and texture. Raman spectroscopy is well known as a technique that can provide a non-contact, non-destructive analysis of chemical composition and molecular structure. Yet, excitation in the visible and near-infrared (532–785 nm) has not been possible for dark or milk chocolate because of the samples’ overwhelming fluorescence. New technologies enabling Raman spectroscopy closer to shortwave infrared wavelengths, closer to 1000 nm, are likely to reduce fluorescence of chocolate and other highly fluorescent samples. Based on the successes of 1064 nm excitation to understand chocolate blooming, we hypothesized that 1000 nm excitation would also reduce fluorescence and enable Raman spectroscopy in dark and milk chocolates. We used dispersive Raman spectroscopy at 1000 nm to measure white, milk, and dark chocolate and cocoa nibs. The use of 1000 nm excitation effectively reduced fluorescence, enabling qualitative and quantitative Raman spectroscopy directly on chocolate samples. These feasibility studies indicate that 1000 nm Raman spectroscopy can be used to measure chocolate in a laboratory or process environment.
Time-and temperature-dependent compressive behavior of woven carbon fabric reinforced polyamide composite laminate
Authors: Nam Tran Huu , Goto Ken , Tobata Yuta , Kubota Yuki , Ueda Masahito , Kobayashi Satoshi 
Published: December 2022

Plain woven carbon fabric reinforced polyamide (CF/PA) composite laminate was developed using hot-pressed processing with a vacuum-assisted system. Temperature-dependent mechanical properties of the CF/PA composite laminate under longitudinal compressive loading were examined. The compressive mechanical properties of the composite laminate decreased considerably with increasing the temperature to 120°C. The compressive strength and strain at maximal stress reduced rapidly below 80°C, while the compressive modulus declined slightly underneath 50°C. The glass transition temperature of the CF/PA composite was found to be about 50°C by the differential scanning calorimetry, which almost corresponded to the slight reduction of the elastic modulus at temperatures below 50°C. The time-dependent creep behavior of the CF/PA laminate under compressive loading at isotherms between 25°C and 50°C was studied. Creep strains of the CF/PA composite samples increased with rising temperature. The smooth creep compliance master curve of the CF/PA composite was obtained by shifting short-term creep compliance curves using the time–temperature superposition principle. The master curve provided a creep prediction to 961.6 days with the measured data in only 12.5 days.
Green and Pleasant Lands: The Affective and Cerebral Hemodynamic Effects of Presence in Virtual Environments During Exercise
Authors: Jones Leighton , Wheat Jonathan 
Published: December 2022

Pleasant exercise experiences increase the likelihood of exercise adherence, and innovative strategies to promote consistently pleasant exercise experiences are needed. In this study we compared a novel nature-based virtual reality environment, a nature-based 360° video, and a control condition to test the hypothesis that greater presence in virtual space would promote positive affective experiences during exercise. Moreover, we assessed prefrontal cerebral hemodynamics using near infrared spectroscopy to explore possible neural underpinnings of dissociative strategies during exercise. Twelve participants ( M = 26.2, SD = 7.7 years; M BMI = 25.5, SD = 5.2 kg/m2) completed a maximal aerobic test and three exercise conditions (Control, Virtual Reality [VR], and 360° video). The two experimental conditions differed in terms of the participants’ sense of presence (VR eliciting greatest presence), and all conditions utilized similar exercise intensity. The VR condition setting was a virtual mountain forest trail, and the 360° video was of a forest road. The 360° video was perceived as the most distracting ( p = .023, d = 1.07), pleasant ( p = .007, d = .75), and enjoyable ( p = .029; d = .82) condition. ΔHbDiff data indicated that the control condition caused the greatest prefrontal brain activation ( p = .008, d = .84). Presence was not a salient factor in distracting participants from bodily sensations during exercise, but immersion in a stimulus was. These results provide support for using head-mounted displays during exercise as a strategy to increase pleasure, with practical implications for practitioners, researchers, and individuals.