bluuebunny/crossref_metadata_2025_split huggingface dataset:
MEK Inhibition Sensitizes Pancreatic Cancer to STING Agonism by Tumor Cell–intrinsic Amplification of Type I IFN Signaling
Authors: Ghukasyan Razmik , Liang Keke , Chau Kevin , Li Luyi , Chan Charlotte , Abt Evan R. , Le Thuc , Park Joon Y. , Wu Nanping , Premji Alykhan , Damoiseaux Robert , Luu Tony , Labora Amanda , Rashid Khalid , Link Jason M. , Radu Caius G. , Donahue Timothy R. 
Published: May 2023

Abstract

Purpose:
Stimulator of interferon genes (STING) agonists are currently in development for treatment of solid tumors, including pancreatic ductal adenocarcinoma (PDAC). Response rates to STING agonists alone have been promising yet modest, and combination therapies will likely be required to elicit their full potency. We sought to identify combination therapies and mechanisms that augment the tumor cell–intrinsic effect of therapeutically relevant STING agonists apart from their known effects on tumor immunity.

Experimental Design:
We screened 430 kinase inhibitors to identify synergistic effectors of tumor cell death with diABZI, an intravenously administered and systemically available STING agonist. We deciphered the mechanisms of synergy with STING agonism that cause tumor cell death in vitro and tumor regression in vivo.

Results:
We found that MEK inhibitors caused the greatest synergy with diABZI and that this effect was most pronounced in cells with high STING expression. MEK inhibition enhanced the ability of STING agonism to induce type I IFN-dependent cell death in vitro and tumor regression in vivo. We parsed NFκB-dependent and NFκB-independent mechanisms that mediate STING-driven type I IFN production and show that MEK signaling inhibits this effect by suppressing NFκB activation.

Conclusions:
Our results highlight the cytotoxic effects of STING agonism on PDAC cells that are independent of tumor immunity and that these therapeutic benefits of STING agonism can be synergistically enhanced by MEK inhibition.
Preclinical Evaluation of 9MW2821, a Site-Specific Monomethyl Auristatin E–based Antibody–Drug Conjugate for Treatment of Nectin-4–expressing Cancers
Authors: Zhou Wei , Fang Peng , Yu Dongan , Ren Hongyuan , You Meng , Yin Long , Mei Fei , Zhu Huikai , Wang Zhenzhen , Xu Hui , Cao Yuxia , Sun Xiaowei , Xu Xiaohong , Bi Jianjun , Wang Jin , Ma Lanping , Wang Xin , Chen Lin , Zhang Yongliang , Cen Xiaowei , Zhu Xi , Lou Liguang , Liu Datao , Tan Xiaoding , Yang Jinliang , Meng Tao , Shen Jingkang 
Published: May 2023

Abstract
Overexpression of nectin cell adhesion protein 4 correlates with cancer progression and poor prognosis in many human malignancies. Enfortumab vedotin (EV) is the first nectin-4–targeting antibody–drug conjugate (ADC) approved by the FDA for the treatment of urothelial cancer. However, inadequate efficacy has limited progress in the treatment of other solid tumors with EV. Furthermore, ocular, pulmonary, and hematologic toxic side effects are common in nectin-4–targeted therapy, which frequently results in dose reduction and/or treatment termination. Thus, we designed a second generation nectin-4–specific drug, 9MW2821, based on interchain-disulfide drug conjugate technology. This novel drug contained a site specifically conjugated humanized antibody and the cytotoxic moiety monomethyl auristatin E. The homogenous drug–antibody ratio and novel linker chemistry of 9MW2821 increased the stability of conjugate in the systemic circulation, enabling highly efficient drug delivery and avoiding off-target toxicity. In preclinical evaluation, 9MW2821 exhibited nectin-4–specific cell binding, efficient internalization, bystander killing, and equivalent or superior antitumor activity compared with EV in both cell line–derived xenograft and patient-derived xenograft (PDX) models. In addition, 9MW2821 demonstrated a favorable safety profile; the highest nonseverely toxic dose in monkey toxicologic studies was 6 mg/kg, with milder adverse events compared with EV. Overall, 9MW2821 is a nectin-4–directed, investigational ADC based on innovative technology that endowed the drug with compelling preclinical antitumor activity and a favorable therapeutic index. The 9MW2821 ADC is being investigated in a phase I/II clinical trial (NCT05216965 and NCT05773937) in patients with advanced solid tumors.
Pure and Other Phenomenologically Oriented Psychology
Authors: Nenon Thomas 
Published: May 2023

Abstract
This paper inquires into the necessity and limits of what Edmund Husserl calls a “pure” phenomenological psychology. It argues that there may be merit to this notion as a kind of philosophical psychology, the notion of purity in clinical psychology would unnecessarily limit the kinds of factors that the psychologist must take into account in understanding and treating most of the psychological conditions the therapist faces. The paper suggests that phenomenological psychology nonetheless has value in providing a counter-balance to naturalistically inclined psychology that for its part neglects the meaning of various life events for the agent and can serve as means of critical reflection on the operative concepts guiding psychological practice. It can also help correct a deterministic tendency in modern psychology that does not take seriously enough human beings’ capacity for self-reflection and for self-responsibility that can often serve as key elements in psychological therapy and healing.
Extraction and normalization of IR indexing terms and phrases in a highly inflectional language
Authors: Gakis Panagiotis , Kokkinos Theodoros , Tsalidis Christos 
Published: May 2023

Abstract
Term-based indexing of documents is conventionally implemented by stemmers or their corpus-based improvements, both of which encode implicit linguistic information. Terms are directly derived from document content such that a unique indexing approach is available at indexing run-time. For highly inflectional languages where term variation is high, such techniques are more error-prone. The main focus of the current study is the extraction and normalization of single terms and phrases and the proposal of authenticated control of indexing. The proposed approach relies on the use of explicit linguistic knowledge, appropriately encoded in large language resources. Such control guarantees the highest possible expansion factor for indexing terms as well as indexing consistency. Moreover, it offers a framework where different and eventually contradicting indexing criteria can be practiced, conventional and Natural Language Processing (NLP)-based Information Retrieval (IR) applications can be served, while adaptations can be made for tuning to a specific domain or corpus.
Devotional Synergy and Expanding Shi’i Space- Times: Preliminary Observations on Changing ‘Azādārī Practices in the Bhit Shah Area
Authors: Huang Pei-ling , Lanjwani Bisharat Ali 
Published: May 2023

Abstract
Bhit Shah is the abode of venerated Sufi mystic Shah Abdul Latif Bhittai. During the last few decades, the saint’s shrine has also become a center for Shi’i practices of ‘azādārī – mourning congregations in memory of Imam Husain. This article contributes to the literature on intertwining Sufi and Shi’i practices by examining how saintly and Husaini devotion repertoires converged in the Bhit Shah area and how this convergence contributed to transformations in ritual action and identity over the twentieth century. We explore how local devotees started adopting the remembrance of Imam Husain and Karbala through devotion to Shah Latif, which initially took place without changes in the devotees’ religious affiliation. However, with the precolonial Talpurs’ influence and interaction with other devotees from Shi’i urban centers of Sindh, many residents began to affirm Twelver Shi’a identification and expand their mourning practices in space and duration.
Distinct Meteorological Mode Associated with High-PM2.5 Episodes in Seoul, South Korea
Authors: Choi Daniel , Lee Hyo-Jung , Chang Lim-Seok , Jo Hyun-Young , Jo Yu-Jin , Park Shin-Young , Yang Geum-Hee , Kim Cheol-Hee 
Published: May 2023

Abstract
In this study, high–particulate matter (PM2.5) pollution episodes were examined in Seoul, the capital city of South Korea, which, based on the episode characteristics, were influenced by a distinct meteorological mode, long-range transport (LRT), from two-level meteorological observations: surface and 850–500-hPa level. We performed two-step statistical analysis including principal component (PC) analysis of meteorological variables based on the observation data, followed by multiple linear regression (MLR). The meteorological variables included surface temperature (Tsfc), wind speed (WSsfc), and the east–west (usfc) and north–south (υsfc) components of wind speed, as well as wind components at 850-hPa geopotential height (u850 and υ850, respectively) and the vertical temperature gradient between 850 and 500 hPa. Our two-step analysis of data collected during the period 2018–19 revealed that the dominant factors influencing high-PM2.5 days in Seoul (129 days) were upper-wind characteristics in winter, including positive u850 and negative υ850, that were controlled by the presence of continental anticyclones that increased the likelihood of LRT of PM2.5 pollutants. Regional-scale meteorological variables, including surface and upper-meteorological variables on normal and high-PM2.5 days, showed distinct covariation over Seoul, a megacity in the eastern part of northeast Asia with large anthropogenic emissions. Although this study examined only two atmospheric layers (surface and 500–850 hPa), our results clearly detected high-PM2.5 episodes with LRT characteristics, suggesting the importance of considering both geographical distinctiveness and seasonal meteorological covariability when scaling down continental to local response to emission reduction.
A Machine Learning Tutorial for Operational Meteorology. Part II: Neural Networks and Deep Learning
Authors: Chase Randy J. , Harrison David R. , Lackmann Gary M. , McGovern Amy 
Published: May 2023

Abstract
Over the past decade the use of machine learning in meteorology has grown rapidly. Specifically neural networks and deep learning have been used at an unprecedented rate. To fill the dearth of resources covering neural networks with a meteorological lens, this paper discusses machine learning methods in a plain language format that is targeted to the operational meteorological community. This is the second paper in a pair that aim to serve as a machine learning resource for meteorologists. While the first paper focused on traditional machine learning methods (e.g., random forest), here a broad spectrum of neural networks and deep learning methods is discussed. Specifically, this paper covers perceptrons, artificial neural networks, convolutional neural networks, and U-networks. Like the Part I paper, this manuscript discusses the terms associated with neural networks and their training. Then the manuscript provides some intuition behind every method and concludes by showing each method used in a meteorological example of diagnosing thunderstorms from satellite images (e.g., lightning flashes). This paper is accompanied with an open-source code repository to allow readers to explore neural networks using either the dataset provided (which is used in the paper) or as a template for alternate datasets.
Predictors of Mortality in Trauma patients Receiving massive Transfusion Protocol
Authors: Jebbia Mallory , Nguyen Jade , Marty Makenna , Carcamo Rosa , Alvarez Claudia , Tay Lasso Erika , Barrios Cristobal , Lugo Brian 
Published: May 2023

Introduction Massive transfusion protocol (MTP) is often defined as the transfusion of ≥10 units of packed red blood cells (PRBCs) in 24 hours. The purpose of this study is to determine which factors most significantly contribute to mortality in patients receiving MTP after trauma. Methods An initial database search followed by retrospective chart review was performed on patients treated at four trauma centers in Southern California. Data were collected on all patients who received MTP, defined as at least 10 units PRBCs within the first 24 hours of admission, between January 2015 and December 2019. Patients with isolated head injuries were excluded. Univariate and multivariate analyses were used to determine which factors most significantly influenced mortality. Results Of 1278 patients who met our inclusion criteria in the database, 596 (46.6%) survived and 682 (53.4%) died. On univariate analysis initial vitals and labs, except for initial hemoglobin and initial platelet count were significant predictors of mortality. A multivariate regression model showed the strongest predictors of mortality were pRBC transfusions at 4 hours (OR 1.073, CI 1.020-1.128, P = .006) and 24 hours (OR 1.045, CI 1.003-1.088, P = .036), and FFP transfusion at 24 hours (OR 1.049, CI 1.016-1.084, P = .003). Conclusion Our data indicates that several factors may contribute to mortality in patients receiving MTP. In particular age, mechanism, initial GCS, and PRBC transfusions at 4 and 24 hours provided the strongest correlation. Further multicenter trials are indicated to provide further guidance in deciding when to discontinue massive transfusion.
Venous Thrombosis Recurrence After Catheter-Related Upper Extremity Deep Venous Thrombosis in Cancer Patients: A Retrospective Analysis
Authors: Hakem Rabiaa , Soudet Simon , Diouf Momar , Sevestre Marie Antoinette 
Published: May 2023

Long-term indwelling central venous catheters (CVC) are frequently used to secure vascular access to deliver injectable treatment. Catheter-related thrombosis (CRT) occurs in approximately 2–6% of cancer patients. We conducted a single-center retrospective study to assess the rate of venous thromboembolism (VTE) recurrence in cancer patients; 200 patients were included. Mean age was 56 ± 15.15 years, median follow-up duration was 16.5 [range: 10–36] months. The incidence of recurrence was estimated using Gray’s method for competing risk with death as the competing event of VTE. Recurrent VTE occurred in 25.5% of patients with a median occurrence time of 6.5 [range: 5–11.25] months. In case of recurrence, 94.6% of patients were treated for cancer and 80.4% of them received anticoagulants; 4 major bleeds and 17 non-major bleeds occurred during follow-up. In multivariate analysis, previous VTE (Hazard Ratio (HR) 2.48 (95% CI 1.42–4.32) and presence of CVC (HR 5.56 (95% CI 1.96–15.75) were significant recurrence risk factors. After a first episode of CRT, 25.5% of patients experienced VTE recurrence as UEDVT in 30 cases (55.5%), PE in 17 cases (31.5%), and DVT in 7 cases (13%), mostly during anticoagulation therapy. Anticoagulation therapy does not avoid CRT in case of cancer and must be balanced with hemorrhagic risk.
Placental weight and its relationship with the birth weight of term infants and body mass index of the mothers
Authors: Sathasivam Raveendran , Selliah Pranavan , Sivalingarajah Raguraman , Mayorathan Uruthirapasupathi , Munasinghe Baththirange Malaka 
Published: May 2023

Objective Placental pathology is a well-known cause of perinatal and neonatal mortality and morbidity, and may correlate with placental growth, which can be assessed indirectly by anthropometric placental measurements. The aim of this cross-sectional study was to investigate mean placental weight and its relationship with birthweight and maternal body mass index (BMI). Methods Fresh (not formalin fixed) consecutively delivered placentae of term newborns (37–42 weeks), collected between February 2022 and August 2022, and the mothers and newborns, were included. Mean placental weight, birthweight and maternal BMI were calculated. Pearson’s correlation coefficient, linear regression, and one-way analysis of variance were used to analyse continuous and categorical data. Results Out of 390 samples, 211 placentae (with 211 newborns and mothers) were included in this study after exclusion criteria were applied. Mean placental weight was 494.45 ± 110.39 g, and mean term birth weight/placental weight ratio was 6.21 ± 1.21 (range, 3.35–11.62 g). Placental weight was positively correlated with birthweight and maternal BMI, but not with newborn sex. Linear regression effect estimation of placental weight on birthweight revealed a medium correlation ( R2 = 0.212; formula, 1.4553 × X + 2246.7, where X is placental weight [g]). Conclusion Placental weight was revealed to positively correlate with birthweight and maternal BMI.
Do Anxiety Symptoms Mediate the Association Between Cannabis Use Frequency and Psychotic-Like Experiences in Emerging Adult Undergraduates?
Authors: Bernusky Haley C. R. , Tibbo Philip G. , Conrod Patricia J. , Yunus Fakir Md. , Keough Matthew T. , Thompson Kara D. , Krank Marvin D. , Hadwin Allyson F. , Stewart Sherry H. 
Published: May 2023

Objective Cannabis is commonly used by Canadian emerging adults (ages 18–25 years), many of whom attend post-secondary institutions. Frequent cannabis use is linked with psychotic-like experiences (PLEs); however, the exact nature of this association remains unclear. Anxiety symptoms may mediate this association, as they are prevalent in emerging adults and have been independently linked with both cannabis use and PLEs. Past work found that anxiety mediated the association between cannabis use frequency and attenuated positive psychotic symptoms (further along the psychosis continuum than PLEs), however this research had yet to be validated in the Canadian population, and trait rather than state anxiety (frequency of anxiety symptoms) was studied. Thus, our primary objective was to examine if anxiety symptoms mediated the association between cannabis use frequency and PLEs in Canadian emerging adult undergraduates. Despite known sex differences in cannabis use, expression of anxiety, and PLEs, past work did not evaluate the potential impact of biological sex on the anxiety-mediated model, and thus is the secondary objective of the present study. Methods 1,266 first-/second-year emerging adult undergraduates from five Canadian universities provided cross-sectional, self-report survey data in fall 2021 semester. Validated measures of cannabis use frequency, anxiety, and PLEs were administered. Results Path analyses supported mediation from cannabis use to PLEs through anxiety ( b  =  0.07, P < 0.001, 95% bootstrap CI [0.03, 0.10]). No direct effect was found ( P  =  0.457), suggesting that the cannabis-to-PLEs association was mediated by anxiety. Mediation did not depend on biological sex (i.e., bootstrapped 95% CIs crossed zero). Conclusions Anxiety symptoms mediated the association between cannabis use and PLEs in emerging adults regardless of their biological sex. Assuming replication in prospective research, results highlight anxiety as an important intervention target in frequent cannabis-using emerging adults, to potentially prevent development/worsening of PLEs, and in turn psychotic illness.
Two variants of ‘constrained participation’ in the care of vulnerable adults: A proof-of-concept study
Authors: Kristjánsson Kristján , Thórarinsdóttir Kristín 
Published: May 2023

There has been a radical turn towards ideals of patient autonomy and person-centred care, and away from historically entrenched forms of medical paternalism, in the last 50 years of nursing practice. However, along the way, some shades of grey between the areas of ideal patient participation and of outright patient non-participation have been missed. The current article constitutes an exploratory proof-of-concept study of the real-world traction of a distinction-straddling concept of ‘constrained participation’ and its two sub-concepts of ‘fought-for participation’ and ‘forced-to participation’. In order to concretise these additions to the conceptual terrain of person-centred participation and its anti-theses, we apply them to themes in the care of vulnerable older adults. In the final section, we close by eliciting some characterological, educational and clinical implications of adding these new tools also to the conceptual repertoire of nursing practice and education.
Part B: Steering and control of an autonomous vehicle in emergency lane change maneuvers based on skilled driver’s performance
Authors: Neisy Minaei Samir , Ghaffari Ali , Najafi Ardekany Ali 
Published: May 2023

This paper considers the vehicle control process in emergency lane change (ELC). The control method is divided into two parts: before crossing the obstacle and after crossing it. The first part is done by a feed-forward controller inspired by the driver’s behavior pattern in the ELC maneuver. This controller is compensated by a neural network system and two proportional-integral (PI) and proportional-derivative (PD) controllers, which correct the output of the feed-forward controller to follow the path more accurately. The second part consists of two PD controllers responsible for controlling and steering the vehicle in the main path after crossing the obstacle. The main novelty of the proposed method is that the computational burden is low because of using a feed-forward controller, which is the main source of the calculation’s burden. So as a result, the controller system can cover the ELC maneuver in under 2 seconds in various lateral displacements to bypass the obstacle and prevent collisions. The co-simulations are performed in CarSim software and MATLAB/Simulink, which shows that the control system can appropriately steer the vehicle and follow the desired at different speeds, in the presence of road friction and parameter uncertainty.
Current Status of Urinary Schistosomiasis Among Communities in Kurmuk District, Western Ethiopia: Prevalence and Intensity of Infection
Authors: Mohammed Tigist , Hu Wei , Aemero Mulugeta , Gebrehiwot Yirgalem , Erko Berhanu 
Published: May 2023

Background: Schistosomiasis is a highly prevalent but neglected tropical disease, particularly in sub-Saharan Africa. In Ethiopia, urogenital schistosomiasis due to Schistosoma haematobium has been known to be endemic in several lowland areas. This study was designed to determine the current prevalence and intensity of the urogenital schistosomiasis among communities in Kurmuk District, western Ethiopia. Methods: Urine filtration technique and urine dipstick test were used to screen for S. haematobium eggs and hematuria, respectively. The data were analyzed with SPSS version 23. Logistic regression and odds ratio were used to measure associations and strength between prevalence, intensity, and independent variables. P-values <.05 at 95% CI were considered statistically significant. Results: The overall prevalence of S. haematobium infection as determined by urine filtration was 34.2% (138/403). In bivariate analysis, the most infected (45.4%) age groups were 5 to 12 years (odds ratio [OR] = 4.16, 95% CI: 1.36-12.67), followed by 13 to 20 years (OR = 3.23, 95% CI: 1.01-10.35) with higher significant mean egg count (MEC). The mean egg intensity ranged from 2.39 in Ogendu (CI: 1.05-3.72) to 14.1 in Dulshatalo (CI: 4.98-23.12) villages. The main predictor of infection was swimming habits (adjusted odds ratio [AOR] = 2.43 [CI: 1.19-4.94]). The prevalence of hematuria was 39.2% (158/403), the odds being 2.64 times higher among participants who resided in Dulshatalo than those who resided in Kurmuk (AOR 2.64 [95% CI: 1.43-4.87], P = .004). Conclusion: To reduce the infection and interrupt transmission, the PC in place in the area using PZQ should be strengthened and continued, alongside with provision of sanitary facilities, safe alternative water supplies and health education. The Federal Ministry of Health of Ethiopia should also collaborate with the health authorities of the Sudan government for the control of trans-boundary transmission of the disease as the transmission foci are shared between the 2 countries.