bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accumulation of T-cell-suppressive PD-L1highextracellular vesicles is associated with GvHD and might impact GvL efficacy
Authors: Baur Rebecca , Karl Franziska , Böttcher-Loschinski Romy , Stoll Andrej , Völkl Simon , Gießl Andreas , Flamann Cindy , Bruns Heiko , Schlötzer-Schrehardt Ursula , Böttcher Martin , Schewe Denis M , Fischer Thomas , Jitschin Regina , Mackensen Andreas , Mougiakakos Dimitrios 
Published: March 2023

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only curative treatment option for a number of hemato-oncological disorders. In fact, allo-HSCT is considered as one of the most successful immunotherapies as its clinical efficacy is based on the donor T-cells’ capacity to control residual disease. This process is known as the graft-versus-leukemia (GvL) reaction. However, alloreactive T-cells can also recognize the host as foreign and trigger a systemic potentially life-threatening inflammatory disorder termed graft-versus-host disease (GvHD). A better understanding of the underlying mechanisms that lead to GvHD or disease relapse could help us to improve efficacy and safety of allo-HSCT. In recent years, extracellular vesicles (EVs) have emerged as critical components of intercellular crosstalk. Cancer-associated EVs that express the immune checkpoint molecule programmed death-ligand 1 (PD-L1) can suppress T-cell responses and thus contribute to immune escape. At the same time, it has been observed that inflammation triggers PD-L1 expression as part of a negative feedback network.Here, we investigated whether circulating EVs following allo-HSCT express PD-L1 and tested their efficacy to suppress the ability of (autologous) T-cells to effectively target AML blasts. Finally, we assessed the link between PD-L1 levels on EVs to (T-)cell reconstitution, GvHD, and disease relapse.We were able to detect PD-L1+EVs that reached a peak PD-L1 expression at 6 weeks post allo-HSCT. Development of acute GvHD was linked to the emergence of PD-L1highEVs following allo-HSCT. Moreover, PD-L1 levels correlated positively with GvHD grade and declined (only) on successful therapeutic intervention. T-cell-inhibitory capacity was higher in PD-L1highEVs as compared with their PD-L1lowcounterparts and could be antagonized using PD-L1/PD-1 blocking antibodies. Abundance of T-cell-suppressive PD-L1highEVs appears to also impact GvL efficacy as patients were at higher risk for relapse. Finally, patients of PD-L1highcohort displayed a reduced overall survival.Taken together, we show that PD-L1-expressing EVs are present following allo-HSCT. PD-L1 levels on EVs correlate with their ability to suppress T-cells and the occurrence of GvHD. The latter observation may indicate a negative feedback mechanism to control inflammatory (GvHD) activity. This intrinsic immunosuppression could subsequently promote disease relapse.
Multistate transition modelling of e-cigarette use and cigarette smoking among youth in the UK
Authors: Parnham Jennie C , Vrinten Charlotte , Radó Márta K , Bottle Alex , Filippidis Filippos T , Laverty Anthony A 
Published: March 2023

Introduction
E-cigarette use remains a controversial topic, with questions over how people transition between e-cigarette use and cigarette smoking. This paper examined transitions into and out of nicotine product use in a representative sample of UK youth.

Methods
We used Markov multistate transition probability models on data from 10 229 participants (10–25 years old) in the UK Household Longitudinal Study (2015–2021). We used four product use states (‘never’, ‘non-current use’, ‘e-cigarette only’ and ‘smoking and dual use’) and estimated likelihood of transitions according to sociodemographic characteristics.

Results
Among participants who had never used nicotine products, most were still non-users a year later (92.9% probability; 95% CI 92.6%, 93.2%); a small proportion transitioned to using e-cigarettes only (4.0%; 95% CI 3.7%, 4.2%) and cigarettes (2.2%; 95% CI 2.0%, 2.4%). Those aged 14–17 years were the most likely to start using a nicotine product. E-cigarette use was less persistent overtime than cigarette smoking, with a 59.1% probability (95% CI 56.9%, 61.0%) of e-cigarette users still using after 1 year compared with 73.8% (95% CI 72.1%, 75.4%) for cigarette smoking. However, there was a 14% probability (95% CI 12.8%, 16.2%) that e-cigarette users went onto smoke cigarettes after 1 year, rising to 25% (95% CI 23%, 27%) after 3 years.

Conclusion
This study found that although overall nicotine product use was relatively rare, participants were more likely to experiment with e-cigarette use than cigarette smoking. This was mostly not persistent over time; however, approximately one in seven transitioned to cigarette smoking. Regulators should aim to deter all nicotine product use among children.
Transition disks: the observational revolution from SEDs to imaging
Authors: van der Marel Nienke 
Published: March 2023

AbstractProtoplanetary disks surrounding young stars are the birth place of planets. Of particular interest are the transition disks with large inner dust cavities of tens of au, hinting at the presence of massive companions. These cavities were first recognized by a deficit in their Spectral Energy Distribution (SED), later confirmed by millimeter interferometry observations. The Atacama Large Millimeter/submillimeter Array (ALMA) has truly revolutionized the field of spatially resolved imaging of protoplanetary disks in both dust and gas, providing important hints for the origin of gaps and cavities. At the same time, new types of substructures have been revealed. Also infrared observations show a large range of substructures both in resolved imaging, interferometry and spectroscopy. Since the last review paper of transition disks in Protostars and Planets VI, a huge amount of data has been taken, which led to numerous new insights in the origin of transition disks. In this review I will summarize the observational efforts from the past decade, compare their insights with the predictions from SED modeling, analyze the properties of the transition disk population and discuss their role in general disk evolution.
PSMA-positive Circulating Tumor Cell Detection and Outcomes with Abiraterone or Enzalutamide Treatment in Men with Metastatic Castrate-resistant Prostate Cancer
Authors: Gupta Santosh , Halabi Susan , Yang Qian , Roy Akash , Tubbs Alisa , Gore Yamini , George Daniel J. , Nanus David M. , Antonarakis Emmanuel S. , Danila Daniel C. , Szmulewitz Russell Z. , Wenstrup Richard , Armstrong Andrew J. 
Published: March 2023

Abstract

Purpose:
In men with metastatic castration-resistant prostate cancer (mCRPC), prostate-specific membrane antigen (PSMA)-targeted radioligand therapy has drastically improved clinical outcomes. A liquid biopsy characterizing PSMA expression could be useful in guiding optimal therapy.

Experimental Design:
We conducted a retrospective analysis of the prospective multicenter PROPHECY (Prospective CiRculating PrOstate Cancer Predictors in HighEr Risk mCRPC StudY) trial of men with mCRPC (n = 118) treated with abiraterone (abi) or enzalutamide (enza). Circulating tumor cells (CTC) were enriched (CTC/mL) and characterized for PSMA protein expression/heterogeneity at baseline and progression. We utilized proportional hazards modeling of the association between PSMA-positive (PSMA+) CTC enumeration with overall survival (OS) and progression-free survival (PFS).

Results:
Overall, 97 men with mCRPC had evaluable blood samples for baseline CTC PSMA detection; 78 men (80%) had detectable CTCs. Of these, 55% (43/78) of men had any PSMA CTC detection, 21% (16/78) had ≥2 PSMA+ CTCs/mL, and 19% (8/43) were 100% PSMA+. At progression on abi/enza, 88% (50/57) of men had detectable CTCs, 68% (34/50) had any PSMA CTCs, and 12% (4/34) had 100% PSMA+ CTCs. Among paired cases (n = 57), PSMA+ CTC detection increased slightly after abi/enza progression. Using an optimal cutoff of ≥2 PSMA+ CTCs/mL, median OS was 26, 21, and 11 months for men without CTCs, PSMA− CTCs, and PSMA+ CTCs. Adjusting for prior abi/enza therapy, Halabi clinical risk score, and CTC enumeration, the HRs for OS and PFS for PSMA+ CTC+ were 3.0 [95% confidence interval (CI) = 1.1–7.8] and 2.3 (95% CI = 0.9–5.8).

Conclusions:
We observed PSMA CTC heterogeneity between and within patients with mCRPC over time during abi/enza progression. CTC PSMA enumeration was adversely prognostic independent of clinical factors and disease burden. Further validation is warranted in the context of PSMA-targeted therapies.
Caste Groups
Authors: Pal Satanik 
Published: March 2023

Abstract
The following article seeks to establish caste groups in India as Weberian status groups. Dumont and Weber’s understanding of caste, while partially correct in this area, sought to establish caste as uniquely Indian, through their orientalist leanings. The Brahmin caste was seen by most orientalists as being an exclusive group of ascetic priests who headed Hindu society. By attempting to demonstrate the political and economic factors behind their dominance, the author here seeks to de-exoticize these assumptions, and calls for the term caste to be replaced by status. This will allow us to compare endogamous caste groups or jatis in India with status groups in premodern and modern complex societies all over the world.
Frag. 2 of 2QRuthb
Authors: Bonanno Beatrice 
Published: March 2023

Abstract
This contribution focuses on fragment 2 of 2QRuthb, which attests several difficulties from a material, palaeographic, and textual perspective. The analysis proposes a hypothesis regarding its composition and the identification of the text. This fragment may be considered a textual witness of Ruth 3:10–11 and it attests a textual variant, which agrees with the Septuagint against the Masoretic Text.
Examining Chinese-foreign Cooperation in Running Schools During the Epidemic Period: A Macro Education Policy Analysis
Authors: Xue Eryong , Li Jian 
Published: March 2023

Abstract
After the epidemic, the increase of the number of Chinese students studying abroad slowed down, and the flow scale of international students entered a downward stage, but the overall trend was still stable. The globalization of education in the epidemic period presents a new feature of “double-edged sword”. Along with the current situation of studying aboard, this study explores China’s new policy on studying abroad in the epidemic era. Overview of China’s new policy on studying abroad during the epidemic period and interpretation of China’s new policy on studying abroad during the epidemic period have been provided in this study. In addition, the suggestions and remarks have been offered in the last.
Public Information Priorities across Weather Hazards and Time Scales
Authors: Krocak Makenzie J. , Ripberger Joseph T. , Ernst Sean , Silva Carol , Jenkins-Smith Hank , Bitterman Abby 
Published: March 2023

Abstract
As the abundance of weather forecast guidance continues to grow, communicators will have to prioritize what types of information to pass on to decision-makers. This work aims to evaluate how members of the public prioritize weather forecast attributes (including information about location, timing, chance, severity, impacts, and protective actions) on average and across event timelines in the severe, tropical, and winter weather domains. Data from three demographically representative surveys of U.S. adults indicate that members of the public generally prioritize information about event location, timing, and severity when evaluating the importance of forecast attributes. This pattern is largely consistent across hazard domains but varies across event timelines. In early stages of a forecast (such as the outlook time scale), people generally prioritize information about chance and location. In middle stages (watch time scale), event timing and severity become more important. In late stages (warning time scale), information about protective actions is a higher priority, especially for people with less exposure to a hazard.
Observed Upper Deep Branch of the Pacific Meridional Overturning Circulation North of New Guinea
Authors: Zhang Hang , Wang Jianing , Wang Fan , Zhang Zhixiang , Ma Qiang 
Published: March 2023

Abstract
The deep channel north of New Guinea (NG) is the choke site for the upper deep branches of the Pacific meridional overturning circulation (U-PMOC). The U-PMOC is a crucial element of the ocean’s climate and biogeochemical systems. It carries the mixed water of the Upper Circumpolar Water and North Pacific Deep Water with a potential temperature over 1.2°–2.2°C. The pathway and volume transport of U-PMOC through the deep channel north of NG are revealed by mooring measurements from 2014 to 2019. Mean U-PMOC is located at ∼2000–3500 m with a velocity core at 2550 m and is directed eastward. The U-PMOC shows a strong seasonal variability with a direction reversal from June to September. The oceanic reanalysis product GLORYS12V1 well reproduces the observed U-PMOC and is thus used to estimate the mean and standard deviation of U-PMOC’s volume transport as 2.19 ± 11.4 Sv (1 Sv ≡ 106 m3 s−1) and to explore the underlying dynamics of the U-PMOC. The seasonality of U-PMOC is induced by the vertical propagation of the Rossby energy through the upper ocean in the eastern Pacific to the deep ocean in the western Pacific. The mean eastward U-PMOC transport is forced by the zonal deep pressure gradient, which is mainly determined by the local upper-ocean processes above 500 m.
Does RAS Status Increase the Prevalence of Positive Resection Margin in Colorectal Liver Metastasis? A Systematic Review and Meta-Analysis
Authors: Brandão Gabriela Rangel , Trindade Bruna Oliveira , Flores Luís Henrique Fernandes , Motter Sarah Bueno , Alves Cassio Bona , Remonti Tiago Auatt Paes , Lucchese Angélica Maria , Junior Antonio Dal Pizzol , Kalil Antonio Nocchi 
Published: March 2023

Background Colorectal liver metastasis has a high incidence, and RAS oncogene mutation status carries significant prognostic information. We aimed to assess whether RAS-mutated patients present more or less frequently with positive margins in their hepatic metastasectomy. Methods We performed a systematic review and meta-analysis of studies from PubMed, Embase, and Lilacs databases. We analyzed liver metastatic colorectal cancer studies, which included information on RAS status and had surgical margin analysis of the liver metastasis. Odds ratios were computed using a random-effect model due to anticipated heterogeneity. We further performed a subanalysis limited to studies that included only patients with KRAS instead of all-RAS mutations. Results From the 2,705 studies screened, 19 articles were included in the meta-analysis. There were 7,391 patients. The prevalence of positive resection margin was not significantly different between patients carrier vs non-carrier for the all-RAS mutations (OR .99; 95% CI 0.83-1.18; P = .87), and for only KRAS mutation (OR .93; 95% CI 0.73-1.19; P = .57). Conclusions Despite the strong correlation between colorectal liver metastasis prognosis and RAS mutation status, our meta-analysis’s results suggest no correlation between the RAS status and the prevalence of positive resection margins. The findings contribute to a better understanding of the RAS mutation’s role in the surgical resections of colorectal liver metastasis.
Sarcopenia in Patients With Rectal Adenocarcinoma: An Opportunity for Preoperative Rehabilitation
Authors: Bliggenstorfer Jonathan T. , Hashmi Ahmad , Bingmer Katherine , Chang Carolyn , Liu Jessica C. , Ginesi Meridith , Stein Sharon L. , Steinhagen Emily 
Published: March 2023

Background Sarcopenia, defined as low skeletal muscle mass, affects up to 60% of rectal adenocarcinoma patients receiving neoadjuvant chemoradiation (NACRT), with negative impact on patient outcomes. Identifying modifiable risk factors may decrease morbidity and mortality. Methods A retrospective review of rectal cancer patients from a single academic center from 2006 to 2020 was performed. Sixty-nine patients with pre- and post-NACRT CT imaging were included. Skeletal muscle index (SMI) was calculated as total L3 skeletal muscle divided by height squared. Sarcopenia thresholds were 52.4 cm2/m2 for men and 38.5 cm2/m2 for women. Student T-test, chi-square test, multivariable regression, and multivariable Cox hazard analysis were performed. Results 62.3% of patients lost SMI from pre- to post-NACRT imaging, with a mean change of −7.8% (±19.9%). Eleven (15.9%) patients were sarcopenic at presentation, increasing to 20 (29.0%) following NACRT. Mean SMI decreased from 49.0 cm2/m2 (95% CI: 42.0 cm2/m2-56.0 cm2/m2) to 38.2 cm2/m2 (95% CI: 33.6 cm2/m2-42.9 cm2/m2) (P = .003). Pre-NACRT sarcopenia correlated with post-NACRT sarcopenia (OR 20.6, P = .002). Percent decrease in SMI was associated with a 5% increased mortality risk. Conclusion The presence of sarcopenia at diagnosis and its association with post-NACRT sarcopenia suggests an opportunity for a high-impact intervention.
Does Vehicle Intrusion Alone Still Predict Injury: A Retrospective Analysis of Mechanism as Trauma Activation Criteria
Authors: Travis Harrison J. , Platt Blake , Muramoto Sara G. , Smith Alison A. , Hunt John P. , Stuke Lance E. , Greiffenstein Patrick P. , Schoen Jonathan E. , Marr Alan B. 
Published: March 2023

Automobile collisions with driver side intrusion >12 inches or >18 elsewhere meet criteria for trauma activation. However, vehicle safety features have improved since this inception. We hypothesized vehicle intrusion (VI) alone as mechanism-of-injury (MOI) criteria inadequately predicts trauma center activation. A retrospective, single-center chart review of adult patients involved in motor vehicle collisions presenting to a level 1 trauma center from July 2016 to March 2022 was performed. Patients were divided by MOI criteria: VI vs. multiple MOI criteria. 2940 patients met inclusion criteria. The VI group reported lower injury severity scores ( P = 0.004), higher incidence of ED discharge ( P = 0.001), lower ICU admissions ( P = 0.004), and fewer in-hospital procedures ( P = 0.03). Vehicle intrusion was found to have a positive likelihood ratio of 0.889 for predicting trauma center need. According to current guidelines, these results suggest that VI criteria alone may not be an accurate predictor for trauma center transport and require further investigation.
Lymph Node Metastases in Papillary Thyroid Carcinoma can be Predicted by a Convolutional Neural Network: a Multi-Institution Study
Authors: Esce Antoinette , Redemann Jordan P. , Olson Garth T. , Hanson Joshua A. , Agarwal Shweta , Yenwongfai Leonard , Ferreira Juanita , Boyd Nathan H. , Bocklage Thèrése , Martin David R. 
Published: March 2023

Objectives: The presence of nodal metastases in patients with papillary thyroid carcinoma (PTC) has both staging and treatment implications. However, lymph nodes are often not removed during thyroidectomy. Prior work has demonstrated the capability of artificial intelligence (AI) to predict the presence of nodal metastases in PTC based on the primary tumor histopathology alone. This study aimed to replicate these results with multi-institutional data. Methods: Cases of conventional PTC were identified from the records of 2 large academic institutions. Only patients with complete pathology data, including at least 3 sampled lymph nodes, were included in the study. Tumors were designated “positive” if they had at least 5 positive lymph node metastases. First, algorithms were trained separately on each institution’s data and tested independently on the other institution’s data. Then, the data sets were combined and new algorithms were developed and tested. The primary tumors were randomized into 2 groups, one to train the algorithm and another to test it. A low level of supervision was used to train the algorithm. Board-certified pathologists annotated the slides. HALO-AI convolutional neural network and image software was used to perform training and testing. Receiver operator characteristic curves and the Youden J statistic were used for primary analysis. Results: There were 420 cases used in analyses, 45% of which were negative. The best performing single institution algorithm had an area under the curve (AUC) of 0.64 with a sensitivity and specificity of 65% and 61% respectively, when tested on the other institution’s data. The best performing combined institution algorithm had an AUC of 0.84 with a sensitivity and specificity of 68% and 91% respectively. Conclusion: A convolutional neural network can produce an accurate and robust algorithm that is capable of predicting nodal metastases from primary PTC histopathology alone even in the setting of multi-institutional data.
Criminal liability and epilepsy: a case report of a postictal attempted homicide from Tunisia
Authors: Omri Sana , Smaoui Najeh , Feki Rim , Gassara Imen , Zouari Lobna , Ben Thabet Jihene , Maalej Mohamed , Maalej Bouali Manel , Charfi Nada 
Published: March 2023

Objective Patients with epilepsy who have been charged with a serious offense may be referred by the courts for forensic psychiatric examination. A detailed psychiatric and neurological examination is often necessary to assist the courts in making the right decision, as exemplified in the current case presentation. Method The forensic case of a 30-year-old Tunisian male with temporal epilepsy who exhibited an inadequate response to the treatment is presented here. The patient attempted to kill his neighbor after a cluster of seizures, showing apparent postictal aggression. An antiepileptic treatment was introduced a few days after the person’s detention and was followed by forensic psychiatric examination, but the latter was not done until three months afterwards. Results On forensic examination, the patient’s thought processes were clear with no evidence of a thought disorder or psychosis. Both medical and psychiatric opinions stated that the attempted homicide was due to a postictal psychosis. The patient was transferred to a psychiatric facility for further management and was found not guilty by reason of insanity. Conclusion This case illustrates the difficulties that experts may encounter in establishing criminal liability after aggressive behavior associated with epilepsy. It highlights shortcomings in Tunisian law (and promptness of forensic psychiatric examination) that should be addressed to ensure fairness of the legal process.
Is this dyspnea because of coronary artery disease? A rare case report of primary neuroendocrine tumor in anterior mediastinum
Authors: Rumbinaitė Eglė , Dirsienė Rūta , Vaitiekus Domas , Poškienė Lina , Žūkaitė Gabrielė , Stankevičienė Šarūnė , Šakalytė Gintarė , Dobilienė Olivija , Benetis Rimantas 
Published: March 2023

Introduction Mediastinal neuroendocrine tumors are rare malignancies with aggressive behavior and a grim prognosis. These malignancies often go undetected until they are diagnosed at advanced stages. Case report We present the case of 74 -years old man who was hospitalized because of non-ST elevation myocardial infarction and in case of three vessels coronary artery disease, coronary bypass surgery was planned. During preoperative investigation, computer tomography revealed a huge tumor (20 cm × 11 cm × 21 cm in size) in the anterior mediastinum. Successful simultaneous operation coronary bypass surgery and removal of the mediastinal tumor was performed. Discussion Surgery is the treatment of choice for neuroendocrine tumors but the relapse rate ranges between 5% and 30% and is higher (65%) in atypical neuroendocrine tumors and patients with mediastinal node involvement. Despite the poor prognosis of neuroendocrine tumors, the spread to the lymph nodes, the patient continues chemotherapy treatment 49 months after the operation.