bluuebunny/crossref_metadata_2025_split huggingface dataset:
WTO Rules for Trade with Disputed Territories
Authors: Kanevskaia Olia 
Published: May 2023

ABSTRACT
The legality of trade with territories over which sovereignty is disputed has recently come to the forefront of policy and academic discussions due to emerging case law and escalating territorial conflicts. While considerations shaping the debate on economic activities with disputed territories are typically informed by concerns of international law, little is known about international trade and customs rules applicable to these regimes. This article aims to fill this literature gap by inquiring into the rules that apply to trade with disputed territories under the relevant World Trade Organization (WTO) Agreements, in particular the General Agreement on Tariffs and Trade, the Agreement on Rules of Origin, and the Agreement on Technical Barriers to Trade. In a broader sense, it contributes to the understanding of interactions between the WTO and other self-containing regimes of international law, illustrating the challenges that arise from their different approaches to territories.
Taking Ideas Seriously in Political Science: The Diffusion of Presidentialism in Latin America after Independence
Authors: Parsons Craig , Garcé Adolfo , Béland Daniel 
Published: May 2023

Abstract
Today it is rare to find a political scientist who rejects that “ideas matter”—at least in the abstract. But if ideationally inclined theorists have gained seats at the disciplinary table, their approaches still occupy disadvantaged positions. Ideational theories typically must confront nonideational alternatives to achieve salient publication, but nonideational theorists routinely design and publish research without considering ideational alternatives. This is even true on topics where all scholars seem to agree a priori on the importance of ideas. Erratic attention to ideas appears to be justified by widespread views that even if ideas plausibly “matter,” they are too intractable to address in concrete research: too difficult to measure empirically, to relate in explanatory ways to action, or to connect to goals of theoretical generalization. This article first highlights major problems with these views in the abstract, and then illustrates them in the example of early Latin American constitutional design. On this terrain, there are good reasons to think that an ideational account connects in more concrete ways to available evidence than leading nonideational hypotheses about constitutional choice. Political science should move toward better balanced debates between plausible explanations, upgrading the rigor of the discipline overall.
Under-The-Nose Versus Over-The-Nose Face Mask to Prevent Facial Pressure Sores During Face Mask-Delivered Noninvasive Ventilation for Acute Hypercapnic Respiratory Failure: A Randomized Controlled Trial
Authors: Lemyze Malcolm , Mallat Jihad , Vangrunderbeek Nicolas , Granier Maxime 
Published: May 2023

OBJECTIVES:
To determine whether an under-the-nose face mask (FM) as the first-line interface strategy reduces the incidence of facial pressure sores with the same clinical improvement as the one obtained by standard over-the-nose face mask-noninvasive ventilation (FM-NIV) in patients with acute hypercapnic respiratory failure (AHRF).

DESIGN:
A multicenter, prospective randomized controlled study.

SETTING:
Two ICUs from two French tertiary hospitals.

PATIENTS:
A total of 108 patients needed NIV for AHRF.

INTERVENTIONS:
participants were randomized (1/1) to receive either the under-the-nose FM (intervention group) or the over-the-nose FM (control group). The primary endpoint was the reduction of facial pressure sores. Secondary endpoints included patients outcome, NIV failure (intubation or death), arterial blood gas improvement, and interface failure (the need to switch to a total face mask).

MEASUREMENTS AND MAIN RESULTS:
Despite less protective dressings in the intervention group (n = 4, 5% vs n = 27, 51%; p < 0.001), pressure sores developed less frequently than in the control group (n = 3, 5% vs n = 39, 74%; p < 0.001). Similar mortality, NIV failure, and arterial blood gas improvement occurred in the two groups. However, under-the-nose FM resulted in a higher interface failure rate than conventional FM (n = 18, 33% vs n = 5, 9%; p = 0.004), mainly because of excessive unintentional air leaks (n = 15, 83% vs n = 0, 0%; p < 0.001).

CONCLUSIONS:
In patients with AHRF, under-the-nose FM significantly reduced the incidence of facial pressure sores compared to the most commonly used first-line interface, the standard FM. However, with this new mask, excessive unintentional air leaks more often compelled the attending clinician to switch to another interface to pursue NIV.
18F-FDG PET/CT in Extensive Follicular Dendritic Cell Sarcoma With Response Assessment to Chemotherapy
Authors: Prakash Kavali David Jaya , Sharma Siddharth , Nazar Aftab Hasan , Ora Manish , Gambhir Sanjay 
Published: May 2023

Abstract
Follicular dendritic cell sarcoma (FDCS) is a low-grade sarcoma of mesenchymal dendritic cell origin, and it constitutes <0.4% of soft tissue sarcomas. We report a rare case of FDCS in a 32-year-old man. 18F-FDG PET/CT demonstrated the involvement of cervical, axillary, mediastinal, abdominal, and pelvic groups of lymph nodes and spleen. A cervical lymph node biopsy suggested FDCS. 18F-FDG PET/CT scan done after 3 cycles of chemotherapy (CHOP regime) revealed a complete metabolic response. This case presents the rarity of extensive presentation and complete response to the CHOP regime.
Comparison of machine-learning and logistic regression models to predict 30-day unplanned readmission: a development and validation study
Authors: Iwagami Masao , Inokuchi Ryota , Kawakami Eiryo , Yamada Tomohide , Goto Atsushi , Kuno Toshiki , Hashimoto Yohei , Michihata Nobuaki , Goto Tadahiro , Shinozaki Tomohiro , Sun Yu , Taniguchi Yuta , Komiyama Jun , Uda Kazuaki , Abe Toshikazu , Tamiya Nanako 
Published: May 2023

AbstractWe compared the predictive performance of gradient-boosted decision tree (GBDT), random forest (RF), deep neural network (DNN), and logistic regression (LR) with the least absolute shrinkage and selection operator (LASSO) for 30-day unplanned readmission, according to the number of predictor variables and presence/absence of blood-test results. We used electronic health records of patients discharged alive from 38 hospitals in 2015–2017 for derivation (n=339,513) and in 2018 for validation (n=118,074), including basic characteristics (age, sex, admission diagnosis category, number of hospitalizations in the past year, discharge location), diagnosis, surgery, procedure, and drug codes, and blood-test results. We created six patterns of datasets having different numbers of binary variables (that ≥5% or ≥1% of patients or ≥10 patients had) with and without blood-test results. For the dataset with the smallest number of variables (102), the c-statistic was highest for GBDT (0.740), followed by RF (0.734), LR-LASSO (0.720), and DNN (0.664). For the dataset with the largest number of variables (1543), the c-statistic was highest for GBDT (0.764), followed by LR-LASSO (0.755), RF (0.751), and DNN (0.720). We found that GBDT generally outperformed LR-LASSO, but the difference became smaller when the number of variables was increased and blood-test results were used.
Optimized sampling method for fecal microbiome and metabolome preservation under room temperature
Authors: Nomaguchi Tatsuhiro , Yamauchi Yohsuke , Nishimoto Yuichiro , Togashi Yuka , Ito Masaki , Salim Felix , Fujisawa Kota , Murakami Shinnosuke , Yamada Takuji , Fukuda Shinji 
Published: May 2023

AbstractBackgroundThe relationship among the human gut microbiome, microbially produced metabolites, and health outcomes remains of great interest. To decrease participant burden, room-temperature storage methods for fecal samples have become increasingly important. However, kits for storing the fecal microbiome and metabolome have not been well explored. We hypothesized that storing fecal samples by drying them with silica gel may be suitable.ObjectivesThe objective was to evaluate the performance of storage at room temperature by drying feces for subsequent examination of the microbiome, microbial pathways, and the metabolome.MethodsFeces from ten healthy adults (6 male and 4 female) were sampled and immediately processed, as controls, and stored at room temperature in an incubator, on an FTA card, in RNAlater, or dried by silica gel. Storage at room temperature continued for 7 days. Drying by the silica gel method was assessed for 14 days. The fecal microbiome was assessed by sequencing the bacterial 16S ribosomal RNA-encoding gene (V1-V2 region), fecal microbial pathway profiles were analyzed by whole-genome shotgun metagenomics, and fecal metabolome profiles were analyzed using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS).ResultsQualitative and β-diversity analyses of the microbiome, microbial pathways, and the metabolome showed that drying by silica gel were closest to those immediately after processing. When focusing on the abundances of individual microbes, microbial pathways, and metabolites, some were found to be significantly different. However, the intra-method ranking of individual items showed that 100%, 87-97%, and 63-76% of microbes, microbial pathways, and metabolites, respectively, were significantly correlated between silica gel preserving and immediately processing method.ConclusionsThe results showed that fecal sample drying could be effectively used for the preservation of the fecal microbiome and metabolome.
COVID-19 in meat plants: activation of a Target Prevention Plan, in Italy
Authors: Di Leone Giorgio , Bertinato Luigi , Brambilla Gianfranco , Manno Valerio , Napolano Flavio , Savi Simona , Settimo Gaetano , Lagravinese Domenico 
Published: May 2023

AbstractDuring the COVID-19 pandemics, several outbreaks have been recorded all other the world in industrial slaughterhouses and meat processing plants. Occupational preventive medicine in such non-healthcare frontline essential services accounts for combined different environmental, social, and economic factors, to reduce the burden of COVID-19 in the workplaces and in the connected residential settings. In Italy, during the first year of the pandemics, an advocacy action has been activated, targeted on meat plant managers and related food business operators. A risk-oriented control plan was agreed by competent Italian Health Authorities at Region/Province level. A questionnaire focused on the inventoried risk factors reported in the literature in such working places have been developped as supporting tool, and administered on voluntary basis to the interested stakeholders. In addition, an outbreak questionnaire was proposed to the Prevention Depts of the Local Health Units. In the 2021 – 2022 years timeframe, we collected 333 advocacy and 24 outbreak questionnaires, respectively, on 4,765 inventoried plants at national level. Responses came mainly from those districts that locally activated the risk-oriented control plan. The lack of awareness to update the Risk Assessment Document of the meat plant for COVID-19, non instrumental body Temperature checks of workers at the entrance, working force from different subcontractors, poor hygiene in the shared places and insufficient ventilation represented the main critical points recorded. The cross-checks between the results from the advocacy and from the outbreak questionnaires are feeding an after-action review for such food-chain related essential work settings within a One Health approach.
A Yersinia effector activates JAK-STAT signaling in human macrophages
Authors: Berneking Laura , Bekere Indra , Schnapp Marie , Huang Jiabin , Ruckdeschel Klaus , Aepfelbacher Martin 
Published: May 2023

AbstractThe multifunctionalYersiniaeffector YopM inhibits effector triggered immunity and increases production of the anti-inflammatory cytokine Interleukin-10 (IL-10) to suppress the host immune response. Previously it was shown that YopM induces IL-10 gene expression by elevating phosphorylation of the serine-threonine kinase RSK1 in the nucleus of human macrophages. Using transcriptomics, we now show that YopM affects expression of genes encoding components of the JAK-STAT signaling pathway. Further analysis revealed that YopM mediates nuclear translocation of the transcription factor Stat3 inY. enterocoliticainfected macrophages and that knockdown of Stat3 inhibited YopM-induced IL-10 gene expression. YopM-induced Stat3 translocation did not depend on autocrine IL-10, activation of RSK1 or tyrosine phosphorylation of Stat3. Thus, besides activation of RSK1, stimulation of nuclear translocation of Stat3 is another mechanism by which YopM increases IL-10 gene expression in macrophages.
Body Shaming vs. Body Positivity: Exploring What Words Hurt and What Words Heal
Authors: Wansink Valerie , Wansink Brian 
Published: May 2023

AbstractWhat can a health professional say to a bullied and body shamed child? This research elicited and categorized the words that were reported as being most memorably hurtful and helpful to 341 young people (79.5% female; average age 25.03 years) who had been body shamed. The most memorably hurtful comments generally involved either vivid comparisons or derogatory nicknames. Fortunately, the supportive words of health professionals, peers, and parents can heal. They include 1)reframing commentsthat redirect attention to positive features (such as feminine, healthy, etc.), 2)impact-related commentsthat emphasize how a physical feature influences or is admired by other people (such one’s eyes or smile that “lights up the room”), and 3)identity-related commentsthat redefine one’s physical identify or self-concept (such as striking or mesmerizing). Knowing the type of words that were helpful in healing can be useful to healthcare professionals as well as parents and peers.
Identification of pan-cancer/testis genes and validation of therapeutic targeting in triple-negative breast cancer: Lin28a- and Siglece-based vaccination induces anti-tumor immunity and inhibits metastasis
Authors: Carter Jason A. , Matta Bharati , Battaglia Jenna , Somerville Carter , Harris Benjamin D. , LaPan Margaret , Atwal Gurinder S. , Barnes Betsy J. 
Published: May 2023

AbstractBackgroundCancer-testis (CT) genes are targets for tumor antigen-specific immunotherapy given that their expression is normally restricted to the immune-privileged testis in healthy individuals with aberrant expression in tumor tissues. While they represent targetable germ-tissue antigens and play important functional roles in tumorigenesis, there is currently no standardized approach for identifying clinically relevant CT genes. Optimized algorithms and validated methods for accurate prediction of reliable CT antigens with high immunogenicity are also lacking.MethodsSequencing data from the Genotype-Tissue Expression (GTEx) and The Genomic Data Commons (GDC) databases was utilized for the development of a bioinformatic pipeline to identify CT exclusive genes. A CT germness score was calculated based on the number of CT genes expressed within a tumor type and their degree of expression. The impact of tumor germness with clinical outcome was evaluated using healthy GTEx and GDC tumor samples. We then used a triple-negative breast cancer mouse model to develop and test an algorithm that predicts epitope immunogenicity based on the identification of germline sequences with strong MHCI and MHCII binding affinities. Germline sequences for CT genes were synthesized as long synthetic peptide vaccines and tested in the 4T1 triple-negative model of invasive breast cancer with Poly(I:C) adjuvant. Vaccine immunogenicity was determined by flow cytometric analysis ofin vitroandin vivoT cell responses. Primary tumor growth and lung metastasis was evaluated by histopathology, flow cytometry and colony formation assay.ResultsWe developed a new bioinformatic pipeline to reliably identify CT exclusive genes as immunogenic targets for immunotherapy. We identified CT genes that are exclusively expressed within the testis, lack detectable thymic expression, and are significantly expressed in multiple tumor types. High tumor germness correlated with tumor progression but not with tumor mutation burden, supporting CT antigens as appealing targets in low mutation burden tumors. Importantly, tumor germness also correlated with markers of anti-tumor immunity. Vaccination of 4T1 tumor bearing mice with Siglece and Lin28a antigens resulted in increased T cell anti-tumor immunity and reduced primary tumor growth and lung metastases.ConclusionOur results present a novel strategy for the identification of highly immunogenic CT antigens for the development of targeted vaccines that induce anti-tumor immunity and inhibit metastasis.
Molecular mechanisms for activation of the 26S proteasome
Authors: Lee Donghoon , Zhu Yanan , Colson Louis , Wang Xiaorong , Chen Siyi , Tkacik Emre , Huang Lan , Ouyang Qi , Goldberg Alfred L. , Lu Ying 
Published: May 2023

SummaryVarious hormones, kinases, and stressors (fasting, heat shock) stimulate 26S proteasome activity. To understand how its capacity to degrade ubiquitylated protein can increase, we studied ZFAND5, which promotes protein degradation during muscle atrophy. Cryo-electron microscopy showed that ZFAND5 induces large conformational changes in the 19S regulatory particle. ZFAND5’s AN1 Zn finger interacts with the Rpt5 ATPase and its C-terminus with Rpt1 ATPase and Rpn1, a ubiquitin-binding subunit. Surprisingly, these C-terminal interactions are sufficient to activate proteolysis. With ZFAND5 bound, entry into the proteasome’s protein translocation channel is wider, and ZFAND5 dissociation causes opening of the 20S gate for substrate entry. Using single-molecular microscopy, we showed that ZFAND5 binds ubiquitylated substrates, prolongs their association with proteasomes, and increases the likelihood that bound substrates undergo degradation, even though ZFAND5 dissociates before substrate deubiquitylation. These changes in proteasome conformation and reaction cycle can explain the accelerated degradation and suggest how other proteasome activators may stimulate proteolysis.
Equivalent physical dose (EPD) for improved precision in voxelized dosimetry
Authors: Abbott Elliot M. , Jones Bleddyn , Vojnovic Borivoj , Falzone Nadia , Turner Adam , Vallis Katherine A. 
Published: May 2023

AbstractPurposeEquivalent dose in 2 Gy fractions (EQD2), based on the original biological effective dose (BED) equation, is frequently used to guide treatment in the clinic. This work addresses the limitations of EQD2 in the context of voxelized dosimetry, clarifies potential sources of confusion, and provides an alternative formulation for improved precision.Methods and MaterialsThe EQD2 formula was evaluated by a simple insertion of the EQD2 dose into the BED equation. The mathematically exact form of EQD2, referred to here as equivalent physical dose (EPD), was provided by solving the linear-quadratic model BED equation for dose using the quadratic formula. The EPD derivation was compared in terms of absolute error to the EQD2 derivation, which separates the Relative Effect term from the BED equation.ResultsThe EQD2 expression implicitly assumed a homogenous dose, demonstrating that its use in voxelized dosimetry can mislead. As an alternative formulation, EPD was shown to adhere more closely to the first principles of radiobiological modeling. An error analysis identified absolute errors from EQD2 sometimes in excess of 10%.ConclusionsAssumptions in the standard EQD2 equation are inappropriate in the context of voxelized dosimetry, where voxels within a structure, such as a target volume, may receive a dose that differs from the prescribed dose. Using EPD (or BED) instead of EQD2 would address these areas of confusion. Optimizing therapy according to biological properties in this way could provide enhanced and more reliable radiobiological input to radiotherapy treatment planning.
Distinct genetic liability profiles define clinically relevant patient strata across common diseases
Authors: Trastulla Lucia , Moser Sylvain , Jiménez-Barrón Laura T. , Andlauer Till F.M. , von Scheidt Moritz ,   Schizophrenia Working Group of the Psychiatric Genomics Consortium, Budde Monika , Heilbronner Urs , Papiol Sergi , Teumer Alexander , Homuth Georg , Falkai Peter , Völzke Henry , Dörr Marcus , Schulze Thomas G. , Gagneur Julien , Iorio Francesco , Müller-Myhsok Bertram , Schunkert Heribert , Ziller Michael J. 
Published: May 2023

AbstractGenome-wide association studies have unearthed a wealth of genetic associations across many complex diseases. However, translating these associations into biological mechanisms contributing to disease etiology and heterogeneity has been challenging. Here, we hypothesize that the effects of disease-associated genetic variants converge onto distinct cell type specific molecular pathways within distinct subgroups of patients. In order to test this hypothesis, we develop the CASTom-iGEx pipeline to operationalize individual level genotype data to interpret personal polygenic risk and identify the genetic basis of clinical heterogeneity. The paradigmatic application of this approach to coronary artery disease and schizophrenia reveals a convergence of disease associated variant effects onto known and novel genes, pathways, and biological processes. The biological process specific genetic liabilities are not equally distributed across patients. Instead, they defined genetically distinct groups of patients, characterized by different profiles across pathways, endophenotypes, and disease severity. These results provide further evidence for a genetic contribution to clinical heterogeneity and point to the existence of partially distinct pathomechanisms across patient subgroups. Thus, the universally applicable approach presented here has the potential to constitute an important component of future personalized medicine concepts.
EphrinB2 knockdown in cervical spinal cord preserves diaphragm innervation in a mutant SOD1 mouse model of ALS
Authors: Urban Mark W. , Charsar Brittany A. , Heinsinger Nicolette M. , Markandaiah Shashirekha S. , Sprimont Lindsay , Zhou Wei , Brown Eric V. , Henderson Nathan T. , Thomas Samantha J. , Ghosh Biswarup , Cain Rachel E. , Trotti Davide , Pasinelli Piera , Wright Megan C. , Dalva Matthew B. , Lepore Angelo C. 
Published: May 2023

ABSTRACTAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron loss. Importantly, non-neuronal cell types such as astrocytes also play significant roles in disease pathogenesis. However, mechanisms of astrocyte contribution to ALS remain incompletely understood. Astrocyte involvement suggests that transcellular signaling may play a role in disease. We examined contribution of transmembrane signaling molecule ephrinB2 to ALS pathogenesis, in particular its role in driving motor neuron damage by spinal cord astrocytes. In symptomatic SOD1G93Amice (a well-established ALS model), ephrinB2 expression was dramatically increased in ventral horn astrocytes. Reducing ephrinB2 in the cervical spinal cord ventral horn via viral-mediated shRNA delivery reduced motor neuron loss and preserved respiratory function by maintaining phrenic motor neuron innervation of diaphragm. EphrinB2 expression was also elevated in human ALS spinal cord. These findings implicate ephrinB2 upregulation as both a transcellular signaling mechanism in mutant SOD1-associated ALS and a promising therapeutic target.