bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment courses and outcomes of oesophageal atresia in patients with trisomy 18: a case series of 271 patients from a nationwide database in Japan
Authors: Kutsukake Mai , Konishi Takaaki , Fujiogi Michimasa , Takamoto Naohiro , Morita Kaori , Yasuhisa Ikuta , Hashimoto Yohei , Matsui Hiroki , Fushimi Kiyohide , Fujishiro Jun , Yasunaga Hideo 
Published: December 2023

ObjectiveTo describe characteristics, treatments and clinical outcomes of patients with trisomy 18 and oesophageal atresia, using a nationwide database in Japan.DesignDescriptive study using a retrospective cohort.SettingA nationwide inpatient database including 90% of hospitals with neonatal intensive care units in Japan.PatientsPatients hospitalised within a day after birth for both oesophageal atresia and trisomy 18 between July 2010 and March 2020.InterventionsRadical surgery for oesophageal atresia.Main outcome measuresCharacteristics, treatment course and outcomes.ResultsAmong 271 patients with both oesophageal atresia and trisomy 18, 70 patients underwent radical surgery for oesophageal atresia. Patients who underwent radical surgery were less likely to have severe cardiac anomalies (17% vs 32%; p=0.020), but more likely to undergo cardiac surgery (21% vs 9.5%; p=0.012) than those who did not. The overall in-hospital mortality was lower (54% vs 79%; p<0.001) and the median age at death was higher (210 days vs 39 days; p<0.001) in patients who underwent radical surgery than the others. Postoperative mortality within 30 days after radical surgery was 5.7%. Patients who underwent radical surgery were likely to be discharged to home (50% vs 18%; p<0.001), whereas the age at home discharge (median 314 days vs 216 days; p=0.19) and the requirement for each home treatment did not differ significantly by radical surgery.ConclusionThis study provides information that will aid the clinical decision-making process for patients with oesophageal atresia and trisomy 18. Radical surgery may be a safe and feasible treatment option.
iPSC-derived natural killer cells expressing the FcγR fusion CD64/16A can be armed with antibodies for multitumor antigen targeting
Authors: Snyder Kristin M , Dixon Kate J , Davis Zachary , Hosking Martin , Hart Geoffrey , Khaw Melissa , Matson Anders , Bjordahl Ryan , Hancock Bryan , Shirinbak Soheila , Miller Jeffrey S , Valamehr Bahram , Wu Jianming , Walcheck Bruce 
Published: December 2023

BackgroundAntibody therapies can direct natural killer (NK) cells to tumor cells, tumor-associated cells, and suppressive immune cells to mediate antibody-dependent cell-mediated cytotoxicity (ADCC). This antigen-specific effector function of human NK cells is mediated by the IgG Fc receptor CD16A (FcγRIIIA). Preclinical and clinical studies indicate that increasing the binding affinity and avidity of CD16A for antibodies improves the therapeutic potential of ADCC. CD64 (FcγRI), expressed by myeloid cells but not NK cells, is the only high affinity IgG Fc receptor and is uniquely capable of stably binding to free monomeric IgG as a physiological function. We have reported on the generation of the FcγR fusion CD64/16A, consisting of the extracellular region of CD64 and the transmembrane and cytoplasmic regions from CD16A, retaining its signaling and cellular activity. Here, we generated induced pluripotent stem cell (iPSC)-derived NK (iNK) cells expressing CD64/16A as a potential adoptive NK cell therapy for increased ADCC potency.MethodsiPSCs were engineered to express CD64/16A as well as an interleukin (IL)-15/IL-15Rα fusion (IL-15RF) protein and differentiated into iNK cells. iNK cells and peripheral blood NK cells were expanded using irradiated K562-mbIL21-41BBL feeder cells and examined. NK cells, ovarian tumor cell lines, and therapeutic monoclonal antibodies were used to assess ADCC in vitro, performed by a DELFIA EuTDA assay or in real-time by IncuCyte assays, and in vivo. For the latter, we developed a xenograft mouse model with high circulating levels of human IgG for more physiological relevance.ResultsWe demonstrate that (1) iNK-CD64/16A cells after expansion or thaw from cryopreservation can be coupled to therapeutic antibodies, creating armed iNK cells; (2) antibody-armed iNK-CD64/16A cells can be redirected by added antibodies to target new tumor antigens, highlighting additional potential of these cells; (3) cytokine-autonomous activity by iNK-CD64/16A cells engineered to express IL-15RF; and that (4) antibody-armed iNK-CD64/16A cells thawed from cryopreservation are capable of sustained and robust ADCC in vitro and in vivo, as determined by using a modified tumor xenograft model with high levels of competing human IgG.ConclusionsiNK cells expressing CD64/16A provide an off-the-shelf multiantigen targeting platform to address tumor heterogeneity and mitigate antigen escape.
Allogeneic NK cells induce monocyte-to-dendritic cell conversion, control tumor growth, and trigger a pro-inflammatory shift in patient-derived cultures of primary and metastatic colorectal cancer
Authors: Toffoli Elisa C , van Vliet Amanda A , Verheul Henk W M , van der Vliet Hans J , Tuynman Jurriaan , Spanholtz Jan , de Gruijl Tanja D 
Published: December 2023

IntroductionNatural killer (NK) cells are innate lymphocytes with a key role in the defense against tumors. Recently, allogeneic NK cell-based therapies have gained interest because of their ability to directly lyse tumor cells without inducing graft-versus-host disease. As NK cells are also able to influence the function of other immune cells (most notably dendritic cells (DC)), a better understanding of the effects of allogeneic NK cell products on the host immune system is required. In this study, we analyzed the effects of an allogeneic off-the-shelf NK cell product, on the tumor microenvironment (TME) of primary and metastatic colorectal cancer (pCRC and mCRC, respectively). Moreover, we explored if the combination of NK cells with R848, a toll-like receptors 7/8 ligand, could further enhance any pro-inflammatory effects.MethodsEx vivo expanded umbilical cord blood stem cell derived NK cells were co-cultured with pCRC or mCRC single-cell suspensions in the presence or absence of R848 for 5 days, during and after which flow cytometry and cytokine release profiling were performed.ResultsNK cells efficiently induced lysis of tumor cells in both pCRC and mCRC single-cell suspensions and thereby controlled growth rates during culture. They also induced differentiation of infiltrating monocytic cells to an activated DC phenotype. Importantly, this NK-mediated myeloid conversion was also apparent in cultures after tumor cell depletion and was further enhanced by combining NK cells with R848. Moreover, NK cells, and to a greater extent, the combination of NK cells and R848, triggered CD8+and CD4+T-cell activation as well as a reduction in activated regulatory T cell rates. Finally, the combination of NK cells and R848 induced a pro-inflammatory shift in the cytokine release profile resulting in higher levels of interferon (IFN)-γ, interleukin (IL)-2, IL-12p70, and IFN-α as well as a reduction in IL-6, in both pCRC and mCRC cultures.ConclusionAllogeneic NK cells engaged in favorable myeloid crosstalk, displayed effective antitumor activity and, when combined with R848, induced a pro-inflammatory shift of the CRC TME. These findings prompt the investigation of NK cells and R848 as a combination therapy for solid tumors.
Caspase-9 inhibition triggers Hsp90-based chemotherapy-mediated tumor intrinsic innate sensing and enhances antitumor immunity
Authors: Li Jingyang , Han Xiaoyu , Sun Mayu , Li Weida , Yang Guanghuan , Chen Huiyi , Guo Bao , Li Jingquan , Li Xiaoguang , Wang Hui 
Published: December 2023

BackgroundAntineoplastic chemotherapies are dramatically efficient when they provoke immunogenic cell death (ICD), thus inducing an antitumor immune response and even tumor elimination. However, activated caspases, the hallmark of most cancer chemotherapeutic agents, render apoptosis immunologically silent. Whether they are dispensable for chemotherapy-induced cell death and the apoptotic clearance of cells in vivo is still elusive.MethodsA rational cell-based anticancer drug library screening was performed to explore the immunogenic apoptosis pathway and therapeutic targets under apoptotic caspase inhibition. Based on this screening, the potential of caspase inhibition in enhancing chemotherapy-induced antitumor immunity and the mechanism of actions was investigated by various cells and mouse models.ResultsHeat shock protein 90 (Hsp90) inhibition activates caspases in tumor cells to produce abundant genomic and mitochondrial DNA fragments and results in cell apoptosis. Meanwhile, it hijacks Caspase-9 signaling to suppress intrinsic DNA sensing. Pharmacological blockade or genetic deletion of Caspase-9 causes tumor cells to secrete interferon (IFN)-β via tumor intrinsic mitochondrial DNA/the second messenger cyclic GMP–AMP (cGAS) /stimulator of interferon genes (STING) pathway without impairing Hsp90 inhibition-induced cell death. Importantly, both Caspase-9 and Hsp90 inhibition triggers an ICD, leading to the release of numerous damage-associated molecular patterns such as high-mobility group box protein 1, ATP and type I IFNs in vitro and remarkable antitumor effects in vivo. Moreover, the combination treatment also induces adaptive resistance by upregulating programmed death-ligand 1 (PD-L1). Additional PD-L1 blockade can further overcome this acquired immune resistance and achieve complete tumor regression.ConclusionsBlockade of Caspase-9 signaling selectively provokes Hsp90-based chemotherapy-mediated tumor innate sensing, leading to CD8+T cell-dependent tumor control. Our findings implicate that pharmacological modulation of caspase pathway increases the tumor-intrinsic innate sensing and immunogenicity of chemotherapy-induced apoptosis, and synergizes with immunotherapy to overcome adaptive resistance.
Fibrinogen-like protein 2 promotes tumor immune suppression by regulating cholesterol metabolism in myeloid-derived suppressor cells
Authors: Wu Lei , Liu Xudong , Lei Juan , Zhang Nan , Zhao Huakan , Zhang Jiangang , Deng Huan , Li Yongsheng 
Published: December 2023

BackgroundMyeloid-derived suppressor cells (MDSCs) are crucial mediators of tumor-associated immune suppression. Targeting the accumulation and activation of MDSCs has been recognized as a promising approach to enhance the effectiveness of immunotherapies for different types of cancer.MethodsThe MC38 and B16 tumor-bearing mouse models were established to investigate the role of Fgl2 during tumor progression. Fgl2 and FcγRIIB-deficient mice, adoptive cell transfer, RNA-sequencing and flow cytometry analysis were used to assess the role of Fgl2 on immunosuppressive activity and differentiation of MDSCs.ResultsHere, we show that fibrinogen-like protein 2 (Fgl2) regulates the differentiation and immunosuppressive functions of MDSCs. The absence of Fgl2 leads to an increase in antitumor CD8+T-cell responses and a decrease in granulocytic MDSC accumulation. The regulation mechanism involves Fgl2 modulating cholesterol metabolism, which promotes the accumulation of MDSCs and immunosuppression through the production of reactive oxygen species and activation of XBP1 signaling. Inhibition of Fgl2 or cholesterol metabolism in MDSCs reduces their immunosuppressive activity and enhances differentiation. Targeting Fgl2 could potentially enhance the therapeutic efficacy of anti-PD-1 antibody in immunotherapy.ConclusionThese results suggest that Fgl2 plays a role in promoting immune suppression by modulating cholesterol metabolism and targeting Fgl2 combined with PD-1 checkpoint blockade provides a promising therapeutic strategy for antitumor therapy.
Model for classification of heart failure severity in patients with hypertrophic cardiomyopathy using a deep neural network algorithm with a 12-lead electrocardiogram
Authors: Togo Sanshiro , Sugiura Yuki , Suzuki Sayumi , Ohno Kazuto , Akita Keitaro , Suwa Kenichiro , Shibata Shin-ichi , Kimura Michio , Maekawa Yuichiro 
Published: December 2023

ObjectivesIn hypertrophic cardiomyopathy (HCM), specific ECG abnormalities are observed. Therefore, ECG is a valuable screening tool. Although several studies have reported on estimating the risk of developing fatal arrhythmias from ECG findings, the use of ECG to identify the severity of heart failure (HF) by applying deep learning (DL) methods has not been established.MethodsWe assessed whether data-driven machine-learning methods could effectively identify the severity of HF in patients with HCM. A residual neural network-based model was developed using 12-lead ECG data from 218 patients with HCM and 245 patients with non-HCM, categorised them into two (mild-to-moderate and severe) or three (mild, moderate and severe) severities of HF. These severities were defined according to the New York Heart Association functional class and levels of the N-terminal prohormone of brain natriuretic peptide. In addition, the patients were divided into groups according to Kansas City Cardiomyopathy Questionnaire (KCCQ)-12. A transfer learning method was applied to resolve the issue of the low number of target samples. The model was trained in advance using PTB-XL, which is an open ECG dataset.ResultsThe model trained with our dataset achieved a weighted average F1 score of 0.745 and precision of 0.750 for the mild-to-moderate class samples. Similar results were obtained for grouping based on KCCQ-12. Through data analyses using the Guided Gradient Weighted-Class Activation Map and Integrated Gradients, QRS waves were intensively highlighted among true-positive mild-to-moderate class cases, while the highlighted part was highly variable among true-positive severe class cases.ConclusionsWe developed a model for classifying HF severity in patients with HCM using a deep neural network algorithm with 12-lead ECG data. Our findings suggest that applications of this DL algorithm for using 12-lead ECG data may be useful to classify the HF status in patients with HCM.
External validation of novel clinical likelihood models to predict obstructive coronary artery disease and prognosis
Authors: Rasmussen Laust Dupont , Williams Michelle Claire , Newby David E , Dahl Jonathan Nørtoft , Schmidt Samuel Emil , Bøttcher Morten , Winther Simon 
Published: December 2023

ObjectivesThe risk factor-weighted and coronary artery calcium score-weighted clinical likelihood (RF-CL and CACS-CL, respectively) models improve discrimination of patients with suspected obstructive coronary artery disease (CAD). However, external validation is warranted.Compared to the 2019 European Society of Cardiology pretest probability (ESC-PTP) model, the aims were (1) to validate the RF-CL and CACS-CL models for identification of obstructive CAD and revascularisation, and (2) to investigate prognosis by CL thresholds.MethodsStable de novo chest pain patients (n=1585) undergoing coronary CT angiography (CTA) were investigated. Obstructive CAD was defined as >70% diameter stenosis in a major epicardial vessel on CTA. Decision of revascularisation within 120 days was based on onsite judgement. The endpoint was non-fatal myocardial infarction or cardiovascular death. The ESC-PTP was calculated based on age, sex and symptom typicality, the RF-CL additionally included number of risk factors, and the CACS-CL incorporated CACS to the RF-CL.ResultsObstructive CAD was present in 386/1585 (24.4%) patients, and 91/1585 (5.7%) patients underwent revascularisation. Both the RF-CL and CACS-CL classified more patients to very-low CL (<5%) of obstructive CAD compared with the ESC-PTP model (41.4% and 52.2% vs 19.2%, p<0.001). In very-low CL patients, obstructive CAD and revascularisation prevalences (≤6% and <1%) remained similar combined with low event risk during 5.0 years follow-up.ConclusionIn an external validation cohort, the novel RF-CL and CACS-CL models improve categorisation to a very-low CL group with preserved prevalences of obstructive CAD, revascularisation and favourable prognosis.
Hepatitis B vaccination associated with low response in patients with rheumatic diseases treated with biologics
Authors: Romão Vasco C , Ávila-Ribeiro Pedro , Gonçalves Maria João , Cruz-Machado Rita , Guerreiro André Bento , Teixeira Vítor , Valido Ana , Silva-Dinis Joana , Vieira-Sousa Elsa , Saavedra Maria João , Sacadura-Leite Ema , Marinho Rui Tato , Fonseca João Eurico 
Published: December 2023

BackgroundHepatitis B virus (HBV) vaccination is recommended for non-immunised patients with rheumatic diseases starting biological disease-modifying antirheumatic drugs (bDMARDs). There is some evidence that HBV vaccination is effective in patients under conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), but it is currently unclear whether this also applies to bDMARDs.ObjectivesTo assess the efficacy and safety of HBV vaccination in patients with inflammatory arthritides treated with bDMARDs.MethodsA prospective cohort with inflammatory arthritides treated with bDMARDs, negative for anti-HBs and anti-HBc and never vaccinated for HBV was recruited. Engerix B was administered at 0, 1 and 6 months and anti-HBs was reassessed ≥1 month after last dose. Response was defined as anti-HBs≥10 IU/L and compared against vaccinated healthy controls. Disease flare, serious adverse events and immune-related disorders not previously present were recorded.Results62 patients, most treated with TNF inhibitors (TNFi), and 38 controls were recruited. Most patients were taking csDMARDs (67.7%) and were in remission/low disease activity (59.4%). Only 20/62 patients (32.3%) had a positive response to vaccination, in comparison to 36/38 age-matched controls (94.7%, p<0.001). Response was seen in 19/51 patients treated with TNFi (37.3%) and in 1/11 (9.1%) patients treated with non-TNFi (p=0.07), including 1/6 treated with tocilizumab (16.7%). Among TNFi, response rates ranged from 4/22 (18.2%) for infliximab to 8/14 (57.1%) for etanercept. No relevant safety issues were identified.ConclusionsHBV vaccination response in patients with rheumatic diseases treated with bDMARDs was poorer than expected. Our data reinforce the recommendation for vaccination prior to starting bDMARDs.
Northern Svalbard Composite Tectono-Sedimentary Element
Authors: Smelror Morten , Olaussen Snorre , Dumais Marie-Andrée , Grundvåg Sten-Andreas , Abay Tesfamariam Berhane 
Published: December 2023

Abstract
The Northern Svalbard Composite Tectono-Sedimentary Element (CTSE) comprises Proterozoic, Early Paleozoic and Devonian sedimentary rocks preserved in northern Svalbard and on the adjacent shelf margin between complexes of metamorphic and crystalline basement rocks. The Northern Svalbard CTSE covers four main tectono-sedimentary elements: Tonian synrift, Neoproterozoic–Cambrian post-rift, Ordovician passive margin and late Silurian?/Devonian synextensional basins. The oldest documented sedimentary strata are greywacke and shale deposited after the Greenvillian Orogeny and assumed to be younger than 980–960 Ma. The present CTSE further includes Cambrian–Ordovician sedimentary rocks in Ny-Friesland and Nordaustlandet, while the dominant part of the CTSE are continental Old Red Sandstone sediments of the late Silurian?/Early Devonian Red Bay and Siktefjellet groups and the Early–Late Devonian Andreé Land Group onshore northern Spitsbergen. Locally, the Cambrian–Ordovician formations contain petroleum source rocks with moderate total organic carbon contents and relatively high hydrogen index values, suggesting a good potential for oil generation. There are possible reservoirs, seals and traps in some of the basins but the CTSE generally holds a very limited potential as a petroleum province, particularly as the region is under strict environmental protection.
Las Calles son nuestras (y las imágenes, también)
Authors: Rocca Paola Cortes 
Published: December 2023

Este artículo aborda una serie de imágenes tomadas por colectivos fotográficos y fotografxs activistas, de las movilizaciones ocurridas en Argentina desde el surgimiento de la marea feminista en 2015 y en torno al reclamo por la ley de aborto seguro, legal y gratuito sancionada en 2020. Desde una perspectiva teórico-crítica pero también desde la experiencia de la participación en el colectivo de activistas Ni Una Menos, se exploran la visualidad feminista como un modo de representación y visibilización de la marea en el espacio público, pero también como una herramienta de autorrepresentación que se enlaza con la masividad del movimiento en el nuevo milenio, la ocupación callera y la intervención digital, las pequeñas y grandes interrupciones en el relato patriarcal. La hipótesis nodal es que el feminismo se constituye como un aparato de inteligibilidad, es decir, como un modo de hablar y producir imágenes, de leer y ver el mundo. Esta relación entre palabra e imagen, implica también una intervención político-estética, que hace uso estratégico de la performatividad e implica un modo distintivo de construir presente y futuro.
The art of baring it all: a reading of Judith Teixeira’s “Satânia”
Authors: Pazos-Alonso Cláudia 
Published: December 2023

ABSTRACT
This article considers Judith Teixeira’s focus on heterosexual relations in “Satânia”. In the light of an emerging military dictatorship and backlash after Nua and De Mim, the writer seeks to uncover the double standards that required women to repress their corporeal desires outside marriage. The article alludes to the scandal caused by Maria Adelaide Coelho da Cunha’s affair with her a young chauffeur, publicly played out in the press, which may have sparked Teixeira’s tale of forbidden lust. Taking its cue from Saint-Point’s Manifeste futuriste de la Luxure (1912), the demise of the protagonist, Maria Margarida, becomes a barely veiled criticism of social prohibitions around female sexuality.
Maritime Pilotage from the Perspective of the International Law of the Sea
Authors: Ehlers Peter 
Published: December 2023

Abstract
Matters concerning maritime pilotage have only been dealt with in a few individual points in international maritime law, as pilotage services generally are regulated in the respective territorial waters in accordance with national law. However, especially in view of the possible further expansion of use of deep-sea pilots, it seems worthwhile taking a closer look at the obligations and powers under international law to provide pilotage services. This applies in particular to the establishment of compulsory pilotage and its limitation by the freedom of navigation rights under international law in the various maritime zones. Considerable legal ambiguities become apparent in this context. Hence there are arguments in favour of explicitly regulating maritime pilotage by including it in the provisions on maritime services in Chapter V of the Annex to the International Convention for the Safety of Life at Sea.