bluuebunny/crossref_metadata_2025 huggingface dataset:
INDONESIA–AUSTRALIA MARITIME COOPERATION AND ITS IMPLICATION ON INDONESIA’S MARITIME SECURITY AND SOVEREIGNTY
Authors: Pangemanan Arcelinocent Emile , Perwita Anak Agung Banyu , Sudibyo Sudibyo
Published: February 2023

Global Maritime Fulcrum (GMF) has provided a roadmap for realizing Indonesia’s maritime security and sovereignty with an active contribution regionally and globally. The research method used in this research is content analysis, which is an approach in qualitative research that in research that refers to systematic data and text collections that can be managed to support the research itself. The rise of transnational maritime crime has a major impact on why Indonesia and Australia are keen on building trust through maritime cooperation, for it has the potential to disrupt and threaten national development, therefore this research aims to the mapped diplomatic mechanism through GMF, as a framework that hostess Indonesia–Australia Maritime Cooperation and its plan of actions in ensuring Indonesia’s maritime security and sovereignty. The maritime cooperation between Indonesia and Australia has improved the integrated defense and security capabilities of both countries through capacity building, although the plan of action will end in 2022, therefore harnessing the longevity of the maritime cooperation is considered crucial.  
Automated production of specific T cells for treatment of refractory viral infections after allogeneic stem cell transplantation
Authors: Heinz Amadeus T , Calkoen Friso G.J. , Derbich Alexander , Miltner Lea , Seitz Christian , Doering Michaela , Braun Christiane , Atar Daniel , Schumm Michael , Heubach Florian , Arendt Anne-Marie , Schulz Ansgar , Schuster Friedhelm R , Meisel Roland , Strahm Brigitte , Finke Juergen , Heineking Beatrice , Stetter Susanne , Silling Gerda , Stachel Daniel , Gruhn Bernd , Debatin Klaus-Michael , Foell Juergen , Schulte Johannes H , Woessmann Wilhelm , Mauz-Körholz Christine , Tischer Johanna , Feuchtinger Tobias , Handgretinger Rupert , Lang Peter
Published: February 2023

Therapy-resistant viral reactivations contribute significantly to mortality after hematopoietic stem cell transplantation. Adoptive cellular therapy with virus-specific T cells (VST) has shown efficacy in various single-center trials. However, the scalability of this therapy is hampered by laborious production methods. In this study we describe the in-house production of VST in a closed system (CliniMACS Prodigy® system, Miltenyi Biotec). In addition, we report the efficacy in 26 patients with viral disease following hematopoietic stem cell transplantation in a retrospective analysis (adenovirus, n=7; cytomegalovirus, n=8; Epstein-Barr virus, n=4; multi-viral, n=7). The production of VST was successful in 100% of cases. The safety profile of VST therapy was favorable (n=2 grade 3 and n=1 grade 4 adverse events; all three were reversible). A response was seen in 20 of 26 patients (77%). Responding patients had a significantly better overall survival than patients who did not respond (P<0.001). Virus-specific symptoms were reduced or resolved in 47% of patients. The overall survival of the whole cohort was 28% after 6 months. This study shows the feasibility of automated VST production and safety of application. The scalability of the CliniMACS Prodigy® device increases the accessibility of VST treatment.
ANKRD26 is a new regulator of type I cytokine receptor signaling in normal and pathological hematopoiesis
Authors: Basso-Valentina Francesca , Donada Alessandro , Manchev Vladimir T , Lisetto Manuel , Balayn Nathalie , Martin Jean Edouard , Muller Delphine , Oyarzun Cecilia Paola Marin , Duparc Hélène , Arkoun Brahim , Cumin Alessandro , Faivre Lionel , Droin Nathalie , Biunno Ida , Pecci Alessandro , Balduini Alessandra , Debili Najet , Antony-Debré Iléana , Marty Caroline , Vainchenker William , Plo Isabelle , Favier Remi , Raslova Hana
Published: February 2023

Sustained ANKRD26 expression associated with germline ANKRD26 mutations causes thrombocytopenia 2 (THC2), an inherited platelet disorder associated with a predisposition to leukemia. Some patients also present with erythrocytosis and/or leukocytosis. Using multiple human-relevant in vitro models (cell lines, primary patients’ cells and patient-derived induced pluripotent stem cells) we demonstrate for the first time that ANKRD26 is expressed during the early steps of erythroid, megakaryocyte and granulocyte differentiation, and is necessary for progenitor cell proliferation. As differentiation progresses, ANKRD26 expression is progressively silenced, to complete the cellular maturation of the three myeloid lineages. In primary cells, abnormal ANKRD26 expression in committed progenitors directly affects the proliferation/differentiation balance for the three cell types. We show that ANKRD26 interacts with and crucially modulates the activity of MPL, EPOR and G-CSFR, three homodimeric type I cytokine receptors that regulate blood cell production. Higher than normal levels of ANKRD26 prevent the receptor internalization that leads to increased signaling and cytokine hypersensitivity. These findings afford evidence how ANKRD26 overexpression or the absence of its silencing during differentiation is responsible for myeloid blood cell abnormalities in patients with THC2.
Mitapivat, a pyruvate kinase activator, improves transfusion burden and reduces iron overload in M-thalassemic mice
Authors: Mattè Alessandro , Kosinski Penelope A. , Federti Enrica , Dang Lenny , Recchiuti Antonio , Russo Roberta , Siciliano Angela , Riccardi Veronica , Janin Anne , Mucci Matteo , Leboeuf Christophe , Iolascon Achille , Brugnara Carlo , De Franceschi Lucia
Published: February 2023

Not available.
Latest Highlights from Guselkumab in Psoriasis from EADV 2019
Authors: Langley Richard G. , Blauvelt Andrew , Armstrong April , Muñoz-Elías Ernesto J. , Reich Kristian
Published: February 2023

Guselkumab was the first monoclonal antibody targeting the p19 subunit of IL-23 (IL-23p19) to be approved for the treatment of psoriasis. The registrational trials VOYAGE 1 and 2 established the efficacy and safety profile of guselkumab to Week 48 and demonstrated the superiority of guselkumab over placebo and adalimumab. A 5-year, open-label extension phase of both trials is currently ongoing. The poster and oral presentations reviewed here represent the latest data to emerge from the guselkumab clinical trial programme in psoriasis, as presented at the 28th European Academy of Dermatology and Venereology (EADV) Congress. The ECLIPSE study was the first head-to-head trial between guselkumab and the IL-17A inhibitor secukinumab. Both agents were the first to be approved in their respective class with proven efficacy for the treatment of moderate-to-severe psoriasis but, until now, no direct comparisons were available to assist clinical decision making. Together with efficacy and safety, ECLIPSE also sought to understand the differential impact of IL-23 versus IL-17 inhibition on the immune profile of psoriatic skin and effector cytokines, providing insights into their respective mechanisms of action. Switching focus to the long term, the latest 3-year safety data from VOYAGE 1 and 2 are now available to accompany the established 3-year efficacy profile, providing unprecedented insights into the long-term response and tolerability of guselkumab for the treatment of psoriasis.
Field Cancerisation of the Upper Aerodigestive Tract: Screening for Second Primary Cancers of the Oesophagus in Cancer Survivors
Authors: Scherübl Hans , Cataldegirmen Güllü , Eick Jan , Ring Wanda , Schwertner Christoph , Steinberg Joachim , Herbst Hermann
Published: February 2023

Tobacco, alcohol, and betel quid are the main causes of squamous cell cancers of the upper aerodigestive tract. These substances can cause multifocal carcinogenesis leading to multiple synchronous or metachronous cancers of the oesophagus, head and neck region, and lungs (‘field cancerisation’). Globally there are several million people who have survived either head and neck squamous cell cancer (HNSCC) or lung cancer (LC). HNSCC and LC survivors are at increased risk of developing second primary malignancies, including second primary cancers of the oesophagus. The risk of second primary oesophageal squamous cell cancer (OSCC) ranges from 8-30% in HNSCC patients. LC and HNSCC survivors should be offered endoscopic surveillance of the oesophagus. Lugol chromoendoscopy is the traditional and best evaluated screening method to detect early squamous cell neoplasias of the oesophagus. More recently, narrow band imaging combined with magnifying endoscopy has been established as an alternative screening method in Asia. Low-dose chest computed tomography (CT) is the best evidencebased screening technique to detect (second primary) LC and to reduce LC-related mortality. Low-dose chest CT screening is therefore recommended in OSCC, HNSCC, and LC survivors. In addition, OSCC survivors should undergo periodic pharyngolaryngoscopy for early detection of second primary HNSCC. Secondary prevention aims at quitting smoking, betel quid chewing, and alcohol consumption. As field cancerisation involves the oesophagus, the bronchi, and the head and neck region, the patients at risk are best surveilled and managed by an interdisciplinary team.
Substitusi Tepung Kedelai (Glycine max) Dengan Tepung Daun Kelor (Moringa oleifera) Dalam Pakan Terhadap Tingkat Kecernaan Ikan Nila (Oreochromis niloticus)
Authors: Andriani Putri , Hamzah Muhaimin , Kurnia Agus
Published: February 2023

Abstrak Penelitian ini bertujuan untuk mengetahui pengaruh subtitusi tepung kedelai dengan tepung daun kelor dalam pakan terhadap tingkat kecernaan ikan nila (O. niloticus). Empat jenis pakan dibuat berdasarkan presentase substitusi Tepung Kedelai (TK) dan Tepung Daun Kelor (TDK) dalam pakan yaitu 100% TK (pakan A), 75% TK + 25% TDK (pakan B), 50% TK + 50% TDK (pakan C) dan 25% TK + 75% TDK (pakan D). Sejumlah 96 ekor ikan Nila (bobot awal: 10,5 ± 0,2 g) dimasukan kedalam 12 unit akuarium (8 ekor/akuarium) yang berukuran 60 × 50 × 40 cm dengan ketinggian air 30 cm. Frekuensi pemberian pakan 2 kali sehari (08:00 dan 16.00 WITA) dengan dosis sebanyak 5% bobot biomassa selama 60 hari pemeliharaan. Penelitian ini menggunakan Rancangan Acak Lengkap (RAL) dengan 4 perlakuan dan 3 ulangan. Hasil penelitian menunjukan bahwa penambahan tepung daun kelor (M. oleifera) ke dalam pakan memberikan pengaruh yang sama atau tidak berbeda nyata terhadap tingkat kecernaan protein, tingkat kecernaan total dan pertumbuhan mutlak rata-rata. Tingkat kecernaan protein dan kecernaan total ikan nila masing –masing berkisar antara 88,72 – 96,16% and 61,54 - 87,18%. Pertumbuhan mutlak rata-rata ikan nila yang diberi pakan uji berkisar antara 9,81 – 8,23 g. Penelitian ini menyimpulkan bahwa tepung daun kelor dapat dijadikan bahan pakan sumber protein nabati sebagai alternatidf dalam pakan pakan dengan tingkat kecernaan yang tinggi pada ikan nila. Kata Kunci: Ikan Nila, Tepung kedelai, Tepung daun kelor, Kecernaan protein, Kecernaan total
Efisiensi Pakan dan Pertumbuhan Ikan Nila (Oreochromis niloticus) yang Diberi Pakan Bersinbiotik, Prebiotik Bawang Hutan (Eleutherine bulbosa) pada Level Probiotik EM4 yang Sama
Authors: Mutia Indah Wa Ode , Muskita Wellem H. , Idris Muhammad
Published: February 2023

Bawang hutan (Eleutherine bulbosa) mengandung senyawa metabolit sekunder yakni alkaloid, glikosida, flavanoid,fenolik, steroid, dan tanin yang merupakan sumber biofarmaka. Senyawa flavanoid memiliki sifat antioksidan sebagai penangkap radikal bebas karena mengandung gugus hidroksil yang bersifat sebagai redukstor dan dapat bertindak sebagai donor hydrogen terhadap radikal bebas. Penelitian ini bertujuan untuk mengetahui pengaruh pemberian pakan bersinbiotik, prebiotik bawang hutan (TBH) pada level probiotik EM4 yang sama terhadap efisiensi pakan dan pertumbuhan ikan nila. Rancangan percobaan yang digunakan yaitu Rancangan Acak Lengkap (RAL) dengan 4 taraf dan 3 ulangan yaitu Perlakuan A (0 TBH + 15 ml EM4), Perlakuan B (7,5% TBH + 15 ml EM4), Perlakuan C (10% TBH + 15 ml EM4) dan Perlakuan D (12,5% TBH + 15 ml EM4). Hasil penelitian menunjukkan bahwa pemberian TBH dalam pakan memberikan pengaruh nyata terhadap pertumbuhan mutlak tapi tidak berpengaruh nyata terhadap efisiensi pakan ikan nila. Pertumbuhan mutlak tertinggi didapatkan pada ikan nila yang diberi pakan C sebesar 2,85 ± 0,26 g disusul pakan D, pakan B, dan pakan A masing - masing sebesar 2,56 ± 0,31 g ; 1,93 ± 0,38 g dan 1,47 ± 0,47 g. nilai efisiensi pakan ikan nila pada penelitian ini berkisar antara 5,99 ± 1,91% - 8,04 ± 0,22%. Berdasarkan hasil penelitian dapat disimpulkan bahwa pemberian tepung bawang hutan 10% + 15 ml EM4 memberikan pengaruh nyataterhadap pertumbuhan mutlak dan tingkat konsumsi pakan, tetapi tidak berpengaruh terhadap rasio konversi pakan, efisiensi pakan dan kelangsungan hidup ikan nila.Kata Kunci : Ikan nila, tepung bawang hutan, efisiensi pakan dan pertumbuhan mutlak
Pengaruh Pakan Rumput Laut Segar Yang Berbeda Terhadap Pertumbuhan Dan Kelangsungan Hidup Ikan Baronang Lingkis (Siganus canaliculatus) (Park, 1797)
Authors: Riano Agus , Ruslaini Ruslaini , Balubi Abdul Muis
Published: February 2023

AbstrakTujuan penelitian adalah untuk mengetahui pertumbuhan, kelangsungan hidup, rasio konversi pakan dan efisiensi pakan ikan baronang lingkis dengan peemberian pakan rumput laut segar yang dipelihara pada karamba jaringapung. Penelitian ini dilaksanakan bulan Maret sampai bulan Mei 2020. Pemeliharaan benih ikan baronang dilakukandalam Karamba Jaring Apung (KJA) di Desa Wawobungi, Kecamatan Lalonggasumeeto, Kabupaten Konawe, ProvinsiSulawesi Tenggara. Pakan yang digunakan pada penelitian ini berupa rumput laut segar jenis Gledium sp (perlakuanA), Sargassum sp (Perlakuan B) dan Padina sp (perlakuan C). Penelitian ini menggunakan Rancangan Acak Kelompok(RAK) yang terdiri atas 3 perlakuan dan 3 kelompok. Parameter yang diamati yaitu pertumbuhan bobot mutlak,pertumbuhan panjang mutlak, laju pertumbuhan spesifik, rasio konversi pakan, efisiensi pakan dan kelangsungan hidupikan baronang. Hasil penelitan menunjukan bahwa rata-rata pertumbuhan bobot tertinggi dihasilkan pakan Gelidiumsp (perlakuan A) yaitu 58,7 g, pertumbuhan panjang 23,31 cm, laju pertumbuhan spesifik 1,60 %, rasio konversi pakan13,82 g, efisiensi pakan 7,52%, kelanngsungan hidup ikan baronang 88,89%. Berdasarkan hasil penelitian dapatdisimpulkan bahwa pakan rumput laut segar jenis Gelidium sp dapat meningkatkan pertumbuhan dan kelangsunganhidup ikan baronang yang dipelihara pada keramba jarring apung.Kata Kunci : Gledium, Sargassum, Padina, Pertumbuhan, Kelangsungan hidup, Ikan Baronang
Biomimetic cardiac tissue chip and murine arteriovenous fistula models for recapitulating clinically relevant cardiac remodeling under volume overload conditions
Authors: Waldrop Tatyana Isayeva , Graham Caleb , Gard William , Ingle Kevin , Ptacek Travis , Nguyen Nguyen , Lose Bailey , Sethu Palaniappan , Lee Timmy
Published: February 2023

Cardiovascular events are the primary cause of death among dialysis patients. While arteriovenous fistulas (AVFs) are the access of choice for hemodialysis patients, AVF creation can lead to a volume overload (VO) state in the heart. We developed a three-dimensional (3D) cardiac tissue chip (CTC) with tunable pressure and stretch to model the acute hemodynamic changes associated with AVF creation to complement our murine AVF model of VO. In this study, we aimed to replicate the hemodynamics of murine AVF models in vitro and hypothesized that if 3D cardiac tissue constructs were subjected to “volume overload” conditions, they would display fibrosis and key gene expression changes seen in AVF mice. Mice underwent either an AVF or sham procedure and were sacrificed at 28 days. Cardiac tissue constructs composed of h9c2 rat cardiac myoblasts and normal adult human dermal fibroblasts in hydrogel were seeded into devices and exposed to 100 mg/10 mmHg pressure (0.4 s/0.6 s) at 1 Hz for 96 h. Controls were exposed to “normal” stretch and experimental group exposed to “volume overload”. RT-PCR and histology were performed on the tissue constructs and mice left ventricles (LVs), and transcriptomics of mice LVs were also performed. Our tissue constructs and mice LV both demonstrated cardiac fibrosis as compared to control tissue constructs and sham-operated mice, respectively. Gene expression studies in our tissue constructs and mice LV demonstrated increased expression of genes associated with extracellular matrix production, oxidative stress, inflammation, and fibrosis in the VO conditions vs. control conditions. Our transcriptomics studies demonstrated activated upstream regulators related to fibrosis, inflammation, and oxidative stress such as collagen type 1 complex, TGFB1, CCR2, and VEGFA and inactivated regulators related to mitochondrial biogenesis in LV from mice AVF. In summary, our CTC model yields similar fibrosis-related histology and gene expression profiles as our murine AVF model. Thus, the CTC could potentially play a critical role in understanding cardiac pathobiology of VO states similar to what is present after AVF creation and may prove useful in evaluating therapies.
Engineering protein glycosylation in CHO cells to be highly similar to murine host cells
Authors: Gupta Shivani , Shah Bhavana , Fung Coral Shek , Chan Pik Kay , Wakefield Devin L. , Kuhns Scott , Goudar Chetan T. , Piret James M.
Published: February 2023

Since 2015 more than 34 biosimilars have been approved by the FDA. This new era of biosimilar competition has stimulated renewed technology development focused on therapeutic protein or biologic manufacturing. One challenge in biosimilar development is the genetic differences in the host cell lines used to manufacture the biologics. For example, many biologics approved between 1994 and 2011 were expressed in murine NS0 and SP2/0 cell lines. Chinese Hamster ovary (CHO) cells, however, have since become the preferred hosts for production due to their increased productivity, ease of use, and stability. Differences between murine and hamster glycosylation have been identified in biologics produced using murine and CHO cells. In the case of monoclonal antibodies (mAbs), glycan structure can significantly affect critical antibody effector function, binding activity, stability, efficacy, and in vivo half-life. In an attempt to leverage the intrinsic advantages of the CHO expression system and match the reference biologic murine glycosylation, we engineered a CHO cell expressing an antibody that was originally produced in a murine cell line to produce murine-like glycans. Specifically, we overexpressed cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) and N-acetyllactosaminide alpha-1,3-galactosyltransferase (GGTA) to obtain glycans with N-glycolylneuraminic acid (Neu5Gc) and galactose-α-1,3-galactose (alpha gal). The resulting CHO cells were shown to produce mAbs with murine glycans, and they were then analyzed by the spectrum of analytical methods typically used to demonstrate analytical similarity as a part of demonstrating biosimilarity. This included high-resolution mass spectrometry, biochemical, as well as cell-based assays. Through selection and optimization in fed-batch cultures, two CHO cell clones were identified with similar growth and productivity criteria to the original cell line. They maintained stable production for 65 population doubling times while matching the glycosylation profile and function of the reference product expressed in murine cells. This study demonstrates the feasibility of engineering CHO cells to express mAbs with murine glycans to facilitate the development of biosimilars that are highly similar to marketed reference products expressed in murine cells. Furthermore, this technology can potentially reduce the residual uncertainty regarding biosimilarity, resulting in a higher probability of regulatory approval and potentially reduced costs and time in development.
Hydrogel systems for targeted cancer therapy
Authors: Li Xinlin , Xu Xinyi , Xu Mengfei , Geng Zhaoli , Ji Ping , Liu Yi
Published: February 2023

When hydrogel materials with excellent biocompatibility and biodegradability are used as excellent new drug carriers in the treatment of cancer, they confer the following three advantages. First, hydrogel materials can be used as a precise and controlled drug release systems, which can continuously and sequentially release chemotherapeutic drugs, radionuclides, immunosuppressants, hyperthermia agents, phototherapy agents and other substances and are widely used in the treatment of cancer through radiotherapy, chemotherapy, immunotherapy, hyperthermia, photodynamic therapy and photothermal therapy. Second, hydrogel materials have multiple sizes and multiple delivery routes, which can be targeted to different locations and types of cancer. This greatly improves the targeting of drugs, thereby reducing the dose of drugs and improving treatment effectiveness. Finally, hydrogel can intelligently respond to environmental changes according to internal and external environmental stimuli so that anti-cancer active substances can be remotely controlled and released on demand. Combining the abovementioned advantages, hydrogel materials have transformed into a hit in the field of cancer treatment, bringing hope to further increase the survival rate and quality of life of patients with cancer.
Generation and characterization of NGLY1 patient-derived midbrain organoids
Authors: Abbott Joshua , Tambe Mitali , Pavlinov Ivan , Farkhondeh Atena , Nguyen Ha Nam , Xu Miao , Pradhan Manisha , York Tate , Might Matthew , Baumgärtel Karsten , Rodems Steven , Zheng Wei
Published: February 2023

NGLY1 deficiency is an ultra-rare, autosomal recessive genetic disease caused by mutations in the NGLY1 gene encoding N-glycanase one that removes N-linked glycan. Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delay, motor disorder and liver dysfunction. To better understand the disease pathogenesis and the neurological symptoms of the NGLY1 deficiency we generated and characterized midbrain organoids using patient-derived iPSCs from two patients with distinct disease-causing mutations–one homozygous for p. Q208X, the other compound heterozygous for p. L318P and p. R390P and CRISPR generated NGLY1 knockout iPSCs. We demonstrate that NGLY1 deficient midbrain organoids show altered neuronal development compared to one wild type (WT) organoid. Both neuronal (TUJ1) and astrocytic glial fibrillary acid protein markers were reduced in NGLY1 patient-derived midbrain organoids along with neurotransmitter GABA. Interestingly, staining for dopaminergic neuronal marker, tyrosine hydroxylase, revealed a significant reduction in patient iPSC derived organoids. These results provide a relevant NGLY1 disease model to investigate disease mechanisms and evaluate therapeutics for treatments of NGLY1 deficiency.
Expression level of CD117 (KIT) on ovarian cancer extracellular vesicles correlates with tumor aggressiveness
Authors: Shnaider Polina V. , Petrushanko Irina Yu. , Aleshikova Olga I. , Babaeva Nataliya A. , Ashrafyan Lev A. , Borovkova Ekaterina I. , Dobrokhotova Julia E. , Borovkov Ivan M. , Shender Victoria O. , Khomyakova Elena
Published: February 2023

Ovarian cancer is known to be the most lethal malignancy among all gynecological cancers affecting a large number of women worldwide. The treatment of ovarian cancer is challenging due to the high recurrence rate of the disease and is further complicated by acquired chemoresistance. Most ovarian cancer deaths are the result of the metastatic spread of drug-resistant cells. The theory of cancer stem cells (CSC) suggests that both tumor initiation and progression are driven by a population of undifferentiated capable of self-renewal, tumor initiation and development of chemoresistance. The CD117 mast/stem cell growth factor receptor (KIT) is the most commonly used marker for ovarian CSCs. Here, we analyze the correlation between CD117 expression and histological tumor type in ovarian cancer cell lines (SK-OV-3 and MES-OV) and in small/medium extracellular vesicles (EVs) isolated from the urine of ovarian cancer patients. We have demonstrated that the abundance of CD117 on cells and EVs is correlated with tumor grade and therapy resistance status. Moreover, using small EVs isolated from ovarian cancer ascites, it was shown that recurrent disease is characterized by a much higher abundance of CD117 on EVs than primary tumor.
Languages and technologies in education at school and outside of school: Perspectives from young people in low-resource countries in Africa and Asia
Authors: Kukulska-Hulme Agnes , Giri Ram Ashish , Dawadi Saraswati , Devkota Kamal Raj , Gaved Mark
Published: February 2023

Disadvantaged young people in low-resource countries are less likely to complete their education or to progress to higher levels, which means that their upward mobility can be severely constrained. Versatile technologies such as smartphones, when combined with an ability to use the English language, can facilitate access to learning resources, thereby helping to support young people's education where the school facilities and local teaching resources are often insufficient and may reinforce existing inequalities. However, technology access and usage vary, and linguistic or other barriers to effective engagement are multifaceted. To gain a deeper understanding of the role of languages and technologies, our research project collected first-hand accounts of the educational experiences of marginalized young people aged 13–15, their parents and teachers in harder-to-reach urban and rural settings, in four low-income countries in Africa and Asia. The research investigated perspectives on the English language and use of technology in education in school and outside of school. Our findings provide original insights into local cultures of technology use and English language use in the context of young people's lived experiences. The paper covers young people's use of English and attitudes toward English alongside other languages in their local settings, and how they are learning with mobile digital devices at school, at home, outdoors, and in the homes of relatives, friends and neighbors. Relationships between languages and technologies are discussed, as well as the sustainability of English- and technology-mediated education in the countries in question, which will have broader applicability in other low-resource settings.
Pre-percutaneous coronary intervention sudden cardiac arrest in ST-elevation myocardial infarction: Incidence, predictors, and related outcomes
Authors: Machado Guilherme Pinheiro , Theobald Andre Luiz , de Araujo Gustavo Neves , Silveira Anderson Donelli da , Wainstein Rodrigo Vugman , Fracasso Julia Fagundes , Niches Matheus , Chies Angelo , Goncalves Sandro Cadaval , Pimentel Mauricio , Wainstein Marco Vugman
Published: February 2023

Background

ST-segment elevation myocardial infarction (STEMI) is a frequent cause of sudden cardiac arrest (SCA) and early percutaneous coronary intervention (PCI) is associated with increased survival. Despite constant improvements in SCA management, survival remains poor. We aimed to assess pre-PCI SCA incidence and related outcomes in patients admitted with STEMI.

Methods

This was a prospective cohort study of patients admitted with STEMI in a tertiary university hospital over 11  years. All patients were submitted to emergency coronary angiography. Baseline characteristics, details of the procedure, reperfusion strategies, and adverse outcomes were assessed. The primary outcome was in-hospital mortality. The secondary outcome was 1-year mortality after hospital discharge. Predictors of pre-PCI SCA was also assessed.

Results

During the study period 1,493 patients were included; the mean age was 61.1 years (±12), and 65.3% were male. Pre-PCI SCA was present in 133 (8.9%) patients. In-hospital mortality was higher in the pre-PCI SCA group (36.8% vs. 8.8%, p < 0.0001). In multivariate analysis, anterior MI, cardiogenic shock, age, pre-PCI SCA and lower ejection fraction remained significantly associated with in-hospital mortality. When we analyzed the interaction between pre-PCI SCA and cardiogenic shock upon admission there is a further increase in mortality risk when both conditions are present. For predictors of pre-PCI SCA, only younger age and cardiogenic shock remained significantly associated after multivariate analysis. Overall 1-year mortality rates were similar between pre-PCI SCA survivors and non-pre-PCI SCA group.

Conclusion

In a cohort of consecutive patients admitted with STEMI, pre-PCI SCA was associated with higher in-hospital mortality, and its association with cardiogenic shock further increases mortality risk. However, long-term mortality among pre-PCI SCA survivors was similar to non-SCA patients. Understanding characteristics associated with pre-PCI SCA may help to prevent and improve the management of STEMI patients.
High-resolution structural-functional substrate-trigger characterization: Future roadmap for catheter ablation of ventricular tachycardia
Authors: Stoks Job , Hermans Ben J. M. , Boukens Bas J. D. , Holtackers Robert J. , Gommers Suzanne , Kaya Yesim S. , Vernooy Kevin , Cluitmans Matthijs J. M. , Volders Paul G. A. , ter Bekke Rachel M. A.
Published: February 2023

Introduction

Patients with ventricular tachyarrhythmias (VT) are at high risk of sudden cardiac death. When appropriate, catheter ablation is modestly effective, with relatively high VT recurrence and complication rates. Personalized models that incorporate imaging and computational approaches have advanced VT management. However, 3D patient-specific functional electrical information is typically not considered. We hypothesize that incorporating non-invasive 3D electrical and structural characterization in a patient-specific model improves VT-substrate recognition and ablation targeting.

Materials and methods

In a 53-year-old male with ischemic cardiomyopathy and recurrent monomorphic VT, we built a structural-functional model based on high-resolution 3D late-gadolinium enhancement (LGE) cardiac magnetic resonance imaging (3D-LGE CMR), multi-detector computed tomography (CT), and electrocardiographic imaging (ECGI). Invasive data from high-density contact and pace mapping obtained during endocardial VT-substrate modification were also incorporated. The integrated 3D electro-anatomic model was analyzed off-line.

Results

Merging the invasive voltage maps and 3D-LGE CMR endocardial geometry led to a mean Euclidean node-to-node distance of 5 ± 2 mm. Inferolateral and apical areas of low bipolar voltage (<1.5 mV) were associated with high 3D-LGE CMR signal intensity (>0.4) and with higher transmurality of fibrosis. Areas of functional conduction delay or block (evoked delayed potentials, EDPs) were in close proximity to 3D-LGE CMR-derived heterogeneous tissue corridors. ECGI pinpointed the epicardial VT exit at ∼10 mm from the endocardial site of origin, both juxtaposed to the distal ends of two heterogeneous tissue corridors in the inferobasal left ventricle. Radiofrequency ablation at the entrances of these corridors, eliminating all EDPs, and at the VT site of origin rendered the patient non-inducible and arrhythmia-free until the present day (20 months follow-up). Off-line analysis in our model uncovered dynamic electrical instability of the LV inferolateral heterogeneous scar region which set the stage for an evolving VT circuit.

Discussion and conclusion

We developed a personalized 3D model that integrates high-resolution structural and electrical information and allows the investigation of their dynamic interaction during arrhythmia formation. This model enhances our mechanistic understanding of scar-related VT and provides an advanced, non-invasive roadmap for catheter ablation.
Artificial intelligence in coronary computed tomography angiography: Demands and solutions from a clinical perspective
Authors: Baeßler Bettina , Götz Michael , Antoniades Charalambos , Heidenreich Julius F. , Leiner Tim , Beer Meinrad
Published: February 2023

Coronary computed tomography angiography (CCTA) is increasingly the cornerstone in the management of patients with chronic coronary syndromes. This fact is reflected by current guidelines, which show a fundamental shift towards non-invasive imaging - especially CCTA. The guidelines for acute and stable coronary artery disease (CAD) of the European Society of Cardiology from 2019 and 2020 emphasize this shift. However, to fulfill this new role, a broader availability in adjunct with increased robustness of data acquisition and speed of data reporting of CCTA is needed. Artificial intelligence (AI) has made enormous progress for all imaging methodologies concerning (semi)-automatic tools for data acquisition and data post-processing, with outreach toward decision support systems. Besides onco- and neuroimaging, cardiac imaging is one of the main areas of application. Most current AI developments in the scenario of cardiac imaging are related to data postprocessing. However, AI applications (including radiomics) for CCTA also should enclose data acquisition (especially the fact of dose reduction) and data interpretation (presence and extent of CAD). The main effort will be to integrate these AI-driven processes into the clinical workflow, and to combine imaging data/results with further clinical data, thus - beyond the diagnosis of CAD- enabling prediction and forecast of morbidity and mortality. Furthermore, data fusing for therapy planning (e.g., invasive angiography/TAVI planning) will be warranted. The aim of this review is to present a holistic overview of AI applications in CCTA (including radiomics) under the umbrella of clinical workflows and clinical decision-making. The review first summarizes and analyzes applications for the main role of CCTA, i.e., to non-invasively rule out stable coronary artery disease. In the second step, AI applications for additional diagnostic purposes, i.e., to improve diagnostic power (CAC = coronary artery classifications), improve differential diagnosis (CT-FFR and CT perfusion), and finally improve prognosis (again CAC plus epi- and pericardial fat analysis) are reviewed.
Combining environmental and socioeconomic data to understand determinants of conflicts in Colombia
Authors: Fiandrino Stefania , Cattuto Ciro , Paolotti Daniela , Schifanella Rossano
Published: February 2023

Conflicts cause immense human suffering, violate human rights, and affect people's stability. Colombia is affected for decades by a high level of armed conflicts and violence. The political and socio-economic situation, drug trafficking in the Colombian economy, and natural disasters events affect the country and foster general violence. In this work, we aim to evaluate the role of the socioeconomic, political, financial, and environmental determinants of conflicts in the Colombian context. To achieve these aims, we apply a spatial analysis to explore patterns and identify areas that suffer from high levels of conflict. We investigate the role of determinants and their relationship with conflicts through spatial regression models. In this study, we do not consider only the entire Colombian territory, but we extend the analysis to a restricted area (Norte de Santander department) to explore the phenomena locally. Our findings indicate a possible diffusion process of conflicts and the presence of spillover effects among regions by comparing the two most known spatial regression models. As regards possible key drivers of conflicts, our results show that surprisingly socioeconomic variables present very little relationship with conflicts, while natural disasters and cocaine areas show a relevant impact on them. Despite some variables seeming to be the more informative to explain the process globally, they highlight a strong relationship for only a few specific areas while considering a local analysis. This result proves the importance of moving to a local investigation to strengthen our understanding and bring out additional interesting information. Our work emphasizes how the identification of key drivers of violence is crucial to have evidence to inform subnational governments and to support the decision-making policies that could assess targeted policy options.
Balancing the evidence: An update on analgesic use in rheumatic and musculoskeletal diseases
Authors: Huang Yun-Ting , McCarthy Craig , Jani Meghna
Published: February 2023

Pain management has been a challenging issue for people living with rheumatic and musculoskeletal diseases (RMDs) and health professionals for decades. Pharmacological treatments remain a core element of pain management of inflammatory arthritis and osteoarthritis. Yet balancing the benefits/harms in pain management within RMDs can be difficult to navigate due to limited effective options, and emerging adverse events in a population where individual risk is important to consider due to patient multimorbidity, immunosuppression and polypharmacy. Paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) analgesics are widely used among RMD patients, however both classes of drugs have been associated with new safety concerns in the last two decades. Perhaps as a result in combination with multifactorial influences, opioid prescribing has increased from the 2000s–2010s in the majority of RMD focussed studies, accompanied with a rising trend of long-term opioid use, despite limited evidence on efficacy. Gabapentinoids have also shown increasing trends more recently, despite an unclear role in chronic pain management for RMDs within current guidelines. Antidepressants are recommended as the first line of pharmacological treatment of chronic primary pain (e.g., fibromyalgia) by the latest National Institute for Health and Care Excellence (NICE) guideline released in April 2021. This concise narrative review will discuss pharmacological options for pain management, based on the latest evidence that includes the main analgesic drug classes: paracetamol, NSAIDs, opioids, antidepressants, and gabapentinoids. We will discuss the efficacy of these analgesics in RMDs and emerging safety concerns to enable more informed shared decisions with patients commencing such medications.
An explicit stable Q-compensated reverse time migration scheme for complex heterogeneous attenuation media
Authors: Li Songling , Shi Ying , Wang Weihong , Wang Ning , Song Liwei , Wang Yinfeng
Published: February 2023

Prestack reverse-time migration (RTM) is a popular imaging technique for complex geological conditions, since the amplitude attenuation and velocity dispersion are common in seismic recordings. To image attenuated seismic recordings accurately, a robust migration algorithm with a stable attenuation compensation approach should be considered. In the context of the Q-compensated RTM approach based on the decoupled fractional Laplacians (DFLs) viscoacoustic wave equation, amplitude compensation can be implemented by flipping the sign of the dissipation term. However, the non-physical magnification of image amplitude could lead to a well-known numerical instability problem. The explicit stabilization operator can rectify the amplitude attenuation and suppress the numerical instability. However, limited by the inconvenient mixed-domain operator, the average Q value rather than the real Q value is often used in the compensation operator, lowering the compensated accuracy of the migration image. To overcome this problem, we propose a novel explicit Q-compensation scheme. The main advantage of the proposed compensation operator is that its order is space-invariant, making it more suitable for handling complex heterogeneous attenuation media. Several two-dimensional (2D) and three-dimensional (3D) synthetic models are used to verify the superiority of the proposed approach in terms of amplitude fidelity and image resolution. Field data further demonstrates that our approach has potential applications and can greatly enhance the resolution of seismic images.
The association between distal symmetric polyneuropathy in diabetes with all-cause mortality – a meta-analysis
Authors: Vági Orsolya E. , Svébis Márk M. , Domján Beatrix A. , Körei Anna E. , Tesfaye Solomon , Horváth Viktor J. , Kempler Péter , Tabák Ádám Gy.
Published: February 2023

Background

Distal symmetric polyneuropathy (DSPN) is a common microvascular complication of both type 1 and 2 diabetes with substantial morbidity burden and reduced quality of life. Its association with mortality is equivocal.

Purpose

To describe the association between DSPN and all-cause mortality in people with diabetes and further stratify by the type of diabetes based on a meta-analysis of published observational studies.

Data Sources

We searched Medline from inception to May 2021.

Study Selection

Original data were collected from case-control and cohort studies that reported on diabetes and DSPN status at baseline and all-cause mortality during follow-up.

Data Extraction

was completed by diabetes specialists with clinical experience in neuropathy assessment.

Data Synthesis

Data was synthesized using random-effects meta-analysis. The difference between type 1 and 2 diabetes was investigated using meta-regression.

Results

A total of 31 cohorts (n=155,934 participants, median 27.4% with DSPN at baseline, all-cause mortality 12.3%) were included. Diabetes patients with DSPN had an almost twofold mortality (HR: 1.96, 95%CI: 1.68-2.27, I2 = 91.7%), I2 = 91.7%) compared to those without DSPN that was partly explained by baseline risk factors (adjusted HR: 1.60, 95%CI: 1.37-1.87, I2 = 78.86%). The association was stronger in type 1 compared to type 2 diabetes (HR: 2.22, 95%CI: 1.43-3.45). Findings were robust in sensitivity analyses without significant publication bias.

Limitations

Not all papers reported multiple adjusted estimates. The definition of DSPN was heterogeneous.

Conclusions

DSPN is associated with an almost twofold risk of death. If this association is causal, targeted therapy for DSPN could improve life expectancy of diabetic patients.
Emerging roles of histone deacetylases in adaptive thermogenesis
Authors: Zhou Ruonan , Cao Yue , Xiang Yingying , Fang Penghua , Shang Wenbin
Published: February 2023

Brown and beige adipose tissues regulate body energy expenditure through adaptive thermogenesis, which converts energy into heat by oxidative phosphorylation uncoupling. Although promoting adaptive thermogenesis has been demonstrated to be a prospective strategy for obesity control, there are few methods for increasing adipose tissue thermogenesis in a safe and effective way. Histone deacetylase (HDAC) is a category of epigenetic modifying enzymes that catalyzes deacetylation on both histone and non-histone proteins. Recent studies illustrated that HDACs play an important role in adipose tissue thermogenesis through modulating gene transcription and chromatin structure as well as cellular signals transduction in both deacetylation dependent or independent manners. Given that different classes and subtypes of HDACs show diversity in the mechanisms of adaptive thermogenesis regulation, we systematically summarized the effects of different HDACs on adaptive thermogenesis and their underlying mechanisms in this review. We also emphasized the differences among HDACs in thermogenesis regulation, which will help to find new efficient anti-obesity drugs targeting specific HDAC subtypes.
Allosteric modulation of G protein-coupled receptor signaling
Authors: Shen Siyuan , Zhao Chang , Wu Chao , Sun Suyue , Li Ziyan , Yan Wei , Shao Zhenhua
Published: February 2023

G protein-coupled receptors (GPCRs), the largest family of transmembrane proteins, regulate a wide array of physiological processes in response to extracellular signals. Although these receptors have proven to be the most successful class of drug targets, their complicated signal transduction pathways (including different effector G proteins and β-arrestins) and mediation by orthosteric ligands often cause difficulties for drug development, such as on- or off-target effects. Interestingly, identification of ligands that engage allosteric binding sites, which are different from classic orthosteric sites, can promote pathway-specific effects in cooperation with orthosteric ligands. Such pharmacological properties of allosteric modulators offer new strategies to design safer GPCR-targeted therapeutics for various diseases. Here, we explore recent structural studies of GPCRs bound to allosteric modulators. Our inspection of all GPCR families reveals recognition mechanisms of allosteric regulation. More importantly, this review highlights the diversity of allosteric sites and presents how allosteric modulators control specific GPCR pathways to provide opportunities for the development of new valuable agents.
Whole blood transcriptome analysis in dairy calves experimentally challenged with bovine herpesvirus 1 (BoHV-1) and comparison to a bovine respiratory syncytial virus (BRSV) challenge
Authors: O’Donoghue Stephanie , Earley Bernadette , Johnston Dayle , McCabe Matthew S. , Kim Jae Woo , Taylor Jeremy F. , Duffy Catherine , Lemon Ken , McMenamy Michael , Cosby S. Louise , Morris Derek W. , Waters Sinéad M.
Published: February 2023

Bovine herpesvirus 1 (BoHV-1), is associated with several clinical syndromes in cattle, among which bovine respiratory disease (BRD) is of particular significance. Despite the importance of the disease, there is a lack of information on the molecular response to infection via experimental challenge with BoHV-1. The objective of this study was to investigate the whole-blood transcriptome of dairy calves experimentally challenged with BoHV-1. A secondary objective was to compare the gene expression results between two separate BRD pathogens using data from a similar challenge study with BRSV. Holstein-Friesian calves (mean age (SD) = 149.2 (23.8) days; mean weight (SD) = 174.6 (21.3) kg) were either administered BoHV-1 inoculate (1 × 107/mL × 8.5 mL) (n = 12) or were mock challenged with sterile phosphate buffered saline (n = 6). Clinical signs were recorded daily from day (d) −1 to d 6 (post-challenge), and whole blood was collected in Tempus RNA tubes on d six post-challenge for RNA-sequencing. There were 488 differentially expressed (DE) genes (p < 0.05, False Discovery rate (FDR) < 0.10, fold change ≥2) between the two treatments. Enriched KEGG pathways (p < 0.05, FDR <0.05); included Influenza A, Cytokine-cytokine receptor interaction and NOD-like receptor signalling. Significant gene ontology terms (p < 0.05, FDR <0.05) included defence response to virus and inflammatory response. Genes that are highly DE in key pathways are potential therapeutic targets for the treatment of BoHV-1 infection. A comparison to data from a similar study with BRSV identified both similarities and differences in the immune response to differing BRD pathogens.
Current research and management of undifferentiated pleomorphic sarcoma/myofibrosarcoma
Authors: Sun Haitao , Liu Jilu , Hu Fangyuan , Xu Meng , Leng Ao , Jiang Feng , Chen Kefu
Published: February 2023

Undifferentiated pleomorphic sarcoma (UPS), once termed as malignant fibrous histiocytoma, has always been diagnosed exclusively in clinical practice because it lacks any defined resemblance to normal mesenchymal tissue. Although myxofibrosarcoma (MFS) has been separated from UPS due to its fibroblastic differentiation with myxoid stroma, UPS and MFS are still identified as a sarcoma group in terms of molecular landscapes. In this review article, we will describe the associated genes and signaling pathways involved in the process of sarcoma genesis and make a summary of conventional management, targeted therapy, immunotherapy, and some novel potential treatments of UPS/MFS. With the progressive advancements in medical technology and a better understanding about the pathogenic mechanism of UPS/MFS in the coming decades, new lights will be shed on the successful management of UPS/MFS.