bluuebunny/crossref_metadata_2025_split huggingface dataset:
Telemonitoring as a Telehealth strategy to contain the COVID-19 pandemic in a Brazilian capital
Authors: de Rezende Valter Luiz Moreira , Pereira Edna Regina Silva , Rocha Barbara Souza , da Silva Marta Maria Alves , Taleb Alexandre Chater 
Published: June 2023

Objective This study aimed to describe and analyze the process of creating and implementing telemonitoring services for COVID-19 cases, focusing on strengths and weaknesses. Methods A single case study incorporating qualitative and quantitative data using descriptive and exploratory approach was performed from 24 March 2020 to 24 March 2021 in a Brazilian capital city. Data collection took place through interviews, document analysis, and direct observation. Thematic content analysis was performed, and the results were presented in categories. Results The project included 512 health professionals, and 102,000 patients were monitored. The service was designed to break the chain of transmission, reinforce biosecurity measures, and provide comprehensive care to patients. Initially, two levels of monitoring were created. The first was a multidisciplinary health team that made calls to patients in the database. If the patients showed warning signs or aggravation, they were referred to the physician's monitoring referral service. Subsequently, a third level was created and staffed by psychologists. The main challenges were the number of patients notified, needing to update the contact forms as COVID-19 knowledge increased, and inconsistent telephone numbers recorded in the notifications. Conclusions Telemonitoring allowed signs of worsening COVID-19 to be identified, monitored thousands of people, and stopped infected patients from circulating. Adapting the existing telehealth structure was a viable, agile, and powerful strategy to reach a large number of people.
Crossing the Rivers by Touching the Stones: Alternative Approaches in Technical and Vocational Education and Training From the People's Republic of China and the Republic of Korea
Authors: Ha (哈巍) Wei , Yang (杨钋) Po , Choi (최영섭) Youngsup , Ra (나성섭) Sungsup , Hayashi (はやし　りょうたろう) Ryotaro , McCutcheon Conor 
Published: June 2023

Purpose This study aims to answer the following questions: (1) Why have attempts to transplant Western vocational education models failed? (2) Is there anything we can learn from the experiences of Eastern Asian countries when developing their own vocational education models? Design/Approach/Methods This study reviews the history of transplanting Western skill formation schemes into developing countries, an often-failed die-hard practice supported by both bilateral and multilateral donors. Findings Our findings suggest that developing countries should design their technical and vocational education and training systems based on their unique cultural, sociological, and economic contexts. It offers two alternative pathways based on the experiences of the People's Republic of China and the Republic of Korea. Originality/Value These East Asian examples could broaden the perspectives of policymakers in developing countries aspiring to develop functional skill formation schemes.
U.S. Preservice Teachers Learning With Multilingual Learners in Korea Through Educational Technology: Bringing Heteroglossic and Global Approaches to TESOL Teacher Education
Authors: Shin (신지혜) Ji Hye , Choi (최자영) Jayoung , Angay-Crowder Tuba , Khote (निहाल खोटे) Nihal 
Published: June 2023

Purpose This study aimed to explore how educational technology influenced a preparatory teacher education program using heteroglossic and global approaches. Design/Approach/Methods The researchers drew upon the theoretical framework of multilingual digital storytelling (MDST), which emphasizes the intercultural awareness attributes of multilingual learners (MLs) and takes a heteroglossic perspective in linguistic pedagogy. This qualitative case study examined the experiences of 11 U.S.-based preservice teachers (PSTs) and 12 MLs elementary students in Korea in the MDST project of a TESOL methods course. Findings The findings showed that PSTs and MLs enhanced their appreciation for educational technology, multilingualism, and intercultural awareness. Although the project aimed to decenter English as a hegemonic language, both PSTs and MLs maintained traditional discourses that privileged English over MLs’ home language and targeted literacy correctness in written English only, moving away from the heterogeneous goals of the course project. PSTs and MLs also faced challenges in navigating technological tools, which negatively affected their perception of the project. Originality/Value This study contributes to heteroglossic approaches in preparatory TESOL teacher education programs and improves the understanding of challenges in educational technology use for global multilingual exchanges to promote global citizenship.
Temporoparietal Fascia Flap for Complex Eyelid Reconstruction: A Case Series and Literature Review
Authors: Jain Arun , Rubin Peter A. D. , Cho Gerald J. , Francis Stacey H. 
Published: June 2023

Purpose: Large, complex eyelid defects involving all layers of the upper and/or lower eyelids still present a challenging problem. Temporoparietal fascia (TPF) flap can be used in some of these cases for reconstruction. The authors review the etiology, presentation, surgical technique, and results of this procedure and review the literature to date. Recommendations are made for optimizing surgical technique and guidelines for when to use the flap. Methods: The authors present a series of 4 cases of large eyelid defects reconstructed using the TPF flap. The etiology of these defects were: congenital, trauma, tumor and complication of maxillofacial surgery. Outcomes reviewed include functional and cosmetic results, and complications. Literature review of eyelid reconstruction using TPF flap is performed. Results: All patients achieved an acceptable cosmetic and functional outcome. There was resolution of both lagophthalmos and severe exposure keratopathy in all patients. Post-operative complication occurred in one patient and involved necrosis of the skin graft over the TPF flap. This was managed with a second skin graft several weeks later with satisfactory results. Conclusion: Trauma, tumors, congenital craniofacial anomalies and maxillofacial surgery for resection of sinus tumors can cause large eyelid defects. Small eyelid defects can be repaired with lid sharing procedures but for exceptionally large defects, these techniques become insufficient. TPF flap is an excellent option and can be used in these cases to achieve an acceptable cosmetic and functional outcome with preservation of the globe. TPF flap is a versatile option which can reconstruct a large eyelid defect with one procedure. Complications can be avoided with meticulous attention to detail. TPF flap is best suited for upper and/or lower eyelid defects which are categorized as Type III or Type IV.
How I approach the prevention and treatment of thrombotic complications in hospitalized patients
Authors: Akpan Imo J. , Hunt Beverley J. 
Published: June 2023

Abstract
This article uses case-based discussion to review prevention and management of thrombotic problems in hospitalized patients that involve a clinical hematologist. There is variation in the clinical hematologist’s role in thrombosis practice throughout the world, and we discuss this where indicated. Hospital-associated venous thromboembolism (VTE), or hospital-associated thrombosis (HAT), is the term to cover VTE occurring during admission and for 90 days postdischarge and is a common patient safety problem. HATs are the most common cause of VTE accounting for 55% to 60% of all VTE, with an estimated 10 million occurring globally. VTE risk assessment alongside evidence-based thromboprophylaxis reduces this risk significantly. Many hospitalized patients, especially older patients, use direct oral anticoagulants (DOACs), mainly to prevent stroke in atrial fibrillation. DOACs require perioperative management and may need urgent reversal. Other complex interventions such as extracorporeal membrane oxygenation which require anticoagulation are also discussed. Lastly, those with uncommon high-risk thrombophilias, especially those with antithrombin deficiency, produce unique challenges when hospitalized.
Inhibition of a new AXL isoform, AXL3, induces apoptosis of mantle cell lymphoma cells
Authors: Gelebart Pascal , Eriksen Gjerstad May , Benjaminsen Susanne , Han Jianhua , Karlsen Ida , Safont Mireia Mayoral , Leitch Calum , Fandalyuk Zinayida , Popa Mihaela , Helgeland Lars , Papp Bela , Baran-Marszak Fanny , McCormack Emmet 
Published: June 2023

Abstract
Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma having a poor overall survival that is in need for the development of new therapeutics. In this study, we report the identification and expression of a new isoform splice variant of the tyrosine kinase receptor AXL in MCL cells. This new AXL isoform, called AXL3, lacks the ligand-binding domain of the commonly described AXL splice variants and is constitutively activated in MCL cells. Interestingly, functional characterization of AXL3, using CRISPR inhibition, revealed that only the knock down of this isoform leads to apoptosis of MCL cells. Importantly, pharmacological inhibition of AXL activity resulted in a significant decrease in the activation of well-known proproliferative and survival pathways activated in MCL cells (ie, β-catenin, Ak strain transforming, and NF-κB). Therapeutically, preclinical studies using a xenograft mouse model of MCL indicated that bemcentinib is more effective than ibrutinib in reducing the tumor burden and to increase the overall survival. Our study highlights the importance of a previously unidentified AXL splice variant in cancer and the potential of bemcentinib as a targeted therapy for MCL.
Loss of miR-144/451 alleviates β-thalassemia by stimulating ULK1-mediated autophagy of free α-globin
Authors: Keith Julia , Christakopoulos Georgios E. , Fernandez Alfonso G. , Yao Yu , Zhang Jingjing , Mayberry Kalin , Telange Rahul , Sweileh Razan B. A. , Dudley Michael , Westbrook Camilla , Sheppard Heather , Weiss Mitchell J. , Lechauve Christophe 
Published: June 2023

Abstract
Most cells can eliminate unstable or misfolded proteins through quality control mechanisms. In the inherited red blood cell disorder β-thalassemia, mutations in the β-globin gene (HBB) lead to a reduction in the corresponding protein and the accumulation of cytotoxic free α-globin, which causes maturation arrest and apoptosis of erythroid precursors and reductions in the lifespan of circulating red blood cells. We showed previously that excess α-globin is eliminated by Unc-51–like autophagy activating kinase 1 (ULK1)-dependent autophagy and that stimulating this pathway by systemic mammalian target of rapamycin complex 1 (mTORC1) inhibition alleviates β-thalassemia pathologies. We show here that disrupting the bicistronic microRNA gene miR-144/451 alleviates β-thalassemia by reducing mTORC1 activity and stimulating ULK1-mediated autophagy of free α-globin through 2 mechanisms. Loss of miR-451 upregulated its target messenger RNA, Cab39, which encodes a cofactor for LKB1, a serine-threonine kinase that phosphorylates and activates the central metabolic sensor adenosine monophosphate–activated protein kinase (AMPK). The resultant enhancement of LKB1 activity stimulated AMPK and its downstream effects, including repression of mTORC1 and direct activation of ULK1. In addition, loss of miR-144/451 inhibited the expression of erythroblast transferrin receptor 1, causing intracellular iron restriction, which has been shown to inhibit mTORC1, reduce free α-globin precipitates, and improve hematological indices in β-thalassemia. The beneficial effects of miR-144/451 loss in β-thalassemia were inhibited by the disruption of Cab39 or Ulk1 genes. Together, our findings link the severity of β-thalassemia to a highly expressed erythroid microRNA locus and a fundamental, metabolically regulated protein quality control pathway that is amenable to therapeutic manipulation.
The genesis of human hematopoietic stem cells
Authors: Calvanese Vincenzo , Mikkola Hanna K. A. 
Published: June 2023

Abstract
Developmental hematopoiesis consists of multiple, partially overlapping hematopoietic waves that generate the differentiated blood cells required for embryonic development while establishing a pool of undifferentiated hematopoietic stem cells (HSCs) for postnatal life. This multilayered design in which active hematopoiesis migrates through diverse extra and intraembryonic tissues has made it difficult to define a roadmap for generating HSCs vs non–self-renewing progenitors, especially in humans. Recent single-cell studies have helped in identifying the rare human HSCs at stages when functional assays are unsuitable for distinguishing them from progenitors. This approach has made it possible to track the origin of human HSCs to the unique type of arterial endothelium in the aorta-gonad-mesonephros region and document novel benchmarks for HSC migration and maturation in the conceptus. These studies have delivered new insights into the intricate process of HSC generation and provided tools to inform the in vitro efforts to replicate the physiological developmental journey from pluripotent stem cells via distinct mesodermal and endothelial intermediates to HSCs.
Pembrolizumab plus vorinostat induces responses in patients with Hodgkin lymphoma refractory to prior PD-1 blockade
Authors: Mei Matthew , Chen Lu , Godfrey James , Song Joo , Egelston Colt , Puverel Sandrine , Budde L. Elizabeth , Armenian Saro , Nikolaenko Liana , Nwangwu Mary , Guo Weihua , Gao Lei , Lee Peter , Chen Robert , Daniels Shari , Kennedy Neena , Peters Lacolle , Zain Jasmine , Rosen Steven , Forman Stephen , Popplewell Leslie , Kwak Larry , Herrera Alex F. 
Published: June 2023

Abstract
This phase 1 study evaluated the addition of vorinostat to pembrolizumab in patients with relapsed/refractory (RR) classical Hodgkin lymphoma (cHL), diffuse large B-cell lymphoma, and follicular lymphoma. We report the results in cases of cHL. Adult patients with RR cHL who had received ≥1 prior lines of therapy and were ineligible for transplantation were treated in a dose-escalation cohort with 2 dose levels (DLs) and then on an expansion cohort at the recommended phase 2 dose (RP2D) in 21-day cycles. Vorinostat 100 mg twice a day (DL1) and 200 mg twice a day (DL2) was administered orally from days 1 to 5 and 8 to 12; all patients received pembrolizumab 200 mg IV every 3 weeks. The primary end point was safety and determination of RP2D. In total, 32 patients with cHL were enrolled, including 30 at DL2 (RP2D); 78% had received prior anti–programmed cell death 1 (anti–PD-1) therapy, and 56% were PD-1 refractory. Grade ≥3 adverse events (AEs) included hypertension (9%), neutropenia (9%), hypophosphatemia (9%), thrombocytopenia (6%), and lymphopenia (6%). Immune-related AEs included grade 1 or 2 thyroiditis (13%), grade 1 rash (6%), and grade 3 esophagitis/duodenitis (3%). The overall response rate (ORR) was 72% and complete response (CR) rate was 34%. Patients refractory to prior PD-1 blockade (n = 18) had ORR and CR rates of 56% and 11%, respectively. Pembrolizumab and vorinostat was well tolerated with a high ORR rate in RR cHL including in anti–PD-1–refractory disease. This trial was registered at www.clinicaltrials.gov as #NCT03150329.
YBX1 as an oncogenic factor in T-cell acute lymphoblastic leukemia
Authors: Li Huan , Zhang Danlan , Fu Qiuxia , Wang Shang , Wang Zhongyuan , Zhang Xin , Chen Xin , Zhu Xiaoyu , An Na , Chen Yun , Zhou Liang , Lu Desheng , Zhao Na 
Published: June 2023

Abstract
Y-box-binding protein 1 (YBX1), a member of the RNA-binding protein family, is a critical regulator of cell survival in various solid tumors and acute myeloid leukemia. However, the function of YBX1 in T-cell acute lymphoblastic leukemia (T-ALL) remains elusive. Here, we found that YBX1 was upregulated in patients with T-ALL, T-ALL cell lines, and NOTCH1-induced T-ALL mice. Furthermore, depletion of YBX1 dramatically reduced cell proliferation, induced cell apoptosis, and induced G0/G1 phase arrest in vitro. Moreover, YBX1 depletion significantly decreased the leukemia burden in the human T-ALL xenograft and NOTCH1-induced T-ALL mice model in vivo. Mechanistically, downregulation of YBX1 markedly inhibited the expression of total AKT serine/threonine kinase (AKT), p-AKT, total extracellular signal-regulated kinase (ERK), and p-ERK in T-ALL cells. Taken together, our results uncovered a critical role of YBX1 in the leukemogenesis of T-ALL, which may have great potential as a biomarker and therapeutic target in T-ALL.
Phase 1/2 study of sorafenib added to cladribine, high-dose cytarabine, G-CSF, and mitoxantrone in untreated AML
Authors: Halpern Anna B. , Rodríguez-Arbolí Eduardo , Othus Megan , Garcia Kelsey-Leigh A. , Percival Mary-Elizabeth M. , Cassaday Ryan D. , Oehler Vivian G. , Becker Pamela S. , Appelbaum Jacob S. , Abkowitz Janis L. , Orozco Johnnie J. , Keel Siobán B. , Hendrie Paul C. , Scott Bart L. , Ghiuzeli M. Cristina , Estey Elihu H. , Walter Roland B. 
Published: June 2023

Abstract
The multikinase inhibitor sorafenib improves event-free survival (EFS) when used with 7 + 3 in adults with newly-diagnosed acute myeloid leukemia (AML), irrespective of the FLT3-mutation status. Here, we evaluated adding sorafenib to cladribine, high-dose cytarabine, granulocyte colony–stimulating factor, and mitoxantrone (CLAG-M) in a phase 1/2 trial of 81 adults aged ≤60 years with newly diagnosed AML. Forty-six patients were treated in phase 1 with escalating doses of sorafenib and mitoxantrone. No maximum tolerated dose was reached, and a regimen including mitoxantrone 18 mg/m2 per day and sorafenib 400 mg twice daily was declared the recommended phase 2 dose (RP2D). Among 41 patients treated at RP2D, a measurable residual disease–negative complete remission (MRD– CR) rate of 83% was obtained. Four-week mortality was 2%. One-year overall survival (OS) and EFS were 80% and 76%, without differences in MRD– CR rates, OS, or EFS between patients with or without FLT3-mutated disease. Comparing outcomes using CLAG-M/sorafenib with those of a matched cohort of 76 patients treated with CLAG-M alone, multivariable-adjusted survival estimates were improved for 41 patients receiving CLAG-M/sorafenib at RP2D (OS: hazard ratio,0.24 [95% confidence interval, 0.07-0.82]; P = .023; EFS: hazard ratio, 0.16 [95% confidence interval, 0.05-0.53]; P = .003). Benefit was limited to patients with intermediate-risk disease (univariate analysis: P = .01 for OS; P = .02 for EFS). These data suggest that CLAG-M/sorafenib is safe and improves OS and EFS relative to CLAG-M alone, with benefits primarily in patients with intermediate-risk disease. The trial was registered at www.clinicaltrials.gov as #NCT02728050.
CMOS compatible 2T pixel for on-wafer in-situ EUV detection
Authors: Lin Wei-Hwa , Huang Han-Lin , Wu Pin-Jiun , Lin Chrong-Jung , King Ya-Chin 
Published: June 2023

AbstractA novel 2-transistor (2T) pixel EUV detector is proposed and demonstrated by advanced CMOS technology. The proposed 2T detector also exhibits high spectral range (< 267 nm) and spatial resolution (67 μm) with high stability and CMOS Compatibility. The compact 2T EUV detector pixels arranged in a test array are capable of on-wafer recording the 2D EUV flux distribution without any external power. The compact 2T EUV detector pixels arranged in a test array are capable of on-wafer recording the 2D EUV flux distribution without any external power. Through proper initialization process, EUV induced discharging mechanism is fully investigated and an EUV induced electron emission efficiency model is established. Finally, a 2D array for in-situ EUV detection is demonstrated to precisely reflect the pattern projected on the chip/wafer surface.
Janus Kinase 3 phosphorylation and the JAK/STAT pathway are positively modulated by follicle-stimulating hormone (FSH) in bovine granulosa cells
Authors: Zareifard Amir , Beaudry Francis , Ndiaye Kalidou 
Published: June 2023

AbstractJanus kinase 3 (JAK3) is a member of the JAK family of tyrosine kinase proteins involved in cytokine receptor-mediated intracellular signal transduction through the JAK/STAT signaling pathway. JAK3 was previously shown as differentially expressed in granulosa cells (GC) of bovine pre-ovulatory follicles suggesting that JAK3 could modulate GC function and activation/inhibition of downstream targets. We used JANEX-1, a JAK3 inhibitor, and FSH treatments and analyzed proliferation markers, steroidogenic enzymes and phosphorylation of target proteins including STAT3, CDKN1B/p27Kip1 and MAPK8IP3/JIP3. Cultured GC were treated with or without FSH in the presence or not of JANEX-1. Expression of steroidogenic enzyme CYP11A1, but not CYP19A1, was upregulated in GC treated with FSH and both were significantly decreased when JAK3 was inhibited. Proliferation markers CCND2 and PCNA were reduced in JANEX-1-treated GC and upregulated by FSH. Western blots analyses showed that JANEX-1 treatment reduced pSTAT3 amounts while JAK3 overexpression increased pSTAT3. Similarly, FSH treatment increased pSTAT3 even in JANEX-1-treated GC. UHPLC-MS/MS analyses revealed phosphorylation of specific amino acid residues within JAK3 as well as CDKN1B and MAPK8IP3 suggesting possible activation or inhibition post-FSH or JANEX-1 treatments. We show that FSH activates JAK3 in GC, which could phosphorylate target proteins and likely modulate other signaling pathways involving CDKN1B and MAPK8IP3, therefore controlling GC proliferation and steroidogenic activity.