bluuebunny/crossref_metadata_2025 huggingface dataset:
Bandgap and wave attenuation optimization of tetra-chiral metamaterial using PSO algorithm
Authors: Tikani Vahid , Ziaei-Rad Saeed , Moosavi Hassan
Published: June 2023

The development of vibration suppression systems with desired efficiency and low cost is one of the significant challenges in engineering. In this study, a parametric lattice model is considered to analyze the wave mitigation features in the metamaterial based on a tetra-chiral topology of the periodic cell equipped with internal resonators. Bloch wave theorem and finite element method are employed to explore the bandgap of the structure and its wave mitigation features. Since the unit cell geometry can be designed to open and shift bandgaps, particle swarm optimization algorithm is used to find the largest possible gap in the desired frequency range. The optimization method is programmed using MATLAB combined with an in-house finite element solver, considering the parameters' ranges to ensure geometric compatibility. In all studied cases, the optimized geometry leads to superior vibration suppression and larger complete bandgaps.
Colonic mucosal diffuse congestion associated with Osimertinib
Authors: Ren Xiao-Jun , Lei Ming-Hong , Cheng Ying-Xia , Luo Yun
Published: June 2023

Introduction

Non-small cell lung cancer (NSCLC) is the most common histological subtype of lung cancer. Osimertinib has been recommended as first-line treatment of advanced NSCLC with EGFR mutations. Previous studies have only reported cases of gastrointestinal bleeding due to Erlotinib and gefitinib, but to date, always no cases of gastrointestinal bleeding due to Osimertinib have been reported.

Case Report

We report a case of a female patient with NSCLC with EFGR mutation. After 1.5 years of treatment with Osimertinib, a colonoscopy showed diffuse congestion of the colonic mucosa.

Management and Outcome

The patient’s symptoms of blood in the stool disappeared, after stopping Osimertinib and giving mucosal protection treatment for 1 week.

Discussion

Osimertinib may have contributed to gastrointestinal bleeding because no recurrent bleeding was observed after discontinuation of treatment. Physicians and patients should be aware that osimertinib may increase the risk of gastrointestinal bleeding.
Expanded stereoscopy: Alternative aesthetics for artistic expression in 3D films
Authors: Hattler Max , Cheung Terrie Man-Chi
Published: June 2023

3D cinema has been defined by a quest for increased realism and immersion and the recreation of realistic depth perception. However, instead of merely seeing stereo vision as a visual enhancement of 2D cinema, some contemporary moving image artists explore unique types of perceptual illusions and ambiguous perceptions in their stereoscopic films. Through the experimental stereoscopic films of Blake Williams and Kazuhiro Goshima, and interviews with the artists, this paper focuses on the artists’ motivations behind their works and their intended impacts on audiences. Drawing mainly on aesthetic, perceptual and technical perspectives, the paper examines how artists use experimental approaches to stereoscopic imaging and theorises the resulting aesthetics and perceptual forms for S3D films.
Monkeypox outbreak: Psychological distance, risk perception, and support for risk mitigation
Authors: Yang Janet Z , Dong Xinxia
Published: June 2023

Building on construal level theory, results from a survey based on a nationally representative sample of U.S. adults ( N = 1000) indicate an indirect effect of social distance and temporal distance perception on emotional response, policy support, and vaccination intention through risk perception. This study also reveals that social dominance orientation contributes to perceived psychological distance of the monkeypox outbreak. These results suggest that communication about a public health crisis such as monkeypox needs to emphasize its broader community impact, rather than focusing on the primary population affected.
A missing piece in the debate about naked statistical evidence
Authors: Giles Alejo Joaquín
Published: June 2023

In this article, I want to draw attention to a class of cases that is ignored, sometimes deliberately, in the debate about the probative value of naked statistical evidence (NSE). I am talking about cases in which ‘statistical’ propositions are the principal subject of proof. I will show that they are legally relevant and remain immune to the arguments against NSE put forward in the evidence literature. All of this, I will conclude, makes it convenient to pay more attention to them. First, I will highlight the hypothetical cases discussed in the NSE debate and the kind of propositions that must be proved in them: ‘singular’ propositions. Second, I will show that there are other cases, also relevant in legal systems, in which the principal factum probandum are ‘statistical’ propositions. Third, I will argue that this difference is substantial for the NSE debate.
Moral and ethical conduct (and their absence) in groups, politics, and society: Introduction to the special issue
Authors: Pagliaro Stefano , Gkinopoulos Theofilos , Pacilli Maria Giuseppina
Published: June 2023

Morality—broadly defined as the distinction between “right” and “wrong” ways to behave—represents one of the most important and appealing inquiries within the realm of social sciences. Past research has consistently shown that morality dominates social perception and serves regulatory functions that help individuals define their social identities, regulate intragroup dynamics, and shape intergroup and political relations. We introduce a special issue that presents 10 articles that center on the theme of morality as a tool for regulating social life at different levels. These articles can be broadly organized into three interrelated macrothemes: intragroup processes, intergroup processes, and political processes. The research studies described in the special issue highlight the societal and political implications of morality; in particular, these studies allow us to map out particular strategies and policy recommendations aimed at diminishing the negative and enhancing the positive implications of morality, and at avoiding moral conflicts.
Dementia in South Africa: A Situational Analysis
Authors: Jacobs Roxanne , Schneider Marguerite , Farina Nicolas , du Toit Petra , Docrat Sumaiyah , Comas-Herrera Adelina , Knapp Martin
Published: June 2023

There is a need in South Africa to understand the status of available care and support to strengthen responses to dementia. This study provides a situational analysis of the current provisions of health, care and support for older persons, people living with dementia and their families in South Africa. It is a first step towards describing the landscape of needs and services available, and provides an evidence base to inform priority-setting for strengthening responses to dementia in South Africa. This situational analysis was conducted in three phases: (1) a desk review guided by a comprehensive topic guide which includes the WHO’s Global Dementia Observatory indicators; (2) multi-sectoral stakeholder interviews to verify the secondary sources used in the desk review, and to identify gaps and opportunities in policy and service provisions; and (3) a SWOT-analysis examining the strengths, weaknesses, opportunities and threats in current care and support provisions in South Africa. Our findings highlight the gaps and opportunities with current service provision and show how structural factors create barriers to diagnosis, support, and care. There is an urgent need for intersectoral policy responses to support and strengthen current health, social care, and long-term support systems so that people living with dementia and their families can live and age well. This paper forms part of a larger study on strengthening responses to dementia (The STRIDE project).
Antioxidant Potential and Improvement Activities ofSterculia setigeraDelile on Insulin Resistance in Type 2 Diabetic Rats Induced by High-Fat Diet and Low Dose of Streptozotocin
Authors: Tchoubou Zacharie , Koubala Benoît Bargui , Ndjonka Dieudonné
Published: June 2023

Background

S. setigera is widely used in traditional medicine throughout the world. Ethnobotanical surveys have revealed its use to handle diabetes. This present research investigated the antioxidant potential and improvement activities of S. setigera Delile on insulin resistance in type 2 diabetic rats.

Methods

Male rats fed high-fat diet for 6 weeks followed by a single-dose intraperitoneal injection of streptozotocin (35 mg/kg) induced hyperglycemia. 72 hours after injection of streptozotocin, diabetic rats received treatment for 21 days. Fasting blood glucose was measured. Serum biochemical and hepatic biomarkers were evaluated. A hepatic histological study was performed. Oxidative stress biomarkers were assessed in liver.

Results

Doses of 200 and 400 mg/kg reduced the blood glucose with the reduction index of 53.75 and 62.1%, respectively. There was also good improvement in lipid profile and insulin. The dose of 400 mg/kg better reduced subcutaneous fat mass with a difference in reduction index (1.5 to 5.8%). The extract resulted in a decrease in malondialdehyde levels and an increase in catalase activities. The extract showed significant inhibitory potential towards α-amylase 18.78% to 55.91% and α-glucosidase 23.91% to 67.76%.

Conclusion

S. setigera extract could thus reverse insulin resistance and oxidative stress in type 2 diabetic rats induced.
Duloxetine prevents bortezomib and paclitaxel large-fiber chemotherapy-induced peripheral neuropathy (LF-CIPN) in sprague dawley rats
Authors: Mansooralavi Niloufar , Khomula Eugen V , Levine Jon D
Published: June 2023

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating, treatment-limiting, side-effect of several classes of chemotherapy drugs. While negatively impacting oncology patients’ quality of life, chemotherapy-induced large-fiber (LF) neuropathy is amongst the least well understood components of CIPN, and one for which there is currently no established therapy. Preliminary clinical observations have led to the suggestion that Duloxetine, which is used for the treatment of pain associated with small-fiber CIPN (SF-CIPN), may be effective against LF-CIPN. In the present experiments we developed a model of LF-CIPN and studied the effect of Duloxetine on LF-CIPN induced by two neurotoxic chemotherapy agents: the proteasome inhibitor, Bortezomib, a first-line treatment of multiple myeloma; and, the anti-microtubule taxane, Paclitaxel, used in the treatment of solid tumors. Since there are currently no models for selective the study of LF-CIPN, our first aim was to establish a pre-clinical model in the rat. LF-CIPN was evaluated with the Current Perception Threshold (CPT) assay, which uses a high frequency (1000 Hz) electrical stimulus protocol that selectively activates large-fiber myelinated afferents. Our second aim was to use this model to test the hypothesis that Duloxetine can prevent LF-CIPN. We report that Bortezomib and Paclitaxel induce elevation of CPT, compatible with loss of large-fiber function, which are prevented by Duloxetine. Our findings support the clinical observation that Duloxetine may be an effective treatment for the large-fiber CIPN. We also suggest that CPT could be used as a biomarker for LF-CIPN in patients receiving neurotoxic chemotherapy.
Outcomes of patients with pre-existing disability managed by mobile stroke units: A sub-analysis of the BEST-MSU study
Authors: Pirlog Bianca O , Jacob Asha P , Rajan Suja S , Yamal Jose-Miguel , Parker Stephanie A , Wang Mengxi , Bowry Ritvij , Czap Alexandra , Bratina Patti L , Gonzalez Michael O , Singh Noopur , Zou Jinhao , Gonzales Nicole R , Jones William J , Alexandrov Anne W , Alexandrov Andrei V , Navi Babak B , Nour May , Spokoyny Ilana , Mackey Jason , Silnes Kelly , Fink Matthew E , Pisarro Sherman Carla , Willey Josh , Saver Jeffrey L , English Joey , Barazangi Nobl , Ornelas David , Volpi Jay , PV Rao Chethan , Griffin Laura , Persse David , Grotta James C
Published: June 2023

Background:

Few data exist on acute stroke treatment in patients with pre-existing disability (PD) since they are usually excluded from clinical trials. A recent trial of mobile stroke units (MSUs) demonstrated faster treatment and improved outcomes, and included PD patients.

Aim:

To determine outcomes with tissue plasminogen activator (tPA), and benefit of MSU versus management by emergency medical services (EMS), for PD patients.

Methods:

Primary outcomes were utility-weighted modified Rankin Scale (uw-mRS). Linear and logistic regression models compared outcomes in patients with versus without PD, and PD patients treated by MSU versus standard management by EMS. Time metrics, safety, quality of life, and health-care utilization were compared.

Results:

Of the 1047 tPA-eligible ischemic stroke patients, 254 were with PD (baseline mRS 2–5) and 793 were without PD (baseline mRS 0–1). Although PD patients had worse 90-day uw-mRS, higher mortality, more health-care utilization, and worse quality of life than non-disabled patients, 53% returned to at least their baseline mRS, those treated faster had better outcome, and there was no increased bleeding risk. Comparing PD patients treated by MSU versus EMS, 90-day uw-mRS was 0.42 versus 0.36 (p = 0.07) and 57% versus 46% returned to at least their baseline mRS. There was no interaction between disability status and MSU versus EMS group assignment (p = 0.67) for 90-day uw-mRS.

Conclusion:

PD did not prevent the benefit of faster treatment with tPA in the BEST-MSU study. Our data support inclusion of PD patients in the MSU management paradigm.
Uncertainty quantification analysis of Reynolds-averaged Navier–Stokes simulation of spray swirling jets undergoing vortex breakdown
Authors: Liberatori Jacopo , Galassi Riccardo M. , Valorani Mauro , Ciottoli Pietro P.
Published: June 2023

The computational fluid dynamics-based design of next-generation aeronautical combustion chambers is challenging due to many geometrical and operational parameters to be optimized and several sources of uncertainty that arise from numerical modeling. The present work highlights the potential benefits of exploiting Bayesian uncertainty quantification at the preliminary design stage. A prototypical configuration of an acetone/air spray swirling jet is investigated through an Eulerian–Lagrangian method under non-reactive conditions. Two direct numerical simulations (DNSs) provide reference data, coping with different vortex breakdown states. Consequently, a set of Reynolds-averaged Navier–Stokes simulations is conducted. Polynomial chaos expansion (PCE) is adopted to propagate the uncertainty associated with the spray dispersion model and the turbulent Schmidt number, delivering confidence intervals and the sensitivity of the output variance to each uncertain input. Consequently, the most significant sources of modeling uncertainty may be identified and eventually removed via a calibration procedure, thus making it possible to carry out a combustion chamber optimization process that is no longer affected by numerical biases. The uncertainty quantification analysis in the current study demonstrates that the spray dispersion model slightly affects the fuel vapor spatial distribution under vortex breakdown flow conditions, compared with the output variance induced by the selection of the turbulent Schmidt number. As a result, additional high-fidelity experimental and numerical campaigns should exclusively address the development of an ad hoc model characterizing the spatial distribution of the latter in the presence of vortex breakdown phenomenology, discarding any effort to improve the spray dispersion formulation.
Clinical scenarios-based guide for tofacitinib in rheumatoid arthritis
Authors: Mortezavi Mahta , Mysler Eduardo F.
Published: June 2023

Tofacitinib was the first Janus kinase inhibitor to be approved for the treatment of rheumatoid arthritis (RA), and there is a large body of data to inform the efficacy and safety of this drug for patients at different places in their treatment journeys and with diverse demographics and characteristics. Here, we summarize tofacitinib clinical efficacy and safety data from some clinical trials, post hoc analyses, and real-world studies, which provide evidence of the efficacy of tofacitinib in treating patients with RA at various stages of their treatment journeys, and with differentiating baseline characteristics, such as age, gender, race, and body mass index. In addition, we review the safety data available from different patient subpopulations in the tofacitinib clinical development program, real-world data, and findings from the ORAL Surveillance post-marketing safety study that included patients aged ⩾50 years with pre-existing cardiovascular risk factors. The available efficacy and safety data in these subpopulations can enable better discussions between clinicians and patients to guide informed decision-making and individualized patient care.
“Governing the urban commons”: DLT, institutions, and citizens in perspective
Authors: Nguyen Long Le Anh , Graaf Shenja van der , Votsis Athanasios
Published: June 2023

Borrowing from insights produced in urban planning, media and governance studies thereby leveraging the Ostrom-nian ideas of institutions and polycentricity, this paper examines how to govern commons in the smart city. It offers a reflection upon whether Distributed Ledger Technologies (DLTs) could be a key notion for the commons discourse which centers around stakeholders, self-organization, and a rights-based framework. By decentralizing ledgers and enabling the interoperability of the various interfaces, DLTs make records more accessible, exchanges more transparent, and reduce costs while increasing efficiency, and permit automation, therefore commoning interactions both offline and online are facilitated. We argue that the use of DLTs to preserve the spatiotemporal integrity of key urban spaces is a common value question that needs to be elucidated or renegotiated in order to provide any useful guidance to DLTs integrity-preserving potential. In doing so, we draw attention to DLT-based urban commons and urban governance, and point to inherent incompatibilities that may lead to radical and not-so-smooth changes in urban institutions, while providing a way of thinking which can move the smart city closer towards a values-centered process and away from a preoccupation with technology and efficiency.
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.
The Internet’s Town Square? A Critical Discourse Analysis of Parler’s “Past Imaginary”
Authors: Cowls Josh , Ma Cindy
Published: June 2023

The discursive construction of sociotechnical imaginaries by the leaders of platform companies can help legitimate their platforms, shaping how they are perceived and ultimately regulated. Scholars have identified the construction of “future imaginaries” by large platform companies such as Meta—but do smaller platforms also seek to construct imaginaries, and if so, what form do they take? In this article we undertake a critical discourse analysis of statements by John Matze, co-founder and CEO of the fringe social media platform Parler, that garnered media coverage in 2020. Parler gained significant popularity among US right-wing users during 2020, before it was removed from Apple and Google’s app stores in January 2021 following the riot at the US Capitol. Using Van Leeuwen’s framework for discursive legitimation, we analyze a curated dataset of 186 news articles to identify the legitimating themes that Matze invoked in media coverage of Parler in 2020. We find that Matze foregrounded free expression, and with it the vision of Parler as a “town square,” which can be seen as an attempt to legitimate the fledgling platform. However, this discursive legitimation must be understood in the context of Parler’s base of predominantly US right-wing users, many of whom turned to Parler because of the perceived “bias” and “censorship” of mainstream platforms. We argue that, in contrast to the future imaginaries constructed for large platform companies such as Meta, Matze’s discursive strategy constructed an imaginary that was fundamentally retrograde. Parler’s “past imaginary” resembles efforts by far-right groups to justify and legitimate hate speech in increasingly platformized societies.
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.
Violence against a backdrop of colours? Ethnographic insights into tensions between urban transformation and ongoing violence in marginalised neighbourhoods
Authors: Griffin Alba , Young Alexandra
Published: June 2023

Since the early 2000s, the two largest cities in Colombia have been lauded as success stories of urban transformation. However, there is a tension between urban transformation narratives disseminated in international media and political discourse, and the realities of ongoing violence and insecurity. Drawing on ethnographic research following creative arts projects, this article offers empirical detail on how people negotiate this tension in marginalised urban neighbourhoods, which are often the most affected by overlapping forms of violence while being key sites of transformation policies. Through in-depth interviews and participant observation in Bogotá and Medellín, we show the complexities of how grassroots creative projects both mobilise transformation politics and negotiate violence in everyday life. By focusing on the local scale, we consider both the important gains that have been made since urban transformation became a key tenet of local government policy, particularly around challenging stigma, and the challenges that local populations continue to face. Ultimately, we argue that the experiences of the creative organisations we speak to reflect the need to negotiate ongoing structural violence and fluctuating support from the state. In contrast to depoliticised transformation narratives, this has implications for understanding the state’s role in the reproduction of violence in everyday life and appreciating the limitations of aesthetic transformation in marginalised urban communities.
Reclaimed ecotones in the climate change era:A long-durée framing of urban expansion in Mumbai, Amsterdam, New York, and Tokyo
Authors: Yıldız Şevin
Published: June 2023

Transition ecologies, namely ecotones, are where life started. Deltas, estuaries, bayous, and wetlands are places where different ecosystems merge and evolutionary processes take place. This paper explores three time periods in four coastal cities to look at the relationship between environmental values and urban expansionist paradigms through reclamation projects. It argues that these thresholds, occurring contemporaneously in expanding metropolitan regions, correspond to changing conceptualizations of urban–nature relationships, in other words urban core's changing relationships to fringe ecosystems. The metropolitan regions used as case studies for this piece are Mumbai, Amsterdam, New York, and Tokyo. Each has used reclamation as a grand expansion strategy during political or economic transitions. During each grand alteration attempt in these regions, the developers, reclamation enthusiasts, or urban planners revisited the city's immediate ecological fringe for expansion, and following these revisitations, a new geographical order formed in their subsequent regions. The urban fringe has become the socio-spatial zone where new and experimental ideas about urban development encounter complex natural systems. The land-use negotiations and reclamation's role in shaping the urban–nature relationships are missing pieces of the planning field. Any future looking climate resiliency plan today should build on the reading of this palimpsest and understand how these environmental values were traded and how global expansion narratives transformed the urban–nature gradient.
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

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

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

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

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

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

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

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

A 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

Janus 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.
General anesthesia with S-ketamine improves the early recovery and cognitive function in patients undergoing modified radical mastectomy: a prospective randomized controlled trial
Authors: Zhang Junxia , Jia Danting , Li Wenbin , Li Xiaohui , Ma Qian , Chen Xuexin
Published: June 2023

Background

Postoperative cognitive dysfunction (POCD) is a common postoperative disorder that is frequently observed after general anesthesia, which seriously threatens the quality of patients’ life. Existing studies have demonstrated that S-ketamine plays an important role in improving neuroinflammation. This trial aimed to explore the effects of S-ketamine on quality of recovery and cognitive function in patients following modified radical mastectomy (MRM).

Methods

Ninety patients aged 45 to 70 years with ASA grades of I or II, who underwent MRM, were selected. Patients were randomly assigned to the S-ketamine or control group. In the S-ketamine group, patients were induced with S-ketamine instead of sufentanil and maintained with S-ketamine and remifentanil. In the control group, patients were induced with sufentanil and maintained with remifentanil. The primary outcome was the Mini-Mental State Examination (MMSE) and Quality of Recovery-15 (QoR-15) score. Secondary outcomes including visual analog scale (VAS) score, cumulative propofol and opioids consumption, post anesthesia care unit (PACU) recovery time, occurrence of remedial analgesia, postoperative nausea and vomiting (PONV), other adverse events, as well as patient satisfaction.

Results

The global QoR-15 scores at postoperative day 1 (POD1) were significantly higher in the S-ketamine group than in the control group (124 [119.5–128.0] vs. 119 [114.0–123.5], P = 0.002), with a median difference of 5 points (95% confidence interval [CI] [-8 to -2]). Similarly, the global QoR-15 scores at postoperative day 2 (POD2) in the S-ketamine group were significantly higher than in the control group (140.0 [133.0–145.0] vs. 132.0 [126.5–141.5], P = 0.004). In addition, among the five subcomponents of the 15-item scale, S-ketamine group had a higher score in terms of physical comfort, pain, and emotional state both at POD1 and POD2. In terms of MMSE score, S-ketamine could promote the recovery of postoperative cognitive function at POD1, but not at POD2. Furthermore, the consumption of opioids, VAS score, and remedial analgesia in the S-ketamine group decreased significantly.

Conclusions

Collectively, our findings support that general anesthesia with S-ketamine as a potential strategy showed high safety and could not only improve the quality of recovery mainly through improving pain, physical comfort, and emotional state but also promote the recovery of cognitive function on POD1 in patients undergoing MRM.

Trial registration

The study was registered in the Chinese Clinical Trial Registry (registration No:ChiCTR2200057226, Date of registration: 04/03/2022).