bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of concurrent chemoradiotherapy with retrograde super selective intra-arterial infusion combined with cetuximab for synchronous multifocal oral squamous cell carcinomas
Authors: Chen Xuefei , Kioi Mitomu , Hayashi Yuichiro , Koizumi Toshiyuki , Koike Izumi , Yamanaka Shoji , Hata Masaharu , Mitsudo Kenji 
Published: May 2023

Abstract
Background
The incidence of multicentric oral cancer is increasing. However, treatment encounters difficulty if each tumor needs to be treated simultaneously. The objective of this clinical case report is to highlight the effect of concurrent chemoradiotherapy with retrograde superselective intra-arterial infusion combined with systemic administration of cetuximab on synchronous multifocal oral squamous cell carcinomas.

Case presentation
A 70-year-old man presented to the hospital with multiple tumors and oral pain. Three independent tumors were found in the right dorsal tongue, left edge of the tongue, and left lower lip. Based on the characteristic appearance of the lesions and further evaluation, clinical diagnoses of right tongue cancer “T3”, left tongue cancer “T2” and lower left lip cancer “T1”, N2cM0 were made. Treatment was initiated with systemic administration of cetuximab, followed by intra-arterial chemoradiotherapy. Treatment results were complete response on all three local lesions, and left neck dissection was performed following the initial treatment. The patient showed no evidence of recurrence during the 4 years follow-up period.

Conclusions
This novel combination treatment seems to be a promising strategy for patients with synchronous multifocal oral squamous cell carcinoma.
CPEB2 enhances cell growth and angiogenesis by upregulating ARPC5 mRNA stability in multiple myeloma
Authors: Zeng Piaorong , Wang Fujue , Long Xingxing , Cao Yixiong , Wen Feng , Li Junjun , Luo Zeyu 
Published: May 2023

Abstract
Background
The process of multiple myeloma (MM) is the result of the combined action of multiple genes. This study aims to explore the role and mechanism of cytoplasmic polyadenylation element binding protein2 (CPEB2) in MM progression.

Methods
The mRNA and protein expression levels of CPEB2 and actin-related protein 2/3 complex subunit 5 (ARPC5) were assessed by quantitative real-time PCR and western blot analysis. Cell function was determined by cell counting kit 8 assay, soft-agar colony formation assay, flow cytometry and tube formation assay. Fluorescent in situ hybridization assay was used to analyze the co-localization of CPEB2 and ARPC5 in MM cells. Actinomycin D treatment and cycloheximide chase assay were performed to assess the stability of ARPC5. The interaction between CPEB2 and ARPC5 was confirmed by RNA immunoprecipitation assay.

Results
CPEB2 and ARPC5 mRNA and protein expression levels were upregulated in CD138+ plasma cells from MM patients and cells. CPEB2 downregulation reduced MM cell proliferation, angiogenesis, and increased apoptosis, while its overexpression had an opposite effect. CPEB2 and ARPC5 were co-localized at cell cytoplasm and could positively regulate ARPC5 expression by mediating its mRNA stability. ARPC5 overexpression reversed the suppressive effect of CPEB2 knockdown on MM progression, and it knockdown also abolished CPEB2-promoted MM progression. Besides, CPEB2 silencing also reduced MM tumor growth by decreasing ARPC5 expression.

Conclusion
Our results indicated that CPEB2 increased ARPC5 expression through promoting its mRNA stability, thereby accelerating MM malignant process.
The Metreleptin Effectiveness and Safety Registry (MEASuRE): concept, design and challenges
Authors: Haymond Morey W , Araújo-Vilar David , Balser John , Lewis James H , Louzado Ruth , Musso Carla , von Schnurbein Julia , Wabitsch Martin ,   on behalf of the MEASuRE group
Published: May 2023

Abstract
Background
Metreleptin, a recombinant analog of human leptin, is an approved therapy, adjunct to diet, to treat the metabolic complications of leptin deficiency in patients with lipodystrophy – a group of rare diseases characterized by a paucity of adipose tissue. MEASuRE (Metreleptin Effectiveness And Safety Registry) is a post-authorization, voluntary registry that gathers long-term safety and effectiveness data on metreleptin. Here, we present the aims and evolution of MEASuRE.

Methods
MEASuRE was established to collect data from patients receiving commercially supplied metreleptin in the United States (US) and European Union (EU). MEASuRE aims to determine the incidence and severity of safety events and describe the clinical characteristics and therapeutic outcomes in the metreleptin-treated population. A key feature of MEASuRE is that it accumulates data from different sources to meet post-authorization objectives. US data are received directly from treating physicians via a contract research organization-mediated electronic data capture system. In the EU, data are received via the European Registry of Lipodystrophies managed by the European Consortium of Lipodystrophies (ECLip), a platform established by researchers and physicians to advance the knowledge of lipodystrophy. MEASuRE complies with applicable regulatory requirements governing privacy, and the storage, management, and access of data.

Results
Leveraging processes, infrastructure, and data from the ECLip registry presented several challenges that were addressed during MEASuRE’s development, including the expansion of the ECLip registry to accommodate MEASuRE-specific data elements, extensive data matching processes to ensure data consistency regardless of source, and rigorous data validation following the amalgamation of global data. Through the support of ECLip, MEASuRE is now a fully operational registry with the capacity for gathering and integrating standardized US- and EU-derived data. As of 31st October 2022, 15 US and four EU sites have participated in the MEASuRE, enrolling 85 patients globally.

Conclusions
Our experiences show that a post-authorization product registry can be successfully integrated into an existing patient registry. We propose that, through collaboration with existing registries and use of their established resources, patient enrolment timelines and data collection for new registries can be expedited. The learnings presented here may be applicable to other registries with similar objectives.

Trial registration
NCT02325674; Registered 25 December 2014 - Retrospectively registered’. https://clinicaltrials.gov/ct2/show/NCT02325674.
LEP promoter methylation in the initiation and progression of clonal cytopenia of undetermined significance and myelodysplastic syndrome
Authors: Kaastrup Katja , Gillberg Linn , Mikkelsen Stine U. , Ørskov Andreas D. , Schöllkopf Claudia , Mortensen Bo K. , Porse Bo , Hansen Jakob W. , Grønbæk Kirsten 
Published: May 2023

Abstract
Background
Idiopathic non-clonal cytopenia (ICUS) and clonal cytopenia (CCUS) are common in the elderly population. While these entities have similar clinical presentations with peripheral blood cytopenia and less than 10% bone marrow dysplasia, their malignant potential is different and the biological relationship between these disorders and myeloid neoplasms such as myelodysplastic syndrome (MDS) is not fully understood. Aberrant DNA methylation has previously been described to play a vital role in MDS and acute myeloid leukemia (AML) pathogenesis. In addition, obesity confers a poorer prognosis in MDS with inferior overall survival and a higher rate of AML transformation. In this study, we measured DNA methylation of the promoter for the obesity-regulated gene LEP, encoding leptin, in hematopoietic cells from ICUS, CCUS and MDS patients and healthy controls. We investigated whether LEP promoter methylation is an early event in the development of myeloid neoplasms and whether it is associated with clinical outcome.

Results
We found that blood cells of patients with ICUS, CCUS and MDS all have a significantly hypermethylated LEP promoter compared to healthy controls and that LEP hypermethylation is associated with anemia, increased bone marrow blast percentage, and lower plasma leptin levels. MDS patients with a high LEP promoter methylation have a higher risk of progression, shorter progression-free survival, and inferior overall survival. Furthermore, LEP promoter methylation was an independent risk factor for the progression of MDS in a multivariate Cox regression analysis.

Conclusion
In conclusion, hypermethylation of the LEP promoter is an early and frequent event in myeloid neoplasms and is associated with a worse prognosis.
Side population cells derived from hUCMSCs and hPMSCs could inhibit the malignant behaviors of Tn+ colorectal cancer cells from modifying their O-glycosylation status
Authors: Hu Wen , Ding Ruisong , Wang Mengyang , Huang Panpan , Wei Xia , Hu Xingyou , Hu Tao 
Published: May 2023

Abstract
Background
Cosmc (C1GalT1C1) mutation could cause aberrant O-glycosylation and result in expression of Tn antigen on the surface of tumor cells (Tn+ cells), which is associated with the metastasis and prognosis of cancer progression. Mesenchymal stem cells (MSCs) could participate in immunoregulation, tissue damage repair, and tumor inhibition and be seen as an ideal candidate for tumor therapy due to their inherent capacity to migrate to tumor sites. However, their therapeutic effectiveness in different tumors is inconsistent and still controversial. Of note, emerging data reveal that side population (SP) cells have a stronger multilineage developmental potential than main population cells and can function as stem/progenitor cells. The effect of SP cells derived from MSCs on the biological behaviors and the O-glycosylation status of tumor cells remains unclear.

Methods
SP cells were isolated from human umbilical cord MSCs (hUCMSCs) and human placenta MSCs (hPMSCs). Tn+ cells (LS174T-Tn+ and HT-29-Tn+ cells) and matching Tn− cells (LS174T-Tn− and HT-29-Tn− cells) were isolated from human colorectal cancer cell (CRC) lines LS174T and HT-29 by immune magnetic beads. The proliferation, migration, apoptosis, Tn antigen expression, and O-glycome in Tn+ and Tn− CRC cells before and after co-cultured with SP-MSCs were detected using real-time cell Analysis (RTCA), flow cytometry (FCM), and cellular O-glycome reporter/amplification (CORA), respectively. Cosmc protein and O-glycosyltransferase (T-synthase and C3GnT) activity in CRC cells were, respectively, assessed using western blotting and fluorescence method.

Results
Both SP cells derived from hUCMSCs and hPMSCs could inhibit proliferation and migration, promote apoptosis of CRC cells, significantly reduce Tn antigen expression on Tn+ CRC cells, generate new core 1-, 2-, and 3-derived O-glycans, increase T-synthase and C3GnT activity, and elevate the levels of Cosmc and T-synthase protein.

Conclusion
SP-hUCMSCs and SP-hPMSCs could inhibit proliferation and migration and promote apoptosis of Tn+ CRC cells via increasing O-glycosyltransferase activity to modify O-glycosylation status, which further adds a new dimension to the treatment of CRC.
The feasibility of negative pressure wound therapy versus standard dressings in paediatric hand and foot burns protocol: a pilot, single-centre, randomised control trial
Authors: Lumsden Emma , Kimble Roy , McMillan Catherine , Storey Kristen , Ware Robert S. , Griffin Bronwyn 
Published: May 2023

Abstract
Introduction
The goal of paediatric hand and foot burn management is hypertrophic scar and/or contracture prevention. The risk of scar formation may be minimised by integrating negative pressure wound therapy (NPWT) as an acute care adjunct as it decreases the time to re-epithelialisation. NPWT has known associated therapeutic burden; however, this burden is hypothesised to be outweighed by an increased likelihood of hypertrophic scar prevention. This study will assess the feasibility, acceptability and safety of NPWT in paediatric hand and foot burns with secondary outcomes of time to re-epithelialisation, pain, itch, cost and scar formation.

Methods and analysis
This is a single-site, pilot randomised control trial. Participants must be aged ≤ 16 years, otherwise well and managed within 24 h of sustaining either a hand or foot burn. Thirty participants will be randomised to either standard care (Mepitel®—a silicone wound interface contact dressing—and ACTICOAT™—a nanocrystalline silver-impregnated dressing) or standard care plus NPWT. Patients will be reviewed until 3 months post-burn wound re-epithelialisation, with measurements taken at dressing changes to assess primary and secondary outcomes. Surveys, randomisation and data storage will be done via online platforms and physical data storage collated at the Centre for Children’s Health Research, Brisbane, Australia. Analysis will be performed using the Stata statistical software.

Ethics and dissemination
Queensland Health and Griffith University Human Research ethics approval including a site-specific assessment was obtained. The findings of this study will be disseminated through clinical meetings, conference presentations and peer reviewed journals.

Trial registration
Registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12622000044729, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381890&isReview=true, registered 17/01/2022).
Anesthetic management for withdrawal from a right ventricular assist device and Fontan procedure in a patient with an implantable left ventricular assist device for fulminant cardiomyopathy
Authors: Kida Naka , Morinaga Masahiro , Tadokoro Naoki , Maeda Takuma , Onishi Yoshihiko 
Published: May 2023

Abstract
Background
We herein report the anesthetic management for extracardiac conduit–total cavopulmonary connection (EC-TCPC) for weaning from an extracorporeal right ventricular assist device (RVAD) in a patient with an implantable left ventricular assist device (LVAD) for fulminant cardiomyopathy.

Case presentation
A 24-year-old man developed fulminant cardiomyopathy and was placed on a biventricular assist device (BiVAD) comprising an implantable LVAD and an extracorporeal RVAD. The Fontan procedure was performed to wean the patient from the RVAD and allow him to be discharged home. Atrial septal defect creation, right ventricular suture, and tricuspid valve closure were then simultaneously performed to ensure sufficient left ventricular preload to drive the LVAD. Furthermore, to keep the central venous pressure lower, the inflow cannula of the LVAD was oriented in the correct direction.

Conclusion
This is the first report of anesthetic management of the Fontan procedure in a patient with a BiVAD.
Global shipping and climate change impacts in Africa: the role of international trade
Authors: Ayesu Enock Kojo , Asaana Clement Agonyim 
Published: May 2023

AbstractThis paper examines the interacting effect of global shipping and trade on climate change in Africa using data on 31 countries for the period 2006–2016. We employ the system generalized method of moments estimation technique for our analysis. The results reveal that, in both the short run and long run, global shipping and trade contribute significantly to climate change in African countries. Furthermore, we document that the impact of shipping on climate change become larger through the aggregate trade channel. Based on these outcomes, policies designed to reduce emissions from global shipping are important in mitigating the menaces of climate change in Africa.
Enhancing tomato resistance by exploring early defense events against Fusarium wilt disease
Authors: Li Jingtao , Wang Chenyang , Yang Limei , Qiu Fahui , Li Yue , Zheng Yaning , Liu Sihui , Song Limin , Liang Wenxing 
Published: May 2023

AbstractStudying plant early immunity, such as the unique immune mechanisms against pathogens, is an important field of research. Tomato wilt resulting from the infection by Fusarium oxysporum f. sp. lycopersici (Fol) is an important soil-borne vascular disease. In this study, we challenged tomato plants with Fol for a time-course RNA sequencing (RNA-seq) analysis. The result indicated that phenylpropanoid and flavonoid pathway genes were significantly enriched during the early invasion stage. Further study revealed that the flavonoids galangin and quercetin could effectively inhibit Fol growth and enhance wilt resistance in tomato. Moreover, the genes involved in plant-pathogen interactions, the MAPK signaling pathway, and plant hormone signal transduction were significantly enriched. These genes were also involved in plant pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) signaling pathways. Strikingly, the transcription levels of pathogen-related protein 1 (SlPR1) were dramatically increased at 2 days post Fol inoculation, implying that SlPR1 is important in early immunity in tomato. SlPR1 does not have direct antifungal activity. Instead, its C-terminal peptide CAPE1 could activate root defense responses, such as the reactive oxygen species (ROS) burst, salicylic acid (SA)/jasmonic acid (JA) production, and defense-related gene expression, which collectively increased tomato resistance to Fol infection. In addition, CAPE1 could induce systemic acquired resistance (SAR). Application of CAPE1 onto tomato leaves induced local resistance to the pathogen Botrytis cinerea and systemic resistance to Fol infection. These results advanced our understanding for the early immunity against Fol in tomato and provide potential strategy for tomato disease control.
Team-focused implementation strategies to improve implementation of mental health screening and referral in rural Children’s Advocacy Centers: study protocol for a pilot cluster randomized hybrid type 2 trial
Authors: McGuier Elizabeth A. , Aarons Gregory A. , Wright Jaely D. , Fortney John C. , Powell Byron J. , Rothenberger Scott D. , Weingart Laurie R. , Miller Elizabeth , Kolko David J. 
Published: May 2023

AbstractBackgroundChildren’s Advocacy Centers (CACs) use multidisciplinary teams to investigate and respond to maltreatment allegations. CACs play a critical role in connecting children with mental health needs to evidence-based mental health treatment, especially in low-resourced rural areas. Standardized mental health screening and referral protocols can improve CACs’ capacity to identify children with mental health needs and encourage treatment engagement. In the team-based context of CACs, teamwork quality is likely to influence implementation processes and outcomes. Implementation strategies that target teams and apply the science of team effectiveness may enhance implementation outcomes in team-based settings.MethodsWe will use Implementation Mapping to develop team-focused implementation strategies to support the implementation of the Care Process Model for Pediatric Traumatic Stress (CPM-PTS), a standardized screening and referral protocol. Team-focused strategies will integrate activities from effective team development interventions. We will pilot team-focused implementation in a cluster-randomized hybrid type 2 effectiveness-implementation trial. Four rural CACs will implement the CPM-PTS after being randomized to either team-focused implementation (n= 2 CACs) or standard implementation (n= 2 CACs). We will assess the feasibility of team-focused implementation and explore between-group differences in hypothesized team-level mechanisms of change and implementation outcomes (implementation aim). We will use a within-group pre-post design to test the effectiveness of the CPM-PTS in increasing caregivers’ understanding of their child’s mental health needs and caregivers’ intentions to initiate mental health services (effectiveness aim).ConclusionsTargeting multidisciplinary teams is an innovative approach to improving implementation outcomes. This study will be one of the first to test team-focused implementation strategies that integrate effective team development interventions. Results will inform efforts to implement evidence-based practices in team-based service settings.Trial registrationClinicaltrials.gov,NCT05679154. Registered on January 10, 2023.
Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations
Authors: Sequist Lecia V. , Yang James Chih-Hsin , Yamamoto Nobuyuki , O'Byrne Kenneth , Hirsh Vera , Mok Tony , Geater Sarayut Lucien , Orlov Sergey , Tsai Chun-Ming , Boyer Michael , Su Wu-Chou , Bennouna Jaafar , Kato Terufumi , Gorbunova Vera , Lee Ki Hyeong , Shah Riyaz , Massey Dan , Zazulina Victoria , Shahidi Mehdi , Schuler Martin 
Published: May 2023

PURPOSE The LUX-Lung 3 study investigated the efficacy of chemotherapy compared with afatinib, a selective, orally bioavailable ErbB family blocker that irreversibly blocks signaling from epidermal growth factor receptor (EGFR/ErbB1), human epidermal growth factor receptor 2 (HER2/ErbB2), and ErbB4 and has wide-spectrum preclinical activity against EGFR mutations. A phase II study of afatinib in EGFR mutation–positive lung adenocarcinoma demonstrated high response rates and progression-free survival (PFS). PATIENTS AND METHODS In this phase III study, eligible patients with stage IIIB/IV lung adenocarcinoma were screened for EGFR mutations. Mutation-positive patients were stratified by mutation type (exon 19 deletion, L858R, or other) and race (Asian or non-Asian) before two-to-one random assignment to 40 mg afatinib per day or up to six cycles of cisplatin plus pemetrexed chemotherapy at standard doses every 21 days. The primary end point was PFS by independent review. Secondary end points included tumor response, overall survival, adverse events, and patient-reported outcomes (PROs). RESULTS A total of 1,269 patients were screened, and 345 were randomly assigned to treatment. Median PFS was 11.1 months for afatinib and 6.9 months for chemotherapy (hazard ratio [HR], 0.58; 95% CI, 0.43 to 0.78; P = .001). Median PFS among those with exon 19 deletions and L858R EGFR mutations (n = 308) was 13.6 months for afatinib and 6.9 months for chemotherapy (HR, 0.47; 95% CI, 0.34 to 0.65; P = .001). The most common treatment-related adverse events were diarrhea, rash/acne, and stomatitis for afatinib and nausea, fatigue, and decreased appetite for chemotherapy. PROs favored afatinib, with better control of cough, dyspnea, and pain. CONCLUSION Afatinib is associated with prolongation of PFS when compared with standard doublet chemotherapy in patients with advanced lung adenocarcinoma and EGFR mutations.