bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions and performance of a rapid diagnostic test for identifying asymptomatic malaria infection in northern Ethiopia, 2015
Authors: Leonard Colleen M. , Assefa Ashenafi , McCaffery Jessica N. , Herman Camelia , Plucinski Mateusz , Sime Heven , Mohammed Hussein , Kebede Amha , Solomon Hiwot , Haile Mebrahtom , Murphy Matt , Hwang Jimee , Rogier Eric 
Published: March 2022

Abstract
Background
Rapid diagnostic tests (RDTs) are widely used for malaria diagnosis of both symptomatic and asymptomatic infections. Although RDTs are a reliable and practical diagnostic tool, the sensitivity of histidine-rich protein 2 (HRP2)-based RDTs can be reduced if pfhrp2 or pfhrp3 (pfhrp2/3) gene deletions exist in the Plasmodium falciparum parasite population. This study evaluated dried blood spot (DBS) samples collected from a national household survey to investigate the presence of pfhrp2/3 deletions and the performance of the RDT used in the cross-sectional survey in a low transmission setting.

Methods
The 2015 Ethiopia Malaria Indicator Survey tested household members by RDT and collected DBS samples. DBS (n = 2648) from three regions in northern Ethiopia were tested by multiplex bead-based antigen detection assay after completion of the survey. The multiplex assay detected pan-Plasmodium lactate dehydrogenase (LDH), pAldolase, and HRP2 antigens in samples. Samples suspected for pfhrp2/3 gene deletions (pLDH and/or pAldolase positive but low or absent HRP2) were further investigated by molecular assays for gene deletions. Antigen results were also compared to each individual’s RDT results. Dose–response logistic regression models were fit to estimate RDT level of detection (LOD) antigen concentrations at which 50, 75, 90, and 95% of the RDTs returned a positive result during this survey.

Results
Out of 2,648 samples assayed, 29 were positive for pLDH or pAldolase antigens but low or absent for HRP2 signal, and 15 of these samples (51.7%) were successfully genotyped for pfhrp2/3. Of these 15 P. falciparum infections, eight showed single deletions in pfhrp3, one showed a single pfhrp2 deletion, and six were pfhrp2/3 double-deletions. Six pfhrp2 deletions were observed in Tigray and one in Amhara. Twenty-five were positive for HRP2 by the survey RDT while the more sensitive bead assay detected 30 HRP2-positive samples. A lower concentration of HRP2 antigen generated a positive test result by RDT compared to pLDH (95% LOD: 16.9 ng/mL vs. 319.2 ng/mL, respectively).

Conclusions
There is evidence of dual pfhrp2/3 gene deletions in the Tigray and Amhara regions of Ethiopia in 2015. As the prevalence of malaria was very low (< 2%), it is difficult to make strong conclusions on RDT performance, but these results challenge the utility of biomarkers in household surveys in very low transmission settings.
De novo generation of the NPM-ALK fusion recapitulates the pleiotropic phenotypes of ALK+ ALCL pathogenesis and reveals the ROR2 receptor as target for tumor cells
Authors: Babin Loélia , Darchen Alice , Robert Elie , Aid Zakia , Borry Rosalie , Soudais Claire , Piganeau Marion , De Cian Anne , Giovannangeli Carine , Bawa Olivia , Rigaud Charlotte , Scoazec Jean-Yves , Couronné Lucile , Veleanu Layla , Cieslak Agata , Asnafi Vahid , Sibon David , Lamant Laurence , Meggetto Fabienne , Mercher Thomas , Brunet Erika 
Published: March 2022

AbstractBackgroundAnaplastic large cell lymphoma positive for ALK (ALK+ ALCL) is a rare type of non-Hodgkin lymphoma. This lymphoma is caused by chromosomal translocations involving the anaplastic lymphoma kinase gene (ALK). In this study, we aimed to identify mechanisms of transformation and therapeutic targets by generating a model of ALK+ ALCL lymphomagenesis ab initio with the specific NPM-ALK fusion.MethodsWe performed CRISPR/Cas9-mediated genome editing of the NPM-ALK chromosomal translocation in primary human activated T lymphocytes.ResultsBoth CD4+ and CD8+ NPM-ALK-edited T lymphocytes showed rapid and reproducible competitive advantage in culture and led to in vivo disease development with nodal and extra-nodal features. Murine tumors displayed the phenotypic diversity observed in ALK+ ALCL patients, including CD4+ and CD8+ lymphomas. Assessment of transcriptome data from models and patients revealed global activation of the WNT signaling pathway, including both canonical and non-canonical pathways, during ALK+ ALCL lymphomagenesis. Specifically, we found that the WNT signaling cell surface receptor ROR2 represented a robust and genuine marker of all ALK+ ALCL patient tumor samples.ConclusionsIn this study, ab initio modeling of the ALK+ ALCL chromosomal translocation in mature T lymphocytes enabled the identification of new therapeutic targets. As ROR2 targeting approaches for other cancers are under development (including lung and ovarian tumors), our findings suggest that ALK+ ALCL cases with resistance to current therapies may also benefit from ROR2 targeting strategies.
Multifunctional photodynamic/photothermal nano-agents for the treatment of oral leukoplakia
Authors: Lin Lin , Song Chuanhui , Wei Zheng , Zou Huihui , Han Shengwei , Cao Zichen , Zhang Xinyu , Zhang Guorong , Ran Jianchuan , Cai Yu , Han Wei 
Published: March 2022

AbstractOral leukoplakia (OLK) has gained extensive attention because of the potential risk for malignant transformation. Photosensitizers (PSs) played an indispensable role in the photodynamic therapy (PDT) of OLK, but the poor light sensitivity greatly hampered its clinical application. Herein, a novel organic photosensitive ITIC-Th nanoparticles (ITIC-Th NPs) were developed for OLK photodynamic/photothermal therapy (PTT). ITIC-Th NPs present both high photothermal conversion efficiency (~ 38%) and suitable reactive oxygen species (ROS) generation ability under 660 nm laser irradiation, making them possess excellent PDT and PTT capability. In 4-nitroquinoline 1-oxide (4NQO)-induced oral precancerous animal models, ITIC-Th NPs effectively suppress the OLK's cancerization without apparent topical or systemic toxicity in vivo. This study offers a promising therapeutic strategy for PDT and PTT in OLK treatment, and this study is the first interdisciplinary research in the field of multimodal therapy for OLK.
Graphical Abstract
A drug-free nanozyme for mitigating oxidative stress and inflammatory bowel disease
Authors: Zeng Feng , Shi Yahong , Wu Chunni , Liang Jianming , Zhong Qixin , Briley Karen , Xu Bin , Huang Yongzhuo , Long Manmei , Wang Cong , Chen Jian , Tang Yonghua , Li Xinying , Jiang Mengda , Wang Luting , Xu Qin , Yang Liu , Chen Peng , Duan Shengzhong , Xie Jingyuan , Li Cong , Wu Yingwei 
Published: March 2022

AbstractInflammatory bowel disease (IBD) is an incurable disease of the gastrointestinal tract with a lack of effective therapeutic strategies. The proinflammatory microenvironment plays a significant role in both amplifying and sustaining inflammation during IBD progression. Herein, biocompatible drug-free ceria nanoparticles (CeNP-PEG) with regenerable scavenging activities against multiple reactive oxygen species (ROS) were developed. CeNP-PEG exerted therapeutic effect in dextran sulfate sodium (DSS)-induced colitis murine model, evidenced by corrected the disease activity index, restrained colon length shortening, improved intestinal permeability and restored the colonic epithelium disruption. CeNP-PEG ameliorated the proinflammatory microenvironment by persistently scavenging ROS, down-regulating the levels of multiple proinflammatory cytokines, restraining the proinflammatory profile of macrophages and Th1/Th17 response. The underlying mechanism may involve restraining the co-activation of NF-κB and JAK2/STAT3 pathways. In summary, this work demonstrates an effective strategy for IBD treatment by ameliorating the self-perpetuating proinflammatory microenvironment, which offers a new avenue in the treatment of inflammation-related diseases.Graphical Abstract
Biomimetic radiosensitizers unlock radiogenetics for local interstitial radiotherapy to activate systematic immune responses and resist tumor metastasis
Authors: Zhang Jiajia , Yang Mengdie , Fan Xin , Zhu Mengqin , Yin Yuzhen , Li Hongyan , Chen Jie , Qin Shanshan , Zhang Han , Zhang Kun , Yu Fei 
Published: March 2022

Abstract
Background
Similar to other local therapeutic methods, local interstitial radiotherapy (IRT) also suffers from insufficient systematic immune activation, resulting in tumor metastasis.

Results
Mn-based IRT radiosensitizers consisting of 131I, MnO2 and bovine serum albumin (BSA) (131I-MnO2-BSA) were engineered. Such Mn-based IRT radiosensitizers successfully unlocked radiogenetics to magnify systematic immune responses of local IRT via remodeling hypoxic and immunosuppressive microenvironments and resist tumor metastasis. The MnO2 in 131I-MnO2-BSA caused decomposition of H2O2 enriched in tumors to generate O2 for alleviating hypoxic microenvironment and removing tumor resistances to IRT. Concurrently, hypoxia mitigation by such radiosensitizers-unlocked radiogenetics can effectively remodel immunosuppressive microenvironment associated with regulatory T (Treg) cells and tumor-associated macrophages (TAMs) infiltration inhibition to induce immunogenic cell death (ICD), which, along with hypoxia mitigation, activates systematic immune responses. More intriguingly, 131I-MnO2-BSA-enabled radiogenetics can upregulate PD-L1 expression, which allows anti-PD-L1-combined therapy to exert a robust antitumor effect on primary tumors and elicit memory effects to suppress metastatic tumors in both tumor models (4T1 and CT26).

Conclusions
IRT radiosensitizer-unlocked radiogenetics and the corresponding design principle provide a general pathway to address the insufficient systematic immune responses of local IRT.

Graphical Abstract
Health-related quality of life among older adults who experienced the Pohang earthquake in South Korea: A cross-sectional survey
Authors: Kim Eun-Mi , Kim Gwang Suk , Kim Heejung , Park Chang Gi , Lee Ogcheol , Pfefferbaum Betty 
Published: March 2022

Abstract
Background
Earthquakes are global natural disasters and can cause loss of property, livelihood and affect human health. A 5.4 magnitude earthquake, the Pohang earthquake, occurred in South Korea in 2017. In this study, based on a health-related quality of life (HRQOL) conceptual model, we examined the HRQOL and its associated factors among older adults who had experienced the earthquake.

Methods
A cross-sectional study was conducted with a quota sample of 312 older adults living in eight villages of a district that was the most damaged area during the Pohang earthquake. Data were collected from January 15–March 19, 2019, via face-to-face interviews using structured questionnaires. Structural equation modeling was performed to explore the associations among depression, posttraumatic stress symptoms, community resilience, social support, disaster preparedness, and HRQOL.

Results
The mean age of the participants was 77.93 ± 6.11 years. HRQOL scores were 49.85 ± 18.07 (physical health), 50.16 ± 18.75 (psychological health), 61.93 ± 19.20 (social relations), and 49.53 ± 16.37 (environment). The structural equation modeling analysis showed a good fit. Depression had direct (β =  − 2.21; p < 0.001), indirect (β =− 0.23; p < 0.001), and total effects on HRQOL (β =  − 2.44; p < 0.001). Community resilience (β = 6.05; p = 0.001) and social support (β = 0.12, p = 0.001) had direct and total effects on HRQOL. Disaster preparedness had indirect (β = 0.40; p = 0.001) and total (β = 0.69, p = 0.031) effects on HRQOL. In contrast, posttraumatic stress symptoms did not have significant effects on HRQOL.

Conclusions
Our findings indicated that lower depression, higher community resilience, social support, and disaster preparedness were associated with increased HRQOL. Thus, it is helpful to decrease depression and strengthen community resilience, social support, and disaster preparedness to promote HRQOL among older adults who have experienced earthquakes. These results can inform the development of HRQOL in socio-psychological improvement programs for older adults in community health centers and disaster-relief psychological support centers.
Pan-cancer analyses of pyroptosis with functional implications for prognosis and immunotherapy in cancer
Authors: Liu Aibin , Shen Lin , Li Na , Shen Liangfang , Li Zhanzhan 
Published: March 2022

AbstractBackgroundProgrammed cell death is an active and orderly form of cell death regulated by intracellular genes that plays an important role in the normal occurrence and development of the immune system, and pyroptosis has been found to be involved in tumorigenesis and development. However, compressive analysis and biological regulation of pyroptosis genes are lacking in cancers.MethodsUsing data from The Cancer Genome Atlas, we established a score level model to quantify the pyroptosis level in cancer. Multiomics bioinformatic analyses were performed to assess pyroptosis-related molecular features and the effect of pyroptosis on immunotherapy in cancer.ResultsIn the present study, we performed a comprehensive analysis of pyroptosis and its regulator genes in cancers. Most pyroptosis genes were aberrantly expressed in different types of cancer, attributed to the CAN frequency and differences in DNA methylation levels. We established a pyroptosis level model and found that pyroptosis had dual roles across cancers, while the pyroptosis levels were different among multiple cancers and were significantly associated with clinical prognosis. The dual role of pyroptosis was also shown to affect immunotherapeutic efficacy in several cancers. Multiple pyroptosis genes showed close associations with drug sensitivity across cancers and may be considered therapeutic targets in cancer.ConclusionsOur comprehensive analyses provide new insight into the functions of pyroptosis in the initiation, development, progression and treatment of cancers, suggesting corresponding prognostic and therapeutic utility.
Mix-and-match: an improved, fast and accessible protocol for hypocotyl micrografting of Arabidopsis seedlings with systemic ACC responses as a case study
Authors: Vanderstraeten L. , Sanchez-Muñoz R. , Depaepe T. , Auwelaert F. , Van Der Straeten D. 
Published: March 2022

Abstract
Background
Grafting is a technique widely used in horticulture that also has been applied in agriculture. In plant physiology, grafting facilitates the elucidation of mechanisms underlying growth and developmental processes, through the construction of chimeric plants with organs of different genotypes. Despite its small size, the model species Arabidopsis thaliana is very amenable for grafting, which can be useful to investigate transport of nutrients, amino acids or secondary metabolites between different tissues, or to investigate developmental processes depending on root-to-shoot communication, such as shoot branching, root and shoot plasticity upon shade avoidance, or disease resistance. Nevertheless, grafting protocols are usually technically challenging and training is required to achieve a reasonable success rate. Additionally, specialized tools and equipment are often needed, such as chips to accommodate the grafted plantlets or collars to maintain the contact between root and shoot.

Results
In this methodology paper, we provide a fast, easy, accessible, and specialized equipment-free protocol that enables high success ratios. Critical steps and notes are detailed, easing the implementation of the procedure for non-trained researchers. An example of the protocol application by three independent non-trained researchers shows that this method allows to achieve a 90–100% of grafting efficiency after 6 days post-grafting recovery. In addition, the grafting of Col-0 with the acs8x mutant, depleted in 1-aminocyclopropane-1-carboxylic acid (ACC), the biosynthetic precursor of the phytohormone ethylene, provides an example of the application of this optimized protocol, showing the suitability of the process to study long-distance transport processes.

Conclusions
We present an optimized protocol for hypocotyl grafting of 4-day-old Arabidopsis thaliana seedlings. The combination of conditions yields a grafting success of 90–100% and provides an easy and accessible methodology, reducing the time frame, and without the necessity of acquiring specialized equipment. The presented protocol is simple, fast and highly efficient, easing the inclusion of hypocotyl grafting assays in any research project. In addition, the description of the protocol is detailed to a level ensuring that even non-trained researchers, are sufficiently prepared to adopt the grafting methodology.
Surgical management of upper limb lipoma arborescens: a systematic review
Authors: Kalifis Georgios , Maffulli Nicola , Migliorini Filippo , Marín Fermín Theodorakys , Hovsepian Jean Michel , Stefanou Nikolaos , Hantes Michael 
Published: March 2022

Abstract
Background
Lipoma arborescens (LA) is a rare benign synovial tumour characterized by the proliferation of mature adipocytes within the synovial cells. Given its rarity, current evidence is mainly based on case reports and case series, and no guidelines are available. The present study investigated the current surgical management and related outcomes of LA in the upper limb.

Methods
This systematic review was conducted following the PRISMA guidelines. PubMed, Scopus, and Virtual Health Library were accessed in September 2021. Clinical studies evaluating patients with LA undergoing surgical treatment were considered eligible for this systematic review. Only studies which reported data on LA located in the upper limb with histopathological confirmation were considered. Articles that reported data from nonsurgical management were not considered.

Results
A total of 21 studies reporting 22 lesions in 21 patients were assessed. The mean age of the patients was 48.48 years (range 22–77). Most studies evaluated the restoration of range of motion and symptom resolution for the functional outcome assessment. Open or arthroscopic excision and synovectomy were the most common surgical procedures for LA. The concomitant lesions were treated in a single-stage procedure. All patients had satisfactory outcomes after open or arthroscopic excision and synovectomy without recurrence at a mean follow-up of 21.14 months (range 2–60). One patient developed postoperative cellulitis (4.55%).

Conclusion
Open and arthroscopic excision combined with synovectomy should be considered the standard treatment option of upper limb LA. Concomitant pathologies can be addressed in a one-stage procedure. Although LA was recognized as a clinical entity decades ago, there is a lack of evidence based guidelines and long term outcome data are unavailable.
CRISPR-Cas gene editing technology and its application prospect in medicinal plants
Authors: Guo Miaoxian , Chen Hongyu , Dong Shuting , Zhang Zheng , Luo Hongmei 
Published: March 2022

AbstractThe clustered regularly interspaced short palindromic repeats (CRISPR)-Cas gene editing technology has opened a new era of genome interrogation and genome engineering because of its ease operation and high efficiency. An increasing number of plant species have been subjected to site-directed gene editing through this technology. However, the application of CRISPR-Cas technology to medicinal plants is still in the early stages. Here, we review the research history, structural characteristics, working mechanism and the latest derivatives of CRISPR-Cas technology, and discussed their application in medicinal plants for the first time. Furthermore, we creatively put forward the development direction of CRISPR technology applied to medicinal plant gene editing. The aim is to provide a reference for the application of this technology to genome functional studies, synthetic biology, genetic improvement, and germplasm innovation of medicinal plants. CRISPR-Cas is expected to revolutionize medicinal plant biotechnology in the near future.
Molecular environment and atypical function: What do we know about enzymes associated with Mucopolysaccharidoses?
Authors: Kong Weijing , Lu Cheng , Ding Yingxue , Meng Yan 
Published: March 2022

AbstractMucopolysaccharidoses are a group of lysosomal storage disorders caused by deficiency of enzymes involved in glycosaminoglycans degradation. Relationship between mucopolysaccharidoses and related enzymes has been clarified clearly. Based on such relationship, lots of therapies have been commercialized or are in the process of research and development. However, many potential treatments failed, because those treatments did not demonstrate expected efficacy or safety data. Molecular environment of enzyme, which is essential for their expression and activity, is fundamental for efficacy of therapy. In addition to enzyme activities, mucopolysaccharidoses-related enzymes have other atypical functions, such as regulation, which may cause side effects. This review tried to discuss molecular environment and atypical function of enzymes that are associated with mucopolysaccharidoses, which is very important for the efficacy and safety of potential therapies.
An international comparative analysis of public reimbursement of orphan drugs in Canadian provinces compared to European countries
Authors: Ward Leanne Marie , Chambers Alexandra , Mechichi Emine , Wong-Rieger Durhane , Campbell Craig 
Published: March 2022

AbstractBackgroundThe Canadian government has committed to developing a national strategy for drugs for rare diseases starting in 2022. Considering this announcement, we conducted a comparative analysis to examine patient access to therapies for rare disease in Canada relative to Europe and the U.S.MethodsGiven its similarity to the Canadian health care system, we used Europe as the reference point to analyze all of the therapies with an orphan drug designation approved by the European Medicine Agency (EMA) from 1 January 2015 to 31 March 2020. We then contrasted access to these drugs in Canada (Health Canada) and the U.S. (Food and Drug Administration, FDA). We focused on: (1) the number of therapies for rare diseases entering the Canadian market; (2) the percentage of these therapies that are publicly available to Canadians; and (3) the timelines for patients to access these therapies in Canada.ResultsSixty-three approved therapies with an orphan drug designation from the EMA were identified. Fifty-three (84%) of these drugs had also been submitted to the FDA for approval, and 41 (65%) were submitted to Health Canada for approval. In Europe, Germany, Denmark, and the U.K. had the highest percentage of publicly reimbursed orphan drugs (84%, 70%, 68%, respectively). In comparison, Ontario (32%), Quebec (25%), and Alberta (25%) had the highest percentage of drugs reimbursed among the Canadian provinces. The shortest median duration (in months) from EMA approval to jurisdictional decision on reimbursement was in Austria (3.2), followed by Germany (4.1), and Finland (6.0). In Canada, the shortest median duration (in months) from regulatory approval to reimbursement was in British Columbia (17.3), Quebec (19.6) and Manitoba (19.6), while the longest duration was in P.E.I (38.5), followed by Nova Scotia (25.9), and Newfoundland (25.1).ConclusionsOur comparative analysis found that relative to the EU Canadians had less frequent and timely access to therapies for rare diseases. This highlights the need for a rare disease strategy in Canada that allows for clear identification and transparent tracking of the pathway for rare disease drugs, and ultimately optimizes the number of patients with access to these therapies.