bluuebunny/crossref_metadata_2025 huggingface dataset:
Double and single mixed-lineage leukemia-rearranged subclones in pediatric acute myeloid leukemia: a case report
Authors: McGrath Mary , Smink Gayle
Published: May 2021

Background

Acute myeloid leukemia (AML) is a disease with a significant amount of cytogenetic heterogeneity including mixed-lineage leukemia (MLL) gene rearrangements. Pediatric AML commonly has genetic rearrangements which involve chromosome 11q23 in 15–20% of cases, and these genetic abnormalities have been associated with a poorer prognosis (Grimwade et al. in Blood 92:2322–2333, 1998; Raimondi et al. in Blood 94:3707–3716, 1999; Lie et al. in Br J Haematol 122: 217–225). MLL rearrangements in AML have been shown to have multiple different fusion partners (Meyer et al. in Leukemia 23:1490–1499). Heterogeneity of these cytogenetic abnormalities makes it difficult to determine how to approach patients from a treatment standpoint. This difficulty is further complicated when patients have more than a single MLL rearrangement.

Case presentation

A 10-year-old Caucasian girl presented with easy bruising and was found to have acute myeloid leukemia. Her cytogenetics showed two different MLL rearrangements, t(9;11)(p22;q23) and t(11;19)(q23;p13.3). At initial presentation she had no other cytogenetic findings. She responded well to initial therapy and achieved remission following the first induction cycle and completed four rounds of chemotherapy. She subsequently had a relapse of her AML, and her cytogenetics were consistent with a single MLL rearrangement, t(9;11)(p22;q23), in addition to monosomy 7. She was treated with reduction therapy and a haplo-identical bone marrow transplant but ultimately succumbed to her disease.

Conclusion

MLL rearrangements are common in AML, but clinical significance continues to be elusive, and there is conflicting data on the prognostic significance. In the setting of multiple MLL rearrangements, there is concern for reduced survival, although treatment modifications are not currently done in this setting. This report details a case with multiple MLL rearrangements that initially responded to therapy but ultimately had disease progression with a selection of a leukemic clone containing a single MLL rearrangement.
MiR-34a suppression targets Nampt to ameliorate bone marrow mesenchymal stem cell senescence by regulating NAD+-Sirt1 pathway
Authors: Pi Chenchen , Ma Cao , Wang Huan , Sun Hui , Yu Xiao , Gao Xingyu , Yang Yue , Sun Yanan , Zhang Haiying , Shi Yingai , Li Yan , Li Yulin , He Xu
Published: May 2021

Background

Expansion-mediated replicative senescence and age-related natural senescence have adverse effects on mesenchymal stem cell (MSC) regenerative capability and functionality, thus severely impairing the extensive applications of MSC-based therapies. Emerging evidences suggest that microRNA-34a (miR-34a) has been implicated in the process of MSC senescence; however, the molecular mechanisms with regard to how miR-34a influencing MSC senescence remain largely undetermined.

Methods

MiR-34a expression in MSCs was evaluated utilizing RT-qPCR. The functional effects of miR-34a exerting on MSC senescence were investigated via gene manipulation. Relevant gene and protein expression levels were analyzed by RT-qPCR and western blot. Luciferase reporter assays were applied to confirm that Nampt is a direct target of miR-34a. The underlying regulatory mechanism of miR-34a targeting Nampt in MSC senescence was further explored by measuring intracellular NAD+ content, NAD+/NADH ratio and Sirt1 activity.

Results

In contrast to Nampt expression, miR-34a expression incremented in senescent MSCs. MiR-34a overexpression in young MSCs resulted in senescence-associated characteristics as displayed by senescence-like morphology, prolonged cell proliferation, declined osteogenic differentiation potency, heightened senescence-associated-β-galactosidase activity, and upregulated expression levels of the senescence-associated factors. Conversely, miR-34a suppression in replicative senescent and natural senescent MSCs contributed to diminished senescence-related phenotypic features. We identified Nampt as a direct target gene of miR-34a. In addition, miR-34a repletion resulted in prominent reductions in Nampt expression levels, NAD+ content, NAD+/NADH ratio, and Sirt1 activity, whereas anti-miR-34a treatment exerted the opposite effects. Furthermore, miR-34a-mediated MSC senescence was evidently rescued following the co-treatment with Nampt overexpression.

Conclusion

This study identifies a significant role of miR-34a playing in MSC replicative senescence and natural senescence via targeting Nampt and further mediating by NAD+-Sirt1 pathway, carrying great implications for optimal strategies for MSC therapeutic applications.
AQP0 is a novel surface marker for deciphering abnormal erythropoiesis
Authors: Wang Tso-Fu , Lin Guan-Ling , Chu Sung-Chao , Chen Chang-Chin , Liou Yu-Shan , Chang Hsin-Hou , Sun Der-Shan
Published: May 2021

Background

Hematopoiesis occurs in the bone marrow, producing a complete spectrum of blood cells to maintain homeostasis. In addition to light microscopy, chromosome analysis, and polymerase chain reaction, flow cytometry is a feasible and fast method for quantitatively analyzing hematological diseases. However, because sufficient specific cell markers are scarce, dyserythropoietic diseases are challenging to identify through flow cytometry.

Methods

Bone marrow samples from C57BL/B6 mice and one healthy donor were analyzed using traditional two-marker (CD71 and glycophorin A) flow cytometry analysis. After cell sorting, the gene expressions of membrane proteins in early and late erythropoiesis precursors and in nonerythroid cells were characterized using microarray analysis.

Results

Among characterized gene candidates, aquaporin 0 (AQP0) expressed as a surface protein in early- and late-stage erythropoiesis precursors and was not expressed on nonerythroid cells. With the help of AQP0 staining, we could define up to five stages of erythropoiesis in both mouse and human bone marrow using flow cytometry. In addition, because patients with dyserythropoiesis generally exhibited a reduced population of APQ0high cells relative to healthy participants, the analysis results also suggested that the levels of APQ0high cells in early erythropoiesis serve as a novel biomarker that distinguishes normal from dysregulated erythropoiesis.

Conclusions

AQP0 was successfully demonstrated to be a marker of erythroid differentiation. The expression levels of AQP0 are downregulated in patients with dyserythropoiesis, indicating a critical role of AQP0 in erythropoiesis. Accordingly, the level of AQP0high in early erythroid precursor cells may serve as a reference parameter for diagnosing diseases associated with dyserythropoiesis.
Adipose-derived mesenchymal stem cells from obese mice prevent body weight gain and hyperglycemia
Authors: Qi Yicheng , Liu Wen , Wang Xiangsheng , Lu Nan , Yang Minglan , Liu Wei , Ma Jing , Liu Wei , Zhang Wenjie , Li Shengxian
Published: May 2021

Changes that occur to the stem cell microenvironment with disease are a major consideration that may affect the behavior and potential therapeutic efficacy of mesenchymal stem cells (MSCs). The purpose of this study is to evaluate the effects of adipose-derived MSCs (ADSCs) from obese mice with hyperglycemia on body weight and glucose homeostasis. After 10 weeks of high-fat diet, mice were injected with phosphate-buffered saline (PBS) and ADSCs derived from normal mice (N-ADSCs) or obese mice (O-ADSCs), respectively. Mice fed with standard rodent chow were injected with PBS and served as normal controls. Obese mice treated with O-ADSCs showed less body weight gain than those receiving PBS or N-ADSCs. The mice that received ADSCs, especially O-ADSCs, also showed improvement in obesity-related hyperglycemia. In particular, the inguinal fat was reduced in obese mice receiving O-ADSCs compared with other groups, probably caused by the increased lipolysis of inguinal fat. Moreover, ADSC infusion restored insulin receptor (INSR) expression in the muscle of obese mice. Differential expression of the CD90 surface marker was slightly increased, while monocyte chemoattractant protein 1 (MCP-1) was reduced in O-ADSCs compared to N-ADSCs. These data provide a theoretical basis that autologous ADSCs from obese individuals may be more effective for treating obesity and related hyperglycemia.
Wireless technologies for the connectivity of the future
Authors: Cardoso Filipe D. , Lipovac Vlatko , Correia Luis M.
Published: May 2021

This Special Issue originates from the international conference EuCNC 2020 (European Conference on Networks and Communications), which was planned to be held in June 2020 in Dubrovnik (Croatia), but due to the COVID-19 pandemic was changed to an Online Conference. The Technical Programme Chairs of the conference have selected the best papers and invited authors to submit an extended version of their paper, by at least one third of their length. Only the top ranked papers were invited to this Special Issue, in order to fulfil its purpose. The main target was to collect and present quality research contributions in the most recent activities related to systems and networks beyond 5G, already presenting ideas for 6G. Through this Special Issue, the state-of-the-art is presented and the new challenges are highlighted, regarding the latest advances on systems and network perspectives that are already being positioned beyond 5G, bridging as well with the evolution of 5G, including applications and trials. Therefore, the motivation for this Special Issue is to present the latest and finest results on the evolution of research of mobile and wireless communications, coming, but not exclusively (since EuCNC is a conference open to the whole research community), from projects co-financed by the European Commission within its R&D programmes.
Factors associated with early antenatal care attendance among women in Papua New Guinea: a population‐based cross‐sectional study
Authors: Seidu Abdul-Aziz
Published: May 2021

Background

Early initiation of antenatal care (ANC) is a key component of antenatal care, as suggested by the World Health Organisation (WHO). It helps in early identification and mitigation of adverse pregnancy-related complications. Despite this, a greater proportion of women worldwide still do not adhere to this recommendation. This study, therefore, sought to assess the prevalence and factors associated with early initiation of ANC among women in Papua New Guinea (PNG).

Methods

A population-based cross-sectional study was conducted among 4,274 women using data from the 2016–2018 PNG Demographic and Health Survey (PDHS). The outcome variable was early initiation of ANC. Bivariate (chi-square) and multivariable logistic regression analyses were done and statistical significance was set at p < 0.05.

Results

The prevalence of early ANC initiation was 23.0 % (CI = 20.8–24.6). The binary logistic regression analysis showed that working women had higher odds of early ANC attendance compared with those who were not working [AOR = 1.37, 95 %CI = 1.17 = 1.60]. The results also showed that women from Islands region had lower odds [AOR = 0.50, 95 %CI = 0.40–0.62] of early ANC attendance compared with those from Southern region. Finally, women with parity 3 had lower odds of early ANC attendance compared to those with parity 1[AOR = 0.64,95 % CI = 0.49–0.84].

Conclusions

This study found a relatively low prevalence of early ANC uptake among women in PNG. The factors associated with early ANC attendance were region of residence, parity, and working status of mothers. To increase early ANC uptake, these factors should be considered when designing new policies or reviewing policies and strategies on ANC uptake to help increase ANC attendance, which can help in the reduction of maternal mortality.
Comparison of appropriateness of Nutri-Score and other front-of-pack nutrition labels across a group of Moroccan consumers: awareness, understanding and food choices
Authors: Aguenaou Hassan , El Ammari Laila , Bigdeli Maryam , El Hajjab Amina , Lahmam Houria , Labzizi Saloua , Gamih Hasnae , Talouizte Anouar , Serbouti Chaimae , El Kari Khalid , Benkirane Hasnae , El Berri Hicham , AL-Jawaldeh Ayoub , Yahyane Abdelhakim
Published: May 2021

Background

The front of pack nutrition label Nutri-Score, intended to help consumers orient their choices towards foods that are more favorable to health, was developed in France and applied in several European countries. Consideration is underway for its use in Morocco. This study aims to assess Moroccan consumers’ perception and objective understanding of Nutri-Score and 4 other nutritional information labels (Health Star Rating, Health warning, Reference Intakes and Multiple Trafic Light) and their impact on purchase intentions.

Methods

814 participants were asked to choose among 3 food classes (yoghurts, biscuits and cold cuts), which ones they would prefer to buy among three products with different nutritional profiles and then to rank them according to their nutritional quality. Participants first performed these tasks without a visible nutritional label, and then, after being randomized to one of five labels tested, with the nutritional label visible on front of packs. Next, the full set of tested labels was presented to the participants who were asked a series of questions regarding their preferences, the attractiveness of the labels, their perceptions, intention to use and the trustworthiness placed in the labels.

Results

Compared to the Reference Intake, the Nutri-Score (OR = 2.48 [1.53–4.05], p < 0.0001), was associated with the highest improvement in the ability to correctly classify foods based on their nutritional quality. The percentage of participants who improved their food choice was higher than those who worsened it for all the labels. For yogurts and cookies, the most significant improvements were observed for the Nutri-Score and the Reference Intakes: Concerning the perception of labels, the Nutri-Score is the label that received the highest number of positive responses, whether concerning the ease of being spotted (82.2%), of being understood (74%), and to provide rapid information (68.8%). The Nutri-Score was ranked as the preferred label by 64.9% of the participants.

Conclusion

The Nutri-Score appears to be the most effective nutritional information system to inform consumers about the nutritional quality of foods in Morocco, where it could constitute a useful tool to help consumers in their food choices in situations of purchase.
Androgen-induced gut dysbiosis disrupts glucolipid metabolism and endocrinal functions in polycystic ovary syndrome
Authors: Han Qixin , Wang Juan , Li Weiping , Chen Zi-Jiang , Du Yanzhi
Published: May 2021

Background

The characteristics of polycystic ovary syndrome (PCOS), a common reproductive endocrinal disorder, are high incidence, complicated aetiology and poor therapeutic effects. PCOS patients frequently exhibit gut dysbiosis; however, its roles in the regulation of metabolic and endocrinal balances in PCOS pathophysiology are not clear.

Results

In this study, gut dysbiosis was reproduced in dehydroepiandrosterone (DHEA)-induced PCOS-like rats. An antibiotic cocktail was used to eliminate gut microbiota during DHEA treatment; however, depletion of the gut microbiota did not prevent the occurrence of PCOS phenotypes in DHEA-treated rats. DHEA-shaped gut microbiota transplanted to pseudo germ-free recipients trigged disturbances in hepatic glucolipid metabolism and reproductive hormone imbalance. The clinical features of PCOS may be correlated with the relative abundance of gut microbes and the levels of faecal metabolites in faecal microbiota transplantation (FMT) recipient rats.

Conclusion

These findings indicate that androgen-induced gut microbiota dysbiosis may aggravate metabolic and endocrinal malfunction in PCOS.
Towards enhancing coral heat tolerance: a “microbiome transplantation” treatment using inoculations of homogenized coral tissues
Authors: Doering Talisa , Wall Marlene , Putchim Lalita , Rattanawongwan Tipwimon , Schroeder Roman , Hentschel Ute , Roik Anna
Published: May 2021

Background

Microbiome manipulation could enhance heat tolerance and help corals survive the pressures of ocean warming. We conducted coral microbiome transplantation (CMT) experiments using the reef-building corals,PocilloporaandPorites, and investigated whether this technique can benefit coral heat resistance while modifying the bacterial microbiome. Initially, heat-tolerant donors were identified in the wild. We then used fresh homogenates made from coral donor tissues to inoculate conspecific, heat-susceptible recipients and documented their bleaching responses and microbiomes by 16S rRNA gene metabarcoding.

Results

Recipients of both coral species bleached at lower rates compared to the control group when exposed to short-term heat stress (34 °C). One hundred twelve (Pocilloporasp.) and sixteen (Poritessp.) donor-specific bacterial species were identified in the microbiomes of recipients indicating transmission of bacteria. The amplicon sequence variants of the majority of these transmitted bacteria belonged to known, putatively symbiotic bacterial taxa of corals and were linked to the observed beneficial effect on the coral stress response. Microbiome dynamics in our experiments support the notion that microbiome community evenness and dominance of one or few bacterial species, rather than host-species identity, were drivers for microbiome stability in a holobiont context.

Conclusions

Our results suggest that coral recipients likely favor the uptake of putative bacterial symbionts, recommending to include these taxonomic groups in future coral probiotics screening efforts. Our study suggests a scenario where these donor-specific bacterial symbionts might have been more efficient in supporting the recipients to resist heat stress compared to the native symbionts present in the control group. These findings urgently call for further experimental investigation of the mechanisms of action underlying the beneficial effect of CMT and for field-based long-term studies testing the persistence of the effect.
Psychotherapists’ emotional reactions to patients’ personality trait in personality disorder treatment settings: an exploratory study
Authors: Cavalera Cesare , Boldrini Annalisa , Merelli Alessia Antonella , Squillari Edoardo , Politi Pierluigi , Pagnini Francesco , Oasi Osmano
Published: May 2021

Background

Therapist’s emotional reactions toward patients in clinical facilities are a key concept in the treatment of personality disorders. Considering only clinical settings specialized in treatment of personality pathology the present paper aimed at: (1) assessing any direct relationship between patient symptom severity and therapist emotional response; (2) exploring patients’ functioning configurations that can be associated with specific therapist reactions (3) investigating whether these relationships remains significant when accounting for other setting variables related to patients or therapist.

Methods

The present study included 43 outpatients with personality disorders who underwent a psychotherapy treatment in two Italian facilities dedicated to outpatients with personality disorders and their 19 psychotherapists. The Symptom Checklist-90-Revised (SCL-90R) was used to explore clinical severity condition. Psychotherapists completed the Therapist Response Questionnaire (TRQ) to identify pattern of therapists’ response and the Shedler-Westen Assessment Procedure-200 (SWAP-200) in order to assess personality traits of the patients.

Results

No significant relationship between the clinical severity of the symptoms and the therapist’ responses was found. Even when controlled for clinical severity condition, duration of the treatment, age and educational level of the patient or years of therapist experience, most of SWAP-200 traits appeared to be significant predictors of therapist’ emotional responses.

Conclusions

The present study confirms the value of therapists’ emotional response as a useful tool in understanding psychological processes related to clinical practice highlighting its context-dependent dimension.
Tumor reversion: a dream or a reality
Authors: Tripathi Avantika , Kashyap Anjali , Tripathi Greesham , Yadav Joni , Bibban Rakhi , Aggarwal Nikita , Thakur Kulbhushan , Chhokar Arun , Jadli Mohit , Sah Ashok Kumar , Verma Yeshvandra , Zayed Hatem , Husain Amjad , Bharti Alok Chandra , Kashyap Manoj Kumar
Published: May 2021

Reversion of tumor to a normal differentiated cell once considered a dream is now at the brink of becoming a reality. Different layers of molecules/events such as microRNAs, transcription factors, alternative RNA splicing, post-transcriptional, post-translational modifications, availability of proteomics, genomics editing tools, and chemical biology approaches gave hope to manipulation of cancer cells reversion to a normal cell phenotype as evidences are subtle but definitive. Regardless of the advancement, there is a long way to go, as customized techniques are required to be fine-tuned with precision to attain more insights into tumor reversion. Tumor regression models using available genome-editing methods, followed by in vitro and in vivo proteomics profiling techniques show early evidence. This review summarizes tumor reversion developments, present issues, and unaddressed challenges that remained in the uncharted territory to modulate cellular machinery for tumor reversion towards therapeutic purposes successfully. Ongoing research reaffirms the potential promises of understanding the mechanism of tumor reversion and required refinement that is warranted in vitro and in vivo models of tumor reversion, and the potential translation of these into cancer therapy. Furthermore, therapeutic compounds were reported to induce phenotypic changes in cancer cells into normal cells, which will contribute in understanding the mechanism of tumor reversion. Altogether, the efforts collectively suggest that tumor reversion will likely reveal a new wave of therapeutic discoveries that will significantly impact clinical practice in cancer therapy.
Current and emerging therapies for primary central nervous system lymphoma
Authors: Yuan Yan , Ding Tianling , Wang Shu , Chen Hong , Mao Ying , Chen Tong
Published: May 2021

Primary central nervous system (CNS) lymphoma (PCNSL) is a rare type of extranodal lymphoma exclusively involving the CNS at the onset, with diffuse large B-cell lymphoma (DLBCL) as the most common histological subtype. As PCNSL is a malignancy arising in an immune-privileged site, suboptimal delivery of systemic agents into tumor tissues results in poorer outcomes in PCNSL than in non-CNS DLBCLs. Commonly used regimens for PCNSL include high-dose methotrexate-based chemotherapy with rituximab for induction therapy and intensive chemotherapy followed by autologous hematopoietic stem cell transplantation or whole-brain radiotherapy for consolidation therapy. Targeted agents against the B-cell receptor signaling pathway, microenvironment immunomodulation and blood-brain barrier (BBB) permeabilization appear to be promising in treating refractory/relapsed patients. Chimeric antigen receptor-T cells (CAR-T cells) have been shown to penetrate the BBB as a potential tool to manipulate this disease entity while controlling CAR-T cell-related encephalopathy syndrome. Future approaches may stratify patients according to age, performance status, molecular biomarkers and cellular bioinformation. This review summarizes the current therapies and emerging agents in clinical development for PCNSL treatment.
Pathophysiological roles of myristoylated alanine-rich C-kinase substrate (MARCKS) in hematological malignancies
Authors: Iyer Deepak Narayanan , Faruq Omar , Zhang Lun , Rastgoo Nasrin , Liu Aijun , Chang Hong
Published: May 2021

The myristoylated alanine-rich C-kinase substrate (MARCKS) protein has been at the crossroads of multiple signaling pathways that govern several critical operations in normal and malignant cellular physiology. Functioning as a target of protein kinase C, MARCKS shuttles between the phosphorylated cytosolic form and the unphosphorylated plasma membrane-bound states whilst regulating several molecular partners including, but not limited to calmodulin, actin, phosphatidylinositol-4,5-bisphosphate, and phosphoinositide-3-kinase. As a result of these interactions, MARCKS directly or indirectly modulates a host of cellular functions, primarily including cytoskeletal reorganization, membrane trafficking, cell secretion, inflammatory response, cell migration, and mitosis. Recent evidence indicates that dysregulated expression of MARCKS is associated with the development and progression of hematological cancers. While it is understood that MARCKS impacts the overall carcinogenesis as well as plays a part in determining the disease outcome in blood cancers, we are still at an early stage of interpreting the pathophysiological roles of MARCKS in neoplastic disease. The situation is further complicated by contradictory reports regarding the role of phosphorylated versus an unphosphorylated form of MARCKS as an oncogene versus tumor suppressor in blood cancers. In this review, we will investigate the current body of knowledge and evolving concepts of the physical properties, molecular network, functional attributes, and the likely pathogenic roles of MARCKS in hematological malignancies. Key emphasis will also be laid upon understanding the novel mechanisms by which MARCKS determines the overall disease prognosis by playing a vital role in the induction of therapeutic resistance. Additionally, we will highlight the importance of MARCKS as a valuable therapeutic target in blood cancers and will discuss the potential of existing strategies available to tackle MARCKS-driven blood cancers.
Different dimensions of teacher and peer assessment of EFL learners’ writing: descriptive and narrative genres in focus
Authors: Pourdana Natasha , Asghari Soheila
Published: May 2021

The present study explored the extent to which teacher assessment (TA) and peer assessment (PA) differ in terms of magnitude and patterns of distribution across English as a Foreign Language (EFL) learners’ descriptive and narrative writing performance. Twenty Persian-speaking EFL learners were non-randomly selected and voluntarily participated in a 12-session writing course at a private language school in Iran. Their performance on descriptive and narrative writing tasks was subjected to PA and TA sequentially. The West Virginia Department of Education descriptive writing rubric (with five components of organization, development, sentence structure, word choice and grammar, and mechanics) and Smarter Balanced narrative writing rubric (with five categories of narrative focus, organization, elaboration of narrative, language and vocabulary, and conventions) were adopted to schematize and analyze the distribution of the TA and PA comments. The results of frequency analysis indicated that TA far outnumbered PA on both descriptive and narrative genres of writing. Furthermore, on both descriptive and narrative writings, TA and PA commentaries were local in scope, form-focused, fluctuating, and inconsistent. Also, the distribution of TA and PA comments mainly focused on the conventions of narrative writings, while other macro-components of narrative writing had a steady and depleted pattern. The statistical results confirmed the significance of the observed differences between the number and the nature of TA and PA on descriptive and narrative genres of writing. The researchers made their concluding remarks on the probable causes of observed diversities, imposed limitations of the study, and a number of topics for future research.
Complex tsunami hazards in eastern Indonesia from seismic and non-seismic sources: Deterministic modelling based on historical and modern data
Authors: Pranantyo Ignatius R. , Heidarzadeh Mohammad , Cummins Phil R.
Published: May 2021

Eastern Indonesia is one of the world’s most complex regions in terms of tsunami hazards, as it accommodates numerous seismic and non-seismic tsunami sources with a history of deadly tsunamis. This study is an effort to enhance tsunami hazard knowledge in eastern Indonesia where limited data and analyses exist. We provide a brief understanding of eastern Indonesia’s tsunami hazards by modelling selected deterministic tsunami scenarios from tectonic, submarine mass failure (SMF), and volcanic sources. To our knowledge, this is the first time that tsunami hazards modelling from such diverse sources in Indonesia has been performed. Our methodology is a deterministic tsunami hazard analysis considering credible tsunami sources from historical and contemporary data, modelling them using state-of-the-art simulation tools. We modelled two Mw7.8 tsunamigenic earthquake scenarios on the Flores back-arc thrust, one rupturing the basal fault (FBT-BF) and the other rupturing the splay fault (FBT-SF), showing that the two scenarios produce maximum tsunami amplitudes of$$\sim$$∼5.3 m and$$\sim$$∼4.2 m, respectively, which are comparable to the deadly 1992 Flores tsunami. We modelled potential SMF-generated tsunamis in the Makassar Strait with SMF volumes of 5$$\hbox {km}^3$$km3and 225$$\hbox {km}^3$$km3which yielded maximum tsunami heights of$$\sim$$∼1.1 m and$$\sim$$∼4.3 m along the eastern coast of Kalimantan Island and$$\sim$$∼2.9 m and$$\sim$$∼11.1 m along the west shore of Sulawesi Island, respectively. The 1871 Ruang volcanic tsunami is studied through existing historical documents and a source model is proposed comprising a flank collapse with volume of$$0.10\ \mathrm{km}^3$$0.10km3. Such a source model successfully reproduced the 25 m runup reported in a historical account.
Continuous multi-component MAX-DOAS observations for the planetary boundary layer ozone variation analysis at Chiba and Tsukuba, Japan, from 2013 to 2019
Authors: Irie Hitoshi , Yonekawa Daichi , Damiani Alessandro , Hoque Hossain Mohammed Syedul , Sudo Kengo , Itahashi Syuichi
Published: May 2021

Ground-based remote sensing using multi-axis differential optical absorption spectroscopy (MAX-DOAS) was used to conduct continuous simultaneous observations of ozone (O3), nitrogen dioxide (NO2), and formaldehyde (HCHO) concentrations at Chiba (35.63° N, 140.10° E, 21 m a.s.l.) and Tsukuba (36.06° N, 140.13° E, 35 m a.s.l.), Japan, for 7 years from 2013 to 2019. These are urban and suburban sites, respectively, in the greater Tokyo metropolitan area. NO2 and HCHO are considered to be proxies for nitrogen oxides (NOx) and volatile organic compounds (VOCs), respectively, both of which are major precursors of tropospheric O3. The mean concentrations below an altitude of 1 km were analyzed as planetary boundary layer (PBL) concentrations. For a more spatially representative analysis around the urban area of Chiba, four MAX-DOAS instruments directed at four different azimuth directions (north, east, west, and south) were operated simultaneously and their data were unified. During the 7-year period, the satellite observations indicated an abrupt decrease in the tropospheric NO2 concentration over East Asia, including China. This suggested that the transboundary transport of O3 originating from the Asian continent was likely suppressed or almost unchanged during the period. Over this time period, the MAX-DOAS observations revealed the presence of almost-constant annual variations in the PBL O3 concentration, whereas reductions in NO2 and HCHO concentrations occurred at rates of approximately 6–10%/year at Chiba. These changes provided clear observational evidence that a decreasing NOx concentration significantly reduced the amount of O3 quenched through NO titration under VOC-limited conditions in the urban area. Under the dominant VOC-limited conditions, the MAX-DOAS-derived concentration ratio of HCHO/NO2 was found to be below unity in all months. Thus, the multi-component observations from MAX-DOAS provided a unique data set of O3, NO2, and HCHO concentrations for analyzing PBL O3 variations.
Clinical exome sequencing facilitates the understanding of genetic heterogeneity in Leber congenital amaurosis patients with variable phenotype in southern India
Authors: Viswarubhiny Sriee , Anjanamurthy Rupa , Vanniarajan Ayyasamy , Bharanidharan Devarajan , Perumalsamy Vijayalakshmi , Sundaresan Periasamy
Published: May 2021

Background

Leber congenital amaurosis (LCA), primarily characterized by retinal degeneration is the most severe form of inherited retinal dystrophy (IRD) responsible for congenital blindness. The presence of phenotypic heterogeneity makes the diagnosis of LCA challenging, especially in the absence of pronounced disease pathognomonic, yet it can be well comprehended by employing molecular diagnosis. Therefore, the present study aimed to reveal the causative mutations in ten LCA patients with variable phenotypes using clinical exome sequencing (CES).

Methods

CES was performed in ten unrelated LCA patients. Ophthalmic information and family history of all patients were obtained to make a meaningful interpretation. The clinical exome data was analyzed and prioritized using a bioinformatics pipeline to identify mutations, which was further validated by Sanger sequencing. Segregation analysis was also performed on available family members.

Results

CES led to the identification of causative mutations in nine LCA patients. Seven patients harbored a mutation in six LCA candidate genes, including RPE65, LCA5 (n = 2), CRX, PRPH2, CEP290, and ALMS1, while two patients possess a mutation in IFT80 and RP1, known to cause other diseases. Three novel mutations in LCA5 (c.1823del), CRX (c.848del) and CEP290 (c.2483G > T) were identified. The current study reports for the first time, a mutation in PRPH2, CEP290, and ALMS1 from the Indian population. Additionally, we observed a novel association of LCA phenotype with IFT80 known to cause Jeune syndrome. Based on the genetic finding, the patient AS09, who harbored a mutation in the RP1 gene, was re-diagnosed with early-onset retinitis pigmentosa.

Conclusion

In conclusion, the results underline the importance of CES in clinically diagnosed LCA patients with variable phenotypes. The correlation between mutations in candidate genes and clinical phenotypes, helps to refine the clinical diagnosis. However, molecular evaluation with a larger cohort of LCA patients is needed for better understanding of the mutational spectrum in southern India.
Usefulness of the Monti–Malone procedure as a reconstruction of the antegrade continence enema procedure: a case report
Authors: Saito Koichi , Kinoshita Yoshiaki , Takahashi Yoshiaki , Kobayashi Takashi , Arai Yuhki , Ohyama Toshiyuki , Yokota Naoki
Published: May 2021

Background

The antegrade continence enema (ACE) procedure is effective for severe constipation in patients with spina bifida and can improve quality of life (QOL). The Monti–Malone procedure (MM), which is a method of creating an enema tract from the colon, has been reported as an alternative to the ACE procedure when the appendix cannot be used. We report the usefulness of MM as a reconstruction of the antegrade continence enema procedure.

Case presentation

Our patient was a 22-year-old man with congenital spina bifida and hydrocephalus. Ventriculoperitoneal (VP) shunt surgery was performed immediately after birth, and preventative appendectomy was carried out during VP shunt repair when 4 months old. At 5 years of age, the ACE procedure using a balloon-button gastrostomy tube was performed for intractable chronic constipation. Simple management was expected, but after 17 years of age, he experienced increased stool leakage around the gastrostomy tube and his QOL declined due to difficulty in managing the ACE. Therefore, reconstruction of the ACE procedure by MM was performed. After reconstruction, the ACE performed well without any complications. The patient is currently satisfied because management of the ACE is easier than before, and his QOL has markedly improved without stool leakage and dermatitis.

Conclusions

MM is less likely to cause complications and is useful as a reconstruction of the ACE procedure.
Osteogenic effects of exosomes derived from human chorion membrane extracts
Authors: Go Yoon Young , Chae Sung-won , Song Jae-Jun
Published: May 2021

Objective

Human chorion membrane extracts (CME) are known to exhibit osteogenic effects when used for treating human osteoblast-like cells (MG63 cells), but the active compound in CME remains unknown. The aim of this study was to identify the presence of exosomes in CME and to determine the osteogenic effect of CME exosomes on MG63 cells.

Methods

Exosomes were isolated from human placenta CME using the ExoQuick-TC solution and were characterized. The activity and deposition of alkaline phosphatase (ALP) on MG63 cells cultured with or without exosomes in osteogenic induction medium (OIM) were determined. Human amniotic membrane extracts (AME) were used as controls as they had not affected the osteogenic differentiation of MG63 cells in our previous study.

Results

Transmission electron microscopy (TEM) revealed that exosomes isolated from CME and AME (CME-Exo and AME-Exo, respectively) had a cup-shaped structure. NanoSight™ particle tracking analysis (NTA) confirmed that the size of these exosomes was 100–150 nm. In vitro osteogenic experiments demonstrated that the exosomes from CME, but not those from AME, presented increased alkaline phosphatase (ALP) activity and resulted in the mineralization of MG63 cells in a dose-dependent manner.

Conclusion

Exosomes were identified in CME and AME from the human placenta. Further, the exosomes from CME were found to be capable of promoting osteogenic differentiation, suggesting that exosomes are a key component of CME that stimulate the osteogenesis of human osteoblast-like cells. CME exosomes can be developed as promising therapeutic candidates for bone regeneration.
A hybrid heterogeneous Pythagorean fuzzy group decision modelling for crowdfunding development process pathways of fintech-based clean energy investment projects
Authors: Meng Yue , Wu Haoyue , Zhao Wenjing , Chen Wenkuan , Dinçer Hasan , Yüksel Serhat
Published: May 2021

This study aims to evaluate the crowdfunding alternatives regarding new service development process pathways of clean energy investment projects. In this framework, a new model has been generated by considering the consensus-based group decision-making with incomplete preferences, Pythagorean fuzzy decision-making trial and evaluation laboratory (DEMATEL) and technique for order preference by similarity to ideal solution (TOPSIS). Moreover, a comparative evaluation has been performed with Vise Kriterijumska Optimizacija I. Kompromisno Resenje methodology and sensitivity analysis has been made by considering 4 different cases. The main contribution is to identify appropriate crowdfunding-based funding alternatives for the improvement of the clean energy investments with a novel MCDM model. By considering the iteration technique and consensus-based analysis, the missing parts in the evaluations can be completed and opposite opinion problems can be reduced. Furthermore, with the help of hybrid MCDM model by combining DEMATEL and TOPSIS, more objective results can be reached. It is concluded that the analysis results are coherent and reliable. The findings indicate that the full launch is the most significant criterion for equity and debt-based crowdfunding alternatives. On the other side, the analysis has the highest weight for reward and donation-based alternatives whereas design is the most essential item regarding the royalty-based alternative. Additionally, it is also defined that equity-based crowdfunding alternative is the most significant for the service development process of clean energy investment projects. In this way, it will be possible to provide a continuous resource for clean energy investment projects. On the other hand, by providing financing with equity, there will be no fixed financing cost for clean energy investors. If these investors make a profit, they distribute dividends with the decision of their authorized bodies.
Relationship between perceived social support and postpartum care attendance in three Latin American countries: a cross-sectional analytic study
Authors: Cardona Cordero Nancy R. , Ramos José Perez , Tavarez Zahira Quiñones , McIntosh Scott , Avendaño Esteban , DiMare Carmen , Ossip Deborah J. , De Ver Dye Timothy
Published: May 2021

Background

Postpartum Care is a strategy to improve survival of women and newborns, especially in low- and middle-income countries. Early post-partum care can promote healthy behaviors and the identification of risk factors associated with poorer pregnancy-related outcomes. The objective of this study was to assess the association of perceived social support with attendance to post-partum care in women from three Latin-American and Caribbean countries: Costa Rica, Dominican Republic and Honduras.

Methods

Women aged 18+ who completed a pregnancy in the past 5 years were interviewed in local healthcare and community settings in each country. Perceived social support (PSS) was the primary explanatory variable and the primary outcome was self-reported attendance to post-partum care. Odds Ratios (OR) with 95% confidence intervals derived from logistic regression documented the association between variables. Adjusted Odds Ratios (AOR) were calculated, controlling for social and pregnancy-related confounders. Hosmer– Lemeshow’s Goodness-of-Fit statistic was computed to assess model fit.

Results

Our cohort of 1199 women across the three Latin-American and Caribbean countries showed relatively high attendance to post-partum care (82.6%, n = 990). However, 51.7% (n = 581) of women reported lower levels of total PSS. Women were more likely to attend postpartum care if they had mean and higher levels of PSS Family subscale (OR: 1.9, 95%CI: 1.4, 2.7), Friends subscale (OR 1.3, 95%CI: 0.9,1.8), Significant Other subscale (OR 1.8, 95%CI: 1.3, 2.4) and the Total PSS (OR 1.8, 95%CI: 1.3, 2.5). All associations were statistically significant at p < 0.05, with exception of the Friends subscale. Women with higher levels of total PSS were more likely to attend to post-partum care (AOR:1.40, 0.97, 1.92) even after controlling for confounders (education, country, and food insecurity).

Conclusions

Women with higher perceived social support levels were more likely to attend to post-partum care. From all countries, women from Dominican Republic had lower perceived social support levels and this may influence attendance at post-partum care for this subgroup. Societal and geographic factors can act as determinants when evaluating perceived social support during pregnancy.
Transarterial embolization with n-butyl cyanoacrylate for the treatment of active abdominopelvic bleeding in the polytraumatized patient
Authors: de Freitas Rafael Kiyuze , Monsignore Lucas Moretti , Castro-Afonso Luis Henrique de , Nakiri Guilherme Seizem , Elias-Junior Jorge , Muglia Valdair Francisco , Scarpelini Sandro , Abud Daniel Giansante
Published: May 2021

Purpose

An increasing number of polytraumatized patient presenting with active abdominal pelvic bleeding (APB) have been treated by endovascular selective embolization. However, reports on evaluate the efficacy, safety and complications caused by this technique have been limited. The aim of this study was to assess the safety and efficacy of embolization of APB using N-butyl cyanoacrylate glue (NBCA).

Materials and methods

Single center retrospective study, that included consecutive 47 patients presenting with traumatic APB treated by embolization with NBCA between January 2013 and June 2019. The efficacy endpoint was defined as the absence of contrast extravasation immediately after procedure and clinical stabilization in the following 24 h after procedure. Clinical stabilization was defined as no rebleeding after embolization or the need for a surgical approach until the patient is discharged. Safety endpoint were any technical or clinical complications related to the embolization procedure.

Results

The mean age of patients was 38.6 years (3–81), with a predominance of males (87.2%). The major causal factor of APB being involvement in a car accident, accounting for 68% of cases. Of the 47 cases, 29.8% presented pelvic trauma and the remaining (70.2%) presented abdominal trauma. The efficacy rate was 100%, while no complications related to the procedure were observed. The mortality rate was 14.8% (7/47) due to neurologic decompensation and other clinical causes.

Conclusion

Endovascular embolization of traumatic abdominopelvic bleedings appear to be a highly safe and effective treatment, while avoiding emergent exploratory open surgeries.
What are the informational pathways that shape people’s use of cannabidiol for medical purposes?
Authors: Zenone Marco A. , Snyder Jeremy , Crooks Valorie A.
Published: May 2021

Background

Cannabidiol (CBD) is commonly used to manage symptoms in conditions and diseases for which there is limited clinical research for its application. How consumers arrive and decide to use CBD for medical treatment, despite lacking clinical evidence, is largely unknown. In this paper, we seek to identify the informational pathways through which consumers arrive at CBD for medical purposes.

Methods

GoFundMe.com campaigns fundraising to purchase CBD between June 2017 and May 2019 were collected using the Crowdfunding for Health Research Portal (CHRP). Product descriptions were thematically analyzed to determine pathways leading to incorporation of CBD into medical treatment. Campaign characteristics such as fundraising ask, funding received, location, campaign title, description, Facebook shares, and number of donors were recorded. Specific medical uses of CBD proposed in campaigns were tabulated.

Results

The study identified 164 crowdfunding campaigns primarily from the USA (n=159), with several from Canada (n=5). The campaigns requested $2,219,284.24 (median, $7000) and raised $610,612.87 (median, $1805) from 6825 donors (median, 26). Many campaigns asked for other treatments or illness-related costs not specific to CBD. The campaigns were shared 42,299 times on Facebook (median, 156 shares). Three informational pathways were identified leading to incorporation of CBD into medical treatment, which were self-directed research (n=149), recommendations from a trusted care provider (n=36), and/or experiential insights shared by someone associated with or influencing the crowdfunders personal network (n=30). The proposed uses of CBD were for cancer (n=96), seizure-inducing diseases/conditions (n=48), other/unspecified (n=6), joint/inflammatory diseases (n=6), mental health disorders (n=3), nervous system diseases (n=3), and autoimmune diseases (n=2).

Conclusions

Our results suggest that consumers crowdfunding come to CBD through internally motivated reasons versus exposure to advertisements or other forms of marketing. Campaign beneficiaries generally had an unmet medical need that other forms of treatment were not satisfying. Then, through one or more of the informational pathways identified, CBD is considered a potential solution.
Plasma brain-derived neurotrophic factor (BDNF) in Egyptian children with attention deficit hyperactivity disorder
Authors: El Ghamry Reem , El-Sheikh Mona , Abdel Meguid Marwa , Nagib Safi , Aly El Gabry Dina
Published: May 2021

Background

To date, researchers do not fully understand what the aetiology of attention deficit hyperactivity disorder (ADHD) is. As a neurotrophin, the brain-derived neurotrophic factor (BDNF) contributes to the growth of neurons as well as to the efficiency and plasticity of the neuronal synapse, which suggests that it may be a contributing aetiological factor in ADHD. Therefore, we sought to investigate the relationship between ADHD and plasma BDNF, including whether there is an association between BDNF and the degree of severity of ADHD and with ADHD subtypes.

Results

We found significantly elevated plasma BDNF in ADHD subjects in comparison with healthy subjects, but differences among the three subtypes of ADHD did not reach statistical significance.

Conclusion

Compared with the control group, elevated plasma BDNF levels were found in the ADHD group, which suggests it may contribute to the aetiology of ADHD.