bluuebunny/crossref_metadata_2025 huggingface dataset:
THE TOPIC OF KOSOVO IN THE WORK OF ISMAIL KADARE
Authors: Muhadri Prof.Asoc.Dr. Besim
Published: May 2021

Ismail Kadare (1936) is one of the most famous writers of contemporary Albanian literature. He is the author of dozens of books of poetry and prose, which have been translated into 45 languages of the world, making him one of the most translated Albanian writers, but also the most famous in the world. He is a laureate of many international awards and several times nominated for the Nobel Prize for literature.
In my paper, I will address the aspects of his contribution in addressing the topic of Kosovo, both in the field of poetry and in that of prose and journalism. With this topic, in addition to some poems, he has published the novels "Krushqit janë të ngrirë", "Tri Këngë zie për Kosovën", as well as the publicist books "Ra ky mort e u pamë", "Bisedë mes grilash" and "Çlirimi I Serbisë Nga Kosova". Kadare's treatment of the Kosovo issue on an artistic level has made the violation of the national rights of the autochthonous Albanians of Kosovo by the Serbian occupying regime, in particular, and the issue of Kosovo, in general, sensitized in the international arena.
The methods used in this paper are that of analysis and synthesis.
Value-Based Leadership in Crowdfunding Digital Startup: A Qualitative Study in iGrow and KITABISA
Authors: Hendrasto Nur , Dharmawan Arya Hadi , Sumardjo Sumardjo , Mohammad Baga Lukman
Published: May 2021

This study aims to identify the basic values of crowdfunding digital startup leaders at iGrow and kitabisa and also to understand how these values were created. Individual value systems are related to people's attitudes and behavior, especially in the leadership decision-making process. iGrow as an investment company for agriculture products has an orientation toward achieving profits, while kitabisa as a social movement platform has a social orientation toward helping others. This study used a qualitative approach through the in-depth interview from snowball sampling that served as the primary data. The research result proposed nine main values identified from leaders of both startup companies. The main values of iGrow leader were achievement goals, hard work, legacy, togetherness, and role models, while those of Kitabisa leader were rational, learning, hustler, genuine caring, and legacy. From the process in which these values were created, this study proposed a theory on a different path of value creation, called the value creation pathway. These research findings were only limited to the two leaders from iGrow and Kitabisa.
Analisis Mitigasi Penanggulangan Bencana di Kabupaten Ogan Komering Ulu
Authors: SUSANTI EVA , Anggara Ikang Putra
Published: May 2021

Bencana alam adalah suatu kondisi yang tidak kita harapkan, oleh karena itu pemahaman terhadap  proses terjadinya bencana serta faktor penyebab terjadinya bencana menjadi sangat penting bagi pemerintah dan masyarakat. Salah satu bencana yang menjadi perhatian pemerintah dan masyarakat adalah tanah longsor yang perlu diketahui dampak dan cara penanggulangannya. Alternatif yang dilakukan dapat berupa mitigasi penanggulangan bencana, hal ini mampu mengurangi resiko yang berkelanjutan terhadap kerentanan terjadinya bahaya tanah longsor. Penelitian ini memiliki tujuan untuk menganalisis dan mengamati bagaimana mitigasi penanggulangan bencana  yang ada di Kabupaten Ogan Komering Ulu. Penelitian ini merupakan jenis penelitian deskriftif menggunakan pendekatan kualitatif, Subjek penelitian merupakan individu dan atau kelompok yang diharapkan peneliti dapat menceritakan apa yang diketahui tentang sesuatu yang berkaitan dengan fenomena atau kasus yang diteliti. Hasil penelitian dan pembahasan, BPBD Ogan Komering Ulu sebagai Badan yang bertugas bidang kebencanaan tremasuk bencana tanah longsor dalam melakukan tahapan mitigasi seperti pemetaan, pemeriksaan, penyelidikan dan sosialisasi belum secara maksimal melakukan mitigasi penanggulangan bencana. Tindakan penanggulangan bencana dilakukan oleh pihak BPBD dilakukan setelah bencana terjadi.
The PENGARUH TEKANAN KETAATAN, KOMPLEKSITAS TUGAS DAN KEAHLIAN AUDIT TERHADAP AUDIT JUDGEMENT
Authors: SAMBODO BAMBANG , Fitriani Ivone
Published: May 2021

Metode penelitian yang digunakan dalam penelitian ini adalah metode penelitian deskriptif kuantitatif dengan populasi penelitian yang diambil oleh penulis adalah Auditor pada kantor BPK RI Perwakilan Kepulauan Riau berjumlah 37 orang dan semua populasi dijadikan sampel penelitian. Teknik analisis data yang digunakan adalah Uji Regresi Linier Berganda lalu melakukan pengujian Hipotesis. Secara parsial Tekanan Ketaatan (X1), Komplekasitas Tugas (X2) dan Keahlian Audit (X3) berpengaruh signifikan terhadap Audit Judgement (Y). Secara simultan Tekanan Ketaatan, Kompleksitas Tugas dan Keahlian Audit Berpengaruh Signifikan terhadap Audit Judgement pada kantor BPK RI perwakilan provinsi Kepulauan Riau.
Towards the Large-Eddy Simulation of a full engine: Integration of a 360 azimuthal degrees fan, compressor and combustion chamber. Part I: Methodology and initialisation
Authors: Pérez Arroyo Carlos , Dombard Jérôme , Duchaine Florent , Gicquel Laurent , Martin Benjamin , Odier Nicolas , Staffelbach Gabriel
Published: May 2021

Optimising the design of aviation propulsion systems using computational fluid dynamics is essential to increase their efficiency and reduce pollutant as well as noise emissions. Nowadays, and within this optimisation and design phase, it is possible to perform meaningful unsteady computations of the various components of a gas-turbine engine. However, these simulations are often carried out independently of each other and only share averaged quantities at the interfaces minimising the impact and interactions between components. In contrast to the current state-of-the-art, this work presents a 360 azimuthal degrees large-eddy simulation with over 2100 million cells of the DGEN-380 demonstrator engine enclosing a fully integrated fan, compressor and annular combustion chamber at take-off conditions as a first step towards a high-fidelity simulation of the full engine. In order to carry such a challenging simulation and reduce the computational cost, the initial solution is interpolated from stand-alone sectoral simulations of each component. In terms of approach, the integrated mesh is generated in several steps to solve potential machine dependent memory limitations. It is then observed that the 360 degrees computation converges to an operating point with less than 0.5% difference in zero-dimensional values compared to the stand-alone simulations yielding an overall performance within 1% of the designed thermodynamic cycle. With the presented methodology, convergence and azimuthally decorrelated results are achieved for the integrated simulation after only 6 fan revolutions.
Pengetahuan dan Sikap Guru Tentang Mitigasi Bencana Gempa Bumi dan Tsunami Di Daerah Rawan Tsunami Kota Palu
Authors: Christine Christine , Politon Fellysca V. M. , Ellen
Published: May 2021

Penelitian ini bertujuan untuk mengetahui pengetahuan dan sikap guru tentang mitigasi bencana gempa bumi dan tsunami di SDN 01 dan SDN 02 Talise Kota Palu. Penelitian ini merupakan penelitian deskriptif, populasi dan sampel adalah guru di SDN 01 dan SDN 02 Talise Kota Palu sejumlah 43 orang (23 orang di SDN 01 Talise dan 20 orang di SDN 02 Talise Kota Palu). Hasil penelitian ini menunjukkan bahwa pengetahuan responden tentang mitigasi bencana gempa bumi dan tsunami, yang berpengetahuan baik sebanyak  22 responden (51,2%), yang cukup sebanyak 20 responden (46,5%), dan yang kurang sebanyak 1 responden (2,3%). Sikap responden tentang mitigasi bencana gempa bumi dan tsunami, lebih banyak yang bersikap positif sebanyak 29 responden (67,4%) dari pada yang bersikap negatif sebanyak 14 responden (32,6%). Saran bagi SDN 01 dan SDN 02 Talise Kota Palu, perlu adanya buku panduan khusus mengenai materi kebencanaan dan mitigasinya baik bagi guru maupun peserta didik
Kombinasi Contrast Bath dengan Foot Massage Menurunkan Edema Kaki Pada Pasien Congestive Heart Failure
Authors: Manggasa Dafrosia Darmi , Agusrianto Agusrianto , Djua Muhamad Fikran
Published: May 2021

Tujuan penelitian menilai efektifitas kombinasi terapi contrast bath dengan foot massage dalam menurunkan edema kaki pada pasien CHF. Metode peneltiian quasi eksperimen desain two group pre-post test. Penelitian di laksanakan di RSUD Poso bulan Januari –April 2021. Sampel yaitu pasien CHF yang mengalami edema kaki sebanyak 30 orang dibagi dalam 2 kelompok yaitu kelompok kontrol dan kelompok perlakuan. Kelompok perlakuan mendapatkan intervensi kombinasi contrast bath dengan foot massage. Hasil peneltiian menunjukkan reerata nilai lingkar kaki pada kelompok perlakuan sebelum intervensi yaitu 22,37 cm dan setelah intervensi 21,59 cm. Hasil uji statistik terdapat perbedaan yang signifikan rerata nilai lingkar kaki sebelum dan setelah intervensi (p = 0,000). Pada kelompok perlakuan rerata kedalaman edema kaki sebelum intervensi 4,97 cm dan setelah intervensi 2,07 cm. Hasil uji statistik terdapat perbedaan yang signifikan rerata kedalaman edema kaki kaki sebelum dan setelah intervensi (p = 0,000). Kesimpulan yaitu kombinasi contrast bath dengan foot massage efektif menurunkan edema kaki pada pasien CHF. Kombinasi contrast bath dengan foot massage dapat diterapkan oleh perawat di Rumah Sakit untuk menurunkan edema kaki pada pasien
The Rhinobiome of Exacerbated Wheezers and Asthmatics: Insights From a German Pediatric Exacerbation Network
Authors: Aydin Malik , Weisser Cornelius , Rué Olivier , Mariadassou Mahendra , Maaß Sandra , Behrendt Ann-Kathrin , Jaszczyszyn Yan , Heilker Tatje , Spaeth Maximilian , Vogel Silvia , Lutz Sören , Ahmad-Nejad Parviz , Graf Viktoria , Bellm Aliyah , Weisser Christoph , Naumova Ella A. , Arnold Wolfgang H. , Ehrhardt Anja , Meyer-Bahlburg Almut , Becher Dörte , Postberg Jan , Ghebremedhin Beniam , Wirth Stefan
Published: May 2021

Although the nose, as a gateway for organism–environment interactions, may have a key role in asthmatic exacerbation, the rhinobiome of exacerbated children with asthma was widely neglected to date. The aim of this study is to understand the microbiome, the microbial immunology, and the proteome of exacerbated children and adolescents with wheeze and asthma. Considering that a certain proportion of wheezers may show a progression to asthma, the comparison of both groups provides important information regarding clinical and phenotype stratification. Thus, deep nasopharyngeal swab specimens, nasal epithelial spheroid (NAEsp) cultures, and blood samples of acute exacerbated wheezers (WH), asthmatics (AB), and healthy controls (HC) were used for culture (n = 146), 16 S-rRNA gene amplicon sequencing (n = 64), and proteomic and cytokine analyses. Interestingly, Proteobacteria were over-represented in WH, whereas Firmicutes and Bacteroidetes were associated with AB. In contrast, Actinobacteria commonly colonized HCs. Moreover, Staphylococcaceae, Enterobacteriaceae, Burkholderiaceae, Xanthobacteraceae, and Sphingomonadaceae were significantly more abundant in AB compared to WH and HC. The α-diversity analyses demonstrated an increase of bacterial abundance levels in atopic AB and a decrease in WH samples. Microbiome profiles of atopic WH differed significantly from atopic AB, whereby atopic samples of WH were more homogeneous than those of non-atopic subjects. The NAEsp bacterial exposure experiments provided a disrupted epithelial cell integrity, a cytokine release, and cohort-specific proteomic differences especially for Moraxella catarrhalis cultures. This comprehensive dataset contributes to a deeper insight into the poorly understood plasticity of the nasal microbiota, and, in particular, may enforce our understanding in the pathogenesis of asthma exacerbation in childhood.
Effect of De-noising by Wavelet Filtering and Data Augmentation by Borderline SMOTE on the Classification of Imbalanced Datasets of Pig Behavior
Authors: Jin Min , Wang Chunguang , Jensen Dan Børge
Published: May 2021

Classification of imbalanced datasets of animal behavior has been one of the top challenges in the field of animal science. An imbalanced dataset will lead many classification algorithms to being less effective and result in a higher misclassification rate for the minority classes. The aim of this study was to assess a method for addressing the problem of imbalanced datasets of pigs' behavior by using an over-sampling method, namely Borderline-SMOTE. The pigs' activity was measured using a triaxial accelerometer, which was mounted on the back of the pigs. Wavelet filtering and Borderline-SMOTE were both applied as methods to pre-process the dataset. A multilayer feed-forward neural network was trained and validated with 21 input features to classify four pig activities: lying, standing, walking, and exploring. The results showed that wavelet filtering and Borderline-SMOTE both lead to improved performance. Furthermore, Borderline-SMOTE yielded greater improvements in classification performance than an alternative method for balancing the training data, namely random under-sampling, which is commonly used in animal science research. However, the overall performance was not adequate to satisfy the research needs in this field and to address the common but urgent problem of imbalanced behavior dataset.
Genetic Screening Revealed Latent Keratoconus in Asymptomatic Individuals
Authors: Chen Shihao , Li Xing-Yong , Jin Jia-Jia , Shen Ren-Juan , Mao Jian-Yang , Cheng Fei-Fei , Chen Zhen-Ji , Linardaki Emmanouela , Voulgaraki Stavroula , Aslanides Ioannis M. , Jin Zi-Bing
Published: May 2021

Purpose

To adopt molecular screening in asymptomatic individuals at high risk of developing keratoconus as a combinative approach to prevent subclinical patients from post-refractive surgery progressive corneal ectasia.

Methods

In this study, 79 Chinese and nine Greek families with keratoconus were recruited, including 91 patients with clinically diagnosed keratoconus as well as their asymptomatic but assumptive high-risk first-degree relatives based on underlying genetic factor. Mutational screening of VSX1, TGFBI, and ZEB1 genes and full clinical assessment including Pentacam Scheimpflug tomography were carried out in these individuals.

Results

Five variants in VSX1 and TGFBI genes were identified in three Chinese families and one Greek family, and four of them were novel ones. Surprisingly, ultra-early corneal changes in Belin/Ambrosio Enhanced Ectasia Display of Pentacam corneal topography together with co-segregated variants were revealed in the relatives who had no self-reported symptoms.

Conclusions

Variants of VSX1 and TGFBI genes identified in both the clinically diagnosed and subclinical patients may cause the keratoconus through an autosomal dominant inheritance pattern, with different variable expressivity. Combining genetic with Belin/AmbrosioEnhanced Ectasia Display can be used to identify patients with latent keratoconus. This study indicates that genetic testing may play an important supplementary role in re-classifying the disease manifestation and evaluating the preoperative examination of refractive surgery.
CRISPR-Cas9 Editing of Human Histone Deubiquitinase Gene USP16 in Human Monocytic Leukemia Cell Line THP-1
Authors: Gažová Iveta , Lefevre Lucas , Bush Stephen J. , Rojo Rocio , Hume David A. , Lengeling Andreas , Summers Kim M.
Published: May 2021

USP16 is a histone deubiquitinase which facilitates G2/M transition during the cell cycle, regulates DNA damage repair and contributes to inducible gene expression. We mutated the USP16 gene in a high differentiation clone of the acute monocytic leukemia cell line THP-1 using the CRISPR-Cas9 system and generated four homozygous knockout clones. All were able to proliferate and to differentiate in response to phorbol ester (PMA) treatment. One line was highly proliferative prior to PMA treatment and shut down proliferation upon differentiation, like wild type. Three clones showed sustained expression of the progenitor cell marker MYB, indicating that differentiation had not completely blocked proliferation in these clones. Network analysis of transcriptomic differences among wild type, heterozygotes and homozygotes showed clusters of genes that were up- or down-regulated after differentiation in all cell lines. Prior to PMA treatment, the homozygous clones had lower levels than wild type of genes relating to metabolism and mitochondria, including SRPRB, encoding an interaction partner of USP16. There was also apparent loss of interferon signaling. In contrast, a number of genes were up-regulated in the homozygous cells compared to wild type at baseline, including other deubiquitinases (USP12, BAP1, and MYSM1). However, three homozygotes failed to fully induce USP3 during differentiation. Other network clusters showed effects prior to or after differentiation in the homozygous clones. Thus the removal of USP16 affected the transcriptome of the cells, although all these lines were able to survive, which suggests that the functions attributed to USP16 may be redundant. Our analysis indicates that the leukemic line can adapt to the extreme selection pressure applied by the loss of USP16, and the harsh conditions of the gene editing and selection protocol, through different compensatory pathways. Similar selection pressures occur during the evolution of a cancer in vivo, and our results can be seen as a case study in leukemic cell adaptation. USP16 has been considered a target for cancer chemotherapy, but our results suggest that treatment would select for escape mutants that are resistant to USP16 inhibitors.
Application Fields, Positions, and Bioinformatic Mining of Non-active Sites: A Mini-Review
Authors: Wang Xiaoxiao , Ma Qinyuan , Shen Jian , Wang Bin , Gao Xiuzhen , Zhao Liming
Published: May 2021

Active sites of enzymes play a vital role in catalysis, and researchhas been focused on the interactions between active sites and substrates to understand the biocatalytic process. However, the active sites distal to the catalytic cavity also participate in catalysis by maintaining the catalytic conformations. Therefore, some researchers have begun to investigate the roles of non-active sites in proteins, especially for enzyme families with different functions. In this mini-review, we focused on recent progress in research on non-active sites of enzymes. First, we outlined two major research methodswith non-active sites as direct targets, including understanding enzymatic mechanisms and enzyme engineering. Second, we classified the positions of reported non-active sites in enzyme structures and studied the molecular mechanisms underlying their functions, according to the literature on non-active sites. Finally, we summarized the results of bioinformatic analysisof mining non-active sites as targets for protein engineering.
Rekindling of a Masterful Precedent; Bacteriophage: Reappraisal and Future Pursuits
Authors: Abd-Allah Israa M. , El-Housseiny Ghadir S. , Yahia Ibrahim S. , Aboshanab Khaled M. , Hassouna Nadia A.
Published: May 2021

Antibiotic resistance is exuberantly becoming a deleterious health problem world-wide. Seeking innovative approaches is necessary in order to circumvent such a hazard. An unconventional fill-in to antibiotics is bacteriophage. Bacteriophages are viruses capable of pervading bacterial cells and disrupting their natural activity, ultimately resulting in their defeat. In this article, we will run-through the historical record of bacteriophage and its correlation with bacteria. We will also delineate the potential of bacteriophage as a therapeutic antibacterial agent, its supremacy over antibiotics in multiple aspects and the challenges that could arise on the way to its utilization in reality. Pharmacodynamics, pharmacokinetics and genetic engineering of bacteriophages and its proteins will be briefly discussed as well. In addition, we will highlight some of the in-use applications of bacteriophages, and set an outlook for their future ones. We will also overview some of the miscellaneous abilities of these tiny viruses in several fields other than the clinical one. This is an attempt to encourage tackling a long-forgotten hive. Perhaps, one day, the smallest of the creatures would be of the greatest help.
Low-Abundant Microorganisms: The Human Microbiome’s Dark Matter, a Scoping Review
Authors: Cena Jéssica Alves de , Zhang Jianying , Deng Dongmei , Damé-Teixeira Nailê , Do Thuy
Published: May 2021

Research on the human microbiome has mainly been restricted to the identification of most abundant microbiota associated with health or disease. Their abundance may reflect their capacity to exploit their niche, however, metabolic functions exerted by low-abundant microrganisms can impact the dysbiotic signature of local microbial habitats. This scoping review aims to map the literature regarding the management of low-abundant microorganisms in studies investigating human microbiome samples. A systematic literature search was performed in 5 electronic databases, as well as grey literature. We selected clinical microbiome studies targeting human participants of any age, from any body site. We also included studies with secondary data which originated from human biofilm samples. All of the papers used next-generation sequencing (NGS) techniques in their methodology. A total of 826 manuscripts were retrieved, of which 42 were included in this review and 22 reported low-abundant bacteria (LB) in samples taken from 7 body sites (breast, gut, oral cavity, skin, stomach, upper respiratory tract (URT), and vagina). Four studies reported microbes at abundance levels between 5 and 20%, 8 studies reported between 1 and 5%, and 18 studies reported below 1%. Fifteen papers mentioned fungi and/or archaea, and from those only 4 (fungi) and 2 (archaea) produced data regarding the abundance of these domains. While most studies were directed towards describing the taxonomy, diversity and abundance of the highly abundant species, low-abundant species have largely been overlooked. Indeed, most studies select a cut-off value at <1% for low-abundant organisms to be excluded in their analyses. This practice may compromise the true diversity and influence of all members of the human microbiota. Despite their low abundance and signature in biofilms, they may generate important markers contributing to dysbiosis, in a sort of ‘butterfly effect’. A detailed snapshot of the physiological, biological mechanisms at play, including virulence determinants in the context of a dysbiotic community, may help better understand the health-disease transition.
Cultural Cognition and Ideological Framing Influence Communication About Zoonotic Disease in the Era of COVID-19
Authors: Beall Justin M. , Casola William R. , Peterson M Nils. , Larson Lincoln R. , Carr Wylie A. , Seekamp Erin , Stevenson Kathryn T. , Jackson S Brent
Published: May 2021

The efficacy of science communication can be influenced by the cultural values and cognitions of target audiences, yet message framing rarely accounts for these cognitive factors. To explore the effects of message framing tailored to specific audiences, we investigated relationships between one form of cultural cognition—political ideology—and perceptions about the zoonotic origins of the COVID-19 pandemic using a nationally representative Qualtrics XM panel (n = 1,554) during August 2020. First, we examined differences in attitudes towards science (in general) and COVID-19 (specifically) based on political ideology. We found that, compared to conservatives and moderates, liberals trusted science more, were less skeptical of science, perceived greater risk from COVID-19, were more likely to believe in a wildlife origin of COVID-19, and were more likely to support restrictions on wildlife trade. Second, we examined the influence of cultural framing on the perceived validity of science related to COVID-19. Respondents were randomly assigned to one of three treatment groups: 1) a technocratic framing that highlighted feats of human ingenuity to overcome zoonoses; 2) a regulatory framing that highlighted regulations and expansions of protected areas for wildlife as a means to prevent zoonoses, and 3) a control article about traffic lights with no cultural framing. After reading the initial framing article, all three groups read the same fictional, yet factually accurate, ‘Nature Science study’ generated by the authors. An OLS regression model revealed a significant interaction between the technocratic framing and political ideology. Relative to the control group, the technocratic framing slightly increased perceived validity of the Nature Science study for conservatives, significantly lowered perceived validity for liberals, and had no impact on moderates. We did not detect any significant interaction between framing and political ideology for the regulatory framing. Findings of this study highlight the need to account for cultural cognitions when communicating about COVID-19 and other zoonotic diseases. Communication strategies carefully designed to resonate with ideologically diverse audiences may ultimately lead to bipartisan support for actions required to promote “One Health” approaches that reduce the impacts of zoonoses on human and environmental health.
Association of ACEi/ARB Use and Clinical Outcomes of COVID-19 Patients With Hypertension
Authors: Ma Jing , Shi Xiaowei , Yu Jiong , Lv Feifei , Wu Jian , Sheng Xinyu , Pan Qiaoling , Yang Jinfeng , Cao Hongcui , Li Lanjuan
Published: May 2021

Objectives: Evidence has shown that angiotensin-converting enzyme 2 (ACE2), which can be upregulated after angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) treatment, may play a dual role in the pathogenesis and progression of coronavirus disease 2019 (COVID-19). We aimed to assess the association between the use of ACEi/ARB and the outcome of COVID-19 patients with preexisting hypertension in non-endemic areas.

Methods: From January 17, 2020, to February 19, 2020, 286 patients with hypertension were enrolled in this retrospective study out of 1,437 COVID-19 patients from 47 centers in Zhejiang and Jiangsu Province. The composite endpoints consisted of mechanical ventilation, intensive care unit (ICU) admission, or death. Cox proportional hazards analysis was performed to assess the association between ACEi/ARB and clinical outcomes of COVID-19 patients with hypertension.

Results: In the main analysis, 103 patients receiving ACEi/ARB were compared with 173 patients receiving other regimens. Overall, 44 patients (15.94%) had an endpoint event. The risk probability of crude endpoints in the ACEi/ARB group (12.62%) was lower than that in the non-ACEi/ARB group (17.92%). After adjusting for confounding factors by inverse probability weighting, the results showed that the use of ACEi/ARB reduced the occurrence of end events by 47% [hazard ratio (HR) = 0.53; 95% CI, 0.34–0.83]. Similar results were obtained in multiple sensitivity analyses.

Conclusions: In this retrospective study, among COVID-19 patients with hypertension, the use of ACEi/ARB is not associated with an increased risk of disease severity compared with patients without ACEi/ARB. The trends of beneficial effects of ACEi/ARB need to be further evaluated in randomized clinical trials.
Case Report: Multimodality Imaging as a Lifeline for Fatal Localization of Valsalva Sinus Fibroelastoma
Authors: Tadic Snezana , Ilic Aleksandra , Stefanovic Maja , Stojsic-Milosavljevic Anastazija , Popov Tanja , Bjelobrk Marija , Milovancev Aleksandra , Maksimovic Nebojsa , Drid Patrik
Published: May 2021

Background: Papillary fibroelastomas are rare benign heart tumors, and is most likely to involve the cardiac valves. We will present an extremely rare localization of a large Valsalva sinus fibroelastoma, with occasional left coronary artery ostial obstruction presented as an acute coronary syndrome. The tumor was removed surgically and histologically confirmed as papillary fibroelastoma. This review points to the crucial importance of multidisciplinary team decision and multimodality imaging methods for diagnosing the fibroelastoma, determination of size, and localization, which avoided complications of fatal embolization during an invasive procedure.

Case Summary: A healthy 55-year-old male with vigorous physical daily training and exercise was admitted to the acute coronary syndrome emergency department. Shortly after admission, expert transthoracic echocardiography was performed. Computed tomography of the chest observed a large irregular hypodense tumor-like lesion in the bulbar aorta that was occasionally prolapsing into the left main coronary artery ostium and which corresponded to fibroelastoma. A few hours after admission, an emergency cardiac surgery was performed with the excision of a Valsalva sinus tumor (size 2 × 2 cm) located between the right and left coronary cusp of the aortic valve.

Conclusions: Focus cardiac ultrasound should be performed for any acute coronary syndrome because of the possible Valsalva sinus fibroelastoma etiology. Its localization next to the left main coronary artery ostium is rare, and dangerous. The timely diagnosis can be made by the multimodality imaging method, however, the final diagnosis will be made pathohistologically. Early cardiac surgery may be a necessitated recourse for these patients in order to prevent a fatal outcome.
What’s Your STEMspiration?: Adaptation and Validation of A Survey Instrument
Authors: Hargraves Rosalyn Hobson , Morgan Kristin L. , Jackson Holly , Feltault Kelly , Crenshaw Jasmine , McDonald Kevin G. , Martin Marcus L.
Published: May 2021

Millions of dollars each year are invested in intervention programs to broaden participation and improve bachelor degree graduation rates of students enrolled in science, technology, engineering, and mathematics (STEM) disciplines. The Virginia–North Carolina Louis Stokes Alliance for Minority Participation (VA-NC Alliance), a consortium of 11 higher education institutions and one federal laboratory funded by the National Science Foundation (NSF), is one such investment., The VA-NC Alliance partners implement evidence-based STEM intervention programs (SIPs) informed by research and specifically designed to increase student retention and graduation rates in STEM majors. The VA-NC Alliance is conducting an Alliance-wide longitudinal research project based in Social Cognitive Career Theory (SCCT) titled “What’s Your STEMspiration?” The goal of the research project is to assess the differentiated impacts and effectiveness of the Alliance’s broadening participation efforts and identify emergent patterns, adding to the field of knowledge about culturally responsive SIPs. In other words, “What’s Your STEMspiration?” explores what influences and inspires undergraduates to pursue a STEM degree and career; and how does the development of a STEM identity support students in achieving their goals. In order to complete this research, the research team developed a survey instrument to conduct the quantitative portion of the study. Two preliminary studies, statistical analysis, and cognitive interviews were used to develop and validate the survey instrument. This paper discusses the theoretical and conceptual frameworks and preliminary studies upon which the survey is built, the methodology used to validate the instrument, and the resulting final survey tool.
Ultra-Long GnRH Agonist Protocol During IVF/ICSI Improves Pregnancy Outcomes in Women With Adenomyosis: A Retrospective Cohort Study
Authors: Lan Jie , Wu Yaoqiu , Wu Zexuan , Wu Yingchen , Yang Rong , Liu Ying , Lin Haiyan , Jiao Xuedan , Zhang Qingxue
Published: May 2021

Objective

This study aimed to compare the ultra-long gonadotropin-releasing hormone agonist (GnRH-a) protocol and the long GnRH-a protocol during in vitro fertilization (IVF) or intracytoplasmic sperm (ICSI) treatment on fertility outcomes in women with adenomyosis.

Materials and Methods

This study was a retrospective cohort study. From January 2011 to May 2018, a total of 371 fresh IVF/ICSI cycles were included. Among the cycles included, 237 cycles of 212 women underwent the ultra-long GnRH-a protocol, while 134 cycles of 116 women underwent the long GnRH-a protocol. The rates of implantation, clinical pregnancy per embryo transfer, live birth, and early miscarriage were estimated between the compared protocols.

Results

In the study, the early miscarriage rate in women undergoing the ultra-long GnRH-a protocol was significantly lower than those undergoing the long GnRH-a protocol (12.0% versus 26.5%, p = 0.045), whereas the differences in the rates of biochemical pregnancy, implantation, clinical pregnancy, and live birth in women between the two groups showed no statistical significance. The pregnancy outcomes were also sub-analyzed according to the adenomyotic region (diffuse and focal). As for diffuse adenomyosis, the rates of clinical pregnancy and live birth in women undergoing the ultra-long GnRH-a protocol were significantly higher than those undergoing the long GnRH-a protocol (55.3% versus 37.9%, p = 0.025; 43.4% versus 25.9%, p = 0.019, respectively). However, pregnancy outcomes showed no difference between the two protocols in women with focal adenomyosis.

Conclusions

The ultra-long GnRH-a protocol during IVF/ICSI improves pregnancy outcomes in women with adenomyosis, especially in women with diffuse adenomyosis when compared with the long GnRH-a protocol.
Single-Cell Trajectory Inference Guided Enhancement of Thyroid Maturation In Vitro Using TGF-Beta Inhibition
Authors: Romitti Mírian , Eski Sema Elif , Fonseca Barbara Faria , Gillotay Pierre , Singh Sumeet Pal , Costagliola Sabine
Published: May 2021

The thyroid gland regulates metabolism and growth via secretion of thyroid hormones by thyroid follicular cells (TFCs). Loss of TFCs, by cellular dysfunction, autoimmune destruction or surgical resection, underlies hypothyroidism. Recovery of thyroid hormone levels by transplantation of mature TFCs derived from stem cells in vitro holds great therapeutic promise. However, the utilization of in vitro derived tissue for regenerative medicine is restricted by the efficiency of differentiation protocols to generate mature organoids. Here, to improve the differentiation efficiency for thyroid organoids, we utilized single-cell RNA-Seq to chart the molecular steps undertaken by individual cells during the in vitro transformation of mouse embryonic stem cells to TFCs. Our single-cell atlas of mouse organoid systematically and comprehensively identifies, for the first time, the cell types generated during production of thyroid organoids. Using pseudotime analysis, we identify TGF-beta as a negative regulator of thyroid maturation in vitro. Using pharmacological inhibition of TGF-beta pathway, we improve the level of thyroid maturation, in particular the induction of Nis expression. This in turn, leads to an enhancement of iodide organification in vitro, suggesting functional improvement of the thyroid organoid. Our study highlights the potential of single-cell molecular characterization in understanding and improving thyroid maturation and paves the way for identification of therapeutic targets against thyroid disorders.
Case Report: Metreleptin and SGLT2 Inhibitor Combination Therapy Is Effective for Acquired Incomplete Lipodystrophy
Authors: Nagayama Ayako , Ashida Kenji , Watanabe Miki , Moritaka Kanoko , Sonezaki Aya , Kitajima Yoichiro , Takahashi Hirokazu , Yoshinobu Satoko , Iwata Shimpei , Yasuda Junichi , Hasuzawa Nao , Ozono Shuichi , Motomura Seiichi , Nomura Masatoshi
Published: May 2021

Childhood cancer survivors (CCSs) who have undergone bone marrow transplantation with systemic chemotherapy and whole-body irradiation often experience impaired glucose tolerance with marked insulin resistance. Incomplete acquired diabetic lipodystrophy should be considered as a late complication of bone marrow transplantation. A 24-year-old Japanese female patient with incomplete acquired lipodystrophy, a CCS of acute lymphocytic leukemia at the age of 3 years, was treated for diabetes mellitus and dyslipidemia at our hospital. Administration of multiple daily insulin injections (70 units/day), and oral administration of 500 mg/day metformin, 15 mg/day pioglitazone, and 200 mg/day bezafibrate had proven ineffective for her metabolic disorders. Subcutaneous administration of metreleptin improved her insulin resistance and hypertriglyceridemia within a month; however, it failed to maintain adequate plasma glucose levels in the long term. When oral administration of 10 mg/day empagliflozin was added to the metreleptin supplementation, her HbA1c value (National Glycohemoglobin Standardization Program) improved from 11% to 8%, which was maintained for an additional 18 months. This is the first case report of incomplete lipodystrophy that shows efficacy of a combination therapy with metreleptin and a sodium glucose cotransporter 2 (SGLT2) inhibitor for the treatment of diabetes and dyslipidemia. An SGLT2 inhibitor attenuates hyperglycemia through urinary glucose excretion and has been suggested to enhance lipid catabolism in the extra-adipose tissues, especially in the liver and skeletal muscles. Furthermore, metreleptin supplementation could enhance the action of the SGLT2 inhibitor by promoting satiety and lipolysis through the central nervous system. Combination therapy with metreleptin and an SGLT2 inhibitor was suggested to recover the volume of adipose tissue, possibly through improvement of insulin resistance in the adipose tissue. This report highlights the pathophysiological mechanism of an SGLT2 inhibitor in the improvement of glucose metabolism in non-healthy lean CCSs with insulin resistance. Administration of SGLT2 inhibitor, along with metreleptin supplementation, could be a good alternative therapy for diabetic lipodystrophy observed in CCSs.
Leaching of Phosphomonoesterase Activities in Beech Forest Soils: Consequences for Phosphorus Forms and Mobility
Authors: Fetzer Jasmin , Loeppmann Sebastian , Frossard Emmanuel , Manzoor Aamir , Brödlin Dominik , Kaiser Klaus , Hagedorn Frank
Published: May 2021

Phosphomonoesterases play an important role in the soil phosphorus (P) cycle since they hydrolyze P monoester to phosphate. Their activity is generally measured in soil extracts, and thus, it remains uncertain how mobile these enzymes are and to which extent they can be translocated within the soil profile. The presence of phosphomonoesterases in soil solutions potentially affects the share of labile dissolved organic P (DOP), which in turn would affect P leaching. Our study aimed at assessing the production and leaching of phosphomonoesterases from organic layers and topsoil horizons in forest soils and its potential effect on dissolved P forms in leachates obtained from zero-tension lysimeters. We measured phosphomonoesterase activities in leached soil solutions and compared it with those in water extracts from litter, Oe/Oa, and A horizons of two beech forests with a contrasting nitrogen (N) and P availability, subjected to experimental N × P fertilization. In addition, we determined phosphate and DOP. In soil solutions leached from litter, Oe/Oa, and A horizons, phosphomonoesterase activities ranged from 2 to 8 μmol L–1 h–1 during summer, but remained below detection limits in winter. The summer values represent 0.1–1% of the phosphomonoesterase activity in soil extracts, indicating that enzymes can be translocated from organic layers and topsoils to greater soil depths. Activities of phosphomonoesterases obtained by water extracts were greater in the organic layer of the P-poor site, while activities of those in soil solutions were similar at the two sites. Nitrogen addition increased phosphomonoesterase activities in leached soil solutions of the organic layer of the N- and P-poor soil. Using a modeling approach, we estimated that approx. 76% of the initial labile DOP was hydrolyzed to dissolved inorganic P within the first 24 h. Back calculations from measured labile DOP revealed an underestimation of approx. 15% of total dissolved P, or 0.03 mg L–1. The observed leaching of phosphomonoesterases implies that labile organic P could be hydrolyzed in deeper soil horizons and that extended sample storage leads to an underestimation of the contribution of DOP to total dissolved P leaching. This has been neglected in the few field studies measuring DOP leaching.
Zebrafish Chromosome 14 Gene Differential Expression in the fmr1hu2787 Model of Fragile X Syndrome
Authors: Barthelson Karissa , Baer Lachlan , Dong Yang , Hand Melanie , Pujic Zac , Newman Morgan , Goodhill Geoffrey J. , Richards Robert I. , Pederson Stephen M. , Lardelli Michael
Published: May 2021

Zebrafish represent a valuable model for investigating the molecular and cellular basis of Fragile X syndrome (FXS). Reduced expression of the zebrafishFMR1orthologous gene,fmr1, causes developmental and behavioural phenotypes related to FXS. Zebrafish homozygous for the hu2787 non-sense mutation allele offmr1are widely used to model FXS, although FXS-relevant phenotypes seen from morpholino antisense oligonucleotide (morpholino) suppression offmr1transcript translation were not observed when hu2787 was first described. The subsequent discovery of transcriptional adaptation (a form of genetic compensation), whereby mutations causing non-sense-mediated decay of transcripts can drive compensatory upregulation of homologous transcripts independent of protein feedback loops, suggested an explanation for the differences reported. We examined the whole-embryo transcriptome effects of homozygosity forfmr1hu2787at 2 days post fertilisation. We observed statistically significant changes in expression of a number of gene transcripts, but none from genes showing sequence homology tofmr1. Enrichment testing of differentially expressed genes implied effects on lysosome function and glycosphingolipid biosynthesis. The majority of the differentially expressed genes are located, likefmr1, on Chromosome 14. Quantitative PCR tests did not support that this was artefactual due to changes in relative chromosome abundance. Enrichment testing of the “leading edge” differentially expressed genes from Chromosome 14 revealed that their co-location on this chromosome may be associated with roles in brain development and function. The differential expression of functionally related genes due to mutation offmr1, and located on the same chromosome asfmr1, is consistent with R.A. Fisher’s assertion that the selective advantage of co-segregation of particular combinations of alleles of genes will favour, during evolution, chromosomal rearrangements that place them in linkage disequilibrium on the same chromosome. However, we cannot exclude that the apparent differential expression of genes on Chromosome 14 genes was, (if only in part), caused by differences between the expression of alleles of genes unrelated to the effects of thefmr1hu2787mutation and made manifest due to the limited, but non-zero, allelic diversity between the genotypes compared.
Integrative Ranking of Enhancer Networks Facilitates the Discovery of Epigenetic Markers in Cancer
Authors: Wang Qi , Wu Yonghe , Vorberg Tim , Eils Roland , Herrmann Carl
Published: May 2021

Regulation of gene expression through multiple epigenetic components is a highly combinatorial process. Alterations in any of these layers, as is commonly found in cancer diseases, can lead to a cascade of downstream effects on tumor suppressor or oncogenes. Hence, deciphering the effects of epigenetic alterations on regulatory elements requires innovative computational approaches that can benefit from the huge amounts of epigenomic datasets that are available from multiple consortia, such as Roadmap or BluePrint. We developed a software tool named IRENE (Integrative Ranking of Epigenetic Network of Enhancers), which performs quantitative analyses on differential epigenetic modifications through an integrated, network-based approach. The method takes into account the additive effect of alterations on multiple regulatory elements of a gene. Applying this tool to well-characterized test cases, it successfully found many known cancer genes from publicly available cancer epigenome datasets.
Co-Resident Grandparent: A Burden or a Relief? A Comparison of Gender Roles between Italians and Migrants
Authors: Trappolini Eleonora , Rimoldi Stefania Maria Lorenza , Terzera Laura
Published: May 2021

In the international literature, the principal task of grandparents is generally recognized as helping their children in providing childcare. Most of those studies analyzed grandparental childcare on the whole population, and few have focused on co-resident grandparent(s), which turns out to be an understudied topic in the European context. Further, most of them investigated the effect of childcare on grandparents’ health status. However, the elderly population can both provide and receive care. Using two Italian surveys released by the Italian National Institute of Statistics, the “Social Condition and Integration of Foreign Citizen (2011–2012)” and the “Multiscopo–Aspetti della vita quotidiana (2011)”, the study aims to analyze differences in grandparental childcare provided by co-resident grandparents between Italian and migrant households, considering both the role played by grandparents’ self-rated health (SRH) and gender. We identify four grandparents’ profiles by combining grandparents’ SRH and their attitude towards looking after their grandchild(ren). Subsequently, we apply multinomial logistic regressions, and we compute average marginal effects to facilitate results interpretations. Results display that migrant co-resident grandparents are less likely to declare bad SRH and no-childcare and are more likely to declare good SRH and to provide childcare than Italian grandparents. Moreover, when considering gender differences, the real role is revealed: we find that women have a higher probability to report poor health and care for their grandchild(ren) than men. Such findings illustrate that grandparents’ cohabitation decision is based upon the difference between their need for care and offer to care, and second, in addition to migrant status and SRH, gender is a determinant of grandparents’ childcare: women look after their grandchild(ren) more than men, whatever their health status.