bluuebunny/crossref_metadata_2025 huggingface dataset:
PERAN ORANG TUA DALAM PENDIDIKAN ANAK DI MASA PANDEMI COVID 19 (STUDI DI DESA SAI KECAMATAN SOROMANDI KABUPATEN BIMA)
Authors: Irfan Irfan , Nurfaidah Nurfaidah
Published: May 2022

Kebijakan pembelajaran daring di masa pandemic covid 19, memiliki kendala yang dihadapi orang tua diantaranya kesiapan orang dalam mendidik anak,  terbatasnya waktu orang tua dalam mendampingi anak, kemampuan orang tua dalam menyediakan fasilitas belajar berupa Hand Phone android dan paket data serta kemauan belajar anak yang menurun. Pendekatan penelitian kualitatif adalah suatu pendekatan penelitian yang mengungkapkan gejala-gejala secara holistic-kontekstual (menyeluruh dan sesuai dengan konteks), melalui pengumpulan data dari latar alami sebagai sumber dengan instrument kunci penelitian itu sendiri. Dengan jumlah informan  sebanyak 12 orang. Teknik pengumpulan data melalui observasi dan wawancara, teknik analisa data secara kualitatif. Hasil analisis data bahwa orang tua sudah berperan dalam mendidik anak pada masa pandemi Covid-19 di Desa Sai Kecamatan Soromandi Kabupaten Bima. Hal ini dikarenakan, orang tua sudah menempatkan diri sebagai guru selama proses pembelajaran jarak jauh (PJJ), baik mendidik dan mengajarkan, meningkatkan pemahaman anak, membagi waktu untuk memperhatikan proses belajar anak di masa pandemic covid 19, melakukan pendampingan, evaluasi belajar dan memperhatikan ketersediaan kuato internet. Namun, terdapat pula kendala orang tua dalam  mendidik anak, diantaranya: pemenuhan HP android dan paket internet bagi keluarga tidak mampu, media pembelajaran yang digunakan para guru dominan monoton dan membuat para murid merasa jenuh atau bosan. Kemudian, kemauan belajar menurun, pembelajarannya cenderung tugas online dan penyerapan materi pelajaran sangat rendah tampa pengawasan langsung dari guru
PERANAN PENGRAJIN SARUNG TENUN DALAM MENINGKATKAN KESEJAHTERAAN EKONOMI KELUARGA DI DESA ROI KECAMATAN PALIBELO KABUPATEN BIMA
Authors: Mukhlis Mukhlis , Mukhsin Zainuddin , Anggriani Rini
Published: May 2022

Rumusan masalah dalam penelitian ini adalah apakah ada peranan pengrajin sarung tenun dalam meningkatkan kesejahteraan ekonomi keluarga di Desa Roi Kecamatan Palibelo Kabupaten Bima. Tujuan dari penelitian ini adalah untuk mengetahui peranan pengrajin sarung tenun dalam meningkatkan kesejahteraan  ekonomi keluarga di Desa Roi Kecamatan Palibelo Kabupaten Bima. Penelitian ini mengunakan penelitian deskriptif kualitatif. Sampel dalam penelitian ini adalah para pengrajin sarung tenun yang berjumlah 70 orang. Instrumen yang digunakan adalah wawancara dan dokumentasi. Jumlah informan penelitian adalah 15 orang. Hasil dari penelitian menunjukan bahwa 1) Keberadaan penenun di desa Roi sudah banyak, karena  ada generasi penerus dalam mengerjakan selembar sarung hanya di butuhkan waktu kurang lebih 3-4 hari itupun kalau mengerjakannya sehari-hari. kalau mengerjakannya dengan waktu yang singkat buat selembar kain membutuhkan waktu 20 hari. 2) Menambah lapangan pekerjaan, karena kerajinan sarung tenun  memiliki harga jual tinggi. 3) Sebagai Peluang usaha bagi masyarakat, sebab kerajinan sarung tenun memiliki nilai jual yang tinggi dan menambah usaha kerja bagi masyarakat. 4) Menambah penghasilan masyarakat, karena tenun dapat memberikan penghasilan tambahan bagi penenunnya yang dapat digunakan untuk memenuhi kebutuhan sehari-hari maupun sebagai sumber modal untuk bertani. 5) Sebagai sumber PAD (Pendapatan Asli Daerah) bagi pemerintahan desa Roi, karena mampu menciptakan lapangan usaha, sehingga mampu memperluas kesempatan kerja, maka dapat meningkatkan standar kesejahteraan hidup masyarakat. 6) Sebagai pelestarian budaya masyarakat, karena memiliki sejarah dan tradisi yang cukup mengakar dan perlu untuk dilestarikan keberadaannya. Oleh sebab itu, diharapkan dapat memotivasi terutama para kaum perempuan untuk lebih bersemangat dalam mengolah kerajinan tenun sebagai salah satu bentuk lapangan kerja bagi masyarakat sekitar.
STRATEGI PEMERINTAH DAERAH DALAM UPAYA MENINGKATKAN PELAYANAN PUBLIK DI KANTOR DUKCAPIL KABUPATEN BIMA
Authors: Iptidaiyah Muhamad , Mulyawan Wawan
Published: May 2022

Tujuan penelitian ini adalah untuk mengetahui strategi dan faktor pendukung dan penghambat pemerintah daerah dalam meningktakan pelayanan publik di dinas Dukcapil Kabupeten Bima. Penelitian ini menggunakan pendekatan kualitatif. Jenis dan sumber data terdiri dari data primer dan data sekunder. Informan penelitian yaitu kepala dinas Dukcapil Kabupaten Bima, kepala bidang, pegawai dan masyarakat. Teknik pengumpulan data menggunakan observasi, wawancara, dan dkumentasi. Teknik analisis data meliputi reduksi data, dislay data, dan verifikasi (penarikan kesimpulan. Uji kredibilitas data dilakukan dengan perpanjangan pengamatan, trianggulasi, diskusi dengan warga. Hasil penelitian menemukan bahwa kualitas pelayanan pada di dinas  kependudukan dan pencatatan sipil Kabupaten Bima  masih kurang maksimal, seperti pelayanan yang diberikan belum menerapkan prinsip-prinsip pelayanan prima yang seharusnya diterapkan dengan baik oleh setiap dinas yang memberikan pelayanan publik.
Migración de retorno en Latinoamérica y el Caribe: Una revisión sistemática exploratoria
Authors: Fernández-Sánchez Higinio , Vásquez-Ventura Ingrid Stephanie , Rivera-Ramírez Pedro Iván , Zahoui Ziad
Published: May 2022

The following article determines the scope and nature of the empirical evidence, that is,academic articles on migrants returning to Latin Americanand Caribbeancountries. Using Systematic Exploratory Reviewsmethodology, 23 empirical studies published in indexed journals were included.The data were synthesized using descriptive statistics and conventional content analysis. Most of the participants are migrants from Mexico (n=19) and the return country is the United States (n=20). Four emerging categories were identified: a) health and well-being,b) social, political,and cultural context,c) addictions,and d) return reasons.The phenomenon under study shows innovation due to the limited scientific literature that analyzes return migration. It is concluded that people returning to their places of origin face unfavorable economic, political,and health situations.
ADEQUAÇÃO DE UMA ATIVIDADE DE MODELAGEM MATEMÁTICA PARA UMA UNIDADE DE ENSINO POTENCIALMENTE SIGNIFICATIVA
Authors: Dalbon Eliane Siviero da Silva , Merli Renato Francisco
Published: May 2022

Esse artigo apresenta uma proposta de adaptação de uma atividade de Modelagem Matemática (MM) aos pressupostos teóricos da Aprendizagem Significativa (AS), em especial, as Unidades de Ensino Potencialmente Significativas (UEPS). Para isso, inicialmente, foi realizada uma pesquisa bibliográfica sobre os principais conceitos de Modelagem Matemática, Aprendizagem Significativa e Unidades de Ensino Potencialmente Significativas. Na sequência, foi apresentada uma atividade de Modelagem Matemática já aplicada em sala de aula e as ações necessárias para suaadaptação em uma Unidade de Ensino Potencialmente Significativa. Dos diversos aspectos que podem ser levantados sobre o uso da UEPS em articulação com a MM, pode-se destacar que a primeira ajuda a pensar no processo cognitivo individual do aluno, fortalecendo ainda mais aspectos que já eram realçados com o uso da MM, como autonomia e tomada de decisão coletiva e individual. Destaca-se, ainda, a necessidade de readequar alguns momentos da atividade para que ela se torne potencialmentesignificativa. Um exemplo está na etapa de avaliação da aprendizagem, a qual, na MM, acontece durante todo o processo e de forma coletiva e na UEPS é sugerido que se realize uma avaliação individual.
Current Advances and Future Perspectives of Advanced Polymer Processing for Bone and Tissue Engineering: Morphological Control and Applications
Authors: Zhang Tongrui , Nie Min , Li Yijun
Published: May 2022

Advanced polymer processing has received extensive attention due to its unique control of complex force fields and customizability, and has been widely applied in various fields, especially in preparation of functional devices for bioengineering and biotechnology. This review aims to provide an overview of various advanced polymer processing techniques including rotation extrusion, electrospinning, micro injection molding, 3D printing and their recent progresses in the field of cell proliferation, bone repair, and artificial blood vessels. This review dose not only attempts to provide a comprehensive understanding of advanced polymer processing, but also aims to guide for design and fabrication of next-generation device for biomedical engineering.
Inhibition of Cyclin-Dependent Kinase 9 Downregulates Cytokine Production Without Detrimentally Affecting Human Monocyte-Derived Macrophage Viability
Authors: McHugh Brian J. , Stephen Jillian , Robb Calum T. , Fox Sarah , Kipari Tiina , Cartwright Jennifer A. , Haslett Christopher , Duffin Rodger , Lucas Christopher D. , Rossi Adriano G.
Published: May 2022

Cyclin-dependent kinase (CDK) inhibitor drugs (CDKi), such as R-roscovitine and AT7519, induce neutrophil apoptosisin vitroand enhance the resolution of inflammation in a number ofin vivomodels. This class of compounds are potential novel therapeutic agents that could promote the resolution of acute and chronic inflammatory conditions where neutrophil activation contributes to tissue damage and aberrant tissue repair. In this study we investigated CDKi effects on macrophage pro-inflammatory mediator production and viability. Treatment of human monocyte-derived macrophages (MDMs) with the CDKi AT7519 and R-roscovitine at concentrations that induce neutrophil apoptosis had no significant effect on control or LPS-activated MDM apoptosis and viability, and did not detrimentally affect MDM efferocytosis of apoptotic cells. In addition, enhanced efferocytosis, induced by the glucocorticoid dexamethasone, was also unaffected after a short time treatment with R-roscovitine. Macrophage cytokine responses to inflammatory stimuli are also of importance during inflammation and resolution. As a key target of CDKi, CDK9, is involved in protein transcription via the RNA polymerase II complex, we investigated the effect of CDKi drugs on cytokine production. Our data show that treatment with AT7519 significantly downregulated expression and release of key MDM cytokines IL-6, TNF, IL-10 and IL-1β, as well as markers of pro-inflammatory macrophage polarisation. R-Roscovitine was also able to downregulate inflammatory cytokine protein secretion from MDMs. Using siRNA transfection, we demonstrate that genetic knock-down of CDK9 replicates these findings, reducing expression and release of pro-inflammatory cytokines. Furthermore, overexpression of CDK9 in THP-1 cells can promote a pro-inflammatory phenotype in these cells, suggesting that CDK9 plays an important role in the inflammatory phenotype of macrophages. Overall, this study demonstrates that pharmacological and genetic targeting of CDK9 inhibits an inflammatory phenotype in human MDMs. As such these data indicate that CDK9 may be key to therapeutically targeting pro-inflammatory macrophage functions during chronic inflammation.
Tissue-Resident Innate Immune Cell-Based Therapy: A Cornerstone of Immunotherapy Strategies for Cancer Treatment
Authors: Busà Rosalia , Bulati Matteo , Badami Ester , Zito Giovanni , Maresca Daniela Claudia , Conaldi Pier Giulio , Ercolano Giuseppe , Ianaro Angela
Published: May 2022

Cancer immunotherapy has led to impressive advances in cancer treatment. Unfortunately, in a high percentage of patients is difficult to consistently restore immune responses to eradicate established tumors. It is well accepted that adaptive immune cells, such as B lymphocytes, CD4+helper T lymphocytes, and CD8+cytotoxic T-lymphocytes (CTLs), are the most effective cells able to eliminate tumors. However, it has been recently reported that innate immune cells, including natural killer cells (NK), dendritic cells (DC), macrophages, myeloid-derived suppressor cells (MDSCs), and innate lymphoid cells (ILCs), represent important contributors to modulating the tumor microenvironment and shaping the adaptive tumor response. In fact, their role as a bridge to adaptive immunity, make them an attractive therapeutic target for cancer treatment. Here, we provide a comprehensive overview of the pleiotropic role of tissue-resident innate immune cells in different tumor contexts. In addition, we discuss how current and future therapeutic approaches targeting innate immune cells sustain the adaptive immune system in order to improve the efficacy of current tumor immunotherapies.
Biology and Model Predictions of the Dynamics and Heterogeneity of Chromatin-Nuclear Lamina Interactions
Authors: Madsen-Østerbye Julia , Bellanger Aurélie , Galigniana Natalia M. , Collas Philippe
Published: May 2022

Associations of chromatin with the nuclear lamina, at the nuclear periphery, help shape the genome in 3 dimensions. The genomic landscape of lamina-associated domains (LADs) is well characterized, but much remains unknown on the physical and mechanistic properties of chromatin conformation at the nuclear lamina. Computational models of chromatin folding at, and interactions with, a surface representing the nuclear lamina are emerging in attempts to characterize these properties and predict chromatin behavior at the lamina in health and disease. Here, we highlight the heterogeneous nature of the nuclear lamina and LADs, outline the main 3-dimensional chromatin structural modeling methods, review applications of modeling chromatin-lamina interactions and discuss biological insights inferred from these models in normal and disease states. Lastly, we address perspectives on future developments in modeling chromatin interactions with the nuclear lamina.
Functional Modules in Gametogenesis
Authors: Kikuchi Mariko , Tanaka Minoru
Published: May 2022

Gametogenesis, the production of eggs and sperm, is a fundamental process in sexually reproducing animals. Following gametogenesis commitment and sexual fate decision, germ cells undergo several developmental processes to halve their genomic size and acquire sex-specific characteristics of gametes, including cellular size, motility, and cell polarity. However, it remains unclear how different gametogenesis processes are initially integrated. With the advantages of the teleost fish medaka (Oryzias latipes), in which germline stem cells continuously produce eggs and sperm in mature gonads and a sexual switch gene in germ cells is identified, we found that distinct pathways initiate gametogenesis cooperatively after commitment to gametogenesis. This evokes the concept of functional modules, in which functionally interlocked genes are grouped to yield distinct gamete characteristics. The various combinations of modules may allow us to explain the evolution of diverse reproductive systems, such as parthenogenesis and hermaphroditism.
Speciation and Bio-Imaging of Chromium in Taraxacum officinale Using HPLC Post-column ID-ICP-MS, High Resolution MS and Laser Ablation ICP-MS Techniques
Authors: Marković Stefan , Levstek Lucija , Žigon Dušan , Ščančar Janez , Milačič Radmila
Published: May 2022

A new analytical procedure for the speciation of chromium (Cr) in plants by high performance liquid chromatography inductively coupled plasma mass spectrometry (HPLC-ICP-MS) was developed using a strong anion-exchange Mono Q column for the separation of the Cr species. To optimize the analytical procedure, Cr complexes were first synthesized from Cr-nitrate with the addition of an excess of ligand (90°C). Cr-oxalate, Cr-malate, Cr-citrate, Cr-aconitate and Cr-quinate complexes and Cr-nitrate (pH 6.5) were chromatographically separated from Cr(VI) by applying linear gradient elution from 100% water to 100% NH4Cl at a flow rate of 1.5 ml min−1 in 10 min. The column recoveries ranged from 100 to 104%. The exception was Cr-aconitate (column recovery 33%), where a quantitative synthesis was not possible. Good repeatability of the measurements (relative standard deviations better than ± 3%) and low limits of detection (below 0.37 ng ml−1 Cr) were achieved for the individual Cr species. The developed analytical procedure was applied to Cr speciation for dandelions (Taraxacum officinale) grown in soil with a high Cr content and a study of the uptake and metabolism of Cr species in dandelions grown in soil with a low Cr content treated with solutions of Cr(VI) or Cr-nitrate (5000 ng ml−1 Cr, pH 6.5) for 48 h. The separated Cr species were quantified by post-column isotope dilution ICP-MS, while the identification was based on retention times and was also supported by mass spectra obtained with high resolution mass spectrometry (HR-MS). The data indicate that for dandelions grown in Cr-rich soil and that treated with Cr-nitrate (pH 6.5), the Cr was mainly accumulated in the roots, while in plants treated with Cr(VI) (pH 6.5), the Cr was evenly distributed between the roots and the leaves. The Cr species found in dandelion roots and leaves were Cr-aconitate, Cr-malate, and Cr-quinate. The results revealed that Cr(VI) was completely reduced and metabolized to Cr(III) complexes. LA-ICP-MS data showed that the Cr in a leaf of dandelion grown in Cr-rich soil was localized mainly at the apex of the leaf.
Intestinal Alkaline Phosphatase Prevents Sulfate Reducing Bacteria-Induced Increased Tight Junction Permeability by Inhibiting Snail Pathway
Authors: Singh Sudha B. , Coffman Cristina N. , Varga Matthew G. , Carroll-Portillo Amanda , Braun Cody A. , Lin Henry C.
Published: May 2022

Tight junctions (TJs) are essential components of intestinal barrier integrity and protect the epithelium against passive paracellular flux and microbial translocation. Dysfunctional TJ leads to leaky gut, a condition associated with diseases including inflammatory bowel disease (IBD). Sulfate-Reducing Bacteria (SRB) are minor residents of the gut. An increased number of Desulfovibrio, the most predominant SRB, is observed in IBD and other diseases associated with leaky gut. However, it is not known whether Desulfovibrio contributes to leaky gut. We tested the hypothesis that Desulfovibrio vulgaris (DSV) may induce intestinal permeability in vitro. Snail, a transcription factor, disrupts barrier function by affecting TJ proteins such as occludin. Intestinal alkaline phosphatase (IAP), a host defense protein, protects epithelial barrier integrity. We tested whether DSV induced permeability in polarized Caco-2 cells via snail and if this effect was inhibited by IAP. Barrier integrity was assessed by measuring transepithelial electric resistance (TEER) and by 4kDa FITC-Dextran flux to determine paracellular permeability. We found that DSV reduced TEER, increased FITC-flux, upregulated snail protein expression, caused nuclear translocation of snail, and disrupted occludin staining at the junctions. DSV-induced permeability effects were inhibited in cells knocked down for snail. Pre-treatment of cells with IAP inhibited DSV-induced FITC flux and snail expression and DSV-mediated disruption of occludin staining. These data show that DSV, a resident commensal bacterium, can contribute to leaky gut and that snail may serve as a novel therapeutic target to mitigate DSV-induced effects. Taken together, our study suggests a novel underlying mechanism of association of Desulfovibrio bloom with diseases with increased intestinal permeability. Our study also underscores IAP as a novel therapeutic intervention for correcting SRB-induced leaky gut via inhibition of snail.
Contribution of Puma to Inflammatory Resolution During Early Pneumococcal Pneumonia
Authors: Kennedy II Daniel E. , Mody Perceus , Gout Jean-Francois , Tan Wei , Seo Keun Seok , Olivier Alicia K. , Rosch Jason W. , Thornton Justin A.
Published: May 2022

Apoptosis of cells at the site of infection is a requirement for shutdown of inflammatory signaling, avoiding tissue damage, and preventing progression of sepsis.Puma+/+andPuma-/-mice were challenged with TIGR4 strain pneumococcus and cytokines were quantitated from lungs and blood using a magnetic bead panel analysis.Puma-/-mice exhibited higher lung and blood cytokine levels of several major inflammatory cytokines, including IL-6, G-CSF, RANTES, IL-12, IFN-ϒ, and IP-10.Puma-/-mice were more susceptible to bacterial dissemination and exhibited more weight loss than their wild-type counterparts. RNA sequencing analysis of whole pulmonary tissue revealed Puma-dependent regulation ofNrxn2,Adam19, andEln. Enrichment of gene ontology groups differentially expressed inPuma-/-tissues were strongly correlated to IFN-β and -ϒ signaling. Here, we demonstrate for the first time the role of Puma in prohibition of the cytokine storm during bacterial pneumonia. These findings further suggest a role for targeting immunomodulation of IFN signaling during pulmonary inflammation. Additionally, our findings suggest previously undemonstrated roles for genes encoding regulatory and binding proteins during the early phase of the innate immune response of pneumococcal pneumonia.
Cost-Effectiveness in Patients Undergoing Revascularization of Chronic Total Occluded Coronary Arteries—A Cohort Study
Authors: Holck Emil Nielsen , Winther Naja Stausholm , Mogensen Lone Juul Hune , Christiansen Evald Høj
Published: May 2022

Background

Revascularization of patients with chronic total occluded coronary arteries (CTO) is recommended if they have symptoms despite medical treatment. The cost-effectiveness of treatment with percutaneous coronary intervention (PCI) was investigated in this cohort study.

Materials and Methods

The study was designed as a cohort study enrolling all patients undergoing PCI for a CTO in the Central Region of Denmark and recorded in the EUROCTO database. Major adverse cardio- and cerebrovascular events (MACCE) and admissions for cardiac symptoms were collected in the Western Denmark Heart Registry and through medical Journal Audits. Exposure was defined as successful revascularization of all CTO lesions compared with having one or more remaining CTOs after PCI attempt(s). Cost-effectiveness was evaluated as the net benefit (NB) at the patient level 3 years after treatment and through cost-effectiveness planes. The cost was defined as the cumulative cost of the index procedure and admissions due to MACCE and cardiac symptoms. Effectiveness was defined as the difference in MACCE for the primary analysis and the difference in death and symptomatic admissions for the secondary.

Results

Between 2009 and 2019, 441 patients with ≥ 3 years of follow-up were treated with PCI for at least one CTO lesion (342 in the successful arm and 99 in the unsuccessful arm). The technical success rate was 85.4%. In total, 155 MACCE and 184 symptomatic admissions occurred in the follow-up period. The mean total cost was EUR 11.719 (11.034; 12.406) in the successful group vs. EUR 13.565 (11.899; 15,231) (p = 0.02) in the unsuccessful group. Net-benefit was EUR 1.846 (64; 3,627) after successful revascularization for MACCE. The adjusted analysis found an NB of EUR 1,481 (–118; 3,079). Bootstrap estimates showed cost-effectiveness planes in favor of successful revascularization.

Conclusion

Patients fully revascularized for all CTO lesions had a more cost-efficient treatment. However, results need confirmation in a randomized controlled trial due to the risk of residual confounding after adjustment.
Alcohol Septal Ablation or Septal Myectomy? An Updated Systematic Review and Meta-Analysis of Septal Reduction Therapy for Hypertrophic Obstructive Cardiomyopathy
Authors: Zheng Xifeng , Yang Bin , Hui Haosheng , Lu Bing , Feng Yinhui
Published: May 2022

Objective

To evaluate the safety and effectiveness of alcohol septal ablation (ASA) and septal myectomy (SM) for the treatment of hypertrophic obstructive cardiomyopathy.

Methods

We searched the PubMed, MEDLINE, EMBASE, and CBM databases for observational research articles related to ASA and SM published from the establishment of the databases to November 2021. All ultimate selected articles were highly related to our target. The Newcastle-Ottawa Scale was used to evaluate the literature quality. A fixed or random effect model was performed in the meta-analysis depending on the heterogeneity of the included studies. The Mantel-Haenszelt test with relative risk ratio (RR) and 95% confidence interval (CI) was used to measure the effect indicator of binary data, while the inverse variance method with weighted mean difference (WMD) and 95% CI was used to measure the effect indicator of continuous data.

Results

A totally of 3,647 cases (1,555 cases treated with ASA and 2,092 cases treated with SM) were included. The results of the systematic review indicated no statistically significant difference in postoperative all-cause mortality (RR = 0.82; 95% CI: 0.65–1.04; P = 0.10) between patients treated with ASA and SM, but both the reduction in the postoperative left ventricular outflow tract pressure gradient (WMD = 9.35 mmHg, 95% CI: 5.38–13.31, P < 0.00001) and the post-operative improvement on cardiac function, assessed by the grade of New York Heart Association (NYHA), compared to pre-operative measurements (WMD = 0.13; 95% CI: 0.00–0.26; P < 0.04) in the ASA group were slightly inferior to those in the SM group. In addition, both the risk of pacemaker implantation (RR = 2.83, 95% CI: 2.06–3.88; P < 0.00001) and the risk of reoperation (RR = 11.23, 95% CI: 6.21–20.31; P < 0.00001) are recorded at a higher level after ASA procedure.

Conclusion

Both ASA and SM have a high degree of safety, but the reduction in the postoperative left ventricular outflow tract pressure gradient and the improvement on cardiac function are slightly inferior to SM. In addition, both the risk of pacemaker implantation and the risk of reoperation are recorded at a higher level after ASA procedure. The operative plan should be chosen through multidisciplinary discussions in combination with the wishes of the patients and the actual clinical situation.
Circulating Extracellular Vesicles Are Strongly Associated With Cardiovascular Risk Markers
Authors: Zhou Ruihan , Bozbas Esra , Allen-Redpath Keith , Yaqoob Parveen
Published: May 2022

Background

Extracellular vesicles (EVs) are submicron membrane-bound vesicles released from various cells, which are emerging as a potential novel biomarker in cardiovascular diseases (CVDs) due to their procoagulatory and prothrombotic properties. However, there is little information about the relationships between circulating EVs and conventional and thrombogenic risk markers of CVDs.

Objective

To investigate the relationships between circulating EVs, conventional cardiovascular risk markers and thrombogenic markers in subjects with moderate risk of CVDs.

Design

Subjects (n = 40) aged 40-70 years with moderate risk of CVDs were recruited and assessed for body mass index, blood pressure and plasma lipid profile, as well as platelet aggregation, clot formation, thrombin generation and fibrinolysis. Numbers of circulating EVs were assessed by Nanoparticle Tracking Analysis and flow cytometry. A range of assays were used to assess the procoagulatory activity of plasma and circulating EVs.

Results

Circulating EV numbers were positively associated with body mass index, blood pressure, plasma triacylglycerol concentration and overall CVD risk. Higher circulating EV numbers were also associated with increased thrombin generation and enhanced clot formation, and EVs isolated from subjects with moderate CVD risk promoted thrombin generation ex vivo. Higher numbers of endothelial-derived EVs were associated with a greater tendency for clot lysis. Plasma triacylglycerol concentration and diastolic blood pressure independently predicted circulating EV numbers, and EV numbers independently predicted aspects of thrombin generation and clot formation and 10-year CVD risk.

Conclusion

Circulating EVs were strongly associated with both conventional and thrombogenic risk markers of CVDs, and also with overall CVD risk, highlighting a potentially important role for EVs in CVDs.
Overcoming Market Failures in Pandemic Drug Discovery Through Open Science: A Canadian Solution
Authors: Gold E. Richard , Edwards Aled M.
Published: May 2022

Among the lessons learned from the COVID-19 pandemic is the need to develop antiviral drugs poised to treat the next pandemic. Unfortunately, traditional drug development economic models, centered principally on patents, are ineffective to induce private sector investment due to unpredictable timing and cause of the next pandemic. As a result, illustrated by the COVID-19 pandemic, it is the public and philanthropic sectors sectors that overwhelmingly fund the development of innovative vaccines and therapies. To meet the need for proactive antiviral medicines in advance of the next pandemic, new models of drug development are needed. Open science partnerships (OSPs) show promise in this regard. Rather than rely principally on patents and private investment, OSPs combine a variety of academic, philanthropic, governmental, and private sector incentives to share knowledge and develop and test antiviral drugs. Private sector investments are, within an OSP, not only leveraged against investments by other actors, but predicated on gaining regulatory data exclusivity, a known and secure form of commercial advantage. Building on domestic expertise in OSPs, Canadian leaders created the Viral Interruption Medicines Initiative, a not-for-profit OSP, to develop pandemic ready-antivirals and address other areas of market failure.
The Reliability and Validity of the Malay Version of Polycystic Ovarian Syndrome Health-Related Quality of Life Questionnaire
Authors: Mei Lim Leek , Abu Muhammad Azrai , Chew Kah Teik , Ismail Aniza , Zainuddin Ani Amelia , Nur Azurah Abdul Ghani
Published: May 2022

The Polycystic Ovary Syndrome Questionnaire is a reliable instrument for measuring health-related quality of life. This study aimed to develop a Malay version of the Polycystic Ovary Syndrome Questionnaire and to evaluate the health-related impact of Malaysian women with polycystic ovary syndrome. The participants were women who were diagnosed with polycystic ovary syndrome using Rotterdam criteria in a gynecology clinic. Reliability was determined by internal consistency using Cronbach’s coefficient alpha and test–retest reliability using an intra-class correlation coefficient. Validity was assessed through convergent and discriminant validity. Examining the correlation between similar content of the Malay version of the Polycystic Ovary Syndrome Questionnaire and the SF-36 assessed the convergent validity. The discriminant validity was assessed using the known group comparison. Cronbach’s alpha coefficient was over 0.70 for the total scale and over 0.60 for each subscale. Known group comparison supported the discriminant validity. The Malay version of the Polycystic Ovary Syndrome Questionnaire differentiated between the subgroups of women who differed in polycystic ovary syndrome-specific symptoms. Convergent validity was consistent with the good positive correlation between related subscales of the two instruments. Polycystic ovary syndrome women in Malaysia scored the lowest for the weight (3.74) and infertility (3.41) domains, thereby indicating worse health status in these domains. Body hair (5.42) was the least troublesome for the local population. The Malay version of the Polycystic Ovary Syndrome Questionnaire is a reliable and valid tool for assessing the health-related quality of life among women in the local population. It can be used to objectively assess the quality of life among Malaysian women with polycystic ovary syndrome and evaluate their responsiveness to treatment modalities.
Relationship Between SGLT-2i and Ocular Diseases in Patients With Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials
Authors: Zhou Bin , Shi Yetan , Fu Rongrong , Ni Haixiang , Gu Lihu , Si Yuexiu , Zhang Mengting , Jiang Ke , Shen Jingyi , Li Xiangyuan , Sun Xing
Published: May 2022

Background

This meta-analysis was conducted to explore the association between sodium-glucose cotransporter 2 inhibitors (SGLT-2is) and ocular diseases in type 2 diabetes mellitus (T2DM) patients.

Methods

PubMed, Cochrane Central Registry of Controlled Trials, Web of Science and Springer were searched for articles on randomized controlled trials (RCTs) involving T2DM patients treated with SGLT-2i versus placebo or other hypoglycemic agents published prior to August 2021. The primary outcome of this meta-analysis was incidence of ocular diseases, which was assessed using risk ratios (RR) and 95% confidence intervals (CI). We reviewed 47 papers and compared the effect of SGLT-2i with the effect of the control groups (placebo and other hypoglycemic drugs) on the incidence of ocular diseases.

Results

Compared with controls, overall SGLT-2i use in T2DM patients was not associated with incidences of cataract, glaucoma, retinal disease and vitreous disease. Ertugliflozin (RR=0.47, P=0.01) reduced the risk for retinal disease, while empagliflozin (RR=0.44, P=0.05) reduced the risk for diabetic retinopathy (DR) compared with controls. SGLT-2i (RR=0.50, P=0.02), perhaps empagliflozin (RR=0.47, P=0.06), reduced the risk of retinal disease compared with active hypoglycemic agents. Canagliflozin (RR=4.50, P=0.03) increased the risk for vitreous disease compared with placebo.

Conclusions

There was no significant correlation between overall SGLT-2i and ocular diseases (cataract, glaucoma, retinal disease, vitreous disease, corneal disease, conjunctival disease, uveal disease, eye haemorrhage and vision problems) in T2DM patients. Ertugliflozin and empagliflozin may protect against ocular diseases, but canagliflozin may promote ocular diseases.
Impacts of Vegetation Changes on Land Evapotranspiration in China During 1982–2015
Authors: MingYue Zhan , Guojie Wang , Hagan Daniel Fiifi Tawia , Waheed Ullah , Giri Kattel , Jiao Lu , ShiJie Li
Published: May 2022

Evapotranspiration (ET) bridges the hydrological and energy cycle through vegetation transpiration (T), soil evaporation (ES), and canopy interception evaporation (EI). Transpiration to evapotranspiration ratio (T/ET) quantifies the water use efficiency of terrestrial ecosystems explaining the mechanism of vegetation water transport and water–carbon interactions. This study employed GIMMS LAI3g data to improve the CLM4.5 land surface scheme of RegCM4.6. We designed two simulation experiments, each with control (CTL) and sensitivity (SEN), simulating the interannual variability of vegetation on ET and T/ET in China from 1982 to 2015. Studies show China has experienced a greening trend, especially in mid-south China and South China. Leaf area index (LAI) increased significantly (0.002 m2m−2yr−1). ∆LAI (SEN input LAI data minus CTL input LAI data) and ∆T/ET (T/ET data output by SEN minus T/ET data output by CTL) have shown significant positive correlations. The impacts of LAI on T/ET are more prominent during spring and winter than in autumn and summer. Compared with T/ET and LAI (R = 0.70), the correlation between ET and LAI is moderate (R < 0.5), indicating that vegetation has a higher impact on T/ET than ET. The impact of vegetation anomalies (positive and negative LAI anomalies) on T/ET and ET is spatially different, mainly due to dominant factors affecting ET and T/ET changes. In spring, summer, and autumn, &T (transpiration changes corresponding to vegetation anomalies) is the leading factor affecting both ET and T/ET regionally, and &T has a stronger influence on T/ET than ET, especially in summer. Vegetation anomalies have a stronger influence on T/ET than ET; and the influence of positive vegetation anomalies on ET and T/ET is greater than that of negative vegetation anomalies, especially in spring and autumn. This study reveals the mechanisms behind vegetation processes and their influences on the water and heat fluxes at the land–atmosphere interface and provides a strong scientific basis for studying the water cycle under climate warming.
Long-Term Effects of Straw and Straw-Derived Biochar on Humic Substances and Aggregate-Associated Humic Substances in Brown Earth Soil
Authors: Sun Qiang , Yang Xu , Meng Jun , Lan Yu , Han Xiaori , Chen Wenfu , Huang Yuwei
Published: May 2022

Turning maize straw into biochar is useful for improving soil fertility and mitigating climate change. However, the difference between straw and straw-derived biochar on soil aggregate associated humic substances has not been sufficiently studied in brown earth soil. The objective of this study was to investigate how different straw management practices affect soil humic substances and aggregate-associated humic substances in the field. As such, an eight-year study (2013–2020) was conducted on brown earth in Northeast China. Three treatments were applied: 1) CK, in which only chemical fertilizer was applied every year; 2) BC, in which biochar was applied at a rate of 2.625 t ha−1 (the same rate of chemical fertilizer as that in the CK was applied); 3) SR, in which straw was returned at a rate of 7.5 t ha−1 (the same rate of chemical fertilizer as that in the CK was applied). Both biochar and straw improved soil aggregate stability that reflected by the mean weight diameter (MWD) and geometric mean diameter (GMD). Compared to the CK treatment, the BC treatment enhanced humic carbon (HMC) both in bulk soil and different aggregate fractions. Biochar decreased the humic acid carbon (HAC) in bulk soil compared to the initial content, but no differences were observed between BC and CK after the eight-year field experiment. All of the aggregate-associated HAC contents were significantly enhanced in response to BC treatment. SR was an effective way to improve soil organic carbon (SOC) and humic substances in bulk soil and aggregate fractions. SR had a relatively small effect on the relative proportions of the C functional groups. Solid-state 13C cross-polarization magic-angle-spinning nuclear magnetic resonance (CPMAS-NMR) spectra of bulk soils revealed that biochar increased the proportion of aromatic C. The ratios of alkyl C/O-alkyl C, aromatic C/aliphatic C, and hydrophobic C/hydrophilic C increased in response to the BC treatment compared to the other treatments. Taken together, biochar amendment can enhance soil aggregate stability, aggregate-associated HMC and stability of SOC on the scale of an eight-year field experiment. Biochar could be an effective approach to sequestrate carbon and improve the quality of brown earth soil.
Prediction of Prognosis and Immunotherapy of Osteosarcoma Based on Necroptosis-Related lncRNAs
Authors: Wang Guowei , Zhang Xiaobo , Feng Wanjiang , Wang Jianlong
Published: May 2022

Background: Osteosarcoma (OS) is the most common primary tumor of bone in adolescents, and its survival rate is generally less than 20% when metastases occur. Necroptosis, a novel form of programmed necrotic cell death distinct from apoptosis, has been increasingly recognized as a promising therapeutic strategy. This study sought to identify long non-coding RNAs (lncRNAs) associated with necrotizing apoptosis to predict prognosis and target drug use to improve patient survival.

Methods: Transcriptomic data and clinical data from 85 OS patients with survival time data and expression profiles from 85 random normal adipose tissue samples were extracted from the UCSC Xena website (http://xena.ucsc.edu/). Nine necroptosis-associated differential prognostic lncRNAs were then identified by analysis of variance, correlation analysis, univariate Cox (uni-Cox) regression, and Kaplan–Meier analysis. Then, patients were randomized into training or testing groups. According to uni-Cox, we obtained prognostic lncRNAs in the training group and intersected them with the abovementioned nine lncRNAs to obtain the final necrotizing apoptosis–related differential prognostic lncRNAs (NRlncRNAs). Next, we performed the least absolute shrinkage and selection operator (LASSO) to construct a risk model of NRlncRNAs. Kaplan–Meier analysis, ROC curves, nomograms, calibration curves, and PCA were used to validate and evaluate the models and grouping. We also analyzed the differences in tumor immunity and drugs between risk groups.

Results: We constructed a model containing three NRlncRNAs (AL391121.1, AL354919.2, and AP000851.2) and validated its prognostic predictive power. The value of the AUC curve of 1-, 3-, and 5-year survival probability was 0.806, 0.728, and 0.731, respectively. Moreover, we found that the overall survival time of patients in the high-risk group was shorter than that in the low-risk group. GSEA and ssGSEA showed that immune-related pathways were mainly abundant in the low-risk group. We also validated the differential prediction of immune checkpoint expression, tumor immunity, and therapeutic compounds in the two risk groups.

Conclusion: Overall, NRlncRNAs have important functions in OS, and these three NRlncRNAs can predict the prognosis of OS and provide guidance for immunotherapy in OS.
A Machine-Learning Approach to Developing a Predictive Signature Based on Transcriptome Profiling of Ground-Glass Opacities for Accurate Classification and Exploring the Immune Microenvironment of Early-Stage LUAD
Authors: Zhao Zhenyu , Yin Wei , Peng Xiong , Cai Qidong , He Boxue , Shi Shuai , Peng Weilin , Tu Guangxu , Li Yunping , Li Dateng , Tao Yongguang , Peng Muyun , Wang Xiang , Yu Fenglei
Published: May 2022

Screening for early-stage lung cancer with low-dose computed tomography is recommended for high-risk populations; consequently, the incidence of pure ground-glass opacity (pGGO) is increasing. Ground-glass opacity (GGO) is considered the appearance of early lung cancer, and there remains an unmet clinical need to understand the pathology of small GGO (<1 cm in diameter). The objective of this study was to use the transcriptome profiling of pGGO specimens <1 cm in diameter to construct a pGGO-related gene risk signature to predict the prognosis of early-stage lung adenocarcinoma (LUAD) and explore the immune microenvironment of GGO. pGGO-related differentially expressed genes (DEGs) were screened to identify prognostic marker genes with two machine learning algorithms. A 15-gene risk signature was constructed from the DEGs that were shared between the algorithms. Risk scores were calculated using the regression coefficients for the pGGO-related DEGs. Patients with Stage I/II LUAD or Stage IA LUAD and high-risk scores had a worse prognosis than patients with low-risk scores. The prognosis of high-risk patients with Stage IA LUAD was almost identical to that of patients with Stage II LUAD, suggesting that treatment strategies for patients with Stage II LUAD may be beneficial in high-risk patients with Stage IA LUAD. pGGO-related DEGs were mainly enriched in immune-related pathways. Patients with high-risk scores and high tumor mutation burden had a worse prognosis and may benefit from immunotherapy. A nomogram was constructed to facilitate the clinical application of the 15-gene risk signature. Receiver operating characteristic curves and decision curve analysis validated the predictive ability of the nomogram in patients with Stage I LUAD in the TCGA-LUAD cohort and GEO datasets.
A Dissenters’ View on AppleSnail Immunobiology
Authors: Rodriguez Cristian , Vega Israel A. , Castro-Vazquez Alfredo
Published: May 2022

We stand as dissenters against the acceptance of scientific knowledge that has not been built on empirical data. With this in mind, this review synthesizes selected aspects of the immunobiology of gastropods and of apple snails (Ampullariidae) in particular, from morphological to molecular and “omics” studies. Our trip went through more than two centuries of history and was guided by an evo-devo hypothesis: that the gastropod immune system originally developed in the mesenchymal connective tissue of the reno-pericardial complex, and that in that tissue some cells differentiated into hematopoietically committed progenitor cells that integrate constitutive hemocyte aggregations in the reno-pericardial territory, whether concentrated in the pericardium or the kidney in a species-specific manner. However, some of them may be freed from those aggregations, circulate in the blood, and form distant contingent aggregations anywhere in the body, but always in response to intruders (i.e., pathogens or any other immune challenge). After that, we reviewed the incipient immunology of the Ampullariidae by critically revising the findings inPomacea canaliculataandMarisa cornuarietis, the only ampullariid species that have been studied in this respect, and we attempted to identify the effectors and the processes in which they are involved. Particularly forP. canaliculata, which is by far the most studied species, we ask which hemocytes are involved, in which tissues or organs are integrated, and what cellular reactions to intruders this species has in common with other animals. Furthermore, we wondered what humoral factors could also integrate its internal defense system. Among the cellular defenses, we give an outstanding position to the generation of hemocyte nodules, which seems to be an important process for these snails, serving the isolation and elimination of intruders. Finally, we discuss hematopoiesis in apple snails. There have been contrasting views about some of these aspects, but we envision a hematopoietic system centered in the constitutive hemocyte islets in the ampullariid kidney.
Cellular Immunity Is Critical for Assessing COVID-19 Vaccine Effectiveness in Immunocompromised Individuals
Authors: Paramithiotis Eustache , Sugden Scott , Papp Eszter , Bonhomme Marie , Chermak Todd , Crawford Stephanie Y. , Demetriades Stefanie Z. , Galdos Gerson , Lambert Bruce L. , Mattison John , McDade Thomas , Pillet Stephane , Murphy Robert
Published: May 2022

COVID-19 vaccine clinical development was conducted with unprecedented speed. Immunity measurements were concentrated on the antibody response which left significant gaps in our understanding how robust and long-lasting immune protection develops. Better understanding the cellular immune response will fill those gaps, especially in the elderly and immunocompromised populations which not only have the highest risk for severe infection, but also frequently have inadequate antibody responses. Although cellular immunity measurements are more logistically complex to conduct for clinical trials compared to antibody measurements, the feasibility and benefit of doing them in clinical trials has been demonstrated and so should be more widely adopted. Adding significant cellular response metrics will provide a deeper understanding of the overall immune response to COVID-19 vaccination, which will significantly inform vaccination strategies for the most vulnerable populations. Better monitoring of overall immunity will also substantially benefit other vaccine development efforts, and indeed any therapies that involve the immune system as part of the therapeutic strategy.
Metabolomic Investigation of Ultraviolet Ray-Inactivated White Spot Syndrome Virus-Induced Trained Immunity in Marsupenaeus japonicus
Authors: Zang Shaoqing , Lv Li-Xia , Liu Chen-Fei , Zhang Peng , Li Cang , Wang Jin-Xing
Published: May 2022

Trained immunity is driven by metabolism and epigenetics in innate immune cells in mammals. The phenomenon of trained immunity has been identified in invertebrates, including shrimp, but the underlying mechanisms remain unclear. To elucidate mechanisms of trained immunity in shrimp, the metabolomic changes in hemolymph of Marsupenaeus japonicus trained by the UV-inactivated white spot syndrome virus (UV-WSSV) were analyzed using tandem gas chromatography–mass/mass spectrometry. The metabolomic profiles of shrimp trained with UV-WSSV followed WSSV infection showed significant differences comparison with the control groups, PBS injection followed WSSV infection. 16 differential metabolites in total of 154 metabolites were identified, including D-fructose-6-phosphate, D-glucose-6-phosphate, and D-fructose-6-phosphate, and metabolic pathways, glycolysis, pentose phosphate pathway, and AMPK signaling pathway were enriched in the UV-WSSV trained groups. Further study found that histone monomethylation and trimethylation at H3K4 (H3K4me1 and H3K4me3) were involved in the trained immunity. Our data suggest that the UV-WSSV induced trained immunity leads to metabolism reprogramming in the shrimp and provide insights for WSSV control in shrimp aquaculture.