bluuebunny/crossref_metadata_2025 huggingface dataset:
What Health Information is Needed to Improve the Vaccination Outcomes of COVID-19? : Study Analysis in COVID-19 Vaccination in Sangihe Island Regency, Indonesia
Authors: Pramardika Dhito Dwi , Hinonaung Jelita Sisika Herlina , Wuaten Grace Angel , Mahihody Astri Juwita
Published: July 2021

The Indonesian government enforces a COVID-19 vaccination policy for all, but the achievement rate for the COVID-19 vaccination in Sangihe Islands Regency at the first dose is only 1.05%, while the achievement at the second dose to date is only 0.47%. With this in mind, the vaccination policy has not been in line with community participation. The purpose of this study was to find out what kind of health information is needed to increase the covid-19 vaccination rate. The method used in this research is a descriptive study with a purposive sampling technique which was held from 7 January to 8 February 2021 with a total sample of 85 respondents who are health workers in the Sangihe Islands Regency. The data analysis used is descriptive analysis with frequency distribution. The results in this study were 15.3% stated that they were not willing to vaccinate COVID-19 because 39% of COVID-19 survivors, 38% had comorbidities, 15% were unsure of safety and 8% feared side effects. The conclusion of this study is to increase health information regarding vaccines for COVID-19 survivors, information about comorbidities such as what is appropriate for COVID-19 vaccination, safety, and side effects resulting from the COVID-19 vaccine.
The Effectiveness of Antidepressant Combined with Quranic CBT in Reducing Anxiety Level of Moslem Outpatient withh Anxiety Disorder in Sultan Agung Islamic Hospital in Semarang
Authors: Novembrina Metrikana , Putri Dinia Eko Kusmianti , Indrasari Ferika , Setyaningsih Wahyu
Published: July 2021

Anxiety disorders is an emotional condition in which a person feels excessively anxious and it is generally caused by the excessive perception of a particular danger threatens the security of an individual and sometimes interferes with the daily activities and social interaction of an individual. This study aimed to determine the effectiveness of the Quranic CBT in reducing the anxiety level of the outpatient with anxiety disorder in Sultan Agung Islamic Hospital, Semarang. This was a treatment trial research using purposive sampling technique. In this study as much as 20 patients diagnosed with anxiety disorders and in the treatment with antidepressants were randomly divided into 2 groups. Group 1 was the patients undergoing therapy with antidepresant and also given Quranic CBT. Group 2 was the patients using antidepressant drugs and not given Quranic CBT therapy. This showed that the Quranic CBT method was effective in reducing the anxiety level.
Historia y futuro del mantenimiento y la vigilancia de los puentes ferroviarios
Authors: Esteras Aldea Luis , Gómez Barquín José Antonio
Published: July 2021

El mantenimiento de las infraestructuras ha venido ocupando un lugar secundario a lo largo de la historia de la Ingeniería siempre eclipsado por las facetas del diseño y la construcción de obra nueva. No obstante, cada vez la conservación y el mantenimiento de las infraestructuras se va haciendo hueco en las Escuelas Técnicas, en la normativa y en las licitaciones públicas gracias al esfuerzo diario de los grandes profesionales que se dedican a ello. Veamos cual ha sido esta tendencia en el caso particular de los puentes ferroviarios.
Sustitución de la membrana de la cubierta del estadio de La Cartuja de Sevilla, España
Authors: Goberna Pérez Enrique Gonzalo , Stockhusen Knut , Schlaich Mike
Published: July 2021

Tras 20 años de servicio, la membrana de la cubierta del Estadio Olímpico de La Cartuja en Sevillla mostró signos claros de envejecimiento, lo que se tradujo en una pérdida de pretensado del sistema estructural y por tanto de su rigidez. Esto, junto con un probable desajuste en las cargas muertas asumidas en el diseño original provocó que, bajo ciertas condiciones de lluvia y carga de viento de presión sobre la cubierta, las aguas de escorrentía no drenaran hacia los puntos adecuados. En marzo de 2018 unas lluvias torrenciales se combinaron con vientos del oeste que, a la vista de los acontecimientos, eran compatibles con las circunstancias que provocaron un mal drenaje de la cubierta, lo cual dio lugar a estancamientos de agua en la membrana. El presente artículo describe los pasos que se dieron para solucionar la patología.
Aplicación de los sistemas mixtos para el refuerzo de patologías en puentes de hormigón
Authors: Millanes Mato Francisco , Ortega Cornejo Miguel , Pulido Sánchez Ignacio , Salas Fernández-Polanco Santiago , Bordó Bujalance Enrique
Published: July 2021

Las estructuras mixtas presentan una amplia gama de posibilidades para la reparación y refuerzo de puentes de hormigón. El uso de este tipo de estructuras supone una serie de ventajas respecto a otros métodos como son en muchos casos la flexibilidad, polivalencia, alta capacidad resistente en proporción al peso, y facilidad de ejecución. Aspectos importantes a tener en cuenta son el montaje de uniones y el control de tolerancias geométricas, así como la conexión entre la estructura metálica y el puente de hormigón existente.

En el artículo se expone un ejemplo reciente de este tipo de soluciones proyectado por IDEAM. Se trata del viaducto sobre el río Duero en la A-66, en Zamora (España). Esta estructura, formada por un cajón de hormigón pretensado que adolecía de patologías en el hormigón, fue reforzada de manera integral mediante el montaje de sendas vigas metálicas adosadas al cajón existente, dando lugar como nueva estructura resistente a un tablero mixto.
Los problemas árido álcali o la necesidad de anticiparse a un proceso irreversible en los puentes
Authors: Martín-Caro Álamo José Antonio , Martínez Martínez José Luis , Arias Hofman Gonzalo
Published: July 2021

Las reacciones expansivas en el hormigón, y en particular las reacciones por reacción árido-álcali, no son un problema desconocido ni novedoso, pero están empezando a adquirir una presencia nada desdeñable en los puentes de las carreteras españolas. Así se ha constatado en el curso de numerosas y recientes campañas de inspección en las que han participado los autores de este artículo, en ocasiones con consecuencias traumáticas cuando la enfermedad se ha manifestado y ha alterado las características del hormigón hasta un extremo que ha obligado a demoler la estructura.

El presente artículo pretende proponer una sistemática para el reconocimiento con distintos niveles de detalle, empezando por la inspección visual de la sintomatología que define estos procesos y una metodología que permita analizar la incidencia de este fenómeno en la disminución de las propiedades mecánicas del hormigón y en el comportamiento resistente del puente.
Association of lifestyle changes due to the COVID-19 pandemic with nutrient intake and physical activity levels during pregnancy in Japan
Authors: Hori Natsuki , Shiraishi Mie , Harada Rio , Kurashima Yuki
Published: July 2021

This study aimed to clarify the association of lifestyle changes due to the coronavirus disease 2019 (COVID-19) pandemic with nutrient intake and physical activity levels during pregnancy in Japan. A cross-sectional study was conducted for pregnant Japanese women in 2020. Nutrient intake and physical activity levels were assessed using validated self-administered questionnaires. Participants who reported experiencing changes in both dietary habits and physical activity due to the COVID-19 pandemic were classified as the lifestyle-affected group. A total of 91 primiparas and 77 multiparas were analyzed. Among primiparas, intake of the following nutrients was significantly higher in the lifestyle-affected group than in the unaffected group: protein, potassium, calcium, magnesium, and vitamin B6. Among multiparas, the intake of total dietary fiber and β-carotene was significantly lower in the lifestyle-affected group. During an infectious disease pandemic, healthcare professionals should provide nutritional guidance taking into consideration the possibility of different effects according to parity.
REPRESENTAÇÕES E IDENTIDADES JUVENIS NA SOCIEDADE ATUAL: PADRONIZAÇÕES E ESTEREÓTIPOS
Authors: Lima Crislaine Pereira de , Polato Adriana Delmira Mendes , Pátaro Cristina Satiê de Oliveira
Published: July 2021

A partir de uma abordagem interdisciplinar, que coaduna interpretações da sociologia, da antropologia, da filosofia e do dialogismo do círculo russo de Bakhtin, nosso objetivo consiste em analisar um artigo intitulado “Os jovens nem nem” publicado na revista “Istoé” online, que mobiliza um discurso sobre os jovens que não estudam e também não trabalham. Na análise do enunciado, buscamos compreender como ele reflete e refrata valorações próprias de partidas ideológicas que buscam analisar o papel social do jovem a partir de uma interpretação de base socioeconômica. Os conceitos de signo ideológico, palavra, ideologia, e consciência socioideológica são mobilizados na análise, na medida em que entendemos que o enunciado é constituído por valorações que sustentam relações sociais, interpretações de mundo e das vivências, sempre a partir de posicionamentos ideológicos. Como resultado, apresentamos a importância do dialogismo na análise dos discursos que ecoam perspectivas sócio-históricas, culturais e ideológicas sobre a temática das juventudes, a destacar como fundamental a presença de vozes sociais e valores que servem a representações refratárias, ou à multiplicidade de identidades e trajetórias dos jovens, de modo a clarificar  como os discursos  constituem e ao mesmo tempo são constituídos pelas relações sociais, sendo sua interpretação subsidiária de prospecções e rupturas de ordens instaladas.
Oregano Essential Oil Micro- and Nanoencapsulation With Bioactive Properties for Biotechnological and Biomedical Applications
Authors: Pontes-Quero Gloria María , Esteban-Rubio Susana , Pérez Cano Juan , Aguilar María Rosa , Vázquez-Lasa Blanca
Published: July 2021

Due to the preservative, antioxidant, antimicrobial, and therapeutic properties of oregano essential oil (OEO), it has received an emerging interest for biotechnological and biomedical applications. However, stability and bioactivity can be compromised by its natural volatile and hydrophobic nature, and by external factors including light, heat, or oxygen. Therefore, micro- and nanoencapsulation are being employed to guarantee oregano oil protection from outside aggressions and to maximize its potential. Oregano oil encapsulation is an interesting strategy used to increase its stability, enhance its bioactivity, and decrease its volatility. At the same time, the versatility that micro- and nanocarriers offer, allows to prepare tailored systems that can provide a controlled and targeted release of the encapsulated principle, influence its bioactive activities, or even provide additional properties. Most common materials used to prepare these carriers are based on lipids and cyclodextrins, due to their hydrophobic nature, polymers due to their versatility in composition, and hybrid lipid-polymer systems. In this context, recently developed micro- and nanocarriers encapsulating oregano oil with applications in the biotechnological and biomedical fields will be discussed.
Acylglycerol Kinase-Targeted Therapies in Oncology
Authors: Chu Binxiang , Hong Zhenghua , Zheng Xiaohe
Published: July 2021

Acylglycerol kinase (AGK) is a recently discovered mitochondrial lipid kinase, and mutation of its gene is the fundamental cause of Sengers syndrome. AGK is not only involved in the stability of lipid metabolism but also closely related to mitochondrial protein transport, glycolysis, and thrombocytopoiesis. Evidence indicates that AGK is an important factor in the occurrence and development of tumors. Specifically, AGK has been identified as an oncogene that partakes in the regulation of tumor cell growth, invasion, metastasis, and drug resistance. The versatility of AGK and its unique role in different types of cancerous and normal cells greatly piqued our interest. We believe that AGK is a promising target for cancer therapy. Therefore, this review summarizes the main research advances concerning AGK, including the discovery of its physiological/pathogenic mechanisms, and provides a reference for the feasible evaluation of AGK as a therapeutic target for human diseases, particularly tumors.
Deletion of the Wilms’ Tumor Suppressor Gene in the Cardiac Troponin-T Lineage Reveals Novel Functions of WT1 in Heart Development
Authors: Díaz del Moral Sandra , Barrena Silvia , Hernández-Torres Francisco , Aránega Amelia , Villaescusa José Manuel , Gómez Doblas Juan José , Franco Diego , Jiménez-Navarro Manuel , Muñoz-Chápuli Ramón , Carmona Rita
Published: July 2021

Expression of Wilms’ tumor suppressor transcription factor (WT1) in the embryonic epicardium is essential for cardiac development, but its myocardial expression is little known. We have found that WT1 is expressed at low levels in 20–25% of the embryonic cardiomyocytes. Conditional ablation of WT1 using a cardiac troponin T driver (Tnnt2Cre) caused abnormal sinus venosus and atrium development, lack of pectinate muscles, thin ventricular myocardium and, in some cases, interventricular septum and cardiac wall defects, ventricular diverticula and aneurisms. Coronary development was normal and there was not embryonic lethality, although survival of adult mutant mice was reduced probably due to perinatal mortality. Adult mutant mice showed electrocardiographic anomalies, including increased RR and QRS intervals, and decreased PR intervals. RNASeq analysis identified differential expression of 137 genes in the E13.5 mutant heart as compared to controls. GO functional enrichment analysis suggested that both calcium ion regulation and modulation of potassium channels are deeply altered in the mutant myocardium. In summary, together with its essential function in the embryonic epicardium, myocardial WT1 expression is also required for normal cardiac development.
Emerging Regulatory Mechanisms Involved in Liver Cancer Stem Cell Properties in Hepatocellular Carcinoma
Authors: Lv Duoduo , Chen Liyu , Du Lingyao , Zhou Lingyun , Tang Hong
Published: July 2021

Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer and one of the leading causes of cancer-related deaths worldwide. A growing body of evidence supports the hypothesis that HCC is driven by a population of cells called liver cancer stem cells (LCSCs). LCSCs have been proposed to contribute to malignant HCC progression, including promoting tumor occurrence and growth, mediating tumor metastasis, and treatment resistance, but the regulatory mechanism of LCSCs in HCC remains unclear. Understanding the signaling pathways responsible for LCSC maintenance and survival may provide opportunities to improve patient outcomes. Here, we review the current literature about the origin of LCSCs and the niche composition, describe the current evidence of signaling pathways that mediate LCSC stemness, then highlight several mechanisms that modulate LCSC properties in HCC progression, and finally, summarize the new developments in therapeutic strategies targeting LCSCs markers and regulatory pathways.
Identification of Potential Binding Sites of Sialic Acids on the RBD Domain of SARS-CoV-2 Spike Protein
Authors: Li Bingqian , Wang Lin , Ge Huan , Zhang Xianglei , Ren Penxuan , Guo Yu , Chen Wuyan , Li Jie , Zhu Wei , Chen Wenzhang , Zhu Lili , Bai Fang
Published: July 2021

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still an emergent pandemic for humans. The virus infection is achieved by penetrating its spike protein to host cells via binding with ACE2. Moreover, recent studies show that SARS-CoV-2 may have multiple receptors that need to be further revealed. SARS-CoV-2 shares similar sequences of the spike protein with the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which can invade host cells by binding to either DPP4 or sialic acids. Sialic acids can be linked to the terminal of glycoproteins and gangliosides are used as one of the receptors of many types of viruses. Therefore, it is very interesting to determine whether sialic acid is a potential receptor of SARS-CoV-2. To address this question, we took N-Acetylneuraminic acid (Neu5Ac), a type of predominant sialic acid found in human cells, as the molecular probe to computationally search the surface of the spike protein to locate the potential binding sites of Neu5Ac. SPR analysis and mass spectrum analysis confirmed the interaction between Neu5Ac and spike protein. This study shows that sialic acids can moderately interact with the spike protein of SARS-CoV-2 by binding between the two RBDs of the spike protein, indicating it could be a potential secondary or auxiliary receptor of SARS-CoV-2.
Synthetic Integrin-Targeting Dextran-Fc Hybrids Efficiently Inhibit Tumor Proliferation In Vitro
Authors: Schneider Hendrik , Englert Simon , Macarrón Palacios Arturo , Lerma Romero Jorge Alberto , Ali Ataurehman , Avrutina Olga , Kolmar Harald
Published: July 2021

Herein, we present the design, synthesis, and biological evaluation of novel integrin-targeting molecular hybrids combining RGD peptides and a potent cytotoxin presented on dextran polysaccharides. Based on an aglycosylated Fc as a centerpiece, endosomal-cleavable cytotoxic agent monomethyl auristatin E (MMAE) and dextran as multimerization site were covalently connected by two bioorthogonal enzyme-mediated reactions site-specifically. Decoration of dextran with cyclic RGD peptides, introduced by copper “click” reaction, resulted in the final constructs with the potential to kill integrin-overexpressing tumor cells. We found that these modifications had little impact on the stability of the Fc scaffold and the RGD-bearing construct showed good binding properties of αvβ3-expressing U87MG cells. Furthermore, the construct showed a remarkable antiproliferative activity. These results demonstrate the general capability of our design to provoke receptor-mediated endocytosis upon binding to the cellular surface, followed by endosomal cleavage of the linkage between Fc-dextran and MMAE and its subsequent release. Our approach opens new avenues to transcribe small molecule binders into tailor-made multimeric molecular hybrids with antitumor potential.
Bridging the 12-6-4 Model and the Fluctuating Charge Model
Authors: Li Pengfei
Published: July 2021

Metal ions play important roles in various biological systems. Molecular dynamics (MD) using classical force field has become a popular research tool to study biological systems at the atomic level. However, meaningful MD simulations require reliable models and parameters. Previously we showed that the 12-6 Lennard-Jones nonbonded model for ions could not reproduce the experimental hydration free energy (HFE) and ion-oxygen distance (IOD) values simultaneously when ion has a charge of +2 or higher. We discussed that this deficiency arises from the overlook of the ion-induced dipole interaction in the 12-6 model, and this term is proportional to 1/r4 based on theory. Hence, we developed the 12-6-4 model and showed it could solve this deficiency in a physically meaningful way. However, our previous research also found that the 12-6-4 model overestimated the coordination numbers (CNs) for some highly charged metal ions. And we attributed this artifact to that the current 12-6-4 scheme lacks a correction for the interactions among the first solvation shell water molecules. In the present study, we considered the ion-included dipole interaction by using the 12-6 model with adjusting the atomic charges of the first solvation shell water molecules. This strategy not only considers the ion-induced dipole interaction between ion and the first solvation shell water molecules but also well accounts for the increased repulsion among these water molecules compared to the bulk water molecules. We showed this strategy could well reproduce the experimental HFE and IOD values for Mg2+, Zn2+, Al3+, Fe3+, and In3+ and solve the CN overestimation issue of the 12-6-4 model for Fe3+ and In3+. Moreover, our simulation results showed good agreement with previous ab initio MD simulations. In addition, we derived the physical relationship between the C4 parameter and induced dipole moment, which agreed well with our simulation results. Finally, we discussed the implications of the present work for simulating metalloproteins. Due to the fluctuating charge model uses a similar concept to the 12-6 model with adjusting atomic charges, we believe the present study builds a bridge between the 12-6-4 model and the fluctuating charge model.
Endothelial Activation in Orientia tsutsugamushi Infection Is Mediated by Cytokine Secretion From Infected Monocytes
Authors: Tantibhedhyangkul Wiwit , Matamnan Sutthicha , Longkunan Asma , Boonwong Chawikan , Khowawisetsut Ladawan
Published: July 2021

Scrub typhus, caused byOrientia tsutsugamushi, is a common systemic infection in Asia. Delay in diagnosis and treatment can lead to vasculitis in the visceral organs and other complications. The mechanisms that drive endothelial activation and the inflammatory response inO. tsutsugamushiinfection remain unknown. In addition, the interaction between monocytes and endothelial cells is still unclear. Here we demonstrate thatO. tsutsugamushi-infected human dermal microvascular endothelial cells produced moderate levels of chemokines and low levels of IL-6 and IFN-β, but not TNF or IL-1β. Recombinant TNF and cytokine-rich supernatants from infected monocytes markedly enhanced chemokine production in infected endothelial cells. We also show that TNF and monocyte supernatants, but notO. tsutsugamushiinfection of endothelial cellsper se, upregulated the endothelial cell surface expression of ICAM-1, E-selectin, and tissue factor. This finding was consistent with the inability ofO. tsutsugamushito induce cytokine secretion from endothelial cells. The upregulation of surface molecules after stimulation with monocyte supernatants was significantly reduced by neutralizing anti-TNF antibodies. These results suggest that endothelial cell activation and response are mainly mediated by inflammatory cytokines secreted from monocytes.
Effect of High-Frequency Oscillatory Ventilation Combined With Pulmonary Surfactant in the Treatment of Acute Respiratory Distress Syndrome After Cardiac Surgery: A Prospective Randomised Controlled Trial
Authors: Zheng Yi-Rong , Lei Yu-Qing , Liu Jian-Feng , Wu Hong-Lin , Xu Ning , Huang Shu-Ting , Cao Hua , Chen Qiang
Published: July 2021

Background: This study aimed to evaluate the effects of pulmonary surfactant (PS) combined with high-frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CMV) in infants with acute respiratory distress syndrome (ARDS) after congenital cardiac surgery.

Methods: A total of 61 infants with ARDS were eligible and were randomised to the CMV + PS group (n = 30) or the HFOV + PS group (n = 31) between January 2020 and December 2020. The primary outcomes were the changes in arterial blood gas parameters. The duration of mechanical ventilation, length of hospitalisation and the incidence of complications were considered secondary outcomes.

Results: A total of 61 infants completed the study. In the HFOV + PS group, the blood gas analysis results were significantly improved (P < 0.05), while the duration of mechanical ventilation and length of hospitalisation were shorter than the CMV + PS group (P < 0.05). However, the incidence of complications was not different between the two groups (P > 0.05).

Conclusions: Compared with the CMV + PS group, the HFOV + PS group showed significantly improved ABG variables and had a shortened length of hospitalisation and mechanical ventilation in infants with ARDS after cardiac surgery.

Clinical Trial Registration: Chinese Clinical Trial Registry; Number: ChiCTR2000039457.
Elevated Serum Levels of Soluble ST2 Are Associated With Plaque Vulnerability in Patients With Non-ST-Elevation Acute Coronary Syndrome
Authors: Luo Guqing , Qian Yuxuan , Sheng Xincheng , Sun Jiateng , Wu Zhinan , Liao Fei , Feng Qi , Yin Yan , Ding Song , Pu Jun
Published: July 2021

Background: Recent studies have suggested that soluble suppression of tumorigenicity-2 (sST2), an inflammation-related protein receptor, is associated with atherosclerotic diseases. This study aimed to investigate the potential predictive value of sST2 on plaque vulnerability by assessing whether elevated serum levels of sST2 are associated with vulnerable plaque features in patients with non-ST-elevation acute coronary syndrome (ACS).

Methods: A total of 120 patients with non-ST-elevation ACS (167 lesions) were prospectively enrolled and evaluated by standard coronary computed tomography angiography (CCTA) and coronary angiography in this study. Serum sST2 levels were measured by ELISA (Presage® ST2 Assay Kit, Critical Diagnostics), and semiautomated software (QAngioCT, Medis) was used to quantify coronary plaques.

Results: The included patients were divided into 4 groups by serum sST2 level quartiles. Volumetric analysis of the whole lesion revealed that patients with higher sST2 levels had a larger absolute necrotic core (NC) volume (Quartile 4 vs. Quartile 1, 86.16 ± 59.71 vs. 45.10 ± 45.80 mm3, P = 0.001; Quartile 4 vs. Quartile 2, 86.16 ± 59.71 vs. 50.22 ± 42.56 mm3, P = 0.002) and a higher NC percentage (Quartile 4 vs. Quartile 1, 35.16 ± 9.82 vs. 23.21 ± 16.18%, P < 0.001; Quartile 4 vs. Quartile 2, 35.16 ± 9.82% vs. 22.50 ± 14.03%, P < 0.001; Quartile 4 vs. Quartile 3, 35.16 ± 9.82% vs. 25.04 ± 14.48%, P < 0.001). Correlation analysis revealed that serum sST2 levels were positively correlated with the NC (r = 0.323, P < 0.001) but negatively correlated with dense calcium (r = −0.208, P = 0.007). Furthermore, among those with plaque calcification, patients with spotty calcification exhibited higher serum sST2 levels than those with large calcification (26.06 ± 16.54 vs. 17.55 ± 7.65 ng/mL, P = 0.002). No significant differences in plaque components at the level of the minimal lumen area (MLA) were found among the groups.

Conclusions: Serum sST2 levels were correlated with different coronary plaque components in patients with non-ST-elevation ACS. A higher serum level of sST2 was correlated with plaque vulnerability.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04797819.
Hyperphosphatemic Familial Tumoral Calcinosis Hidden in Plain Sight for 73 Years: A Case Report
Authors: Lee Alisa E. , Hartley Iris R. , Roszko Kelly L. , Vanek Chaim , Gafni Rachel I. , Collins Michael T.
Published: July 2021

While dental pulp calcifications and root anomalies may be inconsequential incidental findings in dental radiographs, they can, especially in combination, represent a clue, hidden in plain sight, for the diagnosis of hyperphosphatemic familial tumoral calcinosis (HFTC). HFTC is an autosomal recessive disease of mineral metabolism characterized by sometimes massive, painful calcification around large joints, systemic inflammation, dental pulp calcification, and thistle-shaped roots. This paper describes a woman with HFTC who endured not only the symptoms of HFTC for decades, but also the frustration of not knowing the cause. The diagnosis was finally made at the age of 73 years, when the connection between a large right shoulder calcification and hyperphosphatemia was made. The dental findings were likely present on her initial radiographs taken in childhood. Increased awareness of the association between characteristic dental findings and HFTC may allow for earlier diagnosis and interventions to improve the care of patients with this rare condition.
Porous Shallow Water Modeling for Urban Floods in the Zhoushan City, China
Authors: Li Wei , Liu Bingrun , Hu Peng , He Zhiguo , Zou Jiyu
Published: July 2021

Typhoon-induced intense rainfall and urban flooding have endangered the city of Zhoushan every year, urging efficient and accurate flooding prediction. Here, two models (the classical shallow water model that approximates complex buildings by locally refined meshes, and the porous shallow water model that adopts the concept of porosity) are developed and compared for the city of Zhoushan. Specifically, in the porous shallow water model, the building effects on flow storage and conveyance are modeled by the volumetric and edge porosities for each grid, and those on flow resistance are considered by adding extra drag in the flow momentum. Both models are developed under the framework of finite volume method using unstructured triangular grids, along with the Harten-Lax-van Leer-Contact (HLLC) approximate Riemann solver for flux computation and a flexible dry-wet treatment that guarantee model accuracy in dealing with complex flow regimes and topography. The pluvial flooding is simulated during the Super Typhoon Lekima in a 46 km2 mountain-bounded urban area, where efficient and accurate flooding prediction is challenged by local complex building geometry and mountainous topography. It is shown that the computed water depth and flow velocity of the two models agree with each other quite well. For a 2.8-day prediction, the computational cost is 120 min for the porous model using 12 cores of the Intel(R) Xeon(R) Platinum 8173M CPU @ 2.00 GHz processor, whereas it is as high as 17,154 min for the classical shallow water model. It indicates a speed-up of 143 times and sufficient pre-warning time by using the porous shallow water model, without appreciable loss in the quantitative accuracy.
Metformin and Covid-19: Focused Review of Mechanisms and Current Literature Suggesting Benefit
Authors: Ibrahim Sherehan , Lowe Jamie R. , Bramante Carolyn T. , Shah Surbhi , Klatt Nichole R. , Sherwood Nancy , Aronne Louis , Puskarich Michael , Tamariz Leonardo , Palacio Ana , Bomberg Eric , Usher Michael , King Samantha , Benson Brad , Vojta Deneen , Tignanelli Chris , Ingraham Nicholas
Published: July 2021

Metformin is the first-line medication for type 2 diabetes, but it also has a long history of improved outcomes in infectious diseases, such as influenza, hepatitis C, and in-vitro assays of zika. In the current Covid-19 pandemic, which has rapidly spread throughout the world, 4 observational studies have been published showing reduced mortality among individuals with home metformin use. There are several potential overlapping mechanisms by which metformin may reduce mortality from Covid-19. Metformin’s past anti-infectious benefits have been both against the infectious agent directly, as well as by improving the underlying health of the human host. It is unknown if the lower mortality suggested by observational studies in patients infected with Covid-19 who are on home metformin is due to direct activity against the virus itself, improved host substrate, or both.
Histone Deacetylases in the Pathogenesis of Diabetic Cardiomyopathy
Authors: Ke Xiangyu , Lin Zhirui , Ye Zebing , Leng Meifang , Chen Bo , Jiang Chunjie , Jiang Xiaoyun , Li Guowei
Published: July 2021

The global burden of diabetes mellitus and its complications are currently increasing. Diabetic cardiomyopathy (DCM) is the main cause of diabetes mellitus associated morbidity and mortality; therefore, a comprehensive understanding of DCM development is required for more effective treatment. A disorder of epigenetic posttranscriptional modification of histones in chromatin has been reported to be associated with the pathology of DCM. Recent studies have implicated that histone deacetylases could regulate cardiovascular and metabolic diseases in cellular processes including cardiac fibrosis, hypertrophy, oxidative stress and inflammation. Therefore in this review, we summarized the roles of histone deacetylases in the pathogenesis of DCM, aiming to provide insights into exploring potential preventative and therapeutic strategies of DCM.
Insulin Treatment May Increase Adverse Outcomes in Patients With COVID-19 and Diabetes: A Systematic Review and Meta-Analysis
Authors: Yang Yan , Cai Zixin , Zhang Jingjing
Published: July 2021

Background and Objective

Recently, insulin treatment has been found to be associated with increased mortality and other adverse outcomes in patients with coronavirus disease 2019 (COVID-19) and diabetes, but the results remain unclear and controversial, therefore, we conducted this meta-analysis.

Methods

Four databases, namely, PubMed, Web of Science, EMBASE and the Cochrane Library, were used to identify all studies concerning insulin treatment and the adverse effects of COVID-19, including mortality, incidence of severe/critical complications, in-hospital admission and hospitalization time. To assess publication bias, funnel plots, Begg’s tests and Egger’s tests were used. The odds ratios (ORs) with 95% confidence intervals (CIs) were used to access the effect of insulin therapy on mortality, severe/critical complications and in-hospital admission. The association between insulin treatment and hospitalization time was calculated by the standardized mean difference (SMD) with 95% CIs.

Results

Eighteen articles, involving a total of 12277 patients with COVID-19 and diabetes were included. Insulin treatment was significantly associated with an increased risk of mortality (OR=2.10; 95% CI, 1.51-2.93) and incidence of severe/critical COVID-19 complications (OR=2.56; 95% CI, 1.18-5.55). Moreover, insulin therapy may increase in-hospital admission in patients with COVID-19 and diabetes (OR=1.31; 95% CI, 1.06-1.61). However, there was no significant difference in the hospitalization time according to insulin treatment (SMD=0.21 95% CI, -0.02-0.45).

Conclusions

Insulin treatment may increase mortality and severe/critical complications in patients with COVID-19 and diabetes, but more large-scale studies are needed to confirm and explore the exact mechanism.
Highly Symptomatic Progressing Cardiac Paraganglioma With Intracardiac Extension Treated With 177Lu-DOTATATE: A Case Report
Authors: Huot Daneault Alexis , Desaulniers Mélanie , Beauregard Jean-Mathieu , Beaulieu Alexis , Arsenault Frédéric , April Geneviève , Turcotte Éric , Buteau François-Alexandre
Published: July 2021

Introduction

Primary cardiac paragangliomas are rare tumors. Metastatic disease is even rarer. Surgical management is technically challenging, and sometimes even impossible. Available therapeutic modalities for metastatic disease include external beam radiation therapy as well as systemic treatments, namely 131I-MIBG and more recently, peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE. To our knowledge, this is the first case of progressive unresectable cardiac paraganglioma with intracardiac extension treated with dosimetry based personalized PRRT to be reported. This case is of particular interest since it documents for the first time the efficacy, and especially the safety of the 177Lu-DOTATATE PRRT in this precarious context for which therapeutic options are limited.

Case Presentation

A 47-year-old man with no medical history consulted for rapidly decreasing exercise tolerance. The investigation demonstrated an unresectable progressing metastatic cardiac paraganglioma with intracardiac extension. The patient was treated with personalized 177Lu-DOTATATE PRRT and showed complete symptomatic and partial anatomical responses, with a progression-free survival of 13 months.

Conclusions

PRRT with 177Lu-DOTATATE should be considered for inoperable cardiac paraganglioma. No major hemodynamic complications were experienced. Therapy resulted in safety and substantially improved quality of life.
Association Between Paternal Age and Birth Weight in Preterm and Full-Term Birth: A Retrospective Study
Authors: Mao Yiting , Zhang Chen , Wang Yinyu , Meng Yicong , Chen Lei , Dennis Cindy-Lee , Sheng Jianzhong , Wu Yanting , Huang Hefeng
Published: July 2021

Purpose

While it is well documented that maternal adverse exposures contribute to a series defects on offspring health according to the Developmental Origins of Health and Disease (DOHaD) theory, paternal evidence is still insufficient. Advanced paternal age is associated with multiple metabolism and psychiatric disorders. Birth weight is the most direct marker to evaluate fetal growth. Therefore, we designed this study to explore the association between paternal age and birth weight among infants born at term and preterm (<37 weeks gestation).

Methods

A large retrospective study was conducted using population-based hospital data from January 2015 to December 2019 that included 69,964 cases of singleton infant births with complete paternal age data. The primary outcome was infant birth weight stratified by sex and gestational age including small for gestational age (SGA, 10th percentile) and large for gestational age (LGA, 90th percentile). Birth weight percentiles by gestational age were based on those published in the INTERGROWTH-21st neonatal weight-for gestational-age standard. Logistic regression analysis and linear regression model were used to estimate the association between paternal age and infant birth weight.

Results

Advanced paternal age was associated with a higher risk for a preterm birth [35–44 years: adjusted odds ratio (OR) = 1.13, 95%CI (1.03 to 1.24); >44 years: OR = 1.36, 95%CI (1.09 to 1.70)]. Paternal age exerted an opposite effect on birth weight with an increased risk of SGA among preterm infants (35–44years: OR = 1.85, 95%CI (1.18 to 2.89) and a decreased risk among term infant (35–44years: OR = 0.81, 95%CI (0.68 to 0.98); >44 years: OR = 0.50, 95%CI (0.26 to 0.94). U-shaped associations were found in that LGA risk among term infants was higher in both younger (<25 years) (OR = 1.32; 95%CI, 1.07 to 1.62) and older (35–44 years) (OR = 1.07; 95% CI, 1.01 to 1.14) fathers in comparison to those who were 25 to 34 years old at the time of delivery.

Conclusions

Our study found advanced paternal age increased the risk of SGA among preterm infants and for LGA among term infants. These findings likely reflect a pathophysiology etiology and have important preconception care implications and suggest the need for antenatal monitoring.
Sentinel-2 Analysis of Spruce Crown Transparency Levels and Their Environmental Drivers After Summer Drought in the Northern Eifel (Germany)
Authors: Montzka Carsten , Bayat Bagher , Tewes Andreas , Mengen David , Vereecken Harry
Published: July 2021

Droughts in recent years weaken the forest stands in Central Europe, where especially the spruce suffers from an increase in defoliation and mortality. Forest surveys monitor this trend based on sample trees at the local scale, whereas earth observation is able to provide area-wide information. With freely available cloud computing infrastructures such as Google Earth Engine, access to satellite data and high-performance computing resources has become straightforward. In this study, a simple approach for supporting the spruce monitoring by Sentinel-2 satellite data is developed. Based on forest statistics and the spruce NDVI cumulative distribution function of a reference year, a training data set is obtained to classify the satellite data of a target year. This provides insights into the changes in tree crown transparency levels. For the Northern Eifel region, Germany, the evaluation shows an increase in damaged trees from 2018 to 2020, which is in line with the forest inventory of North Rhine-Westphalia. An analysis of tree damages according to precipitation, land surface temperature, elevation, aspect, and slope provides insights into vulnerable spruce habitats of the region and enables to identify locations where the forest management may focus on a transformation from spruce monocultures to mixed forests with higher biodiversity and resilience to further changes in the climate system.
Multi-Omics Data Fusion for Cancer Molecular Subtyping Using Sparse Canonical Correlation Analysis
Authors: Qi Lin , Wang Wei , Wu Tan , Zhu Lina , He Lingli , Wang Xin
Published: July 2021

It is now clear that major malignancies are heterogeneous diseases associated with diverse molecular properties and clinical outcomes, posing a great challenge for more individualized therapy. In the last decade, cancer molecular subtyping studies were mostly based on transcriptomic profiles, ignoring heterogeneity at other (epi-)genetic levels of gene regulation. Integrating multiple types of (epi)genomic data generates a more comprehensive landscape of biological processes, providing an opportunity to better dissect cancer heterogeneity. Here, we propose sparse canonical correlation analysis for cancer classification (SCCA-CC), which projects each type of single-omics data onto a unified space for data fusion, followed by clustering and classification analysis. Without loss of generality, as case studies, we integrated two types of omics data, mRNA and miRNA profiles, for molecular classification of ovarian cancer (n = 462), and breast cancer (n = 451). The two types of omics data were projected onto a unified space using SCCA, followed by data fusion to identify cancer subtypes. The subtypes we identified recapitulated subtypes previously recognized by other groups (all P- values < 0.001), but display more significant clinical associations. Especially in ovarian cancer, the four subtypes we identified were significantly associated with overall survival, while the taxonomy previously established by TCGA did not (P- values: 0.039 vs. 0.12). The multi-omics classifiers we established can not only classify individual types of data but also demonstrated higher accuracies on the fused data. Compared with iCluster, SCCA-CC demonstrated its superiority by identifying subtypes of higher coherence, clinical relevance, and time efficiency. In conclusion, we developed an integrated bioinformatic framework SCCA-CC for cancer molecular subtyping. Using two case studies in breast and ovarian cancer, we demonstrated its effectiveness in identifying biologically meaningful and clinically relevant subtypes. SCCA-CC presented a unique advantage in its ability to classify both single-omics data and multi-omics data, which significantly extends the applicability to various data types, and making more efficient use of published omics resources.
Limitations of Explainability for Established Prognostic Biomarkers of Prostate Cancer
Authors: Manjang Kalifa , Yli-Harja Olli , Dehmer Matthias , Emmert-Streib Frank
Published: July 2021

High-throughput technologies do not only provide novel means for basic biological research but also for clinical applications in hospitals. For instance, the usage of gene expression profiles as prognostic biomarkers for predicting cancer progression has found widespread interest. Aside from predicting the progression of patients, it is generally believed that such prognostic biomarkers also provide valuable information about disease mechanisms and the underlying molecular processes that are causal for a disorder. However, the latter assumption has been challenged. In this paper, we study this problem for prostate cancer. Specifically, we investigate a large number of previously published prognostic signatures of prostate cancer based on gene expression profiles and show that none of these can provide unique information about the underlying disease etiology of prostate cancer. Hence, our analysis reveals that none of the studied signatures has a sensible biological meaning. Overall, this shows that all studied prognostic signatures are merely black-box models allowing sensible predictions of prostate cancer outcome but are not capable of providing causal explanations to enhance the understanding of prostate cancer.
Kaempferol Alleviates Murine Experimental Colitis by Restoring Gut Microbiota and Inhibiting the LPS-TLR4-NF-κB Axis
Authors: Qu Yifan , Li Xinyi , Xu Fengying , Zhao Shimin , Wu Xuemei , Wang Yuzhen , Xie Jiming
Published: July 2021

Intestinal microbiota dysbiosis is an established characteristic of ulcerative colitis (UC). Regulating the gut microbiota is an attractive alternative UC treatment strategy, considering the potential adverse effects of synthetic drugs used to treat UC. Kaempferol (Kae) is an anti-inflammatory and antioxidant flavonoid derived from a variety of medicinal plants. In this study, we determined the efficacy and mechanism of action of Kae as an anti-UC agent in dextran sulfate sodium (DSS)-induced colitis mice. DSS challenge in a mouse model of UC led to weight loss, diarrhea accompanied by mucous and blood, histological abnormalities, and shortening of the colon, all of which were significantly alleviated by pretreatment with Kae. In addition, intestinal permeability was shown to improve using fluorescein isothiocyanate (FITC)–dextran administration. DSS-induced destruction of the intestinal barrier was also significantly prevented by Kae administration via increases in the levels of ZO-1, occludin, and claudin-1. Furthermore, Kae pretreatment decreased the levels of IL-1β, IL-6, and TNF-α and downregulated transcription of an array of inflammatory signaling molecules, while it increased IL-10 mRNA expression. Notably, Kae reshaped the intestinal microbiome by elevating the Firmicutes to Bacteroidetes ratio; increasing the linear discriminant analysis scores of beneficial bacteria, such as Prevotellaceae and Ruminococcaceae; and reducing the richness of Proteobacteria in DSS-challenged mice. There was also an evident shift in the profile of fecal metabolites in the Kae treatment group. Serum LPS levels and downstream TLR4-NF-κB signaling were downregulated by Kae supplementation. Moreover, fecal microbiota transplantation from Kae-treated mice to the DSS-induced mice confirmed the effects of Kae on modulating the gut microbiota to alleviate UC. Therefore, Kae may exert protective effects against colitis mice through regulating the gut microbiota and TLR4-related signaling pathways. This study demonstrates the anti-UC effects of Kae and its potential therapeutic mechanisms, and offers novel insights into the prevention of inflammatory diseases using natural products.
Single-Cell RNA Sequencing Reveals the Immunological Profiles of Renal Allograft Rejection in Mice
Authors: Shen Qixia , Wang Yucheng , Chen Jiaoyi , Ma Lifeng , Huang Xiaoru , Tang Sydney C. W. , Lan Huiyao , Jiang Hong , Chen Jianghua
Published: July 2021

Allograft rejection is a common immunological feature in renal transplantation and is associated with reduced graft survival. A mouse renal allograft rejection model was induced and single-cell RNA sequencing (scRNA-seq) data of CD45+leukocytes in kidney allografts on days 7 (D7) and 15 (D15) after operation was analyzed to reveal a full immunological profiling. We identified 20 immune cell types among 10,921 leukocytes. Macrophages and CD8+T cells constituted the main populations on both timepoints. In the process from acute rejection (AR) towards chronic rejection (CR), the proportion of proliferating and naïve CD8+T cells dropped significantly. Both B cells and neutrophils decreased by about 3 folds. On the contrary, the proportion of macrophages and dendritic cells (DCs) increased significantly, especially by about a 4.5-fold increase in Ly6cloMrc1+macrophages and 2.6 folds increase in Ly6cloEar2+macrophages. Moreover, myeloid cells harbored the richest ligand and receptor (LR) pairs with other cells, particularly for chemokine ligands such as Cxcl9, Cxcl10, Cxcl16 and Yars. However, macrophages with weak response to interferon gamma (IFNg) contributed to rejection chronicization. To conclude, reduction in CD8 T cells, B cells and neutrophils while increasing in Ly6cloMrc1+macrophages and Ly6cloEar2+macrophages, may contribute significantly to the progress from AR towards CR.