bluuebunny/crossref_metadata_2025 huggingface dataset:
Follicular Fluid Metabolite Changes in Dairy Cows with Inactive Ovary Identified Using Untargeted Metabolomics
Authors: Bai YunLong , Zhang Feng , Zhang HongYou , Xu Chuang , Wu Ling , Xia Cheng
Published: November 2020

The metabolism of dairy cows with inactive ovaries differs from that of healthy dairy cows. However, the molecular mechanisms underpinning these physiological and metabolic changes remain unclear. The purpose of this study was to investigate follicular fluid metabolite changes in dairy cows with inactive ovaries. Untargeted metabolomics technology and multivariate statistical analysis were used to screen differential metabolites in follicular fluid samples between inactive ovaries and estrus cows at 45‐60 d postpartum. Fourteen differential metabolites were identified, consisting of amino acids, lipids, sugars, and nucleotides. When compared with healthy animal samples, eight follicular fluid metabolites were significantly increased, and six metabolites were significantly decreased in dairy cows with inactive ovaries. Metabolic pathway analyses indicated that differential metabolites were primarily involved in glycerol phospholipid metabolism, arachidonic acid metabolism, valine, leucine and isoleucine biosynthesis, and phenylalanine metabolism. These metabolites and their enrichment pathways indicate that the enhancement of lipid metabolism and the weakening of carbohydrate production of amino acids in dairy cows with impaired follicular development. Overall, these data provide a better understanding of the changes that could affect follicular development during the postpartum period and lay the ground for further investigations.
Disnea en el servicio de urgencia
Authors: Sandoval Parra Maria Rosa , Lara Hernández Bárbara , Guzman Andres Ignacio
Published: November 2020

La disnea es definida como la sensación subjetiva de ahogo o falta de aire y es un motivo muy frecuente de consulta. Su presentación clínica puede variar, desde manifestaciones leves hasta insuficiencia respiratoria catastrófica, con elevada mortalidad y   requerir de terapias invasivas complejas.
En los servicios de urgencia se inicia el estudio etiológico del paciente agudo, al mismo tiempo que se realizan intervenciones terapéuticas destinadas a la estabilización y manejo tiempo-dependiente del paciente que consulta por disnea.
En vista de las múltiples causas de disnea, es necesario que el especialista en medicina de urgencia conozca los distintos diagnósticos diferenciales y sepa orientar su manejo y estudio.
Este manuscrito pretende dar un marco teórico acerca de la presentación del paciente con disnea en el servicio de urgencia, describir sus principales características y orientar el estudio y tratamientos tiempo-dependientes desde su primera evaluación por el equipo médico.
Se expone un caso clínico y revisan los componentes esenciales de la fisiopatología que explica la disnea, asi como la descripción de herramientas para su evaluación, tratamiento y disposición en el servicio de urgencia. Finalizaremos con la resolución del caso.
Evaluación para el aprendizaje: diseño e implementación de un mini-CEX en el internado profesional de la carrera de kinesiología
Authors: Fuentes Cimma Javiera , Villagrán Gutiérrez Ignacio , Torres Riveros Gustavo , Riquelme Pérez Arnoldo , Isbej Espósito Lorena , Chamorro Lange Claudio
Published: November 2020

Introducción: la evaluación kinesiológica contempla la realización de una rigurosa historia clínica y examen físico que orientan a establecer un diagnóstico, un pronóstico funcional, y es la base del plan de intervención. Esta competencia requiere de experiencia y razonamiento clínico para la toma de buenas decisiones terapéuticas. Los resultados históricos de las evaluaciones de aprendizajes del internado, concluyen que esta competencia tiene bajo nivel de desempeño, por lo que se deben mejorar las estrategias utilizadas para su aprendizaje durante el internado. El mini-CEX, es un instrumento de evaluación para el aprendizaje, que promueve la observación y feedback en el sitio de trabajo. Objetivo: diseñar e implementar un instrumento de evaluación para el aprendizaje de la evaluación kinesiológica durante el internado profesional de la Carrera de Kinesiología de la PUC. Método: estudio prospectivo, utilizando la metodología de investigación acción, diseñado en 4 etapas. Resultados: se obtuvo un instrumento de evaluación para el aprendizaje, el mini-CEX, adaptado a las necesidades del internado profesional de kinesiología. El estudio piloto reportó buena aceptación entre estudiantes y docentes. La percepción de los internos es que son más observados y que las destrezas asociadas a la evaluación kinesiológica mejoraron luego del estudio. Conclusiones: el instrumento reportó un tiempo de aplicación bajo (35 min.), lo que beneficiaría instancias de observación directa y feedback dentro de los internados. Es necesaria una aplicación a gran escala, que contribuya a determinar su validez y confiabilidad. Se requiere una capacitación formal a los docentes evaluadores y ajustar la escala.
circIGHG-Induced Epithelial-to-Mesenchymal Transition Promotes Oral Squamous Cell Carcinoma Progression via miR-142-5p/IGF2BP3 Signaling
Authors: Liu Jingpeng , Jiang Xiao , Zou Ailing , Mai Zhaoyi , Huang Zhijie , Sun Liying , Zhao Jianjiang
Published: November 2020

Circular RNAs (circRNA) are a new member of endogenously produced noncoding RNAs that have been characterized as key regulators of gene expression in a variety of malignances. However, the role of circRNA in oral squamous cell carcinoma (OSCC) remains largely unknown. In this study, we identified unique circRNA that regulate OSCC progression and metastasis and pave roads for future research in early diagnosis, prevention, and treatment of OSCC. Transcriptomic analyses identified a circRNA derived from IGHG locus (circIGHG) as significantly upregulated in OSCC and positively associated with poor prognosis of OSCC. circIGHG directly bound miR-142-5p and consequently elevated IGF2BP3 activity. Knockdown of circIGHG led to impaired expression of IGF2BP3 and attenuated aggressiveness of OSCC cells. Epithelial–mesenchymal transition was the main mechanism through which circIGHG/IGF2BP3 promotes metastasis of OSCC. Overall, these results demonstrate that circIGHG plays a pivotal role in OSCC development and metastasis and has potential to serve as a biomarker and therapeutic target for early-stage diagnosis and treatment of OSCC.

Significance:

These findings broaden our insights regarding regulation of OSCC progression by circular RNA and serve as a reference for future clinical research in OSCC diagnosis and treatment.
Activation of Receptor Tyrosine Kinases Mediates Acquired Resistance to MEK Inhibition in Malignant Peripheral Nerve Sheath Tumors
Authors: Wang Jiawan , Pollard Kai , Calizo Ana , Pratilas Christine A.
Published: November 2020

Malignant peripheral nerve sheath tumors often arise in patients with neurofibromatosis type 1 and are among the most treatment-refractory types of sarcoma. Overall survival in patients with relapsed disease remains poor, and thus novel therapeutic approaches are needed. NF1 is essential for negative regulation of RAS activity and is altered in about 90% of malignant peripheral nerve sheath tumors (MPNST). A complex interplay of upstream signaling and parallel RAS-driven pathways characterizes NF1-driven tumorigenesis, and inhibiting more than one RAS effector pathway is therefore necessary. To devise potential combination therapeutic strategies, we identified actionable alterations in signaling that underlie adaptive and acquired resistance to MEK inhibitor (MEKi). Using a series of proteomic, biochemical, and genetic approaches in an in vitro model of MEKi resistance provided a rationale for combination therapies. HGF/MET signaling was elevated in the MEKi-resistant model. HGF overexpression conferred resistance to MEKi in parental cells. Depletion of HGF or MET restored sensitivity of MEKi-resistant cells to MEKi. Finally, a combination of MEK and MET inhibition demonstrated activity in models of MPNST and may therefore be effective in patients with MPNST harboring genetic alterations in NF1.

Significance:

This study demonstrates that MEKi plus MET inhibitor may delay or prevent a novel mechanism of acquired MEKi resistance, with clinical implications for MPNST patients harboring NF1 alterations.
Repurposing the Antidepressant Sertraline as SHMT Inhibitor to Suppress Serine/Glycine Synthesis–Addicted Breast Tumor Growth
Authors: Geeraerts Shauni Lien , Kampen Kim Rosalie , Rinaldi Gianmarco , Gupta Purvi , Planque Mélanie , Louros Nikolaos , Heylen Elien , De Cremer Kaat , De Brucker Katrijn , Vereecke Stijn , Verbelen Benno , Vermeersch Pieter , Schymkowitz Joost , Rousseau Frederic , Cassiman David , Fendt Sarah-Maria , Voet Arnout , Cammue Bruno P.A. , Thevissen Karin , De Keersmaecker Kim
Published: November 2020

Metabolic rewiring is a hallmark of cancer that supports tumor growth, survival, and chemotherapy resistance. Although normal cells often rely on extracellular serine and glycine supply, a significant subset of cancers becomes addicted to intracellular serine/glycine synthesis, offering an attractive drug target. Previously developed inhibitors of serine/glycine synthesis enzymes did not reach clinical trials due to unfavorable pharmacokinetic profiles, implying that further efforts to identify clinically applicable drugs targeting this pathway are required. In this study, we aimed to develop therapies that can rapidly enter the clinical practice by focusing on drug repurposing, as their safety and cost-effectiveness have been optimized before. Using a yeast model system, we repurposed two compounds, sertraline and thimerosal, for their selective toxicity against serine/glycine synthesis–addicted breast cancer and T-cell acute lymphoblastic leukemia cell lines. Isotope tracer metabolomics, computational docking, enzymatic assays, and drug–target interaction studies revealed that sertraline and thimerosal inhibit serine/glycine synthesis enzymes serine hydroxymethyltransferase and phosphoglycerate dehydrogenase, respectively. In addition, we demonstrated that sertraline's antiproliferative activity was further aggravated by mitochondrial inhibitors, such as the antimalarial artemether, by causing G1–S cell-cycle arrest. Most notably, this combination also resulted in serine-selective antitumor activity in breast cancer mouse xenografts. Collectively, this study provides molecular insights into the repurposed mode-of-action of the antidepressant sertraline and allows to delineate a hitherto unidentified group of cancers being particularly sensitive to treatment with sertraline. Furthermore, we highlight the simultaneous inhibition of serine/glycine synthesis and mitochondrial metabolism as a novel treatment strategy for serine/glycine synthesis–addicted cancers.
Abstract PO-037: The conversion of induced pluripotent stem cells into cancer stem cells under pancreatic cancer microenvironment is inhibiting by lapatinib
Authors: Hassan Ghmkin , Seno Masaharu
Published: November 2020

Cancer stem cells (CSCs) are suggested to be responsible for drug resistance and aggressive phenotypes of tumors. Mechanisms that regulating CSCs are still under investigation. Our lab has established a novel method to produce CSCs from induced pluripotent stem cells (iPSCs) under cancer microenvironment using conditioned medium (CM) from cancer cell lines. By treatment iPSCs with CM, cells gain CSC characteristics. Here, we analyzed transcriptome from CSCs, which converted from iPSCs using CM from pancreatic ductal adenocarcinoma cells, and differentially expressed genes were identified. Pathway enrichment was analyzed by the Kyoto Encyclopedia of Genes and Genomes (KEGG). Comparing iPSCs with CSCs converted from iPSCS showed elevated expression of genes related to ERBB2, ERBB3 and PI3K, while KEGG pathways revealed enrich of pathways known to be involved in cancer including ERBB2/ERBB3 signal pathway by conversion of iPSCs to CSCs. Inhibition of ERBB2 by lapatinib induced cell proliferation arrest and losing of tumorgenicity of converted cells. This study shows a potential involvement of ERBB2/ERBB3 pathway in CSCs generation and could lead to potentially new options for cancer treatment and prevention.

Citation Format: Ghmkin Hassan, Masaharu Seno. The conversion of induced pluripotent stem cells into cancer stem cells under pancreatic cancer microenvironment is inhibiting by lapatinib [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-037.
Influences of Fasting on Stress Response and Withdrawal Symptoms in Habitual Khat Users
Authors: Nakajima Motohiro , al’Absi Mustafa
Published: November 2020

Background: Fasting changes mood and physiological states. Substance use, such as khat use, is prohibited during fasting during Ramadan, a traditional practice among Muslims. Habitual khat use is associated with increased negative affect and altered psychobiological stress responses. Effects of fasting on stress responses, mood, and withdrawal symptoms among khat users have not been examined. Methods: In this study, 80 individuals completed an ambulatory monitoring period and a laboratory assessment session. Participants who completed the study while fasting during Ramadan were matched by gender and khat use status with participants who completed the study while not fasting. This resulted in 40 participants (12 females and 28 males; 25 khat users and 15 nonusers) in each fasting group. Cardiovascular (blood pressure and heart rate) and subjective measures were collected throughout the laboratory stress session. A mental arithmetic challenge was used to induce stress. In addition, self-reported mood and withdrawal measures were collected multiple times during the ambulatory assessment. Results: Khat users reported greater negative affect than nonusers. Results from the ambulatory study indicated that withdrawal symptoms were lower during evening hours in the fasting group than in the no-fasting group. Stress-related changes in positive and negative affects were flattened in the fasting group relative to the no-fasting group. Khat users reported reduced blood pressure responses relative to nonusers. Conclusion: These preliminary results demonstrate that fasting is associated with reduced negative affect and withdrawal symptoms in khat users. Khat use was related to blunted blood pressure stress responses, but this was independent of fasting. Due to the small sample size, these results should be replicated with a large sample and comprehensive stress tasks.
Serum Copeptin, NLPR3, and suPAR Levels among Patients with Autosomal-Dominant Polycystic Kidney Disease with and without Impaired Renal Function
Authors: Raptis Vasileios , Loutradis Charalampos , Boutou Afroditi K. , Faitatzidou Danai , Sioulis Athanasios , Ferro Charles J. , Papagianni Aikaterini , Sarafidis Pantelis A.
Published: November 2020

Background: The pathophysiology of renal disease progression in autosomal-dominant polycystic kidney disease (ADPKD) involves not only cystogenesis but also endothelial dysfunction, leading to the activation of inflammatory and fibrotic pathways. This study evaluated the levels of biomarkers related to osmoregulation, immune system activation, and tubular injury in ADPKD patients with impaired or preserved renal function. Methods: This study included 26 ADPKD patients with modestly impaired renal function (estimated glomerular filtration rate [eGFR] 45–70 mL/min/1.73 m2; Group A), 26 age- and sex-matched ADPKD patients with relatively preserved renal function (eGFR >70 mL/min/1.73 m2; Group B), and 26 age- and sex-matched controls (Group C). Serum levels of copeptin, the inflammasome nucleotide-binding and oligomerization domain-like receptors pyrin domain-containing protein 3 (NLRP3), and soluble urokinase-type plasminogen activator receptor (suPAR) were measured with ELISA techniques. Results: Patients in Group A had higher levels of copeptin (median [interquartile range]: 50.44 [334.85] pg/mL), NLRP3 (5.86 [3.89] ng/mL), and suPAR (390.05 [476.53] pg/mL) compared to patients in Group B (32.38 [58.33], p = 0.042; 2.42 [1.96], p < 0.001; and 313.78 [178.85], p = 0.035, respectively) and Group C (6.75 [6.43]; 1.09 [0.56]; and 198.30 [28.53], respectively; p < 0.001 for all comparisons). Levels of all studied markers were also significantly higher in Group B patients compared to controls (p < 0.001), despite having similar eGFR. In patients with ADPKD, all studied biomarkers were correlated positively with asymmetric-dimethylarginine (ADMA) and endocan levels, and negatively with eGFR. ADMA and endocan levels were the only parameters independently associated with increased copeptin levels. Conclusions: This study showed that ADPKD patients with impaired and preserved renal function had higher copeptin, NLRP3, and suPAR levels than controls. Such findings support that cystogenesis and inflammation are associated with endothelial dysfunction, even in the early stages of ADKPD.
Recent Advances in Systemic Therapy for Hepatocellular Carcinoma in an Aging Society: 2020 Update
Authors: Kudo Masatoshi
Published: November 2020

Systemic therapy for hepatocellular carcinoma (HCC) has changed markedly since the introduction of the molecular targeted agent sorafenib in 2007. Sorafenib increased the available treatment options for patients with extrahepatic spread and vascular invasion and improved survival in patients with advanced HCC; however, various shortcomings such as low response rates and relatively high toxicity (e.g., hand-foot skin reaction) prompted concerted efforts aimed at developing new molecular targeted agents to provide more treatment options and second-line agents for patients with disease progression or intolerance to sorafenib. Despite many attempts to develop new drugs between 2007 and 2016, all first-line and second-line clinical trials conducted during this period failed. However, between 2017 and 2019, 4 drugs (lenvatinib as a first-line agent and regorafenib, cabozantinib, and ramucirumab as second-line agents) emerged in quick succession from clinical trials and became available for clinical use. In addition, nivolumab and pembrolizumab were approved as second-line agents after sorafenib. A recent phase III trial (IMbrave150) showed that combination immunotherapy with atezolizumab plus bevacizumab increases overall survival compared with sorafenib therapy; Food and Drug Agency already approved this combination therapy, and worldwide approval is expected soon. This review describes the recent advances in systemic therapy and the use of tyrosine kinase inhibitors (sorafenib, lenvatinib, regorafenib, and cabozantinib), monoclonal antibodies (ramucirumab and bevacizumab), and immune checkpoint inhibitors (nivolumab, pembrolizumab, and atezolizumab) in elderly patients and the similarity of their efficacy and safety profiles to those in the general population.
Incidence of Cutaneous Melanoma of Eyelid Analysis of the Surveillance, Epidemiology, and End Results Database
Authors: Brunetti Philip , Margo Curtis E. , French Dustin D.
Published: November 2020

Purpose: The aim of this work was to report the annual incidence, incidence trend, histological types, and cause-specific survival of cutaneous melanoma of the eyelid from 1975 through to 2017. Methods: Cases were identified in the Surveillance, Epidemiology, and End Results (SEER) database using the ICD-0–3 standard codes for diagnosis and anatomic location. Cutaneous melanomas of the face and scalp/neck were studied as comparison groups. Incidence rates were calculated using the SEER*Stat statistical analysis software with 95% confidence intervals. Melanoma-specific survival was estimated using the Kaplan-Meier product-limited method. Results: There was an increase in annual incidence of eyelid melanoma over the 43-year study period, ranging from a low of 0.2 × 106 population in 1978 (95% CI 0.04–0.6) to a high of 1.0 × 106 population in 2016 (95% CI 2.3–3.5). The average annual percent change was 1.2% (95% CI 0.5–1.8). Cause-specific survival of melanoma of the eyelid and facial skin were almost identical (approx. 91.7%) at 60 months but significantly worse for melanoma of the scalp/neck (p < 0.05%). Conclusions: Cutaneous melanoma of the eyelid is uncommon compared to melanoma of facial skin and the scalp/neck. This can be explained in part by the comparatively small surface area at risk. Like melanomas elsewhere, the annual incidence of eyelid melanoma has risen over the last 4 decades, but less than of facial skin and the scalp/neck. Over the span of this study, cause-specific survival from eyelid melanoma was comparable to that of facial skin and better than that of the scalp/neck.
The Role of Autophagy-Mediated Dengue Virus Antibody-Dependent Enhancement Infection of THP-1 Cells
Authors: Jiang Liming , Sun Qiangming
Published: November 2020

Background: Antibody-dependent enhancement (ADE) of dengue virus (DENV) infection is identified as the main risk factor of severe dengue diseases. The underlying mechanisms leading to severe dengue fever remain unclear. Methods: THP-1 cells were treated with an autophagy inducer (rapamycin) or inhibitor (3-methyladenine [3-MA]) and infected with DENV and DENV-ADE. In order to investigate the expression profile of autophagy-related genes in DENV-ADE and DENV direct infection of THP-1 cells, the PCR array including 84 autophagy-related genes was selected to detect the expression of related genes, and then heat map and clustergram were established by analysis software to compare the expression differences of these genes between the DENV-ADE and DENV direct infection. Results: Autophagy-inducing complex related genes ATG5 and ATG12 were upregulated, and autophagosomes were also observed by transmission electron microscopy among DENV-ADE- and DENV-infected THP-1 cells, which indicated that autophagy was involved in dengue infection. The results show that 3-MA has a significant inhibitory effect on ATG12 in THP-1 cells; on the contrary, the expression of ATG12 was upreg­ulated in THP-1 cells that were treated with rapamycin. The autophagy-related genes ESR1, INS, BNIP3, FAS, TGM2, ATG9B, and DAPK1 exhibited significant differences between DENV-ADE and DENV direct infection groups. Conclusion: In the present study, an additional mechanism of autophagy was inhibited by the autophagy inhibitor (3-MA) in DENV- and DENV-ADE-infected THP-1 cells. Our finding provided a clear link between autophagy and antibody-enhanced infection of DENV.
Hypersensitivity to Rituximab in Children
Authors: Liccioli Giulia , Simonini Gabriele , Melani Federico , Giovannini Mattia , Ricci Silvia , Sarti Lucrezia , Cavallin Mara , Barni Simona , Marrani Edoardo , Mori Francesca
Published: November 2020

Biological agents have had an increased usage during the past years, also in pediatric population. Monoclonal antibodies can cause adverse drug reactions with different pathomechanisms, including type I IgE-mediated hypersensitivity reactions (HR). In this report, we describe 2 children who had a diagnosis of anaphylaxis to rituximab (RTX), confirmed by positive in vivo tests in both cases and elevated tryptase value in one case. We also made a review of the few cases of HR to RTX in pediatric population reported in literature and discuss differential diagnosis and utility of allergy investigations.
First-Phase Insulin and Amylin after Bariatric Surgery: A Prospective Randomized Trial on Patients with Insulin Resistance or Diabetes after Gastric Bypass or Sleeve Gastrectomy
Authors: Nussbaumer Rahel , Meyer-Gerspach Anne Christin , Peterli Ralph , Peters Thomas , Beglinger Christoph , Chiappetta Sonja , Drewe Juergen , Wölnerhanssen Bettina
Published: November 2020

Background: Most patients with severe obesity show glucose intolerance. Early after sleeve gastrectomy (LSG) or gastric bypass (LRYGB), a marked amelioration in glycemic control occurs. The underlying mechanism is not yet clear. Objective: To determine whether the improvement in glycemic control on the level of endocrine pancreatic function is due to an increased first-phase insulin secretion comparing LRYGB to LSG. Setting: University of Basel Hospital and St. Clara Research Ltd., Basel, Switzerland. Methods: Sixteen morbidly obese patients with severe obesity and different degrees of insulin resistance were randomized to LSG or LRYGB, and islet cell functions were tested by intravenous glucose and intravenous arginine administration before and 4 weeks after surgery. Results: Fasting insulin and glucose levels and homeostasis model assessment insulin resistance were significantly lower in both groups after surgery compared to baseline, while no change was seen in fasting C-peptide, amylin, and glucagon. After intravenous glucose stimulation, no statistically significant pre- to postoperative change in area under the curve (AUC 0–60 min) was seen for insulin, glucagon, amylin, and C-peptide. No statistically significant pre- to postoperative change in incremental AUC for first-phase insulin release (AUC 0–10 min), second-phase insulin secretion (AUC 10–60 min), and insulin/glucose ratio could be shown in either group. Arginine-stimulated insulin and glucagon release showed no pre- to postoperative change. Conclusion: Intravenous glucose and arginine administrations show no pre- to postoperative changes of insulin release, amylin, glucagon, or C-peptide concentrations, and no differences between LRYGB and LSG were found. The postoperative improvement in glycemic control is not caused by changes in endocrine pancreatic hormone secretion.
Prognostic Importance of Right Ventricular-Vascular Uncoupling in Acute Decompensated Heart Failure With Preserved Ejection Fraction
Authors: Nakagawa Akito , Yasumura Yoshio , Yoshida Chikako , Okumura Takahiro , Tateishi Jun , Yoshida Junichi , Abe Haruhiko , Tamaki Shunsuke , Yano Masamichi , Hayashi Takaharu , Nakagawa Yusuke , Yamada Takahisa , Nakatani Daisaku , Hikoso Shungo , Sakata Yasushi ,   on behalf of Osaka CardioVascular Conference (OCVC)-Heart Failure investigators
Published: November 2020

Background:

Recent accumulating evidence reveals that the right ventricular (RV)-pulmonary artery (PA) uncoupling is associated with poor outcome in patients with heart failure (HF), RV dysfunction, and pulmonary hypertension. However, the prognostic utility of RV-PA uncoupling in HF with preserved ejection fraction (HFpEF) remains elusive. In this study, we aim to investigate the associations of RV-PA uncoupling with outcomes of HFpEF inpatients.

Methods:

We prospectively studied 655 patients, registered in PURSUIT-HFpEF (The Prospective Multicenter Obervational Study of Patients with Heart Failure with Preserved Ejection Fraction), a multicenter observational study of Japanese HFpEF inpatients. We assigned registered patients based on the determined value of tricuspid annular plane systolic excursion/pulmonary artery systolic pressure ratio that can predict primary outcome as an indicator of RV-PA uncoupling.

Results:

Univariable Cox regression testing revealed that RV-PA uncoupling was associated with the primary endpoint of all-cause death, HF rehospitalization, and cerebrovascular events (hazard ratio [HR] 1.77 [95% CI, 1.34–2.32],
P
<0.0001) and the secondary endpoints of all-cause death and HF rehospitalization (HR 2.75 [95% CI, 1.77–4.33],
P
<0.0001, HR 1.63 [95% CI, 1.18–2.26],
P
=0.0036, respectively). Multivariable analysis also showed that RV-PA uncoupling was significantly associated with primary endpoint and all-cause death independent of age, sex, atrial fibrillation, renal dysfunction, elevated E/e’, and elevated NT-proBNP (N-terminal pro-B-type natriuretic peptide) (HR 1.38 [95% CI, 1.01–1.88],
P
=0.0413, HR 1.85 [95% CI, 1.14–3.01],
P
=0.0129, respectively).

Conclusions:

Prospective study of a hospitalized cohort revealed that RV-PA uncoupling was independently associated with adverse outcomes in acute decompensated patients with HFpEF.

Registration:

URL:
https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000024414
. Unique identifier: UMIN000021831.
Comparative Effectiveness of Dual Antiplatelet Therapy With Aspirin and Clopidogrel Versus Aspirin Monotherapy in Mild-to-Moderate Acute Ischemic Stroke According to the Risk of Recurrent Stroke
Authors: Lee Hak-Loh , Kim Joon-Tae , Lee Ji Sung , Park Man-Seok , Choi Kang-Ho , Cho Ki-Hyun , Kim Beom Joon , Park Jong-Moo , Kang Kyusik , Lee Soo Joo , Kim Jae Guk , Cha Jae-Kwan , Kim Dae-Hyun , Park Tai Hwan , Park Sang-Soon , Lee Kyung Bok , Lee Jun , Hong Keun-Sik , Cho Yong-Jin , Park Hong-Kyun , Lee Byung-Chul , Yu Kyung-Ho , Sun Oh Mi , Kim Dong-Eog , Ryu Wi-Sun , Choi Jay Chol , Kwon Jee-Hyun , Kim Wook-Joo , Shin Dong-Ick , Sohn Sung Il , Hong Jeong-Ho , Lee Juneyoung , Bae Hee-Joon
Published: November 2020

Background:

This study compared the effectiveness of dual antiplatelet therapy (DAPT) with clopidogrel-aspirin with that of aspirin monotherapy (AM) in mild-to-moderate acute ischemic stroke considering the risk of recurrent stroke using the Stroke Prognosis Instrument II (SPI-II) score.

Methods:

This study is a retrospective analysis of data from a prospective, nationwide, multicenter stroke registry database between January 2011 and July 2018. We included patients with mild-to-moderate (National Institutes of Health Stroke Scale score ≤10), acute (within 24 hours of onset), noncardioembolic ischemic stroke. The primary outcome was a 3-month composite of stroke (either hemorrhagic or ischemic), myocardial infarction, and all-cause mortality. Propensity scores using the inverse probability of treatment weighting method were used to mitigate baseline imbalances between the DAPT and AM groups and within each subgroup considering SPI-II scores.

Results:

Among the 15 430 patients (age, 66±13 years; men, 62.0%), 45.1% (n=6960) received DAPT and 54.9% (n=8470) received AM. Primary outcome events were significantly more frequent in the AM group (16.7%) than in the DAPT group (15.5%;
P
=0.03). Weighted Cox proportional hazards models showed a reduced risk of 3-month primary vascular events in the DAPT group versus the AM group (hazard ratio, 0.84 [0.78–0.92];
P
<0.001), with no interaction between acute treatment type and SPI-II risk subgroups (
P
interaction
=0.44). However, among the high-risk patients with SPI-II scores >7, a substantially larger absolute benefit was observed for 3-month composite vascular events in the DAPT group (weighted absolute risk differences, 5.4%), whereas smaller absolute benefits were observed among patients in the low- or medium-risk SPI-II subgroups (1.7% and 2.4%, respectively).

Conclusions:

Treatment with clopidogrel-aspirin was associated with a reduction in 3-month vascular events compared with AM in mild-to-moderate acute noncardioembolic ischemic stroke patients. Larger magnitudes of the effects of DAPT with clopidogrel-aspirin were observed in the high-risk subgroup by SPI-II risk scores.
Finerenone and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Type 2 Diabetes
Authors: Filippatos Gerasimos , Anker Stefan D. , Agarwal Rajiv , Pitt Bertram , Ruilope Luis M. , Rossing Peter , Kolkhof Peter , Schloemer Patrick , Tornus Ingo , Joseph Amer , Bakris George L. ,   For the FIDELIO-DKD Investigators
Published: November 2020

Background:

The FIDELIO-DKD trial (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease) evaluated the effect of the nonsteroidal, selective mineralocorticoid receptor antagonist finerenone on kidney and cardiovascular outcomes in patients with chronic kidney disease and type 2 diabetes with optimized renin–angiotensin system blockade. Compared with placebo, finerenone reduced the composite kidney and cardiovascular outcomes. We report the effect of finerenone on individual cardiovascular outcomes and in patients with and without history of atherosclerotic cardiovascular disease (CVD).

Methods:

This randomized, double-blind, placebo-controlled trial included patients with type 2 diabetes and urine albumin-to-creatinine ratio 30 to 5000 mg/g and an estimated glomerular filtration rate ≥25 to <75 mL per min per 1.73 m
2
, treated with optimized renin–angiotensin system blockade. Patients with a history of heart failure with reduced ejection fraction were excluded. Patients were randomized 1:1 to receive finerenone or placebo. The composite cardiovascular outcome included time to cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure. Prespecified cardiovascular analyses included analyses of the components of this composite and outcomes according to CVD history at baseline.

Results:

Between September 2015 and June 2018, 13 911 patients were screened and 5674 were randomized; 45.9% of patients had CVD at baseline. Over a median follow-up of 2.6 years (interquartile range, 2.0–3.4 years), finerenone reduced the risk of the composite cardiovascular outcome compared with placebo (hazard ratio, 0.86 [95% CI, 0.75–0.99];
P
=0.034), with no significant interaction between patients with and without CVD (hazard ratio, 0.85 [95% CI, 0.71–1.01] in patients with a history of CVD; hazard ratio, 0.86 [95% CI, 0.68–1.08] in patients without a history of CVD;
P
value for interaction, 0.85). The incidence of treatment-emergent adverse events was similar between treatment arms, with a low incidence of hyperkalemia-related permanent treatment discontinuation (2.3% with finerenone versus 0.8% with placebo in patients with CVD and 2.2% with finerenone versus 1.0% with placebo in patients without CVD).

Conclusions:

Among patients with chronic kidney disease and type 2 diabetes, finerenone reduced incidence of the composite cardiovascular outcome, with no evidence of differences in treatment effect based on preexisting CVD status.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02540993.
Ultrafast Hypothermia Selectively Mitigates the Early Humoral Response After Cardiac Arrest
Authors: Boissady Emilie , Kohlhauer Matthias , Lidouren Fanny , Hocini Hakim , Lefebvre Cécile , Chateau‐Jouber Sophie , Mongardon Nicolas , Deye Nicolas , Cariou Alain , Micheau Philippe , Ghaleh Bijan , Tissier Renaud
Published: November 2020

Background

Total liquid ventilation (TLV) has been shown to prevent neurological damage though ultrafast cooling in animal models of cardiac arrest. We investigated whether its neuroprotective effect could be explained by mitigation of early inflammatory events.

Methods and Results

Rabbits were submitted to 10 minutes of ventricular fibrillation. After resuscitation, they underwent normothermic follow‐up (control) or ultrafast cooling by TLV and hypothermia maintenance for 3 hours (TLV). Immune response, survival, and neurological dysfunction were assessed for 3 days. TLV improved neurological recovery and reduced cerebral lesions and leukocyte infiltration as compared with control (eg, neurological dysfunction score=34±6 versus 66±6% at day 1, respectively). TLV also significantly reduced interleukin‐6 blood levels during the hypothermic episode (298±303 versus 991±471 pg/mL in TLV versus control at 3 hours after resuscitation, respectively), but not after rewarming (752±563 versus 741±219 pg/mL in TLV versus control at 6 hours after resuscitation, respectively). In vitro assays confirmed the high temperature sensitivity of interleukin‐6 secretion. Conversely, TLV did not modify circulating high‐mobility group box 1 levels or immune cell recruitment into the peripheral circulation. The link between interleukin‐6 early transcripts (<8 hours) and neurological outcome in a subpopulation of the previously described Epo‐ACR‐02 (High Dose of Erythropoietin Analogue After Cardiac Arrest) trial confirmed the importance of this cytokine at the early stages as compared with delayed stages (>8 hours).

Conclusions

The neuroprotective effect of hypothermic TLV was associated with a mitigation of humoral interleukin‐6 response. A temperature‐dependent attenuation of immune cell reactivity during the early phase of the post–cardiac arrest syndrome could explain the potent effect of rapid hypothermia.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT00999583.
Daoists, the Imperial Cult of Sage-Kings, and Mongol Rule
Authors: Jinping Wang
Published: November 2020

This article demonstrates the central position that Daoists occupied in the representations of state power in north China under Mongol rule. In the mid-thirteenth century, Daoist Master Jiang Shanxin and his disciples, under Khubilai Khan’s patronage, actively rebuilt several temples of Confucian sage-kings in southern Shanxi province. Jiang Shanxin’s lineage was a product of dynamic interactions between the Mongol conquerors and local Chinese Daoists in which the two found common ground in sage-kings worship that had served to strengthen imperial legitimacy in previous dynasties. The strong Mongol-Daoist alliance in reordering the empire’s ritual space resulted in not just the revival of but also the creation of new ritual precedents for the Chinese imperial cult of sage-kings.
Establishing a Literati Spirit-Writing Altar in Early Qing Suzhou: The Optimus Prophecy of Peng Dingqiu (1645-1719)
Authors: Burton-Rose Daniel
Published: November 2020

In recent years the Suzhou literatus Peng Dingqiu (1645-1719) has attracted scholarly attention as a figure embodying the rich diversity of elite religiosity in the early Qing dynasty Yangzi delta. The present article employs Peng Dingqiu’s previously neglected manuscript autobiography Shijiang gong nianpu to hone in on a prophecy he claimed to have received in 1674 of his two-fold optimus success in 1676. It provides detail on the social conventions of verification of spirit-altar communications and probes the challenges Peng Dingqiu’s solitary method of communicating posed to communal verification. Concurrently, the article establishes a baseline of historically plausible events and identifies the narrative elements most likely modified by Peng Dingqiu and his admirers after the achievement of the prophecy.
Catholic Youth Ministry between 1896 and Today
Authors: Höring Patrik C.
Published: November 2020

The involvement (participation) of young people is the central characteristic of youth work in Germany. Where does this approach come from? And what role does it play in practice today? The following article gives a short introduction into youth work in Germany and traces how the idea of participation has developed in Catholic youth associations and what demands and challenges it poses in practice today.
Althenia tzvelevii (Potamogetonaceae), a new species from SW Western Australia with bilocular anthers: morphology and molecular phylogenetic relationships

Authors: MACFARLANE TERRY D. , DEGTJAREVA GALINA V. , SAMIGULLIN TAHIR H. , VALIEJO-ROMAN CARMEN M. , FOMICHEV CONSTANTIN I. , SOKOLOFF DMITRY D.
Published: November 2020

A new species Althenia tzvelevii is described from south western Australia. This is the second species after A. bilocularis described with bilocular anthers. Illustrations of plant morphology are provided by means of SEM images and habitat photographs are included. The phylogenetic relationships of the new species were investigated using five plastid DNA markers (matK, ndhF, rbcL, rpoB, and rpoC1), with published sequences augmented by several new sequences resulting in coverage of all described species in the genus. Althenia tzvelevii forms a clade with A. patentifolia and A. bilocularis and other relationships within the genus are clarified. The Western Australian Althenia hearnii is strongly supported as sister to the Eurasian-African clade composed by A. filiformis and A. orientalis.
One new Gomphonema Ehrenberg (Bacillariophyta) from Guangxi Zhuang Autonomous Region, China

Authors: ZHANG FAN , LIU YAN , KULIKOVSKIY MAXIM , KOCIOLEK JOHN PATRICK , LU XINXIN , FAN YAWEN
Published: November 2020

A new Gomphonema species is described from the Shiwan Mts. in Guangxi Zhuang Autonomous Region, Southwest China. This new species differs from other known members of the genus Gomphonema by its linear-lanceolate shape, wide axial area, slit-like areolae openings, one short spine at the headpole externally, and large pseudoseptum at each end internally. Morphological features of the new species are detailed with light and scanning electron microscopy. Comparisons with other similar species are made. This species appears to be closely related to other species of this genus possessing wide axial areas.
The Image of Africa in Ghana's Press
Authors: Serwornoo Michael
Published: November 2020

The Image of Africa in Ghana’s Press is a comprehensive and highly analytical study of the impact of foreign news organisations on the creation of an image of Africa in its own press. Identifying a problematic focus on the Western media in previous studies of the African media image, Serwornoo uses the Ghanaian press as a case study to explore the effects of centuries of Afro-pessimistic discourse in the foreign press on the continent’s self-description.

This study brings together a number of theoretical approaches, including newsworthiness, intermedia agenda setting, postcolonial theory and the hierarchy of influences, to question the processes underpinning the creation of media content. It is particularly innovative in its application of the methodological frameworks of ethnographic content analysis and ethnographic interview techniques to unveil the perspectives of journalists and editors.

The Image of Africa in Ghana’s Press presents a vital contribution of the highest academic standard to the growing literature surrounding Afro-pessimism and postcolonial studies. It will be of great value to scientists in the field of journalism studies, as well as researchers interested in the merging of journalism research, postcolonial studies, and ethnography.
Fluctuations in Inner-Core Structure during the Rapid Intensification of Super Typhoon Nepartak (2016)
Authors: Hardy Sam , Schwendike Juliane , Smith Roger K. , Short Chris J. , Reeder Michael J. , Birch Cathryn E.
Published: November 2020

The key physical processes responsible for inner-core structural changes and associated fluctuations in the intensification rate for a recent, high-impact western North Pacific tropical cyclone that underwent rapid intensification [Nepartak (2016)] are investigated using a set of convection-permitting ensemble simulations. Fluctuations in the inner-core structure between ringlike and monopole states develop in 60% of simulations. A tangential momentum budget analysis of a single fluctuation reveals that during the ringlike phase, the tangential wind generally intensifies, whereas during the monopole phase, the tangential wind remains mostly constant. In both phases, the mean advection terms spin up the tangential wind in the boundary layer, whereas the eddy advection terms deepen the storm’s cyclonic circulation by spinning up the tangential wind between 1.5 and 4 km. Calculations of the azimuthally averaged, radially integrated vertical mass flux suggest that periods of near-constant tangential wind tendency are accompanied by a weaker eyewall updraft, which is unable to evacuate all the mass converging in the boundary layer. Composite analyses calculated from 18 simulations produce qualitatively similar results to those from the single case, a finding that is also in agreement with some previous observational and modeling studies. Above the boundary layer, the integrated contribution of the eddy term to the tangential wind tendency is over 80% of the contribution from the mean term, irrespective of inner-core structure. Our results strongly indicate that to fully understand the storm’s three-dimensional evolution, the contribution of the eddies must be quantified.
Implementing a systems approach to suicide prevention in a mental health service using the Zero Suicide Framework
Authors: Turner Kathryn , Sveticic Jerneja , Almeida-Crasto Alice , Gaee-Atefi Taralina , Green Vicki , Grice Diana , Kelly Petra , Krishnaiah Ravikumar , Lindsay Luke , Mayahle Brian , Patist Carla , Van Engelen Heidy , Walker Sarah , Welch Matthew , Woerwag-Mehta Sabine , Stapelberg Nicolas JC
Published: November 2020

Objective:

The Zero Suicide Framework, a systems approach to suicide prevention within a health service, is being implemented across a number of states in Australia, and internationally, although there is limited published evidence for its effectiveness. This paper aims to provide a description of the implementation process within a large health service in Australia and describes some of the outcomes to date and learnings from this process.

Method:

Gold Coast Mental Health and Specialist Services has undertaken an implementation of the Zero Suicide Framework commencing in late 2015, aiming for high fidelity to the seven key elements. This paper describes the practical steps undertaken by the service, the new practices embedded, emphasis on supporting staff following the principles of restorative just culture and the development of an evaluation framework to support a continuous quality improvement approach.

Results:

Improvements have been demonstrated in terms of processes implementation, enhanced staff skills and confidence, positive cultural change and innovations in areas such as the use of machine learning for identification of suicide presentations. A change to ‘business as usual’ has benefited thousands of consumers since the implementation of a Suicide Prevention Pathway in late 2016 and achieved reductions in rates of repeated suicide attempts and deaths by suicide in Gold Coast Mental Health and Specialist Services consumers.

Conclusion:

An all-of-service, systems approach to suicide prevention with a strong focus on cultural shifts and aspirational goals can be successfully implemented within a mental health service with only modest additional resources when supported by engaged leadership across the organisation. A continuous quality improvement approach is vital in the relentless pursuit of zero suicides in healthcare.
Book review: Wang Jing, The Other Digital China Nonconfrontational Activism on the Social Web
Authors: Kamtam Mahesh Kumar
Published: November 2020

Wang Jing, The Other Digital China Nonconfrontational Activism on the Social Web (Cambridge, MA: Harvard University Press, 2019), pp. 320, $39.95, ISBN: 9780674980921.
Book review: Bertil Lintner, The Costliest Pearl: China’s Struggle for India’s Ocean
Authors: Marwah Reena
Published: November 2020

Bertil Lintner, The Costliest Pearl: China’s Struggle for India’s Ocean (Chennai, India: Westland Publications Pvt. Ltd, 2019), pp. 325, ₹699 (Hardbound), ISBN: 978-938-868-9717.
The Cross-Cultural Relevance of Indigenous Measures: The South African Personality Inventory (SAPI), Family Orientation, and Well-Being in New Zealand
Authors: Fetvadjiev Velichko H. , Neha Tia , van de Vijver Fons J. R. , McManus Martin , Meiring Deon
Published: November 2020

Indigenous personality research often remains limited to its cultural context of origin. Previous cross-cultural examinations of indigenous models have typically focused on East–West comparisons and have paid scant attention to the predictive validity of indigenous models in new contexts. The present study addresses the replicability of the South African Personality Inventory (SAPI) and its predictive validity for family orientation and well-being in New Zealand European ( n = 428) and Māori students ( n = 226). The structure of the SAPI in New Zealand was equivalent to the structure identified in South Africa and had metric invariance between the two New Zealand groups. The SAPI social-relational scales explained additional variance above neuroticism, extraversion, conscientiousness, and openness in family orientation, but not in well-being. Mediation path analyses suggested that personality played a similar role for family orientation and well-being in the two groups when assessed by the SAPI, although group differences were suggested when using the Big Five Inventory. Our findings indicate that indigenously derived models, developed with the aim to represent culturally salient concepts, can be relevant well beyond their culture of origin and offer an enriched understanding of personality’s role for important outcomes across cultures.