bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of ion transport genes in ionocytes isolated from larval zebrafish (Danio rerio) exposed to acidic or Na+-deficient water
Authors: Shir-Mohammadi K. , Perry S. F.
Published: August 2020

In zebrafish ( Danio rerio), a specific ionocyte subtype, the H+-ATPase-rich (HR) cell, is presumed to be a significant site of transepithelial Na+uptake/acid secretion. During acclimation to environments differing in ionic composition or pH, ionic and acid–base regulations are achieved by adjustments to the activity level of HR cell ion transport proteins. In previous studies, the quantitative assessment of mRNA levels for genes involved in ionic and acid–base regulations relied on measurements using homogenates derived from the whole body (larvae) or the gill (adult). Such studies cannot distinguish whether any differences in gene expression arise from adjustments of ionocyte subtype numbers or transcriptional regulation specifically within individual ionocytes. The goal of the present study was to use fluorescence-activated cell sorting to separate the HR cells from other cellular subpopulations to facilitate the measurement of gene expression of HR cell-specific transporters and enzymes from larvae exposed to low pH (pH 4.0) or low Na+(5 μM) conditions. The data demonstrate that treatment of larvae with acidic water for 4 days postfertilization caused cell-specific increases in H+-ATPase ( atp6v1aa), ca17a, ca15a, nhe3b, and rhcgb mRNA in addition to increases in mRNA linked to cell proliferation. In fish exposed to low Na+, expression of nhe3b and rhcgb was increased owing to HR cell-specific regulation and elevated numbers of HR cells. Thus, the results of this study demonstrate that acclimation to low pH or low Na+environmental conditions is facilitated by HR cell-specific transcriptional control and by HR cell proliferation.
Innovative methods measure the neural correlates of proprioception in multiple sclerosis
Authors: Whittier Tyler T. , Bandera Victoria
Published: August 2020

The authors of the recently published article “Position sense deficits at the lower limbs in early multiple sclerosis: clinical and neural correlates” (Iandolo R, Bommarito G, Falcitano L, Schiavi S, Piaggio N, Mancardi GL, Casadio M, Inglese M. Neurorehabil Neural Repair 34: 260–270, 2020) provide strong evidence for the neural correlates leading to deficits in proprioception in multiple sclerosis. We believe their findings and innovative methodology show promise for how proprioception is measured in this and other clinical populations. We also suggest that further work should investigate the role of the corpus callosum in proprioceptive balance control.
Contributions of exercise-induced fatigue versus intertrial tendon vibration on visual-proprioceptive weighting for goal-directed movement
Authors: Manzone Damian M. , Tremblay Luc
Published: August 2020

Previous work has used muscle fatigue or tendon vibration to perturb proprioceptive limb position estimates. This study sought to determine whether exercise-induced muscle fatigue versus intertrial tendon vibration can alter multisensory weighting for upper limb-aiming movements. By introducing a discrepancy between participants’ actual proprioceptive and visual finger position, this study provides seminal evidence for the reduction of proprioceptive-to-visual weighting using intertrial tendon vibration but no evidence for a systematic reduction following exercise-induced fatigue.
Enabling respiratory control after severe chronic tetraplegia: an exploratory case study
Authors: Gad Parag , Kreydin Evgeniy , Zhong Hui , Edgerton V. Reggie
Published: August 2020

Noninvasive spinal neuromodulation improves breathing and coughing in a patient with severe and complete tetraplegia.
Neurophysiological response properties of medullary pain-control neurons following chronic treatment with morphine or oxycodone: modulation by acute ketamine
Authors: Viisanen Hanna , Lilius Tuomas O. , Sagalajev Boriss , Rauhala Pekka , Kalso Eija , Pertovaara Antti
Published: August 2020

Morphine and oxycodone are two clinically used strong opioids. Chronic treatment with oxycodone as well as morphine can lead to analgesic tolerance and paradoxical hyperalgesia. Here we show that an N-methyl-d-aspartate receptor-dependent pronociceptive change in discharge properties of rostroventromedial medullary neurons controlling spinal nociception has an important role in antinociceptive tolerance to morphine but not oxycodone. Interestingly, chronic oxycodone did not induce pronociceptive changes in the rostroventromedial medulla.
Neck muscle fatigue impacts plasticity and sensorimotor integration in cerebellum and motor cortex in response to novel motor skill acquisition
Authors: Zabihhosseinian Mahboobeh , Yielder Paul , Berkers Victoria , Ambalavanar Ushani , Holmes Michael , Murphy Bernadette
Published: August 2020

Normally motor learning decreases cerebellar inhibition (CBI) to facilitate learning of a novel skill. In this study, neck fatigue before motor skill acquisition led to less of a decrease in CBI and significantly less improvement in performance accuracy relative to a control group. This study demonstrated that neck fatigue impacts the cerebellar-motor cortex interaction to distal hand muscles, a highly relevant finding due to the altered neck postures and fatigue accompanying increased technology use.
Study on the Mechanism of Sarsasapogenin in Treating Precocious Puberty by Regulating the HPG Axis
Authors: Hu Kaili , Sun Wenyan , Li Yu , Zhang Bo , Zhang Meng , Guo Chunyan , Chang HongSheng , Wang Xiaoling
Published: August 2020

The present study aims to investigate the effects and mechanisms of sarsasapogenin resistance to precocious puberty. Female Sprague Dawley rats were divided into a normal (N) group, model (M) group, leuprolide (L) group, and sarsasapogenin (Sar) group. Rats at 5 days of age were given a single subcutaneous injection of 300 micrograms of danazol to establish the precocious puberty model. After 10 days of modeling, drug intervention was started. The development of the uterus and ovary was observed by hematoxylin and eosin (HE) staining. The levels of the serum luteinizing hormone (LH), follicle‐stimulating hormone (FSH), and estradiol (E2) were determined by radioimmunoassay. Also, the expressions of the hypothalamic gonadotropin releasing hormone (GnRH), Kiss‐1, G protein‐coupled receptor 54 (GPR54), and pituitary gonadotropin releasing hormone receptor (GnRH‐R) were detected by RT‐PCR. The results showed that compared with the model group, sarsasapogenin could significantly delay the opening time of vaginal, decreased uterine and ovarian coefficients, and reduced uterine wall thickness. Moreover, it can significantly downregulate the levels of serum hormones and reduce the expression of GnRH, GnRH‐R, and kiss‐1. In summary, our results indicate that sarsasapogenin can regulate the HPG axis through the kiss‐1/GPR54 system for therapeutic precocious puberty.
Obtaining and Characterization of TiO2-GO Composites for Photocatalytic Applications
Authors: Ramos D. K. Calvo , González M. Vega , Muñóz R. A. Esparza , Cruz J. Santos , De Moure-Flores F. J. , Mayén-Hernández S. A.
Published: August 2020

Titanium dioxide (TD) and graphene oxide (GO) were synthesized by sol-gel and improved Hummers method, respectively. This study shows the results of the incorporation through four different conditions (sol-gel, sol-gel and ultrasonic, annealed, and UV radiation, C1 to C4, respectively). It was observed that a homogeneous incorporation of TD on sheets of GO was obtained satisfactorily. The composites of TiO2/GO were characterized using different techniques such as X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), scanning transmission electron microscopy (STEM), energy dispersive X-ray spectroscopy (EDS), Raman spectroscopy, and infrared spectroscopy (IR). The photocatalytic activity of the composites was determined from the degradation of the dye azo tartrazine using UV and solar radiation. The best incorporation of TD nanoparticles on GO was obtained with condition C3 (thermal incorporation method) at a temperature of 65°C. This shows a uniformity in the size and shape of the TD as well as an excellent adherence to the sheet of GO. This addition is accomplished by ionic bonding in the presence of electrostatic Coulomb forces. The C3 composite degraded the tartrazine dye using UV radiation and sunlight. With the latter, the degradation time was three times faster than using UV light.
Adaptive Finite-Time Control for Spacecraft Rendezvous under Unknown System Parameters
Authors: Liu Yuan , Tang Guojian , Li Yuhang , Li Hang , Ren Jing , Zhang Sai
Published: August 2020

In this study, we investigated the sliding mode control (SMC) technology for the spacecraft rendezvous maneuver under unknown system parameters and external disturbance. With no knowledge of the mass and inertial matrix of the pursuer spacecraft, an adaptive SMC approach was devised using the hyperbolic tangent function to realize the control objective of reducing the chattering problem. In addition, the finite-time stability of the relative dynamics and the boundedness of the signals in the closed-loop system were derived under proposed method. The effectiveness and advantages of the proposed method were verified through theoretical analysis and numerical simulations.
The Effect of Kinesitherapy on Bone Mineral Density in Primary Osteoporosis: A Systematic Review and Meta‐Analysis of Randomized Controlled Trial
Authors: Wang Shanxi , Li Shuzhen , Xie Xing , Xie Juying
Published: August 2020

Objective. Osteoporosis (OP) is a well‐established age‐related disease, pathologically characterized by bone microarchitectural deterioration, increased fragility, and low BMD. Primary osteoporosis (POP) is the most common type of OP. Methods. Publications pertaining to the effectiveness of kinesitherapy on BMD in POP from PubMed, SCI, Cochrane Library, Embase, VIP, CNKI, and Wanfang Database were retrieved from their inception to October 2019. Results. A total of 21 studies with 1840 participants were included. The results of the meta‐analysis revealed that kinesitherapy plus antiosteoporosis medications had a positive effect on lumbar spine BMD when the duration of intervention was 6 months (MD = 0.11 g/cm2; 95% CI: 0.06–0.15; P < 0.0001) or >6 months (MD = 0.04 g/cm2; 95% CI: 0.02–0.06; P < 0.0001) compared with antiosteoporosis medications alone. Additional kinesitherapy plus antiosteoporosis medications were associated with improved femoral neck BMD compared with antiosteoporosis medications alone (MD = 0.09 g/cm2; 95% CI: 0.03–0.16; P = 0.004). Conclusions. Kinesitherapy plus antiosteoporosis medications significantly improved lumbar spine and femoral neck BMD in the current low‐quality evidence. Additional high‐quality evidence is required to confirm the effect of kinesitherapy on BMD in patients with POP.
Global Stability for Fractional Diffusion Equations in Biological Systems
Authors: Hattaf Khalid , Yousfi Noura
Published: August 2020

This paper proposes a new method of construction of Lyapunov functionals for the dynamical systems described by fractional differential equations and fractional partial differential equations. The proposed method is rigorously presented. Furthermore, the method is applied to establish the global stability of some fractional biological models with and without diffusion.
Visual Binocular Disorders and Their Relationship with Baropodometric Parameters: A Cross‐Association Study
Authors: Sánchez-González María Carmen , Gutiérrez-Sánchez Estanislao , Elena Pinero-Pinto , Ruiz-Molinero Carmen , Pérez-Cabezas Verónica , Jiménez-Rejano José-Jesús , Rebollo-Salas Manuel
Published: August 2020

The aim of this study was to establish a relationship between nonstrabismic binocular dysfunction and baropodometric parameters. A total of 106 participants underwent binocular vision assessment by evaluating horizontal heterophoria, horizontal and vertical fusional vergence ranges, and vergence facility. Posturography was measured using the FreeMED baropodometric platform. Among the variables that the software calculates are foot surface, foot load, and foot pressure. Our results showed that in the participants with positive fusional vergence (PFV) (near) blur and recovery values outside the norm, there are statistically significant differences between the total foot area (p < 0.05), forefoot area (p < 0.05), forefoot load (p < 0.05), and rearfoot load (p < 0.05), in all of the cases of left foot vs. right foot. In the group of subjects who did not meet Sheard’s criterion (distance), that is, those with unstable binocular vision, there was a statistically significant difference (p < 0.01) between maximum left and right foot pressure. In conclusion, our results establish a relationship between nonstrabismic binocular dysfunctions and some baropodometric parameters.
A Systematic Approach for Cybersecurity Design of In-Vehicle Network Systems with Trade-Off Considerations
Authors: Yu Jinghua , Luo Feng
Published: August 2020

With the increasing connectivity of modern vehicles, protecting systems from attacks on cyber is becoming crucial and urgent. Meanwhile, a vehicle should guarantee a safe and comfortable trip for users. Therefore, how to design a cybersecurity-critical system in vehicles with safety and user experience (UX) considerations is increasingly essential. However, most co-design methods focus on safety engineering with attack concerns and do not discuss conflicts and integration, and few contain the UX aspect. Besides, most existing approaches are abstract at a high level without practical guidelines. This paper presents a literature review of existing safety and security design approaches and proposes a systematic approach for cybersecurity design of in-vehicle network systems based on the guideline in SAE J3061. The trade-off analysis is performed by using association keys and the proposed affecting map. The design process of an example Diagnostic on Internet Protocol (DoIP) system is reported to show how the approach works. Compared with the existing approaches, the proposed one considers safety, cybersecurity, and UX simultaneously, solves conflicts qualitatively or quantitatively, and obtains trade-off design requirements. This approach is applicable to the cybersecurity-driven design of in-vehicle network systems in the early stage with safety and UX considerations.
Methodology and Reporting Quality Evaluation of Acupuncture for Mild Cognitive Impairment: An Overview of Systematic Reviews
Authors: Hou Tinghui , Zheng Qianhua , Feng Xiumei , Wang Lu , Liu Ying , Li Ying
Published: August 2020

Objective. Since there is no consistent evidence on the effectiveness of acupuncture in the treatment of mild cognitive impairment, this review aims to summarize and critically evaluate the methodological and reporting quality of systematic reviews (SRs). Methods. We comprehensively searched PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Chinese Biomedical Literature (CBM), and Wanfang databases from the date of establishment to April 2019. Two authors independently selected the articles, collected the data, and assessed the identified and included SRs with the revised measurement tool to assess systematic reviews (AMSTAR 2) and preferred reporting items for SRs and meta‐analyses (PRISMA). The quality of outcomes was evaluated by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Results. Eleven SRs were included in this overview. The items of AMSTAR 2 in most SRs were poorly reported; only 3 SRs were rated as low quality by AMSTAR 2, and the remaining were rated as very low quality. A total of 8 SRs obtained a decent rating by PRISMA. With the GRADE tool, we have not found high‐quality evidence that acupuncture is effective for mild cognitive impairment (MCI), so there is no certain conclusion on the effectiveness of acupuncture treatment for MCI. Conclusion. The methodological and reporting quality of SRs on acupuncture for MCI is substandard, and the quality of evidence is poor. In future research, more efforts are needed to improve the quality of SRs in this field.
Synthesis and Characterization of 5-Hydroxymethylfurfural from Corncob Using Solid Sulfonated Carbon Catalyst
Authors: Mengstie Moges Admasie , Habtu Nigus Gabbiye
Published: August 2020

5-Hydroxymethylfurfural as a versatile organic compound is considered as a promising biomass-derived product via hydrolysis followed by dehydration of lignocellulosic biomass using solid catalysts. In this study, lignocellulosic materials (corncob) were utilized to synthesize 5-hydroxymethylfurfural via solid acid catalytic conversion. The precursor of the catalyst material was chemically impregnated with ZnCl2 prior to carbonization. The solid catalyst was prepared with three different acid concentrations of 98%, 96%, and 94% of sulfuric acid. The prepared catalyst was characterized by acid density elemental analysis, FTIR, XRD, and SEM. The maximum result of the total acid density and amount of SO3H group was recorded as 3.5 mmol/g and 0.61 mmol/g, respectively, with high sulfur content of 1.87%. The result from FTIR spectra of BC-SO3H−1 confirms the incorporation of -SO3H groups into the carbon material. BC-SO3H−1 was selected based on the acid density and elemental analysis of the catalyst. The activity of the selected catalyst (BC-SO3H−1) was studied on the transformation of corncob to 5-hydroxymethylfurfural using biphasic solvent (water: ethyl acetate) and NaCl in the reaction medium. The intermediate result in the hydrolysis\dehydration reaction was analyzed using FTIR and the functional groups observed confirm the occurrence of 5-HMF in the intermediate reaction result.
Associations between Phase Angle Values Obtained by Bioelectrical Impedance Analysis and Nonalcoholic Fatty Liver Disease in an Overweight Population
Authors: Chen Guangya , Lv Yi , Ni Wei , Shi Qingxin , Xiang Xingliang , Li Sen , Song Chengwu , Xiao Mingzhong , Jin Shuna
Published: August 2020

Objective. There is a limited diagnosis of nonalcoholic fatty liver disease (NAFLD). Thus, the noninvasive assessments are worth exploring. We determined the associations of phase angles (PhAs) obtained from bioelectric impedance analysis (BIA) with the risk of NAFLD in an overweight population. Methods. A study involving 953 overweight participants was conducted in Wuhan city, China. The associations between PhAs (right arm, left arm, body trunk, right leg, left leg, and whole body) and the risk of NAFLD were conducted using multivariate logistic regression analyses. The associations of PhAs with the controlled attenuation parameter (CAP), a noninvasive assessment of liver steatosis and fibrosis, were also evaluated by both linear and logistic regression analyses. Results. The PhA values of the whole body, trunk, and legs were significantly lower (P<0.05) in the NAFLD group than the non-NAFLD group. After adjustment for BMI, gender, education, income/year, hyperlipidemia, hypertension, diabetes, smoking, passive smoking, and drinking, significant associations of PhA values of the right leg, left leg, and whole body with the risk of NAFLD were observed. In addition, the PhA of the right leg, left leg, and whole body were significantly related to the CAP values. Further stratified analyses indicated that these associations were significant in the participants with BMI <30, but not in the participants with BMI ≥30. Conclusions. PhAs might be effective indicators in the management of NAFLD among overweight people.
Several Turán-Type Inequalities for the Generalized Mittag-Leffler Function
Authors: Dou Xiang Kai , Yin Li , Lin Xiu-Li
Published: August 2020

In this paper, several Turán-type inequalities for the more generalized Mittag-Leffler function are proved. In addition, we also gave affirmative answers to two open problems posed by Mehrez and Sitnik.
Quest for Ideal Composite Biomarkers for Response to Immunotherapies
Authors: Swami Umang , Nussenzveig Roberto H. , Agarwal Neeraj
Published: August 2020

In the CheckMate 275 study, composite biomarkers appear to better predict response to immunotherapy over individual ones. Nevertheless, the path forward needs consensus guidelines for biomarker interpretation. Thereafter, prospective validation with real-time, serial biospecimen collection along with the development of composite biomarker models leads to the goal of personalized therapy.

See related article by Galsky et al., p. 5120
MicroRNA-31 Can Positively Regulate the Proliferation, Differentiation and Migration of Keratinocytes
Authors: Wang Fei , Gao Yuantao , Yuan Yitong , Du Ruochen , Li Pengfei , Liu Fang , Tian Ye , Wang Yali , Zhang Ruxin , Zhao Bichun , Wang Chunfang
Published: August 2020

In the past decades, the key roles of most microRNA in dermatosis and skin development have been explored one after another. Among them, microRNA-31 (miR-31) has a prominent role in the regulation of keratinocytes. Numerous studies show that miR-31 can positively regulate the proliferation, differentiation and cell activity of keratinocytes via regulating the NF-κB, RAS/MAPK, Notch signaling pathways, and some cytokines. At present, the interaction between miR-31 and the NF-κB signaling pathway in keratinocytes is a hot research topic. The positive feedback loop formed by miR-31 and NF-κB signaling may bring new ideas for the prevention of psoriasis. The abnormal state of keratinocytes is usually the pathological basis of many skin and immune system diseases. Therefore, strengthening the ability to regulate keratinocytes may be a breakthrough for a variety of diseases. At the same time, miR-31’s capacity to accelerate wound healing via positively regulating keratinocytes should be further investigated in the treatment of chronic ulcers and trauma.
Inpatient Care during the COVID-19 Pandemic: A Survey of Italian Physicians
Authors: Attanasi Marina , Pasini Simone , Caronni Antonio , Pellegrino Giulia Michela , Faverio Paola , Di Pillo Sabrina , Cimino Matteo Maria , Cipolla Giuseppe , Chiarelli Francesco , Centanni Stefano , Sferrazza Papa Giuseppe Francesco ,   Collaborators for the RECOVER Investigators Study Group
Published: August 2020

Background: Coronavirus disease 2019 (COVID-19) is a potentially fatal disease that is of great global public health concern. Objective: We explored the clinical management of inpatients with COVID-19 in Italy. Methods: A self-administered survey was sent by email to Italian physicians caring for adult patients with COVID-19. A panel of experts was selected according to their clinical curricula and their responses were analyzed. Results: A total of 1,215 physicians completed the survey questionnaire (17.4% response rate). Of these, 188 (15.5%) were COVID-19 experts. Chest computed tomography was the most used method to detect and monitor COVID-19 pneumonia. Most of the experts managed acute respiratory failure with CPAP (56.4%), high flow nasal cannula (18.6%), and non-invasive mechanical ventilation (8%), while an intensivist referral for early intubation was requested in 17% of the cases. Hydroxychloroquine was prescribed as an antiviral in 90% of cases, both as monotherapy (11.7%), and combined with protease inhibitors (43.6%) or azithromycin (36.2%). The experts unanimously prescribed low-molecular-weight heparin to patients with severe COVID-19 pneumonia, and half of them (51.6%) used a dose higher than standard. The respiratory burden in patients who survived the acute phase was estimated as relevant in 28.2% of the cases, modest in 39.4%, and negligible in 9%. Conclusions: In our survey some major topics, such as the role of non-invasive respiratory support and drug treatments, show disagreement between experts, likely reflecting the absence of high-quality evidence studies. Considering the significant respiratory sequelae reported following COVID-19, proper respiratory and physical therapy programs should be promptly made available.
Aberrant Expression of Prohibitin Is Related to Prognosis of Nasal Extranodal Natural Killer/T Cell Lymphoma, Nasal Type
Authors: Guo Wen Wen , Chen Ling Hui , Yin Wu , Mo Lan Xiang
Published: August 2020

Introduction: Nasal extranodal natural killer (NK)/T cell lymphoma, nasal type (ENKTCL) is a high-grade Epstein-Barr virus (EBV)-associated malignancy with poor outcomes. There are few biomarkers for the accurate diagnosis and prognostic prediction of the disease. The aim of this study was to investigate the clinicopathological significance of prohibitin (PHB) expression in nasal ENKTCL. Methods: The expression level of PHB was detected via immunohistochemical staining in 49 nasal ENKTCL tissues and age- and sex-matched controls of 30 nasal mucosa-reactive lymphoid hyperplasia (NRLH) tissues. The correlations between the PHB expression and clinicopathological features of patients with nasal ENKTCL were evaluated. Results: The results indicated a significantly decreased expression of PHB in nasal ENKTCL tissues compared with in NRLH tissues. Low-level PHB expression was significantly associated with younger age and fever (p = 0.008 and 0.018, respectively). The Kaplan-Meier analysis showed that the cytoplasm expression level of PHB in nasal ENKTCL was inversely related to overall survival (p = 0.046). Conclusions: PHB may be a potential diagnostic marker and prognostic predictor of nasal ENKTCL.
Aberrant Differentiation of Human Pluripotent Stem Cell-Derived Kidney Precursor Cells inside Mouse Vascularized Bioreactors
Authors: Ranjzad Parisa , Jinks Jessica , Salahi Amir P. , Bantounas Ioannis , Derby Brian , Kimber Susan J. , Woolf Adrian S. , Wong Jason K.F.
Published: August 2020

Background: Numerous studies have documented the in vitro differentiation of human pluripotent stem cells (hPSCs) into kidney cells. Fewer studies have followed the fates of such kidney precursor cells (KPCs) inside animals, a more life-like setting. Here, we tested the hypothesis that implanting hPSC-derived KPCs into an in vivo milieu surgically engineered to be highly vascular would enhance their maturation into kidney tissues. Methods: 3D printed chambers containing KPCs were implanted into the thighs of adult immunodeficient mice. In some chambers, an arterial and venous flow-through (AVFT) was surgically fashioned. After 3 weeks and 3 months, implants were studied by histology, using qualitative and quantitative methods. Results: After 3 weeks, chambers containing AVFTs were richer in small vessels than contralateral chambers without AVFTs. Glomeruli with capillary loops and diverse types of tubules were detected in all chambers. At 3 months, chambers contained only rudimentary tubules and glomeruli that appeared avascular. In chambers with AVFTs, prominent areas of muscle-like cells were also detected near tubules and the abnormal tissues immunostained for transforming growth factor β1. These features have similarities to renal dysplasia, a typical histological signature of human congenital kidney malformations. Conclusions: This study urges a note of caution regarding the in vivo fates of hPSC-derived kidney precursors, with pathological differentiation appearing to follow a period of increased vascularity.
miR-18a Inhibits BMP4 and HIF-1α Normalizing Brain Arteriovenous Malformations
Authors: Marín-Ramos Nagore I. , Thein Thu Zan , Ghaghada Ketan B. , Chen Thomas C. , Giannotta Steven L. , Hofman Florence M.
Published: August 2020

Rationale:

Brain arteriovenous malformations (AVMs) are abnormal tangles of vessels where arteries and veins directly connect without intervening capillary nets, increasing the risk of intracerebral hemorrhage and stroke. Current treatments are highly invasive and often not feasible. Thus, effective noninvasive treatments are needed. We previously showed that AVM-brain endothelial cells (BECs) secreted higher VEGF (vascular endothelial growth factor) and lower TSP-1 (thrombospondin-1) levels than control BEC; and that microRNA-18a (miR-18a) normalized AVM-BEC function and phenotype, although its mechanism remained unclear.

Objective:

To elucidate the mechanism of action and potential clinical application of miR-18a as an effective noninvasive treatment to selectively restore the phenotype and functionality of AVM vasculature.

Methods and Results:

The molecular pathways affected by miR-18a in patient-derived BECs and AVM-BECs were determined by Western blot, RT-qPCR (quantitative reverse transcription polymerase chain reaction), ELISA, co-IP, immunostaining, knockdown and overexpression studies, flow cytometry, and luciferase reporter assays. miR-18a was shown to increase TSP-1 and decrease VEGF by reducing PAI-1 (plasminogen activator inhibitor-1/SERPINE1) levels. Furthermore, miR-18a decreased the expression of BMP4 (bone morphogenetic protein 4) and HIF-1α (hypoxia-inducible factor 1α), blocking the BMP4/ALK (activin-like kinase) 2/ALK1/ALK5 and Notch signaling pathways. As determined by Boyden chamber assays, miR-18a also reduced the abnormal AVM-BEC invasiveness, which correlated with a decrease in MMP2 (matrix metalloproteinase 2), MMP9, and ADAM10 (ADAM metallopeptidase domain 10) levels.

In vivo pharmacokinetic studies showed that miR-18a reaches the brain following intravenous and intranasal administration. Intranasal co-delivery of miR-18a and NEO100, a good manufacturing practices-quality form of perillyl alcohol, improved the pharmacokinetic profile of miR-18a in the brain without affecting its pharmacological properties. Ultra-high-resolution computed tomography angiography and immunostaining studies in an Mgp
−
/−
AVM mouse model showed that miR-18a decreased abnormal cerebral vasculature and restored the functionality of the bone marrow, lungs, spleen, and liver.

Conclusions:

miR-18a may have significant clinical value in preventing, reducing, and potentially reversing AVM.
Characteristics and Outcomes of Patients With Takotsubo Syndrome: Incremental Prognostic Value of Baseline Left Ventricular Systolic Function
Authors: Alashi Alaa , Isaza Nicolas , Faulx Jackson , Popovic Zoran B. , Menon Venu , Ellis Stephen G. , Faulx Michael , Kapadia Samir R. , Griffin Brian P. , Desai Milind Y.
Published: August 2020

Background

We sought to determine (1) long‐term outcomes in patients presenting with documented Takotsubo syndrome (TS), (2) whether left ventricular global longitudinal strain (LV‐GLS) provides incremental prognostic value, and (3) prognostic cutoffs of LV ejection fraction (LVEF) and LV‐GLS during an acute TS episode.

Methods and Results

We studied 650 patients with TS (aged 66±14 years, 88% women) who were diagnosed clinically and angiographically between 2006 and 2018. Baseline LVEF and LV‐GLS (using velocity vector imaging) were recorded. The primary end point was all‐cause mortality. TS triggers were unknown (34%), emotional (16%), physical (41%), and neurologic (10%). Mean LVEF and LV‐GLS were 36±10% and −11.6±0.4%; in addition, 94% patients had LVEF <52%, and 80% had apical ballooning. No patient had obstructive coronary artery disease. At a median of 2.2 years (interquartile range, 0.7–4.4), 175 (27%) had died (9% in‐hospital deaths). Multivariate Cox survival analysis revealed that higher age (hazard ratio [HR], 1.35), male sex (HR, 1.75), lower baseline LVEF (HR, 1.02), worse LV‐GLS (HR, 1.04), neurologic trigger (HR, 2.66), and physical trigger (HR, 2.64) were associated with mortality, whereas aspirin (HR, 0.70) and β‐blockers (HR, 0.73) improved survival (all
P
<0.049). The addition of LVEF and LV‐GLS to clinical markers (age, sex, cardiogenic shock at presentation, and peak troponin I) significantly increased log‐likelihood ratios: clinical (−521.48), clinical plus LVEF (−511.32,
P
<0.001), and clinical plus LVEF and LV‐GLS (−500.68,
P
<0.001). On penalized spline analysis, LVEF of 38% and LV‐GLS of −10% were cutoffs below which survival was significantly worse.

Conclusions

Patients with TS with a neurologic or physical trigger had significantly worse survival than those without such a trigger, with baseline LVEF and LV‐GLS providing incremental prognostic value.
Degree of Blood Pressure Control and Incident Diabetes Mellitus in Chinese Adults With Hypertension
Authors: Zhang Yuanyuan , Nie Jing , Zhang Yan , Li Jianping , Liang Min , Wang Guobao , Tian Jianwei , Liu Chengzhang , Wang Binyan , Cui Yimin , Wang Xiaobin , Huo Yong , Xu Xiping , Hou Fan Fan , Qin Xianhui
Published: August 2020

Background

The association between blood pressure (BP) control and incident diabetes mellitus remains unknown. We aim to investigate the association between degree of time‐averaged on‐treatment systolic blood pressure (SBP) control and incident diabetes mellitus in hypertensive adults.

Methods and Results

A total of 14 978 adults with hypertension without diabetes mellitus at baseline were included from the CSPPT (China Stroke Primary Prevention Trial). Participants were randomized double‐masked to daily enalapril 10 mg and folic acid 0.8 mg or enalapril 10 mg alone. BP measurements were taken every 3 months after randomization. The primary outcome was incident diabetes mellitus, defined as physician‐diagnosed diabetes mellitus, or use of glucose‐lowering drugs during follow‐up, or fasting glucose ≥126 mg/dL at the exit visit. Over a median of 4.5 years, a significantly higher risk of incident diabetes mellitus was found in participants with time‐averaged on‐treatment SBP 130 to <140 mm Hg (10.3% versus 7.4%; odds ratio [OR], 1.37; 95% CI, 1.15‒1.64), compared with those with SBP 120 to <130 mm Hg. Moreover, the risk of incident diabetes mellitus increased by 24% (OR, 1.24; 95% CI, 1.00‒1.53) and the incidence of regression to normal fasting glucose (<100 mg/dL) decreased by 29% (OR, 0.71; 95% CI, 0.57‒0.89) in participants with intermediate BP control (SBP/diastolic blood pressure, 130 to <140 and/or 80 to <90 mm Hg), compared with those with a tight BP control of <130/<80 mm Hg. Similar results were found when the time‐averaged BP were calculated using the BP measurements during the first 6‐ or 24‐month treatment period, or in the analysis using propensity scores.

Conclusions

In this non‐diabetic, hypertensive population, SBP control in the range of 120 to <130 mm Hg, compared with the 130 to <140 mm Hg, was associated with a lower risk of incident diabetes mellitus.
Cerebral Microbleeds and Leukoencephalopathy in Critically Ill Patients With COVID-19
Authors: Agarwal Shashank , Jain Rajan , Dogra Siddhant , Krieger Penina , Lewis Ariane , Nguyen Vinh , Melmed Kara , Galetta Steven
Published: August 2020

Background and Purpose:

We conducted this study to investigate the prevalence and distribution of cerebral microbleeds and leukoencephalopathy in hospitalized patients with coronavirus disease 2019 (COVID-19) and correlate with clinical, laboratory, and functional outcomes.

Methods:

We performed a retrospective chart review of 4131 COVID-19 positive adult patients who were admitted to 3 tertiary care hospitals of an academic medical center at the epicenter of the COVID-19 pandemic in New York City from March 1, 2020, to May 10, 2020, to identify patients who had magnetic resonance imaging (MRI) of the brain. We evaluated the MRIs in detail, and identified a subset of patients with leukoencephalopathy and/or cerebral microbleeds. We compared clinical, laboratory, and functional outcomes for these patients to patients who had a brain MRI that did not show these findings.

Results:

Of 115 patients who had an MRI of the brain performed, 35 (30.4%) patients had leukoencephalopathy and/or cerebral microbleeds. Patients with leukoencephalopathy and/or cerebral microbleeds had neuroimaging performed later during the hospitalization course (27 versus 10.6 days;
P
<0.001), were clinically sicker at the time of brain MRI (median GCS 6 versus 14;
P
<0.001), and had higher peak D-dimer levels (8018±6677 versus 3183±3482;
P
<0.001), lower nadir platelet count (116.9±62.2 versus 158.3±76.2;
P
=0.03), higher peak international normalized ratio (2.2 versus 1.57;
P
<0.001) values when compared with patients who had a brain MRI that did not show these findings. They required longer ventilator support (34.6 versus 9.1 days;
P
<0.001) and were more likely to have moderate and severe acute respiratory distress syndrome score (88.6% versus 23.8%,
P
<0.001). These patients had longer hospitalizations (42.1 versus 20.9 days;
P
<0.001), overall worse functional status on discharge (mRS 5 versus 4;
P
=0.001), and higher mortality (20% versus 9%;
P
=0.144).

Conclusions:

The presence of leukoencephalopathy and/or cerebral microbleeds is associated with a critical illness, increased mortality, and worse functional outcome in patients with COVID-19.
A new species of Microlicia (Melastomataceae) from Bolivia and Brazil, a new synonym, and an identification key for the genus in Mato Grosso, Brazil

Authors: VERSIANE ANA FLÁVIA ALVES , DA SILVA DIEGO NUNES , ROMERO ROSANA
Published: August 2020

Microlicia windischii is a new species described from Noel Kempff Mercado National Park, Santa Cruz de la Sierra, Bolivia, and Serra Ricardo Franco State Park, Mato Grosso, Brazil. We provide a detailed description of the new species and comparisons with its morphological relatives M. acuminata, M. arenariifolia, M. consimilis, M. juniperina, and M. multicaulis. Microlicia windischii is characterized by the linear-oblong leaf blades and subisomorphic stamens with concolorous and polysporangiate anthers. We also include an identification key for the four species of Microlicia from Mato Grosso and propose to synonymize M. souzae-limae under M. helvola.
Contributions to species of Xylariales in China—4. Hypoxylon wujiangensis sp. nov.

Authors: PI YIN-HUI , ZHANG XU , LIU LI-LI , LONG QING-DE , SHEN XIANG-CHUN , KANG YING-QIAN , HYDE KEVIN D. , BOONMEE SARANYAPHAT , KANG JI-CHUAN , LI QI-RUI
Published: August 2020

A species of Hypoxylon, found on dead wood in China, differs from H. hypomiltum and H. samuelsii in having highly carbonaceous stromata, asci with a long stipe and wider ascospores. Based on morphology and molecular phylogeny, it is described as a new species, H. wujiangensis sp. nov. A detailed description and illustration are provided, along with molecular evidence for the new species.
Molecular phylogeny and morphology of Cunninghamella guizhouensis sp. nov. (Cunninghamellaceae, Mucorales), from soil in Guizhou, China

Authors: ZHANG ZHI-YUAN , ZHAO YI-XUAN , SHEN XIN , CHEN WAN-HAO , HAN YAN-FENG , HUANG JIAN-ZHONG , LIANG ZONG-QI
Published: August 2020

During a survey of keratinolytic fungi in China, three Cunninghamella strains were isolated. Phylogenetic analyses of ITS and ITS+LSU+EF-1α sequence data showed that these strains constitute a new species related to C. blakesleeana, C. bigelovii, C. multiverticillata and C. phaeospora. The new species differs from C. multiverticillata and C. phaeospora in the shape and size of its teminal and lateral vesicles and can be distinguished from C. blakesleeana and C. bigelovii by the absent of zygosporangia, and the shape and size of it sporangioles. The results of phylogenetic and morphological analyses indicate that the three strains are a new species of Cunninghamella. Descriptions and illustrations of this novel species are provided in this paper.
New generic concepts for orphaned lineages formerly treated as part of the genus Ocyptamus Macquart, 1834 (Diptera, Syrphidae)
Authors: MIRANDA GIL FELIPE GONÇALVES , SKEVINGTON JEFFREY H. , MARSHALL STEPHEN A.
Published: August 2020

The large syrphid genus Ocyptamus Macquart has been subject to scrutiny in recent years, resulting in a more narrowly defined monophyletic Ocyptamus sensu stricto. Some of the species excluded from this narrower concept of the genus are in evolutionary lineages for which generic names are available, but other species are in lineages for which generic names do not exist. The current paper presents five new genera to correct this: Fragosa gen. nov. (former Ocyptamus stenogaster group), Hypocritanus gen. nov. (former Ocyptamus fascipennis group), Maiana gen. nov. (former Ocyptamus callidus group), Nuntianus gen. nov. (former Ocyptamus lepidus group) and Victoriana gen. nov. (former Ocyptamus melanorrhinus group). In addition to the new combinations related to these new genera, Argentinomyia aenea (Williston) comb. nov., Hybobathus pola (Curran) comb. nov., H. subchalybeus (Walker) comb. nov., H. wilhelmina (Doesburg) comb. nov., and Leucopodella nasuta (Williston) comb. nov. are moved out of Ocyptamus. Ocyptamus isthmus Thompson is a jun. syn. of Callostigma panamensis Curran stat. rev. Relevant morphological characters and their taxonomic and evolutionary implications are discussed.
The genus Aivalykus Nixon, 1938 (Hymenoptera: Braconidae: Doryctinae) with description of a new species from India and Arabian Peninsula
Authors: RANJITH A.P. , BELOKOBYLSKIJ SERGEY A. , SURESHAN P.M. , NASSER M.
Published: August 2020

The ecphyline genus Aivalykus Nixon, 1938 is discussed. A new species, A. microaciculatus Ranjith et Belokobylskij, sp. nov. from India and United Arab Emirates is described and illustrated. A key to all extant species of the genus Aivalykus is provided.
Decadal to Multidecadal Variability of the Mixed Layer to the South of the Kuroshio Extension Region
Authors: Wu Baolan , Lin Xiaopei , Yu Lisan
Published: August 2020

The decadal to multidecadal mixed layer variability is investigated in a region south of the Kuroshio Extension (130°E–180°, 25°–35°N), an area where the North Pacific subtropical mode water forms, during 1948–2012. By analyzing the mixed layer heat budget with different observational and reanalysis data, here we show that the decadal to multidecadal variability of the mixed layer temperature and mixed layer depth is covaried with the Atlantic multidecadal oscillation (AMO), instead of the Pacific decadal oscillation (PDO). The mixed layer temperature has strong decadal to multidecadal variability, being warm before 1970 and after 1990 (AMO positive phase) and cold during 1970–90 (AMO negative phase), and so does the mixed layer depth. The dominant process for the mixed layer temperature decadal to multidecadal variability is the Ekman advection, which is controlled by the zonal wind changes related to the AMO. The net heat flux into the ocean surface Qnet acts as a damping term and it is mainly from the effect of latent heat flux and partially from sensible heat flux. While the wind as well as mixed layer temperature decadal changes related to the PDO are weak in the western Pacific Ocean. Our finding proposes the possible influence of the AMO on the northwestern Pacific Ocean mixed layer variability, and could be a potential predictor for the decadal to multidecadal climate variability in the western Pacific Ocean.
Ethical Implications of Cultural Barriers to the Depression Diagnosis: Conversations with Primary Care Physicians
Authors: Cagliero Diana
Published: August 2020

This article explores ethical issues raised by Primary Care Physicians (PCPs) when diagnosing depression and caring for cross-cultural patients. This study was conducted in three primary care clinics within a major metropolitan area in the Southeastern United States. The PCPs were from a variety of ethnocultural backgrounds including South Asian, Hispanic, East Asian and Caucasian. While medical education training and guidelines aim to teach physicians about the nuances of cross-cultural patient interaction, PCPs report that past experiences guide them in navigating cross-cultural conversations and patient care. In this study, semi-structured interviews were conducted with seven PCPs which were transcribed and underwent thematic analysis to explore how patients’ cultural backgrounds and understanding of depression affected PCPs’ reasoning and diagnosing of depression in patients from different cultural backgrounds. Ethical issues that arose included: limiting treatment options, expressing a patient’s mental health diagnosis in a biomedical sense to reduce stigma, and somatization of mental health symptoms. Ethical implications, such as lack of autonomy, unnecessary testing, and the possible misuse of healthcare resources are discussed.
Longing for Purity: Fascism and Nazism in the Italian and German Satirical Press (1943/1945–1963)
Authors: Pasquini Dario
Published: August 2020

This article compares Italian and German memory cultures of Fascism and Nazism using an analysis of Italian and West- and East-German satirical magazines published from 1943 to 1963. In the early post-war period, as a consequence of the anti-Fascist and anti-Nazi policies in Italy and in Germany that had been put into effect by the Allied occupation authorities, a significant part of the Italian and German public felt anxiety regarding the Fascist and the Nazi past and feared these past regimes as potential sources of contamination. But many, both in Italy and Germany, also reacted by denying that their country needed any sort of ‘purification’. This article’s main argument is that the interaction between these two conflicting positions exercised different effects in the three contexts considered. In Italy, especially during the years after 1948, the satirical press produced images that either rendered Fascism banal or praised it, representing it as a phenomenon which was an ‘internal’ and at least partly positive product of Italian society. I define this process as a sweetening ‘internalization’ of Fascism. In East Germany, by contrast, Nazism was represented through images linking the crimes committed in the Nazi concentration camps, depicted as a sort of ‘absolute evil’, with the leadership of the FRG, considered ‘external’ to ‘true’ German society. I define this process as a ‘demonizing’ externalization of Nazism, by which I mean a tendency to represent Nazism as a ‘monstrous’ phenomenon. In the West German satirical press, on the other hand, Nazism was not only ‘externalized’ by comparing it to the East German Communist dictatorship, but also ‘internalized’ by implying that it was a negative product of German society in general and by calling for public reflection on responsibility for the Nazi crimes, including West Germany as the Nazi regime’s successor. The demonization of the regime also played a crucial role in this self-critical ‘internalization’ of Nazism.
Transnational Policing after the 1848–1849 Revolutions: The Habsburg Empire in the Mediterranean
Authors: Aliprantis Christos
Published: August 2020

This article investigates the policing measures of the Habsburg Empire against the exiled defeated revolutionaries in the Mediterranean after the 1848–1849 revolutions. The examination of this counter-revolutionary policy reveals the pioneering role Austria played in international policing. It shows, in particular, that Vienna invested more heavily in policing in the Mediterranean after 1848 than it did in other regions, such as Western Europe, due to the multitude of ‘Forty-Eighters’ settled there and the alleged inadequacy of the local polities (e.g., the Ottoman Empire, Greece) to satisfactorily deal with the refugee question themselves. The article explains that Austria made use of a wide array of both official and unofficial techniques to contain these allegedly dangerous political dissidents. These methods ranged from official police collaboration with Greece and the Ottoman Empire to more subtle regional information exchanges with Naples and Russia. However, they also included purely unilateral methods exercised by the Austrian consuls, Austrian Lloyd sailors and ship captains, and ad hoc recruited secret agents to monitor the émigrés at large. Overall, the article argues that Austrian policymakers in the aftermath of 1848 invented new policing formulas and reshaped different pre-existing institutions (e.g., consuls, Austrian Lloyd), channelling them against their opponents in exile. Therefore, apart from surveying early modes of international policing, this study also adds to the discussion about Austrian (and European) state-building and, furthermore, to the more specific discussion of how European states dealt with political dissidents abroad in the nineteenth century.