bluuebunny/crossref_metadata_2025 huggingface dataset:
Fasting Status and Circadian Variation Must be Considered When Performing AUC‐based Therapeutic Drug Monitoring of Tacrolimus in Renal Transplant Recipients
Authors: Gustavsen Marte Theie , Midtvedt Karsten , Robertsen Ida , Woillard Jean‐Baptiste , Debord Jean , Klaasen Rolf Anton , Vethe Nils Tore , Bergan Stein , Åsberg Anders
Published: July 2020

Therapeutic drug monitoring (TDM) is mandatory for the immunosuppressive drug tacrolimus (Tac). For clinical applicability, TDM is performed using morning trough concentrations. With recent developments making tacrolimus concentration determination possible in capillary microsamples and Bayesian estimator predicted area under the concentration curve (AUC), AUC‐guided TDM may now be clinically applicable. Tac circadian variation has, however, been reported, with lower systemic exposure following the evening dose. The aim of the present study was to investigate tacrolimus pharmacokinetic (PK) after morning and evening administrations of twice‐daily tacrolimus in a real‐life setting without restrictions regarding food and concomitant drug timing. Two 12 hour tacrolimus investigations were performed; after the morning dose and the following evening dose, respectively, in 31 renal transplant recipients early after transplantation both in a fasting‐state and under real‐life nonfasting conditions (14 patients repeated the investigation). We observed circadian variation under fasting‐conditions: 45% higher peak‐concentration and 20% higher AUC following the morning dose. In the real‐life nonfasting setting, the PK‐profiles were flat but comparable after the morning and evening doses, showing slower absorption rate and lower AUC compared with the fasting‐state. Limited sampling strategies using concentrations at 0, 1, and 3 hours predicted AUC after fasting morning administration, and samples obtained at 1, 3, and 6 hours predicted AUC for the other conditions (evening and real‐life nonfasting). In conclusion, circadian variation of tacrolimus is present when performed in patients who are in the fasting‐state, whereas flatter PK‐profiles and no circadian variation was present in a real‐life, nonfasting setting.
Left‐sided congenitally unguarded tricuspid valve with congenitally corrected transposition of the great arteries: A rare diagnosis confirmed by three‐dimensional echocardiography
Authors: Williams Jason L. , Lockhart John L. , Miller Stephen G. , Barker Piers C. A. , Campbell M. Jay
Published: July 2020

Left‐sided unguarded tricuspid valve disease with congenitally corrected transposition of the great arteries (ccTGA) is a rare cardiac malformation, only reported a few times in the literature. Two‐dimensional echocardiography (2DE) uses standard views to diagnose tricuspid valve disease. Advanced imaging techniques, such as three‐dimensional echocardiography, allow for simultaneous visualization of the tricuspid valve annulus and all leaflets. Three‐dimensional echocardiography (3DE) may be useful in distinguishing unguarded tricuspid valve orifice from other forms of tricuspid valve disease.
Unexpected mechanism of mitral regurgitation in a patient post ALCAPA repair: Added value of three‐dimensional echocardiography
Authors: Danylenko Oleksandr , Surkova Elena , Senior Roxy , Li Wei
Published: July 2020

Accurate assessment of etiology of mitral regurgitation (MR) is one of the key steps in the decision‐making process and further clinical management of patients with severe MR. Our clinical case illustrates the added value of three‐dimensional echocardiography (3DE) in assessment of mitral valve morphology and identification of an unexpected mechanism of MR which was not previously diagnosed using conventional echocardiography. 3DE helped to choose appropriate management strategy in this patient.
A time‐efficient method to determine parameters for measurement of short‐interval intracortical inhibition for quadriceps
Authors: Ruas Cassio V. , Taylor Janet L. , Nosaka Kazunori , Haff G. Gregory , Latella Christopher
Published: July 2020

Short‐interval intracortical inhibition (SICI) is often assessed to investigate inhibitory responses in the primary motor cortex representation of the quadriceps. However, determining appropriate paired‐pulse transcranial magnetic stimulation (TMS) parameters to optimise SICI measurement can be impractical and time‐consuming. This study investigated the intensity required to elicit maximal and 50% of maximum inhibition, and the test‐retest reliability of a time‐efficient approach for SICI measurement in quadriceps. Nine men and six women (26.6 ± 4.4 years) underwent single and paired‐pulse (3‐ms interval) TMS during 10% maximal voluntary isometric contraction on two days. Responses were recorded from vastus lateralis (VL), rectus femoris (RF) and vastus medialis (VM). Test stimulus intensity was 140% of active motor threshold (AMT), and conditioning stimulus intensities (CSIs) ranged from 55% to 90% (eight intensities) of AMT (five test and five paired responses for each intensity). With CSI of 55% AMT, SICI was minimal (conditioned:test motor evoked potential [MEP]; 1.00, 0.96 and 0.95 for VL, RF and VM, respectively, <1.00 indicates inhibition). Inhibition was greater at 70%–90% AMT for VL (0.67–0.85), at 75%–90% AMT for RF (0.70–0.78) and at 80%–90% AMT for VM (0.59–0.68) when compared to 55% AMT. The CSIs that elicited maximal and 50% maximal inhibition were ~84% and ~75% AMT, respectively. Reliability for individual CSIs ranged from “poor‐to‐good” for all muscles. SICI averaged across all CSIs demonstrated “moderate” reliability for VL and VM, but “poor” reliability for RF. This method may offer a practical approach to individualise and select CSIs to investigate quadriceps inhibitory networks in neurophysiological studies.
Photoplethysmographic evaluation of generalized tonic‐clonic seizures
Authors: Mohammadpour Touserkani Fatemeh , Tamilia Eleonora , Coughlin Francesca , Hammond Sarah , El Atrache Rima , Jackson Michele , Bendsen‐Jensen Megan , Kim Boram , Connolly Jack , Manganaro Sheryl , Papadelis Christos , Kapur Kush , Loddenkemper Tobias
Published: July 2020

Objective

Photoplethysmography (PPG) is an optical technique measuring variations of blood perfusion in peripheral tissues. We evaluated alterations in PPG signals in relationship to the occurrence of generalized tonic‐clonic seizures (GTCSs) in patients with epilepsy to evaluate the feasibility of seizure detection.

Methods

During electroencephalographic (EEG) long‐term monitoring, patients wore portable wristband sensor(s) on their wrists or ankles recording PPG signals. We analyzed PPG signals during three time periods, which were defined with respect to seizures detected on EEG: (1) baseline (>30 minutes prior to seizure), (2) preseizure period, and (3) postseizure period. Furthermore, we selected five random control segments during seizure‐free periods. PPG features, including frequency, amplitude, duration, slope, smoothness, and area under the curve, were automatically calculated. We used a linear mixed‐effect model to evaluate changes in PPG features between different time periods in an attempt to identify signal changes that detect seizures.

Results

We prospectively enrolled 174 patients from the epilepsy monitoring unit at Boston Children's Hospital. Twenty‐five GTCSs were recorded from 13 patients. Data from the first recorded GTCS of each patient were included in the analysis. We observed an increase in PPG frequency during pre‐ and postseizure periods that was higher than the changes during seizure‐free periods (frequency increase: preseizure = 0.22 Hz, postseizure = 0.58 Hz vs changes during seizure‐free period = 0.05 Hz). The PPG slope decreased significantly by 56.71 nW/s during preseizure periods compared to seizure‐free periods. Additionally, the smoothness increased significantly by 0.22 nW/s during the postseizure period compared to seizure‐free periods.

Significance

Monitoring of PPG signals may assist in the detection of GTCSs in patients with epilepsy. PPG may serve as a promising biomarker for future seizure detection systems and may contribute to future seizure prediction systems.
Functional and behavioral signatures of Kv7 activator drug subtypes
Authors: Kanyo Richard , Wang Caroline K. , Locskai Laszlo F. , Li Jingru , Allison W. Ted , Kurata Harley T.
Published: July 2020

Objective

Voltage‐gated potassium channels of the KCNQ (Kv7) family are targeted by a variety of activator compounds with therapeutic potential for treatment of epilepsy. Exploration of this drug class has revealed a variety of effective compounds with diverse mechanisms. In this study, we aimed to clarify functional criteria for categorization of Kv7 activator compounds, and to compare the effects of prototypical drugs in a zebrafish larvae model.

Methods

In vitro electrophysiological approaches with recombinant ion channels were used to highlight functional properties important for classification of drug mechanisms. We also benchmarked the effects of representative antiepileptic Kv7 activator drugs using behavioral seizure assays of zebrafish larvae and in vivo Ca2+ imaging with the ratiometric Ca2+ sensor CaMPARI.

Results

Drug effects on channel gating kinetics, and drug sensitivity profiles to diagnostic channel mutations, were used to highlight properties for categorization of Kv7 activator drugs into voltage sensor‐targeted or pore‐targeted subtypes. Quantifying seizures and ratiometric Ca2+ imaging in freely swimming zebrafish larvae demonstrated that while all Kv7 activators tested lead to suppression of neuronal excitability, pore‐targeted activators (like ML213 and retigabine) strongly suppress seizure behavior, whereas ICA‐069673 triggers a seizure‐like hypermotile behavior.

Significance

This study suggests criteria to categorize antiepileptic Kv7 activator drugs based on their underlying mechanism. We also establish the use of in vivo CaMPARI as a tool for screening effects of anticonvulsant drugs on neuronal excitability in zebrafish. In summary, despite a shared ability to suppress neuronal excitability, our findings illustrate how mechanistic differences between Kv7 activator subtypes influence their effects on heteromeric channels and lead to vastly different in vivo outcomes.
Reduced expression of the glucocorticoid receptor in the hippocampus of patients with drug‐resistant temporal lobe epilepsy and comorbid depression
Authors: D’Alessio Luciana , Mesarosova Lucia , Anink Jasper J. , Kochen Silvia , Solís Patricia , Oddo Silvia , Konopka Hector , Iyer Anand M. , Mühlebner Angelika , Lucassen Paul J. , Aronica Eleonora , van Vliet Erwin A.
Published: July 2020

Objective

Depressive disorders are common among about 50% of the patients with drug‐resistant temporal lobe epilepsy (TLE). The underlying etiology remains elusive, but hypothalamus‐pituitary‐adrenal (HPA) axis activation due to changes in glucocorticoid receptor (GR) protein expression could play an important role. Therefore, we set out to investigate expression of the GR in the hippocampus, an important brain region for HPA axis feedback, of patients with drug‐resistant TLE, with and without comorbid depression.

Methods

GR expression was studied using immunohistochemistry on hippocampal sections from well‐characterized TLE patients with depression (TLE + D, n = 14) and without depression (TLE − D, n = 12) who underwent surgery for drug‐resistant epilepsy, as well as on hippocampal sections from autopsy control cases (n = 9). Video–electroencephalography (EEG), magnetic resonance imaging (MRI), and psychiatric and memory assessments were performed prior to surgery.

Results

Abundant GR immunoreactivity was present in dentate gyrus granule cells and CA1 pyramidal cells of controls. In contrast, neuronal GR expression was lower in patients with TLE, particularly in the TLE + D group. Quantitative analysis showed a smaller GR+ area in TLE + D as compared to TLE − D patients and controls. Furthermore, the ratio between the number of GR+/NeuN+ cells was lower in patients with TLE + D as compared to TLE − D and correlated negatively with the depression severity based on psychiatric history. The expression of the GR was also lower in glial cells of TLE + D compared to TLE − D patients and correlated negatively to the severity of depression.

Significance

Reduced hippocampal GR expression may be involved in the etiology of depression in patients with TLE and could constitute a biological marker of depression in these patients.
Emerging role of local and extended range molecular structures on functionalities of topological phases of (Na2O)x(P2O5)100‐x glasses using Raman scattering and modulated DSC
Authors: Mandal Avik , Gogi Vamshi Kiran , Mohanty Chandi , Chbeir Ralph , Boolchand Punit
Published: July 2020

Raman scattering is a powerful probe of local structure (LS) of glasses. In Sodium Phosphate Glasses (SPGs), we show that both LS composed of Qn species and Extended Range Structures (ERS) composed of Long Chains (LCs), Large Rings (LRs), and Small Rings (SRs) can be decoded by Raman scattering. The trimodal distribution of P‐Oterminal stretch modes of Q2 species and P‐Obridging at x < 50% are manifestations of these ERS. These two pairs of triads of modes are uniquely identified with Q2 units present in either LCs, or LRs, or SRs. The existence three phases of c‐NaPO3 composed of 3‐membered rings, 6‐membered rings, and infinitely long chains has facilitated the identification. The Intermediate Phase (IP) in SPGs extends in the 37.5 < x < 46.0% range, the Stressed‐rigid Phase in the 46.0% < x < 50%, and the Flexible Phase in the 18% < x < 37.5% range of soda. We show the IP consists predominantly of LCs (82%), with a minority of LRs (15%) and SRs (3%). The LR‐ and SR‐fractions increase measurably in the non‐IP phases. The structural finding is in harmony with the high configurational entropy of the IP glasses that leads aging to be qualitatively suppressed.
Structure promoted electrochemical behavior and chemical stability of AgI‐doped solid electrolyte in sulfide glass system
Authors: Ma Baochen , Jiao Qing , Zhang Yeting , Lin Changgui , Zhang Xianghua , Ma Hongli , Dai Shixun
Published: July 2020

Ion‐conducting chalcogenide glass is a promising solid electrolyte with excellent conductivity and energy density for all‐solid‐state batteries. A suitable ionic channel for carriers in the amorphous network is urgently needed. In this work, the structural evolution of co‐doped metal cations (Ge and Ga) in the glass matrix and its influence on electrochemical behavior were studied using a series of GexGa16‐xSb64S128‐40AgI glass samples. The macroscopic properties of samples were examined by X‐ray diffraction (XRD), differential scanning calorimetry (DSC), and Raman tests. The electrochemical behavior of samples was investigated by AC impendence spectroscopy and cyclic voltammetry (CV) measurement. Furthermore, a deliquescence experiment was applied for the chemical stability test of glass samples. The ionic conductivity of samples was developed by adding Ga components. Notably, the electrochemical window of electrolytes was remarkably wide at approximately 5 V. The resistance of samples to humidity was characterized by the decreased Raman peaks. Analysis results show that the Ga‐related bonding structure evidently increased the chemical stability compared with the non‐Ga sample. This work provides an insight into the effective and stable ions transport, especially in the Ge(Ga)SbS glass system. These results promote the further investigation of sulfide solid electrolytes and practical application of all‐solid‐state batteries.
Chiropteran metacommunity structure in the Atlantic Forest of South America
Authors: Stevens Richard D. , Stuhler John D. , Grimshaw Jenna R.
Published: July 2020

Aim

Spatial patterns of local species composition are shaped by dispersal ability. Here we examine the effects of dispersal ability on metacommunity structure of bats throughout the Atlantic Forest of South America considering differences among communities, functional groups and species regarding environmental, spatial and connectivity‐related drivers of composition. We also examined phylogenetic and ecological correlates, such as incidence (i.e. frequency of occurrence across sites) and wing morphology, of the degree to which species respond to spatial and environmental drivers.

Location

Atlantic Forest of Argentina, Brazil and Paraguay.

Taxon

Phyllostomid bats.

Methods

Data from the Atlantic Bats dataset were compiled for 39 species at 120 sites. Variation was partitioned into pure environmental, pure space, pure connectivity, joint and unaccounted variation fractions. Redundancy analyses or linear regression determined amount of variation in variation fractions that was accounted for by phylogeny or ecological characteristics of species.

Results

The metacommunity of Atlantic Forest phyllostomid bats was significantly structured by environmental, space and connectivity characteristics. Animalivore, nectarivores and sanguinivore species composition was significantly related only to connectivity. Frugivores exhibited structure that was significantly related to all three kinds of characteristics (pure environmental, pure spatial and pure connectivity) and similar to that of the overall metacommunity. Species‐specific responses to environmental, spatial and connectivity drivers were variable but exhibited strong affinities related to phylogeny and functional group. As incidence of a species increased, variation in distribution and abundance was more related to environmental characteristics. There was no significant relationship between forearm length and magnitude of the connectivity variation partition.

Main Conclusions

Metacommunity structure of bats in the Atlantic Forest is complex and includes variation across multiple scales of ecological organization. Structure is strongly associated with phylogenetic, functional and distributional characteristics of species, with these, in turn, related to responses to spatial and environmental gradients in the Atlantic Forest.
A new system to classify global climate zones based on plant physiology and using high temporal resolution climate data
Authors: Gardner Alexandra S. , Maclean Ilya M. D. , Gaston Kevin J.
Published: July 2020

Aim

Climate classification systems (CCSs) can be used to predict how species’ distributions might be altered by climate change and to increase the reliability of these estimates is an important goal in biogeographical research. We produce an objective, global climate classification system (CCS) at high temporal resolution based on plant physiology as a robust way to predict how climate change may impact terrestrial biomes.

Location

Global

Taxon

Plantae

Methods

We construct ten climate variables that capture the physiological processes that determine plant distributions and use cluster analysis to present a new global CCS which accounts for variation in these aspects of climate. We use Kappa statistics to compare the distribution of climate zones in a five‐ and six‐cluster CCS constructed using the physiology variables to the popular Köppen‐Geiger and Köppen‐Trewartha CCSs, respectively, and find good correlation in both cases.

Results

Our CCS highlights ten climate zones for plants. We show that clustering of the physiologically relevant variables reproduces known, present‐day patterns of vegetation but also indicates important areas where zone assignment in our physiological CCSs is different to that of the Köppen systems.

Main conclusions

The existing Köppen CCSs do not entirely reflect the physiological processes that determine plant distributions. Predictions of climate‐driven changes in plant distributions may thus be unreliable in areas where zone assignment by clustering of physiologically relevant variables is different to that of the Köppen systems. Both the physiological relevance and temporal resolution of climate variables used to construct CCSs should be considered in order to predict reliably how climate change may alter plant distributions and to support an appropriate global response to conserve plant biodiversity for the future.
Catheter ablation of atrial tachycardias after mitral valve surgery: A systematic review and meta‐analysis
Authors: Marazzato Jacopo , Cappabianca Giangiuseppe , Angeli Fabio , Crippa Matteo , Golino Michele , Ferrarese Sandro , Beghi Cesare , De Ponti Roberto
Published: July 2020

Introduction

Data regarding catheter ablation (CA) of atrial tachycardias (ATs) occurring after mitral valve surgery (MVS) are scarce. The aim of this study was to assess the safety and efficacy of CA of ATs in this surgical population through a systematic review of the literature and meta‐analysis.

Methods

A systematic search on PubMed/MEDLINE, EMBASE, and Web of Science was performed considering patients undergoing CA for ATs occurring after MVS. Periprocedural thromboembolic and hemorrhagic complications were assessed. The acute success and maintenance of sinus rhythm (SR) at a mid (<24 months) and long‐term follow‐up (FU) after CA were investigated along with the burden of arrhythmic recurrence at FU.

Results

Fourteen studies for a total of 227 patients were considered. Three‐dimensional (3D) mapping systems were used in all studies. Only two major bleedings were recorded with a pooled estimate of periprocedural major complications of 0%. The acute success after CA was 95% with a clear improvement over time. Although maintenance of SR was 71% at a midterm FU, long‐term efficacy was as low as 47% due to an increased burden of atrial fibrillation (AF) recurrence despite multiple procedures/patient.

Conclusion

In this meta‐analysis, CA of postsurgical ATs after MVS proved safe and effective but with still a significant burden of AF recurrence at more than 24 months of FU due to a progressive atrial substrate deterioration. The improvement of procedural success over time might suggest a learning curve in optimizing the use of 3D mapping systems.
Probability of sinus rhythm conversion and maintenance in cardiac resynchronization therapy patients with atrial fibrillation during 5‐year follow‐up
Authors: Ziegelhoeffer Tibor , Pecha Simon , Rahmani Rilind , Thaqi Nobel , Ackermann Xenia , Hakmi Samer , Choi Yeong‐Hoon , Burger Heiko
Published: July 2020

Introduction

There is a high prevalence of atrial fibrillation (AF) in patients with heart failure presented for cardiac resynchronization therapy (CRT). It remains unclear whether an atrial lead should be implanted in these patients. We, therefore, analyzed outcomes and course of rhythm in AF patients undergoing CRT implantation during long‐term follow‐up.

Methods and Results

Between 2004 and 2018, 328 consecutive patients with a history of AF receiving CRT implantation were included in this study. 132 patients had preoperatively paroxysmal AF (px‐AF), while 70 and 126 patients had persistent AF (ps‐AF) and long‐standing persistent AF (lp‐AF), respectively. The outcome data were collected in our institutional database and analyzed retrospectively.

Two hundred and seventy‐seven patients received an atrial lead at the time of implantation, nine during follow‐up. No major lead implantation‐associated complications were observed. In patients with px‐AF, sinus rhythm (SR) was present in 78.8% at admission, 95.5% (p < .001) at discharge, and 85.7% (p = .965) after 5 years. In ps‐AF patients SR was present in 28.6%, 91.4% (p < .001) and 69.7% (p < .001), while all lp‐AF patients showed AF at admission and had SR rate of 50.8% (p < .001) at discharge and 44.1% after 5 years (p < .001).

Conclusion

We observed a high rate of conversion and long‐term persistence of SR in AF patients undergoing CRT implantation. Due to the low rate of lead implantation‐associated complications and the high successful SR conversion rates, we recommend the implantation of an atrial lead in CRT patients with AF.
Relationship between health‐related quality of life and blood pressure control in patients with uncontrolled hypertension
Authors: Lee Chan Joo , Park Woo Jung , Suh Jung‐Won , Choi Eue‐Keun , Jeon Dong Woon , Lim Sang‐Wook , Kim Dae‐Hyeok , Cha Kwang Soo , Lee Bong‐Ryeol , Kim Nam‐Ho , Kang Tae‐Soo , Ha Jong‐Won
Published: July 2020

We sought to investigate the psychosocial characteristics of patients with uncontrolled hypertension and examine factors that influence blood pressure (BP) control. A total of 1011 patients with uncontrolled hypertension were enrolled in 13 tertiary hospitals. Uncontrolled hypertension was defined as systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg despite on antihypertensive therapy. Socio‐demographics, anthropometrics, behavioral risk factors, medication pattern, adherence, and measures of health‐related quality of life (HRQoL; EuroQol 5D visual analog scale [EQ‐5D VAS]) were assessed at baseline and during follow‐up visits (3 and 6 months). Patients were divided into 2 groups based on BP control status at 6 months (controlled group [n = 532] vs uncontrolled group [n = 367]). There were no differences in clinical characteristics except the proportion of smokers and baseline BP between patients with controlled BP and uncontrolled BP. At 6 months, the adherence of antihypertensive medication did not differ between the groups but the proportion of combination therapy with ≥3 antihypertensives was significantly higher in patients with uncontrolled BP. EQ‐5D VAS at follow‐up was significantly lower in patients with uncontrolled BP despite similar baseline values. Multivariate logistic regression analysis revealed that EQ‐5D VAS at follow‐up significantly correlated with BP control. Patients with worse HRQoL had higher Charlson Comorbidity Index and higher proportion of taking ≥3 antihypertensives, but medication adherence was similar to those with better HRQoL. These findings suggest that along with pharmacologic intervention of hypertension, management of comorbid conditions or psychological support might be helpful for optimizing BP control in patients with uncontrolled hypertension.
LINC00160 mediated paclitaxel‐And doxorubicin‐resistance in breast cancer cells by regulating TFF3 via transcription factor C/EBPβ
Authors: Wu Huaiguo , Gu Juan , Zhou Daoping , Cheng Wei , Wang Yueping , Wang Qingping , Wang Xuedong
Published: July 2020

Chemoresistance represents a major challenge in breast cancer (BC) treatment. This study aimed to probe the roles of LINC00160 in paclitaxel‐ and doxorubicin‐resistant BC cells. Three pairs of BC and adjacent normal tissue were used for lncRNA microarray analysis. Paclitaxel‐resistant MCF‐7 (MCF‐7/Tax) and doxorubicin‐resistant BT474 (BT474/Dox) cells were generated by exposure of parental drug‐sensitive MCF‐7 or BT474 cells to gradient concentrations of drugs. Correlation between LINC00160 expression and clinical response to paclitaxel in BC patients was examined. Short interfering RNAs specifically targeting LINC00160 or TFF3 were designed to construct LINC00160‐ and TFF3‐depleted BC cells to discuss their effects on biological episodes of MCF‐7/Tax and BT474/Dox cells. Interactions among LINC00160, transcription factor C/EBPβ and TFF3 were identified. MCF‐7/Tax and BT474/Dox cells stable silencing of LINC00160 were transplanted into nude mice. Consequently, up‐regulated LINC00160 led to poor clinical response to paclitaxel in BC patients. LINC00160 knockdown reduced drug resistance in MCF‐7/Tax and BT474/Dox cells and reduced cell migration and invasion. LINC00160 recruited C/EBPβ into the promoter region of TFF3 and increased TFF3 expression. LINC00160‐depleted MCF‐7/Tax and BT474/Dox cells showed decreased tumour growth rates in nude mice. Overall, we identified a novel mechanism of LINC00160‐mediated chemoresistance via the C/EBPβ/TFF3 axis, highlighting the potential of LINC00160 for treating BC with chemoresistance.
SNPs in SNCA, MCCC1, DLG2, GBF1 and MBNL2 are associated with Parkinson's disease in southern Chinese population
Authors: Zhao Aonan , Li Yuanyuan , Niu Mengyue , Li Guanglu , Luo Ningdi , Zhou Liche , Kang Wenyan , Liu Jun
Published: July 2020

Numerous single nucleotide polymorphisms (SNPs), which have been identified as susceptibility factors for Parkinson's disease (PD) as per genome‐wide association studies, have not been fully characterized for PD patients in China. This study aimed to replicate the relationship between 12 novel SNPs of 12 genes and PD risk in southern Chinese population. Twelve SNPs of 12 genes were detected in 231 PD patients and 249 controls, using the SNaPshot technique. Meta‐analysis was used to assess heterogeneity of effect sizes between this study and published data. The impact of SNPs on gene expression was investigated by analysing the SNP‐gene association in the expression quantitative trait loci (eQTL) data sets. rs8180209 of SNCA (allele model: P = .047, OR = 0.77; additive model: P = .047, OR = 0.77), rs2270968 of MCCC1 (dominant model: P = .024, OR = 1.52), rs7479949 of DLG2 (recessive model; P = .019, OR = 1.52), rs10748818 of GBF1 (additive model: P < .001, OR = 0.37), and rs4771268 of MBNL2 (recessive model: P = .003, OR = 0.48) were replicated to be significantly associated with the increased risk of PD. Noteworthy, a meta‐analysis of previous studies suggested rs8180209, rs2270968, rs7479949 and rs4771268 were in line with those of our cohort. Our study replicated five novel functional SNPs in SNCA, MCCC1, DLG2, GBF1 and MBNL2 could be associated with increased risk of PD in southern Chinese population.
Safely finishing a half marathon by an adult with type 1 diabetes using a commercially available hybrid closed‐loop system
Authors: van den Boom Louisa , Ziko Haris , Mader Julia K
Published: July 2020

Glycemic targets are often difficult to achieve in people with type 1 diabetes, especially during exercise. Consequently, many people with type 1 diabetes avoid sports as a result of fear of hypoglycemia. Strenuous physical activity, such as a half marathon, imposes difficulties on people with type 1 diabetes. The first commercial hybrid closed‐loop (HCL) system with the potential to facilitate better diabetes management during exercise has recently been marketed. So far, no data on HCL performance during strenuous exercise have been published. A woman with well‐controlled type 1 diabetes participated in and safely finished a half marathon while undergoing HCL therapy. HCL could safely establish glycemic control without causing either hypo‐ or relevant hyperglycemia, and without the need for rescue carbohydrates while running. In the days after the half marathon, there was no change in glycemic control compared with the period before.
Length measurement accuracy of adaptive resolution imaging sonar and a predictive model to assess adult Atlantic salmon (Salmo salar) into two size categories with long‐range data in a river
Authors: Helminen Jani , Dauphin Guillaume J. R. , Linnansaari Tommi
Published: July 2020

Imaging sonars are used around the world for fish population monitoring. The accuracy of the length measurements has been reported in multiple studies for relatively short (<15 m) ranges and high image resolution. However, imaging sonars are often used at longer ranges (i.e., >15 m) where the images produced from sonar returns become less detailed. The accuracy of the length measurements from the Adaptive Resolution Imaging Sonar (ARIS) was tested by releasingn= 69 known‐sized adult Atlantic salmon (Salmo salar) directly into the sonar field at ranges between 15 and 29 m, and measuring their echoes manually by four users and semi‐automatically using a computer workflow in Echoview software. Overall, the length measurements were very variable: compared to true (fork) lengths, the mean of differences varied between −9.9 cm and 7.8 cm in the human‐generated datasets, and between −42.8 cm and −20 cm in the computer‐generated dataset. In addition, the length measurements in different datasets were only in poor or moderate agreement with each other (intraclass correlation <0.61). Contrary to our expectations, the distance from the transducer or the subjectively assessed echo quality did not have an effect on the measurement accuracy in most of the datasets and when it did, the effect was not systematic between the datasets. Therefore, a size class and length prediction model was implemented in a Bayesian framework to group salmon into two size categories: One‐Sea‐Winter (<63 cm) and Multi‐Sea‐Winter (≥63 cm) groups. The model correctly predicted the size category in 83% of the fish in the computer‐generated dataset and ranged from 68% to 74% in the human‐generated datasets. We conclude that fish length measurements derived from long‐range imaging sonar data should be used with caution, but post‐processing can improve the usefulness of the data for specific purposes, such as adult Atlantic salmon population monitoring.
Adjuvant transarterial chemoembolization to sorafenib in unresectable hepatocellular carcinoma: A meta‐analysis
Authors: Chen Anxin , Li Shijie , Yao Zhiyuan , Hu Jiahao , Cao Jiasheng , Topatana Win , Juengpanich Sarun , Yu Hong , Shen Jiliang , Chen Mingyu
Published: July 2020

Background and Aim

An increasing number of transarterial chemoembolization (TACE) plus sorafenib combination therapy has been applied for unresectable hepatocellular carcinoma (HCC). However, it remains controversial whether combination therapy is superior to sorafenib monotherapy. Therefore, we aimed to perform a meta‐analysis to evaluate the efficacy and safety of the combination therapy of TACE plus sorafenib for unresectable HCC.

Methods

This meta‐analysis was based on the relative outcomes from a specific search of online databases between January 2008 and November 2019, and subgroup analyses were conducted to identify potential predictive factors.

Results

A total of 3868 patients (TACE plus sorafenib vs sorafenib, 1181 vs 2687) were identified from nine studies, including one randomized controlled trial and eight retrospective cohort studies. The pooled results revealed that TACE plus sorafenib combination therapy significantly improves overall survival with the combined hazard ratio 0.74 (95% confidence interval [CI] = 0.66–0.84, P < 0.001), time to progression (hazard ratio = 0.73, 95%CI = 0.65–0.82, P < 0.001), and objective response rate (odds ratio = 2.19, 95% CI = 1.31–3.66, P = 0.003). Subgroup analysis indicated that patients who developed macrovascular invasion achieve significantly great overall survival (P for interaction = 0.001) with combination therapy, in contrast to nonmacrovascular invasion patients. In addition, no significant differences in adverse events were observed.

Conclusion

This meta‐analysis demonstrated that TACE plus sorafenib combination therapy is superior to sorafenib monotherapy and should be recommended as an optimal treatment choice for unresectable HCC.
Freedom and struggling openly in psychotherapy: A qualitative inquiry with LGBQ young adults from religious families
Authors: Heiden‐Rootes Katie , Ross Kristin , Moore Rachel , Hasan Shah , Gulotta Samantha
Published: July 2020

Lesbian, gay, bisexual, and queer (LGBQ) young people from religious families are at increased risk of family rejection, poor mental health outcomes, and are overrepresented in mental health services. This article describes a two‐part qualitative study aimed at exploring the experiences of LGBQ young adults from religious families in psychotherapy, identifying positive and negative psychotherapy experiences, and understanding the influence of family and religion on the psychotherapy experience. Data were collected through a web‐based survey (n = 77) and interviews (n = 7) with LGBQ young adults (ages 18–25) from religious families. The study followed an interpretative phenomenological approach. Integrated results found often invisible, relational therapy processes, and religious discourses as significant to LGBQ young people who seek psychotherapy. Implications for future research, effective systemic family therapy practices with LGBQ young people from religious families, and a critique on ethical and legal limits of confidentiality with policy implications are outlined.
Anxiety and Depression of Nurses in a North West Province in China During the Period of Novel Coronavirus Pneumonia Outbreak
Authors: Han Lin , Wong Frances Kam Yuet , She Dong Li M , Li Si Yan , Yang Yun Fang , Jiang Meng Yao , Ruan Yue , Su Qian , Ma Yuxia , Chung Loretta Yuet Foon
Published: July 2020

Purpose

To investigate the anxiety and depression levels of frontline clinical nurses working in 14 hospitals in Gansu Province, China, during this period.

Design

A cross‐sectional survey was conducted online between February 7 and 10, 2020, with a convenience sample of 22,034 nurses working in 14 prefecture and city hospitals in Gansu Province, located in northwest China.

Methods

A self‐reported questionnaire with four parts (demographic characteristics, general questions related to novel coronavirus‐infected pneumonia, self‐rating anxiety scale, and self‐rating depression scale) was administered. Descriptive statistics including frequencies, means, and SDs were computed. The associations between anxiety and depression with sociodemographic characteristics, work‐related concerns, and impacts were analyzed, followed by multiple stepwise linear regression to identify factors that best predicted the nurses’ anxiety and depression levels.

Findings

A total of 21,199 questionnaires were checked to be valid, with an effective recovery rate of 96.21%. The mean ± SD age of the respondents was 31.89 ± 7.084 years, and the mean ± SD length of service was 9.40 ± 7.638 years. The majority of the respondents were female (98.6%) and married (73.1%). Some demographic characteristics, related concerns, and impacts of COVID‐19 were found to be significantly associated with both anxiety (p < .001) and depression (p < .001). Nurses who needed to take care of children or elderly relatives, took leave from work because they were worried about COVID‐19, avoided contact with family and friends, and wanted to obtain more COVID‐19‐related knowledge had higher levels of both anxiety and depression.

Conclusions

Results show that nurses faced with the COVID‐19 outbreak are at risk for experiencing anxiety and depression. Demographic background, psychosocial factors, and work‐related factors predicted the psychological responses. The family responsibilities and burdens of women may explain the higher levels of anxiety and depression among nurses with these obligations as compared to those without. On the other hand, nurses who chose not to take leave from work or who did not avoid going to work during this period were less anxious and depressed.

Clinical Relevance

Professional commitment might be a protective factor for adverse psychological responses. It is pertinent to provide emotional support for nurses and recognize their professional commitment in providing service to people in need.
Induction of allergic contact dermatitis and pervasive face edema due to Brazilian keratin treatment
Authors: Celik Ebru , Esin Korkmaz Kubra , Dogramaci Asena Cigdem
Published: July 2020

Brazilian keratin treatment (BKT) is a prevalent hair straightening method widely used by women in the world. The degree of concentration of formaldehyde safe for sensitive patients is still obscure. Report claims that these products contain intolerably high levels of formaldehyde. Yet, hair straightening products may lead to severe allergic contact dermatitis, by means of the responsible allergens such as formaldehyde and its releasers. This case report presents the case of a 37‐year‐old female patient developing extensive edema of the face and acute inflammatory changes in the scalp from chemical‐induced irritation, on the day following the application of BKT to straighten her hair.
Measuring Mutual Fund Flow Pressure as Shock to Stock Returns
Authors: WARDLAW MALCOLM
Published: July 2020

A large and rapidly growing literature examines the impact of misvaluation on firm policies by using mutual fund outflow‐induced price pressure to isolate nonfundamental price variation. I demonstrate that the standard approach to computing outflow‐induced price pressure produces a measure that is inadvertently a direct function of a stock's actual realized return during the outflow quarter, raising doubts about its orthogonality to fundamentals. After removing these direct measurements of return, outflows generate a fairly negligible quarterly decline in returns, with no subsequent reversal, and many established results in this literature no longer hold. I provide suggestions for future analysis.
The link between vitamin D and COVID‐19: distinguishing facts from fiction
Authors: Bergman P.
Published: July 2020

Click here to view the Perspective by Rhodes et al.
The Mobilization of Noncooperative Spaces: Reflections from Rohingya Refugee Camps
Authors: Chowdhury Rashedur
Published: July 2020

In this essay, I challenge key assumptions in the mainstream entrepreneurship literature that individuals have the capability to change their fate through entrepreneurial activities wherever in the world they may be. I advance the concept of a coordinated and regulative cooperative market to argue that the rebalancing of power between marginalized actors such as refugees and ordinary locals, and powerful agents of what I term the ‘uncooperative sociostructure’ is essential in order to improve the wellbeing of refugees. Without a cooperative sociostructural intervention, capitalistic market mechanisms such as bottom of the pyramid (BoP) and microfinance as means to individual freedom simply imprison refugees further.
Patch‐level facilitation fosters high‐Andean plant diversity at regional scales
Authors: Gavini Sabrina S. , Ezcurra Cecilia , Aizen Marcelo A.
Published: July 2020

Aim

Local effects of ecosystem engineers on biodiversity can scale up to the landscape level, stressing the importance of ecological processes as determinants of species richness at larger spatial scales. In harsh environments, cushion plants often act as ecosystem engineers given their ability to buffer extreme abiotic conditions, thus providing unique and more favorable niches for the establishment of less stress‐tolerant plant species. We assessed if facilitation by cushion plants influences patterns of plant diversity at increasing spatial scales.

Location

Northern Patagonian Andes, Argentina.

Methods

Based on plant species records within and outside cushions, we compared plant diversity in the presence and absence of cushions at the community, mountain and regional scale. Specifically, observed and estimated numbers of species occurring in either cushion plants or in the surrounding open areas were compared with the species numbers of the open areas.

Results

The presence of cushion plants significantly increased species richness at all spatial levels analyzed. At the patch level, a higher number of species was recorded growing within cushion plants than in open area plots of similar size. Consistently, hypothetical communities lacking cushion plants showed significantly lower species richness than observed communities with cushion plants. These differences in species richness at patch and community scales increased with altitude, hence facilitation by cushion plants became more important at higher elevations. Moreover, according to asymptotic non‐parametric estimators, cushion plants could increase overall regional species richness up to 40%.

Conclusions

Our findings suggest that about one third of the high‐Andean flora of the region owes its presence to the existence of nursing plants, defying the view that abiotic factors alone are enough to fully determine species occurrences at large spatial scales. This study provides evidence that local‐scale ecological processes can be crucial in promoting and maintaining biodiversity at any spatial scale.
MR elastography‐based liver fibrosis correlates with liver events in nonalcoholic fatty liver patients: A multicenter study
Authors: Han Ma Ai Thanda , Vipani Aarshi , Noureddin Nabil , Ramirez Kim , Gornbein Jeffrey , Saouaf Rola , Baniesh Nader , Cummings‐John Oladuni , Okubote Toluwalase , Setiawan Veronica Wendy , Rotman Yaron , Loomba Rohit , Alkhouri Naim , Noureddin Mazen
Published: July 2020

Background & Aims

Liver fibrosis assessed by liver biopsy is predictive of clinical liver events in patients with nonalcoholic fatty liver disease (NAFLD). Magnetic resonance elastography (MRE) correlates with liver biopsy in assessing liver fibrosis. However, data assessing the relationship between MRE and clinical liver events are lacking. We investigated the association between MRE and clinical liver events/death and identified the cut‐off to predict clinical liver events in NAFLD patients.

Methods

We conducted a multicenter retrospective study of NAFLD patients who underwent MRE between 2016 and 2019. Clinical liver events were defined as decompensation events and death. We categorized patients into noncirrhosis, compensated cirrhosis and decompensated cirrhosis. Fisher's exact test was used to test association strength. Receiver operative curve methods were used to determine the optimal cut‐off of MRE liver stiffness and to maximize the accuracy for classifying noncirrhosis, compensated cirrhosis and decompensated cirrhosis. Logistic regression modelling was used to predict decompensation.

Results

The study included 320 NAFLD patients who underwent MRE. The best threshold for distinguishing cirrhosis from noncirrhosis was 4.39 kPa (AUROC 0.92) and from decompensated cirrhosis was 6.48 kPa (AUROC 0.71). Odds of decompensation increased as liver stiffness increased (OR 3.28) (P < .001). Increased liver stiffness was associated with ascites, hepatic encephalopathy, oesophageal variceal bleeding and mortality (median 7.10, 10.15 and 10.15 kPa respectively).

Conclusion

In NAFLD patients, liver stiffness measured by MRE with a cut‐off of ≥6.48 kPa is associated with decompensation and mortality, and specific MRE cut‐offs are predictive of individual clinical liver events.
High‐protein diet more effectively reduces hepatic fat than low‐protein diet despite lower autophagy and FGF21 levels
Authors: Xu Chenchen , Markova Mariya , Seebeck Nicole , Loft Anne , Hornemann Silke , Gantert Thomas , Kabisch Stefan , Herz Kathleen , Loske Jennifer , Ost Mario , Coleman Verena , Klauschen Frederick , Rosenthal Anke , Lange Volker , Machann Jürgen , Klaus Susanne , Grune Tilman , Herzig Stephan , Pivovarova‐Ramich Olga , Pfeiffer Andreas F. H.
Published: July 2020

Background and aims

Non‐alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent and nutrition intervention remains the most important therapeutic approach for NAFLD. Our aim was to investigate whether low‐ (LP) or high‐protein (HP) diets are more effective in reducing liver fat and reversing NAFLD and which mechanisms are involved.

Methods

19 participants with morbid obesity undergoing bariatric surgery were randomized into two hypocaloric (1500‐1600 kcal/day) diet groups, a low protein (10E% protein) and a high protein (30E% protein), for three weeks prior to surgery. Intrahepatic lipid levels (IHL) and serum fibroblast growth factor 21 (FGF21) were measured before and after the dietary intervention. Autophagy flux, histology, mitochondrial activity and gene expression analyses were performed in liver samples collected during surgery.

Results

IHL levels decreased by 42.6% in the HP group, but were not significantly changed in the LP group despite similar weight loss. Hepatic autophagy flux and serum FGF21 increased by 66.7% and 42.2%, respectively, after 3 weeks in the LP group only. Expression levels of fat uptake and lipid biosynthesis genes were lower in the HP group compared with those in the LP group. RNA‐seq analysis revealed lower activity of inflammatory pathways upon HP diet. Hepatic mitochondrial activity and expression of β‐oxidation genes did not increase in the HP group.

Conclusions

HP diet more effectively reduces hepatic fat than LP diet despite of lower autophagy and FGF21. Our data suggest that liver fat reduction upon HP diets result primarily from suppression of fat uptake and lipid biosynthesis.