bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of BDNF in the pathophysiology and treatment of depression: Activity‐dependent effects distinguish rapid‐acting antidepressants
Authors: Duman Ronald S. , Deyama Satoshi , Fogaça Manoela Viar
Published: December 2019

The pathophysiology and treatment of depression have been the focus of intense research and while there is much that remains unknown, modern neurobiological approaches are making progress. This work demonstrates that stress and depression are associated with atrophy of neurons and reduced synaptic connectivity in brain regions such as the hippocampus and prefrontal cortex that contribute to depressive behaviors, and conversely that antidepressant treatment can reverse these deficits. The role of neurotrophic factors, particularly brain‐derived neurotrophic factor (BDNF), has been of particular interest as these factors play a key role in activity‐dependent regulation of synaptic plasticity. Here, we review the literature demonstrating that exposure to stress and depression decreases BDNF expression in the hippocampus and PFC and conversely that antidepressant treatment can up‐regulate BDNF in the adult brain and reverse the effects of stress. We then focus on rapid‐acting antidepressants, particularly the NMDA receptor antagonist ketamine, which produces rapid synaptic and antidepressant behavioral actions that are dependent on activity‐dependent release of BDNF. This rapid release of BDNF differs from typical monoaminergic agents that require chronic administration to produce a slow induction of BDNF expression, consistent with the time lag for the therapeutic action of these agents. We review evidence that other classes of rapid‐acting agents also require BDNF release, demonstrating that this is a common, convergent downstream mechanism. Finally, we discuss evidence that the actions of ketamine are also dependent on another growth factor, vascular endothelial growth factor (VEGF) and its complex interplay with BDNF.
The dentate gyrus in depression
Authors: Umschweif Gali , Greengard Paul , Sagi Yotam
Published: December 2019

Extensive preclinical research has been conducted in recent years to reveal the cell types, neuronal circuits and molecular and morphological changes implicated in the function of the dentate gyrus in depression. This was profoundly facilitated by the emergence of methods such as gene targeting, neuronal cell activity manipulation, including optogenetics and chemogenetics, and the development of novel RNA sequencing technology and powerful MRI imagers that were used in clinical studies. These advancements provided researchers with the precise skills needed to evaluate the changes in the dentate gyrus structure and cell function in rodent models as well as in brains of depressed and medicated patients. Here, we review these latest findings and discuss the existing gaps in our knowledge of the role of the dentate gyrus in depression and in mediating the response to antidepressant therapies.
Using time‐series analysis techniques to enhance the understanding of musculoskeletal injury in Thoroughbred racehorses
Authors: Johnston Anna S. , Riggs Christopher M. , Cogger Naomi , Benschop Jackie , Rogers Chris W. , Rosanowski Sarah M.
Published: December 2019

Background

Many racing jurisdictions monitor race‐day musculoskeletal injury (MSI) but fail to evaluate injuries occurring during training. Additionally, previous risk factor analyses have failed to explore temporal trends in injury occurrence.

Objectives

To use time‐series analysis techniques to identify trends, cyclicity and peaks in MSI incidence, in racehorses training and racing at the Hong Kong Jockey Club (HKJC) from July 2010 to June 2018.

Study design

Retrospective longitudinal study.

Methods

The monthly incidence of all MSI, superficial digital flexor tendon (SDFT) injury, suspensory ligament injury and appendicular skeletal fracture occurring in training and racing were collected from veterinary records. The number of horses in training was collated monthly from trainer records. Time‐series analysis techniques were used to describe trends and cyclical patterns for injury types. For each injury, incidence risks above the 90th percentile were identified as peaks in incidence.

Results

A total of 1471 injuries were recorded over eight racing seasons; 605 fractures (41.1%), 550 SDFT injuries (37.4%), and 316 suspensory ligament injuries (21.5%). Evidence of seasonality was detected in fracture incidence risk; increasing from October (median 0.25 per 1000 horses) until May (median 0.71 per 1000 horses), coinciding with the racing season (ending mid‐July). Elevated incidence of MSI occurred throughout 2012; however, the greatest incidence risks of SDFT (14.8 per 1000 horses) and fracture (1.3 per 1000 horses) occurred since 2017.

Main limitations

Monthly (opposed to daily) incidence risk of injury reduced the resolution of the data. Additionally, fracture was not described according to bone or fracture type, which may have confounded overall trends.

Conclusions

Evidence for seasonal variation in the incidence of fracture occurrence has been demonstrated. Based on using time‐series techniques, further epidemiological studies, retrospectively targeting periods of high peaks in injury incidence risk could be used to aid identification of risk factors for injury.
Probing structural changes during amyloid aggregation of the sweet protein MNEI
Authors: Donnarumma Federica , Leone Serena , Delfi Masoud , Emendato Alessandro , Ami Diletta , Laurents Douglas V. , Natalello Antonino , Spadaccini Roberta , Picone Delia
Published: December 2019

Protein self‐assembly is a ubiquitous phenomenon, traditionally studied for its links to amyloid pathologies, which has also gained attention as its physiological roles and possible biotechnological applications emerged over time. It is also known that varying the conditions to which proteins are exposed can lead to aggregate polymorphism. To understand the factors that trigger aggregation and/or direct it toward specific outcomes, we performed a multifaceted structural characterization of the thermally induced self‐assembly process of MNEI, a model protein able to form amyloid aggregates under nondenaturing conditions. MNEI is also known for its extreme sweetness which, combined with a considerable thermal stability, makes the protein a promising alternative sweetener. Fourier‐transformed infrared spectroscopy and electron microscopy data showed that the presence of NaCl accelerates the kinetics of fibrillar aggregation, while disfavoring the population of off‐pathway states that are instead detected by native gel electrophoresis at low ionic strength. NMR studies revealed how NaCl modulates the self‐assembling mechanism of MNEI, switching the process from soluble oligomeric forms to fibrils. Comparative analysis demonstrated that the presence of NaCl induces local differences in the protein dynamics and surface accessibility, without altering the native fold. We identified the regions most affected by the presence of NaCl, which control the aggregation process, and represent hot spots on the protein surface for the rational design of new mutants with controlled aggregation propensity.
Light and warming drive forest understorey community development in different environments
Authors: Blondeel Haben , Perring Michael P. , Depauw Leen , De Lombaerde Emiel , Landuyt Dries , De Frenne Pieter , Verheyen Kris
Published: December 2019

Plant community composition and functional traits respond to chronic drivers such as climate change and nitrogen (N) deposition. In contrast, pulse disturbances from ecosystem management can additionally change resources and conditions. Community responses to combined environmental changes may further depend on land‐use legacies. Disentangling the relative importance of these global change drivers is necessary to improve predictions of future plant communities. We performed a multifactor global change experiment to disentangle drivers of herbaceous plant community trajectories in a temperate deciduous forest. Communities of five species, assembled from a pool of 15 forest herb species with varying ecological strategies, were grown in 384 mesocosms on soils from ancient forest (forested at least since 1850) and postagricultural forest (forested since 1950) collected across Europe. Mesocosms were exposed to two‐level full‐factorial treatments of warming, light addition (representing changing forest management) and N enrichment. We measured plant height, specific leaf area (SLA) and species cover over the course of three growing seasons. Increasing light availability followed by warming reordered the species towards a taller herb community, with limited effects of N enrichment or the forest land‐use history. Two‐way interactions between treatments and incorporating intraspecific trait variation (ITV) did not yield additional inference on community height change. Contrastingly, community SLA differed when considering ITV along with species reordering, which highlights ITV’s importance for understanding leaf morphology responses to nutrient enrichment in dark conditions. Contrary to our expectations, we found limited evidence of land‐use legacies affecting community responses to environmental changes, perhaps because dispersal limitation was removed in the experimental design. These findings can improve predictions of community functional trait responses to global changes by acknowledging ITV, and subtle changes in light availability. Adaptive forest management to impending global change could benefit the restoration and conservation of understorey plant communities by reducing the light availability.
Rust and reinvention: Im/migration and urban change in the American Rust Belt
Authors: Pottie‐Sherman Yolande
Published: December 2019

Immigration represents a promising counternarrative for Rust Belt cities in the 21st century. Increasingly, both immigrants and refugees are part of the comeback stories of Northeastern and Midwestern cities from Buffalo to Dayton and Pittsburgh. This review explores recent research in urban geography and allied disciplines focusing on the international migration patterns, processes, and politics reshaping the urban geography of the American Rust Belt. Recent research sheds crucial light on how im/migrant lives are reshaping urban landscapes of Rust Belt cities, and conversely, how local immigration policies in these cities are rearranging the uneven geographies of immigrant receptivity across the United States. Overall, this review highlights the limitations of the singular spatial imaginary of the Rust Belt advanced previously by many urbanists. Rather, this review illustrates the rich, complex, and tangled contemporary spatial nuances associated with international migration in this region. These spatial nuances are complicated by increasingly exclusionary immigration policy and rhetoric at the federal level since January of 2017.
Content Validity of HIT‐6 as a Measure of Headache Impact in People With Migraine: A Narrative Review
Authors: Houts Carrie R. , Wirth R.J. , McGinley James S. , Gwaltney Chad , Kassel Eric , Snapinn Steven , Cady Roger
Published: December 2019

Background

The short‐form Headache Impact Test (HIT‐6) is a widely used patient‐reported outcome measure that assesses the negative effects of headaches on normal activity. It was developed using the general headache population and prior to the establishment of the now well‐accepted FDA patient‐reported guidance.

Objective

The objective of this narrative review was to examine existing qualitative research in patients with migraine and headache, providing insight into the relevance and meaningfulness of HIT‐6 items to the lives of migraine patients.

Methods

Articles were identified through database searches (National Library of Medicine and Google Scholar) and review of reference lists of candidate articles.

Results

A total of 3227 articles were identified through database and hand searching. Of these, 12 contained patient‐ or expert‐generated qualitative information regarding headache patients’ experience (8 specific to migraine [episodic and chronic] patients and 4 citing general headache patients). The combined publications described a total of 283 patient interviews. Overarching themes and specific information were identified that provide support of the relevance of content for each HIT‐6 item to migraine patients’ lives. Identified effects of headaches on patients with migraine included limitations in daily activities, needing to lie down during headaches, feeling tired, being irritated by headaches, difficulty concentrating, and the experience of pain. Further, previous research specific to the HIT‐6 indicated that patients understood the instructions, items, and response scales as intended by the instrument authors.

Conclusions

This narrative literature review demonstrates qualitative research support for the relevance of the items of the HIT‐6 in migraine patients, supporting its ongoing use in clinical migraine research and practice.
Root canal obturation materials and filling techniques for primary teeth: In vitro evaluation in polymer‐based prototyped incisors
Authors: Aragão Amanda Carneiro , Pintor Andréa Vaz Braga , Marceliano‐Alves Marília , Primo Laura Guimarães , Silva Aline Saddock de Sá , Lopes Ricardo Tadeu , Neves Aline de Almeida
Published: December 2019

Background

Achieving a void‐free root canal filling is a challenge in current clinical pulpectomy practice.

Aim

To compare filling effectiveness and internal voids of root filling materials and obturation techniques in resin‐prototyped primary incisors by micro‐CT.

Design

Fifty prototypes were instrumented and randomly divided (n = 10) according to the filling materials (Vitapex®, ZOE, Calcicur®, Feapex, and Calen®‐ZO) and obturation technique: lentulo or pressure syringe (n = 5). The specimens were micro‐CT scanned (pixel size = 7.83 μm) and reconstructed, and the total volume of filled canal (%FC) and internal voids (%IV) of the bulk filling material was calculated. Kruskal‐Wallis and Mann‐Whitney tests were used to detect differences and interactions among groups.

Results

Calen®‐ZO, Vitapex®, and ZOE showed similar %FC. Calcicur® showed lower %FC compared with Calen®‐ZO, Vitapex®, and ZOE (P < .05) but similar to Feapex. No statistically significant differences in %FC between lentulo or pressure syringe were disclosed. Regarding %IV, Vitapex®, and Calen®‐ZO performed better with syringe, although Calcicur® was better with lentulo. The number of voids in the obturation bulk was similar among materials, but always lower (P < .05) in syringe filled specimens.

Conclusion

Vitapex®, Calen®‐ZO, and ZOE outperformed Calcicur® and Feapex in %FC and if the syringe technique is used, %IV of the obturation bulk and presence of defects was lower.
New apatite‐type phosphor Ca9La(PO4)5(SiO4)F2:Tb3+,Dy3+ with improved color rendering index
Authors: Zhang Yuanyuan , Mei Lefu , Aksenov Sergey M. , Deyneko Dina , Liu Haikun , Zhang Dian , Huang Zhaohui
Published: December 2019

Ca9La(PO4)5(SiO4)F2:Tb3+,Dy3+ (CLPSF:Tb3+,Dy3+) phosphors were successfully prepared using the traditional solid‐state technique. The crystal structure was refined and the luminescence properties have been examined in detail. The band gap and electronic structure of Ca9La(PO4)5(SiO4)F2 were performed by the periodic density functional theory (DFT) calculation. The spectral and fluorescence decay dynamics of CLPSF:Tb3+,Dy3+ show that the energy transfer behavior between Tb3+ and Dy3+ ions is observed. The CLPSF:Tb3+,Dy3+ phosphors can be efficiently excitable at the wavelengths range from 300 to 500 nm. The emission spectrum covers the whole visible part of the spectra with the sharp emission bands in red, green, and blue regions. The correlated color temperature (CCT) and color rendering index (CRI) of white light emission could be improved by the fine‐tuning of the Tb3+ and Dy3+ ions ration in accordance with the energy transfer behavior. Thus, the CLPSF:Tb3+,Dy3+ phosphor could be used as a material for the near‐ultraviolet (n‐UV) and white light‐emitting diodes (w‐LEDs).
Circulating exosome‐derived bona fide long non‐coding RNAs predicting the occurrence and metastasis of hepatocellular carcinoma
Authors: Lu Yunjie , Duan Yunfei , Xu Qinghua , Zhang Li , Chen Weibo , Qu Zhen , Wu Baoqiang , Liu Wensong , Shi Longqing , Wu Di , Yang Yan , Sun Donglin , Chen Xuemin
Published: December 2019

Although the diagnosis and therapy approach developed, techniques for the early diagnosis of HCC remain insufficient which results in poor prognosis of patients. The traditional biomarker AFP, however, has been proved with low specificity. Circulating exosomal ncRNAs revealed different profiles reflecting the characteristics of tumour. In this study, we mainly focused on circulating exosomal ncRNAs which might be the fingerprint for HCC, especially for the diagnosis or metastasis prediction. A high throughput lncRNA microarray in exosomes extracted from cell‐free plasma was applied. The risk score analysis was employed to screen the potential exosome‐derived lncRNAs in two independent sets based on different clinical parameters in 200 paired HCC patients. After a multi‐stage validation, we finally revealed three lncRNAs, ENSG00000248932.1, ENST00000440688.1 and ENST00000457302.2, increased in HCC comparing with the both chronic hepatitis (CH) patients and cancer‐free controls. ROC curve revealed a higher sensitivity and specificity in predicting the occurrence of HCC from cancer‐free controls and CH patients with the area under curve (AUC) of 0.905 and 0.879 by combining AFP. The three lncRNA panel combined with AFP also indicted a fingerprint function in predicting the metastasis of HCC with the AUC of 0.870. In conclusion, ENSG00000248932.1, ENST00000440688.1 and ENST00000457302.2 might be the potential biomarker for the tumorigenesis prediction from CH patients or healthy controls and may also be applied for dynamic monitoring the metastasis of HCC.
Fuziline alleviates isoproterenol‐induced myocardial injury by inhibiting ROS‐triggered endoplasmic reticulum stress via PERK/eIF2α/ATF4/Chop pathway
Authors: Fan Cai‐lian , Yao Zhi‐hong , Ye Meng‐nan , Fu Lei‐lei , Zhu Guo‐nian , Dai Yi , Yao Xin‐sheng
Published: December 2019

Fuziline, an aminoalcohol‐diterpenoid alkaloid derived fromAconiti lateralisradix preparata, has been reported to have a cardioprotective activity in vitro. However, the potential mechanism of fuziline on myocardial protection remains unknown. In this study, we aimed to explore the efficacy and mechanism of fuziline on isoproterenol (ISO)‐induced myocardial injury in vitro and in vivo. As a result, fuziline effectively increased cell viability and alleviated ISO‐induced apoptosis. Meanwhile, fuziline significantly decreased the production of ROS, maintained mitochondrial membrane potential (MMP) and blocked the release of cytochrome C, suggesting that fuziline could play the cardioprotective role through restoring the mitochondrial function. Fuziline also could suppress ISO‐induced endoplasmic reticulum (ER) stress via the PERK/eIF2α/ATF4/Chop pathway. In addition, using ROS scavenger NAC could decrease ISO‐induced apoptosis and block ISO‐induced ER stress, while PERK inhibitor GSK2606414 did not reduce the production of ROS, indicating that excess production of ROS induced by ISO triggered ER stress. And fuziline protected against ISO‐induced myocardial injury by inhibiting ROS‐triggered ER stress. Furthermore, fuziline effectively improved cardiac function on ISO‐induced myocardial injury in rats. Western blot analysis also showed that fuziline reduced ER stress‐induced apoptosis in vivo. Above these results demonstrated that fuziline could reduce ISO‐induced myocardial injury in vitro and in vivo by inhibiting ROS‐triggered ER stress via the PERK/eIF2α/ATF4/Chop pathway.
Coronally advanced flap and composite restoration of the enamel with or without connective tissue graft for the treatment of single maxillary gingival recession with non‐carious cervical lesion. A randomized controlled clinical trial
Authors: Cairo Francesco , Cortellini Pierpaolo , Nieri Michele , Pilloni Andrea , Barbato Luigi , Pagavino Gabriella , Tonetti Maurizio
Published: December 2019

Background

Aim of this study was to compare coronally advanced flap (CAF) and composite restoration of the cement–enamel junction (CEJ) with or without connective tissue graft (CTG) for treatment of single maxillary gingival recession with non‐carious cervical lesion (NCCL).

Material and Methods

Thirty patients with single gingival recessions and previously restored NCCL were randomly allocated to the two groups. A masked examiner evaluated recession reduction (RecRed), complete root coverage (CRC), keratinized tissue (KT) gain, increase in gingival thickness (GT), patient satisfaction and Root coverage Esthetic Score (RES).

Results

No significant difference for RecRed and CRC was detected at 12 months. CAF + CTG resulted in greater increase of KT width and thickness (p < .001). An interaction between baseline GT and type of treatment was reported, suggesting that when baseline GT was ≤0.84 mm adding CTG led to higher RecRed, while for values >0.84 mm the use of CAF was associated with better outcomes. Similarly, CAF alone provided better final RES score for baseline GT > 0.82 mm.

Conclusion

Both procedures were effective for root coverage at single RT1 recession with previously restored CEJ. Adding a CTG under CAF should be considered for Rec with thin gingival phenotype.
Morphology and Phylogeny of Two Novel Pleurostomatids (Ciliophora, Litostomatea), Establishing a New Genus
Authors: Pan Hongbo , Zhang Qianqian , Dong Jingyi , Jiang Jiamei
Published: December 2019

Pleurostomatida Schewiakoff, 1896 is a cosmopolitan order of ciliates. In the present study, we investigated two new pleurostomatid species, Apolitonotus lynni gen. et sp. nov. and Protolitonotus clampi sp. nov., with state‐of‐the‐art methods. Apolitonotus lynni lacks its oral extrusomes and its right kineties form an anterior semi‐suture near the dorsal margin. Based on these two features, the new genus Apolitonotus was established within the Protolitonotidae Wu et al., 2017. Protolitonotus clampi differs from its congeners by its size of 80–130 × 15–30 μm, 4–6 left, and 9–11 right kineties, extrusomes arranged along the oral slit, and two macronuclear nodules. Because Litonotus antarcticus possesses an anterior semi‐suture and oral extrusomes, it was transferred to the genus Protolitonotus, becoming P. antarctius comb. nov. (basionym Litonotus antarcticus Song and Wilbert, 2002). Phylogenetic analyses based on SSU rDNA sequences suggest a sister group relationship of P. clampi and the family Kentrophyllidae, and A. lynni is adelphotaxon to Litonotus gracilis, both within the order Pleurostomatida. Based on the new findings, an improved diagnosis for Protolitonotus was also provided.
Characteristics and composition of emulsion‐based functional low‐fat chicken meat balls fortified with dietary fiber sources
Authors: Santhi Dhanasekar , Kalaikannan Athiappan , Natarajan Amirthalingam
Published: December 2019

This study was conducted with the objective of fortifying emulsion‐based low‐fat chicken meat balls with dietary fiber sources and studying their characteristics and composition. Three experiments were conducted in which chicken meat balls were performed with the addition of pearl millet flour (PMF) and wheat flour (WF) combination in Experiment 1, with grape pomace powder (GPP) and pomegranate pomace powder (PPP) combination in Experiment 2, and with carrot pomace powder (CPP) and beetroot pomace powder (BPP) combination in Experiment 3 along with a control in each experiment and assessed for physicochemical and sensory characteristics. One best treatment from each experiment was selected based on the physicochemical and sensory characteristics, and the proximate composition of those treatments was assessed. Ether extract level was significantly (p ≤ .01) lower in the CPP–BPP treatment. Total ash was significantly (p ≤ .01) higher in the PMF–WF treatment. Insoluble fiber level was significantly (p ≤ .01) higher in GPP–PPP and CPP–BPP treatments. Inclusion of the fruit and vegetable sources had improved the fiber level, and inclusion of millets had enhanced the total ash content of the chicken meat balls.

Practical applications

Meat is protein‐rich food with high biological value containing various vitamins, minerals, and polyunsaturated fatty acids. Since meat is devoid of dietary fiber, which is considered as its major disadvantage, adding dietary fiber sources to meat products would enhance the nutritional value of meat. At present, chicken meat is mostly preferred by the consumers due to its leanness and low cost, and hence developing a functional chicken meat product would be an apt choice. Utilization of the common sources that are used in the regular cuisine/diet would satisfy the consumers to accept the product without any hesitation. In this study, common food ingredients such as pearl millet, wheat, grape, pomegranate, carrot, and beetroot had been used as functional components to fortify the chicken meat balls.
Microbial safety and probiotic potential of packaged yogurt products in Pakistan
Authors: Aziz Ghazal , Zaidi Arsalan , Bakht Urooj , Parveen Naila , Ahmed Ibrar , Haider Zeeshan , Muhammad Tariq
Published: December 2019

Yogurt is a health food with notable market production and demand. Because of this, we conducted a study on prominent commercial brands of yogurts in Pakistan for microbial content and the probiotic potential of the contained lactic acid bacteria (LAB), in the context of their label claims. All contained viable LAB, but the numbers (cfu g−1) varied considerably. Three of the products made explicit probiotic claims, but LAB from these displayed no probiotic attributes per WHO‐FAO guidelines. The yogurt starter and nonstarter Lactobacillus strains had no gelatinase or hemolytic activity and exhibited significant antibacterial activity against some human pathogens. One brand with a probiotic claim contained an L. acidophilus strain that showed cholesterol assimilation activity in vitro. Some potential human pathogens that were hemolytic and resistance to β‐lactam antibiotics were also detected in the products. The findings demonstrate a need for better quality control and regulation to ensure safety and efficacy of yogurt products.
Combined treatment with the histone deacetylase inhibitor LBH589 and a splice‐switch antisense oligonucleotide enhances SMN2 splicing and SMN expression in Spinal Muscular Atrophy cells
Authors: Pagliarini Vittoria , Guerra Marika , Di Rosa Valentina , Compagnucci Claudia , Sette Claudio
Published: December 2019

Spinal muscular atrophy (SMA) is a motor neuron disease caused by loss of function mutations in the Survival Motor Neuron 1 (SMN1) gene and reduced expression of the SMN protein, leading to spinal motor neuron death, muscle weakness and atrophy. Although humans harbour the highly homologous SMN2 gene, its defective splicing regulation yields a truncated and unstable SMN protein. The first therapy for SMA was recently approved by the Food and Drug Administration and consists of an antisense oligonucleotide (Nusinersen) rendering SMN2 functional and thus improving patients’ motor activity and quality of life. Nevertheless, not all patients equally respond to this therapy and the long‐term tolerability and safety of Nusinersen are still unknown. Herein, in vivo splicing assays indicated that the HDAC inhibitor LBH589 is particularly efficient in rescuing the SMN2 splicing defect in SMA fibroblasts and SMA type‐I mice‐derived neural stem cells. Western blot analyses showed that LBH589 also causes a significant increase in SMN protein expression in SMA cells. Moreover chromatin immunoprecipitation analyses revealed that LBH589 treatment induces widespread H4 acetylation of the entire SMN2 locus and selectively favors the inclusion of the disease‐linked exon 7 in SMN2 mature mRNA. The combined treatment of SMA cells with sub‐optimal doses of LBH589 and of an antisense oligonucleotide that mimic Nusinersen (ASO_ISSN1) elicits additive effects on SMN2 splicing and SMN protein expression. These findings suggest that HDAC inhibitors can potentiate the activity of Nusinersen and support the notion that ‘SMN‐plus’ combinatorial therapeutic approaches might represent an enhanced opportunity in the scenario of SMA therapy.

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Lacunar syndromes: Are they all equally benign?
Authors: Narasimhalu Kaavya , Woon Fung Peng , Ng Szu Chyi , De Silva Deidre Anne
Published: December 2019

Background

There is a paucity of prognostic data following clinical lacunar syndromes, particularly comparisons between the various lacunar syndromes.

Aims

To compare the outcomes, disability at discharge, at 1 and 3 months, use of rehabilitation facilities and duration to return to work/daily activities, between patients with various clinical lacunar syndromes.

Methods

Ischemic stroke patients with clinical lacunar syndromes were prospectively recruited. Functional outcomes were measured by the modified Rankin Scale (mRS), with unfavorable outcome defined as mRS > 1. Use of rehabilitation facilities and duration to return to work/ daily activities was also ascertained. Logistic regression analyses were performed to determine predictors of outcome measures.

Results

Of the 192 ischemic stroke patients (mean age 62 ± 11 years) with clinical lacunar syndromes, 72(37%) patients had ataxic hemiparesis, 53(28%) patients had pure motor syndrome, 41(21%) had sensorimotor syndrome, 17(9%) had pure sensory syndrome, and 9(5%) had clumsy hand dysarthria syndrome. Compared to pure sensory strokes, patients with pure motor syndrome (OR 7.72 CI 1.5‐38), sensorimotor syndrome (OR 6.06, CI 1.18‐31), and ataxic hemiparesis (OR 18.1 CI 3.79‐91) were more likely to have unfavorable outcome at 1 month, but there was no difference at 3 months. There was no independent association between specific lacunar syndromes with use of rehabilitation facilities and duration to return to work/ daily activities.

Conclusions

Nearly 1/3 of patients with clinical lacunar syndromes have unfavorable 3‐month functional outcome. There were differences in the functional status at discharge between clinical lacunar syndromes, but not for other outcomes.
Sjögren syndrome combined with myositis which is pathologically compatible with inclusion body myositis
Authors: Mitsutake Akihiko , Arakawa Akira , Sato Tatsuya , Katsumata Junko , Seki Tomonari , Maekawa Risa , Hideyama Takuto , Nishino Ichizo , Shiio Yasushi
Published: December 2019

A 60‐year‐old woman previously diagnosed as Sjögren syndrome (SjS) presented with a three‐year history of progressive muscle weakness in the neck and predominantly proximal part of the four limbs. Pathological study showed patchy, dot‐like p62 aggregates in muscle fibers in combination with increased HLA‐ABC and ‐DR expression, which is pathologically consistent with sporadic inclusion body myositis (sIBM). Oral prednisolone improved muscle strength. Three years after the initiation of treatment, the patient still can walk. Myositis in our patient, albeit pathologically characterized by features of sIBM, responded well to prednisolone.
Tumor genetic heterogeneity analysis of chronic sun‐damaged melanoma
Authors: Sanna Adriana , Harbst Katja , Johansson Iva , Christensen Gustav , Lauss Martin , Mitra Shamik , Rosengren Frida , Häkkinen Jari , Vallon‐Christersson Johan , Olsson Håkan , Ingvar Åsa , Isaksson Karolin , Ingvar Christian , Nielsen Kari , Jönsson Göran
Published: December 2019

Chronic sun‐damaged (CSD) melanoma represents 10%–20% of cutaneous melanomas and is characterized by infrequent BRAF V600E mutations and high mutational load. However, the order of genetic events or the extent of intra‐tumor heterogeneity (ITH) in CSDhigh melanoma is still unknown. Ultra‐deep targeted sequencing of 40 cancer‐associated genes was performed in 72 in situ or invasive CMM, including 23 CSDhigh cases. In addition, we performed whole exome and RNA sequencing on multiple regions of primary tumor and multiple in‐transit metastases from one CSDhigh melanoma patient. We found no significant difference in mutation frequency in melanoma‐related genes or in mutational load between in situ and invasive CSDhigh lesions, while this difference was observed in CSDlow lesions. In addition, increased frequency of BRAF V600K, NF1, and TP53 mutations (p < .01, Fisher's exact test) was found in CSDhigh melanomas. Sequencing of multiple specimens from one CSDhigh patient revealed strikingly limited ITH with >95% shared mutations. Our results provide evidence that CSDhigh and CSDlow melanomas are distinct molecular entities that progress via different genetic routes.
Clinical course of porokeratosis ptychotropica over 7 years in an otherwise healthy child
Authors: Ho Tina , Schwentker Ann R. , Barron David R. , Lucky Anne W.
Published: December 2019

Porokeratosis ptychotropica is an unusual variant of porokeratosis characterized by papules and plaques located on the buttocks and gluteal cleft and showing multiple coronoid lamellae on histology. In this case report, we present the longitudinal clinical course of porokeratosis ptychotropica in a pediatric patient with individual red‐brown hyperkeratotic lesions that enlarged and became confluent prior to surgical intervention. We also discuss the etiology of porokeratosis ptychotropica and review current as well as future treatment options for the disease.
The impact of depressive mood and cognitive impairment on quality of life of the elderly
Authors: Voros Viktor , Martin Gutierrez David , Alvarez Federico , Boda‐Jorg Adrienn , Kovacs Attila , Tenyi Tamas , Fekete Sandor , Osvath Peter
Published: December 2019

Background

The quality of life (QOL) of the elderly can be influenced by numerous factors. We assessed QOL, cognitive functions, depression and clinical data in elderly aged 65 and over with the aim of analysing factors affecting their QOL.

Methods

Semi‐structured interviews were conducted with elderly over the age of 65, and their QOL, cognitive functions and depressive symptoms were assessed by validated clinical tests and screening tools.

Results

The correlation between QOL scales and cognitive tests was not significant. In contrast, the results of depression scales showed significant negative correlation with the scores of the QOL scales. A better QOL was determined by lower age, lack of depressive symptoms, and higher scores in the QOL‐AD (Alzheimer's disease) scale. Depressive mood has much more negative impact on the QOL of the elderly than cognitive impairment.

Conclusions

Our results demonstrated a close correlation between QOL and depressive mood in the elderly. The early detection and effective management of affective and cognitive symptoms in the elderly can not only restore mental health but may also improve their QOL.
Efficiency‐adjusted public capital, capital grants, and growth
Authors: Crivelli Ernesto
Published: December 2019

A debate on whether capital grants, and especially European Union (EU) funds, actually contribute to growth has gained prominence lately. This article empirically assesses the relationship between the quality of public investment, capital grants, and growth in a sample of 43 emerging and peripheral economies over 1991–2015. To this end, the contribution of public capital to growth is estimated using efficiency‐adjusted public capital stock series, which reflects the quality of public investment management institutions. In addition, the determinants of effective public investment are analyzed. The results suggest that capital grants contribute positively to effective public investment, and the latter is significant in explaining variations in economic growth. Finally, the article illustrates the impact of raising EU funds absorption on potential growth in emerging and peripheral EU countries.
Beneficiary Work: The Hidden Labor of Medicaid Users Pursuing Cross‐State Moves
Authors: Grossman Brian R. , Mullin Courtney
Published: December 2019

For users of Medicaid personal care assistance (PCA) services and their families, interstate variation in eligibility and service availability act as structural barriers to cross‐state movement. However, program users desire and pursue cross‐state moves. In this article, we provide a grounded theory analysis of 18 interviews with Medicaid PCA users with physical disabilities who expressed desire for or pursued cross‐state moves. Our analysis identified six forms of previously unnamed and unrecognized work. As PCA users plan or pursue cross‐state moves, they are also (1) assessing service ecosystems, (2) finding the right door, (3) persisting through the bureaucratic gauntlet, (4) advocating for systems cooperation, (5) reestablishing networks of support, and (6) responding to service gaps/lapses. Collectively, we describe this hidden labor as beneficiary work, the unremunerated work that program users must do in order to retain access to benefits for which they qualify. Beneficiary work, while hidden, is not optional; it is necessary for continued access to community and broadly, for survival. Identifying and describing beneficiary work expands on Feminist and interactionist perspectives on disability, poverty, and work, and highlights the need for changes to Medicaid policy that address PCA users as mobile citizens.
Disaster Relief as Social Action: A Weberian Look at Postdisaster Donation Behavior
Authors: Penta Samantha , Wachtendorf Tricia , Nelan Mary M.
Published: December 2019

Disaster relief involves a broad range of participants, which often results in a disjunction between actual disaster needs and the perception of appropriate strategies in relief provision. This research examines data collected through interviews with donation drive operators responding to Superstorm Sandy in 2012 and the May 2013 Oklahoma tornadoes. Using Weber's ideal types of social action to understand motivations for engaging in disaster relief, this article argues that motivations for participating in and organizing such drives influence donation strategies, and these motivations can be used to explain persistent donation of nonuseful materiel items. Findings indicate several different motivations for involvement and that donation type appeared linked to motivation. We suggest that motivation for engaging in social action is a valuable approach to better understanding donation behavior and, consequently, addressing the social problem of materiel convergence in the postdisaster environment.
Radiogenic trigger and driver for continental rifting and initial ocean spreading
Authors: Maystrenko Yuriy Petrovich , Slagstad Trond
Published: December 2019

Closure and opening of oceans on time‐scales of a few hundred million years is a fundamental tectonic process on Earth, typically referred to as a “Wilson cycle”. Subduction of oceanic and continental crust leading up to and during continent–continent collision can refertilize and enrich the orogenic continental lithospheric mantle in heat‐producing elements. The resulting thermal anomaly weakens the lithosphere and, along with structural weaknesses (e.g. sutures), make this orogenic lithosphere more prone to rifting given an extensional stress field. Thermal modelling shows that anomalously hot lithosphere can focus asthenospheric upwellings over time‐scales of a few hundred million years. Processes related to closure of oceans thus provide a mechanism for later localization of rifting and an extensional driving force.
Detrital zircon geochronology analysis of the Late Mesozoic deposition in the Turpan‐Hami basin: Implications for the uplift history of the Eastern Tian Shan, north‐western China
Authors: Shen Tianyi , Chen Yue , Wang Guocan , Ji Junliang , Wang Yong , Zhang Pan , Sotiriou Paul , Guo Rong , Xu Zezhuang
Published: December 2019

Analysing the provenance changes of synorogenic sediments in the Turpan‐Hami basin by detrital zircon geochronology is an efficient tool to examine the uplift and erosion history of the easternmost Tian Shan. We present detrital zircon U‐Pb analysis from nine samples that were collected within marginal lacustrine Middle‐Late Jurassic and aeolian‐fluvial Early Cretaceous strata in the basin. Middle‐Early Jurassic (159–172 Ma) zircons deriving from the southern Junggar dominated the Middle Jurassic sample from the western Turpan‐Hami basin, whereas Permian‐Carboniferous (270–330 Ma) zircons from the Bogda mountains were dominant in the Late Jurassic to Early Cretaceous samples. Devonian‐Silurian (400–420 Ma) and Triassic (235–259 Ma) zircons from the Jueluotage and Harlik mountains constituted the subordinate age groups in the Late Jurassic and Early Cretaceous samples from the eastern basin respectively. These provenance transitions provide evidence for uplift of the Bogda mountains in the Late Jurassic and the Harlik mountains since the Early Cretaceous.
Effect of nurse‐led care on quality of care and level of HbA1C in patients with diabetic foot ulcer: A randomized clinical trial
Authors: Dehghan Nayeri Nahid , Samadi Nasrin , Larijani Bagher , Sayadi Leila
Published: December 2019

Diabetic foot ulcer (DFU) is a serious and costly complication in diabetes which affects different aspects of life and can reduce patient's quality of life. Various views to manage DFU have been introduced. The nurse‐led team, as a multidisciplinary team, can be effective due to a holistic approach to some disease management; but in patients with DFU it has not been assessed. Therefore, this study was designed to determine the effect of nurse‐led care on quality of care (QOC) and improvement of HbA1C in Patients with DFU. This was a randomized clinical trial study performed on 52 patients with DFU. Patients were randomly assigned into two groups: nurse‐led care intervention and standard care. The study was conducted in one of the hospitals affiliated to Tehran University of Medical Sciences. Data were collected using two questionnaires: Demographic characteristics and Quality Patient Care Scale (QUALPACS) and taking a blood sample for HbA1C. The nurse‐led Care interventions were conducted in three stages: Integrated, Interdisciplinary, and Comprehensive. Descriptive and analytic statistical methods were used to analyze the data. P < .05 was considered significant. The results demonstrated that according to repeated measures test, (before, 4 and 12 weeks after the intervention), the level of QOC dimensions (Psychosocial, communication and physical aspect) in the nurse‐led group had a significant difference with control group (P < .0001). Also, according to the results of Independent t test, there was a significant difference in total QOC scoring and HbA1c between intervention and control groups after the intervention and follow up (P < .0001). Considering the burden of diabetes and DFUs, it seems that the establishment of a nurse‐led care approach can be an effective strategy to manage and treat these patients, and eliminate the disruption of care and achieve optimal care quality.
Fluorescence microscopy visualization of the roughness-induced transition between lubrication regimes
Authors: Petrova Dina , Weber Bart , Allain Cleménce , Audebert Pierre , Venner Cees H. , Brouwer Albert M. , Bonn Daniel
Published: December 2019

We use fluorescence microscopy to investigate how surface roughness affects the transition between different lubrication regimes.
A minimally invasive lens-free computational microendoscope
Authors: Shin Jaewook , Tran Dung N. , Stroud Jasper R. , Chin Sang , Tran Trac D. , Foster Mark A.
Published: December 2019

A distal lensless microendoscope is developed to enable minimally invasive imaging with wide field of view and digital refocusing.
Inverting singlet and triplet excited states using strong light-matter coupling
Authors: Eizner Elad , Martínez-Martínez Luis A. , Yuen-Zhou Joel , Kéna-Cohen Stéphane
Published: December 2019

Molecules sandwiched in an optical cavity can form hybrid light-matter states at energies below the dark spin triplet state.
Dalton’s and Amagat’s laws fail in gas mixtures with shock propagation
Authors: Wayne P. , Cooper S. , Simons D. , Trueba-Monje I. , Freelong D. , Vigil G. , Vorobieff P. , Truman C. R. , Vorob’ev V. , Clark T.
Published: December 2019

We present an experimental study of a fundamental case where gas mixture models fail: shock propagation through a gas mixture.
Tailoring solvent coordination for high-speed, room-temperature blading of perovskite photovoltaic films
Authors: Deng Yehao , Van Brackle Charles H. , Dai Xuezeng , Zhao Jingjing , Chen Bo , Huang Jinsong
Published: December 2019

An alternative ink design is introduced that enables fast coating of perovskite at room temperature for low-cost solar modules.
FeSe quantum dots for in vivo multiphoton biomedical imaging
Authors: Kwon J. , Jun S. W. , Choi S. I. , Mao X. , Kim J. , Koh E. K. , Kim Y.-H. , Kim S.-K. , Hwang D. Y. , Kim C.-S. , Lee J.
Published: December 2019

FeSe quantum dots of multiphoton absorption were used to image tumor cells in deeper tissue.
Spin-dependent charge transport through 2D chiral hybrid lead-iodide perovskites
Authors: Lu Haipeng , Wang Jingying , Xiao Chuanxiao , Pan Xin , Chen Xihan , Brunecky Roman , Berry Joseph J. , Zhu Kai , Beard Matthew C. , Vardeny Zeev Valy
Published: December 2019

Chiral molecules in Pb-halide 2D-layered films achieve up to 86% spin-polarized transport, enabling novel spintronic applications.
Grain boundary decohesion by nanoclustering Ni and Cr separately in CrMnFeCoNi high-entropy alloys
Authors: Ming Kaisheng , Li Linlin , Li Zhiming , Bi Xiaofang , Wang Jian
Published: December 2019

Nanoclustering Cr, Ni, and Mn separately at GBs reduces GB cohesion in single-phase CrMnFeCoNi high-entropy alloys.
Carboxylated branched poly(β-amino ester) nanoparticles enable robust cytosolic protein delivery and CRISPR-Cas9 gene editing
Authors: Rui Yuan , Wilson David R. , Choi John , Varanasi Mahita , Sanders Katie , Karlsson Johan , Lim Michael , Green Jordan J.
Published: December 2019

New biodegradable nanoparticles shuttle proteins inside cells and enable robust gene editing.
Clec10a regulates mite-induced dermatitis
Authors: Kanemaru Kazumasa , Noguchi Emiko , Tahara-Hanaoka Satoko , Mizuno Seiya , Tateno Hiroaki , Fujisawa Yasuhiro , Nakamura Yoshiyuki , Denda-Nagai Kaori , Irimura Tatsuro , Matsuda Hiroshi , Sugiyama Fumihiro , Takahashi Satoru , Shibuya Kazuko , Shibuya Akira
Published: December 2019

Clec10a on skin macrophages recognizes a mucin-like molecule of house dust mite and suppresses mite-induced dermatitis.
IFN-γ: The T cell’s license to kill stem cells in the inflamed intestine
Authors: Kretzschmar Kai , Clevers Hans
Published: December 2019

IFN-γ produced by T cells directly induces intestinal stem cell death upon inflammation-induced intestinal injury (see the related Research Article by

Takashima
et al
.

).
It takes 2 TOXes to Tfh Tango
Authors: Chen Jennifer S. , Eisenbarth Stephanie C.
Published: December 2019

TOX and TOX2 promote T follicular helper cell development through transcriptional changes and epigenetic remodeling.
Fast-acting autoantibodies muscle in on encephalitis
Authors: Fichtner Miriam L. , O’Connor Kevin C.
Published: December 2019

Autoantibodies that recognize the glycine receptor mediate pathology by directly interrupting glycinergic neurotransmission that manifests as a disorder characterized by muscle stiffness and spasms.