bluuebunny/crossref_metadata_2025_split huggingface dataset:
Re‐imagining Alzheimer's disease – the diminishing importance of amyloid and a glimpse of what lies ahead
Authors: Tse Kai‐Hei , Herrup Karl 
Published: May 2017

AbstractMany have criticized the amyloid cascade hypothesis of Alzheimer's disease for its inconsistencies and failures to either accurately predict disease symptoms or guide the development of productive therapies. In addition to criticisms, however, we believe that the field would benefit from having alternative narratives and disease models that can either replace or function alongside of an amyloid‐centric view of Alzheimer's. This review is an attempt to meet that need. We offer three experimentally verified amyloid‐independent mechanisms, each of which plausibly contributes substantially to the aetiology of Alzheimer's disease: loss of DNA integrity, faulty cell cycle regulation, regression of myelination. We outline the ways in which the failure of each can contribute to AD initiation and progression, and review how, acting alone or in combination with each other, they are sufficient for explaining the full range of AD pathologies. Yet, these three alternatives represent only a few of the many non‐amyloid mechanisms that can explain AD pathogenesis. Therefore instead of proposing a single ‘alternative hypothesis’ to the amyloid cascade theory, sporadic AD is pictured as the result of independent yet intersecting age‐related pathologies that afflict the ageing human brain.This article is part of the series “Beyond Amyloid”.Cover Image for this issue: doi. 10.1111/jnc.13823.
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Ghrelin receptors mediate ghrelin‐induced excitation of agouti‐related protein/neuropeptide Y but not pro‐opiomelanocortin neurons
Authors: Chen Shao‐Rui , Chen Hong , Zhou Jing‐Jing , Pradhan Geetali , Sun Yuxiang , Pan Hui‐Lin , Li De‐Pei 
Published: May 2017

AbstractGhrelin increases food intake and body weight by stimulating orexigenic agouti‐related protein (AgRP)/neuropeptide Y (NPY) neurons and inhibiting anorexic pro‐opiomelanocortin (POMC) neurons in the hypothalamus. Growth hormone secretagogue receptor (Ghsr) mediates the effect of ghrelin on feeding behavior and energy homeostasis. However, the role of Ghsr in the ghrelin effect on these two populations of neurons is unclear. We hypothesized that Ghsr mediates the effect of ghrelin on AgRP and POMC neurons. In this study, we determined whether Ghsr similarly mediates the effects of ghrelin on AgRP/NPY and POMC neurons using cell type‐specific Ghsr‐knockout mice. Perforated whole‐cell recordings were performed on green fluorescent protein‐tagged AgRP/NPY and POMC neurons in the arcuate nucleus in hypothalamic slices. In Ghsr+/+ mice, ghrelin (100 nM) significantly increased the firing activity of AgRP/NPY neurons but inhibited the firing activity of POMC neurons. In Ghsr−/− mice, the excitatory effect of ghrelin on AgRP/NPY neurons was abolished. Ablation of Ghsr also eliminated ghrelin‐induced increases in the frequency of GABAergic inhibitory postsynaptic currents of POMC neurons. Strikingly, ablation of Ghsr converted the ghrelin effect on POMC neurons from inhibition to excitation. Des‐acylated ghrelin had no such effect on POMC neurons in Ghsr−/− mice. In both Ghsr+/+ and Ghsr−/− mice, blocking GABAA receptors with gabazine increased the basal firing activity of POMC neurons, and ghrelin further increased the firing activity of POMC neurons in the presence of gabazine. Our findings provide unequivocal evidence that Ghsr is essential for ghrelin‐induced excitation of AgRP/NPY neurons. However, ghrelin excites POMC neurons through an unidentified mechanism that is distinct from conventional Ghsr.
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Heparan sulfate alterations in extracellular matrix structures and fibroblast growth factor‐2 signaling impairment in the aged neurogenic niche
Authors: Yamada Taihei , Kerever Aurelien , Yoshimura Yusuke , Suzuki Yuji , Nonaka Risa , Higashi Kyohei , Toida Toshihiko , Mercier Frederic , Arikawa‐Hirasawa Eri 
Published: May 2017

AbstractAdult neurogenesis in the subventricular zone of the lateral ventricle decreases with age. In the subventricular zone, the specialized extracellular matrix structures, known as fractones, contact neural stem cells and regulate neurogenesis. Fractones are composed of extracellular matrix components, such as heparan sulfate proteoglycans. We previously found that fractones capture and store fibroblast growth factor 2 (FGF‐2) via heparan sulfate binding, and may deliver FGF‐2 to neural stem cells in a timely manner. The heparan sulfate (HS) chains in the fractones of the aged subventricular zone are modified based on immunohistochemistry. However, how aging affects fractone composition and subsequent FGF‐2 signaling and neurogenesis remains unknown. The formation of the FGF‐fibroblast growth factor receptor‐HS complex is necessary to activate FGF‐2 signaling and induce the phosphorylation of extracellular signal‐regulated kinase (Erk1/2). In this study, we observed a reduction in HS 6‐O‐sulfation, which is critical for FGF‐2 signal transduction, and failure of the FGF‐2‐induced phosphorylation of Erk1/2 in the aged subventricular zone. In addition, we observed increased HS 6‐O‐endo‐sulfatase, an enzyme that may be responsible for the HS modifications in aged fractones. In conclusion, the data revealed that heparan sulfate 6‐O‐sulfation is reduced and FGF‐2‐dependent Erk1/2 signaling is impaired in the aged subventricular zone. HS modifications in fractones might play a role in the reduced neurogenic activity in aging brains.image
Scalloped tongue is associated with nocturnal intermittent hypoxia among community‐dwelling Japanese: the Toon Health Study
Authors: Tomooka K. , Tanigawa T. , Sakurai S. , Maruyama K. , Eguchi E. , Nishioka S. , Miyoshi N. , Kakuto H. , Shimizu G. , Yamaoka D. , Saito I. 
Published: May 2017

SummaryScalloped tongue is considered as a possible clinical finding of obstructive sleep apnoea (OSA). There are few evidence of the association between scalloped tongue and OSA. To examine the association between scalloped tongue and nocturnal intermittent hypoxia (NIH), a surrogate marker of OSA, among a general Japanese population. Study participants were 398 men and 732 women aged 30–79 years who participated in the Toon Health Study from 2011 to 2014. Scalloped tongue was classified into three categories: none, mild and moderate‐to‐severe. Moderate‐to‐severe NIH was defined as the 3% oxygen desaturation index of ≥15 events/h during sleep for one night with pulse oximetry. The multivariable‐adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for moderate‐to‐severe NIH were calculated according to scalloped tongue categories using a logistic regression model. There were 69 (6·1%) moderate‐to‐severe NIH cases in this population. The multivariable‐adjusted ORs (95% CIs) of moderate‐to‐severe NIH were 1·59 (0·85–2·95) for mild and 2·39 (1·10–5·17) for the moderate‐to‐severe scalloped tongue group compared with the group without scalloped tongues. When stratified by overweight status (BMI <25 or ≥25 kg m−2), the respective ORs (95% CIs) were 2·83 (1·06–7·55) and 4·74 (1·28–17·49) among overweight individuals, and 0·94 (0·40–2·70) and 1·52 (0·57–4·05) among non‐overweight individuals. Scalloped tongue was associated with higher prevalence of moderate‐to‐severe NIH among the general Japanese population and this association was more evident in overweight individuals.
Delayed‐onset muscle soreness does not influence occlusal sensitivity and position sense of the mandible
Authors: Bucci R. , Lobbezoo F. , Michelotti A. , Orfanou C. , Koutris M. 
Published: May 2017

SummaryMasticatory muscle‐pain patients often complain about sensorimotor changes, but the effects of pain on the psychophysical properties remain unclear. This study aimed to investigate the effects of delayed‐onset muscle soreness (DOMS) on the jaw's position sense (PS) and occlusal sensitivity (OS). In all, 12 participants underwent intense concentric–eccentric jaw exercises. Self‐reported muscle fatigue and pain, pain‐free maximum mouth opening (MMO), pain pressure thresholds (PPTs) at right and left masseter and right and left anterior temporalis, maximum voluntary bite force (MVBF), PS and OS were recorded before, immediately after, 24 h, 48 h and 1 week after the exercises. Data were analysed with repeated measures anova. Pain and fatigue increased significantly after the exercises, while fatigue also increased 24 h afterwards. Time and site had a significant effect for PPTs, not for MVBF. MMO decreased significantly 24 h after the exercises. OS and PS did not change significantly. Experimentally induced DOMS does not influence the psychophysical properties of the masticatory system.
The anatomy and physiology of normal and abnormal swallowing in oropharyngeal dysphagia
Authors: Sasegbon A. , Hamdy S. 
Published: May 2017

AbstractBackgroundEating and drinking are enjoyable activities that positively impact on an individual's quality of life. The ability to swallow food and fluid is integral to the process of eating. Swallowing occupies a dual role being both part of the enjoyment of eating and being a critically important utilitarian activity to enable adequate nutrition and hydration. Any impairment to the process of swallowing can negatively affect a person's perception of their quality of life. The process of swallowing is highly complex and involves muscles in the mouth, pharynx, larynx, and esophagus. The oropharynx is the anatomical region encompassing the oral cavity and the pharynx. Food must be masticated, formed into a bolus and transported to the pharynx by the tongue whereas fluids are usually held within the mouth before being transported ab‐orally. The bolus must then be transported through the pharynx to the esophagus without any matter entering the larynx. The muscles needed for all these steps are coordinated by swallowing centers within the brainstem which are supplied with sensory information by afferent nerve fibers from several cranial nerves. The swallowing centers also receive modulatory input from higher centers within the brain. Hence, a swallow has both voluntary and involuntary physiologic components and the term dysphagia is given to difficult swallowing while oropharyngeal dysphagia is difficult swallowing due to pathology within the oropharynx.PurposeProblems affecting any point along the complex swallowing pathway can result in dysphagia. This review focuses on the anatomy and physiology behind normal and abnormal oropharyngeal swallowing. It also details the common diseases and pathology causing oropharyngeal dysphagia.
Economic evaluation of the randomized European Achalasia trial comparing pneumodilation with Laparoscopic Heller myotomy
Authors: Moonen A. , Busch O. , Costantini M. , Finotti E. , Tack J. , Salvador R. , Boeckxstaens G. , Zaninotto G. 
Published: May 2017

AbstractBackgroundA recent multicenter randomized trial in achalasia patients has shown that pneumatic dilation resulted in equivalent relief of symptoms compared to laparoscopic Heller myotomy. Additionally, the cost of each treatment should be also taken in consideration. Therefore, the aim of the present study was to perform an economic analysis of the European achalasia trial.MethodsPatients with newly diagnosed achalasia were enrolled from to 2003 to 2008 in 14 centers in five European countries and were randomly assigned to either pneumatic dilation (PD) or laparoscopic Heller (LHM). The economic analysis was performed in the three centers in three different countries where most patients were enrolled (Amsterdam [NL], Leuven, [B] and Padova [I]) and then applied to all patients included in the study. The total raw costs of the two treatments per patient include the initial costs, the costs of complications, and the costs of retreatments.ResultsTwo hundred and one patients, 107 (57 males and 50 females, mean age 46 CI: 43‐49 years) were randomized to LHM and 94 (59 males and 34 females, mean age 46 CI 43‐50 years) to PD. The total cost of PD per patient was quite comparable in the three different centers; €3397 in Padova, €3259 in Amsterdam and €3792 in Leuven. For LHM, the total costs per patient were highest in Amsterdam: €4488 in Padova, €6720 in Amsterdam, and €5856 in Leuven.ConclusionIn conclusion, the strategy of treating achalasia starting with PD appears the most economic approach, independent of the health system.
Pull out Strength of Dual Outer Diameter Pedicle Screws Compared to Uncemented and Cemented Standard Pedicle Screws: A Biomechanical in vitro Study
Authors: Lorenz Andrea , Leichtle Carmen I , Frantz Sandra , Bumann Marte , Tsiflikas Ilias , Shiozawa Thomas , Leichtle Ulf G 
Published: May 2017

ObjectiveTo analyze the potential of the dual outer diameter screw and systematically evaluate the pull‐out force of the dual outer diameter screw compared to the uncemented and cemented standard pedicle screws with special regard to the pedicle diameter and the vertebra level.MethodsSixty vertebrae of five human spines (T
6–L
5) were sorted into three study groups for pairwise comparison of the uncemented dual outer diameter screw, the uncemented standard screw, and the cemented standard screw, and randomized with respect to bone mineral density (BMD) and vertebra level. The vertebrae were instrumented, insertion torque was determined, and pull‐out testing was performed using a material testing machine. Failure load was evaluated in pairwise comparison within each study group. The screw‐to‐pedicle diameter ratio was determined and the uncemented dual outer diameter and standard screws were compared for different ratios as well as vertebra levels.ResultsSignificantly increased pull‐out forces were measured for the cemented standard screw compared to the uncemented standard screw (+689 N, P < 0.001) and the dual outer diameter screw (+403 N, P < 0.001). Comparing the dual outer diameter screw to the uncemented standard screw in the total study group, a distinct but not significant increase was measured (+149 N, P = 0.114). Further analysis of these two screws, however, revealed a significant increase of pull‐out force for the dual outer diameter screw in the lumbar region (+247 N, P = 0.040), as well as for a screw‐to‐pedicle diameter ratio between 0.6 and 1 (+ 488 N, P = 0.028).ConclusionsFor clinical application, cement augmentation remains the gold standard for increasing screw stability. According to our results, the use of a dual outer diameter screw is an interesting option to increase screw stability in the lumbar region without cement augmentation. For the thoracic region, however, the screw‐to‐pedicle diameter should be checked and attention should be paid to screw cut out, if the dual outer diameter screw is considered.
Mating biology, nuclear DNA content and genetic diversity in spider plant (Cleome gynandra) germplasm from various African countries
Authors: Omondi Emmanuel O. , Debener Thomas , Linde Marcus , Abukutsa‐Onyango Mary , Dinssa Fekadu F. , Winkelmann Traud 
Published: May 2017

AbstractCleome gynandra (L.) Briq. is an African leafy vegetable with a potential to improve food security and micronutrient deficiencies. Cytological traits, breeding biology and genetic diversity of 30 selected entries of C. gynandra from six African countries were investigated. The entries consisted of advanced lines, gene bank accessions and farmers’ cultivars. Our study revealed chromosome numbers of 2n = 34 in root tip metaphase cells from one entry. The 30 entries were found to be diploid with genome sizes ranging from 2.31 to 2.45 pg/2C. Hand pollination experiments were carried out to assess self‐incompatibility within the entries and revealed that they are self‐ and cross‐compatible. For genetic diversity studies within and among the entries, the pooled data of 499 polymorphic bands from 11 amplified fragment length polymorphism primer combinations and nine simple sequence repeat markers were used. The genetic distance among the entries ranged from 0.13 to 0.77. In a principal coordinate analysis, the farmers’ cultivars formed a cluster separate from the advanced lines and the gene bank entries, and the latter were not well resolved.
Quantification of excitation energy distribution between photosystems based on a mechanistic model of photosynthetic electron transport
Authors: Murakami Keach , Matsuda Ryo , Fujiwara Kazuhiro 
Published: May 2017

AbstractAbsorbed light energy is converted into excitation energy. The excitation energy is distributed to photosystems depending on the wavelength and drives photochemical reactions. A non‐destructive, mechanistic and quantitative method for estimating the fraction of the excitation energy distributed to photosystem II (f) was developed. For the f values for two simultaneously provided actinic lights (ALs) with different spectral distributions to be estimated, photochemical yields of the photosystems were measured under the ALs and were then fitted to an electron transport model assuming the balance between the electron transport rates through the photosystems. For the method to be tested using leaves with different properties in terms of the long‐term and short‐term acclimation (adjustment of photosystem stoichiometry and state transition, respectively), the f values for red and far‐red light (R and FR) were estimated in leaves grown (~1 week) under white light without and with supplemental FR and adapted (~10 min) to R without and with supplemental FR. The f values for R were clearly greater than those for FR and those of leaves grown with and adapted to supplemental FR tended to be higher than the controls. These results are consistent with previous studies and therefore support the validity of the proposed method.
SUV2, which encodes an ATR‐related cell cycle checkpoint and putative plant ATRIP, is required for aluminium‐dependent root growth inhibition in Arabidopsis
Authors: Sjogren Caroline A. , Larsen Paul B. 
Published: May 2017

AbstractA suppressor mutagenesis screen was conducted in order to identify second site mutations that could reverse the extreme hypersensitivity to aluminium (Al) seen for the Arabidopsis mutant, als3‐1. From this screen, it was found that a loss‐of‐function mutation in the previously described SUV2 (SENSITIVE TO UV 2), which encodes a putative plant ATRIP homologue that is a component of the ATR‐dependent cell checkpoint response, reversed the als3‐1 phenotype. This included prevention of hallmarks associated with als3‐1 including Al‐dependent terminal differentiation of the root tip and transition to endoreduplication. From this analysis, SUV2 was determined to be required for halting cell cycle progression and triggering loss of the quiescent centre (QC) following exposure to Al. In conjunction with this, SUV2 was found to have a similar role as ATR, ALT2 and SOG1 in Al‐dependent stoppage of root growth, all of which are required for promotion of expression of a suite of genes that likely are part of an Al‐dependent DNA damage transcriptional response. This work argues that these Al response factors work together to detect Al‐dependent damage and subsequently activate a DNA damage response pathway that halts the cell cycle and subsequently promotes QC differentiation and entrance into endocycling.
Re‐adjusting the cut‐off score of the Korean version of the Childhood Autism Rating Scale for high‐functioning individuals with autism spectrum disorder
Authors: Kwon Hyuk‐Jin , Yoo Hee‐Jeong , Kim Joo‐Hyun , Noh Dong‐Hyun , Sunwoo Hyun‐Jung , Jeon Ye Seul , Lee Sang‐youn , Jo Ye‐ul , Bong Gui‐Young 
Published: May 2017

AimThe current cut‐off score of the Korean version of the Childhood Autism Rating Scale (K‐CARS) does not seem to be sensitive enough to precisely diagnose high‐functioning autism. The aim of this study was to identify the optimal cut‐off score of K‐CARS for diagnosing high‐functioning individuals with autism spectrum disorders (ASD).MethodsA total of 329 participants were assessed by the Korean versions of the Autism Diagnostic Interview – Revised (K‐ADI‐R), Autism Diagnostic Observation Schedule (K‐ADOS), and K‐CARS. IQ and Social Maturity Scale scores were also obtained.ResultsThe true positive and false negative rates of K‐CARS were 77.2% and 22.8%, respectively. Verbal IQ (VIQ) and Social Quotient (SQ) were significant predictors of misclassification. The false negative rate increased to 36.0% from 19.8% when VIQ was >69.5, and the rate increased to 44.1% for participants with VIQ > 69.5 and SQ > 75.5. In addition, if SQ was >83.5, the false negative rate increased to 46.7%, even if the participant’s VIQ was ≤69.5. Optimal cut‐off scores were 28.5 (for VIQ ≤ 69.5 and SQ ≤ 75.5), 24.25 (for VIQ > 69.5 and SQ > 75.5), and 24.5 (for SQ > 83.5), respectively.ConclusionThe likelihood of a false negative error increases when K‐CARS is used to diagnose high‐functioning autism and Asperger's syndrome. For subjects with ASD and substantial verbal ability, the cut‐off score for K‐CARS should be re‐adjusted and/or supplementary diagnostic tools might be needed to enhance diagnostic accuracy for ASD.
Assessment of Infantile Hemangiomas Using a Handheld Wireless Diffuse Optical Spectroscopic Device
Authors: Fong Christopher J. , Garzon Maria C. , Hoi Jennifer W. , Kim Hyun K. , Lauren Christine T. , Morel Kimberly , Geller Lauren , Antonov Nina , Weitz Nicole , Wu June , Hielscher Andreas H. 
Published: May 2017

AbstractBackground/ObjectivesInfantile hemangiomas (IHs) are vascular tumors with the potential for significant morbidity. There is a lack of validated objective tools to assess IH severity and response to treatment. Diffuse optical spectroscopy (DOS), a noninvasive, nonionizing imaging modality, can measure total hemoglobin concentration and hemoglobin oxygen saturation in tissue to assess IH vascularity and response to treatment. Our objective was to evaluate the utility of a wireless, handheld DOS system to assess IH characteristics at selected points during their clinical course.MethodsThirteen subjects (initial age 5.8 ± 2.0 mos) with 15 IHs were enrolled. IHs were classified as proliferative, plateau phase, or involuting. Nine patients with 11 IHs were untreated; four patients with 4 IHs were treated with timolol or propranolol. Each IH was evaluated by placing the DOS system directly on the lesion as well a normal contralateral skin site. IH vascularity and oxygenation were scored using a newly defined normalized hypoxia fraction (NHF) coefficient. Measurements were recorded at various intervals from the initial visit to 1 to 2 years of age.ResultsFor the nine untreated IHs, the NHF was highest at 6 months of age, during proliferation. Differences in NHFs between the proliferation and the plateau (p = 0.02) and involuting (p < 0.001) stages were statistically significant. In treated patients, the NHF normalized to 60% after 2 months. One treated IH came within 5% of the NHF for normal skin after 12 months.ConclusionsDOS can be used to assess the vascularity and tissue oxygenation of IHs and monitor their progression and response to treatment.