bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining the phenotypic spectrum of SLC6A1 mutations
Authors: Johannesen Katrine M. , Gardella Elena , Linnankivi Tarja , Courage Carolina , de Saint Martin Anne , Lehesjoki Anna‐Elina , Mignot Cyril , Afenjar Alexandra , Lesca Gaetan , Abi‐Warde Marie‐Thérèse , Chelly Jamel , Piton Amélie , Merritt J. Lawrence , Rodan Lance H. , Tan Wen‐Hann , Bird Lynne M. , Nespeca Mark , Gleeson Joseph G. , Yoo Yongjin , Choi Murim , Chae Jong‐Hee , Czapansky‐Beilman Desiree , Reichert Sara Chadwick , Pendziwiat Manuela , Verhoeven Judith S. , Schelhaas Helenius J. , Devinsky Orrin , Christensen Jakob , Specchio Nicola , Trivisano Marina , Weber Yvonne G. , Nava Caroline , Keren Boris , Doummar Diane , Schaefer Elise , Hopkins Sarah , Dubbs Holly , Shaw Jessica E. , Pisani Laura , Myers Candace T. , Tang Sha , Tang Shan , Pal Deb K. , Millichap John J. , Carvill Gemma L. , Helbig Kathrine L. , Mecarelli Oriano , Striano Pasquale , Helbig Ingo , Rubboli Guido , Mefford Heather C. , Møller Rikke S. 
Published: January 2018

SummaryObjectivePathogenic SLC6A1 variants were recently described in patients with myoclonic atonic epilepsy (MAE) and intellectual disability (ID). We set out to define the phenotypic spectrum in a larger cohort of SCL6A1‐mutated patients.MethodsWe collected 24 SLC6A1 probands and 6 affected family members. Four previously published cases were included for further electroclinical description. In total, we reviewed the electroclinical data of 34 subjects.ResultsCognitive development was impaired in 33/34 (97%) subjects; 28/34 had mild to moderate ID, with language impairment being the most common feature. Epilepsy was diagnosed in 31/34 cases with mean onset at 3.7 years. Cognitive assessment before epilepsy onset was available in 24/31 subjects and was normal in 25% (6/24), and consistent with mild ID in 46% (11/24) or moderate ID in 17% (4/24). Two patients had speech delay only, and 1 had severe ID. After epilepsy onset, cognition deteriorated in 46% (11/24) of cases. The most common seizure types were absence, myoclonic, and atonic seizures. Sixteen cases fulfilled the diagnostic criteria for MAE. Seven further patients had different forms of generalized epilepsy and 2 had focal epilepsy. Twenty of 31 patients became seizure‐free, with valproic acid being the most effective drug. There was no clear‐cut correlation between seizure control and cognitive outcome. Electroencephalography (EEG) findings were available in 27/31 patients showing irregular bursts of diffuse 2.5‐3.5 Hz spikes/polyspikes‐and‐slow waves in 25/31. Two patients developed an EEG pattern resembling electrical status epilepticus during sleep. Ataxia was observed in 7/34 cases. We describe 7 truncating and 18 missense variants, including 4 recurrent variants (Gly232Val, Ala288Val, Val342Met, and Gly362Arg).SignificanceMost patients carrying pathogenic SLC6A1 variants have an MAE phenotype with language delay and mild/moderate ID before epilepsy onset. However, ID alone or associated with focal epilepsy can also be observed.
Cytotoxic edema at onset in West syndrome of unknown etiology: A longitudinal diffusion tensor imaging study
Authors: Ogawa Chikako , Kidokoro Hiroyuki , Fukasawa Tatsuya , Yamamoto Hiroyuki , Ishihara Naoko , Ito Yuji , Sakaguchi Yoko , Okai Yu , Ohno Atsuko , Nakata Tomohiko , Azuma Yoshiteru , Hattori Ayako , Kubota Tetsuo , Tsuji Takeshi , Hirakawa Akihiro , Kawai Hisashi , Natsume Jun 
Published: January 2018

SummaryObjectiveTo clarify longitudinal changes in white matter microstructures from the onset of disease in patients with West syndrome (WS) of unknown etiology.MethodsDiffusion tensor imaging (DTI) was prospectively performed at onset and at 12 and 24 months old in 17 children with WS of unknown etiology. DTI was analyzed using tract‐based spatial statistics (TBSS) and tract‐specific analysis (TSA) of 13 fiber tracts, and fractional anisotropy (FA) and mean diffusivity (MD) were compared with those of 42 age‐matched controls. Correlations of FA and MD with developmental quotient (DQ) at age 24 months were analyzed. Multiple comparisons were adjusted for using the false discovery rate (q‐value).ResultsTBSS analysis at onset showed higher FA and lower MD in the corpus callosum and brainstem in patients. TSA showed lower MD in bilateral uncinate fasciculi (UF) (right: q < 0.001; left: q = 0.03) at onset in patients. TBSS showed a negative correlation between FA at onset and DQ in the right frontal lobe, whereas FA at 24 months old exhibited a positive correlation with DQ in the diffuse white matter. MD for bilateral UF at 24 months old on TSA correlated positively with DQ (q = 0.04, both).SignificanceThese findings may indicate the existence of cytotoxic edema in the immature white matter and dorsal brainstem at onset, and subsequent alterations in the diffuse white matter in WS of unknown etiology. Microstructural development in the UF might play important roles in cognitive development in WS.
Neonatal phenobarbital exposure disrupts GABAergic synaptic maturation in rat CA1 neurons
Authors: Al‐Muhtasib Nour , Sepulveda‐Rodriguez Alberto , Vicini Stefano , Forcelli Patrick A. 
Published: January 2018

SummaryObjectivePhenobarbital is the most commonly utilized drug for the treatment of neonatal seizures. The use of phenobarbital continues despite growing evidence that it exerts suboptimal seizure control and is associated with long‐term alterations in brain structure, function, and behavior. Alterations following neonatal phenobarbital exposure include acute induction of neuronal apoptosis, disruption of synaptic development in the striatum, and a host of behavioral deficits. These behavioral deficits include those in learning and memory mediated by the hippocampus. However, the synaptic changes caused by acute exposure to phenobarbital that lead to lasting effects on brain function and behavior remain understudied.MethodsPostnatal day (P)7 rat pups were treated with phenobarbital (75 mg/kg) or saline. On P13‐14 or P29‐37, acute slices were prepared and whole‐cell patch‐clamp recordings were made from CA1 pyramidal neurons.ResultsAt P14 we found an increase in miniature inhibitory postsynaptic current (mIPSC) frequency in the phenobarbital‐exposed as compared to the saline‐exposed group. In addition to this change in mIPSC frequency, the phenobarbital group displayed larger bicuculline‐sensitive tonic currents, decreased capacitance and membrane time constant, and a surprising persistence of giant depolarizing potentials. At P29+, the frequency of mIPSCs in the saline‐exposed group had increased significantly from the frequency at P14, typical of normal synaptic development; at this age the phenobarbital‐exposed group displayed a lower mIPSC frequency than did the control group. Spontaneous inhibitory postsynaptic current (sIPSC) frequency was unaffected at either P14 or P29+.SignificanceThese neurophysiological alterations following phenobarbital exposure provide a potential mechanism by which acute phenobarbital exposure can have a long‐lasting impact on brain development and behavior.
Climate change and interspecific interactions drive species alternations between anchovy and sardine in the western North Pacific: Detection of causality by convergent cross mapping
Authors: Nakayama Shin‐Ichiro , Takasuka Akinori , Ichinokawa Momoko , Okamura Hiroshi 
Published: January 2018

AbstractThe abundance and recruitment of anchovy Engraulis spp. and sardine Sardinops spp. alternate in a synchronized way across the Pacific. Convergent cross mapping (CCM) indicated that climate change drives the alternation of the two species in the California Current System. However, climate indices patterns in the western North Pacific contrast with those in the eastern North Pacific, despite synchronous species alternations occurring. Therefore, it is of great interest to clarify whether climate change, or any other factors, affects the population dynamics of Japanese anchovy and Japanese sardine in the western North Pacific. Using CCM, we tested whether climate change and interspecific interactions affect the population dynamics of these two species. We found that climate change affected recruitment, and we clarified the spatiotemporal pattern of this effect. This result supports the existing hypotheses that population dynamics are regulated by climate change in the western North Pacific. The present study also detected interspecific interactions between sardine and anchovy, which might promote the alternation of the two species, and has not been reported in other regions.
Regional forcing explains local species diversity and turnover on tropical islands
Authors: Ibanez Thomas , Keppel Gunnar , Baider Cláudia , Birkinshaw Chris , Culmsee Heike , Cordell Susan , Florens F. B. Vincent , Franklin Janet , Giardina Christian P. , Gillespie Thomas W. , Laidlaw Melinda , Litton Creighton M. , Martin Tara G. , Ostertag Rebecca , Parthasarathy Narayanaswamy , Randrianaivo Richard , Randrianjanahary Miramasoandro , Rajkumar Muthu , Rasingam Ladan , Ratovoson Fidy , Reza Ludovic , Sack Lawren , Aiba Shin‐ichiro , Webb Edward , Whitfeld Timothy J. S. , Zang Runguo , Birnbaum Philippe 
Published: January 2018

AbstractAimTo determine the role of regional forcing on plot‐level species diversity and composition, and to quantify the relative importance of biogeographical and climatic factors in explaining woody plant diversity and composition at the local‐, island‐ and archipelago‐scale.LocationForty‐one tropical islands of the Indo‐Pacific region from Madagascar to Hawai‘i Island.MethodsWe analysed the diversity and composition of tropical woody plant communities located across 113 plots, 41 islands and 19 archipelagos. We used generalized linear mixed‐effects models and generalized dissimilarity models to determine the role of regional forcing at the island and archipelago scale and to assess the relative importance of biogeographical (area and isolation of islands or archipelagos, geographical distance between plots) and climatic factors in explaining differences in local diversity and composition (species turnover). Analyses were conducted at different geographical scales (local, island and archipelago) and taxonomic levels (species, genus and family).ResultsVariation in local (plot‐level) diversity (as species density, the number of species per 100 woody plants) was primarily explained by island and archipelago identity. Maximum species density was positively correlated with the area of an island (or archipelago) and negatively correlated with the isolation of an archipelago. Local climatic variability was also a significant predictor of species density, but less important than regional forcing. Climate variables explained < 20% of the variation in species turnover across all plots. The importance of geographical distance between plots relative to climate in driving species turnover decreased from the species to family level, and from the regional to island level.Main conclusionsRegional forcing was the key driver of local diversity and composition on islands. Island area and archipelago isolation are likely driving local diversity through their effects on the pool of island species. Geographical distance between plots is the main factor explaining species turnover, while at higher taxonomic levels, climatic factors and niche conservatism are the main drivers.
Deletion of endoplasmic reticulum stress‐responsive co‐chaperone p58IPK protects mice from diet‐induced steatohepatitis
Authors: Bandla Harikrishna , Dasgupta Debanjali , Mauer Amy S. , Nozickova Barbora , Kumar Swarup , Hirsova Petra , Graham Rondell P. , Malhi Harmeet 
Published: January 2018

AimActivation of PKR‐like endoplasmic reticulum kinase (PERK), an endoplasmic reticulum stress sensor, is a feature of non‐alcoholic steatohepatitis (NASH), yet regulators of PERK signaling remain undefined in this context. The protein p58IPK regulates PERK; however, its role in NASH has not been examined. The aim of this study was to assess the in vivo role of p58IPK in the pathogenesis of dietary NASH.MethodsParameters of hepatocyte cell death, liver injury, inflammation, fibrosis, indirect calorimetry and PERK activation were assessed in p58IPK knockout (p58ipk−/−) mice and their wild‐type littermate controls. All animals were fed a diet enriched in fat, fructose, and cholesterol (FFC) for 20 weeks.ResultsActivation of PERK was attenuated in FFC‐fed p58ipk−/− mice. Accordingly, FFC‐fed p58ipk−/− mice showed a reduction in hepatocyte apoptosis and death receptor expression, with a significant reduction in serum alanine transaminase values. Correspondingly, macrophage accumulation and fibrosis were significantly lower in FFC‐fed p58ipk−/− mice.ConclusionWe have shown that, in an in vivo dietary NASH model, p58IPK mediates hepatocyte apoptosis and liver injury, likely through PERK phosphorylation. In the absence of p58IPK, PERK phosphorylation and NASH are attenuated. Inhibition of hepatic p58IPK could be a future target for NASH therapy.
Dermoscopic characterization of cutaneous lymphomas: a pilot survey
Authors: Ghahramani Grant K. , Goetz Kirsten E. , Liu Vincent 
Published: January 2018

AbstractBackgroundWhile substantial dermoscopic analysis of melanocytic lesions has been performed, dermoscopic characterization of cutaneous lymphoid proliferations has been limited. Cutaneous lymphoma, particularly early mycosis fungoides (MF) and its variants, is often challenging to clinically and pathologically distinguish from inflammatory processes of the skin. This study aimed to survey the dermoscopic findings of cutaneous lymphomas and to discern whether any patterns might potentially serve as specific signatures.MethodsFifteen patients with an established diagnosis of cutaneous lymphoma were prospectively recruited and seen in the university multidisciplinary cutaneous lymphoma program with MF, an MF‐ variant, CD30‐positive lymphoproliferative disorder, or cutaneous B‐cell lymphomas and were included in our study. Dermoscopic findings, histologic features, clinical characteristics, and demographic data were analyzed.ResultsPatch stage MF was characterized by interconnected white structureless patches encircling small fine linear vessels, yielding an overall trabeculated to fenestrated pattern under dermoscopy. Corresponding histopathologic findings for these patterns included epidermotropism, atypical pleomorphic cells, and lichenoid infiltrates. Folliculotropic mycosis fungoides (FMF) was characterized by folliculocentric erosions surrounded by dotted and fine linear vessels, loss of terminal follicles, comedo‐like openings, and interconnected regular‐appearing structureless patches. Corresponding histopathologic findings in these FMF cases were typical of FMF. Notably, these changes were not appreciated in lymphomatoid papulosis. Primary cutaneous follicle center B cell lymphoma showed crystalline structures and vascular pseudopods.ConclusionsCutaneous lymphomas appear to demonstrate characteristic dermoscopic patterns, reflective of the specific lymphoma type and its corresponding histopathology, which have not been seen in inflammatory skin conditions, such as psoriasis and eczematous dermatitis.
Efficacy and safety of noncultured melanocyte‐keratinocyte transplant procedure for vitiligo and other leukodermas: a critical analysis of the evidence
Authors: Vakharia Paras P. , Lee Dylan E. , Khachemoune Amor 
Published: January 2018

AbstractVitiligo is an acquired pigmentary skin of depigmentation occurring secondary to melanocyte destruction. Vitiligo and other leukodermas have a profound impact on quality of life. Current therapies include medical options, such as phototherapy, topical and systemic corticosteroids, topical calcineurin inhibitors, immunomodulators, and antioxidiants, and surgical options. Surgical options provide melanocytic cells to previously depigmented areas and use either tissue grafting or cellular grafting methods. Topical treatments are often insufficient, and many of the current surgical procedures have shown variable response rates. In this review, we discuss the process of the cellular grafting melanocyte‐keratinocyte transplantation procedure (MKTP) and critically analyze its efficacy and safety in the treatment of vitiligo and other leukodermas. PubMed was searched for studies (2001–2017) describing the use of MKTP in patients with vitiligo or other leukodermas. Articles or trials discussing the use of MKTP for these patients were selected for in‐depth review. Clinically relevant results regarding efficacy and safety of MKTP in vitiligo and leukoderma patients were analyzed. Numerous trials and case series/reports have demonstrated tolerability and efficacy of MKTP with repigmentation for patients with refractory, stable vitiligo. However, the response rates have been variable, likely influenced by vitiligo type and affected areas. Future research and clinical reporting will provide more insight on which phenotypes may benefit from MKTP.
Differences in pre‐service teachers' knowledge and readiness to use ICT in education
Authors: Valtonen Teemu , Kukkonen Jari , Kontkanen Sini , Mäkitalo‐Siegl Kati , Sointu Erkko 
Published: January 2018

AbstractThe aim of this paper is to provide insights into differences between pre‐service teachers based on the areas of technological pedagogical content knowledge (TPACK) and the areas of theory of planned behaviour (TPB) in the context of using information and communication technology in education. The target group consisted of 267 first‐year pre‐service teachers at 3 Finnish universities. Differences between pre‐service teachers were outlined using cluster analysis based on their knowledge of different TPACK areas (the respondents' weak and strong areas). To see how the TPB areas aligned with the 4 TPACK clusters, 1‐way analysis of variance was used. Statistically significant differences between the 4 clusters were found in all the TPB areas except subjective norms. These results provide insights into the differences among pre‐service teachers in the context of TPACK and the TPB. They also suggest that instead of considering pre‐service teachers as one homogenous group, we need to understand the variations among their abilities and knowledge in order to be able to provide them with support they need within teacher education.
Larvicidal activities of limonoids from Turraea abyssinica (Meliaceae) on Tuta absoluta (Meyrick)
Authors: Essoung F. R. E. , Chhabra S. C. , Mba'ning B. M. , Mohamed S. A. , Lwande W. , Lenta B. N. , Ngouela S. A. , Tsamo E. , Hassanali A. 
Published: January 2018

AbstractPreliminary screening of extracts of the leaves and stems of four Turraea plant species (Meliaceae) on second instar larvae of Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) showed that the methanolic extract of Turraea abyssinica leaves possess good toxic potential with LD50 of 270.7 ppm. Fractionation of this extract led to isolation of a new limonoid derivative, 12α‐diacetoxywalsuranolide (1) and three other known limonoids [1α,7α,12α‐triacetoxy‐4α‐carbomethoxy‐11β‐hydroxy‐14β,15β‐epoxyhavanensin (2), 11‐epi‐21‐hydroxytoonacilide (3), 11β,12α‐diacetoxycedrelone (4)]. The structures of the compounds were established by IR, UV, mass spectrometry and 1D/2D NMR analyses, and in the case of the known compounds, also by comparison with reported data. All the isolates were tested for their larvicidal activities at different dose range against second instar larvae of T. absoluta. They were found to be more active (with LD50 < 7.0 ppm) compared to the reference compound azadirachtin (LD50 value of 7.8 ppm).
Complexity in internal medicine wards: A novel screening method and implications for management
Authors: Bandini Fabrizio , Guidi Stefano , Blaszczyk Silvia , Fumarulo Antonietta , Pierini Michela , Pratesi Paolo , Spolveri Stefano , Padeletti Margherita , Petrone Pasquale , Zoppi Paolo , Landini Giancarlo 
Published: January 2018

AbstractRationaleComplexity is increasingly recognized as a critical variable in health care. However, there is still lack of practical tools to assess it and tackle the challenges that stem from it, particularly within hospitals.Aims and objectiveTo validate a simple novel screening method based on both objective and subjective criteria to identify patients with clinically complex hospitalization events. To evaluate the prevalence of patients with complex events, identify their features, and compare them with those of the other patients and to those of patients with multimorbidities.MethodWe monitored the level of complexity of the hospitalization events of 240 patients admitted to an internal medicine ward in Tuscany over the course of 56 days. We compared the demographic features, the length of stay, and the prognosis of patients with and without complex events.ResultsSixty‐nine patients (28.8% of the sample) had a complex episode during their stay, and 115 (47.9%) had phases of low complexity. Patients with complex episodes were younger and more comorbid than patients without. They stayed longer in‐hospital (+4.5 days; 95% CI: 2.5‐6.5) and had higher mortality (OR: 24.93; 95% CI: 6.97‐171.63) and a lower probability of home discharge (OR: 0.25; 95% CI: 0.13‐0.48).ConclusionsThe results show that using a simple screening method is possible to identify complex patients within IM wards and that every day, about one‐third of the patients are complex. The results are discussed in implications for the dynamic management of patients with complex and simple phases during hospitalization.
First identification and characterization of Streptococcus iniae obtained from tilapia (Oreochromis aureus) farmed in Mexico
Authors: Ortega C , García I , Irgang R , Fajardo R , Tapia‐Cammas D , Acosta J , Avendaño‐Herrera R 
Published: January 2018

AbstractThis is the first study to isolate, identify and characterize Streptococcus iniae as the causative disease agent in two tilapia (Oreochromis aureus) populations. The populations were geographically isolated, of distinct origins, and did not share water sources. Affected fish showed various external (e.g., exophthalmia and cachexia, among others) and internal (e.g., granulomatous septicaemia and interstitial nephritis, among others) signs. All internal organ samples produced pure cultures, two of which (one from each farm, termed S‐1 and S‐2) were subjected to biochemical, PCR and 16S rRNA sequencing (99.5% similarity) analyses, confirming S. iniae identification. The two isolates presented genetic homogeneity regardless of technique (i.e., RAPD, REP‐PCR and ERIC‐PCR analyses). Pathogenic potentials were assessed through intraperitoneal injection challenges in rainbow trout (Oncorhynchus mykiss) and zebrafish (Danio rerio). Rainbow trout mortalities were respectively 40% and 70% at 104 and 106 CFU per fish with the S‐1 isolate, while 100% mortality rates were recorded in zebrafish at 102 and 104 CFU per fish with the S‐2 isolate. The obtained data clearly indicate a relationship between intensified aquaculture activities in Mexico and new disease appearances. Future studies should establish clinical significances for the tilapia industry.