bluuebunny/crossref_metadata_2025_split huggingface dataset:
Severe Insulin Resistance Alters Metabolism in Mesenchymal Progenitor Cells
Authors: Balhara Bharti , Burkart Alison , Topcu Vehap , Lee Youn-Kyoung , Cowan Chad , Kahn C. Ronald , Patti Mary-Elizabeth 
Published: March 2015

AbstractDonohue syndrome (DS) is characterized by severe insulin resistance due to mutations in the insulin receptor (INSR) gene. To identify molecular defects contributing to metabolic dysregulation in DS in the undifferentiated state, we generated mesenchymal progenitor cells (MPCs) from induced pluripotent stem cells derived from a 4-week-old female with DS and a healthy newborn male (control). INSR mRNA and protein were significantly reduced in DS MPC (for β-subunit, 64% and 89% reduction, respectively, P &lt; .05), but IGF1R mRNA and protein did not differ vs control. Insulin-stimulated phosphorylation of INSR or the downstream substrates insulin receptor substrate 1 and protein kinase B did not differ, but ERK phosphorylation tended to be reduced in DS (32% decrease, P = .07). By contrast, IGF-1 and insulin-stimulated insulin-like growth factor 1 (IGF-1) receptor phosphorylation were increased in DS (IGF-1, 8.5- vs 4.5-fold increase; INS, 11- vs 6-fold; P &lt; .05). DS MPC tended to have higher oxygen consumption in both the basal state (87% higher, P =.09) and in response to the uncoupler carbonyl cyanide-p-triflouromethoxyphenylhydrazone (2-fold increase, P =.06). Although mitochondrial DNA or mass did not differ, oxidative phosphorylation protein complexes III and V were increased in DS (by 37% and 6%, respectively; P &lt; .05). Extracellular acidification also tended to increase in DS (91% increase, P = .07), with parallel significant increases in lactate secretion (34% higher at 4 h, P &lt; .05). In summary, DS MPC maintain signaling downstream of the INSR, suggesting that IGF-1R signaling may partly compensate for INSR mutations. However, alterations in receptor expression and pathway-specific defects in insulin signaling, even in undifferentiated cells, can alter cellular oxidative metabolism, potentially via transcriptional mechanisms.
A Mouse Model Suggests Two Mechanisms for Thyroid Alterations in Infantile Cystinosis: Decreased Thyroglobulin Synthesis Due to Endoplasmic Reticulum Stress/Unfolded Protein Response and Impaired Lysosomal Processing
Authors: Gaide Chevronnay H. P. , Janssens V. , Van Der Smissen P. , Liao X. H. , Abid Y. , Nevo N. , Antignac C. , Refetoff S. , Cherqui S. , Pierreux C. E. , Courtoy P. J. 
Published: March 2015

Abstract
Thyroid hormones are released from thyroglobulin (Tg) in lysosomes, which are impaired in infantile/nephropathic cystinosis. Cystinosis is a lysosomal cystine storage disease due to defective cystine exporter, cystinosin. Cystinotic children develop subclinical and then overt hypothyroidism. Why hypothyroidism is the most frequent and earliest endocrine complication of cystinosis is unknown. We here defined early alterations in Ctns−/− mice thyroid and identified subcellular and molecular mechanisms. At 9 months, T4 and T3 plasma levels were normal and TSH was moderately increased (∼4-fold). By histology, hyperplasia and hypertrophy of most follicles preceded colloid exhaustion. Increased immunolabeling for thyrocyte proliferation and apoptotic shedding indicated accelerated cell turnover. Electron microscopy revealed endoplasmic reticulum (ER) dilation, apical lamellipodia indicating macropinocytic colloid uptake, and lysosomal cystine crystals. Tg accumulation in dilated ER contrasted with mRNA down-regulation. Increased expression of ER chaperones, glucose-regulated protein of 78 kDa and protein disulfide isomerase, associated with alternative X-box binding protein-1 splicing, revealed unfolded protein response (UPR) activation by ER stress. Decreased Tg mRNA and ER stress suggested reduced Tg synthesis. Coordinated increase of UPR markers, activating transcription factor-4 and C/EBP homologous protein, linked ER stress to apoptosis. Hormonogenic cathepsins were not altered, but lysosome-associated membrane protein-1 immunolabeling disclosed enlarged vesicles containing iodo-Tg and impaired lysosomal fusion. Isopycnic fractionation showed iodo-Tg accumulation in denser lysosomes, suggesting defective lysosomal processing and hormone release. In conclusion, Ctns−/− mice showed the following alterations: 1) compensated primary hypothyroidism and accelerated thyrocyte turnover; 2) impaired Tg production linked to ER stress/UPR response; and 3) altered endolysosomal trafficking and iodo-Tg processing. The Ctns−/− thyroid is useful to study disease progression and evaluate novel therapies.
TLR4 at the Crossroads of Nutrients, Gut Microbiota, and Metabolic Inflammation
Authors: Velloso Licio A. , Folli Franco , Saad Mario J. 
Published: March 2015

AbstractObesity is accompanied by the activation of low-grade inflammatory activity in metabolically relevant tissues. Studies have shown that obesity-associated insulin resistance results from the inflammatory targeting and inhibition of key proteins of the insulin-signaling pathway. At least three apparently distinct mechanisms–endoplasmic reticulum stress, toll-like receptor (TLR) 4 activation, and changes in gut microbiota–have been identified as triggers of obesity-associated metabolic inflammation; thus, they are expected to represent potential targets for the treatment of obesity and its comorbidities. Here, we review the data that place TLR4 in the center of the events that connect the consumption of dietary fats with metabolic inflammation and insulin resistance. Changes in the gut microbiota can lead to reduced integrity of the intestinal barrier, leading to increased leakage of lipopolysaccharides and fatty acids, which can act upon TLR4 to activate systemic inflammation. Fatty acids can also trigger endoplasmic reticulum stress, which can be further stimulated by cross talk with active TLR4. Thus, the current data support a connection among the three main triggers of metabolic inflammation, and TLR4 emerges as a link among all of these mechanisms.
High-resolution live imaging reveals axon-glia interactions during peripheral nerve injury and repair in zebrafish
Authors: Xiao Yan , Faucherre Adèle , Pola-Morell Laura , Heddleston John M. , Liu Tsung-Li , Chew Teng-Leong , Sato Fuminori , Sehara-Fujisawa Atsuko , Kawakami Koichi , López-Schier Hernán 
Published: March 2015

ABSTRACT
Neural damage is a devastating outcome of physical trauma. The glia are one of the main effectors of neuronal repair in the nervous system, but the dynamic interactions between peripheral neurons and Schwann cells during injury and regeneration remain incompletely characterized. Here, we combine laser microsurgery, genetic analysis, high-resolution intravital imaging and lattice light-sheet microscopy to study the interaction between Schwann cells and sensory neurons in a zebrafish model of neurotrauma. We found that chronic denervation by neuronal ablation leads to Schwann-cell death, whereas acute denervation by axonal severing does not affect the overall complexity and architecture of the glia. Neuronal-circuit regeneration begins when Schwann cells extend bridging processes to close the injury gap. Regenerating axons grow faster and directionally after the physiological clearing of distal debris by the Schwann cells. This might facilitate circuit repair by ensuring that axons are guided through unoccupied spaces within bands of Büngner towards their original peripheral target. Accordingly, in the absence of Schwann cells, regenerating axons are misrouted, impairing the re-innervation of sensory organs. Our results indicate that regenerating axons use haptotaxis as a directional cue during the reconstitution of a neural circuit. These findings have implications for therapies aimed at neurorepair, which will benefit from preserving the architecture of the peripheral glia during periods of denervation.
Phenotype-driven chemical screening in zebrafish for compounds that inhibit collective cell migration identifies multiple pathways potentially involved in metastatic invasion
Authors: Gallardo Viviana E. , Varshney Gaurav K. , Lee Minnkyong , Bupp Sujata , Xu Lisha , Shinn Paul , Crawford Nigel P. , Inglese James , Burgess Shawn M. 
Published: March 2015

ABSTRACT
In the last decade, high-throughput chemical screening has become the dominant approach for discovering novel compounds with therapeutic properties. Automated screening using in vitro or cultured cell assays have yielded thousands of candidate drugs for a variety of biological targets, but these approaches have not resulted in an increase in drug discovery despite major increases in expenditures. In contrast, phenotype-driven screens have shown a much stronger success rate, which is why we developed an in vivo assay using transgenic zebrafish with a GFP-marked migrating posterior lateral line primordium (PLLp) to identify compounds that influence collective cell migration. We then conducted a high-throughput screen using a compound library of 2160 annotated bioactive synthetic compounds and 800 natural products to identify molecules that block normal PLLp migration. We identified 165 compounds that interfere with primordium migration without overt toxicity in vivo. Selected compounds were confirmed in their migration-blocking activity by using additional assays for cell migration. We then proved the screen to be successful in identifying anti-metastatic compounds active in vivo by performing orthotopic tumor implantation assays in mice. We demonstrated that the Src inhibitor SU6656, identified in our screen, can be used to suppress the metastatic capacity of a highly aggressive mammary tumor cell line. Finally, we used CRISPR/Cas9-targeted mutagenesis in zebrafish to genetically validate predicted targets of compounds. This approach demonstrates that the migrating PLLp in zebrafish can be used for large-scale, high-throughput screening for compounds that inhibit collective cell migration and, potentially, anti-metastatic compounds.
Funding source and primary outcome changes in clinical trials registered on ClinicalTrials.gov are associated with the reporting of a statistically significant primary outcome: a cross-sectional study
Authors: Ramagopalan Sreeram V , Skingsley Andrew P. , Handunnetthi Lahiru , Magnus Daniel , Klingel Michelle , Pakpoor Julia , Goldacre Ben 
Published: March 2015

Background: We and others have shown a significant proportion of interventional trials registered on ClinicalTrials.gov have their primary outcomes altered after the listed study start and completion dates. The objectives of this study were to investigate whether changes made to primary outcomes are associated with the likelihood of reporting a statistically significant primary outcome on ClinicalTrials.gov.Methods: A cross-sectional analysis of all interventional clinical trials registered on ClinicalTrials.gov as of 20 November 2014 was performed. The main outcome was any change made to the initially listed primary outcome and the time of the change in relation to the trial start and end date.Findings: 13,238 completed interventional trials were registered with ClinicalTrials.gov that also had study results posted on the website. 2555 (19.3%) had one or more statistically significant primary outcomes. Statistical analysis showed that registration year, funding source and primary outcome change after trial completion were associated with reporting a statistically significant primary outcome.Conclusions: Funding source and primary outcome change after trial completion are associated with a statistically significant primary outcome report on clinicaltrials.gov.
Caregiving burden and psychological distress among spouses of bipolar patients – comparative analysis of subtype I and II
Authors: Arciszewska Aleksandra , Siwek Marcin , Dudek Dominika 
Published: March 2015

CelOcena poczucia obciążenia opieką nad chorym oraz poziomu dystresu psychicznego wśród małżonków pacjentów z chorobą afektywną dwubiegunową – ChAD
(I i II).MetodaDo badania włączono 77 osób – 41 kobiet oraz 36 mężczyzn. 44 badanych pozostawało w związku z pacjentami z ChAD I, a 33 – z pacjentami z ChAD II. Narzędzia badawcze: Kwestionariusz Oceny Zaangażowania - IEQ oraz Kwestionariusz Ogólnego Stanu Zdrowia - GHQ-12.WynikiMania w przebiegu ChAD I jest bardziej obciążająca, niż epizod obniżonego nastroju (ChAD I) i hipomania (ChAD II). Depresja w przebiegu ChAD II jest bardziej obciążająca, niż hipomania. Małżonkowie osób
z rozpoznaniem ChAD I są bardziej obciążeni, niż małżonkowie pacjentów z ChAD II. Kobiety doświadczają większego brzemienia, niż mężczyźni. Partnerzy/partnerki związani z osobą z ChAD (I i II) odczuwają ten sam, wysoki poziom dystresu psychicznego.WnioskiPoszczególne typy ChAD (I i II) wpływają odmiennie na partnerów/partnerki osób chorujących, oddziałując na ich subiektywne i obiektywne poczucie brzemienia oraz relacje z chorym, co wskazuje na realną potrzebę zaoferowania im adekwatnej (w zależności od podtypu choroby pacjenta, a także płci małżonka) pomocy.
Changes in intensity of neurotic symptoms associated with reduction of suicidal ideation in patients who underwent psychotherapy in the day hospital for the treatment of neurotic and behavioral disorders
Authors: Rodziński Paweł , Rutkowski Krzysztof , Murzyn Agnieszka , Sobański Jerzy , Cyranka Katarzyna , Dembińska Edyta , Grządziel Karolina , Klasa Katarzyna , Mielimąka Michał , Müldner-Nieckowski Łukasz , Smiatek-Mazgaj Bogna 
Published: March 2015

CelAnaliza związków pomiędzy zmianami w nasileniu dolegliwości nerwicowych a redukcją myśli samobójczych (MS) – tj. ich ustąpieniem lub redukcją ich nasilenia – lub brakiem redukcji MS u pacjentów, którzy przebyli cykl intensywnej psychoterapii prowadzonej w podejściu integracyjnym z przewagą podejścia psychodynamicznego w oddziale dziennym.MetodaKwestionariusze objawowe KO”0” i Ankiety życiorysowe wypełnione przez 473 kobiety i 207 mężczyzn leczonych w dziennym oddziale psychoterapeutycznym z powodu zaburzeń nerwicowych, behawioralnych i zaburzeń osobowości w latach 2005-2013. Podczas kwalifikacji MS zadeklarowało 134 kobiet i 80 mężczyzn, z czego poprawę uzyskało odpowiednio 84,3% oraz 77,5%.WynikiU pacjentów obu płci, którzy uzyskali poprawę w zakresie MS zaobserwowano istotnie większą, niż u pacjentów bez owej poprawy, redukcję nasilenia objawów neurotycznych. Dotyczyło to globalnego nasilenia objawów nerwicowych (współczynnik OWK) u obu płci (p<0,001), jak również większości rodzajów objawów nerwicowych u obu płci (p<0,05): Zaburzenia fobiczne, Inne zaburzenia lękowe, Zaburzenia obsesyjno-kompulsyjne, Konwersje, Zaburzenia autonomiczne, Zaburzenia somatyzacyjne, Neurastenia, Unikanie i zależność, Dysfunkcje seksualne, Dystymia; oraz wyłącznie u kobiet (p<0,05): Zaburzenia hipochondryczne, Depersonalizacje i derealizacje, Impulsywność i histrioniczność, Nieorganiczne zaburzenia snu.WnioskiNiniejsze badanie dostarczyło wyników, które potwierdzają skuteczność i kompleksowość intensywnej psychoterapii, jako metody leczenia prowadzącej do poprawy zarówno w zakresie MS, jak i w zakresie objawów zaburzeń nerwicowych. Pozwala to przypuszczać, że zastosowana forma psychoterapii może stanowić efektywną metodę prewencji suicydalności w tej grupie pacjentów. Zaobserwowane powiązania przemawiają także za trafnością hipotez o zbliżonej etiopatogenezie i częściowo tożsamych czynnikach osobowościowych predysponujących do wystąpienia MS i zaburzeń nerwicowych.
Changes in ego strength in patients with neurotic and personality disorders treated with a short-term comprehensive psychodynamic psychotherapy
Authors: Cyranka Katarzyna , Rutkowski Krzysztof , Mielimąka Michał , Sobański Jerzy , Klasa Katarzyna , Müldner-Nieckowski Łukasz , Dembińska Edyta , Smiatek-Mazgaj Bogna , Rodziński Paweł 
Published: March 2015

CelZbadanie zmiany siły ego w toku psychoterapii grupowej pacjentów leczonych z powodu zaburzeń nerwicowych i wybranych zaburzeń osobowości (F40-F61 ICD-10).MetodaW badaniu uczestniczyło 82 pacjentów (61 kobiet i 21 mężczyzn) leczonych intensywną krótkoterminową psychoterapią grupową w oddziale dziennym leczenia nerwic i zaburzeń behawioralnych. Dokonano oceny funkcjonowania osobowości pacjentów na początku i na końcu psychoterapii przy użyciu skali siły ego kwestionariusza MMPI-2.WynikiW wyniku zastosowania psychoterapii u większości pacjentów zaobserwowano znaczący wzrost siły ego.
Zaobserwowano, iż znaczący przyrost w zakresie siły ego dotyczy zarówno grupy kobiet jak i mężczyzn. Nie odnotowano także różnic pomiędzy pacjentami z rozpoznaniem specyficznych zaburzeń osobowości i zaburzeń nerwicowych zarówno jeśli chodzi o wyniki początkowe, jak i końcowe. U pacjentów, którzy rozpoczynają leczenie z wartościami siły ego w zakresie niskim także dochodzi do korzystnych i istotnych klinicznie zmian.WnioskiKrótkoterminowa, intensywna psychoterapia grupowa z elementami psychoterapii indywidualnej prowadzi do uzyskania pożądanych zmian w funkcjonowaniu osobowości wyrażonych znaczącym wzrostem siły ego.
Effect of Integrated Pest Management Modules against Diamond Back Moth Plutella xylostella (L) and parasitoid Cotesia plutellae (Kurdjumov)
Authors: Manisegaran S. , Vinoth R. 
Published: March 2015

Two field experiments were carried out during Kharif 2012 and Rabi 2013 to assess the effect of IPM module against Diamond Back Moth, (DBM) Plutella xylostella (L) and its parasitoid Cotesia plutellae (Kurdjumov). Among five IPM modules tested, the suggestive module was found effective against DBM P. xylostella irrespective of the seasons. The suggestive module (M4) has recorded the lowest mean larval population (0.90 and 0.75 nos. / head) and registered 66 and 64. 76 percent reduction in damage over control besides recorded the highest yield of 35.13 and 35.67 t/ha and incremental cost benefit ratio of 3:26 in Kharif 2012 and Rabi 2013 respectively. Further, a maximum parasitization by C. plutellae to the tune of 30.00 percent was noticed in Suggestive module when cabbage was intercropped with onion.
Physiological Responses of Young Plants of Carpobrotus edulis (L.) N.E. Br (Aizoaceae) to Salt and Water Stress
Authors: Duarte Vilma , Fonseca Filomena 
Published: March 2015

Coastal sand-dune ecosystems have a high conservational value worldwide, but are frequently subjected to the introduction of exotic floral species by man. One of these species, cohabiting successfully with the native flora of Mediterranean-type coastal habitats, is the succulent Carpobrotus edulis. This species is native to South Africa and is considered an invasive species due to its capability to compete with the local flora, invading and quickly establishing itself in cleared areas. Studies at the ecological level, on the impact of this species and its hybrids on native flora of different countries, are available in the literature. However C. edulis seemingly competitive advantages remain poorly characterized at the physiological level. To investigate the responses of this species to the main stresses present in sand-dune habitats, C. edulis plants, grown from seed under controlled conditions, were subjected to water stress and salt stress. Rapid light response curves, shoot growth and concentration of photosynthetic pigments and soluble protein were determined, and the detection of differentially expressed genes was initiated. It was found that both types of stress did not negatively affect photosynthetic electron transport rate and shoot concentration of photosynthetic pigments in this species. However, shoot soluble protein concentration was significantly decreased by salt and water stress, in relation to control levels. Both types of stress induced differential gene expression. Although work is still under way, the set of genes affected by water stress appears to be different from the set of genes affected by salt stress.
Does tranexamic acid alter the risk of thromboembolism after total hip arthroplasty in the absence of routine chemical thromboprophylaxis?
Authors: Nishihara S. , Hamada M. 
Published: March 2015

Tranexamic acid (TXA) has been used to reduce blood loss during total hip arthroplasty (THA), but its use could increase the risk of venous thromboembolic disease (VTE). Several studies have reported that TXA does not increase the prevalence of deep vein thrombosis (DVT), but most of those used routine chemical thromboprophylaxis, thereby masking the potential increased risk of TXA on VTE. We wished to ascertain whether TXA increases the prevalence of VTE in patients undergoing THA without routine chemical thromboprophylaxis. We carried out a retrospective case-control study in 254 patients who underwent a primary THA, 127 of whom received TXA (1 g given pre-operatively) and a control group of 127 who did not. All patients had mechanical but no chemical thomboprophylaxis. Each patient was examined for DVT by bilateral ultrasonography pre-operatively and on post-operative days 1 and 7. TXA was found to statistically significantly increase the incidence of total DVT on post-operative day 7 compared with the control group (24 (18.9%) and 12 (9.4%), respectively; p < 0.05) but most cases of DVT were isolated distal DVT, with the exception of one patient with proximal DVT in each group. One patient in the control group developed a non-fatal symptomatic pulmonary embolism (PE). The use of TXA did not appear to affect the prevalence of either proximal DVT or PE. Cite this article: Bone Joint J 2015; 97-B:458–62.
Changing trends in the management of children’s fractures
Authors: Kosuge D. , Barry M. 
Published: March 2015

The management of children’s fractures has evolved as a result of better health education, changes in lifestyle, improved implant technology and the changing expectations of society. This review focuses on the changes seen in paediatric fractures, including epidemiology, the increasing problems of obesity, the mechanisms of injury, non-accidental injuries and litigation. We also examine the changes in the management of fractures at three specific sites: the supracondylar humerus, femoral shaft and forearm. There has been an increasing trend towards surgical stabilisation of these fractures. The reasons for this are multifactorial, including societal expectations of a perfect result and reduced hospital stay. Reduced hospital stay is beneficial to the social, educational and psychological needs of the child and beneficial to society as a whole, due to reduced costs. Cite this article: Bone Joint J 2015; 97-B:442–8.
Validation of a prediction model that allows direct comparison of the Oxford Knee Score and American Knee Society clinical rating system
Authors: Maempel J. F. , Clement N. D. , Brenkel I. J. , Walmsley P. J. 
Published: March 2015

This study demonstrates a significant correlation between the American Knee Society (AKS) Clinical Rating System and the Oxford Knee Score (OKS) and provides a validated prediction tool to estimate score conversion.A total of 1022 patients were prospectively clinically assessed five years after TKR and completed AKS assessments and an OKS questionnaire. Multivariate regression analysis demonstrated significant correlations between OKS and the AKS knee and function scores but a stronger correlation (r = 0.68, p < 0.001) when using the sum of the AKS knee and function scores. Addition of body mass index and age (other statistically significant predictors of OKS) to the algorithm did not significantly increase the predictive value.The simple regression model was used to predict the OKS in a group of 236 patients who were clinically assessed nine to ten years after TKR using the AKS system. The predicted OKS was compared with actual OKS in the second group. Intra-class correlation demonstrated excellent reliability (r = 0.81, 95% confidence intervals 0.75 to 0.85) for the combined knee and function score when used to predict OKS.Our findings will facilitate comparison of outcome data from studies and registries using either the OKS or the AKS scores and may also be of value for those undertaking meta-analyses and systematic reviews.Cite this article: Bone Joint J 2015;97-B:503–9.