bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thalidomide and Lenalidomide for Refractory Systemic/Cutaneous Lupus Erythematosus Treatment
Authors: Yuki Emily Figueiredo Neves , Silva Clovis A. , Aikawa Nadia E. , Romiti Ricardo , Heise Carlos Otto , Bonfa Eloisa , Pasoto Sandra Gofinet 
Published: November 2019

Background
Thalidomide has shown exceptional results in systemic/cutaneous lupus erythematosus(SLE/CLE). Recently, lenalidomide has been also prescribed for SLE/CLE treatment. Literature regarding efficacy/adverse events for these drugs is scarce with a single systematic review and meta-analysis focused solely on thalidomide for refractory cutaneous lupus subtypes.

Objective
We, therefore, addressed in this narrative review the efficacy/adverse effects of thalidomide and lenalidomide for SLE and CLE. In addition, we provide a specialist approach for clinical practice based on the available evidence.

Results
Efficacy of thalidomide for refractory cutaneous lupus treatment was demonstrated by several studies, mostly retrospective with small sample size(≤20). The frequency of peripheral polyneuropathy is controversial varying from 15-80% with no consistent data regarding cumulative dose and length of use. Drug withdrawn results in clinical partial/complete reversibility for most cases (70%). For lenalidomide, seven studies (small sample sizes) reported its efficacy for SLE/CLE with complete/partial response in all patients with a mean time to response of 3 months. Flare rate varied from 25-75% occurring 0.5-10 months after drug withdrawn. There were no reports of polyneuropathy/worsening of previous thalidomide-induced neuropathy, but most of them did not perform nerve conduction studies. Teratogenicity risk exist for both drugs and strict precautions are required.

Conclusions
Thalidomide is very efficacious as an induction therapy for patients with severe/refractory cutaneous lupus with high risk of scarring, but its longstanding use should be avoided due to neurotoxicity. Lenalidomide is a promising drug for skin lupus treatment, particularly regarding the apparent lower frequency of nerve side effects.
FDG PET/CT and Ultrasound Evaluation of Breast Implant–Associated Anaplastic Large Cell Lymphoma
Authors: Pandika Veska , Covington Matthew F. 
Published: November 2019

Abstract
Breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) is a rare malignancy with isolated case reports of FDG uptake on FDG PET/CT. We present 4 cases of pathology-confirmed BIA-ALCL to illustrate varying presentations and imaging features of this disease process. Breast implant–associated anaplastic large cell lymphoma presents most commonly approximately 10 years after implantation of textured silicone or saline breast implants. Patients may present with breast enlargement, peri-implant effusion, a palpable breast or axillary mass, lymphadenopathy, breast skin erythema, or pain. Diagnosis of BIA-ALCL may be confirmed by sampling of peri-implant fluid or biopsy of peri-implant masses or regional lymph nodes.
Pulmonary Vein Varix Mimicking Prostate Cancer Metastasis on 68Ga–Prostate Specific Membrane Antigen-11 PET/CT
Authors: Sgard Brian , Montravers Françoise , Fourquet Aloÿse , de la Taille Alexandre , Gauthé Mathieu 
Published: November 2019

Abstract
The use of PET/CT with prostate-specific membrane antigen radioligands for staging prostate cancer patients presenting a biochemical recurrence is increasing. As a consequence, the number of reports of diagnostic pitfall of this imaging modality is also increasing. A 75-year-old man referred for a second episode of biochemical recurrence of prostate cancer presented an isolated intense prostate-specific membrane antigen-11 uptake from a right lung abnormality. This abnormality was suggestive of pulmonary vein varix on contrast-enhanced lung CT. The uptake remained stable 1 month after starting androgen deprivation therapy, which confirmed the diagnostic of pulmonary vein varix.
Pharmacokinetic Analysis of [18F]FAZA Dynamic PET Imaging Acquisitions for Highlighting Sacrum Tumor Profiles
Authors: Provost Claire , Mammar Hamid , Belly-Poinsignon Anne , Madar Olivier , Champion Laurence 
Published: November 2019

Abstract
A patient enrolled in a clinical trial (NCT02802969) with suspicion of chordoma underwent an [18F]FAZA PET/CT, a radiolabeled nitroimidazole analog of hypoxia PET imaging. The patient's images showed a different tumor profile compared to those observed in other hypoxic or nonhypoxic chordoma patients. The motivation for using [18F]FAZA pharmacokinetic imaging was to compare this profile with histologically confirmed cases of chordoma. Through visual imaging and quantification of blood and tumor time-activity curves, we excluded the hypothesis that it was a chordoma, diagnosing a paraganglioma.
Discriminating Progressive Supranuclear Palsy from Parkinson’s Disease using wearable technology and machine learning
Authors: De Vos Maarten , Prince John , Buchanan Tim , FitzGerald James J. , Antoniades Chrystalina A. 
Published: November 2019

AbstractBackgroundProgressive supranuclear palsy (PSP), a neurodegenerative conditions may be difficult to discriminate clinically from idiopathic Parkinson’s disease (PD). It is critical that we are able to do this accurately and as early as possible in order that future disease modifying therapies for PSP may be deployed at a stage when they are likely to have maximal benefit. Analysis of gait and related tasks is one possible means of discrimination.Research QuestionHere we investigate a wearable sensor array coupled with machine learning approaches as a means of disease classification.Methods21 participants with PSP, 20 with PD, and 39 healthy control (HC) subjects performed a two minute walk, static sway test, and timed up-and-go task, while wearing an array of six inertial measurement units. The data were analysed to determine what features discriminated PSP from PD and PSP from HC. Two machine learning algorithms were applied, Logistic Regression (LR) and Random Forest (RF).Results17 features were identified in the combined dataset that contained independent information. The RF classifier outperformed the LR classifier, and allowed discrimination of PSP from PD with 86% sensitivity and 90% specificity, and PSP from HC with 90% sensitivity and 97% specificity. Using data from the single lumbar sensor only resulted in only a modest reduction in classification accuracy, which could be restored using 3 sensors (lumbar, right arm and foot). However for maximum specificity the full six sensor array was needed.SignificanceA wearable sensor array coupled with machine learning methods can accurately discriminate PSP from PD. Choice of array complexity depends on context; for diagnostic purposes a high specificity is needed suggesting the more complete array is advantageous, while for subsequent disease tracking a simpler system may suffice.
Findings of a feasibility study of pre-operative pulmonary rehabilitation to reduce post-operative pulmonary complications in people with chronic obstructive pulmonary disease scheduled for major abdominal surgery
Authors: Marlow Lucy L , Lee Angeline HY , Hedley Emma , Grocott Michael P , Steiner Michael C , Young J. Duncan , Rahman Najib M , Snowden Christopher P , Pattinson Kyle T S 
Published: November 2019

AbstractBackgroundPatients with chronic obstructive pulmonary disease (COPD) are at increased risk of complications and death following surgery. Pulmonary complications are particularly prominent. Pulmonary rehabilitation is a course of physical exercise and education that helps people with COPD manage their condition. Although proven to improve health outcomes in patients with stable COPD, it has never been formally tested as a pre-surgical intervention in patients scheduled for non-cardiothoracic surgery. If a beneficial effect were to be demonstrated, pulmonary rehabilitation for pre-surgical patients with COPD might be rapidly implemented across the National Health Service, as pulmonary rehabilitation courses are already well established across much of the United Kingdom (UK).MethodsWe performed a feasibility study to test study procedures and barriers to identification and recruitment to a randomised controlled trial testing whether pulmonary rehabilitation, delivered before major abdominal surgery in a population of people with COPD, would reduce the incidence of post-operative pulmonary complications. This study was run in two UK centres (Oxford and Newcastle upon Tyne).ResultsWe determined that a full randomised controlled trial would not be feasible, due to failure to identify and recruit participants. We identified an unmet need to identify more effectively patients with COPD earlier in the surgical pathway. Service evaluations suggested that barriers to identification and recruitment would likely be the same across other UK hospitals.ConclusionsAlthough pulmonary rehabilitation is a potentially beneficial intervention to prevent post-operative pulmonary complications, a randomised controlled trial is unlikely to recruit sufficient participants to answer our study question conclusively at the present time, when spirometry is not automatically conducted in all patients planned for surgery. As pulmonary rehabilitation is a recommended treatment for all people with COPD, alternative study methods combined with earlier identification of candidate patients in the surgical pathway should be considered.Trial registrationISRCTN 29696295, http://www.isrctn.com/ISRCTN29696295, registered 31st August 2017
An enhancer:involucrin regulatory module impacts human skin barrier adaptation out-of-Africa and modifies atopic dermatitis risk
Authors: Mathyer Mary Elizabeth , Brettmann Erin A. , Schmidt Alina D. , Goodwin Zane A. , Quiggle Ashley M. , Oh Inez Y. , Tycksen Eric , Zhou Lisa , Estrada Yeriel D. , Wong X.F. Colin C. , Denil Simon L.I.J. , Matkovich Scot A. , Shemer Avner , Common John E. A. , Guttman-Yassky Emma , de Guzman Strong Cristina 
Published: November 2019

ABSTRACTThe genetic modules that contribute to human evolution are poorly understood. We identified positive selection for two independent involucrin (IVL) haplotypes in European (CEU) and Asian (JPT/CHB) populations for skin epidermis. CEUIVLassociated with increasedIVLand a known epidermal-specific enhancer underwent a recent selective sweep out-of-Africa correlating with increased northern latitude. CRISPR/Cas9 deletion of the mouse enhancer revealed enhancer-mediatedcisregulation forIvlexpression with human population-specific enhancer reporter assays confirming the additive effect. Furthermore,IVLenhancer eQTLs associated with decreasedIVLtogether with filaggrin loss-of-function variants are enriched in atopic dermatitis cases vs. controls. Together, our enhancer-IVLcis regulatory module findings reveal an emerging paradigm for recently evolved traits to impact skin disease risk in contemporary populations.
Molecular identification of the Trypanosoma (Herpetosoma) lewisi clade in black rats (Rattus rattus) from Australia
Authors: Egan Siobhon L. , Taylor Casey L. , Austen Jill M. , Banks Peter B. , Ahlstrom Liisa A. , Ryan Una M. , Irwin Peter J. , Oskam Charlotte L. 
Published: November 2019

AbstractInvasive rodent species are known hosts for a diverse range of infectious microorganisms and have long been associated with the spread of disease globally. The present study describes molecular evidence for the presence of a Trypanosoma sp. from black rats (Rattus rattus) in northern Sydney, Australia. Sequences of the 18S ribosomal RNA (rRNA) locus were obtained in two out of eleven (18%) blood samples with subsequent phylogenetic analysis confirming the identity within the Trypanosoma lewisi clade.
Comparison of the Gut Microbiota Composition Between Captive and Wild Roe Deer
Authors: Liu Jinyue , Liang Xue , Liu Yanhua 
Published: November 2019

ABSTRACTIn this paper, 16S-rRNA gene Illumina HiSeq sequencing was used to analyze the structural diversity of captive and wild roe deer gut flora. The results show that the microbial diversity in the feces of wild roe deer is higher than in that of captive roe deer. Both roe deer have similar flora at the phylum level, but the main genus has significant differences. The microbial group that plays an important role in captive roe deer is Bacteroidetes; in wild roe deer it is Firmicutes. This difference is mainly due to the differences in living environment, diet, and physiological functions of the two groups. In conclusion, our study makes people have a better understanding of the intestinal flora of roe deer. By comparing the intestinal microbial structure differences between captive and wild roe deer, it provides theoretical basis for people to raise captive roe deer and provides reference for the protection of wild roe deer.IMPORTANCEMany studies have shown that large and complex microbes in the gut of humans and non-human animals, intestinal microbes are thought to co-evolve with the host, help the host acquire nutrients, regulate immunity and to help maintain host homeostasis. The roe deer (Capreolus spp.) is a ruminant. Wild roe deer are listed on the List of Terrestrial Wild Animals Protected by the State or Have Important Economic and Scientific Values, wild roe deer is also a Chinese national protected animal under second class protection. However, current research on the gut microbiota of roe deer has not been reported.
Primary cilia are present on endothelial cells of the hyaloid vasculature but are not required for the development of the blood-retinal barrier
Authors: Pollock Lana M. , Perkins Brian , Anand-Apte Bela 
Published: November 2019

AbstractEndothelial cilia are found in a variety of tissues including the cranial vasculature of zebrafish embryos. Recently, endothelial cells in the developing mouse retina were reported to also possess primary cilia that are potentially involved in vascular remodeling. Fish carrying mutations in intraflagellar transport (ift) genes have disrupted cilia and have been reported to have an increased rate of spontaneous intracranial hemorrhage (ICH), potentially due to disruption of the sonic hedgehog (shh) signaling pathway. However, it remains unknown whether the endothelial cells forming the retinal microvasculature in zebrafish also possess cilia, and whether endothelial cilia are necessary for development and maintenance of the blood-retinal barrier (BRB). In the present study, we found that the endothelial cells lining the zebrafish hyaloid vasculature possess primary cilia during development. To determine whether endothelial cilia are necessary for BRB integrity,ift57, ift88, andift172mutants, which lack cilia, were crossed with the double-transgenic zebrafish strainTg(l-fabp:DBP-EGFP;flk1:mCherry). This strain expresses a vitamin D-binding protein (DBP) fused to enhanced green fluorescent protein (EGFP) as a tracer in the blood plasma, while the endothelial cells forming the vasculature are tagged by mCherry. The Ift mutant fish develop a functional BRB, indicating that endothelial cilia are not necessary for early BRB integrity. Additionally, although treatment of zebrafish larvae with shh inhibitor cyclopamine results in BRB breakdown, the Ift mutant fish were not sensitized to cyclopamine-induced BRB breakdown.
SPOP Promotes Ubiquitination and Degradation of MyD88 to Suppress the Innate Immune Response
Authors: Li Qinghe , Wang Fei , Wang Qiao , Zheng Maiqing , Liu Ranran , Cui Huanxian , Wen Jie , Zhao Guiping 
Published: November 2019

AbstractAs a canonical adaptor for Toll-like receptor (TLR) family, MyD88 has crucial roles in host defence against infection of microbial pathogens and its dysregulation might induce autoimmune diseases. Here we demonstrate that the Cullin 3-based ubiquitin ligase adaptor SPOP recognizes the intermediate domain and degrades chMyD88 through the proteasome pathway. Knockdown or genetic ablation of chSPOP leads to aberrant elevation of the chMyD88 protein. Consequently, ChSPOP negatively regulates the activity of NF-κB pathway and thus the production of IL-1β and IL-8 upon LPS challenge. Furthermore, SPOP deficiency mice are more susceptible to infection of Salmonella typhimurium. Collectively, these findings demonstrate chMyD88 as a bona fide substrate of chSPOP and uncover a mechanism by which chSPOP suppresses the innate immune signaling.Author SummaryMyD88 is a central adaptor mediating the initiate of innate immune response and production of proinflammatory cytokines that restrain pathogens and activate adaptive immunity. Although MyD88 is crucial for the host to prevent pathogenic infection, misregulation of MyD88 abundance might lead to autoimmune diseases. Thus, degradation of MyD88 is a canonical mechanism to terminate cytokines production. Here we characterized a novel E3 ligase SPOP that target MyD88 for degradation. SPOP attenuated IL1β and IL8 production through K48-linked polyubiquitination and degradation of MyD88 and thus impaired immune responses. SPOP deficient mice show more susceptibility to infection by Salmonella typhimurium. These findings demonstrate that SPOP is a negative regulator of MyD88-dependent pathway activation triggered by LPS and Salmonella typhimurium, which helps the host to maintain immune homeostasis.
Metastatic function of METTL18 in breast cancer via actin methylation and Src
Authors: Kim Han Gyung , Kim Ji Hye , Yang Woo Seok , Park Jae Gwang , Lee Yong Gyu , Hong Yo Han , Kim Eunji , Jo Minkyeong , Lee Chae Young , Kim Shi Hyung , Sung Nak Yoon , Yi Young-Su , Ratan Zubair Ahmed , Kim Sunggyu , Yoo Byong Chul , Kang Sung-Ung , Kim Young Bong , Kim Sangmin , Paik Hyun-June , Lee Jeong Eon , Nam Seok Jin , Parameswaran Narayanan , Han Jeung-Whan , Cho Jae Youl 
Published: November 2019

AbstractRecently, a SET domain containing 3 (SETD3) was identified as an actin histidine methyltransferase, functioning to control replication and pathogenesis in multiple mouse models for enterovirus infection as well as the regulation of smooth muscle contractility linked to primary dystocia. Here, in this study, we report another type of actin histidine methyltransferase, METTL18, that regulates the metastatic potential of breast cancer in human. Among methyltransferases, METTL18 was highly amplified in human breast cancer. In particular, poor prognosis was associated with high expression of METTL18 in HER2-negative breast cancer patients. This gene product was also found to be a critical component of metastatic responses. Loss of METTL18 expression significantly reduced metastatic responses of breast tumor cells both in vitro and in vivo. Mechanistically, it was observed that METTL18 increased actin polymerization, upregulated complex formation with HSP90AA1 and Src, enhanced the activity of an intermediate form of Src with tyrosine phosphorylation at both Y416 and Y527, and induced cellular metastatic responses, including morphological change, migration, and invasion of MDA-MB-231 cells in vitro and in mice. Methylated actin at His73 served as a critical site for interaction with HSP90AA1 and Src to activate p85/PI3K and STAT3. Our findings suggest that METTL18 plays critical roles in metastatic responses of HER2-negative breast cancer cells via actin polymerization and the generation of an intermediate form of Src.
Exome Sequencing in Individuals with Isolated Biliary Atresia
Authors: Rajagopalan Ramakrishnan , Tsai Ellen A. , Grochowski Christopher M. , Kelly Susan M. , Loomes Kathleen M. , Spinner Nancy B. , Devoto Marcella 
Published: November 2019

AbstractBiliary atresia (BA) is a severe pediatric liver disease resulting in necroinflammatory obliteration of the extrahepatic biliary tree. BA presents within the first few months of life as either an isolated finding or with additional syndromic features. The etiology of isolated BA is unknown, with evidence for infectious, environmental, and genetic risk factors described. However, to date, there are no definitive causal genes identified for isolated BA in humans, and the question of whether single gene defects play a major role remains open. We performed exome-sequencing in 100 North American patients of European descent with isolated BA (including 30 parent-child trios) and considered several experimental designs to identify potentially deleterious protein-altering variants that may be involved in the disease. In a case-only analysis, we did not identify genes with variants shared among more than two probands, and burden tests of rare variants using a case-case control design did not yield significant results. In the trio analysis of 30 simplex families (patient and parent trios), we identified 66de novovariants in 66 genes including a nonsense variant, p.(Cys30Ter), in the geneSTIP1. STIP1is a co-chaperone for the heat-shock protein,HSP90AA1, and has been shown to have diverse functions in yeast, flies and mammals, including stress-response.ConclusionOur results do not support the hypothesis that a simple genetic model is responsible for the majority of cases of isolated BA. Our finding of ade novomutation in a candidate gene for BA (STIP1) linked to evolutionarily conserved stress responses suggests further exploration of how genetic susceptibility and environmental exposure interact to cause BA is warranted.
Temperature sensitive SMA-causing point mutations lead to SMN instability, locomotor defects, and premature lethality inDrosophila
Authors: Raimer Amanda C. , Singh Suhana S. , Edula Maina R. , Paris-Davila Tamara , Vandadi Vasudha , Spring Ashlyn M. , Gregory Matera A. 
Published: November 2019

ABSTRACTSpinal muscular atrophy (SMA) is the leading genetic cause of death in young children, arising from homozygous deletion or mutation of theSMN1gene. SMN protein expressed from a paralogous gene,SMN2, is the primary genetic modifier of SMA; small changes in overall SMN levels cause dramatic changes in disease severity. Thus, deeper insight into mechanisms that regulate SMN protein stability should lead to better therapeutic outcomes. Here, we show that SMA patient-derived missense mutations in theDrosophilaSMN Tudor domain exhibit a pronounced temperature sensitivity that affects organismal viability, larval locomotor function, and adult longevity. These disease-related phenotypes are domain-specific and result from decreased SMN stability at elevated temperature. This system was utilized to manipulate SMN levels during various stages ofDrosophiladevelopment. Due to a large maternal contribution of mRNA and protein,Smnis not expressed zygotically during embryogenesis. Interestingly, we find that only baseline levels of SMN are required during larval stages, whereas high levels of protein are required during pupation. This previously uncharacterized period of elevated SMN expression, during which the majority of adult tissues are formed and differentiated, could be an important and translationally relevant developmental stage in which to study SMN function. Altogether, these findings illustrate a novelin vivorole for the SMN Tudor domain in maintaining SMN homeostasis and highlight the necessity for high SMN levels at critical developmental timepoints that is conserved fromDrosophilato humans.
‘Synergistic-cidal’ effect of amoxicillin conjugated silver nanoparticles againstEscherichia coli
Authors: Kirthi Arivarasan Vishnu , Karthik Loganathan , Venkatesan Jayachandran , Chaskar Atul Changdev 
Published: November 2019

AbstractWe are reporting the synergistic effects of amoxicillin coated silver nanoparticles, and sodium cholate is used as the stabilizer. Following, the synthesis of AgNPs physicochemical characterization was carried out using UV spectroscopy, XRD, FTIR, FESEM, AFM and NC-AFM analysis. The confirmation of AgNPs was confirmed UV spectral peak at 426 nm, the morphology of the nanoparticles was found to be spherical, oval with an average size of 35.50 nm. The cytotoxic effect was carried out using MTT assay with IC50 of 50.78 µg/mL and the antibacterial effect was observed as zone of inhibition of 12 mm for E.coli. The drug release was determined as 69%, which contributes to the therapeutic efficacy of water soluble based nanoparticles/nanomedicines for biomedical applications.