bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impacts of Tumor Location, Nature and Bone Destruction of Extremity Osteosarcoma on Selection of Limb Salvage Operative Procedure
Authors: Chen Yu , Yu Xiu‐chun , Xu Song‐feng , Xu Ming , Song Ruo‐xian 
Published: July 2016

ObjectiveTo study the impacts of tumor location, nature and extent of bone destruction on selection of operative protocol for extremity osteosarcoma (OS).MethodsThe medical records of 201 patients with extremity OS treated in our institute from December 1999 to June 2014 were retrospectively reviewed. Ninety eligible patients (56 males and 34 females) of average age 20 ± 11 years (range, 4–40 years) were enrolled. Tumor locations were categorized as diaphyseal (4; diaphysis group) or juxta‐articular (86); the latter being subclassified as with (51, type III, epiphysis group) or without invasion beyond the epiphyseal line or plate (35, type I and II, metaphysis group) according to MRI images. Tumor nature (osteogenic, 51; osteolytic, 39) was determined radiologically. Extent of bone destruction was quantitated according to Mirel's scoring system to obtain an “invasion score”. Regular postoperative follow‐up included physical examination and imaging evaluation.ResultsFifty‐four patients underwent biological reconstruction and 36 mechanical reconstruction. The mean follow‐up duration was 51 months (range, 6–176 months, including four deaths within 12 months). Biological reconstruction was performed more frequently in the diaphysis and metaphysis groups (31/39, 79.5%) than mechanical reconstruction (8/39, 20.5%, P < 0.05). Biological reconstruction and articular preservation were associated with more satisfactory limb function (MSTS scores: 25.0 ± 3.3 and 25.1 ± 3.6) than mechanical reconstruction and articular resection (MSTS scores: 23.4 ± 3.7 and 23.1 ± 3.4, P < 0.05). Reconstruction methods and articular preservation had no relationship with overall or tumor‐free survival (P > 0.05). Osteolytic lesions were associated with more extensive bone destruction than osteogenic lesions according to invasion scores (P < 0.05). Following biological reconstruction, high invasion scores (>8) had a 13.5‐fold risk of fracture compared with low scores (≤8) (P < 0.05). Twenty‐one subjects had recurrences, 30 metastases and 26 died. Postoperative complications included infection (6), fracture (10), and prosthesis loosening (4). Kaplan‐Meier analysis indicated 5‐ and 10‐year survival rates of 68.9% and 62.8%, respectively, and 5‐ and 10‐year tumor‐free survival rates of 66.7% and 57.8%, respectively.ConclusionSelection of limb salvage operative protocol for extremity OS should rely on tumor location, nature and extent of bone destruction. Regardless of tumor site, mechanical reconstruction is indicated for tumors with high invasion scores (>8), whereas biological reconstruction is preferred for those with low invasion scores (≤8). Tumors sparing the epiphyseal line or plate are ideal candidates for articular preservation.
Preliminary Application of Precision Genomic Medicine Detecting Gene Variation in Patients with Multifocal Osteosarcoma
Authors: Zhang Hao‐qiang , Li Ming‐hui , Gao Peng , Lan Ping‐heng , Fan Bo , Xiao Xin , Lu Ya‐jie , Chen Guo‐jing , Wang Zhen 
Published: July 2016

ObjectivesThe purpose of this study was to present our clinical experience of treating multifocal osteosarcoma (MFOS) in our center and gain more insight into the biology of this rare condition; in particular, to address with the help of precision genomic medicine the issue of whether the multiple osteosarcoma (OS) lesions in such patients are multi‐centric or originate from one primary lesion and metastasize to other sites. Finally, we aimed to identify particular gene phenotypes and mutations that differentiate MFOS from OS with only one tumor.MethodsClinical data of patients with MFOS treated at our center between June 2007 and October 2014 were collected and analyzed retrospectively. High throughput sequencing of the whole exome of normal tissue and multiple lesions had been performed on samples from two patients (HJF and JZ) diagnosed in 2014. To explore the particular gene phenotype and clinical significance of MFOS, these sequencing results were analyzed and compared with those from patients with osteosarcoma in a single site. Seven patients with MFOS (three male and four female; average age 19.71 ± 3.35 years were enrolled in this study. Two of these patients declined treatment and died after 4 and 6 months, respectively. The remaining patients received standard treatment comprising neoadjuvant chemotherapy, surgery and chemotherapy. The chemotherapy regimen was lobaplatin (45 mg/m2), doxorubicin (60 mg/m2) and ifosfamide (12 g/m2). Patients were followed up every 3 months after completing treatment and evaluated by the Enneking and Response Evaluation Criteria in Solid Tumors scoring systems.ResultsUp to the last follow‐up on 1 December 2015, three patients were still alive. The event‐free survival ranged from 4 to 144 weeks (median, 50.14 weeks), the mean (±SD) being 55.45 ± 45.47 weeks. Overall survival ranged from 16 to 388 weeks (median, 89 weeks; mean ± SD, 118.7 ± 147.7 weeks). The rates of mutation of the targeted drug‐related genes were 133.5% ± 3.0% in the proximal tibia lesion and 113.1% ± 1.9% in the distal femur of patient HJF (P < 0.01) and 136.1% ± 10.8% in the proximal tibial lesion and 122.3% ± 5.5% in the proximal humerus of patient JZ (P = 0.0335). Furthermore, there were several anti‐oncogenes in the somatic copy number variation lists analyzed from the two patients, especially TP53. However, no kataegis was found.ConclusionsEarly and radical surgery accompanied by appropriate chemotherapy is the optimal means of treating MFOS. These patients may benefit from precision genomic medicine.
Loss of strumpellin in the melanocytic lineage impairs theWASHComplex but does not affect coat colour
Authors: Tyrrell Benjamin J. , Woodham Emma F. , Spence Heather J. , Strathdee Douglas , Insall Robert H. , Machesky Laura M. 
Published: July 2016

SummaryThe five‐subunitWASHcomplex generates actin networks that participate in endocytic trafficking, migration and invasion in various cell types. Loss of one of the two subunitsWASHor strumpellin in mice is lethal, but little is known about their role in mammals in vivo. We explored the role of strumpellin, which has previously been linked to hereditary spastic paraplegia, in the mouse melanocytic lineage. Strumpellin knockout in melanocytes revealed abnormal endocytic vesicle morphology but no impairment of migration in vitro or in vivo and no change in coat colour. Unexpectedly,WASHand filamentous actin could still localize to vesicles in the absence of strumpellin, although the shape and size of vesicles was altered. Blue nativePAGErevealed the presence of two distinctWASHcomplexes, even in strumpellin knockout cells, revealing that theWASHcomplex can assemble and localize to endocytic compartments in cells in the absence of strumpellin.
Longitudinal Antibiotic Susceptibility Profiles of Staphylococcus aureus Cutaneous Infections in a Pediatric Outpatient Population
Authors: Slater Nathaniel A. , Gilligan Peter H. , Morrell Dean S. 
Published: July 2016

AbstractThis longitudinal update on Staphylococcus aureus prevalence and antibiotic resistance patterns surveyd 291 cultures from 188 patients in a pediatric outpatient dermatology clinic with suspected skin and soft tissue infections. The prevalence of methicillin‐resistant Staphylococcus aureus remained stable at 24%. Staphylococcus aureus resistance to tetracyclines modestly but demonstrably increased in the interval since 2009.
A unique chromosomal in‐frame deletion identified among seven XP‐C patients
Authors: Schubert Steffen , Rieper Petra , Ohlenbusch Andreas , Seebode Christina , Lehmann Janin , Gratchev Alexei , Emmert Steffen 
Published: July 2016

SummaryBackgroundThe nucleotide excision repair (NER) pathway, defective in xeroderma pigmentosum (XP) patients, removes DNA photolesions in order to prevent carcinogenesis. Complementation group C (XP‐C) is the most frequent group of XP patients worldwide.MethodsWe analyzed seven XP‐C patients clinically and molecular‐genetically applying: post‐UV cell survival (MTT‐assay), quantitative Real‐time PCR, sequencing on chromosomal as well as cDNA level, and in silico interpretation of sequencing data.ResultsAll cases displayed diminished post‐UV cell survival as well as reduced XPC mRNA levels. Five homozygous and two heterozygous disease causing mutations were identified. A large chromosomal deletion of ~5.8 kb identified in XP174MA leads to an unique in frame deletion of XPC exon 2 and exon 3. In silico analysis revealed the deletion of 102 amino acids in the N‐terminal part of XPC while leaving the C‐terminal domain intact. The novel c.361delA mutation in XP168MA leads to a frameshift in exon 3 resulting in a premature stop codon 27 codons downstream of the deleted adenine.ConclusionOur analysis confirms that XP‐C patients without increased sun sensitivity develop non‐melanoma skin cancers earlier than sun‐sensitive XP‐C patients. Reduced cellular mRNA levels are characteristic for XP complementation group C and qRT‐PCR represents a rapid diagnostic tool.
Theoretical Analysis on Strain Transfer Error of FBG Sensors Attached on Steel Structures Subjected to Fatigue Load
Authors: Wang H. P. , Xiang P. , Li X. 
Published: July 2016

AbstractFibre Bragg grating (FBG) sensors have been increasingly adopted to detect the dynamic strain of structures. When the sensor is attached on the surface, adhesive material is employed to assist the installation, which leads to indirect contact of sensing fibre and the monitored structure. To correct the strain transfer error induced by the shear lag effect and improve the measurement accuracy of FBG sensors under dynamic response, strain transfer mechanism of a three‐layered testing model constituted of sensing fibre, adhesive layer and host material has been studied in this paper. Laboratory test on steel beam attached with FBG sensor under fatigue load has been projected to investigate the feasibility of the derived strain transfer formula, and numerical simulation by MATLAB has been used as a supporting tool to offer the reference dynamic strain. Based on the analysis, sensitive parameters that affect the strain transfer coefficient have been discussed to instruct the application design of FBG sensors. Results indicate that strain transfer coefficient under dynamic response is much lower than that in static state, and error modification is particularly significant; in the dynamic testing model, bonded length, shear modulus and thickness of adhesive layer are more sensitive, which should be precisely selected in practical engineering to guarantee the effective strain measurement.
Intensive adherence counselling for HIV‐infected individuals failing second‐line antiretroviral therapy in Johannesburg, South Africa
Authors: Fox Matthew P. , Berhanu Rebecca , Steegen Kim , Firnhaber Cindy , Ive Prudence , Spencer David , Mashamaite Sello , Sheik Sadiyya , Jonker Ingrid , Howell Pauline , Long Lawrence , Evans Denise 
Published: July 2016

AbstractObjectiveIn resource‐limited settings, where genotypic drug resistance testing is rarely performed and poor adherence is the most common reason for treatment failure, programmatic approaches to handling treatment failure are essential. This study was performed to describe one such approach to adherence optimisation.MethodsThis was a single‐arm study of patients on second‐line protease inhibitor (PI)‐based antiretroviral therapy (ART) with a HIV‐1 RNA ≥400 copies/ml in Johannesburg, South Africa, between 1 March 2012 and 1 December 2013. Patients underwent enhanced adherence counselling. Those with improved adherence and a repeat viral load of >1000 copies/ml underwent HIV‐1 drug resistance testing. We describe results using simple proportions and 95% confidence intervals.ResultsOf the 400 patients who underwent targeted adherence counselling after an elevated viral load on second‐line ART, 388 (97%) underwent repeat viral load testing. Most of these (n = 249; 64%, 95% CI 59–69) resuppressed (<400 copies/ml) on second line. By the end of follow‐up (1 March 2014), among the 139 (36%, 95% CI: 31–41%), who did not initially resuppress after being targeted, 106 had a viral load >400 copies/ml, 11 switched to third line, 5 were awaiting third line, 4 had died and 13 were lost to follow‐up. Among the unsuppressed, 48 successfully underwent resistance testing with some resistance detected in most (41/48).ConclusionsMost (64%) second‐line treatment failure in this clinic is related to adherence and can be overcome with careful adherence support. Controlled interventions are needed to determine what the optimal approach is to improving second‐line outcomes and reducing the need for third‐line ART.
Factor predicting total nucleated cell counts in cord blood units
Authors: Al‐Qahtani Reham , Al‐Hedythi Sara , Arab Suha , Aljuhani Amal , Jawdat Dunia 
Published: July 2016

BACKGROUNDCord blood (CB) stem cells have been used worldwide in transplant medicine to treat various diseases. The efficacy of stem cells in umbilical CB (UCB) can be predicted by the number of total nucleated cells (TNCs). To optimize the clinical use of stem cells in our population, this study addresses several variables affecting the TNC count.STUDY DESIGN AND METHODSThis observational, cross‐sectional study was conducted in a single center from 2012 to 2014. In total, 957 CB units (CBUs) were collected from consented mothers. Data analyses of clinically accepted CBUs were correlated with maternal and infant factors.RESULTSBased on the TNC accepted level of banking, 188 CBUs (19.64%) were rejected. Of the 16 maternal and infant variables evaluated, three factors demonstrated a statistically significant predictive value for the accepted TNC level. CB volume was the best predictive factor (p ≤ 0.0001), followed by newborn birth weight (p = 0.025), and the method of delivery (p = 0.002).CONCLUSIONSSeveral maternal, neonatal, and obstetric factors appear to play a major role in predicting an accepted TNC count, which can be used to improve criteria for the donation of stem cells in CBUs.
cis Retinol oxidation regulates photoreceptor access to the retina visual cycle and cone pigment regeneration
Authors: Sato Shinya , Kefalov Vladimir J. 
Published: July 2016

Key points
This study explores the nature of the cis retinol that Müller cells in the retina provide to cones for the regeneration of their visual pigment.
We report that the retina visual cycle provides cones exclusively with 11‐cis chromophore in both salamander and mouse and show that this selectivity is dependent on the 11‐cis‐specific cellular retinaldehyde binding protein (CRALBP) present in Müller cells.
Even though salamander blue cones and green rods share the same visual pigment, only blue cones but not green rods are able to dark‐adapt in the retina following a bleach and to use exogenous 9‐cis retinol for pigment regeneration, suggesting that access to the retina visual cycle is cone‐specific and pigment‐independent.
Our results show that the retina produces 11‐cis retinol that can be oxidized and used for pigment regeneration and dark adaptation selectively in cones and not in rods.
AbstractChromophore supply by the retinal Müller cells (retina visual cycle) supports the efficient pigment regeneration required for cone photoreceptor function in bright light. Surprisingly, a large fraction of the chromophore produced by dihydroceramide desaturase‐1, the putative all‐trans retinol isomerase in Müller cells, appears to be 9‐cis retinol. In contrast, the canonical retinal pigment epithelium (RPE) visual cycle produces exclusively 11‐cis retinal. Here, we used the different absorption spectra of 9‐cis and 11‐cis pigments to identify the isoform of the chromophore produced by the visual cycle of the intact retina. We found that the spectral sensitivity of salamander and mouse cones dark‐adapted in the isolated retina (with only the retina visual cycle) was similar to that of cones dark‐adapted in the intact eye (with both the RPE and retina visual cycles) and consistent with pure 11‐cis pigment composition. However, in mice lacking the cellular retinaldehyde binding protein (CRALBP), cone spectral sensitivity contained a substantial 9‐cis component. Thus, the retina visual cycle provides cones exclusively with 11‐cis chromophore and this process is mediated by the 11‐cis selective CRALBP in Müller cells. Finally, despite sharing the same pigment, salamander blue cones, but not green rods, recovered their sensitivity in the isolated retina. Exogenous 9‐cis retinol produced robust sensitivity recovery in bleached red and blue cones but not in red and green rods, suggesting that cis retinol oxidation restricts access to the retina visual cycle to cones.
Virion Structure of Israeli Acute Bee Paralysis Virus
Authors: Mullapudi Edukondalu , Přidal Antonín , Pálková Lenka , de Miranda Joachim R. , Plevka Pavel 
Published: July 2016

ABSTRACT

The pollination services provided by the western honeybee (
Apis mellifera
) are critical for agricultural production and the diversity of wild flowering plants. However, honeybees suffer from environmental pollution, habitat loss, and pathogens, including viruses that can cause fatal diseases. Israeli acute bee paralysis virus (IAPV), from the family
Dicistroviridae
, has been shown to cause colony collapse disorder in the United States. Here, we present the IAPV virion structure determined to a resolution of 4.0 Å and the structure of a pentamer of capsid protein protomers at a resolution of 2.7 Å. IAPV has major capsid proteins VP1 and VP3 with noncanonical jellyroll β-barrel folds composed of only seven instead of eight β-strands, as is the rule for proteins of other viruses with the same fold. The maturation of dicistroviruses is connected to the cleavage of precursor capsid protein VP0 into subunits VP3 and VP4. We show that a putative catalytic site formed by the residues Asp-Asp-Phe of VP1 is optimally positioned to perform the cleavage. Furthermore, unlike many picornaviruses, IAPV does not contain a hydrophobic pocket in capsid protein VP1 that could be targeted by capsid-binding antiviral compounds.

IMPORTANCE
Honeybee pollination is required for agricultural production and to sustain the biodiversity of wild flora. However, honeybee populations in Europe and North America are under pressure from pathogens, including viruses that cause colony losses. Viruses from the family
Dicistroviridae
can cause honeybee infections that are lethal, not only to individual honeybees, but to whole colonies. Here, we present the virion structure of an
Aparavirus
, Israeli acute bee paralysis virus (IAPV), a member of a complex of closely related viruses that are distributed worldwide. IAPV exhibits unique structural features not observed in other picorna-like viruses. Capsid protein VP1 of IAPV does not contain a hydrophobic pocket, implying that capsid-binding antiviral compounds that can prevent the replication of vertebrate picornaviruses may be ineffective against honeybee virus infections.
Porcine Epidemic Diarrhea Virus Infection Inhibits Interferon Signaling by Targeted Degradation of STAT1
Authors: Guo Longjun , Luo Xiaolei , Li Ren , Xu Yunfei , Zhang Jian , Ge Jinying , Bu Zhigao , Feng Li , Wang Yue 
Published: July 2016

ABSTRACT
Porcine epidemic diarrhea virus (PEDV) is a worldwide-distributed alphacoronavirus, but the pathogenesis of PEDV infection is not fully characterized. During virus infection, type I interferon (IFN) is a key mediator of innate antiviral responses. Most coronaviruses develop some strategy for at least partially circumventing the IFN response by limiting the production of IFN and by delaying the activation of the IFN response. However, the molecular mechanisms by which PEDV antagonizes the antiviral effects of interferon have not been fully characterized. Especially, how PEDV impacts IFN signaling components has yet to be elucidated. In this study, we observed that PEDV was relatively resistant to treatment with type I IFN. Western blot analysis showed that STAT1 expression was markedly reduced in PEDV-infected cells and that this reduction was not due to inhibition of STAT1 transcription. STAT1 downregulation was blocked by a proteasome inhibitor but not by an autophagy inhibitor, strongly implicating the ubiquitin-proteasome targeting degradation system. Since PEDV infection-induced STAT1 degradation was evident in cells pretreated with the general tyrosine kinase inhibitor, we conclude that STAT1 degradation is independent of the IFN signaling pathway. Furthermore, we report that PEDV-induced STAT1 degradation inhibits IFN-α signal transduction pathways. Pharmacological inhibition of STAT1 degradation rescued the ability of the host to suppress virus replication. Collectively, these data show that PEDV is capable of subverting the type I interferon response by inducing STAT1 degradation.

IMPORTANCE
In this study, we show that PEDV is resistant to the antiviral effect of IFN. The molecular mechanism is the degradation of STAT1 by PEDV infection in a proteasome-dependent manner. This PEDV infection-induced STAT1 degradation contributes to PEDV replication. Our findings reveal a new mechanism evolved by PEDV to circumvent the host antiviral response.
Pharmacy workers’ knowledge and provision of medication for termination of pregnancy in Kenya
Authors: Reiss Kate , Footman Katharine , Akora Vitalis , Liambila Wilson , Ngo Thoai D 
Published: July 2016

ObjectiveTo assess pharmacy workers’ knowledge and provision of abortion information and methods in Kenya.MethodsIn 2013 we interviewed 235 pharmacy workers in Nairobi, Mombasa and Kisumu about the medical abortion services they provide. We also used mystery clients, who made 401 visits to pharmacies to collect first-hand information on abortion practices.ResultsThe majority (87.5%) of pharmacy workers had heard of misoprostol but only 39.2% had heard of mifepristone. We found that pharmacy workers had limited knowledge of correct medical abortion regimens, side effects and complications and the legal status of abortion drugs. 49.8% of pharmacy workers reported providing abortion information to clients and 4.3% reported providing abortion methods. 75.2% of pharmacies referred mystery clients to another provider, though 64.2% of pharmacies advised mystery clients to continue with their pregnancy. Pharmacy workers reported that they were experiencing demand for abortion services from clients.ConclusionsPharmacy workers are important providers of information and referrals for women seeking abortion, however their medical abortion knowledge is limited. Training pharmacy workers on medical abortion may improve the quality of information provided and access to safe abortion.