bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of breast reconstruction in older women: patterns of uptake and clinical outcomes in a large metropolitan practice
Authors: Oh Daniel D. , Flitcroft Kathy , Brennan Meagan E. , Snook Kylie L. , Spillane Andrew J. 
Published: April 2019

BackgroundOlder age is associated with lower rates of breast reconstruction (BR) following mastectomy. This study compared a range of factors in women aged 60 years and older who had received mastectomy and BR with those who received no BR (NBR).MethodsAn audit of 338 women aged 60 or over treated with mastectomy with (n = 86) or without (n = 252) BR for primary breast cancer from 2009 to 2016 was conducted. Demographic, tumour, treatment, comorbidity and surgical complication data were obtained from patient medical records.ResultsNBR patients were associated with older age (P ≤ 0.001), more comorbidities (P = 0.038) and more extensive disease (P = 0.001) than BR patients. Total number of complications was not significantly different between BR and NBR patients (P = 0.286), or the different types of BR (P = 0.697). BR patients had higher rates of unplanned returns to the operating theatre, particularly in the late post‐operative period (P = 0.025). Implant‐based reconstruction was associated with more unplanned operating theatre returns than autologous reconstruction in the late post‐operative period (P = 0.013).ConclusionPost‐mastectomy BR in elderly patients has a clinical complication profile similar to NBR patients. This audit found no clinical‐based reasons to not offer oncologically suitable and clinically fit elderly women the option of BR.
Overexpression and activation of colony‐stimulating factor 1 receptor in the SIV/macaque model of HIV infection and neuroHIV
Authors: Irons Derek L. , Meinhardt Timothy , Allers Carolina , Kuroda Marcelo J. , Kim Woong‐Ki 
Published: April 2019

AbstractIn the present study, we investigated whether colony‐stimulating factor 1 receptor (CSF1R) is expressed on brain macrophages and microglia in the human and macaque brain and whether it is upregulated and activated after lentivirus infection in vivo and contributes to development of encephalitic lesions. We examined, using multi‐label and semi‐quantitative immunofluorescence microscopy, the protein expression level and cellular localization of CSF1R in brain tissues from uninfected controls and SIV‐infected adult macaques with or without encephalitis and also from uninfected controls, HIV‐infected encephalitic subjects and virally suppressed subjects. In the normal uninfected brain, CSF1R protein was detected only on microglia and brain macrophages but not on neurons, astrocytes or oligodendrocytes. Microglia constitutively expressed CSF1R at low levels, and its expression was largely unchanged in non‐encephalitic and encephalitic animals. Brain macrophages, including perivascular macrophages (PVMs), expressed higher levels of CSF1R compared to microglia. Interestingly, we found significantly increased expression of CSF1R on the infected PVMs and lesional macrophages in the brains of encephalitic macaques. Moreover, the per cell expression of CSF1R determined by its mean pixel intensity (MPI) correlated positively with the MPI of SIV Gag p28 in SIV‐infected PVMs. Using phosphorylated CSF1R at tyrosine residue 723 and phosphorylated signal transducer and activator of transcription 5 at tyrosine reside 694 as markers for CSF1R activation, we found selective activation of CSF1R signaling in infected brain macrophages in encephalitis. We also found colocalization of CSF1R and its ligand CSF1 in PVMs and lesional macrophages in the brains of encephalitic macaques and humans. Notably, elevated brain CSF1R expression was found in virally suppressed subjects. These findings point to opportunities for developing a specific approach targeting infected brain macrophages, with several brain‐penetrant CSF1R inhibitors that are available now, in order to eliminate central nervous system macrophage reservoirs, while not affecting resting uninfected microglia and PVMs that show no CSF1R activation.
Association between certain non–small cell lung cancer driver mutations and predictive markers for chemotherapy or programmed death‐ligand 1 inhibition
Authors: Liang Wenhua , Guo Minzhang , Pan Zhenkui , Cai Xiuyu , Li Caichen , Zhao Yi , Liang Hengrui , Yang Haiying , Wang Zhen , Chen Wenting , Xu Chuhong , Yang Xinyun , Sun Jianyu , He Ping , Gu Xia , Yin Weiqiang , He Jianxing 
Published: April 2019

AbstractThis study aimed to analyze the association between driver mutations and predictive markers for some anti–tumor agents in non–small cell lung cancer (NSCLC). A cohort of 785 Chinese patients with NSCLC who underwent resection from March 2016 to November 2017 in the First Affiliated Hospital of Guangzhou Medical University was investigated. The specimens were subjected to hybridization capture and sequence of 8 important NSCLC‐related driver genes. In addition, the slides were tested for PD‐L1, excision repair cross‐complementation group 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1), thymidylate synthase (TS) and β‐tubulin III by immunohistochemical staining. A total of 498 (63.4%) patients had at least 1 driver gene alteration. Wild‐type, EGFR rare mutation (mut), ALK fusion (fus), RAS mut, RET fus and MET mut had relatively higher proportions of lower ERCC1 expression. EGFR 19del, EGFR L858R, EGFR rare mut, ALK fus, HER2 mut, ROS1 fus and MET mut were more likely to have TS low expression. Wild‐type, EGFR L858R, EGFR rare mut and BRAF mut were associated with lower β‐tubulin III expression. In addition, wild‐type, RAS mut, ROS1 fus, BRAF and MET mut had higher proportion of PD‐L1 high expression. As a pilot validation, 21 wild‐type patients with advanced NSCLC showed better depth of response and response rate to taxanes compared with pemetrexed/gemcitabine (31.2%/60.0% vs 26.6%/45.5%). Our study may aid in selecting the optimal salvage regimen after targeted therapy failure, or the chemo‐regimen where targeted therapy has not been a routine option. Further validation is warranted.
Analysing invisibility: The decision‐making ecology and home visits
Authors: Saltiel David , Lakey Rebecca 
Published: April 2019

AbstractThe decisions social workers make are often under the spotlight. Increasingly professional decision‐making is seen not as a stand‐alone single act but a continuum shaped by a range of factors making up a decision ecology. Social work has been described as an invisible trade, and one of its most private and invisible arenas is the home visit. Despite being a long established core activity in social work and an important site for social work judgement and decision‐making, the home visit has often been taken for granted, leaving it under‐researched and under‐theorized. We use a case study of a visit drawn from one of the authors' practice to examine the range of ecological variables that shaped the encounter. The intention is not to produce a generalized prescription for best practice but to provide a detailed exploration of a piece of practice and contribute to the development of practice‐based theory about social work decision‐making and home visiting.
Gold nanoflower‐based surface‐enhanced Raman probes for pH mapping of tumor cell microenviroment
Authors: Xie Mo , Li Fan , Gu Peilin , Wang Fei , Qu Zhibei , Li Jiang , Wang Lihua , Zuo Xiaolei , Zhang Xueli , Shen Jianlei 
Published: April 2019

AbstractObjectivesEarly diagnosis of tumour cells is critically important for cancer treatment. Given that the tumour environment is slightly acidic, the pH value of the cell environment can be used as a criterion for tumour diagnosis. However, mapping pH in the cell environment with high resolution, high sensitivity and accuracy remains challenging.Materials and MethodsBased on gold nanoflower as surface‐enhanced Raman scattering (SERS) substrate loading with p‐mercaptobenzoic acid (MPA) as pH‐responsive Raman reporter, a new SERS nanoprobe for pH mapping was developed.ResultsThis probe showed a characteristic Raman spectrum signal in response to the different pH in solutions or cells. The signal intensity is positively correlated to the pH value. Moreover, this probe is self‐correctable, which can help eliminate the influence of probe concentration on the accuracy of pH measuring.ConclusionsWe demonstrate the pH mapping of cell environment using the probe, which can be used to distinguish normal cells and tumour cells. This method may provide a new imaging tool for early diagnosis of cancer.
Systems thinking for planning and evaluating conservation interventions
Authors: Mahajan Shauna L. , Glew Louise , Rieder Erica , Ahmadia Gabby , Darling Emily , Fox Helen E. , Mascia Michael B. , McKinnon Madeleine 
Published: April 2019

AbstractAs conservation shifts to meet the challenges of our globalized world, approaches for planning and evaluating interventions must evolve to account for the increasing complexity of conservation problems and the dynamic, multiscalar relationships between humans and the environment. Systems thinking offers approaches that could help conservation be more adaptive, transparent, and evidence‐based. Using case studies and the literature, we trace the evolution of systems thinking and demonstrate how systems mapping could support the process of planning and evaluating interventions. Systems mapping helps disentangle the context of conservation and encourage collaborative planning that integrates diverse views. It can also change the way interventions are characterized and communicated by emphasizing the systems targeted for change as opposed to actions. Last, it can encourage evidence‐based decision‐making by identifying indicators attune to complexity, prompting discussion on knowledge gaps, and filling gaps through qualitative mapping or computational modeling. Integrating systems thinking in practice will help practitioners foster the capacity for learning and adaptation required for conservation to deliver global results.
Genomic Association Analysis Reveals Variants Associated With Blood Pressure Response to Beta‐Blockers in European Americans
Authors: Singh Sonal , El Rouby Nihal , McDonough Caitrin W. , Gong Yan , Bailey Kent R. , Boerwinkle Eric , Chapman Arlene B. , Gums John G. , Turner Stephen T. , Cooper‐DeHoff Rhonda M. , Johnson Julie A. 
Published: April 2019

European Americans (EA) have a better antihypertensive response to β‐blockers when compared with African Americans, albeit with some variability. We undertook a genomewide association study to elucidate the underlying genetic determinants in EA contributing to this variability in blood pressure (BP) response. A discovery genomewide association study of change in BP post–metoprolol treatment was performed in EA participants (n = 201) from the Pharmacogenomic Evaluation of Antihypertensive Responses‐2 (PEAR‐2) study and tested for replication in the atenolol‐treated EA from the PEAR study (n = 233). Rs294610 in the FGD5, which encodes for FYVE, RhoGEF and PH Domain Containing 5, (expression quantitative trait loci for FGD5 in the small intestine) was significantly associated with increased diastolic BP response to β‐blockers in the PEAR‐2 study (P = 3.41 × 10−6, β = −2.70) and replicated (P = 0.01, β = −1.17) in the PEAR study. Post–meta‐analysis of these studies, an additional single nucleotide polymorphism rs45545233 in the SLC4A1, encoding for Solute Carrier Family 4 Member 1, (expression quantitative trait loci for dual specificity phosphatase 3 in the artery tibial) was identified that was significantly associated with a poor response to β‐blockers (P = 3.43 × 10−6, β = 4.57) and was replicated in the atenolol add‐on cohort (P = 0.007, β = 4.97). We identified variants in FGD5 and SLC4A1, which have been previously cited as candidate genes for hypertension, to be associated with a β‐blocker BP response in EA. Further elucidation is warranted of the underlying mechanisms of these variants and genes by which they influence the BP response to β‐blockers.
Efficacy and safety of direct‐acting antivirals for hepatitis C in the elderly: A systematic review and meta‐analysis
Authors: Mücke Marcus M. , Herrmann Eva , Mücke Victoria T. , Graf Christiana , Zeuzem Stefan , Vermehren Johannes 
Published: April 2019

AbstractBackground&AimsSince the introduction of direct‐acting antivirals (DAAs) several studies have reported high efficacy and safety in Hepatitis C infected patients, even in those earlier considered difficult‐to‐treat. We aimed to assess the efficacy and safety of DAA therapy in elderly patients.MethodsThe PubMed MEDLINE, Embase and Cochrane databases were searched through July 2018. Two independent researchers extracted data and assessed the quality and risk of bias. Risk ratios (RRs) were pooled using random effects models. The primary outcome was efficacy of DAA therapy assessed by the RR for non‐sustained virologic response (SVR) among patients aged <65 vs ≥65 years.ResultsOverall, we identified 63 studies including 34 082 patients treated with different DAAs. Risk for non‐SVR was comparable in patients <65 and ≥65 years of age (RR 1.00, 95% CI 0.86‐1.15; P = 0.979) and even lower in a subgroup analysis of cirrhotic patients ≥65 years of age (RR 0.59, 95% CI 0.35‐0.99, P = 0.044). Risk for non‐SVR was similar between age groups in all other subgroup analyses. Elderly patients had a significantly increased risk of adverse events (AEs) (RR 1.30, 95% CI 1.11‐1.52, P = 0.001), but not for serious adverse events (P = 0.43) or treatment discontinuation (P = 0.15). Risk for anaemia if treated with additional ribavirin was 2.84 (95% CI 1.73‐4.66, P < 0.001) in elderly patients compared to patients <65 years.ConclusionOur results show that DAAs are highly effective and safe in elderly patients. Ribavirin should be avoided in the elderly as more AEs and particularly anaemia is observed. Further cost‐effectiveness analyses are needed to evaluate the socio‐economic benefit of treating elderly people without advanced liver disease.
Novel biomarkers for primary biliary cholangitis to improve diagnosis and understand underlying regulatory mechanisms
Authors: Bombaci Mauro , Pesce Elisa , Torri Anna , Carpi Donatella , Crosti Mariacristina , Lanzafame Manuela , Cordiglieri Chiara , Sinisi Antonia , Moro Monica , Bernuzzi Francesca , Gerussi Alessio , Geginat Jens , Muratori Luigi , Terracciano Luigi M. , Invernizzi Pietro , Abrignani Sergio , Grifantini Renata 
Published: April 2019

AbstractBackground and aimsPrimary biliary cholangitis is an autoimmune biliary disease characterized by injury of bile ducts, eventually leading to cirrhosis and death. In most cases, anti‐mitochondrial antibodies and persistently elevated serum alkaline phosphatase are the basis for the serological diagnosis. Anti‐nuclear antibodies are also useful and may indicate a more aggressive diseases course. In patients in which anti‐mitochondrial antibodies are not detected, an accurate diagnosis requires liver histology. This study aims at identifying specific biomarkers for the serological diagnosis of primary biliary cholangitis.MethodsSera from patients affected by primary biliary cholangitis, primary sclerosing cholangitis, hepatitis C virus (with and without cryoglobulinemia), hepatocarcinoma and healthy donors were tested on a protein array representing 1658 human proteins. The most reactive autoantigens were confirmed by DELFIA analysis on expanded cohorts of the same mentioned serum classes, and on autoimmune hepatitis sera, using anti‐PDC‐E2 as reference biomarker.ResultsTwo autoantigens, SPATA31A3 and GARP, showed high reactivity with primary biliary cholangitis sera, containing or not anti‐mitochondrial antibodies. Their combination with PDC‐E2 allowed to discriminate primary biliary cholangitis from all tested control classes with high sensitivity and specificity. We found that GARP expression is upregulated upon exposure to biliary salts in human cholangiocytes, an event involving EGFR and insulin pathways. GARP expression was also detected in biliary duct cells of PBC patients.ConclusionsThis study highlighted SPATA31A3 and GARP as new biomarkers for primary biliary cholangitis and unravelled molecular stimuli underlying GARP expression in human cholangiocytes.
Genetic influences on the variability of response to repetitive transcranial magnetic stimulation in human pharyngeal motor cortex
Authors: Raginis‐Zborowska Alicja , Cheng Ivy , Pendleton Neil , Payton Antony , Ollier William , Michou Emilia , Hamdy Shaheen 
Published: April 2019

AbstractBackgroundRecent studies have reported substantial variability in response to repetitive transcranial magnetic stimulation (rTMS). We hypothesized that an individual's genetic predisposition may contribute to such variability in the pharyngeal motor cortex. This study aimed to investigate the response to 1 and 5 Hz rTMS paradigms on pharyngeal motor cortex in healthy participants and its relationship with genetic predisposition.MethodsForty‐one healthy participants (25.4 ± 4.6 years old) received either or both 1 Hz (n = 39) and 5 Hz rTMS (n = 40) over pharyngeal motor cortex. Pharyngeal and thenar motor–evoked potentials were recorded at baseline and for 1 hour post‐rTMS. The participants were then classified according to their response. The associations between rTMS response and gender, time of day of the stimulation, and eight prespecified single nucleotide polymorphisms (SNPs) were analyzed.Key ResultsThere was no direction‐specific response to either paradigm (1 Hz: F[3.69, 129.21] = 0.78, P = 0.56; 5 Hz: F[4.08, 146.85] = 1.38, P = 0.25). Only 13% of participants showed the expected bidirectional response (inhibition for 1 Hz and excitation for 5 Hz). Significant associations were found between response and COMT (1 Hz: P = 0.03) and DRD2 (1 Hz: P = 0.02; 5 Hz: P = 0.04) polymorphisms. Carriers of minor allele G from SNP rs6269 (COMT) were more likely to show inhibitory or excitatory outcomes after 1 Hz rTMS. By contrast, carriers of minor allele A from SNP rs1800497 (DRD2) were more likely to show no response to 1 Hz rTMS and inhibition after 5 Hz rTMS.Conclusions & InferencesTwo SNPs from COMT and DRD2 genes may partially explain the response variability to rTMS in the pharyngeal motor system. Further research should focus on stratified approaches for neurostimulatory dysphagia treatment using rTMS.
Benefits of supplementation with multiple micronutrients in pregnancy
Authors: Black Robert E. , Dewey Kathryn G. 
Published: April 2019

AbstractA task force was convened by the New York Academy of Sciences to evaluate new evidence that was not available at the time of, and to help countries interpret, recent World Health Organization guidelines for nutrition interventions in pregnancy as they relate to multiple micronutrient supplementation. The report of the task force is published in a recent special issue of Annals of the New York Academy of Sciences. Here, we provide a short introduction to the special issue.
Medium‐chain acyl‐coenzyme A dehydrogenase deficiency: Six cases in the Chinese population
Authors: Li Yanhan , Zhu Ruoxin , Liu Yi , Song Jinqing , Xu Jing , Yang Yanling 
Published: April 2019

AbstractBackgroundMedium‐chain acyl‐coenzyme A dehydrogenase deficiency (MCADD) is a rare autosomal recessive disorder that affects the degradation of medium‐chain fatty acids. Few cases of MCADD have been documented to date in mainland China.MethodsMedium‐chain acyl‐coenzyme A dehydrogenase deficiency was diagnosed in six patients (three girls and three boys) from six unrelated Chinese families at ages ranging from 10 days to 3 years old. The diagnosis was confirmed by the identification of a primary biomarker of serum octanoyl‐carnitine (C8) and genetic pathogenic mutations.ResultsOnly two patients were admitted because of vomiting, diarrhea, myasthenia, and coma; the other four patients were diagnosed via the newborn screening process. Six mutations were found in acyl‐CoA dehydrogenase medium chain (ACADM). One mutation (c.727C>T) was novel and the others (c.158G>A, c.387+1delG, c.449_452del, c.1045C>T, and c.1085G>A) have been previously reported.ConclusionsSix Chinese cases of MCADD were identified. One novel mutation was found. c.449_452del and c.1085G>A were common mutations in this study.
Between one event and two: The locus of the effect of stimulus contrast on temporal integration
Authors: Akyürek Elkan G. , Wijnja Eria 
Published: April 2019

AbstractThe effects of relative stimulus contrast on temporal integration were investigated in a missing element task. Integration frequency was strongly modulated when the contrast of either the first or the second stimulus display was reduced. When the contrast of the first display was low, integration was enhanced, while it was reduced when the contrast of the second display was low. To reveal the processing phases implicated in these modulations of integration, the amplitude of ERP components was examined. N1 component amplitude was increased when the second display was low contrast, matching a full contrast condition. At the N2pc component, amplitude was strongly suppressed only in the former condition. P3 amplitude was also lowest when contrast on the second display was low but with successively increasing amplitudes observed for the other conditions, largely matching the pattern observed in behavioral performance. Taken together, contrast effects on temporal integration seem to originate from increased discriminative processing of the first stimulus display in particular (N1), which is consequently followed by an impairment in attentional processing (N2pc) and working memory consolidation (P3) of the missing element location.
Response to random apheresis platelets versus HLA‐selected platelets versus pooled platelets in HLA‐sensitized patients
Authors: Gavva Chakri , Barroso Jeffrey , Gernsheimer Terry , Metcalf Ryan A. , Warner Paul , Pagano Monica B. 
Published: April 2019

BACKGROUNDIt is unknown how pooled platelets (PPs) compare to random apheresis platelets (RAPs) when HLA‐selected platelets (PLTs) are unavailable for HLA‐sensitized patients. The aim of this study was to compare patient responses to RAPs, HLA‐selected PLTs, and PPs in HLA‐sensitized patients.STUDY DESIGN AND METHODSThis is a single‐institution retrospective study of patients from January 2014 to April 2017 with a class I calculated panel‐reactive antibody of 60% or more. Response to transfusion was determined by a corrected count increment (CCI) up to 1 hour after completion of transfusion. A CCI of 5 or more was considered successful.RESULTSSeventy‐seven units of RAPs, 412 units of HLA‐selected PLT, and 388 units PPs were transfused. Mean CCIs when transfusing RAPs, HLA‐selected PLTs, and PPs were 2.82, 11.44, and 4.77, respectively (p < 0.0001). Posttest comparison between RAPs and PPs revealed no significant difference in mean CCI while there was a significant difference between HLA‐selected PLTs versus RAPs and HLA‐selected PLTs versus PPs. The success rates of RAPs, HLA‐selected PLTs, and PPs were 31%, 80%, and 35% respectively. There was no significant association of type of PLT and success rate when comparing RAPs versus PPs (p = 0.51) while there was a significant association between success rate and type of PLT transfusion when comparing HLA‐selected PLTs with RAPs and PPs.CONCLUSIONHLA‐selected PLTs resulted in higher mean CCIs and more successful transfusions. There was no significant difference in mean CCI or success rate when transfusing RAPs versus PPs to HLA‐sensitized patients. Future studies should assess clinical outcomes in HLA‐sensitized patients receiving each type of PLT product.