bluuebunny/crossref_metadata_2025 huggingface dataset:
Linking single-cell measurements of mass, growth rate, and gene expression
Authors: Kimmerling Robert J. , Prakadan Sanjay M. , Gupta Alejandro J. , Calistri Nicholas L. , Stevens Mark M. , Olcum Selim , Cermak Nathan , Drake Riley S. , Shalek Alex K. , Manalis Scott R.
Published: May 2018

We introduce a microfluidic platform that enables single-cell mass and growth rate measurements upstream of single-cell RNA-sequencing (scRNA-seq) to generate paired single-cell biophysical and transcriptional data sets. Biophysical measurements are collected with a serial suspended microchannel resonator platform (sSMR) that utilizes automated fluidic state switching to load individual cells at fixed intervals, achieving a throughput of 120 cells per hour. Each single-cell is subsequently captured downstream for linked molecular analysis using an automated collection system. From linked measurements of a murine leukemia (L1210) and pro-B cell line (FL5.12), we identify gene expression signatures that correlate significantly with cell mass and growth rate. In particular, we find that both cell lines display a cell-cycle signature that correlates with cell mass, with early and late cell-cycle signatures significantly enriched amongst genes with negative and positive correlations with mass, respectively. FL5.12 cells also show a significant correlation between single-cell growth efficiency and a G1-S transition signature, providing additional transcriptional evidence for a phenomenon previously observed through biophysical measurements alone. Importantly, the throughput and speed of our platform allows for the characterization of phenotypes in dynamic cellular systems. As a proof-of-principle, we apply our system to characterize activated murine CD8+ T cells and uncover two unique features of CD8+ T cells as they become proliferative in response to activation: i) the level of coordination between cell cycle gene expression and cell mass increases, and ii) translation-related gene expression increases and shows a correlation with single-cell growth efficiency. Overall, our approach provides a new means of characterizing the transcriptional mechanisms of normal and dysfunctional cellular mass and growth rate regulation across a range of biological contexts.
Pioneering, chromatin remodeling, and epigenetic constraint in early T-cell gene regulation by PU.1
Authors: Ungerbäck Jonas , Hosokawa Hiroyuki , Wang Xun , Strid Tobias , Williams Brian A. , Sigvardsson Mikael , Rothenberg Ellen V.
Published: May 2018

PU.1 is a dominant but transient regulator in early T-cell precursors and a potent transcriptional controller of developmentally important pro-T cell genes. Before T-lineage commitment, open chromatin is frequently occupied by PU.1, and many PU.1 sites lose accessibility when PU.1 is later downregulated. Pioneering activity of PU.1 was tested in in this developmentally dynamic context, by quantitating the relationships between PU.1 occupancy and site quality and accessibility as PU.1 levels naturally declined in pro-T cell development, and by using stage-specific gain and loss of function perturbations to relate binding to effects on target genes. PU.1 could bind closed genomic sites, but rapidly opened many of them, despite the absence of its frequent collaborators, C/EBP factors. The dynamic properties of PU.1 engagements implied that PU.1 binding affinity and concentration determine its occupancy choices, but with quantitative tradeoffs for occupancy between site sequence quality and stage-dependent site accessibility in chromatin. At non-promoter sites PU.1 binding criteria were more stringent than at promoters, and PU.1 was also much more effective as a transcriptional regulator at non-promoter sites where local chromatin accessibility depended on the presence of PU.1. Runx motifs and Runx1 binding were often linked to PU.1 at open sites, but highly expressed PU.1 could bind its sites without Runx1. Notably, closed chromatin presented a qualitative barrier to occupancy by the PU.1 DNA binding domain alone. Thus, effective pioneering at closed chromatin sites also depends on requirements beyond site recognition served by non-DNA binding domains of PU.1.
Protein design under competition for amino acids availability
Authors: Nerattini F. , Tubiana L. , Cardelli C. , Bianco V. , Dellago C. , Coluzza I.
Published: May 2018

Understanding the origin of the 20 letter alphabet of proteins is a long-lasting biophysical problem. In particular, studies focused extensively on the effect of a reduced alphabet size on the folding properties. However, the natural alphabet is a compromise between versatility and optimisation of the available resources.

Here, for the first time, we include the additional impact of the relative availability of the amino acids. We present a protein design scheme that involves the competition for resources between a protein and a potential interaction partner that, additionally, gives us the chance to investigate the effect of the reduced alphabet on protein-protein interactions. We identify the optimal reduced set of letters for the design of the protein, and we observe that even alphabets reduced down to 4 letters allow for single protein folding. However, it is only with 6 letters that we achieve optimal folding, thus recovering experimental observations.

Additionally, we notice that the binding between the protein and a potential interaction partner could not be avoided with the investigated reduced alphabets. Therefore, we suggest that aggregation could have been a driving force for the evolution of the large protein alphabet.
Estrogen Regulates the Satellite Cell Compartment in Females
Authors: Collins Brittany C. , Arpke Robert W. , Larson Alexie A. , Baumann Cory W. , Cabelka Christine A , Nash Nardina L. , Juppi Hanna-Kaarina , Laakkonen Eija K. , Sipilä Sarianna , Kovanen Vuokko , Spangenburg Espen E. , Kyba Michael , Lowe Dawn A.
Published: May 2018

Skeletal muscle mass, strength, and regenerative capacity decline with age, with many measures showing greater deterioration in females about the time estrogen levels decrease at menopause. Here we show that maintenance of muscle stem cells, satellite cells, as well as self-renewal and differentiation into muscle fibers, are severely compromised by estrogen deficiency. Mechanistically, by hormone replacement, use of a selective estrogen-receptor modulator (bazedoxifene), and conditional estrogen receptor knockout, we implicate 17β-estradiol and satellite cell expression of estrogen receptorα(ERα) and show that estrogen signaling through this receptor is necessary to prevent apoptosis of satellite cells. Early data from a biopsy study of women who transitioned from peri-to post-menopause are consistent with the loss of satellite cells coincident with the decline in estradiol in humans. Together, these results demonstrate an important role for estrogen in satellite cell maintenance and muscle regeneration in females.
Clinical significance of weak interleukin‐35 expression in patients with psoriasis
Authors: Li Tengda , Gu Mingli , Liu Peng , Liu Yun , Guo Jie , Zhang Weiwei , Qian Cheng , Deng Anmei
Published: May 2018

CD4+T cells and their related cytokines play an important role in the pathogenesis of psoriasis, a chronic, recurrent, inflammatory skin disease. The role of IL‐35, an immunosuppressive cytokine involved in many autoimmune diseases, in the pathogenesis of psoriasis is unclear. In this study IL‐35 expression and its clinical significance in patients with psoriasis were evaluated. Protein and mRNA levels of specified markers were measured by ELISA and qRT‐PCR, respectively. It was found that plasma IL‐35 concentrations were lower in patients with psoriasis than in healthy individuals (Z = −6.525, P < 0.0001). mRNA titers of Ebi3 and p35 were lower in peripheral blood mononuclear cells from patients with psoriasis than in those from healthy individuals (Z = −5.078, P < 0.0001; Z = −2.609, P = 0.009, respectively). The areas under the receiver‐operating characteristic (ROC) curves for IL‐35, Ebi3 and p35 in patients with psoriasis versus controls were 0.86, 0.78 and 0.64, respectively. Pearson correlation analysis showed that, in patients with psoriasis, plasma IL‐35 expression correlated negatively with concentrations of INF‐γ, tumor necrosis factor‐alpha, IL‐23, −17, and −22, and the Psoriasis Activity and Severity Index and positively with concentrations of transforming growth factor beta and IL‐10 . In summary, IL‐35 may mediate pathogenesis of psoriasis by influencing expression of Th1/Th17/Treg‐related cytokines and may therefore be a putative target for monitoring or treating psoriasis.
Sickness‐induced lethargy can increase host contact rates and pathogen spread in water‐limited landscapes
Authors: Franz Mathias , Kramer‐Schadt Stephanie , Greenwood Alex D. , Courtiol Alexandre
Published: May 2018

Severe infections in vertebrates commonly elicit sickness behaviour that includes anorexia and lethargy. Intuitively, sickness‐induced lethargy (SIL) should reduce contact among hosts. Therefore, for directly transmitted pathogens, sickness behaviour should reduce pathogen spread. However, there are indications that the relationship betweenSILand host contact rates can be reversed under specific social conditions.

Here, we used an agent‐based model to investigate the possibility that the nonsocial environment can also impact the relationship betweenSILand host contact rates.

Our results demonstrate that in water‐limited landscapes,SILcan increase host contact rates and associated pathogen spread. Based on our results, we hypothesize that a sickness‐induced increase in contact rates should be particularly likely and most pronounced in animals that are highly water dependent such as African buffaloes living in savanna environments.

In the context of virulence evolution, our findings contradict the expectation that the direct transmission of pathogens generally favours the evolution of reduced pathogen virulence compared to vector‐ and water‐borne transmission. Instead, our findings suggest that the opposite effect is possible in water‐limited landscapes: compared to vector‐ and water‐borne transmission, direct transmission can favour the evolution of increased virulence.

Our findings could be relevant in contexts other than direct transmission in water‐limited landscapes. For example, in addition to aggregating around limited water sources, sick individuals might aggregate at, or around, limited food sources, which could facilitate the spread of pathogens with different transmission modes. Therefore, sickness‐induced behavioural changes could critically affect the transmission of many pathogens in different environmental contexts.

Aplain language summaryis available for this article.
50‐year anniversary of Lloyd's “mean crowding”: Ideas on patchy distributions
Authors: Wade Michael J. , Fitzpatrick Courtney L. , Lively Curtis M.
Published: May 2018

This year marks the 50th anniversary of Monte B. Lloyd's “Mean Crowding” (1967) paper, in which he introduced a metric that accounts for an individual's experience of conspecific density.

Mean crowding allows ecologists to measure the degree of spatial aggregation of individuals in a manner relevant to intraspecific competition for resources.

We take the concept of mean crowding a step beyond its most common usage and that it has a mathematical relationship to many of the most important concepts in ecology and evolutionary biology.

Mean crowding, a first‐order approximation of the degree of nonrandomness in a distribution, can function as a powerful heuristic that can unify concepts across disciplines in a more general way that Lloyd originally envisioned.
Previous exposure to myxoma virus reduces survival of European rabbits during outbreaks of rabbit haemorrhagic disease
Authors: Barnett Louise K. , Prowse Thomas A. A. , Peacock David E. , Mutze Gregory J. , Sinclair Ron G. , Kovaliski John , Cooke Brian D. , Bradshaw Corey J. A.
Published: May 2018

Exploiting synergies among diseases or parasites could increase the efficacy of biological control of invasive species. In Australia, two viruses were introduced to control European rabbits Oryctolagus cuniculus: myxoma virus in 1950 and rabbit haemorrhagic disease virus in 1995. While these biological controls caused initial declines of >95% in affected populations, and despite recurring outbreaks of both diseases, rabbits remain a problem in many areas.

We used 18 years of capture–mark–recapture, dead recovery, and antibody assay data from a sentinel population in South Australia to test whether these two diseases interact to modify the survival of individual wild rabbits. We compared four joint, multistate, dead‐recovery models to test the hypotheses that rabbit haemorrhagic disease and myxoma viruses have synergistic (i.e., previous exposure to one virus affects survival during outbreaks of the other virus) or additive effects (i.e., previous exposure to one virus does not affect survival during outbreaks of the other virus).

Rabbit haemorrhagic disease outbreaks reduced the survival of individuals with no immunity by more than half during the 58‐day capture‐trip intervals, i.e., from 0.86–0.90 to 0.37–0.48. Myxomatosis outbreaks had a smaller effect, reducing survival to 0.74–0.82; however, myxomatosis outbreaks were more prolonged, spanning more than twice as many trips.

There was considerable information‐theoretic support (wAICc = 0.69) for the model in which exposure to myxomatosis affected survival during rabbit haemorrhagic disease outbreaks. Rabbits previously exposed to myxoma virus had lower survival during rabbit haemorrhagic disease outbreaks than rabbits never exposed to either virus. There was negligible support for the model in which previous exposure to rabbit haemorrhagic disease affected survival in myxomatosis outbreaks (wAICc < 0.01).

Synthesis and applications. Our results indicate that biological control agents can have a greater impact than single‐pathogen challenge studies might suggest. Introducing additional biological control agents might therefore increase the mortality of rabbits beyond the additive effects of individual biological controls. Furthermore, our results show that by understanding and exploiting disease synergies, managers could increase the efficacy of biological controls for other invasive animals.
Asset Location, Timing Ability and the Cross‐Section of Commercial Real Estate Returns
Authors: Ling David C. , Naranjo Andy , Scheick Benjamin
Published: May 2018

This study examines the sensitivity of equity REIT returns to time‐varying MSA allocations of REIT property portfolios. Using a large sample of individual commercial property holdings, we find significant cross‐sectional and time variation in REIT geographic exposures and the ability of these exposures to explain the cross‐section of REIT returns. We further find evidence consistent with REIT managers being able, on average, to time allocation decisions ahead of MSA outperformance. This effect is most prevalent in non‐gateway markets, varies significantly across MSAs and over time, and is concentrated in financially flexible firms with a more diversified geographic portfolio.
Influence of emotional coping on decision to stay in dysfunctional mentoring relationship
Authors: Ng Jhony Choon Yeong , Song Karen Kai Wen , Liu Yiping
Published: May 2018

The question of why mentees stay with a dysfunctional mentor has puzzled many scholars. In this paper, we argue that fresh graduates in an ongoing mentoring relationship are bombarded with feedback from both good and bad events that happen between them and their mentor, making it difficult for the mentee to know, with certainty, if their relationship with the mentor is objectively positive or negative. To decide whether they should stay with a mentor, we propose that mentees will constantly seek clues from their daily interactions with the mentor to judge if they will receive future benefits from the relationship. Drawing inferences from the intimate partner violence literature, we propose that fresh graduate mentees might misinterpret negative interactions with the mentor in a positive light, thus deciding to stay in the relationship because they expect to receive future benefits despite having experienced negative mentoring experiences.
Detection of Enterotoxin Genes and Methicillin‐Resistance inStaphylococcus aureusIsolated from Water Buffalo Milk and Dairy Products
Authors: Saka Erdem , Terzi Gulel Goknur
Published: May 2018

The aim of this study was to analyze the presence of genes encoding staphylococcal enterotoxins and methicillin resistance inStaphylococcus aureusisolates obtained from water buffalo milk and dairy products. A total of 200 samples (100 raw milk, 50 clotted cream, and 50 cheese samples) was collected from different dairy farms and smallholders in Samsun, Turkey. All samples were analyzed using the standard procedure EN ISO 6888‐1 and isolates were confirmed for the presence of the target 16S rRNA specific forStaphylococcusgenus specific andnucgene specific forS. aureusspecies by PCR.S. aureuswas identified in 30 of 100 milk (30%), 9 of 50 clotted cream (18%), and 17 of 50 cheese (34%) samples. A total of 99 isolates was confirmed asS. aureus. Genotypic methicillin resistance was evaluated using PCR for themecAgene. Out of 99 isolates, nine (9%) were found to be methicillin resistant (mecAgene positive). Twelve out of 99 (12%)S. aureusisolates were found positive for one or more genes encoding the enterotoxins. The gene coding for enterotoxin,sea, was the most frequent (five isolates, 41.6%), followed bysec(two isolates, 16.6%),sed(1 isolates, 8.3%) andsee(1 isolate, 8.3%). While three isolates (25%) contained bothsecandsed, none of the samples was positive forseb. In conclusion, the presence ofsegene‐positive and methicillin‐resistantS. aureusin buffalo milk and products revealed that consumption of these products is a potential risk of foodborne infection in this region.

Practical Application

Enterotoxigenic and methicillin‐resistantS. aureus (MRSA) in milk and dairy products is an important public health problem. Especially in traditional dairy products, Staphylococcal enterotoxins may cause food poisoning due to consumption of raw or unpasteurized milk products.
Low FT3 is a valuable predictor of severe acute pancreatitis in the emergency department
Authors: Yang Wei Qiang , Yang Qian , Chen Wan Jun , Zhang Xiao Bin , Xu Qing Qing , Qiao Yun , Xu Xin Hui , Liu Li , Lu Xiao Ye , Zhu Chang Qing
Published: May 2018

OBJECTIVE

To investigate the relationship between serum levels of thyroid hormones and disease severity at the early stage of acute pancreatitis (AP).

METHODS

Cohort data from 172 patients with AP attending the Emergency Department of our hospital from 2012 to 2017 were retrospectively reviewed and analyzed. Patients were categorized into mild (MAP), moderately severe (MSAP) and severe AP (SAP) groups based on the disease severity. The MSAP and SAP groups were combined into a non‐MAP group for analysis. The predictive values of C‐reactive protein (CRP) levels, Ranson score, APACHE II score and serum thyroid hormone levels were analyzed.

RESULTS

In total, 76 (44.2%), 85 (49.4%) and 11 (6.4%) patients were included in the MAP, MSAP and SAP groups, respectively. The free triiodothyronine (FT3) levels were significantly lower in the combined non‐MAP group than in the MAP group. The tetraiodothyronine (T4) levels were significantly lower in the SAP group than in the MAP and MSAP groups (P = 0.002). Logistic regression analysis revealed that a low FT3 level was an independent risk factor for the incidence of non‐MAP (P = 0.004). The area under the receiver operating characteristic curve and sensitivity of FT3 were 0.729 and 88.2%, respectively, which were higher than those of CRP, Ranson and APACHE II scores.

CONCLUSION

Monitoring FT3 levels in the early stage of AP is helpful for evaluating disease severity and predicting the incidence of non‐MAP, making it a useful tool for guiding AP treatment.
Fatty liver mediated by peroxisome proliferator‐activated receptor‐α DNA methylation can be reversed by a methylation inhibitor and curcumin
Authors: Li Yu Yuan , Tang Dan , Du Yan Lei , Cao Chuang Yu , Nie Yu Qiang , Cao Jie , Zhou Yong Jian
Published: May 2018

OBJECTIVE

Our studies in vitro and in vivo aimed to investigate the influence of DNA methylation of peroxisome proliferator activated receptor‐α (PPAR‐α) gene in non‐alcoholic fatty liver disease (NAFLD) pathogenesis and to observe whether the DNA methylation inhibitor 5‐Aza‐2'‐deoxycytidine (5‐Aza‐CdR) and the herbal medicine curcumin might reverse the effect both in vivo and in vitro.

METHODS

Steatotic hepatocyte model of cell lines and NAFLD rat models were established following protocols documented in previous studies. Subsequently, the models received 5‐Aza‐CdR and curcumin treatment. Morphological, histological and laboratory variables in each group were determined by routine methods, including PPAR‐α mRNA expression by polymerase chain reaction (PCR), PPAR‐α protein expression by Western blot and DNA methylation by pyrosequencing.

RESULTS

The steatotic hepatocyte model and NAFLD rat model were completely established. The expressions of PPAR‐α mRNA and protein were significantly lower in the steatotic hepatocyte and NAFLD rat model groups than in the controls (P < 0.05). The mean DNA methylation levels of the PPAR‐α gene were significantly higher in the two steatotic model groups than in the controls, especially at several CpG sites (P < 0.05). 5‐Aza‐CdR and curcumin treatment significantly reversed the DNA methylation levels, increased PPAR‐α mRNA and protein expression, and improved lipid accumulation in the two steatotic models (P < 0.05).

CONCLUSIONS

DNA methylation at the PPAR‐α gene is involved in the pathogenesis of NAFLD and is possibly reversible by 5‐Aza‐CdR and curcumin. Curcumin may be a promising candidate for NAFLD therapy.
Negative association between serum aryl hydrocarbon receptor concentrations and β‐cell function in patients with no history of diabetes undergoing coronary angiography
Authors: Wang Jun‐Sing , Lee Wen‐Jane , Lee I‐Te , Lin Shih‐Yi , Lee Wen‐Lieng , Liang Kae‐Woei , Lin Shing‐Jong , Sheu Wayne Huey‐Herng
Published: May 2018

Background

The aim of the present study was to investigate the association between serum aryl hydrocarbon receptor (AhR) levels and insulin resistance and β‐cell function in patients undergoing coronary angiography with no history of diabetes.

Methods

Patients with no history of diabetes who had undergone coronary angiography underwent an oral glucose tolerance test (OGTT) 2–4 weeks after discharge from hospital; blood samples were collected for measurements of glucose, insulin, and AhR. Patients’ glucose regulation status was determined on the basis of the OGTT. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA‐IR). β‐Cell function was assessed using the insulinogenic index (IGI).

Results

The study included 473 patients (mean (±SD) age 61 ±12 years, 81.8% male, mean body mass index 26.1 ±3.6 kg/m2). Overall, mean serum AhR concentrations were 25.1 ±12.2 pg/mL. Patients with normal glucose tolerance had a lower serum AhR concentrations than patients with prediabetes or newly diagnosed diabetes (23.4 ±10.8 vs 26.2 ±13.2 and 26.9 ±12.3 pg/mL, respectively; P = 0.029). Linear regression analysis revealed that serum AhR concentrations were not associated with HOMA‐IR, but were negatively associated with IGI after adjustment for several confounders, including HOMA‐IR (β = −0.162; 95% confidence interval − 0.302, −0.022; P = 0.023).

Conclusions

In patients with no history of diabetes, serum AhR concentrations were negatively associated with β‐cell function, independent of several confounders, including insulin resistance.
Optimal body mass index cut‐off points for prediction of incident diabetes in a Chinese population
Authors: Ma Hao , Wu Xiaoyan , Guo Xiaoyu , Yang Jianjun , Ma Xiaohui , Lv Mengfan , Li Ying
Published: May 2018

Background

The current body mass index (BMI) classifications have been established based on the risk of obesity‐related conditions, but not specifically on type 2 diabetes mellitus (T2DM). The aim of this study was to identify the optimal BMI cut‐off points for assessing incident T2DM risk in the Chinese population.

Methods

The longitudinal study cohort consisted of 8735 non‐diabetic participants aged 20–74 years at baseline, with a mean follow‐up period of 6.0 years. Body mass index, 2‐h plasma glucose after a 75‐g oral glucose tolerance test, and HbA1c were measured at baseline and follow‐up.

Results

During the follow‐up period, 825 participants were diagnosed with T2DM. In multivariable Cox regression analyses, after adjusting for covariates, a strong positive association between BMI and incident T2DM was found in the whole population; however, when stratified by age groups (20–39, 40–59, and 60–74 years), the risk associations between BMI and incident T2DM decreased with increasing age and were no longer evident in the 60–74 years group (Pinteraction < 0.001). The optimal BMI cut‐off points for predicting T2DM risk for men and women were 25.5 and 24.4 kg/m2, respectively, in the 20–39 years group, and 23.5 and 23.0 kg/m2, respectively, in the 40–59 years group. There was no predictive performance of BMI in the 60–74 years group for either sex.

Conclusions

The results suggest that the performance of BMI in predicting T2DM risk was best in subjects of younger age and decreased with age. Age‐ and sex‐specific BMI cut‐off points should be considered for T2DM risk stratification in the Chinese population.
Evaluation of redundancy analysis to identify signatures of local adaptation
Authors: Capblancq Thibaut , Luu Keurcien , Blum Michael G. B. , Bazin Eric
Published: May 2018

Ordination is a common tool in ecology that aims at representing complex biological information in a reduced space. In landscape genetics, ordination methods such as principal component analysis (PCA) have been used to detect adaptive variation based on genomic data. Taking advantage of environmental data in addition to genotype data, redundancy analysis (RDA) is another ordination approach that is useful to detect adaptive variation. This study aims at proposing a test statistic based on RDA to search for loci under selection. We compare redundancy analysis to pcadapt, which is a nonconstrained ordination method, and to a latent factor mixed model (LFMM), which is a univariate genotype–environment association method. Individual‐based simulations identify evolutionary scenarios where RDA genome scans have a greater statistical power than genome scans based on PCA. By constraining the analysis with environmental variables, RDA performs better than PCA in identifying adaptive variation when selection gradients are weakly correlated with population structure. In addition, we show that if RDA and LFMM have a similar power to identify genetic markers associated with environmental variables, the RDA‐based procedure has the advantage to identify the main selective gradients as a combination of environmental variables. To give a concrete illustration of RDA in population genomics, we apply this method to the detection of outliers and selective gradients on an SNP data set of Populus trichocarpa (Geraldes et al., ). The RDA‐based approach identifies the main selective gradient contrasting southern and coastal populations to northern and continental populations in the north‐western American coast.
Thoracoscopic decortication for the management of trapped lung caused by 14‐year pneumothorax: A case report
Authors: Tian Yan , Zheng Wenqi , Zha Nashunbayaer , Wang Yufei , Huang Shaojun , Guo Zhanlin
Published: May 2018

Trapped lung is defined by the lung's inability to expand and fill the thoracic cavity because of a restricting “peel” caused by benign or malignant pleural disease. However, trapped lung secondary to pneumothorax is rarely reported. We present a case of trapped lung caused by a pneumothorax that occurred some 14 years before the patient presented to our hospital with a complaint of incapacitating dyspnea. Computed tomography (CT) scans revealed trapping of the right lung with abnormal thickening of the visceral pleura. In view of the patient's history of pneumothorax, we concluded that his dyspnea was attributable mainly to the trapping of his lung by the earlier pneumothorax. We therefore scheduled thoracoscopic decortication, which was successfully completed. The patient's recovery after the operation was uneventful, and seven weeks after surgery the right lung had re‐expanded well.
Performance Measure Aggregation in Multi‐Task Agencies
Authors: Şabac Florin , Yoo Junwook
Published: May 2018

In multi‐task environments, the efficiency of aggregating managerial performance information and the degree of customization/standardization are closely related. Aggregation without information loss (i.e., statistically sufficient) requires at least as many measures as there are effective tasks (which arise through a task aggregation process analogous to that applied to homogeneous activities in activity‐based costing) and can be used uniformly for evaluation across similar jobs. Aggregation without economic loss (i.e., economically sufficient) can be achieved with a single performance measure but requires customization even across similar jobs. The main implication is that job complexity, the number of aggregate performance measures, and the degree of customization in performance measurement are interrelated. In particular, at the same level of performance measure aggregation, we predict highly customized performance evaluation in complex multi‐task jobs and standardized (uniform) performance evaluation only in simpler jobs with fewer tasks. We discuss additional empirical implications in the conclusion.
Th2 cytokines orchestrate the secretion of MUC5AC and MUC5B in IL‐5‐positive chronic rhinosinusitis with nasal polyps
Authors: Zhang Y. , Derycke L. , Holtappels G. , Wang X. D. , Zhang L. , Bachert C. , Zhang N.
Published: May 2018

Background

Mucin over‐secretion is a significant characteristic of chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to investigate the relationship between Th2 cytokines and MUC5AC or MUC5B, and the mechanism of mucin over‐secretion in the type‐2 inflammatory endotype of CRSwNP.

Methods

Main Th‐cell cytokines, associated mediators, and mucins were determined in the homogenates of nasal polyp samples from 21 CRSwNP patients and inferior turbinate samples from 8 controls, by ELISA or UniCAP system. Secretion of MUC5AC and MUC5B was measured in the supernatants of IL‐5, IL‐4, or IL‐13 primed nasal polyp fragments. Co‐localization of MUC5AC, MUC5B, and IL‐4 receptor α (IL‐4Rα) in CRSwNP and controls was evaluated by immunohistochemistry. Gene expression of IL‐4Rα in the samples was measured by real‐time reverse transcription‐polymerase chain reaction.

Results

Baseline protein levels of the Th2‐cytokines IL‐4, IL‐5, and IL‐13, and mucins MUC5AC and MUC5B were significantly higher in the IL‐5(+) CRSwNP group, compared to control and IL‐5(−) CRSwNP groups. MUC5AC and MUC5B secretions were significantly increased in IL‐4‐ or IL‐13‐primed, but not IL‐5‐primed fragments of nasal polyps. Immuno‐stained serial sections demonstrated that IL‐4Rα was widely expressed in the epithelium and submucosal glands in control and nasal polyp tissues. Gene expression of IL‐4Rα was elevated in nasal polyp tissues, specifically in the IL‐5(+) CRSwNP group.

Conclusions

In type‐2 inflammatory nasal polyps, characterized by the tissue expression of IL‐5, MUC5AC and MUC5B are overexpressed. Both IL‐4 and IL‐13 may upregulate mucin expression via IL‐4Rα, which is also overexpressed in IL‐5(+) CRSwNP.
Lack of fit tests based on sums of ordered residuals for linear models
Authors: Hattab Mohammad W. , Christensen Ronald
Published: May 2018

Christensen & Lin () suggested two lack of fit tests to assess the adequacy of a linear model based on partial sums of residuals. In particular, their tests evaluated the adequacy of the mean function. Their tests relied on asymptotic results without requiring small sample normality. We propose four new tests, find their asymptotic distributions, and propose an alternative simulation method for defining tests that is remarkably robust to the distribution of the errors. To assess their strengths and weaknesses, the Christensen & Lin () tests and the new tests were compared in different scenarios by simulation. In particular, the new tests include two based on partial sums of absolute residuals. Previous partial sums of residuals tests have used signed residuals whose values when summed can cancel each other out. The use of absolute residuals requires small sample normality, but allows detection of lack of fit that was previously not possible with partial sums of residuals.
Using high‐flow nasal cannulas for infants with bronchiolitis admitted to paediatric wards is safe and feasible
Authors: Heikkilä Paula , Sokuri Paula , Mecklin Minna , Nuolivirta Kirsi , Tapiainen Terhi , Peltoniemi Outi , Renko Marjo , Korppi Matti
Published: May 2018

Aim

Using a high‐flow nasal cannula (HFNC) for infant bronchiolitis is increasingly common, but insufficiently studied. In this retrospective study, we examined the outcomes of HFNC and compared infants who did and did not respond to this oxygen delivery method.

Methods

This 2012–2015 study of six Finnish hospitals focused on 88 infants under 12 months who received HFNC: 53 on paediatric wards and 35 in paediatric intensive care units (PICUs). We reviewed patient files for underlying factors, clinical parameters and HFNC treatment. The treatment failed if the patient was transferred to another respiratory support.

Results

We found HFNC treatment was successful in 76 (86%) infants, including all 53 on the paediatric wards and 23/35 PICU patients. The responders' heart rates were significantly lower, and their oxygen saturation was significantly higher at 60 minutes after HFNC treatment started and then stayed relatively constant. Their respiratory rate was only significantly lower after 360 minutes. In non‐responders, the respiratory rate initially decreased but was higher at 180 and 360 minutes after the start of HFNC.

Conclusion

We found preliminary evidence that oxygen support needs and heart rate were useful early predictors of HFNC therapy success in infants hospitalised with bronchiolitis, but respiratory rate was not.
Parental questionnaire study showed that annular ligament displacement was common in three‐year‐old children and almost a half had reoccurring episodes
Authors: Kimura Masahiko , Taketani Takeshi , Kurozawa Youichi
Published: May 2018

Aim

This study sought to determine the incidence of annular ligament displacement (ALD), also known as nursemaid's elbow, in the first 3 years of life.

Methods

A questionnaire was sent to 1098 families between August 2014 and July 2015 before their child attended a routine health check at 3 years of age in Izumo, Shimane prefecture, Japan. The questionnaire included a brief description about ALD, the age when ALD occurred and how the condition was managed.

Results

We received 784 (71.4%) responses and these showed that 61 (7.8%) children had a history of ALD and 31 (51%) were girls. The incidence was 2.6%, calculated by multiplying the number of children by the 3‐year observation period. The mean and median ages of the first ALD occurrence were both 25 months. In addition, 28 (46%) children with ALD had a recurrence and the mean number of ALD episodes was 1.8 (range 1‐5). The total number of ALD episodes was 108, and of these, 33 (30%) were seen at the hospital emergency department and 17 (16%) spontaneously resolved.

Conclusion

This study confirmed that ALD was a common occurrence in 3‐year‐old children and that there was a high rate of recurrence.
Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations
Authors: Bancroft Elizabeth K. , Saya Sibel , Page Elizabeth C. , Myhill Kathryn , Thomas Sarah , Pope Jennifer , Chamberlain Anthony , Hart Rachel , Glover Wayne , Cook Jackie , Rosario Derek J. , Helfand Brian T. , Hutten Selkirk Christina , Davidson Rosemarie , Longmuir Mark , Eccles Diana M. , Gadea Neus , Brewer Carole , Barwell Julian , Salinas Monica , Greenhalgh Lynn , Tischkowitz Marc , Henderson Alex , Evans David Gareth , Buys Saundra S. ,   IMPACT Study Steering Committee,   IMPACT Collaborators, Eeles Rosalind A. , Aaronson Neil K.
Published: May 2018

Objectives

To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi‐national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes.

Particpants and Methods

Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36‐item short‐form health survey (SF‐36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale‐Revised, risk perception and knowledge. The results of the baseline questionnaire are presented.

Results

A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants’ perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF‐36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status.

Conclusion

This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer‐specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening.
Impact of bowel management in alleviating symptoms of urinary incontinence in patients with spina bifida associated with overactive bladder and detrusor sphincter dyssynergia
Authors: Radojicic Zoran , Milivojevic Sasa , Milic Natasa , Lazovic Jelena Milin , Lukac Marija , Sretenovic Aleksandar
Published: May 2018

Objective

To examine the effects of bowel management on urinary incontinence in patients with spina bifida associated with overactive bladder (OAB) and detrusor sphincter dyssynergia (DSD).

Materials and Methods

The research was carried out during the period 2014–2017. A total of 35 patients (group 1) were administered bowel management combined with anticholinergic medication therapy and clean intermittent catheterization (CIC) and 35 patients (group 2) were treated only with anticholinergic medication therapy and CIC. Bowel management included daily enema, laxative application and a special diet, with the aim of treating constipation, evaluated according to the Roma III criteria and echosonographically determined transversal rectal diameter. The effects of the administered bowel management on urinary incontinence were assessed according to the mean dry interval between two CICs for all patients. All patients were followed up for 1 year, during which data were prospectively collected.

Results

There was no statistically significant difference with regard to age, gender and baseline clinical features between the two groups. In group 1, the mean ± sd dry interval between two CICs was 150.0 ± 36.4 min, and group 2 it was 101.3 ± 51.6 min. There was a significant difference in urinary incontinence, i.e. in the mean dry interval, between the two groups (P < 0.001).

Conclusion

Administering bowel management considerably increased the mean dry interval, thus greatly alleviating the symptoms of urinary incontinence. For this reason, bowel management should form an integral part of the treatment of patients with spina bifida and OAB and DSD.
Matrix metalloproteinase 7, soluble Fas and Fas ligand serum levels for predicting docetaxel resistance and survival in castration‐resistant prostate cancer
Authors: Szarvas Tibor , Sevcenco Sabina , Módos Orsolya , Keresztes Dávid , Nyirády Péter , Csizmarik Anita , Ristl Robin , Puhr Martin , Hoffmann Michèle J. , Niedworok Christian , Hadaschik Boris , Maj‐Hes Agnieszka , Shariat Shahrokh F. , Kramer Gero
Published: May 2018

Objective

To assess the predictive value of pre‐chemotherapy matrix metalloproteinase 7 (MMP‐7), soluble Fas (sFas) and Fas ligand (FasL) serum levels, as well as their changes during therapy.

Patients and Methods

Serum levels of MMP‐7, Fas and FasL were determined by ELISA in 96 patients with castration‐resistant prostate cancer (CRPC): 21 docetaxel‐resistant patients who received one single series and 75 docetaxel‐sensitive patients who received repeated series of docetaxel. In addition to the 96 pretreatment serum samples, 987 sera collected during chemotherapy were also analysed.

Results

Higher pretreatment serum MMP‐7, sFas and prostate‐specific antigen (PSA) levels were significantly associated with both docetaxel resistance (P = 0.007, P = 0.001, P < 0.001, respectively) and shorter cancer‐specific survival (P < 0.001, P = 0.041, P < 0.001, respectively). High MMP‐7 level remained an independent predictor of both docetaxel resistance (hazard ratio [HR] 2.298, 95% confidence interval [CI]: 1.354–3.899; P = 0.002) and poor cancer‐specific survival (HR 2.11, 95% CI: 1.36–3.30; P = 0.001) in multivariable analyses. Greater increase in MMP‐7 levels in the second treatment holiday and greater increase in PSA levels in the first and second treatment holidays were predictive of survival.

Conclusions

Pretreatment serum MMP‐7 levels may help to select patients with CRPC who are likely to benefit from docetaxel chemotherapy. Furthermore, MMP‐7 levels alone or in combination with PSA levels could be used for therapy monitoring. Correlative studies embedded in clinical trials are necessary to validate these biomarkers for clinical decision‐making.
Does mirabegron relieve ureteric stent‐related discomfort? A prospective, randomized, multicentre study
Authors: Tae Bum Sik , Cho Seok , Jeon Byung Jo , Choi Hoon , Park Jae Young , Cho Sung Yong , Lee Keon‐Cheol , Bae Jae Hyun
Published: May 2018

Objectives

To evaluate the effects of 50 mg mirabegron once daily for ureteric stent‐related discomfort after ureteroscopic procedures by conducting a multicentre randomized study.

Patients and Methods

A total of 100 patients with indwelling ureteric stents after ureteroscopic stone removal or retrograde intrarenal surgery (RIRS) were randomized 1:1 to receive either no treatment or mirabegron during the stenting period. At the time of stent removal, the validated Ureteral Stent Symptom Questionnaire (USSQ), International Prostate Symptom Score (IPSS), total amount of analgesics administered, and post‐voiding residual urine volume were reported for each patient.

Results

Overall, 96 patients were enrolled for analysis. The postoperative USSQ body pain score (21.96 vs 13.96; P = 0.007) and overall pain score (5.58 vs 2.83; P = 0.002) were lower in the mirabegron group than in the control group. The USSQ urinary symptom scores (32.58 vs 27.92; P = 0.582) and USSQ general health score (17.71 vs 14.00; P = 0.281) were also lower in the mirabegron group, but the difference was not significant. Postoperative IPSS total scores and quality‐of‐life scores were lower in the mirabegron group, but the difference was not significant. The change in IPSS storage symptom score, however, was lower in the mirabegron group than in the control group (3.58 ± 3.58 vs 1.83 ± 4.39; P = 0.035). Post‐void residual urine volume did not differ between the two groups (P > 0.05).

Conclusion

The use of 50 mg mirabegron once daily has the potential to reduce ureteric stent‐related discomfort. Prospective larger‐scale, placebo‐controlled studies are warranted to further evaluate the beneficial effects of mirabegron on stent‐related symptoms.
Prevalence of reduced visual acuity among preschool children in eastern China and comparison at a 5‐year interval
Authors: Zhang Xiaohan , Wang Yue , Huang Dan , Sun Qigang , Zhao Xiaoyan , Ding Hui , Bai Jing , Chen Ji , Chen Xuejuan , Liu Hu
Published: May 2018

Importance

Assessing the prevalence of reduced visual acuity and its change over time has significant public health importance. This study evaluated prevalence of reduce visual acuity in children aged 48–60 months, and compared it with previous data.

Background

Previous studies reported prevalence of reduced visual acuity in preschool children, but none has evaluated prevalence change in the same area.

Design

Nanjing Eye Study, a longitudinal population‐based study.

Participants

Two thousand three hundred eligible children.

Methods

Comprehensive eye examinations.

Main Outcome Measures

Uncorrected visual acuity, presenting visual acuity, best‐corrected visual acuity, anterior segment and fundus examination, cycloplegic refraction.

Results

Based on the worse and better eye, respectively, 6.8% and 3.5% had reduced uncorrected visual acuity and 4.0% and 1.4% had reduced presenting visual acuity. Compared to rates in the Nanjing Paediatric Vision Project carried out 5 years ago in the same area, the prevalence rates of reduced uncorrected visual acuity were significantly higher (6.8% vs. 5.3%, P = 0.04 for worse eye; 3.5% vs. 2.1%, P = 0.0049 for better eye), but there was no significant increase in rates of reduced presenting visual acuity (4.0% vs. 3.7%, P = 0.63 for better eye; 1.4% vs. 1.7%, P = 0.43 for worse eye). The prevalence rate of glasses prescription is higher in this study (4.5% vs. 3.1%, P = 0.02).

Conclusions and Relevance

Prevalence of reduced uncorrected visual acuity increased significantly, indicating that Chinese children are faced with more vision‐threatening factors. However, more children with refractive errors got appropriate correction.
Lessons for modern insulin development
Authors: Herring R. , Russell‐Jones D. D. L.
Published: May 2018

There have been many advances in insulin with a realistic possibility of mimicking nature to improve insulin replacement, with a view to achieving improved metabolic control. Lessons can be learnt from the evolution of insulin, insulin development, and new advances in technology. This may lead to fewer side effects of therapy resulting in a lower risk of hypoglycaemia and less weight gain, which could in turn could reduce long‐term complications for people with diabetes.