bluuebunny/crossref_metadata_2025_split huggingface dataset:
NECAPs are negative regulators of the AP2 clathrin adaptor complex
Authors: Beacham Gwendolyn M , Partlow Edward A , Lange Jeffrey J , Hollopeter Gunther 
Published: September 2017

ABSTRACTEukaryotic cells internalize transmembrane receptors via clathrin-mediated endocytosis, but it remains unclear how the machinery underpinning this process is regulated. We recently discovered that membrane-associated muniscin proteins such as FCHo and SGIP initiate endocytosis by converting the AP2 clathrin adaptor complex to an open, active conformation that is then phosphorylated (Hollopeter et al., 2014). Here we report that loss ofncap-1, the soleC.elegansgene encoding an adaptiN Ear-binding Coat-Associated Protein (NECAP), bypasses the requirement for FCHO-1. Biochemical analyses reveal AP2 accumulates in an open, phosphorylated state inncap-1mutant worms, suggesting NECAPs promote the closed, inactive conformation of AP2. Consistent with this model, NECAPs preferentially bind open and phosphorylated forms of AP2in vitroand localize with constitutively open AP2 mutantsin vivo. NECAPs do not associate with phosphorylation-defective AP2 mutants, implying that phosphorylation precedes NECAP recruitment. We propose NECAPs function late in endocytosis to inactivate AP2.
Comprehensive survey of vitiligo patients in the northeast of China using a predesigned questionnaire
Authors: Lin Zheng , Tian Yaping , Bai Bingxue , Liu Mei , Wu Yan , Xiao Bihuan , Gao Xing‐Hua , Chen Hong‐Duo 
Published: September 2017

AbstractTo assess the sociodemographic data and clinical information of outpatients affected by vitiligo in the northeast of China, vitiligo patients or guardians who presented to the clinic were invited to participate in an exploratory questionnaire. The questionnaire consisted of two sections related to vitiligo, including sociodemographic data and clinical information. A total of 983 vitiligo patients answered the questionnaire. The rates of female and male patients were comparable. The investigated patients were mostly young and middle‐aged. Most patients suffered from vitiligo in childhood or young adulthood. Vitiligo vulgaris was the most common type of vitiligo in clinic and 53.0% of patients were categorized as body surface area (BSA) of 10% or less. In response to the latest treatment, 43.6% of patients achieved good response (completely stopped or almost disappeared). More patients at active stage showed good response than the patients at stable stage (χ2 = 7.866, P < 0.05). Chronic comorbid condition(s) were observed in 12.6% of patients with BSA of more than 10%, whereas those were seen in 6.0% of patients with BSA of 10% or less (χ2 = 12.969, P < 0.05). In conclusion, active vitiligo seems to respond better than stable vitiligo and complications with other autoimmune diseases more frequently observed in severe patients than mild patients. The current study presented a comprehensive understanding of vitiligo in the northeast of China.
Competition induces increased toxin production in toad larvae without allelopathic effects on heterospecific tadpoles
Authors: Bókony Veronika , Üveges Bálint , Móricz Ágnes M. , Hettyey Attila 
Published: September 2017

Abstract

Inducible defences are a form of phenotypic plasticity by which organisms respond to and mitigate the threat posed by predators, parasites and competitors. While anti‐predatory defences are often in trade‐off with anti‐competitor responses, chemicals that deter predators may have negative effects on competitors as well. Allelopathy is well known in plants and plant‐like animals, but whether the toxins of mobile, behaviourally and morphologically complex animals are induced by and exert allelopathic effects on competitors is poorly known.

Common toads Bufo bufo synthesize bufadienolides which make them unpalatable or toxic to many predators. However, bufadienolide content of toad tadpoles correlates positively with the density of competitors in natural populations, suggesting that they may upregulate their toxin production to inhibit their competitors, such as heterospecific tadpoles that may be vulnerable to toad toxins.

We conducted a microcosm experiment with tadpoles of common toads and agile frogs Rana dalmatina, in which we manipulated the density of conspecific and heterospecific competitors. We measured the bufadienolide content of toad tadpoles to test for competitor‐induced changes in toxin production, and we assessed the growth and development of agile frog tadpoles to test for allelopathy.

We found that toad tadpoles contained higher amounts of bufadienolides at higher densities; however, heterospecific competitors did not have a stronger effect than conspecifics. Furthermore, the presence or density of toad tadpoles had no effect on the body mass and development rate of agile frog tadpoles.

Our results demonstrate competitor‐induced plasticity in toxin production, but we found no support for an allelopathic function of bufadienolides. Instead, we suggest that inducible changes in bufadienolide production may serve to mitigate risks posed by competitors, including aggression, cannibalism or disease. Therefore, bufadienolides are intriguing candidates for multi‐purpose defences that may provide protection not only against predators but also against competitors.

A plain language summary is available for this article.
Do instability markers predict satisfactory reduction and requirement for later surgery in emergency department patients with wrist fracture?
Authors: Winayak Amar , Gossat Alyza , Cooper Jenny , Ritchie Peter , Lim Wei , Klim Sharon , Kelly Anne‐Maree 
Published: September 2017

AbstractObjectiveResearch suggests that the presence of instability markers in patients with displaced distal radial fractures is associated with poorer outcome. Our aims were to determine whether the presence of previously defined instability markers could predict the likelihood of successful ED reduction and requirement for a secondary procedure after ED reduction.MethodsRetrospective cohort study performed by medical record review. Adult ED patients coded as having an isolated wrist fracture and having fracture reduction in ED were eligible for inclusion. Data collected included demographics, history of osteoporosis, mechanism of injury, radiological features on X‐rays and performance of a secondary procedure. Outcomes of interest were the rate of successful fracture reduction in ED (against defined radiological criteria), the rate of secondary procedures and the association between the number of defined instability risk factors and successful reduction and performance of a secondary surgical procedure. Analysis was by χ2 test, receiver operating characteristic curve, logistic regression analyses.ResultsThree hundred and nineteen patients were studied; median age 62 years, 77% female. Sixty‐five per cent of patients had satisfactory fracture reduction in ED (95% CI 59%–70%). Eighty‐six patients underwent a secondary procedure to reduce/stabilise their fracture (28%, 95% CI 23%–33%). Younger age, lack of satisfactory ED reduction and increased number of instability factors were independently predictive of the performance of a secondary procedure.ConclusionInstability risk factors are common in patients with wrist fractures requiring reduction in ED. The number of instability factors is not a strong predictor of the performance of secondary procedures.
Characteristics of the local recurrence pattern after curative resection and values in target region delineation in postoperative radiotherapy for lower thoracic esophageal squamous cell cancer
Authors: Liu Jun , Cai Xuwei , Liu Qi , Li Hongxuan , Cheng Yan , Fu Xiaolong 
Published: September 2017

BackgroundThe aim of this study was to investigate the patterns and influencing factors of local‐regional recurrence of lower thoracic esophageal squamous cell carcinoma (TESCC) after curative resection and to delineate the clinical target volume (CTV) of postoperative radiotherapy (PORT).MethodsFrom January 2009 to December 2013, the clinical data of patients who experienced local‐regional recurrence after curative esophagectomy were collected and analyzed to determine local‐regional recurrence patterns and to evaluate whether a proposed T‐shaped PORT CTV could cover regions of local‐regional failure.ResultsA total of 108 patients were eligible for this study. All patients experienced postoperative recurrence of lower TESCC. The time to local‐regional failure varied from one to 52 months (average 13.4 ± 11.0). Among the 108 patients, 127 recurrence sites were detected as the first recurrence event: 37 cases in the bilateral supraclavicular region, 56 in the upper mediastinum, 14 in the middle mediastinum, 15 in the upper abdominal lymph nodes, and five cases of anastomotic recurrence. The proposed PORT CTV could successfully cover 89 (82.4%) out of the 108 recurrences and 84.2% of the sites (107/127) of recurrence in our sample.ConclusionLocal‐regional recurrence of lower TESCC is mainly distributed in the supraclavicular, upper‐middle mediastinum, anastomotic stoma, and upper abdominal lymph node regions. The proposed T‐shaped PORT CTV field could cover over 80% of local‐regional failure in our sample; therefore, we suggest that PORT should focus on this area.
Measuring Emergency Department Acuity
Authors: Yiadom Maame Yaa A. B. , Baugh Christopher W. , Barrett Tyler W. , Liu Xulei , Storrow Alan B. , Vogus Timothy J. , Tiwari Vikram , Slovis Corey M. , Russ Stephan , Liu Dandan ,   The ED Operations Study Group 2015
Published: September 2017

AbstractBackgroundEmergency department (ED) acuity is the general level of patient illness, urgency for clinical intervention, and intensity of resource use in an ED environment. The relative strength of commonly used measures of ED acuity is not well understood.MethodsWe performed a retrospective cross‐sectional analysis of ED‐level data to evaluate the relative strength of association between commonly used proxy measures with a full spectrum measure of ED acuity. Common measures included the percentage of patients with Emergency Severity Index (ESI) scores of 1 or 2, case mix index (CMI), academic status, annual ED volume, inpatient admission rate, percentage of Medicare patients, and patients seen per attending‐hour. Our reference standard for acuity is the proportion of high‐acuity charts (PHAC) coded and billed according to the Centers for Medicare and Medicaid Service's Ambulatory Payment Classification (APC) system. High‐acuity charts included those APC 4 or 5 or critical care. PHAC was represented as a fractional response variable. We examined the strength of associations between common acuity measures and PHAC using Spearman's rank correlation coefficients (rs) and regression models including a quasi‐binomial generalized linear model and linear regression.ResultsIn our univariate analysis, the percentage of patients ESI 1 or 2, CMI, academic status, and annual ED volume had statistically significant associations with PHAC. None explained more than 16% of PHAC variation. For regression models including all common acuity measures, academic status was the only variable significantly associated with PHAC.ConclusionEmergency Severity Index had the strongest association with PHAC followed by CMI and annual ED volume. Academic status captures variability outside of that explained by ESI, CMI, annual ED volume, percentage of Medicare patients, or patients per attending per hour. All measures combined only explained only 42.6% of PHAC variation.
Sexual identity differences in high‐intensity binge drinking: findings from a US national sample
Authors: Fish Jessica N. , Hughes Tonda L. , Russell Stephen T. 
Published: September 2017

AbstractAimTo estimate sexual identity differences in high‐intensity binge drinking.Design and settingCross‐sectional US adult health survey from 2014 and 2015.ParticipantsUS adults aged 18 and older (n = 215 684; n = 203 562 heterosexual, n = 2784 lesbian/gay, n = 2892 bisexual, n = 686 ‘other’ and n = 1947 don't know/unsure).MeasurementsSelf‐reported past 30‐day standard binge and high‐intensity binge drinking. Standard binge drinking cut‐off values were 4+/5+ drinks for women and men, respectively. High‐intensity binge drinking was measured as two and three times the standard level (8+ and 12+ drinks for women and 10+ and 15+ drinks for men).FindingsLesbian and bisexual women were more likely than heterosexual women to report consuming 4+ drinks (adjusted odds ratio [aOR] =1.57, confidence interval [CI] = 1.18, 2.09 and aOR = 1.83, CI = 1.45, 2.30 for lesbian and bisexual women, respectively); 8+ drinks (aOR = 3.86, CI = 2.39, 6.24, aOR = 2.07, CI = 1.39, 3.07); and 12+ drinks (aOR = 3.81, CI = 1.77, 8.19, aOR = 2.54, CI = 1.25, 5.14) on a single occasion in the past 30 days. Generally, gay and bisexual men were no more likely than heterosexual men to report standard or high‐intensity binge drinking. However, bisexual men were more likely than heterosexual men to consume 15+ drinks (aOR = 1.76, 95% CI = 1.01, 3.06). Rates of standard and high‐intensity binge drinking were similar between heterosexual and unsure men and women. Men and women who indicated ‘other’ sexual identities were generally less likely than heterosexuals to report standard and high‐intensity binge drinking, with the exception of 4+ drinks for women and 10+ drinks for men.ConclusionsIn the United States, sexual minority women are more likely, and sexual minority men are equally likely, to drink at standard and high‐intensity binge drinking levels as their heterosexual counterparts.
Symptom management and psychological support for families are the cornerstones of end‐of‐life care for children with spinal muscular atrophy type 1
Authors: Di Pede Chiara , Agosto Caterina , De Tommasi Valentina , De Gregorio Alessandra , Benini Franca 
Published: September 2017

AbstractAimThis study described end‐of‐life care for children affected by spinal muscular atrophy type 1 (SMA1), which is characterised by progressive muscle weakness and develops in the first six months of life.MethodsWe retrospectively analysed 17 children (13 boys) who attended the University of Padua's paediatric palliative care centre in Italy from March 2000 to March 2015. All the children received supportive care without proactive respiratory intervention to prolong survival.ResultsThe median age at admission was 3.57 months, and the median age at death was 6.80 months. The most frequent symptoms were dyspnoea and pain. In the last 72 hours of life, 15/17 children required more intense doses of morphine and, or, benzodiazepines for intractable dyspnoea and pain, but deep palliative sedation was not needed. Airway suction to manage secretions and nasogastric tubes was required in all cases. The place of death was previously planned by the parents in all cases – home, hospital or hospice – and 15/17 deaths occurred in that place. We also interviewed 16 of the 17 parents after their child died.ConclusionOur study found that symptom management and psychological support for families were the cornerstones of end‐of‐life care for children with SMA1.
Performing a urine dipstick test with a clean‐catch urine sample is an accurate screening method for urinary tract infections in young infants
Authors: Herreros María Luisa , Tagarro Alfredo , García‐Pose Araceli , Sánchez Aida , Cañete Alfonso , Gili Pablo 
Published: September 2017

AbstractAimThis study evaluated using urine dipstick tests with the clean‐catch method to screen for urinary tract infection (UTI) in febrile infants under 90 days of age.MethodsWe carried out a comparative diagnostic accuracy study of infants under 90 days old, who were studied for unexplained fever without any source, in the emergency room of a hospital in Madrid from January 2011 to January 2013. We obtained matched samples of urine using two different methods: a clean‐catch, standardised stimulation technique and catheterisation collection. The results of the leucocyte esterase test and nitrite test were compared with their urine cultures.ResultsWe obtained 60 pairs of matched samples. A combined analysis of leukocyte esterase and, or, nitrites yielded a sensitivity of 86% and a specificity of 80% for the diagnosis of UTIs in clean‐catch samples. The sensitivity of leukocyte esterase and, or, nitrites in samples obtained by catheterisation were not statistically different to the clean‐catch samples (p = 0.592).ConclusionPerforming urine dipstick tests using urine samples obtained by the clean‐catch method was an accurate screening test for diagnosing UTIs in febrile infants of less than 90 days old. This provided a good alternative to bladder catheterisation when screening for UTIs.
Molecular mechanisms regulating perivascular adipose tissue – potential pharmacological targets?
Authors: Kennedy Simon , Salt Ian P 
Published: September 2017

Linked ArticlesThis article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue – Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc
Lon protease: a novel mitochondrial matrix protein in the interconnection between drug‐induced mitochondrial dysfunction and endoplasmic reticulum stress
Authors: Polo Miriam , Alegre Fernando , Moragrega Angela B , Gibellini Lara , Marti‐Rodrigo Alberto , Blas‐Garcia Ana , Esplugues Juan V , Apostolova Nadezda 
Published: September 2017

Background and PurposeMitochondria‐associated membranes (MAMs) are specific endoplasmic reticulum (ER) domains that enable it to interact directly with mitochondria and mediate metabolic flow and Ca2+ transfer. A growing list of proteins have been identified as MAMs components, but how they are recruited and function during complex cell stress situations is still not understood, while the participation of mitochondrial matrix proteins is largely unrecognized.Experimental ApproachThis work compares mitochondrial/ER contact during combined ER stress/mitochondrial dysfunction using a model of human hepatoma cells (Hep3B cell line) treated for 24 h with classic pharmacological inducers of ER stress (thapsigargin), mitochondrial dysfunction (carbonyl cyanide m‐chlorophenyl hydrazone or rotenone) or both (the antiretroviral drug efavirenz used at clinically relevant concentrations).Key ResultsMarkers of mitochondrial dynamics (dynamin‐related protein 1, optic atrophy 1 and mitofusin 2) were expressed differently with these stimuli, pointing to a specificity of combined ER/mitochondrial stress. Lon, a matrix protease involved in protein and mtDNA quality control, was up‐regulated at mRNA and protein levels under all conditions. However, only efavirenz decreased the mitochondrial content of Lon while increasing its extramitochondrial presence and its localization to MAMs. This latter effect resulted in an enhanced mitochondria/ER interaction, as shown by co‐immunoprecipitation experiments of MAMs protein partners and confocal microscopy imaging.Conclusion and ImplicationsA specific dual drug‐induced mitochondria‐ER effect enhances the MAMs content of Lon and its extramitochondrial expression. This is the first report of this phenomenon and suggests a novel MAMs‐linked function of Lon protease.
Complement regulatory proteins in kidneys of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis
Authors: Cheng L , Gou S-J , Qiu H-Y , Ma L , Fu P 
Published: September 2017

Summary
The complement system activation is involved in the development of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). The study aimed to investigate the expression of complement regulatory proteins (CRPs) CD46, CD55 and CD59 in kidneys of 51 AVV patients. The expression of CD46, CD55 and CD59 in kidneys was detected by immunohistochemistry and double immunofluorescence staining. The immunohistochemical examination revealed that expression of the three CRPs could be detected in the glomeruli and tubules of both AAV patients and normal controls. The expression levels of the three CRPs in glomeruli of patients with AAV were significantly lower than those of normal controls. The scores of CD46 and CD55 expression in the tubules of AAV patients were significantly lower than those of normal controls, while there was no significant difference between the scores of CD59 expression in tubules of AAV patients and those of normal controls. Among AAV patients, the expression level of CD46 in glomeruli correlated inversely with the proportion of normal glomeruli, while it correlated with tubular atrophy in renal interstitium (r = –0·305, P = 0·026; r = 0·330, P = 0·023, respectively). The expression levels of CD55 and CD59 in glomeruli correlated with the proportion of total crescents (r = 0·384, P = 0·006; r = 0·351, P = 0·011, respectively). Double immunofluorescence staining indicated that all three CRPs were expressed on endothelial cells, podocytes and mesangial cells in glomeruli. The expression levels of the three CRPs were dysregulated in kidneys of patients with AAV. The expression levels of CD46, CD55 and CD59 were associated with the severity of renal injury of AAV patients.
An increased CD25-positive intestinal regulatory T lymphocyte population is dependent upon Cox-2 activity in the Apcmin/+ model
Authors: Faluyi O O , Fitch P , Howie S E M 
Published: September 2017

Summary
Only mismatch repair (MMR)-deficient colorectal cancer (CRC) appears to respond well to programmed death (PD)-1 inhibition at the present time. Emerging evidence suggests a role for micro-environmental factors such as CD25+ cells modulating response to PD-1 inhibition. In the ApcMin/+ model of familial adenomatous polyposis (MMR-proficient CRC), increased Cyclooxygenase-2 (Cox-2) expression by cells which include alternatively activated mononuclear phagocytes promotes intestinal tumorigenesis by mechanisms which may include immune suppression. To gain insight into this, we compared regulatory T cell (Treg) populations between ApcMin/+ and wild-type mice prior to and after the phase of increased intestinal Cox-2-dependent prostaglandin E2 (PGE2) production. There was no difference in systemic Treg function or numbers between ApcMin/+ and wild-type mice. However, increased numbers of small intestinal CD25+ Tregs were observed with increased Cox-2 activity in the absence of any difference in the expression of Tgf-β or Tslp between ApcMin/+ and wild-type mice. Cox-2 inhibitor therapy (Celecoxib) reversed the increase in ApcMin/+ intestinal CD25+ Treg numbers, without decreasing numbers of CD25+ systemic Tregs. Forkhead box protein 3 (FoxP3+) and Cox-2+ cells were co-localized to the interstitium of adenomas of Apcmin/+ mice. These results suggest selective dependence of an ‘activated Treg’ phenotype on paracrine Cox-2 activity in ApcMin/+ small intestine. For therapeutic potential, further studies are required to evaluate the relevance of these findings to human cancer as well as the functional significance of CD25+ intestinal Tregs in cancer.