bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure and mechanism of a cyclic trinucleotide-activated bacterial endonuclease mediating bacteriophage immunity
Authors: Lau Rebecca K. , Ye Qiaozhen , Patel Lucas , Berg Kyle R. , Mathews Ian T. , Watrous Jeramie D. , Whiteley Aaron T. , Lowey Brianna , Mekalanos John J. , Kranzusch Philip J. , Jain Mohit , Corbett Kevin D.
Published: July 2019

Bacteria possess an array of defenses against foreign invaders, including diverse nucleases that target and destroy the genome of an invading bacteriophage or foreign DNA element. A recently-described bacteriophage immunity pathway employs a cGAS/DncV-like nucleotidyltransferase to produce a cyclic tri-AMP second messenger, which activates the DNA endonuclease effector NucC. Here, we show that NucC is related to restriction enzymes but uniquely assembles into a homotrimer in solution. cAAA binding in a conserved allosteric pocket promotes assembly of two NucC trimers into a homohexamer competent for double-strand DNA cleavage. We propose that NucC mediates bacteriophage immunity either through global activation, causing altruistic cell death and abortive infection, or through local activation and targeted phage genome destruction. Finally, we identify NucC homologs in type III CRISPR-Cas systems, where they likely function as accessory nucleases activated by cyclic oligoadenylate second messengers synthesized by these systems’ effector complexes.
Gsα stimulation of mammalian adenylate cyclases regulated by their hexahelical membrane anchors
Authors: Seth Anubha , Finkbeiner Manuel , Grischin Julia , Schultz Joachim E.
Published: July 2019

Mammalian adenylate cyclases (ACs) are pseudoheterodimers with dissimilar hexahelical membrane-anchors, isoform-specifically conserved for more than half a billion years. We exchanged both membrane anchors of the AC isoform 2 by the isosteric quorum-sensing receptor fromVibrio, CqsS, which has a ligand,Cholera-Autoinducer-1 (CAI-1). In the chimera, AC activity was stimulated by Gsα, CAI-1 had no effect. Surprisingly, CAI-1 inhibited Gsα stimulation. We report that Gsα stimulation of human AC isoforms 2, 3, 5, and 9 expressed in Sf9 cells is inhibited by serum as is AC activity in membranes from rat brain cortex. AC2 activation by forskolin or forskolin/Gsα was similarly inhibited. Obviously, serum contains as yet unidentified factors affecting AC activity. The data establish a linkage in ACs, in which the membrane anchors, as receptors, transduce extracellular signals to the cytosolic catalytic dimer. A mechanistic three state model of AC regulation is presented compatible with all known regulatory inputs into mammalian ACs. The data allow designating the membrane anchors of mammalian ACs as orphan receptors and establish a new level of AC regulation.
Molecular determinants of large cargo transport into the nucleus
Authors: Paci Giulia , Lemke Edward A
Published: July 2019

Transport of molecules between the nucleus and the cytoplasm is tightly regulated by the nuclear pore complex (NPC). Even very large cargoes such as many pathogens, mRNAs and pre-ribosomal subunits can pass the NPC intact. Compared to small import complexes, for such large cargoes >15 nm there is very little quantitative understanding of the mechanism for efficient transport, the role of multivalent binding to nuclear transport receptors via nuclear localisation sequences (NLSs) and effects of size differences. Here, we assayed nuclear import kinetics in cells for a total of 30 large cargo models based on four capsid-like particles in the size range of 17-36 nm, with tuneable numbers of up to 240 NLSs. We show that the requirements for transport scale non-linearly with size and obey a minimal cut off of functional import requiring more than 10 NLS in the lowest case. Together, our results reveal the key molecular determinants on large cargo import kinetics in cells.
Centrioles are amplified via rosette formation in cycling progenitors of olfactory sensory neurons
Authors: Ching Kaitlin , Stearns Tim
Published: July 2019

Olfaction in most animals is mediated by neurons bearing cilia that are accessible to the environment. Olfactory sensory neurons (OSNs) in chordates usually have multiple cilia, each with a centriole at its base. OSNs differentiate from stem cells in the olfactory epithelium, and how the epithelium generates cells with many centrioles—about 16 in mouse—is not yet understood. We show that centrioles are amplified via centriole rosette formation in both embryonic development and turnover of the olfactory epithelium in adults, and rosette-bearing cells often have free centrioles in addition. Cells with amplified centrioles can go on to divide, with centrioles clustered at each pole. Additionally, we found that immediate neuronal precursors amplify centrioles concomitantly with elevation of mRNA for Plk4 and Stil, key regulators of centriole duplication. Our findings highlight the importance of accounting for centriole amplification in neuron regeneration therapies derived from olfactory epithelia.
Proactive review by the emergency department before inter‐hospital transfer (the PREVENT study)
Authors: Mitra Biswadev , Carter Annie , Smit De Villiers , Rahman Fatima , O'Donovan Shane , Olaussen Alexander , Pui Jiun Kae , Abetz Jeremy , Hunter Peter , Cameron Peter A
Published: July 2019

Objectives

To determine the population of patients where patient transfer may be prevented by assessment of a senior ED registrar at the referring hospital.

Methods

Patients transferred from Caulfield Hospital, specialising in community services, rehabilitation, aged care and aged mental health to The Alfred Emergency and Trauma Centre, an adult major referral centre within the same clinical network were identified from 1 July 2016 to 31 December 2016. Medical records were reviewed independently by two clinicians to determine preventability of transfer and whether attendance by a senior ED registrar could have prevented the transfer.

Results

There were 221 patients included with a mean age of 73.6(15.1) years. The median time spent in the ED was 4 h (interquartile range 2–8) and 197 (89.1%) were admitted. There were 107 (48.6%) transfers deemed preventable or potentially preventable, with 104 preventable by attendance of a senior ED registrar. The most common indication for transfer was acute trauma (n = 55; 24.9%), and the odds of a case being preventable or potentially preventable if transferred for the primary indication of trauma was 3.9 (95% confidence interval 2.1–7.1; P < 0.001). Among the preventable cases, the total cost of transfer was AU$105 984 over 6 months, not accounting for the costs of duplication of care.

Conclusions

This proof‐of‐concept study suggests that strategies to expand the provision of acute care to outreach within specialist networks and reduce patient transfers should be further explored. An outreach programme for improved acute assessment of patients at the referring hospital particularly after acute trauma may prevent transfers, improving care pathways.
Australian Retirement System: Significance of Pillars 3 and 4 in Achieving an Adequate Standard of Living in Retirement
Authors: Evans John R. , Razeed Abdul
Published: July 2019

Most research relating to the adequacy of the Australian retirement system has concentrated on Pillars 1 and 2. This paper indicates that there is a high probability that Pillars 3 and 4 will be needed to ensure an adequate standard of living in retirement, and in most scenarios, the contribution to retirement adequacy from Pillars 3 and 4 is very significant. We include an international comparison of equivalent Pillars 1 and 2 costs and conclude this analysis supports our results.
Potentially Preventable Mortality in Young Australian Women, 2001 to 2016
Authors: Rawlings Louise , O’Shaughnessy Pauline , Robson Stephen J.
Published: July 2019

We examined mortality rates in Australian women aged twenty to fifty years during 2001–2016, demonstrating continued disparity by socioeconomic status. Mortality has declined but the reduction occurred in the first decade with no evidence of improved rates since 2010. There have been steady improvements in death rates from causes not considered preventable, while potentially preventable deaths increased in all but the highest socioeconomic quintiles. These rises are particularly alarming in what have been termed “deaths of despair.” As well as the obvious compassionate responses to death in prime aged women, there are important economic considerations that should prompt further research and a policy response.
Perceived relative harm of using e‐cigarettes predicts future product switching among US adult cigarette and e‐cigarette dual users
Authors: Persoskie Alexander , O'Brien Erin Keely , Poonai Karl
Published: July 2019

Background and aims

People's perceptions of the harmfulness of e‐cigarettes, compared with cigarettes, may influence their product use decisions. We tested if perceiving e‐cigarettes as less harmful than cigarettes predicted whether cigarette and e‐cigarette dual users switched their product use status 1 year later, becoming exclusive e‐cigarette users, exclusive cigarette smokers, or non‐users of both product types.

Design

Longitudinal analyses of waves 2 (2014–15) and 3 (2015–16) of the prospective, national Population Assessment of Tobacco and Health (PATH) Study.

Setting

United States.

Participants

Adults who reported using both cigarettes and e‐cigarettes within the past 30 days at wave 2 reported their perceptions of e‐cigarette harm at wave 2, and reported whether they used cigarettes and e‐cigarettes within the past 30 days at wave 3 (n = 2211).

Measurements

The key predictor was wave 2 perceptions of e‐cigarette harm compared with cigarettes (‘less harmful,' ‘about the same', ‘more harmful' or ‘don't know'). The key outcome was wave 3 past 30‐day use of e‐cigarettes and cigarettes, classified into four categories: exclusive e‐cigarette use (i.e. use of e‐cigarettes but not cigarettes), exclusive cigarette smoking (i.e. use of cigarettes but not e‐cigarettes), dual use of both product types and non‐use of both product types.

Findings

At wave 2, 59.4% of dual users perceived e‐cigarettes as less harmful than cigarettes [95% confidence interval (CI) = 56.9, 61.9]. Compared with those with other perceptions of e‐cigarette harm, dual users who perceived e‐cigarettes as less harmful than cigarettes were more likely to become exclusive e‐cigarette users 1 year later [7.5 versus 2.7%; adjusted odds ratio (aOR) = 2.9, 95% CI = 1.7–4.8], more likely to remain dual users (39.6 versus 29.9%; aOR = 1.5, 95% CI = 1.2–1.8), less likely to become exclusive cigarette smokers (44.8 versus 59.4%; aOR = 0.6, 95% CI = 0.5–0.7) and similarly likely to become non‐users of both product types (8.2 versus 8.0%; aOR = 1.1, 95% CI = 0.7–1.7).

Conclusions

US adult dual users of e‐cigarettes and cigarettes who perceive e‐cigarettes as less harmful than cigarettes appear to be more likely to switch to exclusive e‐cigarette use, more likely to remain dual users and less likely to switch to exclusive cigarette use 1 year later than dual users with other perceptions of e‐cigarette harm.
General Surgeons Australia's 12‐point plan for emergency general surgery
Authors: Ang Zhen Hao , Wong Shing , Truskett Philip
Published: July 2019

In the last decade, emergency general surgery (EGS) in Australia and New Zealand has seen a transition from the traditional on‐call system to the acute surgical unit (ASU) model. The importance and growing demand for EGS has resulted in the implementation of the General Surgeons Australia's 12‐point plan for emergency surgery. Since its release, the 12‐point plan has been used as a benchmark of a well‐functioning ASU, both locally and abroad. This study aims to provide a descriptive review on the relevance of the 12‐point plan to the ASU model and review the current evidence to support this framework. The review concludes that the establishment of the ASU model has met the aims set out by the Royal Australasian College of Surgeons for EGS. The 12‐point plan is relevant and has good evidence to support its framework.
Paediatric appendicitis: increased disease severity and complication rates in rural children
Authors: Elliott Brodie M. , Witcomb Cahill Henry , Harmston Christopher
Published: July 2019

Background

Appendicitis is the most common surgical emergency affecting children. Rurality has been shown to be a predictor of worse surgical outcomes in patients with acute appendicitis compared to urban residents. There are no previously published studies investigating this in Australasia.

Methods

A 10‐year retrospective study of all patients aged ≤16 years who underwent an acute appendicectomy in Northland, New Zealand, was conducted. The cohort was identified by searching the hospital database for theatre events and admission diagnoses coded as appendicitis. Primary outcome of interest was the difference in the American Association for the Surgery of Trauma (AAST) anatomical severity grading of appendicitis and the Clavien–Dindo complication rate. The role of ethnicity was also examined.

Results

A total of 470 children underwent appendicectomy during this period. On multivariate analysis, increased AAST grade was twice as likely in rural patients (odds ratio 2.04). Post‐operatively, rural patients had higher Clavien–Dindo complication grade (P = 0.001), longer median length of stay and increased rates of intra‐abdominal collection (19% versus 4%; P = 0.018), 30‐day readmission (19% versus 4%; P = 0.020) and perforation (27% versus 19%; P = 0.031). Māori children had increased perforation rates (28.9% versus 19.0%; P = 0.014) but ethnicity was not found to be independently associated with increasing AAST grade.

Conclusion

Accounting for ethnicity, socio‐economic deprivation and age, we implicate rural patient status as being associated with increasing severity and complicated paediatric appendicitis. This work adds to the evolving description of inequities in rural health outcomes. Further prospective studies are needed to confirm these findings at a national level.
Impact of preoperative percutaneous transhepatic biliary drainage on post‐operative survival in patients with distal cholangiocarcinoma
Authors: Mori Shozo , Aoki Taku , Park Kyung‐Hwa , Shiraki Takayuki , Sakuraoka Yuki , Iso Yukihiro , Kato Masato , Kubota Keiichi
Published: July 2019

Background

The aim of this study was to investigate the long‐term impact of the type of preoperative biliary drainage used for patients undergoing pancreatoduodenectomy for distal cholangiocarcinoma (DCC).

Methods

A total of 84 patients with DCC who underwent preoperative biliary drainage between June 2000 and December 2016 were divided into groups for whom percutaneous transhepatic biliary drainage (PTBD) (n = 24) or endoscopic biliary drainage (EBD) (n = 60) was used.

Results

The 5‐year overall survival in the PTBD group was significantly worse than that in the EBD group (16.7% versus 52.3%, P = 0.007). After propensity score matching (22 patients in each group), the 5‐year overall survival in the PTBD group was still worse than that in the EBD group (13.6% versus 61.2%, P = 0.003). Multivariate analysis revealed that PTBD was independent risk factor for both poor survival (P = 0.028) and peritoneal recurrence (P = 0.018). The incidence of multiple sites at initial recurrence tended to be higher in the PTBD group than in the EBD group (P = 0.080).

Conclusions

PTBD should not be performed for patients undergoing pancreatoduodenectomy for DCC, except when EBD is contraindicated, as PTBD is significantly associated with shorter survival and peritoneal recurrence.
Outcome of a second hepatectomy in octogenarians with hepatocellular carcinoma recurrence: single centre's experience
Authors: Ochiai Toshiya , Inoue Hiroyuki , Watanabe Nobuyuki , Ito Hiroshi , Toma Atsushi , Morimura Ryo , Ikoma Hisashi , Otsuji Eigo
Published: July 2019

Background

Physicians rarely select surgery a second time as the treatment for octogenarians with hepatocellular carcinoma (HCC) recurrence.

Methods

We encountered eight male and three female octogenarians underwent surgery a second time as the treatment for HCC recurrence (octo group). We studied these cases clinically and compared them with 25 younger people underwent surgery a second time (young group). All patients of octo group have resectable HCC according to the Japanese guideline, that is HCC patients with Child‐Pugh status A or B and who have solitary or only a few HCC nodules, in addition, no serious comorbidities, no serious dementia, a performance status of 0–1 and the will to receive hepatectomy.

Results

The average maximum tumour size at the first hepatectomy was significantly larger than that at the second hepatectomy (P < 0.05). The extent of the first hepatectomy was significantly greater than that of the second one (P < 0.05). There were no mortalities at either hepatectomy. The morbidities of the first and the second hepatectomies were 9.1% and 18.2%, respectively. All complications were bile leakage. Furthermore, there were no significant differences in the clinical features, including the prognosis, between the octo and young groups.

Conclusion

Selected octogenarians who received a second hepatectomy showed a relatively good post‐operative course after the first and second hepatectomies. Repeated hepatectomy for octogenarians seems to have same positive influence on the prognosis in comparison to the young group. But on the data analysed, we have not shown repeated hepatectomy is superior to non‐surgical treatments.
Accelerating the learning curve in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy using an external mentor model
Authors: Ansari Nabila , Brown Kilian G. M. , McBride Kate E. , Steffens Daniel , Koh Cherry E. , Young Christopher J. , Solomon Michael J. , Moran Brendan J.
Published: July 2019

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is an accepted therapeutic approach in selected patients with peritoneal malignancy. The aim of this study was to describe early outcomes in the first 50 patients managed with CRS and HIPEC in a newly established peritoneal malignancy centre in Sydney, Australia, under the guidance of an experienced peritoneal malignancy mentor.

Methods

This is a retrospective review of a prospective maintained database of early outcomes in the first 50 patients who underwent CRS and HIPEC between April 2017 and April 2018 at a newly established peritoneal malignancy centre. Type of primary, surgery time, length of hospital stay, blood loss, peritoneal carcinomatosis index, completeness of surgery, complications, recurrence rate and 30‐day mortality were reviewed.

Results

A total of 135 patients were referred and reviewed at the multidisciplinary team meeting with 50 (26 male) patients undergoing CRS and HIPEC. Of these 50 patients, 47 (94%) underwent complete cytoreduction while three (6%) had maximal tumour debulking surgery. Tumour pathology was of appendix origin (44%) and colorectal peritoneal metastases (44%). Median surgical time was 7.4 h (interquartile range 5.7–10.0). Median length of hospital stay was 13 days (interquartile range 9.7–19.0). Six (12%) patients experienced a grade III or IV Clavien–Dindo complication. There was no 30‐day mortality.

Conclusion

This study reports the successful establishment of a peritoneal malignancy centre under the guidance of an experienced peritoneal malignancy mentor. The short‐term surgical outcomes observed in the first 50 cases are promising and comparable to other more experienced centres.
High efficacy and patient satisfaction with a nurse‐led colorectal cancer surveillance programme with 10‐year follow‐up
Authors: Moloney Jayson , Partridge Carolynne , Delanty Sue , Lloyd David , Nguyen M. Hung
Published: July 2019

Background

Surveillance after colorectal cancer resection remains contentious, and faces several contemporary issues. Patient‐centred care, intensive surveillance programmes and patient complexity increase the burden of surveillance on consultant‐led clinics. Recent years have seen reshaping of nursing roles to meet healthcare demand. Nurse‐led follow‐up after colorectal cancer has been piloted, but not validated. We report outcomes from a nurse‐led colorectal cancer surveillance clinic functioning in our institution since 2008, the longest term follow‐up in the published literature.

Methods

Included patients were surveilled through the clinic from 2008 to 2018 by credentialled nurses who performed history, examination and investigations as per the local protocol. Demographic, tumour‐related, outcome‐related and patient satisfaction data were extracted from a prospectively maintained database. Primary outcomes were compliance with surveillance protocol and patient satisfaction.

Results

A total of 138 patients were included in the analysis. Mean time in surveillance was 25.4 months. Surveillance investigation protocol compliance was 97.4% overall. Five recurrences (3.6%) were detected during surveillance. In patients who developed recurrence, protocol compliance was 100%, and no clinical features of recurrence were newly found when patients were reviewed by a consultant surgeon. All recurrences during surveillance were detected by nursing staff. Response rate to the patient satisfaction survey was 90%. 96.3% of patients reported receiving adequate explanation regarding cancer surveillance and nurse‐led care. 90.7% of patients rated the clinic as ‘excellent’ and 9.3% as ‘good’.

Conclusion

Our results show a high level of efficacy and patient satisfaction associated with a nurse‐led colorectal cancer surveillance clinic over a prolonged time period, the longest in the published literature.
An overview of how on‐call consultant paediatricians can recognise and manage severe primary immunodeficiencies
Authors: Wekell Per , Hertting Olof , Holmgren Daniel , Fasth Anders
Published: July 2019

Severe primary paediatric immunodeficiency syndromes are rare and potentially fatal unless suspected, diagnosed and treated early. We provide clinical guidance and support for on‐call consultant paediatricians working in secondary level hospitals on how to recognise and manage children with these conditions. Our paper addresses four conditions that risk the most severe outcomes if they are not adequately cared for during on‐call periods, such as weekends: severe combined immunodeficiency, haemophagocytic lymphohistiocytosis, severe congenital neutropaenia and chronic granulomatous disease.

Conclusion

On‐call paediatricians are provided with advice on handling the most severe primary immunodeficiencies.
FF‐10832 enables long survival via effective gemcitabine accumulation in a lethal murine peritoneal dissemination model
Authors: Higuchi Tamami , Yokobori Takehiko , Takahashi Ryo , Naito Tomoharu , Kitahara Hiromu , Matsumoto Takeshi , Kakinuma Chihaya , Hagiwara Shinji , Kuwano Hiroyuki , Shirabe Ken , Asao Takayuki
Published: July 2019

Chemotherapy has been the treatment of choice for unresectable peritoneal dissemination; however, it is difficult to eradicate such tumors because of poor drug delivery. To solve this issue, we developed FF‐10832 as liposome‐encapsulated gemcitabine to maintain a high concentration of gemcitabine in peritoneal tumors from the circulation and ascites. A syngeneic mouse model of peritoneal dissemination using murine Colon26 cell line was selected to compare the drug efficacy and pharmacokinetics of FF‐10832 with those of gemcitabine. Despite the single intravenous administration, FF‐10832 treatment enabled long‐term survival of the lethal model mice as compared with those treated with gemcitabine. Pharmacokinetic analysis clarified that FF‐10832 could achieve a more effective gemcitabine delivery to peritoneal tumors owing to better stability in the circulation and ascites. The novel liposome‐encapsulated gemcitabine FF‐10832 may be a curative therapeutic tool for cancer patients with unresectable peritoneal dissemination via the effective delivery of gemcitabine to target tumors.
Kinesin family member C1 accelerates bladder cancer cell proliferation and induces epithelial–mesenchymal transition via Akt/GSK3β signaling
Authors: Xiao Kang‐hua , Teng Kai , Ye Yun‐lin , Tan Lei , Chen Ming‐kun , Liang Hai‐tao , Feng Zi‐hao , Duan Jin‐ling , Deng Min‐hua , Wei Wen‐su , Luo Jun‐hang , Qin Zi‐ke , Xie Dan
Published: July 2019

Kinesin family member C1 (KIFC1) is implicated in the clustering of multiple centrosomes to maintain tumor survival and is thought to be an oncogene in several kinds of cancers. In our experiments, we first performed bioinformatics analysis to investigate the expression levels of KIFC1 in bladder cancer (BC) specimens and normal bladder epitheliums and then, using our samples, verified findings by quantitative real‐time PCR and western blotting assays. All data showed that KIFC1 was significantly upregulated in BC specimens at both the mRNA and protein levels. Immunohistochemical studies in a cohort of 152 paraffin‐embedded BC tissues displayed that upregulated expression of KIFC1 clearly correlated with pT status (P = .014) and recurrent status (P = .002). Kaplan‐Meier survival analysis and log‐rank test indicated that patients with BC with high KIFC1 expression had both shorter cancer‐specific survival (P < .001) and recurrence‐free survival time (P < .001) than those with low KIFC1 expression. Furthermore, ectopic downregulation of KIFC1 weakened BC cell proliferation and migration both in vitro and in vivo, whereas upregulation of KIFC1 enhanced this in vitro. Overexpression of KIFC1 phosphorylated GSK3β and promoted Snail through activating AKT (protein kinase B0) to induce proliferation and epithelial–mesenchymal transition (EMT) and, therefore, substantially promoted BC migration and metastasis. Our study revealed an oncogenic role for KIFC1 to promote BC cell proliferation and EMT via Akt/GSK3β signaling; KIFC1 might be a promising prognostic biomarker as well as a therapeutic target for BC.
Development and validation of a predictive model for predicting cardiovascular morbidity in patients after pheochromocytoma surgery
Authors: Bai Song , Wu Bin , Yao Zichuan , Zhu Xianqing , Jiang Yunzhong , Bu Renge
Published: July 2019

Objective

Although surgical resection is the primary treatment method for pheochromocytoma, it carries a high risk of morbidity, especially cardiovascular‐related morbidity. There are no models for predicting cardiovascular morbidity after pheochromocytoma surgery. Thus, we developed and validated a model for the preoperative prediction of cardiovascular morbidity after pheochromocytoma surgery.

Design

The development cohort consisted of 262 patients who underwent unilateral laparoscopic or open pheochromocytoma surgery at our centre between 1 January 2007 and 31 December 2016. Patient's clinicopathologic data were recorded. The LASSO regression was used for data dimension reduction and feature selection; then, multivariable logistic regression analysis was used to develop the prediction model. An independent cohort consisting of 112 consecutive patients from 1 January 2017 and 31 December 2018 was used for validation. The performance of this prediction model was assessed with respect to discrimination, calibration and clinical usefulness.

Results

The predictors in this prediction model included body mass index, history of coronary heart disease, tumour size, intraoperative hemodynamic instability and use of crystal/colloid fluids preoperatively. In the validation cohort, the model showed good discrimination with an AUROC of 0.869 (95% CI, 0.797, 0.940) and good calibration (unreliability test, P = .852). Decision curve analysis demonstrated that the model was also clinically useful.

Conclusion

This study presented a good nomogram that could facilitate the preoperative individualized prediction of cardiovascular morbidity after pheochromocytoma surgery, which may help improve perioperative strategy and good treatment outcomes.
Effect of exosomes from adipose‐derived stem cells on the apoptosis of Schwann cells in peripheral nerve injury
Authors: Liu Cai‐Yue , Yin Gang , Sun Yi‐Dan , Lin Yao‐Fa , Xie Zheng , English Arthur W. , Li Qing‐Feng , Lin Hao‐Dong
Published: July 2019

Aims

Recovery after peripheral nerve injury (PNI) is often difficult, and there is no optimal treatment. Schwann cells (SCs) are important for peripheral nerve regeneration, so SC‐targeting treatments have gained importance. Adipose‐derived stem cells (ADSCs) and their exosomes can promote peripheral nerve repair, but their interactions with SCs are unclear.

Methods

Purified SCs from sciatic nerve injury sites were harvested, and apoptosis and proliferation of SCs at post‐PNI 24 hours were analyzed. The effects of coculture with ADSCs and different concentrations of ADSC‐derived exosomes (ADSC‐Exo) were studied through in vitro experiments by flow cytometry, CCK8 assay, immunofluorescence staining, and histological analysis. The expression of the apoptosis‐related genes Bcl‐2 and Bax was also analyzed by qRT‐PCR.

Results

ADSC‐Exo reduced the apoptosis of SCs after PNI by upregulating the anti‐apoptotic Bcl‐2 mRNA expression and downregulating the pro‐apoptotic Bax mRNA expression. Further, it also improved the proliferation rate of SCs. This effect was confirmed by the morphological and histological findings in PNI model rats.

Conclusion

Our results present a novel exosome‐mediated mechanism for ADSC‐SC cross talk that reduces the apoptosis and promotes the proliferation of SCs and may have therapeutic potential in the future.
Corporate board structure and foreign equity investments in weak institutional regimes
Authors: Banerjee Sujata , Oriani Raffaele , Peruffo Enzo
Published: July 2019

Research Question/Issue

Concentrated ownership is more the rule than the exception in weak institutional environments, and the absence of external control mechanisms, leading to ineffective legal enforcement, intensifies principal–principal agency issues. Our study examines how the structuring of the corporate board plays a vital role in informing foreign investors about the risk of being expropriated, which affects their decisions to make equity investments in firms in weak institutional regimes.

Research Findings/Insights

Using a sample of large listed Indian firms in the period 2010–2014, we hypothesize that the presence of affiliate directors on the board has a negative impact on foreign investments. Likewise, the presence of controlling owners‐directors on the board together with chief executive officers' additional directorial positions has an inverted U‐shaped impact on foreign investments.

Theoretical/Academic Implications

By making use of agency theory and focusing on the importance of foreign financing, our study highlighted the factors that deter foreign investors from providing capital to firms in weak institutional regimes. The use of this theoretical perspective, by emphasizing the differences in agency problems prevalent in strong versus weak institutional regimes, further suggested that examination of the structure of corporate boards is an important way to detect and gauge the potential for expropriation in countries suffering from weaknesses in investor protection.

Practitioner/Policy Implications

Our study has important implications for corporations operating in markets suffering from a legal environment that offers little investor protection. Investors are less prone to invest in these countries, as the risk of expropriation by dominant shareholders means they cannot be sure of actually getting the putative return. Our work shows how corporations can structure their boards effectively to convince investors that they face less danger of expropriation and so attract foreign capital.
Measurement of airway inflammation in current smokers by positron emission tomography
Authors: Garpered Sabine , Minarik David , Diaz Sandra , Valind Sven , Edenbrandt Lars , Wollmer Per
Published: July 2019

Background

Accumulation of activated neutrophilic leucocytes is known to increase uptake of 18F‐fluorodeoxyglucose (18F‐FDG) into lung tissue. Available evidence suggests that smokers and subjects with chronic obstructive pulmonary disease (COPD) have neutrophilic inflammation in peripheral airways. The aim of this study was to examine whether current smokers have higher lung tissue uptake of 18F‐FDG than never‐smokers when correcting for air fraction of the lungs.

Methods

We prospectively recruited 33 current smokers and 33 never‐smokers among subjects referred for diagnosis or staging of cancer, other than lung cancer, with combined positron emission tomography/computed tomography (PET/CT) with 18F‐FDG. Subjects with focal 18F‐FDG uptake or focal CT abnormalities in the lungs were excluded. The lungs were segmented in the CT image, and lung density measured. 18F‐FDG uptake was measured in the corresponding volume and corrected for air fraction.

Results

Lung uptake of 18F‐FDG, corrected for air fraction, was 12·5 and 8 per cent higher in the right and left lungs, respectively, in current smokers than in never‐smokers (P<0·05).

Conclusion Abnormal lung tissue uptake of 18F‐FDG may be masked by reduced lung density if the uptake is not related to air fraction. Increased uptake of 18F‐FDG in lung tissue in current smokers relative to never‐smokers may reflect inflammation in peripheral airways. Measurements of 18F‐FDG uptake in the lung tissue may be useful for animal and human studies of airways disease in COPD and the relation between airway and systemic inflammation.
Systematic expression analysis of the mitochondrial respiratory chain protein subunits identifies COX5B as a prognostic marker in clear cell renal cell carcinoma
Authors: Stein Johannes , Tenbrock Julia , Kristiansen Glen , Müller Stefan C , Ellinger Jörg
Published: July 2019

Objective

To analyze the expression of mitochondrial respiratory chain protein subunits in clear cell renal cell carcinoma.

Methods

Possible prognostic candidates were determined using The Cancer Genome Atlas database (n = 605). The database provided valid messenger ribonucleic acid expression data for 93 genes encoding for the subunits. Selected subunits were further investigated at the messenger ribonucleic acid and protein level by real‐time polymerase chain reaction, western blot and immunohistochemistry with the cohorts of the University Hospital Bonn.

Results

The Cancer Genome Atlas messenger ribonucleic acid expression data indicated univariate and multivariate prognostic impact for seven subunits (NDUFS8, NDUFS7, COX5B, COX6B1, SDHD, COX15 and COX19). Using real‐time polymerase chain reaction, significant downregulation (P < 0.05, n = 74) could be shown for COX5B, COX6B1, NDUFS7 and NDUF8 in clear cell renal cell carcinoma tissue. Survival analysis of polymerase chain reaction data showed a non‐significant relationship (P = 0.067) of high COX5B expression and poor overall survival. Western blot (n = 8) and immunohistochemistry analysis (n = 167) confirmed significant COX5B downregulation on the protein level. Immunohistochemistry analysis identified COX5B as a prognostic marker for overall (P = 0.017) and cancer‐specific survival (P = 0.042).

Conclusions

The present study findings suggest downregulation of additional subunits of mitochondrial respiratory chain proteins in clear cell renal cell carcinoma. Remarkably, COX5B, a subunit of the respiratory chain complex IV, can be identified as a novel prognostic marker.
Staphylococcus epidermidis role in the skin microenvironment
Authors: Leonel Caroline , Sena Isadora F. G. , Silva Walison N. , Prazeres Pedro H. D. M. , Fernandes Gabriel R. , Mancha Agresti Pamela , Martins Drumond Mariana , Mintz Akiva , Azevedo Vasco A. C. , Birbrair Alexander
Published: July 2019

Wound healing is a complex dynamic physiological process in response to cutaneous destructive stimuli that aims to restore the cutaneous’ barrier role. Deciphering the underlying mechanistic details that contribute to wound healing will create novel therapeutic strategies for skin repair. Recently, by using state‐of‐the‐art technologies, it was revealed that the cutaneous microbiota interact with skin immune cells. Strikingly, commensal Staphylococcus epidermidis‐induced CD8+ T cells induce re‐epithelization of the skin after injury, accelerating wound closure. From a drug development perspective, the microbiota may provide new therapeutic candidate molecules to accelerate skin healing. Here, we summarize and evaluate recent advances in the understanding of the microbiota in the skin microenvironment.
Juvenile silver grunter Mesopristes argenteus shift benthic objects to access food
Authors: Ebner Brendan C. , Donaldson James A. , Starrs Danswell
Published: July 2019

Juvenile silver grunter Mesopristes argenteus were observed, photographed and filmed manoeuvring objects with their snout and nape to expose benthic prey in two short steep coastal streams, including in the micro‐estuary of one of these streams within the Australian Wet Tropics. Objects that were moved included leaves, sticks, bark, wood, seed pods, rainforest fruit, coral fragments and pebbles. Follower fish were sometimes associated with the foraging behaviour.
Funding Liquidity without Banks: Evidence from a Shock to the Cost of Very Short‐Term Debt
Authors: RESTREPO FELIPE , CARDONA‐SOSA LINA , STRAHAN PHILIP E.
Published: July 2019

In 2011, Colombia instituted a tax on repayment of bank loans, which increased the cost of short‐term bank credit more than long‐term credit. Firms responded by cutting short‐term loans for liquidity management purposes and increasing the use of cash and trade credit. In industries in which trade credit is more accessible (based on U.S. Compustat firms), we find substitution into accounts payable and little effect on cash and investment. Where trade credit is less available, firms increase cash and cut investment. Thus, trade credit provides an alternative source of liquidity that can insulate some firms from bank liquidity shocks.
The changing epidemiology of community‐acquired pneumonia: nationwide register‐based study in Sweden
Authors: Naucler P. , Henriques‐Normark B. , Hedlund J. , Galanis I. , Granath F. , Örtqvist Å.
Published: July 2019

Background

There is limited evidence on the impact of pneumococcal conjugate vaccine childhood immunization programmes (PCV‐CIP) on community‐acquired pneumonia (CAP) in individuals with underlying diseases.

Methods

A nationwide cohort study using Swedish health registers to assess the incidence of hospitalization with all‐cause (AC‐CAP) and pneumococcal or lobar (PL‐CAP) CAP between 2005 and 2015, in relation to PCV‐CIP introduction in 2007–09.

Results

In total, 303 691 episodes of AC‐CAP occurred, of which 14 225 were PL‐CAP. Comparing before (2005–06) with after (2014–15) PCV‐CIP, relative incidence reductions were 36% (95% Confidence Interval 32–40), 20% (14–25) and 16% (11–22) of AC‐CAP for age groups < 2, 2–4 and 5–17 years, respectively, with similar reductions in young children with and without comorbidities. The reductions were more pronounced for PL‐CAP. In the age groups 40–64, 65–74, 75–84 and ≥85 years there were relative increases of 11% (8–14), 18% (15–22), 15% (12–17) and 30% (27–34) of AC‐CAP, respectively, but these increases were attenuated after adjustment for admittance practices using four control conditions. In adults with comorbidities, there was an increase in incidence of AC‐CAP, and PL‐CAP, in contrast to adults without reported underlying diseases where the incidence was stable or diminished for some age groups. Over the study period, there was an increased proportion of pneumonia patients with underlying diseases in all ages.

Conclusion

This emphasizes that direct preventive interventions should be targeted towards individuals with underlying diseases. Future studies should investigate reasons for the observed increased risk in adults with comorbidities, for example due to pneumococcal nonvaccine serotypes, or other pathogens, preferentially affecting subjects with underlying diseases.
Complications during catheter‐mediated patent ductus arteriosus closure and pulmonary balloon valvuloplasty
Authors: Claretti M. , Lopez B. S. , Boz E. , Martelli F. , Pradelli D. , Bussadori C. M.
Published: July 2019

Objectives

To evaluate and illustrate complications of cardiac catheterisation and the associated risk factors of the most common cardiac intervention procedures.

Materials and Methods

Retrospective study of clinical records of client‐owned dogs presented to a cardiology referral centre between January 2006 and December 2017.

Results

Five hundred and twenty‐four dogs were included, 62 of which had complications. Complications were divided into technical complications and those due to unexpected additional anatomical abnormalities. Seven procedures (1.33%) were interrupted; five dogs (0.95%) subsequently underwent surgery, and four dogs died during the interventional procedure, indicating a mortality rate of 0.76%

Clinical Significance

There is a low risk of complications following closure of patent ductus arteriosus or pulmonary balloon valvuloplasty when carried out by a trained team using standardised procedures in a referral centre.
Molecular detection of Streptococcus equi subspecies equi in face flies (Musca autumnalis) collected during a strangles outbreak on a Thoroughbred farm
Authors: Pusterla N. , Bowers J. , Barnum S. , Hall J. A.
Published: July 2019

The objective of this study was to detect Streptococcus equi subspecies equi (S. equi) (Lactobacillales: Streptococcaceae) using quantitative polymerase chain reaction (qPCR) in flies collected from a farm with a documented outbreak of strangles. A total of 1856 face flies [Musca autumnalis (Diptera: Muscidae)] were collected using conventional fly traps. The flies were processed for nucleic acid purification and tested for the presence of S. equi by qPCR. A total of 10/1856 flies (0.54%) tested qPCR‐positive for S. equi. The results may implicate the presence of face flies as a risk factor for the transmission of S. equi and highlight the need to institute proper husbandry measures, biosecurity protocols and fly control in order to reduce the potential for infection in at‐risk horses.
Open for Learning: Encouraging Generalization Fosters Knowledge Transfer in Negotiation
Authors: Kim Jihyeon , Thompson Leigh , Loewenstein Jeffrey
Published: July 2019

We examined whether encouraging managers to attend to underlying principles in negotiation training examples rather than contextual specifics fosters openness to learning and enhances subsequent knowledge transfer to new negotiation situations. In an experimental study, 420 managers read a negotiation case study example set in a familiar or unfamiliar industry and answered either broadening or narrowing questions about an example. Managers given broadening questions about an example set in an unfamiliar industry were more open to learning than managers who were asked narrowing questions about an example set in a familiar industry. Openness to learning in turn fostered successfully applying the key negotiation principle to resolve a subsequent face‐to‐face negotiation. The findings suggest that negotiation training for professionals is unlikely to meet its intended purpose if it relies on offering managers examples set in their own industries and encouraging them to answer questions about the contextual specifics of those examples.
Improvement of dry mouth following intraductal irrigation of salivary glands
Authors: Aframian Doron J. , Baaton Sagit , Mazor Sigal , Nadler Chen , Keshet Naama , Haviv Yaron , Zadik Yehuda , Schwimmer‐Noy Rinat , Shay Boaz , Almoznino Galit
Published: July 2019

Objectives

To assess the effect of major salivary gland intraductal irrigations (IGs) to relieve mouth dryness.

Methods

We retrospectively analyzed the records of patients with mouth dryness who underwent major salivary gland IG during 2013–2015. Records included demographics, medical background, dry mouth etiologies and symptomatology, and results of sialometry and sialo‐cone‐beam computerized tomography. Subjective improvement following the IG procedure (yes/no) and sustained subjective improvement (mouth dryness relief for ≥1 month) were recorded. Objective improvement was assessed by comparing the mean unstimulated (USF) and stimulated (SSF) whole salivary flow (WSF) rate before and after the IG.

Results

Seventy‐four patients were included [mean age: 59.08 ± 12.46 years]. Improvement was detected in the USF (p = .027), but not in the SSF (p = .878). Fifty‐five (84.6%) noted subjective improvement, while 10 (15.4%) did not. Subjective improvement was positively associated with the USF following IG (p = .037), with salivary gland swelling episodes (p = .033), and with difficulties in swallowing dry foods (p = .014).

Of those with subjective improvement, 45 (81.8%) reported sustained improvement, which was positively associated with lack of a gritty eye sensation (p = .042) and abnormal sialo‐CBCT findings (p = .001).

Conclusions

Major salivary gland IG is a simple and safe procedure that may relieve dry mouth for a relatively extended duration. Further studies are needed to confirm these preliminary findings and assess their underlying mechanisms.
Identification of loci controlling adaptation in Chinese soya bean landraces via a combination of conventional and bioclimatic GWAS
Authors: Li Ying‐hui , Li Delin , Jiao Yong‐qing , Schnable James C. , Li Yan‐fei , Li Hui‐hui , Chen Huai‐zhu , Hong Hui‐long , Zhang Ting , Liu Bin , Liu Zhang‐xiong , You Qing‐bo , Tian Yu , Guo Yong , Guan Rong‐xia , Zhang Li‐juan , Chang Ru‐zhen , Zhang Zhiwu , Reif Jochen , Zhou Xin‐an , Schnable Patrick S. , Qiu Li‐juan
Published: July 2019

Landraces often contain genetic diversity that has been lost in modern cultivars, including alleles that confer enhanced local adaptation. To comprehensively identify loci associated with adaptive traits in soya bean landraces, for example flowering time, a population of 1938 diverse landraces and 97 accessions of the wild progenitor of cultivated soya bean, Glycine soja was genotyped using tGBS®. Based on 99 085 high‐quality SNPs, landraces were classified into three sub‐populations which exhibit geographical genetic differentiation. Clustering was inferred from STRUCTURE, principal component analyses and neighbour‐joining tree analyses. Using phenotypic data collected at two locations separated by 10 degrees of latitude, 17 trait‐associated SNPs (TASs) for flowering time were identified, including a stable locus Chr12:5914898 and previously undetected candidate QTL/genes for flowering time in the vicinity of the previously cloned flowering genes, E1 and E2. Using passport data associated with the collection sites of the landraces, 27 SNPs associated with adaptation to three bioclimatic variables (temperature, daylength, and precipitation) were identified. A series of candidate flowering genes were detected within linkage disequilibrium (LD) blocks surrounding 12 bioclimatic TASs. Nine of these TASs exhibit significant differences in flowering time between alleles within one or more of the three individual sub‐populations. Signals of selection during domestication and/or subsequent landrace diversification and adaptation were detected at 38 of the 44 flowering and bioclimatic TASs. Hence, this study lays the groundwork to begin breeding for novel environments predicted to arise following global climate change.