bluuebunny/crossref_metadata_2025 huggingface dataset:
Programmed death‐ligand 1 expression at tumor invasive front is associated with epithelial‐mesenchymal transition and poor prognosis in esophageal squamous cell carcinoma
Authors: Tsutsumi Satoshi , Saeki Hiroshi , Nakashima Yuichiro , Ito Shuhei , Oki Eiji , Morita Masaru , Oda Yoshinao , Okano Shinji , Maehara Yoshihiko
Published: March 2017

Programmed death‐ligand 1 (PD‐L1) plays a crucial role in the host immune system in cancer progression. The gene promoter region of PD‐L1 also contains a binding site for ZEB1, a transcription factor related to epithelial‐mesenchymal transition (EMT). The purpose of this study was to clarify the relationship between PD‐L1 and EMT and its clinical importance in esophageal squamous cell carcinoma (ESCC). PD‐L1 and ZEB1 expression at the tumor invasive front was examined by immunohistochemistry in resected specimens from 90 patients with ESCC who underwent surgery without preoperative therapy, and their expression and clinicopathological factors were compared. ZEB1 and PD‐L1 expression was determined in TE8 cells, which demonstrate the EMT phenotype, following ZEB1 knockdown by siZEB1. TE5, TE6 and TE11 cells with non‐EMT phenotype were also used for studies of TGF‐β1‐dependent EMT induction and ZEB1 and PD‐L1 expression. In cases of high PD‐L1 expression at the invasive front, significantly greater depth of tumor invasion, EMT, and less CD8+ lymphocyte infiltration were observed. High PD‐L1 expression was also associated with worse overall and relapse‐free survival. A correlation was observed between PD‐L1 and ZEB1 expression. In TE8 cells, siZEB1 suppressed PD‐L1 and promoted E‐cadherin mRNA and protein expression. TGF‐β1 induced EMT and surface expression of PD‐L1 in TE5, TE6 and TE11 cell lines. PD‐L1 expression at the ESCC invasive front was related to ZEB1 expression, EMT and poor prognosis. We suggest that a cooperative mechanism bridging between tumor immune avoidance and EMT contributes to tumor malignancy in ESCC.
N‐hydroxy‐substituted 2‐aryl acetamide analogs: A novel class of HIV‐1 integrase inhibitors
Authors: Debnath Utsab , Kumar Prachi , Agarwal Aakanksha , Kesharwani Ajay , Gupta Satish K. , Katti Seturam B.
Published: March 2017

An in silico method has been used to discover N‐hydroxy‐substituted 2‐aryl acetamide analogs as a new class of HIV‐1 integrase inhibitors. Based on the molecular requirements of the binding pocket of catalytic active site, two molecules (compounds 2 and 4b) were designed as fragments. These were further synthesized and biologically evaluated. In vitro potency along with docking studies highlighted compound 4b as an active fragment which was further used to synthesize new leads as HIV‐1 integrase inhibitors. Finally, six promising compounds (compounds 5b, 5c, 5e, 6–2c, 6–3b, and 6–5b) were identified by integrase inhibition assay (>50% inhibition). Based on in vitro anti‐HIV‐1 activity in a reporter gene‐based cell assay system, compounds 5d, 6s, and 6k were found as novel HIV‐1 integrase inhibitors due to its better selectivity index. Additionally, docking study revealed the importance of H‐bond as well as hydrophobic interactions with Asn155, Lys156, and Lys159 which were required for their anti‐HIV‐1 activity.
The interpersonal work of dental conscious sedation: A qualitative analysis
Authors: Woolley Stephen M. , Chadwick Barbara , Pugsley Lesley
Published: March 2017

Aims

Whilst there is a considerable body of literature examining the pharmacology of conscious sedation, the social tasks required to successfully provide conscious sedation have not been reported. This paper discusses data regarding the interpersonal work integral to effective conscious sedation provision, from a larger qualitative study exploring how patients and clinicians engage with secondary care conscious sedation provided within theUK.

Method

Semi‐structured interviews were conducted with 13 conscious sedation providers and nine patients withinUK‐based secondary care sedation settings. Digital audio‐recordings were transcribed verbatim and subsequently analysed using a constant comparative method withinNVivo Data Analysis Software.

Results

Four main themes of interpersonal work were reported by participants: displaying care, containing emotions, demonstrating competence and maximizing the effect.

Conclusion

This study shows that performing conscious sedation requires more than technical delivery, and involves the projection of attributes in a literal “performance.” The importance of managing outward emotional appearance reflects previous dental research. The need to manage outward appearance, and the emotional impact this has, is of relevance to all clinicians.
Immunologic regulatory effects of human umbilical cord blood‐derived mesenchymal stem cells in a murine ovalbumin asthma model
Authors: Kang S.‐Y. , Park D.‐E. , Song W.‐J. , Bae B.‐R. , Lee J.‐W. , Sohn K.‐H. , Lee H.‐S. , Kang H.‐R. , Park H.‐W. , Chang Y.‐S. , Choi S.‐J. , Oh W.‐I. , Min K.‐U. , Cho S.‐H.
Published: March 2017

Background

Mesenchymal stem cells (MSCs) have multiple immunomodulatory properties and hold therapeutic potential for inflammatory diseases. However, the therapeutic and immunologic effects of human umbilical cord blood‐derived MSCs (huMSCs) remain largely unexamined for asthma.

Objective

This study was to investigate the immunomodulatory properties of huMSCs in an ovalbumin (OVA)‐induced murine asthma model.

Methods

Mice were injected intraperitoneally with OVA and an aluminium hydroxide adjuvant. huMSCs were administered via the tail vein (5×105 cells/100 uL) to female BALB/c mice prior to the initial OVA challenge. The effects of huMSCs were assessed by investigating airway hyperresponsiveness, histological changes, inflammatory cell numbers, serum allergen‐specific antibodies, cytokine production in spleen, lung tissue, and bronchoalveolar lavage (BAL) fluid as well as expansion of regulatory T cells.

Results

Administration of huMSCs significantly reduced methacholine bronchial hyperresponsiveness and eosinophil counts in BAL cells. Similarly, there was a significant decrease in serum OVA‐specific IgE and IgG1 levels along with Th2 cytokine production (IL‐4, IL‐5, and IL‐13) in the lung and spleen tissues, whereas increased percentage of regulatory T cells was observed after treatment with huMSCs.

Conclusions

Our results suggest that huMSC treatment reduces OVA‐induced allergic inflammation, which could be mediated by regulatory T cells.
Allergic disease in 8‐year‐old children is preceded by delayed B cell maturation
Authors: Strömbeck A. , Nordström I. , Andersson K. , Andersson H. , Johansen S. , Maglio C. , Rabe H. , Adlerberth I. , Wold A. E. , Hesselmar B. , Rudin A. , Lundell A‐C.
Published: March 2017

Background

We previously reported that exposure to a farming environment is allergy‐protective, while high proportions of neonatal immature/naïve CD5+ B cells and putative regulatory T cells (Tregs) are risk factors for development of allergic disease and sensitization up to 3 years of age.

Objective

To examine if B and T cell maturation are associated with allergic disease and farming environment over the first 8 years in life.

Methods

In the prospective FARMFLORA study, including both farming and non‐farming families, 48 of 65 children took part in the 8‐year follow‐up study. Various B and T cell maturation variables were examined in blood samples obtained at several occasions from birth to 8 years of age and related to doctors' diagnosed allergic disease and sensitization, and to farming environment.

Results

We found that the incidence of allergic disease was lower among farmers' compared to non‐farmers' children during the 8‐year follow‐up period, and that farmers' children had higher proportions of memory B cells at 8 years of age. Moreover, a high proportion of neonatal CD5+ B cells was a risk factor for and may predict development of allergic disease at 8 years of age. A high proportion of Tregs was not protective against development of these conditions.

Conclusion and Clinical Relevance

High proportions of neonatal naïve B cells remained as a risk factor for allergic disease in school‐aged children. Thus, the accelerated B cell maturation observed among farmers' children may be crucial for the allergy‐protective effect of a farming environment.
Measuring TSH receptor antibody to influence treatment choices in Graves’ disease
Authors: Hesarghatta Shyamasunder Asha , Abraham Prakash
Published: March 2017

TSH receptor antibody (TRAb) plays a key role in the pathogenesis of Graves’ disease (GD), and its levels correlate with the clinical course. The second‐ and third‐generation TRAb assays have >95% sensitivity and specificity for the diagnosis of GD and have improved the utility of TRAb to predict relapse. TRAb levels decline with antithyroid drug (ATD) therapy and after thyroidectomy. Its level increases for a year following radioactive iodine (RAI) therapy, with a gradual fall thereafter. TRAb level >12 IU/l at diagnosis of GD is associated with 60% risk of relapse at 2 years and 84% at 4 years. The prediction of risk of relapse improves further to >90% with TRAb >7·5 IU/l at 12 months or >3·85 IU/l at cessation of ATD therapy. TRAb tests are not expensive, and hence, TRAb measurements at presentation, after 12 months and/or 18 months (at cessation) of ATD therapy, could potentially guide treatment choices in GD. Elevated TRAb favours definitive treatment in the form of RAI or thyroidectomy, depending on the presence or absence of moderate‐to‐severe Graves’ ophthalmopathy (GO) and the ability to comply with radiation protection requirements. Use of ATDs in early pregnancy is associated with increased risk of congenital anomalies; early ablative treatment (RAI/surgery) should be considered in women of childbearing age at higher risk of relapse of GD. TRAb ≥5 IU/l in pregnant women with current or previously treated GD is associated with increased risk of foetal and neonatal thyrotoxicosis, and hence needs close monitoring. TRAb levels parallel the course of GO, and elevated TRAb is an indication for steroid prophylaxis to prevent progression of GO with RAI therapy.
PLA2G6 mutations associated with a continuous clinical spectrum from neuroaxonal dystrophy to hereditary spastic paraplegia
Authors: Ozes B. , Karagoz N. , Schüle R. , Rebelo A. , Sobrido M.‐J. , Harmuth F. , Synofzik M. , Pascual S.I.P. , Colak M. , Ciftci‐Kavaklioglu B. , Kara B. , Ordóñez‐Ugalde A. , Quintáns B. , Gonzalez M.A. , Soysal A. , Zuchner S. , Battaloglu E.
Published: March 2017

PLA2G6‐associated neurodegeneration (PLAN) and hereditary spastic paraplegia (HSP) are 2 groups of heterogeneous neurodegenerative diseases. In this study, we report
PLA2G6
gene mutations in 3 families from Turkey, Morocco, and Romania. Two affected Turkish siblings presenting HSP adds the disease to PLAN phenotypes. They were homozygous for the
PLA2G6
missense c.2239C>T, p.Arg747Trp variant and the ages of onset were 9 and 21. Parkinsonism, dystonia or cognitive decline were not the clinical elements in these patients contrary to the cases that has been previously reported with the same variant, however, iron accumulation was evident in their cranial magnetic resonance imaging. The Moroccan patient was homozygous for a novel missense c.1786C>T, p.Leu596Phe variant and the Romanian patient had 2 novel mutations; c.1898C>T, p.Ala633Val and c.1765_1768del, p.Ser589ThrfsTer76. Both of these patients conformed better to childhood onset PLAN with the age of onset at 4 and 7 years, respectively. Interestingly, all identified mutations were affecting the highly conserved patatin‐like phospholipase domain of the PLA2G6 protein.
Learning the Structure of Social Influence
Authors: Gershman Samuel J. , Pouncy Hillard Thomas , Gweon Hyowon
Published: March 2017

We routinely observe others’ choices and use them to guide our own. Whose choices influence us more, and why? Prior work has focused on the effect of perceived similarity between two individuals (self and others), such as the degree of overlap in past choices or explicitly recognizable group affiliations. In the real world, however, any dyadic relationship is part of a more complex social structure involving multiple social groups that are not directly observable. Here we suggest that human learners go beyond dyadic similarities in choice behaviors or explicit group memberships; they infer the structure of social influence by grouping individuals (including themselves) based on choices, and they use these groups to decide whose choices to follow. We propose a computational model that formalizes this idea, and we test the model predictions in a series of behavioral experiments. In Experiment 1, we reproduce a well‐established finding that people's choices are more likely to be influenced by someone whose past choices are more similar to their own past choices, as predicted by our model as well as dyadic similarity models. In Experiments 2–5, we test a set of unique predictions of our model by looking at cases where the degree of choice overlap between individuals is equated, but their choices indicate a latent group structure. We then apply our model to prior empirical results on infants’ understanding of others’ preferences, presenting an alternative account of developmental changes. Finally, we discuss how our model relates to classical findings in the social influence literature and the theoretical implications of our model. Taken together, our findings demonstrate that structure learning is a powerful framework for explaining the influence of social information on decision making in a variety of contexts.
What Am I Looking at? Interpreting Dynamic and Static Gaze Displays
Authors: van Wermeskerken Margot , Litchfield Damien , van Gog Tamara
Published: March 2017

Displays of eye movements may convey information about cognitive processes but require interpretation. We investigated whether participants were able to interpret displays of their own or others' eye movements. In Experiments 1 and 2, participants observed an image under three different viewing instructions. Then they were shown static or dynamic gaze displays and had to judge whether it was their own or someone else's eye movements and what instruction was reflected. Participants were capable of recognizing the instruction reflected in their own and someone else's gaze display. Instruction recognition was better for dynamic displays, and only this condition yielded above chance performance in recognizing the display as one's own or another person's (Experiments 1 and 2). Experiment 3 revealed that order information in the gaze displays facilitated instruction recognition when transitions between fixated regions distinguish one viewing instruction from another. Implications of these findings are discussed.
Comparison between traditional and small‐diameter tube‐assisted bronchoscopic balloon dilatation in the treatment of benign tracheal stenosis
Authors: Li Li‐Hua , Liang Yi‐Lin , Li Yu , Xu Ming‐Peng , Li Wen‐Tao , Liu Guang‐Nan
Published: March 2017

Objective

To compare the safety and efficacy between using a small‐diameter tube‐assisted bronchoscopic balloon dilatation (BBD) and the traditional BBD in the treatment of benign tracheal stenosis.

Methods

A retrospective study included 58 patients with benign tracheal stenosis from August 2009 to December 2014 was made. The patients who underwent traditional BBD were divided into group A, and who underwent a small‐diameter tube‐assisted BBD were divided into group B. The tracheal diameter, dyspnea index and blood gas analysis results were detected before and after BBD. Efficacy and complications were evaluated after BBD.

Results

There were significant differences in oxygen saturation (PaO2) during the operations comparing with before and after operations in group A (P = .005), while there was no significant difference in group B (P = .079). The tracheal diameter obviously increased (in group A, from 4.16 ± 1.43 mm to 12.47 ± 1.41 mm, P = .000; in group B: from 4.94 ± 1.59 mm to 12.61 ± 1.41 mm, P = .000). Dyspnea index obviously decreased (group A: from 3.21 ± 0.93 to 0.50 ± 0.59, P = .000; group B: from 3.24 ± 0.89 to 0.65 ± 0.69, P = .000). The immediately cure rate in both groups was 100%. Long‐term effect was significantly better in group B than that in group A (85.3% vs 59.1%, P = .021), at the end of the follow‐up period.

Conclusions

Small‐diameter tube‐assisted BBD obtains better safety and long‐term efficacy than the traditional BBD in the treatment of benign tracheal stenosis. However, close attention should be given to the risk of the adverse effects caused by carbon dioxide retention.
Endoscopic shielding technique with a newly developed hydrogel to prevent thermal injury in two experimental models
Authors: Lorenzo‐Zúñiga Vicente , Boix Jaume , Moreno de Vega Vicente , Bon Ignacio , Marín Ingrid , Bartolí Ramón
Published: March 2017

Background and Aim

A newly developed hydrogel, applied through the endoscope as an endoscopic shielding technique (EndoSTech), is aimed to prevent deep thermal injury and to accelerate the healing process of colonic induced ulcers after therapeutic endoscopy.

Methods

Lesions were performed in rats (n = 24) and pigs (n = 8). Rats were randomized to receive EndoSTech (eight rats each) with: saline (control), hyaluronic acid and product. In pigs, three ulcer sites were produced in each pig: endoscopic mucosal resection (EMR)‐ulcer with prior saline injection (A; EMR‐saline), EMR‐saline plus EndoSTech with product (B; EMR‐saline‐P), and EMR with prior injection of product plus EndoSTech‐P (C; EMR‐P‐P). At the end of the 14‐day study, the same lesions were performed again in healthy mucosa to assess acute injury. Animals were sacrificed after 7 (rats) and 14 (pigs) days. Ulcers were macroscopically and histopathologically evaluated. Thermal injury (necrosis) was assessed with a 1‐4 scale.

Results

In rats, treatment with product improved mucosal healing comparing with saline and hyaluronic acid (70% vs 30.3% and 47.2%; P = 0.003), avoiding mortality (0% vs 50% and 25%; P = 0.038), and perforation (0% vs 100% and 33.3%; P = 0.02); respectively. In pigs, submucosal injection of product induced a marked trend towards a less deep thermal injury (C = 2.25‐0.46 vs A and B = 2.75‐0.46; P = 0.127). Mucosal healing rate was higher with product (B = 90.2‐3.9%, C = 91.3‐5.5% vs A = 73.1‐12.6%; P = 0.002).

Conclusions

This new hydrogel demonstrates strong healing properties in preclinical models. In addition, submucosal injection of this product is able to avoid high thermal load of the gastrointestinal wall.
Improving glycaemic control in type 2 diabetes: Stimulate insulin secretion or provide beta‐cell rest?
Authors: van Raalte Daniël H. , Verchere C. Bruce
Published: March 2017

Type 2 diabetes (T2D) is characterized by a gradual decline in pancreatic beta cell function that determines the progressive course of the disease. While beta‐cell failure is an important contributor to hyperglycaemia, chronic hyperglycaemia itself is also detrimental for beta‐cell function, probably by inducing prolonged secretory stress on the beta cell as well as through direct glucotoxic mechanisms that have not been fully defined. For years, research has been carried out in search of therapies targeting hyperglycaemia that preserve long‐term beta‐cell function in T2D, a quest that is still ongoing. Current strategies aim to improve glycaemic control, either by promoting endogenous insulin secretion, such as sulfonylureas, or by mechanisms that may impact the beta cell indirectly, for example, providing beta‐cell rest through insulin treatment. Although overall long‐term success is limited with currently available interventions, in this review we argue that strategies that induce beta‐cell rest have considerable potential to preserve long‐term beta‐cell function. This is based on laboratory‐based studies involving human islets as well as clinical studies employing intensive insulin therapy, thiazolidinediones, bariatric surgery, short‐acting glucagon‐like peptide (GLP)‐1 receptor agonists and a promising new class of diabetes drugs, sodium‐glucose‐linked transporter (SGLT)‐2 inhibitors. Nevertheless, a lack of long‐term clinical studies that focus on beta‐cell function for the newer glucose‐lowering agents, as well as commonly used combination therapies, preclude a straightforward conclusion; this gap in our knowledge should be a focus of future studies.
The albuminuria‐lowering response to dapagliflozin is variable and reproducible among individual patients
Authors: Petrykiv Sergei I. , Laverman Gozewijn D. , de Zeeuw Dick , Heerspink Hiddo J. L.
Published: March 2017

Aims

Albuminuria reduction is essential for renal and cardiovascular protection. We characterized the efficacy of dapagliflozin, a sodium‐glucose co‐transporter 2 inhibitor, on albuminuria. Secondly, we assessed whether the albuminuria‐lowering effect varies among patients, and whether this variability in response is reproducible.

Material and methods

A double‐blind, randomized, placebo controlled crossover trial was conducted. Patients with type 2 diabetes and albumin:creatinine ratio > 100 mg/g on a stable dose of an angiotensin‐converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) were enrolled. Patients were assigned to 6‐week treatment periods with dapagliflozin 10 mg/d or placebo in random order, separated by 6‐weeks wash‐out periods. After the 2 treatment periods, half of the patients were re‐exposed for 6 weeks to dapagliflozin 10 mg/d. Primary outcome was change in 24‐hour urinary albumin excretion rate (24 h UAE). To assess reproducibility in individual albuminuria response, responses from the first and second exposure to dapagliflozin were correlated.

Results

A total of 33 patients (age, 61 years; female gender, 24.2%; median 24 h UAE, 470 mg/24 h) completed the study. Dapagliflozin, as compared to placebo, reduced 24 h UAE by 36.2% (95% CI, 22.9‐47.2;
P
 < .001). Systolic blood pressure fell by 5.2 mm Hg (95% CI, 0.5‐10.0) and eGFR by 5.3 (95% CI, 2.7‐8.0). All effects were reversible directly after treatment discontinuation. In a subgroup of 15 patients who were exposed twice to dapagliflozin, 24 h UAE responses showed a large variation among individuals: first exposure (range, −76% to +52%) and second exposure (−90% to +95%) and first and second individual response were significantly correlated (r = 0.69 [95% CI, 0.27‐0.89];
P
 < .004).

Conclusion

Dapagliflozin significantly reduces albuminuria when given as adjunct to ACEi or ARB. The albuminuria response to dapagliflozin markedly varies among patients. This variation is not a random phenomenon, but is reproducible upon re‐exposure. These data support personalized therapy approaches to optimize diabetic kidney disease.
Cardioembolic strokes resulting from a self‐inflicted needle puncture involving both sides of the heart
Authors: Tan Mark Zheng Yi , Brunswicker Annemarie , Abdelraheem Shamsaldeen , Sheehan Alison
Published: March 2017

Foreign bodies in the heart are rare occurrences with a limited evidence base to guide recommendations on management. We report a case of multiple cardioembolic strokes as a result of a self‐inflicted sewing needle puncture from the anterior chest through the right ventricle and interventricular septum with its tip in the left ventricle close to the subvalvular apparatus in a 39‐year‐old psychiatric patient. We discuss issues surrounding decision making and ongoing care and highlight the importance of further follow‐up and reporting of cases to form a robust evidence base to guide future recommendations.
Five‐year follow‐up two‐dimensional speckle tracking echocardiography in a juvenile with a double‐chambered left ventricle
Authors: Harada Kenji , Mori Kazuhiro , Ichimiya Chiyo , Terada Naho , Iima Tsutomu , Harada Takafumi , Fujisawa Kazutoshi , Kawata Atsushi , Okada Ayumi , Yamamoto Hirofumi , Fujinaga Hiroyuki
Published: March 2017

Double‐chambered left ventricle (DCLV) is a particularly rare congenital entity characterized by the presence of two ventricular cavities separated by an abnormal muscle band. An asymptomatic 15‐year‐old boy was referred to our hospital because of electrocardiographic (ECG) abnormalities. His initial transthoracic echocardiography (TTE) demonstrated a DCLV with mild left ventricular systolic dysfunction. During a 5‐year follow‐up period, he remained symptom free with no changes in ECG and conventional TTE findings. However, two‐dimensional speckle tracking echocardiography revealed a subtle progressive deterioration of left ventricular systolic function during the 5‐year follow‐up.
Dyspnea following thoracostomy closure after right pneumonectomy: An uncommon echocardiographic diagnosis and therapeutic approach
Authors: Pernigo Matteo , Canneto Barbara , Betta Davide , Molinari Gionata , Ribichini Flavio , Zannini Guido , Vassanelli Corrado , Rossi Andrea
Published: March 2017

Dyspnea and hypoxemia are common postoperative problems after pneumonectomy. One of the rarer causes of respiratory distress after right pneumonectomy is the development of a significant right‐to‐left shunt across a patent foramen ovale (PFO), which can evolve at a variable interval of time after the operation. We report here our experience with a patient who underwent right pneumonectomy, followed by several complications, and who presented severe dyspnea 7 months later, after the closure of a right thoracostomy. This report outlines the management of this challenging clinical condition; transesophageal echocardiography (TOE) provided a clear diagnosis and guided an effective percutaneous treatment.
Advantages and pitfalls of pocket ultrasound vs daily chest radiography in the coronary care unit: A single‐user experience
Authors: Phillips Colin T. , Manning Warren J.
Published: March 2017

Background

Pocket ultrasonography may enhance patient diagnosis and care. We sought to assess pocket ultrasound in detecting common conditions in the coronary care unit (CCU) compared to portable daily chest radiography (CXR) and conventional transthoracic echocardiography (TTE).

Methods

An experienced pocket ultrasound user performed a pocket ultrasound examination for interstitial edema, pneumonia, central line seen in the right ventricle, pleural and pericardial effusions, left atrial enlargement, and cardiomegaly. Data were blindly compared to the radiologist CXR interpretation and cardiologist TTE interpretation.

Results

A total of 102 CXR and pocket ultrasound examinations were performed in 66 patients. The most common CXR indication was “interval change” (37%) and finding central line (65%). Pocket ultrasound demonstrated overall good concordance with CXR ranging from 77% for pleural effusion to 92% for pneumonia. Additionally, the pocket ultrasound examination appeared to anticipate resolution of pulmonary edema prior to the CXR. Compared to TTE, pocket ultrasound had excellent sensitivity for cardiac findings with values ranging from 85% for left atrial enlargement to 100% for cardiomegaly, but limited specificity of cardiomegaly at just 51%.

Conclusion

In the CCU, bedside pocket ultrasound reliably diagnoses common conditions identified by CXR with the advantage of lack of ionizing radiation and the suggestion of detecting the resolution of pulmonary edema prior to CXR. Pitfalls include only modest concordance for pleural effusions and limited specificity for cardiomegaly. Larger, multicenter studies are needed to determine whether pocket ultrasound can reduce routine daily CXR in the CCU and other intensive care settings.
With no gap to mind: a shallow genealogy within the world's most widespread small pelagic fish
Authors: Stern Nir , Douek Jacob , Goren Menachem , Rinkevich Baruch
Published: March 2017

Species‐delimitation studies across wide geographic ranges often reveal insights that ultimately improve our understanding of biogeographic and evolutionary processes. Here we investigated species delimitation and the global coastal pelagic population structures of the marine sardine species from the economically important subgenus Sardinella (Clupeidae). The main purpose of this study was to relate morphological and genetic discontinuities to biogeography, in a taxonomic and systematic context. Morphological examinations have first reduced the currently recognized five species of the subgenus to two distinct morphospecies with parapatric relationship. Genetic analyses further showed a remarkable shallow genealogy across a global scale, yet to be encountered among small pelagic fishes. Additional three species‐delimitation analyses have failed to delimit the five putative species, indicating the possible existence of only a single cosmopolitan species with two ecophenotypic variations, thus entitling Sardinella aurita as the world's most widespread small pelagic fish. Subsequent population‐structure investigations revealed distinct geographical intraspecific sub‐divisions, flagging the West Pacific Ocean through gene‐flow computations as the probable source of future speciation for the subgenus. Considering its utmost importance to fisheries, this finding of a remarkable global genetic homogeneity should attract future attention among population geneticists and fishery researchers.
Insect biodiversity meets ecosystem function: differential effects of habitat and insects on carrion decomposition
Authors: BARTON PHILIP S. , EVANS MALDWYN J.
Published: March 2017

1. Ecological processes are maintained in different environments by different species performing similar functional roles. Yet, little is known about the role of the environment in shaping insect biodiversity associated with a process that is ephemeral and patchy.

2. In this study, the mass loss of carrion in response to contrasting habitat types (grassland or tree) was quantified experimentally, as well as the presence, diversity and composition of insect assemblages. Differences in insect assemblages between these two habitats were also examined.

3. It was found that the presence of insects led to a doubling in mass loss, but that grassland or tree habitat type had no effect on this process. By contrast, habitat type had a significant effect on the composition of generalist ant and beetle assemblages, but not on specialist fly assemblages. Given the colonisation of insects, carrion mass loss was negatively associated with increasing evenness of fly assemblages and increasing ant abundance. Variation in fly assemblage composition was also found to correlate with variation in carrion mass loss.

4. This study highlights the major role of habitat type in shaping the composition of generalist insects at carrion, but the minor role in affecting specialist and highly vagile insects. This complements the authors' findings that insect colonisation of carrion was critical to accelerated mass loss, and that fly assemblages were responsible for variation in this process, regardless of habitat. The present study sheds new light on the contribution of insect biodiversity to decomposition in variable environments, with consequences for carrion food webs and nutrient cycling.
Population viability and perturbation analyses to support recovery of imperilled Eastern Sand Darter(Ammocrypta pellucida)
Authors: Finch Mary , Koops Marten A. , Doka Susan E. , Power Michael
Published: March 2017

Small‐bodied freshwater fishes are often understudied, with the result that data gaps create uncertainties that can complicate and constrain conservation strategies aimed at species recovery. Use of matrix models and perturbation population viability analyses (PVA) are ideally suited for use in studying the consequences of life‐history parameter variation and environmental stochasticity to better understand the fate of threatened small‐bodied fishes. We use data for Eastern Sand Darter (Ammocrypta pellucida)populations from the Thames River, Canada, to explore the consequences of life‐history uncertainties such as age at maturation, multiple clutch sizes and age‐specific fertility for population recovery in this species. Environmental stochasticity acting on all life‐history parameters was found to pose significant risks for the continued viability of lower Thames River populations, with significant chances of local extinction predicted under current conditions. The intrinsic rate of population increase was most sensitive to 0+ survival rates, clutch size and clutch number. As demonstrated here, population models can successfully provide a means of exploring the population dynamics of small‐bodied fishes and can inform managers of risks posed by factors acting on life‐history parameters to affect continued population viability. Management actions for Eastern Sand Darter should focus on strategies designed to ensure successful spawning and improvement of 0+ survival rates, through programmes aimed at the protection, enhancement or recovery of additional spawning and juvenile rearing habitats.
Wrong postural hygiene and ergonomics in dental students of the University of Valencia (Spain) (part I)
Authors: Cervera‐Espert J. , Pascual‐Moscardó A. , Camps‐Alemany I.
Published: March 2017

Introduction

Failure to adopt a correct working posture can lead to occupational diseases.

Objectives

Evaluate knowledge in relation to ergonomics about BHOP concept and its application to routine clinical practice amongst undergraduate and postgraduate dental students in the University of Valencia (Valencia, Spain).

Material and methods

A study based on interviews of undergraduate and postgraduate dental students in the University of Valencia (Valencia, Spain) was carried out. The information from a total of 336 interviews was used for the statistical analysis, differentiating according to gender and academic year: knowledge of ergonomics, pain prevalence and antecedents, assessment of the possible necessity for improved training in ergonomics, and evaluation of postural hygiene.

Results

Only 28.6% of the students were found to sit correctly in the dentist chair. Furthermore, in the opinion of the students, very few subjects during the career afforded adequate teaching in relation to ergonomics and working posture. The analysis of postural hygiene showed great variability. There were no significant differences in posture between males and females, although some incorrect postures appeared to be associated with the academic year (P<.05). However, no significant improvements in postural hygiene were noted on progressing from one academic year to the next.

Conclusions

The students in our study were not familiar with the principles of ergonomics and did not sit correctly in the dentist chair. Improved training in this field is required in dental school.
Concealing and Concealment in Heidegger
Authors: Withy Katherine
Published: March 2017

The self‐concealing of being is a primary preoccupation of Heidegger's later thought, but neither Heidegger nor his interpreters have made clear precisely what it is. In this paper, I identify the self‐concealing of being as the concealing of the worlding of the world (note: not of the world), which is essential to and simultaneous with that worlding. In order to establish this, I sketch a taxonomy of the various phenomena of concealing and concealment in Heidegger's work by building on Mark Wrathall's four ‘planks’ of unconcealing and concealment. Importantly, I distinguish the procedurally prior concealment (lēthē) that all unconcealing (alētheia) presupposes from the simultaneous concealing (kruptein, kruptesthai) that Heidegger frequently confuses it with. This distinction not only allows us to get clear on what it means to say that being conceals itself but also reveals various confusions and obscurities in Heidegger's own thought as well as in that of his readers.
Caecal intussusceptions and typhlocolitis in horses with severeGastrodiscus aegyptiacusinfestation
Authors: Gratwick Z. , Donnellan C. , Page P. C. , Viljoen A. , Williams J. , Lyle C. H.
Published: March 2017

The intestinal trematodeGastrodiscus aegyptiacus(G. aegyptiacus) has been recognised in equids around the world for many years, but its pathogenicity is yet to be confirmed. This report describes seven cases of severeG. aegyptiacusinfestation, including six cases of caecal intussusception.
The circular RNA ciRS‐7 promotes APP and BACE1 degradation in an NF‐κB‐dependent manner
Authors: Shi Zhemin , Chen Ting , Yao Qingbin , Zheng Lina , Zhang Zhen , Wang Jingzhao , Hu Zhimei , Cui Hongmei , Han Yawei , Han Xiaohui , Zhang Kun , Hong Wei
Published: March 2017

The aberrant accumulation of β‐amyloid peptide (Aβ) in the brain is a key feature of Alzheimer's disease (AD), and enhanced cleavage of β‐amyloid precursor protein (APP) by β‐site APP‐cleaving enzyme 1 (BACE1) has a major causative role in AD. Despite their prominence in AD pathogenesis, the regulation of BACE1 and APP is incompletely understood. In this study, we report that the circular RNA circular RNA sponge for miR‐7 (ciRS‐7) has an important role in regulating BACE1 and APP protein levels. Previous studies have shown that ciRS‐7, which is highly expressed in the human brain, is down‐regulated in the brain of people with AD but the relevance of this finding was not clear. We have found that ciRS‐7 is not involved in the regulation of APP and BACE1 gene expression, but instead reduces the protein levels of APP and BACE1 by promoting their degradation via the proteasome and lysosome. Consequently, overexpression of ciRS‐7 reduces the generation of Aβ, indicating a potential neuroprotective role of ciRS‐7. Our data also suggest that ciRS‐7 modulates APP and BACE1 levels in a nuclear factor‐κB (NF‐κB)‐dependent manner: ciRS‐7 expression inhibits translation of NF‐κB and induces its cytoplasmic localization, thus derepressing expression of UCHL1, which promotes APP and BACE1 degradation. Additionally, we demonstrated that APP reduces the level of ciRS‐7, revealing a mutual regulation of ciRS‐7 and APP. Taken together, our data provide a molecular mechanism implicating reduced ciRS‐7 expression in AD, suggesting that ciRS‐7 may represent a useful target in the development of therapeutic strategies for AD.
Unmodified and pyroglutamylated amyloid β peptides form hypertoxic hetero‐oligomers of unique secondary structure
Authors: Goldblatt Greg , Cilenti Lucia , Matos Jason O. , Lee Briana , Ciaffone Nicholas , Wang Qing X. , Tetard Laurene , Teter Ken , Tatulian Suren A.
Published: March 2017

Amyloid β (Aβ) peptide plays a major role in Alzheimer's disease (AD) and occurs in multiple forms, including pyroglutamylated Aβ (AβpE). Identification and characterization of the most cytotoxic Aβ species is necessary for advancement in AD diagnostics and therapeutics. While in brain tissue multiple Aβ species act in combination, structure/toxicity studies and immunotherapy trials have been focused on individual forms of Aβ. As a result, the molecular composition and the structural features of “toxic Aβ oligomers” have remained unresolved. Here, we have used a novel approach, hydration from gas phase coupled with isotope‐edited Fourier transform infrared (FTIR) spectroscopy, to identify the prefibrillar assemblies formed by Aβ and AβpE and to resolve the structures of both peptides in combination. The peptides form unusual β‐sheet oligomers stabilized by intramolecular H‐bonding as opposed to intermolecular H‐bonding in the fibrils. Time‐dependent morphological changes in peptide assemblies have been visualized by atomic force microscopy. Aβ/AβpE hetero‐oligomers exert unsurpassed cytotoxic effect on PC12 cells as compared to oligomers of individual peptides or fibrils. These findings lead to a novel concept that Aβ/AβpE hetero‐oligomers, not just Aβ or AβpE oligomers, constitute the main neurotoxic conformation. The hetero‐oligomers thus present a new biomarker that may be targeted for development of more efficient diagnostic and immunotherapeutic strategies to combat AD.
Coupling dissolved organic carbon, CO2 and productivity in boreal lakes
Authors: Hessen Dag O. , Håll Johnny P. , Thrane Jan‐Erik , Andersen Tom
Published: March 2017

Lakes worldwide are in rapid change because of direct or indirect climate impacts. In boreal areas, the increased concentrations of dissolved organic matter (DOM) are profoundly affecting light climate and productivity in multiple ways. Photochemical and microbial mineralisation of DOM are major sources of CO2 in these lakes. It has been suggested that this CO2 could potentially promote primary production and offset negative impacts of increased light attenuation.

A synoptic survey of 76 Scandinavian lakes along gradients of DOM and total phosphorus (TP) revealed a major negative impact of DOM on primary production and algal biomass primarily related to light attenuation, whilst a strong positive impact of TP. The negative impact of DOM on lake productivity is thus partly offset by DOM‐associated P.

Concentrations of CO2 did not relate significantly to either production, biomass, or seston stoichiometry, and thus whilst elevated CO2 may promote primary production in more productive lakes, it does not in these CO2‐supersaturated boreal lakes.

Zooplankton biomass correlated strongly with TP and total algal biomass, less so with primary production, and was negatively related to DOM, likely reflecting the autotroph responses to DOM.
Potential for an Arctic‐breeding migratory bird to adjust spring migration phenology to Arctic amplification
Authors: Lameris Thomas K. , Scholten Ilse , Bauer Silke , Cobben Marleen M. P. , Ens Bruno J. , Nolet Bart A.
Published: March 2017

Arctic amplification, the accelerated climate warming in the polar regions, is causing a more rapid advancement of the onset of spring in the Arctic than in temperate regions. Consequently, the arrival of many migratory birds in the Arctic is thought to become increasingly mismatched with the onset of local spring, consequently reducing individual fitness and potentially even population levels. We used a dynamic state variable model to study whether Arctic long‐distance migrants can advance their migratory schedules under climate warming scenarios which include Arctic amplification, and whether such an advancement is constrained by fuel accumulation or the ability to anticipate climatic changes. Our model predicts that barnacle geeseBranta leucopsissuffer from considerably reduced reproductive success with increasing Arctic amplification through mistimed arrival, when they cannot anticipate a more rapid progress of Arctic spring from their wintering grounds. When geese are able to anticipate a more rapid progress of Arctic spring, they are predicted to advance their spring arrival under Arctic amplification up to 44 days without any reproductive costs in terms of optimal condition or timing of breeding. Negative effects of mistimed arrival on reproduction are predicted to be somewhat mitigated by increasing summer length under warming in the Arctic, as late arriving geese can still breed successfully. We conclude that adaptation to Arctic amplification may rather be constrained by the (un)predictability of changes in the Arctic spring than by the time available for fuel accumulation. Social migrants like geese tend to have a high behavioural plasticity regarding stopover site choice and migration schedule, giving them the potential to adapt to future climate changes on their flyway.
Effects of increased flooding on riparian vegetation: Field experiments simulating climate change along five European lowland streams
Authors: Garssen Annemarie G. , Baattrup‐Pedersen Annette , Riis Tenna , Raven Bart M. , Hoffman Carl Christian , Verhoeven Jos T. A. , Soons Merel B.
Published: March 2017

In many parts of the world, the magnitude and frequency of cold‐season precipitation are expected to increase in the near future. This will result in an increased magnitude and duration of winter and spring flooding by rain‐fed streams and rivers. Such climate‐driven increases in flooding are likely to affect riparian plant communities, but future vegetation changes are hard to predict due to current lack of data. To fill this knowledge gap, we experimentally modified the hydrology of five streams across three countries in north‐western Europe during late winter/early spring over a period of 3 years. We assessed the responses in riparian plant species richness, biomass, plant‐available nitrogen and phosphorus and seed deposition to increased flooding depth (+18 cm on average at the lowest positions along the riparian gradient) and prolonged flooding duration (6 weeks on average). After 3 years of increased flooding, there was an overall decline in riparian species richness, while riparian plant biomass increased. Extractable soil nitrogen and phosphorus also increased and are likely to have contributed to the increased biomass. Increased flooding resulted in the arrival of more seeds of additional species to the riparian zone, thereby potentially facilitating the shifts in riparian plant species composition we observed. The results of our concerted experimental effort demonstrate that changes in stream riparian plant communities can occur rapidly following increased winter flooding, leading to strong reductions in plant species diversity.
Understanding development impact in international development volunteering: A relational approach
Authors: Chen Jinwen
Published: March 2017

This paper focuses on the question of how interpersonal relationships in international development volunteering (IDV) affect its development impact. While the IDV literature examines care, power and cross‐cultural relationships between volunteers and hosts, it has not clearly elucidated the link between these relationships and development impact. Moreover, although scholars and practitioners posit IDV as a less‐hierarchical and relationship‐focused way to do development, others particularly critique short‐term volunteers’ abilities in providing development impact. This paper thus seeks to understand development impact through a relational approach, by unpacking how and why interpersonal relationships matter in the process of doing development. It also explores the notion of temporality in development impact in terms of impact sustainability and volunteering duration. I analyse the Singapore International Foundation's capacity building Specialist Projects in Cambodia through qualitative fieldwork in 2014 and 2015 with various Cambodian and Singaporean IDV actors. I show how reciprocal relationships over time are crucial in creating intangible and sustainable development impact. More significantly, these findings shed light on the indispensable role of hosts in successful development impact, and make a case for the re‐centring of IDV on host perspectives and contributions.