bluuebunny/crossref_metadata_2025 huggingface dataset:
CBFA2T3‐GLIS2‐positive acute myeloid leukaemia. A peculiar paediatric entity
Authors: Masetti Riccardo , Bertuccio Salvatore N. , Pession Andrea , Locatelli Franco
Published: December 2018

The scenario of paediatric acute myeloid leukaemia (AML), particularly non‐Down syndrome acute megakaryoblastic leukaemia (non‐DS‐AMKL), has been recently revolutionized by the advent of large‐scale, genomic sequencing technologies. In this changing landscape, a significantly relevant discovery has been represented by the identification of the CBFA2T3‐GLIS2 fusion gene, which is the result of a cryptic inversion of chromosome 16. It is the most frequent chimeric oncogene identified to date in non‐DS‐AMKL, although it seems not to be exclusively restricted to the French‐American‐British M7 subgroup. The CBFA2T3‐GLIS2 fusion gene characterizes a subtype of leukaemia that is specific to paediatrics, having never been identified in adults. It characterizes an extremely aggressive leukaemia, as the presence of this fusion is associated with a grim outcome in almost all of the case series reported, with overall survival rates ranging between 15% and 30%. Although the molecular basis that underlies this leukaemia subtype is still far from being completely elucidated, unique functional properties induced by CBFA2T3‐GLIS2 in the leukaemogenesis driving process have been recently identified. We here review the peculiarities of CBFA2T3‐GLIS2‐positive AML, describing its intriguing clinical and biological behaviour and providing some challenging targeting opportunities.
Immediate provisionalization of bone level implants with a hydrophilic surface. A five‐year follow‐up of a randomized controlled clinical trial
Authors: Donos Nikolaos , Horvath Attila , Calciolari Elena , Mardas Nikos
Published: December 2018

Objectives

To follow‐up the radiographic bone level changes and the clinical outcomes of immediately provisionalized and conventionally restored implants with a hydrophilic surface following 5 years of function.

Materials and methods

This was a 5‐year follow‐up of a prospective, randomized, single‐blind controlled study involving 16 of the 24 originally recruited patients in need of a single‐tooth replacement in the esthetic area. Implants were either immediately provisionalized with a non‐occluding temporary crown (test group, n = 7), or left without a crown (control group, n = 9). In both groups, the definitive restoration was placed 16 weeks after implant placement. Radiographic and clinical parameters were evaluated at 36, 48, and 60 months post‐implant placement, together with implant survival and success rates. The esthetic outcomes were measured with the Papilla Fill Index (PFI) and the Pink Esthetic Score (PES).

Results

At 60 months, similar peri‐implant bone loss was observed in the test (−0.42 mm ±0.17 mm) and in the control (−0.37 mm ±0.35 mm) groups. A tendency for an improved esthetic outcome from implant loading to the subsequent follow‐ups was noticed in both groups. Both groups presented with high levels of long‐term implant survival and success.

Conclusions

This study supports non‐functional immediate provisionalization as a viable long‐term option for the management of single‐tooth implants in the esthetic area. However, the small sample size does not allow statistical inference at 60 months of follow‐up and future adequately powered studies are warranted.
Audience segmentation to improve targeting of conservation interventions for hunters
Authors: Jones Sorrel , Keane Aidan , St John Freya , Vickery Juliet , Papworth Sarah
Published: December 2018

Audience segmentation could help improve the effectiveness of conservation interventions. Marketers use audience segmentation to define the target audience of a campaign. The technique involves subdividing a general population into groups that share similar profiles, such as sociodemographic or behavioral characteristics. Interventions are then designed to target the group or groups of interest. We explored the potential of audience segmentation for use in defining conservation target groups with a case study of hunters in Liberia. Using 2 data sets describing households (n = 476) and hunters (n = 205), we applied a clustering method in which infinite binomial mixture models group hunters and households according to livelihood and behavior variables and a simple method to define target groups based on hunting impact (hunting households and high‐impact hunters). Clusters of hunters and households differed in their experiences with confiscation of catch at roadblocks and participation in livelihood‐support programs, indicating that these interventions operate unevenly across subsets of the population. By contrast, the simple method masked these insights because profiles of hunting households and high‐impact hunters were similar to those of the general population. Clustering results could be used to guide the development of livelihood and regulatory interventions. For example, a commonly promoted agricultural activity, cocoa farming, was practiced by only 2% (out of 87) of the largest hunter cluster of nonlocal gun hunters but was prevalent among local trappers, suggesting that assistance aimed at cocoa farmers is less appropriate for the former group. Our results support the use of audience segmentation across multiple variables to improve targeted intervention designs in conservation.
Abundance and species diversity hotspots of tracked marine predators across the North American Arctic
Authors: Yurkowski David J. , Auger‐Méthé Marie , Mallory Mark L. , Wong Sarah N. P. , Gilchrist Grant , Derocher Andrew E. , Richardson Evan , Lunn Nicholas J. , Hussey Nigel E. , Marcoux Marianne , Togunov Ron R. , Fisk Aaron T. , Harwood Lois A. , Dietz Rune , Rosing‐Asvid Aqqalu , Born Erik W. , Mosbech Anders , Fort Jérôme , Grémillet David , Loseto Lisa , Richard Pierre R. , Iacozza John , Jean‐Gagnon Frankie , Brown Tanya M. , Westdal Kristin H. , Orr Jack , LeBlanc Bernard , Hedges Kevin J. , Treble Margaret A. , Kessel Steven T. , Blanchfield Paul J. , Davis Shanti , Maftei Mark , Spencer Nora , McFarlane‐Tranquilla Laura , Montevecchi William A. , Bartzen Blake , Dickson Lynne , Anderson Christine , Ferguson Steven H.
Published: December 2018

Aim

Climate change is altering marine ecosystems worldwide and is most pronounced in the Arctic. Economic development is increasing leading to more disturbances and pressures on Arctic wildlife. Identifying areas that support higher levels of predator abundance and biodiversity is important for the implementation of targeted conservation measures across the Arctic.

Location

Primarily Canadian Arctic marine waters but also parts of the United States, Greenland and Russia.

Methods

We compiled the largest data set of existing telemetry data for marine predators in the North American Arctic consisting of 1,283 individuals from 21 species. Data were arranged into four species groups: (a) cetaceans and pinnipeds, (b) polar bears Ursus maritimus (c) seabirds, and (d) fishes to address the following objectives: (a) to identify abundance hotspots for each species group in the summer–autumn and winter–spring; (b) to identify species diversity hotspots across all species groups and extent of overlap with exclusive economic zones; and (c) to perform a gap analysis that assesses amount of overlap between species diversity hotspots with existing protected areas.

Results

Abundance and species diversity hotpots during summer–autumn and winter–spring were identified in Baffin Bay, Davis Strait, Hudson Bay, Hudson Strait, Amundsen Gulf, and the Beaufort, Chukchi and Bering seas both within and across species groups. Abundance and species diversity hotpots occurred within the continental slope in summer–autumn and offshore in areas of moving pack ice in winter–spring. Gap analysis revealed that the current level of conservation protection that overlaps species diversity hotspots is low covering only 5% (77,498 km2) in summer–autumn and 7% (83,202 km2) in winter–spring.

Main conclusions

We identified several areas of potential importance for Arctic marine predators that could provide policymakers with a starting point for conservation measures given the multitude of threats facing the Arctic. These results are relevant to multilevel and multinational governance to protect this vulnerable ecosystem in our rapidly changing world.
Gastrointestinal defects in gallstone and cholecystectomized patients
Authors: Di Ciaula Agostino , Molina‐Molina Emilio , Bonfrate Leonilde , Wang David Q.‐H. , Dumitrascu Dan L. , Portincasa Piero
Published: December 2018

Background and aim

Several gallstone patients complain of dyspeptic symptoms, irrespective of the presence of typical colicky pain. Symptoms often persist after a cholecystectomy. Systematic studies on dyspepsia and dynamic gastrointestinal motor function are missing in gallstone patients with preserved gallbladder or after a cholecystectomy.

Materials and methods

Forty‐six gallstone patients (age 55 ± 2 years; 15M, 31F) and 24 cholecystectomized patients (age 57 ± 2 years; 6M, 18F) (no difference in type and volume of gallstones between the two groups) were compared against a group of 65 healthy controls (age 51 ± 2 years; 30M, 35F). Dyspepsia occurring in the prior months was assessed by a questionnaire, gastric and gallbladder emptying by functional ultrasonography and orocecal transit time by a hydrogen breath test using a lactulose‐enriched standard liquid meal.

Results

Gallstone patients had significantly greater dyspepsia, fasting and residual gallbladder volumes, and slower gallbladder emptying, gastric emptying and small intestinal transit time than controls. In cholecystectomized patients, gastric emptying further delayed, compared to gallstone patients and controls.

Conclusion

Gallstone patients with the gallbladder “in situ” or after a cholecystectomy display dyspeptic symptoms. Symptoms are associated with multiple gastrointestinal motility defects involving the gallbladder, stomach and small intestine. After cholecystectomy, gastric emptying worsens.
Student experiences of two small group learning‐teaching formats: Seminar and fishbowl
Authors: Tricio Jorge , Montt Juan , Orsini Cesar , Gracia Benjamín , Pampin Francisco , Quinteros Camilo , Salas Macarena , Soto Reinaldo , Fuentes Nelson
Published: December 2018

Introduction

As teaching strategies, the seminar and fishbowl approaches promote active learning and shift the focus from the teacher to the learner. The aim of this study was to compare the self‐reported perceptions of each student‐centred teaching technique amongst a group of dental students as well as resultant quiz scores after each teaching technique.

Material and Methods

During the first semester of 2017, all year‐3 (N = 88) Semiology and year‐5 (N = 71) Oral Surgery students participated in weekly seminars in which teams of students from both cohorts were given an actual clinical case to study; a diagnosis and treatment plan would be rendered, and an oral case presentation would be presented to the rest of the class. In the second semester, the same students tried to solve similar clinical cases using the fishbowl training format. A course coordinator provided final feedback, and the session culminated with a quiz. Students were invited to provide quantitative and qualitative perceptions whilst quiz scores obtained during seminar and fishbowl teaching formats were compared.

Results and Discussion

A total of 97 (61%) seminar and 92 (58%) fishbowl students provided insights regarding these teaching techniques. Both cohorts believed the fishbowl format allowed them to be actively involved. However, only year‐3 students gave the fishbowl format a significantly higher score than the seminar format, considering it an attractive format that allowed them to learn. In contrast, year‐5 students believed the seminars met their expectations better than the fishbowl format. Interesting clinical cases as well as the final round of feedback were qualitative themes reported by both cohorts. The mean seminar and fishbowl quiz scores were statistically significant different for year‐3 students (P < 0.0001), but not for year‐5 students (P = 0.09).

Conclusions

These findings suggest that a more structured small‐group learning‐teaching format can be implemented for younger students whilst at the same time allowing more flexible organisation for senior students.
White matter integrity disruption in the pre‐dementia stages of Alzheimer's disease: from subjective memory impairment to amnestic mild cognitive impairment
Authors: Shao W. , Li X. , Zhang J. , Yang C. , Tao W. , Zhang S. , Zhang Z. , Peng D.
Published: December 2018

Background and purpose

Subjective memory impairment (SMI) and amnestic mild cognitive impairment (aMCI) are thought to represent the pre‐dementia stages of Alzheimer's disease (AD). SMI is considered a more advanced pre‐clinical status prior to aMCI. Understanding the neuromechanism of SMI will have great benefits for monitoring the disease progression of AD. The study aims to explore whether SMI shows alterations of white matter (WM) integrity similar to the patterns of aMCI.

Methods

The atlas‐based analyses were performed to investigate the diffusion changes in the major WM tracts amongst 22 individuals with normal cognition (NC), 22 SMI patients and 25 aMCI patients. The correlations between the altered diffusion metrics and cognitive performance in the SMI and aMCI groups were assessed.

Results

The diffusion tensor metrics of SMI were intermediate between the NC and aMCI groups. The aMCI group presented disrupted integrity in multiple WM tracts, including the left anterior thalamic radiation, right corticospinal tract and left cingulum of the hippocampus (CgH), compared to the NC group. The left CgH showed diffusion alterations in the SMI group. In the aMCI group, the mean diffusivity of the left CgH was negatively correlated with episodic memory, whilst the radial diffusivity of the right corticospinal tract was negatively correlated with executive function. No significant relationship was found in the SMI group.

Conclusion

The study suggested that SMI patients might present detectable WM integrity changes in the left CgH before exhibiting objective cognitive dysfunction, which may provide novel insights into the pathological mechanisms of AD.
Self‐reported dry mouth among ageing people: a longitudinal, cross‐national study
Authors: Åstrøm Anne N. , Lie Stein A. , Ekback Gunnar , Gülcan Ferda , Ordell Sven
Published: December 2018

Focusing on Swedish and Norwegian cohorts of community‐dwelling older adults between age 65 and 70, this study aimed to identify predictors of the prevalence and incident cases of daytime and night‐time xerostomia. It was hypothesized that the prevalence increases with increasing age and is higher in women than in men and that the prevalence of persistent xerostomia and the 5‐yr‐incident cases are higher in people with consistent use of medication and need for health care. Of the Norwegian participants who completed the 2007 survey (age 65 yr), 70% (n = 2,947) participated in 2012. Individuals participating in both 2007 and 2012 constituted the Swedish panel (80%, n = 4,862). The prevalence of xerostomia was higher in women than in men and increased from age 65 to age 70, most markedly in the Swedish cohort. The risk of persistent xerostomia was greatest for participants with consistent use of medication (OR = 1.3) and contact with a physician (OR = 2.3). The risk of incident cases of xerostomia during daytime was greatest for participants with recent and consistent use of medication and recent contact with a physician. Dental professionals should identify patients with xerostomia, emphasize early prevention, and alleviate oral symptoms in collaboration with physicians.
Individual‐ and population‐level personalities in a floriphilic katydid
Authors: Tan Ming Kai , Tan Hugh Tiang Wah
Published: December 2018

Behaviour, including personality, informs us about the response of animals towards their changing environment. Despite the widespread occurrence of florivorous insects and the important but often underrated ecological roles that they play, the study of florivore behaviour is neglected relative to that of pollinators and other herbivores. Specifically, we do not know how different personality types can develop among florivores and enable them to persist in habitats with an ephemeral and dynamic availability of food resources. To address this knowledge gap, we investigated the following questions: whether the (a) inter‐individual differences of exploration and boldness are consistent; (b) inter‐population differences of exploration and boldness are consistent; (c) exploration and boldness are correlated. We collected individuals of the polyphagous floriphilic katydid, Phaneroptera brevis from four populations from wasteland sites in Singapore and performed a personality assay conducted in an insectary to investigate the exploratory and boldness levels of the individuals and populations. The major novel finding was that the floriphilic P. brevis katydids exhibit population‐level personality types for boldness, but not for exploration. Some katydid individuals were consistently more exploratory and bolder than other individuals. However, contrary to our predictions, we did not find any evidence of behavioural syndromes in the katydid individuals, as the boldness level for individuals was not significantly correlated with exploration for individuals. This suggests that an individual which is more exploratory may not be equally keen to take risks and consume novel food that it encounters. Our findings also suggest that boldness and exploration are linked to ecologically important behaviours, but more studies are needed to better understand population‐level personality and how and why natural selection may favour the evolution of personality in certain populations.
Multi‐objective robust fuzzy fractional order proportional–integral–derivative controller design for nonlinear hydraulic turbine governing system using evolutionary computation techniques
Authors: Piraisoodi Thiagarajan , Maria Siluvairaj Willjuice Iruthayarajan , Kappuva Mohaideen Abdul Kadhar
Published: December 2018

The present paper proposes a novel multi‐objective robust fuzzy fractional order proportional–integral–derivative (PID) controller design for nonlinear hydraulic turbine governing system (HTGS) by using evolutionary computation techniques. The fuzzy fractional order PID (FOPID) controller takes closed loop error and its fractional derivative as inputs and performs fuzzy logic operations. Then, it produces the output through the fractional order integrator. The predominant advantages of the proposed controller are its capability to handle complex nonlinear processes like HTGS in heuristic manner, due to fuzzy incorporation and extending an additional flexibility in tuning the order of fractional derivative/integral terms to enhance the closed loop performance. The present work formulates the optimal tuning problem of fuzzy FOPID controller for HTGS as a multi‐objective one instead of a traditional single‐objective one towards satisfying the conflicting criteria such as less settling time and minimum damped oscillations simultaneously to ensure the improved dynamic performance of HTGS. The multi‐objective evolutionary computation techniques such as non‐dominated sorting genetic algorithm‐II (NSGA‐II) and modified NSGA‐II have been utilized to find the optimal input/output scaling factors of the proposed controller along with the order of fractional derivative/integral terms for HTGS system under no load and load turbulence conditions. The performance of the proposed fuzzy FOPID controller is compared with PID and FOPID controllers. The simulations have been conducted to test the tracking capability and robust performance of HTGS during dynamic set point changes for a wide range of operating conditions and model parameter variations, respectively. The proposed robust fuzzy FOPID controller has ensured better fitness value and better time domain specifications than the PID and FOPID controllers, during optimization towards satisfying the conflicting objectives such as less settling time and minimum damped oscillations simultaneously, due to its special inheritance of fuzzy and FOPID properties.
Metabolic impacts of climate change on marine ecosystems: Implications for fish communities and fisheries
Authors: Carozza David A. , Bianchi Daniele , Galbraith Eric D.
Published: December 2018

Aim

Climate change will reshape marine ecosystems over the 21st century through diverse and complex mechanisms that are difficult to assess quantitatively. Here, we characterize expectations for how marine community biomass will respond to the energetic consequences of changes in primary production and temperature‐dependent metabolic rates, under a range of fishing/conservation scenarios.

Location

Global ocean.

Time period

1950–2100.

Major taxa studied

Commercially harvested marine ectotherms (‘fish’).

Methods

We use a size‐structured macroecological model of the marine ecosystem, coupled with a catch model that allows for calibration with global historical data and simulation of fishing. We examine the four energetic mechanisms that, within the model framework, determine the community response to climate change: net primary production, phytoplankton cell size, and the temperature dependencies of growth and natural mortality.

Results

Climate change decreases the modelled global fish community biomass by as much as 30% by 2100. This results from a diminished energy supply to upper trophic levels as photosynthesis becomes more nutrient limited and phytoplankton cells shrink, and from a temperature‐driven increase of natural mortality that, together, overwhelm the effect of accelerated somatic growth rates. Ocean circulation changes drive regional variations of primary production, producing patterns of winners and losers that largely compensate each other when averaged globally, whereas decreasing phytoplankton size drives weaker but more uniformly negative changes. The climate impacts are similar across the range of conservation scenarios but are slightly amplified in the strong conservation scenarios owing to the greater role of natural mortality.

Main conclusions

The spatial pattern of climate impacts is mostly determined by changes in primary production. The overall decline of community biomass is attributed to a temperature‐driven increase of natural mortality, alongside an overall decrease in phytoplankton size, despite faster somatic growth. Our results highlight the importance of the competition between accelerated growth and mortality in a warming ocean.
The fission yeast Greatwall–Endosulfine pathway is required for proper quiescence/G0 phase entry and maintenance
Authors: Aono Soma , Haruna Yui , Watanabe Yo‐hei , Mochida Satoru , Takeda Kojiro
Published: December 2018

Cell proliferation and cellular quiescence/G0 phase must be regulated in response to intra‐/extracellular environments, and such regulation is achieved by the orchestration of protein kinases and protein phosphatases. Here, we investigated fission yeast potential orthologs (Cek1, Ppk18 and Ppk31) of the metazoan Greatwall kinase (Gwl), which inhibits type‐2A protein phosphatase with B55 subunit (PP2AB55) by phosphorylating and activating the PP2AB55 inhibitors, α‐endosulfine/ARPP‐19 (Ensa/ARPP‐19). Gwl and Ensa/ARPP‐19 regulate mitosis; however, we found Ppk18, Cek1 and Mug134/Igo1, the counterpart of Ensa/ARPP‐19, are not essential for normal mitosis but regulate nitrogen starvation (−N)‐induced proper G0 entry and maintenance. Genetic and biochemical analyses indicated that the conserved Gwl site (serine 64) was phosphorylated in the G0 phase in a Ppk18‐dependent manner, and the phosphorylated Mug134/Igo1 inhibited PP2AB55 in vitro. The alanine substitution of the serine 64 caused defects in G0 entry and maintenance as well as the mug134/igo1+ deletion. These results indicate that PP2AB55 activity must be regulated properly to establish the G0 phase. Consistently, simultaneous deletion of the B55 gene with mug134/igo1+ partially rescued the Mug134/Igo1 mutant phenotype. We suggest that in fission yeast, PP2AB55 regulation by the Ppk18‐Mug134/Igo1 pathway is required for G0 entry and establishment of robust viability during the G0 phase.
Pharmacy students’ opinions and experiences working on board the Transnet-Phelophepa Health Care Trains
Authors: Johnston Deanne M G , Truter Ilse , Irwin Yoland L , Naidoo Panjasaram , Coetzee Barbara C , Basson Willem D
Published: December 2018

Objectives

The Transnet-Phelophepa Health Care Trains provide primary healthcare services to patients in under-resourced rural communities across South Africa. Selected final-year pharmacy students work on the trains for 1 week. The aim of the study was to determine the experiences and document the work-based activities of pharmacy students engaged in.

Methods

A hyperlink to an online questionnaire was sent to 106 pharmacy students from five Pharmacy Schools (70.75% response rate). Both closed- and open-ended questions were included. Data were captured in Excel.

Key findings

Respondents expressed that their motivation to volunteer to work on the train was threefold: they wanted to help the community, experience this unparalleled work environment, as well as having heard positive responses from previous volunteers. Students were exposed to a variety of pharmacy-related activities; however, the majority of their time was spent dispensing. Although less than half (n = 33) found it difficult to communicate with patients, almost all responded that the translator helped them communicate with patients. A few saw this as an opportunity to learn a new language. The pharmacy staff was described as approachable, knowledgeable and willing to teach. Most respondents agreed that they were able to apply their knowledge and skills whilst working on the train (mean 4.52 ± 0.93; n = 75).

Conclusions

Pharmacy students felt valued by the community and found it to be a rewarding experience while reporting to apply knowledge and information, improve their communication skills and work as part of a team.
The role of leader relationship quality in the development of employee fit perceptions
Authors: Badawy Rebecca L. , Gazdag Brooke A. , Brouer Robyn L. , Treadway Darren C.
Published: December 2018

Despite being a subject of scholarly inquiry for nearly a century, some components of person–environment fit remain enigmatic. This research seeks to explore the relational factors that are associated with employee identity and how this lens can provide explanatory factors that link leader–employee relationships to employee performance. Across a two‐study, multi‐rater constructive replication design, our results support the tenets of the identity theory that suggests the quality of the leader–employee relationships informs employees of their person–organization (PO) and person–job (PJ) fit, leading to higher performance. Across both the studies, high‐quality leader–employee relations (conceptualized as LMX and trust in leader) were related to higher levels of PO and PJ fit. Our results also indicate that PO and PJ fit uniquely drive higher levels of performance as rated by multiple constituents, helping delineate the impact of PO and PJ fit on work outcomes. Specifically, in Study One (N = 111), PJ fit mediated the relationship between LMX and leader‐rated performance, whereas in Study Two (N = 94), PO fit mediated the relationship between trust in leader and peer‐rated performance. This work provides preliminary support that leaders, through their relationships, can help shape employee fit perceptions and ultimately impact performance. Such knowledge can inform organizations and leaders, and emphasizes the formative role that leaders play in the organizational lives of their employees.
Chemically modified liposomes carrying TRAIL target activated hepatic stellate cells and ameliorate hepatic fibrosis in vitro and in vivo
Authors: Li Qinghua , Ding Youcheng , Guo Xinlai , Luo Shenggen , Zhuang Huiren , Zhou JingE , Xu Nan , Yan Zhiqiang
Published: December 2018

At present, no satisfactory anti‐liver fibrosis drugs have been used clinically due to the poor targeting ability and short half‐life period. This study aimed to explore the effects of a new TRAIL (TNF‐related apoptosis‐inducing ligand) preparation that can target aHSCs (activated hepatic stellate cells) on liver fibrosis and explain the possible underlying mechanism. Using our self‐made drug carrier pPB‐SSL that specifically targets aHSCs, recombinant human TRAIL (rhTRAIL) protein was embedded in (named as pPB‐SSL‐TRAIL) and applied to treat liver fibrotic mice as well as 3T3 fibroblast cells and aHSCs. Through in vitro and in vivo experiments, we found that, compared with the groups treated with TRAIL (free rhTRAIL) and SSL‐TRAIL (rhTRAIL capsulated within unmodified liposome), the group treated with pPB‐SSL‐TRAIL nanoparticles showed significantly lower cell viability and higher cell apoptosis in vitro. The targeting delivering system pPB‐SSL also significantly enhanced the anti‐fibrotic effect, apoptosis induction and long circulation of rhTRAIL. After the treatment with pPB‐SSL‐TRAIL, apoptosis of aHSCs was notably increased and hepatic fibrosis in mice was remarkably alleviated. In vitro, pPB‐SSL‐TRAIL nanoparticles were mainly transported and located on membrane or into cytoplasm, but the particles were distributed mainly in mouse fibrotic liver and most on the cell membrane of aHSCs. In conclusion, rhTRAIL carried by pPB‐SSL delivering system has prolonged circulation in blood, be able to target aHSCs specifically, and alleviate fibrosis both in vitro and in vivo. It presents promising prospect in the therapy of liver fibrosis, and it is worthwhile for us to develop it for clinical use.
Key genes and co‐expression network analysis in the livers of type 2 diabetes patients
Authors: Li Lu , Pan Zongfu , Yang Xi
Published: December 2018

Aims/Introduction

The incidence of type 2 diabetes is increasing worldwide. Hepatic insulin resistance and liver lipid accumulation contributes to type 2 diabetes development. The aim of the present study was to investigate the key gene pathways and co‐expression networks in the livers of type 2 diabetes patients.

Materials and Methods

Dataset GSE15653 containing nine healthy individuals and nine type 2 diabetes patients was downloaded from the National Center for Biotechnology Information Gene Expression Omnibus database. Differentially expressed genes were obtained from the livers of type 2 diabetes patients, annotated pathway enrichment and protein–protein interaction network analysis. Next, functional modules and transcription factor networks were constructed. Gene co‐expression networks were analyzed by weighted correlation network analysis to identify key modules related to clinical traits, and the candidate key genes were validated in hepatic insulin resistance models in vitro.

Results

A total of 778 differentially expressed genes were filtered in the livers of type 2 diabetes patients, pathway enrichment analysis identified ke y pathways, such as the mitogen‐activated protein kinase signaling pathway, Hippo signaling pathway and hypoxia‐inducible factor‐1 signaling pathway, that were associated with type 2 diabetes. Several transcription factors of three functional modules identified from protein–protein interaction networks are likely to be implicated in type 2 diabetes. Furthermore, weighted correlation network analysis identified five modules that were shown to be highly correlated with type 2 diabetes and other clinical traits. Functional annotation showed that these modules were mainly enriched in pathways such as metabolic pathways, phosphoinositide 3‐kinase‐protein kinase B signaling pathway and natural killer cell‐mediated cytotoxicity. UBE2M and GPER were upregulated in L02 and HepG2 models, whereas P2RY11 only upregulated in L02 model, and UBE2N only downregulated in HepG2 model at a significant level.

Conclusions

These results would offer new insights into hepatic insulin resistance, type 2 diabetes pathogenesis, development and drug discovery.
Regulatory Measures Expedited Hip Fracture Surgery Without Lowering Overall Patient Mortality
Authors: Schermann Haggai , Gurel Ron , Rotman Dani , Chechik Ofir , Sternheim Amir , Salai Moshe , Ben‐Tov Tomer , Kadar Assaf
Published: December 2018

OBJECTIVES

Previous observational research has shown that elderly patients with hip fractures who are operated early (within 48 hours from admission) benefit from less short‐ and long‐term mortality compared to those operated later. The objective of this study was to present regulatory measures aimed at promotion of early hip fracture surgery and their effect on the rates of early surgery and on postoperative mortality.

DESIGN

Retrospective cohort.

SETTING

Single inner‐city medical center.

PARTICIPANTS

Elderly patients with hip fractures operated during three time periods: 2006 to 2009 (n = 1735, no intervention), 2010 to 2013 (n = 2104, first intervention, positive reinforcement), and 2014 to 2016 (n = 1538, second intervention, positive and negative reinforcement).

INTERVENTION

Two regulatory measures were introduced consecutively: staff extra wages for afternoon operations (positive reinforcement) in 2010 and making early operation rates publicly available as the Ministry of Health Quality Care Indexes (negative reinforcement) in 2013.

MEASUREMENTS

Percentage of early surgeries and mortality at 1 month and 1 year postoperatively.

RESULTS

A total of 5377 patients (1595 men, 3782 women; mean age, 83.1 ± 7.2 years) underwent hip surgery between 2006 and 2016. The three study groups did not differ significantly in age on admission, sex, type of hip fracture (intracapsular or extracapsular), American Society of Anesthesiologists’ score, mean hemoglobin on admission, and mean socioeconomic status. The percentage of operations performed within 48 hours was 55%, 65%, and 85%, respectively (P < .001). One‐month mortality was 3.9%, 5.1%, and 5%, respectively (P > .05), and one‐year mortality was 19.2%, 18.7%, and 19.6%, respectively (P > .05).

CONCLUSIONS

Management pressure on the staff to expedite hip surgery and avoid negative publicity in conjunction with additional wages for afternoon surgeries was successful at promoting earlier hip surgery. Despite the substantial increase in the rates of early surgery, however, mortality rates were not affected. J Am Geriatr Soc 67:777–783, 2019.
Long‐Run Inflation and the Distorting Effects of Sticky Wages and Technical Change
Authors: PHANEUF LOUIS , VICTOR JEAN GARDY
Published: December 2018

We show that the Calvo price‐setting model is not necessarily inconsistent with evidence of a weak relation between positive trend inflation and price dispersion. We identify the interaction between sticky wages and technical change as factors disrupting the allocative role of the wage system under positive trend inflation. In turn, this interaction generates inefficient wage dispersion, as opposed to price dispersion, which fuels inflation costs. We conclude that it is too early to dismiss the New Keynesian model as a useful vehicle to assess the costs of inflation.
The partial equilibration of garnet porphyroblasts in pelitic schists and its control on prograde metamorphism, Glen Roy, Scotland
Authors: Dempster Tim J. , Gilmour Mairi I. , Chung Peter
Published: December 2018

Garnet porphyroblasts in sillimanite‐bearing pelitic schists contain complex textural and compositional zoning, with considerable variation both within and between adjacent samples. The sillimanite‐bearing schists locally occur in regional Barrovian garnet zone assemblages and are indicative of a persistent lack of equilibrium during prograde metamorphism. Garnet in these Dalradian rocks from the Scottish Highlands preserves evidence of a range of metamorphic responses including initial growth and patchy coupled dissolution–reprecipitation followed by partial dissolution. Individual porphyroblasts each have a unique and variable response to prograde metamorphism and garnet with mainly flat compositional profiles co‐exists with those containing largely unmodified characteristic bell‐shaped Mn profiles. This highlights the need for caution in applying traditional interpretations of effective volume diffusion eliminating compositional variation. Cloudy garnet with abundant fluid inclusions is produced during incomplete modification of the initial porphyroblasts and these porous garnet are then particularly prone to partial replacement in sillimanite‐producing reactions. The modification of garnet via a dissolution–reprecipitation process releases Ca into the effective whole‐rock composition, displacing the pressure–temperature positions of subsequent isograd reactions. This represents the first report of internal metasomatism controlling reaction pathways. The behaviour of garnet highlights the importance of kinetic factors, especially deformation and fluids, in controlling reaction progress and how the resulting variability influences subsequent prograde history. The lack of a consistent metamorphic response, within and between adjacent schists, suggests that on both local and regional scales these rocks have largely not equilibrated at peak metamorphic conditions.
Use of shared milk among breastfeeding mothers with lactation insufficiency
Authors: Cassar‐Uhl Diana , Liberatos Penny
Published: December 2018

Social media platforms have facilitated the use of shared breast milk for infant feeding since 2010. This study aims to assess the prevalence of shared milk use among breastfeeding mothers with insufficient milk supply; and compare shared milk users with non‐users. Data were collected from breastfeeding mothers with low milk supply through an anonymous Internet‐based survey in 2013. Shared milk users were those who used shared milk for at least 10% of their infant's needs; the rest were considered non‐users. Chi‐square comparisons between these groups assessed reasons and information sources for supplementation options; breastfeeding and supplement choice satisfaction; and breastfeeding duration. One hundred thirty‐eight (29.1%) of 475 participants reported shared milk use. Healthfulness and reduced risk were most important to users (p < .001), whereas non‐users cited convenience and lack of knowledge about other options (p < .001). Users reported receiving information from medical/breastfeeding professionals and online discussion forums, whereas non‐users were more likely to not seek information about supplementation options. Users of shared milk were significantly more likely to provide breast milk at 6 months (59.3% vs. 39.6%, p = .001) and be satisfied with their supplementation choice (p < .001) compared with non‐users. For women with self‐reported lactation insufficiency, this study found that shared milk users were more likely to breastfeed longer, seek resources, identify healthful options, and report greater satisfaction with their supplementation choice than non‐users. Importantly, shared milk may play a role in achieving U.S. Healthy People 2020 targets for breastfeeding duration.
TFS and Spt4/5 accelerate transcription through archaeal histone‐based chromatin
Authors: Sanders Travis J. , Lammers Marshall , Marshall Craig J. , Walker Julie E. , Lynch Erin R. , Santangelo Thomas J.
Published: December 2018

RNA polymerase must surmount translocation barriers for continued transcription. In Eukarya and most Archaea, DNA‐bound histone proteins represent the most common and troublesome barrier to transcription elongation. Eukaryotes encode a plethora of chromatin‐remodeling complexes, histone‐modification enzymes and transcription elongation factors to aid transcription through nucleosomes, while archaea seemingly lack machinery to remodel/modify histone‐based chromatin and thus must rely on elongation factors to accelerate transcription through chromatin‐barriers. TFS (TFIIS in Eukarya) and the Spt4–Spt5 complex are universally encoded in archaeal genomes, and here we demonstrate that both elongation factors, via different mechanisms, can accelerate transcription through archaeal histone‐based chromatin. Histone proteins in Thermococcus kodakarensis are sufficiently abundant to completely wrap all genomic DNA, resulting in a consistent protein barrier to transcription elongation. TFS‐enhanced cleavage of RNAs in backtracked transcription complexes reactivates stalled RNAPs and dramatically accelerates transcription through histone‐barriers, while Spt4–Spt5 changes to clamp‐domain dynamics play a lesser‐role in stabilizing transcription. Repeated attempts to delete TFS, Spt4 and Spt5 from the T. kodakarensis genome were not successful, and the essentiality of both conserved transcription elongation factors suggests that both conserved elongation factors play important roles in transcription regulation in vivo, including mechanisms to accelerate transcription through downstream protein barriers.
Higher risk of malignant neoplasms in young adults with end‐stage renal disease receiving haemodialysis: A nationwide population‐based study
Authors: Pan Heng‐Chih , Sun Chiao‐Yin , Wu I‐Wen , Tsai Tien‐Ling , Sun Chi‐Chin , Lee Chin‐Chan
Published: December 2018

Aim

Previous investigations have shown that end‐stage renal disease (ESRD) is associated with an increased risk of malignancies. The aim of this study was to explore the association between ESRD in patients undergoing maintenance haemodialysis (HD) and the incidence of malignancies according to age.

Methods

We analysed a nationwide cohort retrieved from Taiwan's National Health Insurance Research Database to study the incidence of malignancies in patients who were and were not receiving HD. One million beneficiaries were randomly selected and followed from 2005 to 2013. Of these 1 000 000 patients, 3055 developed ESRD and commenced maintenance HD during this period. For each HD patient, four age‐, gender‐ and diabetes‐matched controls were selected from the database (n = 12 220). We further stratified the patients according to age. The study endpoint was the occurrence of malignancy.

Results

The incidence rates of malignancy were 6.8% and 4.9% in the HD and control groups, respectively. Competing risk regression analysis indicated that age, HD, male gender and diabetes were associated with an increased risk of malignancy. When further stratified according to age, the odds ratios of developing cancer were 5.8, 1.9, 1.9 and 1.5 among the HD patients aged <40 years, 40–49 years, 50–59 years and 60–69 years, respectively.

Conclusion

The patients with ESRD who received HD had a significantly higher cumulative risk of malignancy, especially those with a young age. Therefore, specialized cancer screening protocols for young HD patients might help to prolong their lifespan.
Sense of Coherence mediates the association between temporomandibular disorders and quality of life
Authors: Luz Fernanda W. Machado , Perroni Ana Paula , Nascimento Gustavo G. , Goettems Marília L. , Boscato Noéli
Published: December 2018

Objective

This study aimed to evaluate whether sense of coherence (SOC) mediates the association between temporomandibular disorders (TMD) and oral health‐related quality of life (OHRQoL) and general quality of life (QoL) in Brazilian elders.

Methods

Informations on sociodemographic, psychological, and presence or absence of temporomandibular disorders (TMD) were collected by trained dentists among non‐institutionalized elders (n = 110). OHRQoL was measured with the Oral Health Impact Profile (OHIP‐14) and QoL using the WHOQOL‐BREF. Structural equation modeling (SEM) was used to estimate the standardized direct effect of TMD on OHRQoL and on QoL, and the indirect effect mediated by SOC.

Results

Temporomandibular disorders had no direct effect on OHRQoL (coef. −0.10), whereas indirect effect mediated by SOC was noted (coef. 0.35). Regarding QoL, the indirect effect of TMD, mediated by SOC, on QoL (coef. 0.58) was higher than the direct effect (coef. 0.34).

Conclusion

Sense of coherence mediated the effect of TMD on oral and general quality of life among elders.
Anesthesia for high‐risk procedures in the catheterization laboratory
Authors: Daaboul Dima G. , DiNardo James A. , Nasr Viviane G.
Published: December 2018

Recent advances in catheterization and imaging technology allow for more complex procedures to be performed in the catheterization laboratory. A number of lesions are now amenable to a percutaneous procedure, eliminating or at least postponing the need for a surgical intervention. Due to the increase in the complexity of the procedures performed, the involvement of anesthesiologists and their close collaboration with the interventional cardiologists have increased. It is important to understand the physiology and pathophysiology of the patients and to anticipate the plans and the potential complications in order to manage them. We are witnessing a rise in the number of complex interventions in newborns and infants, such as balloon valvotomy (critical aortic stenosis, pulmonary stenosis), radio frequency perforation (of pulmonary atresia and intact ventricular septum), right ventricular outflow tract stenting (in Tetralogy of Fallot), ductal stenting (in some ductus‐dependent pulmonary circulation), and combined with a surgical procedure (hybrid procedure for hypoplastic left heart syndrome). Multiple registries have been created in order to understand and improve outcomes of patients with congenital heart disease undergoing catheterization procedures and to develop performance and quality metrics, from which data regarding anesthetic‐related risks can be extrapolated. Experienced personnel and a multidisciplinary team approach with direct communication among the team members is a must to ensure anticipation and management of critical events when they occur.
Facies and sedimentology of a carbonate delta drift (Miocene, Maldives)
Authors: Reolid Jesús , Betzler Christian , Lüdmann Thomas
Published: December 2018

The identification of sediment drifts typically relies on interpretation of reflection seismic data sets. This study sedimentologically analyzed an example of a carbonate delta drift previously identified in seismics in order to provide a catalogue of characteristic features at core and seismic scale for allowing testing the occurrence of this poorly known type of deposit elsewhere. Cores and downhole logs recovered during International Ocean Discovery Program Expedition 359 to the Maldives, in combination with seismic data, were analyzed with this objective. The diagnostic criteria for the sedimentological recognition of a delta drift are: (i) the development of sigmoidal clinoforms that thin out towards proximal and distal settings; (ii) a proximal part characterized by coarse‐grained facies with abundant shallow‐water components and distal areas dominated by fine‐grained facies with rare to absent shallow‐water components; (iii) winnowing of the finer fraction in proximal facies; (iv) extensive fragmentation of most of the bioclasts with minor intervals of well‐preserved components; (v) bigradational intervals in the proximal part and large channels in proximal to distal settings; and (vi) the lobe to delta shaped outline of the sediment accumulation. The characteristic shallow‐water fossil assemblage of the Mid to Upper Miocene delta drift consists of large benthic foraminifera (Amphistegina, Cycloclypeus, Lepidocyclina, Operculina and Heterostegina), fragmented red algae and bryozoans, equinoid debris, and Halimeda plates. The deeper‐water part of the drift bodies consists of fine‐grained planktonic foraminifera‐rich wackestone. Condensed intervals may occur as result of enhanced bottom‐current activity. In contrast to siliciclastic drift bodies, the carbonate delta drift has an important contribution by in situ shallow‐water carbonate production reminiscent of a shoal. In situ carbonate production is proposed as a major controlling factor which is as important as the pelagic settling or the shaping by density and bottom currents in siliciclastic drifts. In the absence of three‐dimensional data and in two‐dimensional views the carbonate delta drift sediment bodies resemble carbonate ramps, which indicates that there may be the need to re‐evaluate various cases of such systems described from the geological record.