bluuebunny/crossref_metadata_2025 huggingface dataset:
Liver macrophages: Friend or foe during hepatitis B infection?
Authors: Faure‐Dupuy Suzanne , Durantel David , Lucifora Julie
Published: May 2018

The Hepatitis B virus chronically infects the liver of 250 million people worldwide. Over the past decades, major advances have been made in the understanding of Hepatitis B virus life cycle in hepatocytes. Beside these parenchymal cells, the liver also contains resident and infiltrating myeloid cells involved in immune responses to pathogens and much less is known about their interplay with Hepatitis B virus. In this review, we summarized and discussed the current knowledge of the role of liver macrophages (including Kupffer cells and liver monocyte‐derived macrophages), in HBV infection. While it is still unclear if liver macrophages play a role in the establishment and persistence of HBV infection, several studies disclosed data suggesting that HBV would favour liver macrophage anti‐inflammatory phenotypes and thereby increase liver tolerance. In addition, alternatively activated liver macrophages might also play in the long term a key role in hepatitis B‐associated pathogenesis, especially through the activation of hepatic stellate cells. Therapies aiming at a transient activation of pro‐inflammatory liver macrophages should therefore be considered for the treatment of chronic HBV infection.
Trophic relationships in tidepool fish assemblages of the tropical Southwestern Atlantic
Authors: Pimentel Caio R. , Soares Lucy S. H. , Macieira Raphael M. , Joyeux Jean‐Christophe
Published: May 2018

Trophic studies are fundamental to understanding the dynamics of assemblages and functional roles of species within ecosystems, contributing to the identification of factors responsible for the organization and structure of communities. This study aimed to analyse the trophic organization of tidepool fish assemblages in the tropical Southwestern Atlantic, based on the underlying idea that food resources are not limiting and that trophic guild formation is not driven by food competition. Diets were based on feeding index values of food categories for 12 representative species collected in six tidepools (20º49′ S, 40º36′ W) at quarterly intervals (2005 to 2007). The main food categories were small crustaceans, polychaetes and macroalgae. Multivariate techniques evidenced two multispecific trophic guilds: small‐prey carnivores, includingBathygobius soporator,Bathygobius geminatus,Malacoctenus delalandiiandHalichoeres poeyi, and herbivores, includingSparisoma axillareandAcanthurus bahianus. Other species presented significantly different diets and were classified into the following guilds: omnivores feeding on filamentous algae and copepods (Abudefduf saxatilis); large‐prey carnivores (Labrisomus nuchipinnis); omnivores feeding on polychaetes and filamentous algae (Stegastes fuscus); and polychaete feeders (Ahlia egmontis).Gymnothorax funebrisandGymnothorax moringawere classified as carcinophagores and piscivores, respectively. Trophic organization appears related to species convergence toward the use of abundant food resources, driven by a combination of factors allowing some resource partitioning through inter‐specific differences in consumer size, microhabitat, behavior, and trophic specialization.
Accumulation mechanisms of micrometeorites in an ancient supraglacial moraine at Larkman Nunatak, Antarctica
Authors: Genge Matthew J. , van Ginneken Matthias , Suttle Martin D. , Harvey Ralph P.
Published: May 2018

We report the discovery of a large accumulation of micrometeorites (MMs) in a supraglacial moraine at Larkman Nunatak in the Grosvenor Mountains of the Transantarctic Range in Antarctica. The MMs are present in abundances of ~600 particles kg−1 of moraine sediment and include a near‐complete collection of MM types similar to those observed in Antarctic blue ice and within bare‐rock traps in the Antarctic. The size distribution of the observed particles is consistent with those collected from snow collections suggesting the moraine has captured a representative collection of cosmic spherules with significant loss of only the smallest particles (<100 μm) by wind. The presence of microtektites with compositions similar to those of the Australasian strewn field suggests the moraine has been accumulating for 780 ka with dust‐sized debris. On the basis of this age estimate, it is suggested that accumulation occurs principally through ice sublimation. Direct infall of fines is suggested to be limited by snow layers that act as barriers to accumulation and can be removed by wind erosion. MM accumulation in many areas in Antarctica, therefore, may not be continuous over long periods and can be subject to climatic controls. On the basis of the interpretation of microtektites as Australasian, Larkman Nunatak deposit is the oldest known supraglacial moraine and its survival through several glacial maxima and interglacial periods is surprising. We suggest that stationary ice produced by the specific ice flow conditions at Larkman Nunatak explains its longevity and provides a new type of record of the East Antarctic ice sheet.
Establishment and characterization of an embryonic pericyte cell line
Authors: Zhao Huaning , Darden Jordan , Chappell John C.
Published: May 2018

Objective

Pericytes are specialized perivascular cells embedded within the basement membrane. These cells envelope the abluminal surface of endothelial cells and promote microvessel homeostasis. Recent discoveries of unique pericyte functions, particularly in neural tissues, underscore the need for overcoming existing challenges in establishing a functionally validated pericyte cell line. Here, we present methodologies for addressing these challenges as well as an embryonic pericyte cell line for use with in vitro and ex vivo experimental models.

Methods

We isolated an enriched population of NG2:DsRed+ pericytes from E12.5 mice. This pericyte cell line was compared to MEFs with respect to gene expression, cell morphology and migration, and engagement with endothelial cells during junction stabilization and angiogenesis.

Results

NG2+ pericytes displayed gene expression patterns, cell morphology, and 2D migration behaviors distinct from MEFs. In three different vessel formation models, pericytes from this line migrated to and incorporated into developing vessels. When co‐cultured with HUVECs, these pericytes stimulated more robust VE‐Cadherin junctions between HUVECs as compared to MEFs, as well as contributed to HUVEC organization into primitive vascular structures.

Conclusions

Our data support use of this pericyte cell line in a broad range of models to further understand pericyte functionality during normal and pathological conditions.
PROMs for Pain in Adult Cancer Patients: A Systematic Review of Measurement Properties
Authors: Abahussin Asma A. , West Robert M. , Wong David C. , Ziegler Lucy E.
Published: May 2018

Context

Pain is one of the most devastating symptoms for cancer patients. One third of patients who experience pain do not receive effective treatment. A key barrier to effective pain management is lack of routine measurement and monitoring of pain. Patient‐reported outcome measures (PROMs) are recommended for measuring cancer pain. However, evidence to guide the selection of the most appropriate measure to identify and monitor cancer pain is limited. A systematic review of measurement properties of PROMs for pain in cancer patients is needed to identify the best validated measure for adoption to an electronic platform.

Objectives

To systematically review measurement properties of PROMs used for adult cancer patients to measure pain and, as a secondary goal, to investigate the evidence of validated mobile health (mHealth) applications used to measure pain (registration number: CRD42017065575).

Methods

Medline, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) were systematically searched in March 2018 for studies examining measurement properties for PROMs for pain in adult cancer patients. The methodological quality of the studies and their results were appraised using the Consensus‐based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist and specific measurement properties criteria, respectively.

Results

Sixteen studies evaluating 8 instruments were included. No studies using a PROM in an mHealth application were identified. The methodological quality of the measurement properties ranged between poor and fair. No instrument showed strong positive evidence for all the evaluated measurement properties. Based on the available evidence, the Brief Pain Inventory‐Short Form (BPI‐SF) had the strongest evidence to support its selection for the measurement of cancer pain.

Conclusion

The BPI‐SF was the best performing measure across all properties evaluated through COSMIN. Better quality validation studies of PROMs for cancer pain are needed to explore the full range of measurement properties. Utilizing mHealth applications to measure pain in cancer patients is an innovative approach worthy of further investigation.
Psychosocial risk screening of expectant fathers in an urban home visiting service population
Authors: Carlson Richard E. , Caines Mageen C. , Harrison Patricia A.
Published: May 2018

Objective

To examine the occurrence of psychosocial risk factors among expectant fathers whose female partners were enrolled in prenatal home visiting services.

Design

Cross‐sectional, exploratory, quantitative design.

Sample

Expectant father–mother pairs were recruited from two urban home visiting programs to participate in a randomized controlled trial of a father advocate intervention. The study sample consisted of 66 father–mother pairs who completed structured interviews at baseline, before randomization.

Measurements

Participants were interviewed using a structured questionnaire. This study focused on their responses related to 11 psychosocial risk factors, as measured by the Brief Risk Overview (BRO) for men and the Prenatal Risk Overview (PRO) for pregnant women.

Results

Moderate‐ or high‐risk classification of psychosocial risk factors was prevalent among expectant fathers. The risk factors that fathers reported were diverse, related to their basic needs, social support, mental health, and substance use; risk factors frequently co‐occurred. Fathers' and mothers' total risk scores, calculated as a composite of all 11 risk factors, were significantly correlated.

Conclusions

Expectant fathers who have a partner enrolled in home visiting would benefit from psychosocial risk screening. Addressing fathers' risk factors may improve paternal health, their involvement in parenting, and the well‐being of their partners and children.
Suitability of structure from motion for rock‐slope assessment
Authors: O'Banion Matt S. , Olsen Michael J. , Rault Claire , Wartman Joseph , Cunningham Keith
Published: May 2018

This study examines three sites in Alaska with unstable rock slopes that were surveyed using both terrestrial laser scanning (TLS) and structure‐from‐motion (SfM) techniques. The datasets were acquired simultaneously and linked to a rigorous survey control network. An accuracy evaluation of the SfM‐derived surface models was performed using the TLS data and numerous reflectorless total station observations collected across the rock slopes. A quality evaluation was conducted to examine differences in point density, model completeness and distributions of morphological properties between the SfM and TLS datasets. The results indicate that SfM is a viable option for unstable rock‐slope assessment when a sufficient number of images with adequate overlap are acquired and the reconstruction is tied to a survey control network. The best results, in terms of accuracy and completeness, were achieved when combining both unmanned aerial vehicle (UAV) and terrestrial imagery for the SfM reconstruction. However, issues such as over‐smoothing and geometric inconsistencies bring into question the suitability of SfM for the detection of small changes over time.
An unusual case of pulmonary hamartoma with predominant bronchial mucous glands in the peripheral lung
Authors: Yamada Rin , Tonooka Akiko , Horiguchi Shin‐ichiro , Motoi Toru , Horio Hirotoshi , Hishima Tsunekazu
Published: May 2018

Pulmonary hamartoma (PH) is the most common benign lung tumor, comprising various amounts of mescenchymal components with entrapped epithelial components. We describe an unusual case of PH in the left lower lung lobe of a 60‐year‐old female. The tumor was 9 × 9 mm in size, light brown, weakly glistening, and microscopically found to be composed of well‐developed epithelial and mesenchymal components without atypia. Both components were intermingled but without apparent transition. Epithelial components were occupied by predominant bronchial mucous glands. Serous glands, entrapped bronchioles, and clefts lined by respiratory epithelium were also apparent. Mesenchymal components including cartilage and fat were scattered, and swirling smooth muscle fascicles were interlaced with epithelial components. Collision tumor or other biphasic tumors were unlikely, and hyperplastic change in bronchial glands as in the rare conditions of intraoral minor salivary glands and epithelial entrapments by PH may explain these interesting histological findings. It is important to be aware of the possibility that a large number of bronchial mucous glands may be noted in the peripheral lung, and not to mistake this for other malignancies.
Narrative Strategies in the Gun Policy Debate: Exploring Proximity and Social Construction
Authors: Merry Melissa K.
Published: May 2018

While much scholarship has explored the framing of gun policy, the bulk of that work has focused on general themes or arguments made in support or opposition to gun control. This study offers a more nuanced examination of the framing in the gun policy debate, utilizing the Narrative Policy Framework (NPF) to identify rhetorical and political strategies of gun control and gun rights organizations. Drawing on a data set of more than 58,000 Facebook posts by 15 gun policy organizations, I examine how groups portray the victims of gun violence, particularly with respect to the race and age of victims. I also examine the types of gun violence that groups emphasize on social media. The findings suggest that gun control organizations seek to broaden the scope of debate by focusing on child victims and on mass shootings. Gun rights organizations pursue a similar strategy, but with a focus on self‐defense shootings. Despite the fact that gun violence primarily affects minorities, both types of organizations rarely mentioned race. I attribute this to groups' efforts to emphasize proximate and positively constructed characters. This research suggests that both types of organizations systematically distort the nature of the gun policy problem.
A critical review on control methods for harmful algal blooms
Authors: Gallardo‐Rodríguez Juan J. , Astuya‐Villalón Allisson , Llanos‐Rivera Alejandra , Avello‐Fontalba Veronica , Ulloa‐Jofré Viviana
Published: May 2018

The impacts of harmful algal blooms on human health, tourism, fisheries and ecosystems have increased in recent decades. Eutrophication and the feared climate change are believed to further challenge authorities and those whose activity depends on coastal resources. While in most of the affected countries, regulatory steps have been taken to protect consumers of contaminated food, there has been an unequal focus on management systems. Some countries such as EEUU and Canada have focused on monitoring and prediction programs, whereas others (e.g. Korea, China) have relied on direct control of blooms in the sea. Here, we review current control methods for HABs including their fundamentals and the last scientific advances. A thorough revision of all considered approaches so far has been included. Ecological studies of the impact of the countermeasures were also considered.
Leaders promote attendance in sport and exercise sessions by fostering social identity
Authors: Stevens M. , Rees T. , Coffee P. , Haslam S. A. , Steffens N. K. , Polman R.
Published: May 2018

Sport and exercise participation exert a positive effect on numerous aspects of individuals' health. Although sport and exercise leaders have generally been observed to play a key role in shaping group members' behavior, our understanding of their impact on group members' attendance in sport and exercise sessions is limited. To address this, and building on promising findings in other domains, we examined the associations between perceptions of sport and exercise leaders' engagement in social identity leadership, group identification, and attendance. A sample of 583 participants from sports teams (n = 307) and exercise groups (n = 276) completed questionnaires measuring identity leadership, group identification, and attendance. Analyses demonstrated that perceptions of leader engagement in social identity leadership were positively associated with members' group identification, and that this in turn was positively associated with their attendance in either a sports group or an exercise group. Moreover, there was a significant indirect effect for perceptions of leader engagement in identity leadership on group members' attendance through their greater identification with these groups. Findings highlight the importance of considering the impact sport and exercise leaders have on group members' attendance and suggest that leaders who represent, advance, create, and embed a shared sense of identity (ie, a shared sense of “us”) among attendees can promote participation in sport and exercise.
Morphology and Memory: Toward an Integrated Theory
Authors: Jackendoff Ray , Audring Jenny
Published: May 2018

Framed in psychological terms, the basic question of linguistic theory is what is stored in memory, and in what form. Traditionally, what is stored is divided into grammar and lexicon, where grammar contains the rules and the lexicon is an unstructured list of exceptions. We develop an alternative view in which rules of grammar are simply lexical items that contain variables, and in which rules have two functions. In theirgenerativefunction, they are used to build novel structures, just as in traditional generative linguistics. In theirrelationalfunction, they capture generalizations over stored items in the lexicon, a role not seriously explored in traditional linguistic theory. The result is a highly structured lexicon with rich patterns among stored items. We further explore the possibility that this sort of structuring is not specific to language, but appears in other cognitive domains as well, such as the structure of physical objects, of music, and of geographical and social knowledge. The differences among cognitive domains do not lie in this overall texture, but in the materials over which stored relations are defined. The challenge is to develop theories of representation in these other domains comparable to that for language.
Arabidopsis VQ18 and VQ26 proteins interact with ABI5 transcription factor to negatively modulate ABA response during seed germination
Authors: Pan Jinjing , Wang Houping , Hu Yanru , Yu Diqiu
Published: May 2018

Seed germination and early seedling establishment, critical developmental stages in the life cycle of seed plants, are modulated by diverse endogenous hormones and the surrounding environment. Arabidopsis ABSCISIC ACID‐INSENSITIVE5 (ABI5) is a central transcription factor of abscisic acid (ABA) signaling that represses those processes. ABI5 is precisely modulated at post‐translational level; however, whether it interacts with other crucial transcriptional regulators remains to be investigated. In this study, VQ18 and VQ26, two members of the recently‐identified VQ family, were found to interact with ABI5 in vitro and in vivo. Phenotypic analysis showed that VQ18 and VQ26 are responsive to ABA and negatively mediate ABA signaling redundantly during seed germination. Simultaneously decreasing VQ18 and VQ26 expression levels enhanced ABA signaling to suppress seed germination, whereas overexpressing these two VQ genes resulted in the germinated seeds being less ABA‐sensitive. Consistently, the expression levels of several ABI5 targets were modulated by VQ18 and VQ26. The increased ABA signaling of plants in which VQ18 and VQ26 were simultaneously suppressed required ABI5. Additionally, VQ18 and VQ26 acted as negative interactors of the ABI5 transcription factor. Our study reveals a previously unidentified regulatory role of VQ proteins, which act antagonistically with ABI5 to maintain the appropriate ABA signaling level to fine‐tune seed germination and early seedling establishment.
Trade and economic impacts of destination‐based business cash‐flow taxes
Authors: Martin Will
Published: May 2018

Proposals for destination‐based business cash‐flow taxes (DBCFT) that effectively combine a value‐added tax and a wage subsidy have received enormous attention in the United States and are being proposed as a major tax reform worldwide. Much controversy has focused on trade impacts, but this paper shows that a DBCFT would not create long‐term trade barriers or export subsidies if prices and wages are flexible. It would leave business profits and rents untaxed, providing an unambiguous benefit to foreign investors relative to an origin‐based corporate tax. Domestic wage earners would be compensated for higher prices by the wage deduction, while the position of domestic investors would depend on whether their gains from abolition of origin‐based taxes outweighed their losses from higher consumer prices. A key concern is small, volatile and vulnerable net revenues even with high‐tax rates. At current US consumption and labour shares, a 20% corporate cash‐flow tax with a wage subsidy would generate less than 2% of GDP in net revenues, which could be obtained with much less volatility from a 2.8% consumption tax alone. Under a DBCFT, revenues would become negative if consumption and labour shares returned to their historical norms or if difficult‐to‐tax sectors like owner‐occupied housing were excluded.
Use of antibiotic impregnated resorbable beads reduces pressure ulcer recurrence: A retrospective analysis
Authors: Khansa Ibrahim , Barker Jenny C. , Ghatak Piya Das , Sen Chandan K. , Gordillo Gayle M.
Published: May 2018

Recurrence of pressure ulcers remains common. We have employed resorbable antibiotic beads as a therapeutic strategy to deliver high local antibiotic concentrations to the debridement site. Our objective was to determine whether the use of resorbable antibiotic‐ beads would reduce pressure ulcer recurrence. We reviewed all stage IV pressure ulcers treated with excision, partial ostectomy and flap coverage over 16 years. Baseline patient factors (location of ulcer, presence of osteomyelitis, preoperative prealbumin), surgical factors (type of flap, use of antibiotic beads, bone culture results) and postoperative outcomes (ulcer recurrence at 1 year, dehiscence, seroma, cellulitis) were collected. Outcomes of patients who received antibiotic‐impregnated beads were compared to those who did not. Eighty‐six patients with 120 stage IV pressure ulcers underwent excision and flap coverage. This included 16 ulcers where antibiotic beads were used and 104 where they were not. The overall ulcer recurrence rate at 12 months was 35.8%. The recurrence rate in the group treated with antibiotic beads was significantly lower than the group without beads (12.5% vs. 39.4%, p = 0.03). Overall, complication rates between the two groups were similar (43.8% vs. 51.9%, p = 0.54). No systemic or local toxicity from antibiotic beads occurred. Scanning electron microscopy images of sacral bone from one case showed bacterial biofilm even after debridement. Pressure ulcer recurrence at 1 year after excision and flap coverage decreased significantly with the use of resorbable antibiotic beads.
Effectiveness of extracellular matrix dressings and topical agents in the treatment of leg ulcers: a systematic review protocol
Authors: de Fátima Cordeiro Petz Francislene , Meier Marineli Joaquim , Roehrs Hellen , Pott Franciele Soares
Published: May 2018

Review question/objective:

The objective of this review is to synthesize the best available evidence on the effectiveness of the application of extracellular matrix products as dressings or in topical form as treatment for venous, arterial and mixed leg ulcers, compared to compression therapy alone, any type of dressings and topical agents, or placebos in adults over 18 years in any care setting.
Subtle errors of bladder wall thickness measurement have a significant impact on the calculation of ultrasound-estimated bladder weight. A pilot study
Authors: Sakalis Vasileios I. , Sfiggas Vasileios , Vouros Ioannis , Salpiggidis Georgios , Papathanasiou Athanasios , Apostolidis Apostolos
Published: May 2018

Aims: Ultrasound-estimated bladder weight (UEBW), is an emerging diagnostic tool, which has been used in both males and females with lower urinary tract dysfunction. The currently acknowledged UEBW calculation methods rely on the accurate measurement of bladder wall thickness (BWT). We aim to identify if subtle errors in BWT measurement have a significant impact on UEBW calculations.Materials and methods: Twenty patients were randomly selected from an overactive bladder patient cohort. The primary endpoint was to identify the range of false BWT measurements outside which significant changes in UEBW calculation occur. We used the Kojima method and a semi-automatic 3-D model that is based on Chalana’s principle. Measurements were performed using the correct BWT and a series of faulty calculations from +0.5 mm to -0.5 mm using steps of 0.05 mm from true BWT. The effect of a fixed 0.5 mm BWT error was checked in bladder volumes above and below 250 ml and in three UEBW groups (<35 gr; 36-50 gr; >51gr).Results: BWT measurement errors above 0.25 mm cause statistically significant changes in UEWB calculation when a 3-D model is used and errors above 0.15 mm when Kojima’s method is used. At a fixed BWT error of 0.5 mm and bladder volume <250 ml, there is a 23.76% deviation from true UEBW, while at volumes >250 ml the deviation is 32.72%. The deviation is inversely proportional to the UEBW result, and heavier bladders deviate less.Conclusions: UEBW is a promising diagnostic tool, but small errors in BWT measurement might cause significant deviation from the true values. A 3-D calculation model appears to minimize such risks.
Diagnostic value of acustic radiation force impulse imaging in the assessment of salivary gland involvement in primary Sjögren’s sydrome
Authors: Turnaoglu Hale , Kural Rahatli Feride , Pamukcu Melih , Haberal Kemal Murat , Uslu Nihal
Published: May 2018

Aims: The aim of this study is to investigate the diagnostic value of Acoustic Radiation Force Impulse (ARFI) imaging in the assessment of salivary gland involvement in primary Sjögren’s syndrome (pSS).Material and methods: Twenty five patients with pSS and 25 healthy volunteers were included. First, echostructures and the thickness of the submandibular and parotid glands were evaluated by B-mode ultrasonography. Then, ARFI imaging with Virtual Touch Quantification® was performed. Ten independent shear wave velocity measurements were taken from each gland. Finally, the mean shear wavevelocity (SWV) values were calculated, and used for further analysis.Results: The mean SWV values of parotid and submandibular glands were significantly higher in the pSS patients than in the healthy control group (p<0.001). The cut-off of SWV values were calculated to be 1.98 m/s for submandibular glands, and 1.93 m/s for parotid glands. In pSS patients, the mean SWV values of parotid glands were higher than those of the submandibular glands (p<0.001) and no statistically significant relationships between symptom duration or the degree of xerostomia and mean SWV values of parotid and submandibularglands were found (all p>0.005).Conclusions: Our findings indicate that ARFI imaging may provide a non-invasive, simple and fast means of assessment of glandular impairment as an alternative test when other salivary gland tests are inconclusive or cannot be performed. ARFI may be a valuable adjunct for the clinical diagnosis of pSS.
High altitude may have driven short stature in Peruvians
Authors: Pennisi Elizabeth
Published: May 2018

Study reveals new gene with a major impact on height.
Notch ligand Dll1 mediates cross-talk between mammary stem cells and the macrophageal niche
Authors: Chakrabarti Rumela , Celià-Terrassa Toni , Kumar Sushil , Hang Xiang , Wei Yong , Choudhury Abrar , Hwang Julie , Peng Jia , Nixon Briana , Grady John J. , DeCoste Christina , Gao Jie , van Es Johan H. , Li Ming O. , Aifantis Iannis , Clevers Hans , Kang Yibin
Published: May 2018

Cross-talk in the mammary gland

Macrophages engulf damaged and dead cells to clear infection, but they also participate in tissue regeneration. Chakrabarti
et al.
expand the macrophage repertoire for mammary gland development (see the Perspective by Kannan and Eaves). Mammary gland stem cells secrete the Notch ligand Dll1 and activate Notch signaling, which promotes survival of adjacent macrophages. This stimulates production of Wnt ligands, which signal back to the mammary gland stem cells. This cross-talk plays an important role in coordinating mammary gland development, tissue homeostasis, and, not least, breast cancer.

Science
, this issue p.
eaan4153
; see also p.
1401
Unresolved endoplasmic reticulum stress engenders immune-resistant, latent pancreatic cancer metastases
Authors: Pommier Arnaud , Anaparthy Naishitha , Memos Nicoletta , Kelley Z. Larkin , Gouronnec Alizée , Yan Ran , Auffray Cédric , Albrengues Jean , Egeblad Mikala , Iacobuzio-Donahue Christine A. , Lyons Scott K. , Fearon Douglas T.
Published: May 2018

Chronic stress as a survival tactic

Most patients with pancreatic ductal adenocarcinoma (PDA) develop liver metastases after surgical removal of their primary tumor. These metastases are thought to potentially arise from quiescent disseminated cancer cells, likely present at the time of surgery, which evade elimination by the immune system. Pommier
et al.
explored how these quiescent cells survive by analyzing mouse models and tissue samples from patients with PDA. They found that disseminated cancer cells do not express a cell surface molecule that triggers killing by T cells. This phenotypic feature is linked to their inability to resolve endoplasmic reticulum stress. When this stress is resolved, the disseminated cells begin proliferating and form metastases.

Science
, this issue p.
eaao4908
Genomic insights into the emergence and spread of antimicrobial-resistant bacterial pathogens
Authors: Baker Stephen , Thomson Nicholas , Weill François-Xavier , Holt Kathryn E.
Published: May 2018

Whole-genome sequencing (WGS) has been vital for revealing the rapid temporal and spatial evolution of antimicrobial resistance (AMR) in bacterial pathogens. Some antimicrobial-resistant pathogens have outpaced us, with untreatable infections appearing in hospitals and the community. However, WGS has additionally provided us with enough knowledge to initiate countermeasures. Although we cannot stop bacterial adaptation, the predictability of many evolutionary processes in AMR bacteria offers us an opportunity to channel them using new control strategies. Furthermore, by using WGS for coordinating surveillance and to create a more fundamental understanding of the outcome of antimicrobial treatment and AMR mechanisms, we can use current and future antimicrobials more effectively and aim to extend their longevity.
Response to Comment on “Maxima in the thermodynamic response and correlation functions of deeply supercooled water”
Authors: Kim Kyung Hwan , Späh Alexander , Pathak Harshad , Perakis Fivos , Mariedahl Daniel , Amann-Winkel Katrin , Sellberg Jonas A. , Lee Jae Hyuk , Kim Sangsoo , Park Jaehyun , Nam Ki Hyun , Katayama Tetsuo , Nilsson Anders
Published: May 2018

Caupin
et al
. have raised several issues regarding our recent paper on maxima in thermodynamic response and correlation functions in deeply supercooled water. We show that these issues can be addressed without affecting the conclusion of the paper.
Chemical storage of renewable energy
Authors: Ager Joel W. , Lapkin Alexei A.
Published: May 2018

A stable electrochemical cell selectively produces ethylene from carbon dioxide
Pharmacokinetics of Piperaquine and Safety Profile of Dihydroartemisinin-Piperaquine Coadministered with Antiretroviral Therapy in Malaria-Uninfected HIV-Positive Malawian Adults
Authors: Banda Clifford G. , Dzinjalamala Fraction , Mukaka Mavuto , Mallewa Jane , Maiden Victor , Terlouw Dianne J. , Lalloo David G. , Khoo Saye H. , Mwapasa Victor
Published: May 2018

There are limited data on the pharmacokinetic and safety profiles of dihydroartemisinin-piperaquine (DHA-PQ) among human immunodeficiency virus-infected (HIV-positive [HIV
+
]) individuals taking antiretroviral therapy (ART). In a two-step (parallel-group) pharmacokinetic trial with intensive blood sampling, we compared the area under the concentration-time curve from days 0 to 28 (AUC
0–28 days
) and the safety outcomes of piperaquine among malaria-uninfected HIV
+
adults.
HIV-1 Activation of Innate Immunity Depends Strongly on the Intracellular Level of TREX1 and Sensing of Incomplete Reverse Transcription Products
Authors: Kumar Swati , Morrison James H. , Dingli David , Poeschla Eric
Published: May 2018

Much remains unknown about how TREX1 influences HIV-1 replication: whether it targets full-length viral DNA versus partial intermediates, how intracellular TREX1 protein levels correlate with ISG induction, and whether TREX1 digestion of cytoplasmic DNA and subsequent cGAS pathway activation affects both initial and subsequent cycles of infection. To answer these questions, we experimentally varied the intracellular level of TREX1 and showed that this strongly determines the innate immunogenicity of HIV-1. In addition, several lines of evidence, including time-of-addition experiments with drugs that impair reverse transcription or capsid integrity, showed that the pathogen-associated molecular patterns sensed after viral entry contain DNA, are TREX1 and cGAS substrates, and are derived from incomplete reverse transcriptase (RT) products. In contrast, the experiments demonstrate that full-length integration-competent viral DNA is immune to TREX1. Treatment approaches that reduce TREX1 levels or facilitate release of DNA intermediates may advantageously combine enhanced innate immunity with antiviral effects.
Rab5, Rab7, and Rab11 Are Required for Caveola-Dependent Endocytosis of Classical Swine Fever Virus in Porcine Alveolar Macrophages
Authors: Zhang Yun-Na , Liu Ya-Yun , Xiao Fu-Chuan , Liu Chun-Chun , Liang Xiao-Dong , Chen Jing , Zhou Jing , Baloch Abdul Sattar , Kan Lin , Zhou Bin , Qiu Hua-Ji
Published: May 2018

Classical swine fever, is caused by classical swine fever virus (CSFV). The disease is notifiable to World Organisation for Animal Health (OIE) in most countries and causes significant financial losses to the pig industry globally. Understanding the processes of CSFV endocytosis and postinternalization will advance our knowledge of the disease and provide potential novel drug targets against CSFV. With this objective, we used systematic approaches to dissect these processes in CSFV-infected 3D4/21 cells. The data presented here demonstrate for the first time to our knowledge that CSFV is able to enter cells via caveola-mediated endocytosis that requires Rab5, Rab7 and Rab11, in addition to the previously described classical clathrin-dependent pathway that requires Rab5 and Rab7. The characterization of CSFV entry will further promote our current understanding of
Pestivirus
cellular entry pathways and provide novel targets for antiviral drug development.
Which anthropometric measures best indicate type 2 diabetes among Russian, Somali and Kurdish origin migrants in Finland? A cross-sectional study
Authors: Skogberg Natalia , Laatikainen Tiina , Lundqvist Annamari , Lilja Eero , Härkänen Tommi , Koponen Päivikki
Published: May 2018

Objectives

To compare the performance of body mass index (BMI), waist-to-height ratio (WHtR), waist circumference (WC) and waist-to-hip ratio (WHR) in detecting type 2 diabetes among Russian, Somali and Kurdish (born in Iraq/Iran) origin migrants and Finns.

Design and participants

Cross-sectional study comparing health examination survey data of Russian, Somali and Kurdish origin migrants (n=917) aged 30–64 years who took part in the Migrant Health and Wellbeing Survey with the general Finnish population in the Health 2011 Survey (n=887). Participants were randomly selected from the National Population Register.

Setting

Six cities in Finland, where a substantial majority of migrants live.

Outcome measures

Anthropometric measures included objectively measured BMI, WHtR, WC and WHR. Type 2 diabetes was defined based on self-report, laboratory measures of glycated haemoglobin and register data. Test performance was assessed using receiver operating characteristics curves, using area under the curve (AUC) as a measure of accuracy.

Results

Among Finns, test performance was highest for WC (AUC=0.81, 95% CI 0.74 to 0.87) and WHtR (AUC=0.81, 95% CI 0.75 to 0.87). Test performance was similar for BMI (AUC=0.80, 95% CI 0.67 to 0.92), WC (AUC=0.79, 95% CI 0.67 to 0.91) and WHtR (AUC=0.70, 95% CI 0.66 to 0.93) among Russians. WC and WHtR had highest test performance also among Somali (AUC=0.74, 95% CI 0.64 to 0.84 for WC and AUC=0.75, 95% CI 0.65 to 0.85 for WHtR) and Kurds (AUC=0.71, 95% CI 0.61 to 0.81 for WC and AUC=0.70, 95% CI 0.59 to 0.80 for WHtR).Among migrants, WHR had the poorest test performance.

Conclusion

WC and WHtR performed overall the best across all study groups, however, accuracy of detection was lower particularly among Somali and Kurds. Currently used diabetes risk assessment tools assume a strong association between anthropometrics and diabetes. These tools need to be validated among non-Western populations.
Implications of involving pharmacy technicians in obtaining a best possible medication history from the perspectives of pharmaceutical, medical and nursing staff: a qualitative study
Authors: Niederhauser Andrea , Zimmermann Chantal , Fishman Liat , Schwappach David L B
Published: May 2018

Objectives

In recent years, the involvement of pharmacy technicians in medication reconciliation has increasingly been investigated. The aim of this study was to assess the implications on professional roles and collaboration when a best possible medication history (BPMH) at admission is obtained by pharmacy technicians.

Design

Qualitative study with semistructured interviews. Data were analysed using a qualitative content analysis approach.

Setting

Internal medicine units in two mid-sized Swiss hospitals.

Participants

21 staff members working at the two sites (6 pharmacy technicians, 2 pharmacists, 6 nurses, 5 physician residents and 2 senior physicians).

Results

Pharmacy technicians generally appreciated their new tasks in obtaining a BPMH. However, they also experienced challenges associated with their new role. Interviewees reported unease with direct patient interaction and challenges with integrating the new BPMH tasks into their regular daily duties. We found that pharmacists played a key role in the BPMH process, since they act as coaches for pharmacy technicians, transmit information to the physicians and reconcile preadmission medication lists with admission orders. Physicians stated that they benefitted from the delegation of administrative tasks to pharmacy technicians. Regarding the interprofessional collaboration, we found that pharmacy technicians in the study acted on a preliminary administrative level and did not become part of the larger treatment team. There was no direct interaction between pharmacy technicians and physicians, but rather, the supervising pharmacists acted as intermediaries.

Conclusion

The tasks assumed by pharmacy technicians need to be clearly defined and fully integrated into existing processes. Engaging pharmacy technicians may generate new patient safety risks and inefficiencies due to process fragmentation. Communication and information flow at the interfaces between professional groups therefore need to be well organised. More research is needed to understand if and under which circumstances such a model can be efficient and contribute to improving medication safety.
Vapour, gas, dust and fume occupational exposures in male patients with rheumatoid arthritis resident in Cornwall (UK) and their association with rheumatoid factor and anti-cyclic protein antibodies: a retrospective clinical study
Authors: Murphy Dan , Bellis Katy , Hutchinson David
Published: May 2018

Objectives

To quantify exposure to vapour, gas, dust and fumes (VGDF) and smoking in male rheumatoid arthritis (RA) and investigate impact on rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) levels.

Design

A retrospective observational study.

Setting

The Royal Cornwall Hospital Trust, UK. A single university hospital setting.

Participants

726 men followed up between February 2015 and August 2016, fulfilling RA diagnostic criteria.

Main outcome measures

Prevalence of VGDF exposure and smoking prior to RA diagnosis. Determination of association between VGDF, smoking and autoantibody levels.

Results

546/726 (75%) had been exposed to VGDF for >1 year. 561/726 (77%) had been smokers. Only 58/726 (8%) had no exposure to VGDF and had never smoked. A significant difference in RF levels was observed between unexposed and VGDF exposed never smokers (median RF 24 vs 36, p=0.03), more marked when comparing unexposed with ≥2 VGDF exposures (median RF 24 vs 57, p=0.02). A significant difference in RF levels was also observed between unexposed and VGDF exposed smokers (median RF 71 vs RF 95, p=0.04), more marked when comparing unexposed with ≥2 VGDF exposures (median RF 71 vs RF 113, p=0.01). A significant difference in RF titre was observed between never smokers >2 VGDF exposures and smokers with >2 VGDF exposures (RF 57 vs RF 113, p=0.02). No association of ACPA seropositivity rates or titres with VGDF exposure was observed. Smokers with >2 VGDF exposures had a significantly lower age of RA diagnosis than smokers with no VGDF exposure (53 years vs 57 years, p=0.03). All results remained similar when corrected for social class.

Conclusions

VGDF exposure increases RF levels. Combination exposure to smoking and VDGF results in higher RF levels, particularly with multiple exposures. These compelling findings demonstrate the importance of combined inhaled exposures in RF generation.
Review of the role of NICE in promoting the adoption of innovative cardiac technologies
Authors: Groves Peter H , Pomfrett Chris , Marlow Mirella
Published: May 2018

The National Institute for Health and Care Excellence (NICE) Medical Technologies Evaluation Programme (MTEP) promotes the adoption of innovative diagnostic and therapeutic technologies into National Health Service (NHS) clinical practice through the publication of guidance and briefing documents. Since the inception of the programme in 2009, there have been 7 medical technologiesguidance, 3 diagnostics guidance and 23 medtechinnovation briefing documents published that are relevant to the heart and circulation. Medical technologies guidance is published by NICE for selected single technologies if they offer plausible additional benefits to patients and the healthcare system. Diagnostic guidance is published for diagnostic technologies if they have the potential to improve health outcomes, but if their introduction may be associated with an increase in overall cost to the NHS. Medtechinnovation briefings provide evidence-based advice to those considering the implementation of new medical devices or diagnostic technologies. This review provides reference to all of the guidance and briefing medical technology documents that NICE has published that are relevant to the heart and circulation and reflect on their diverse recommendations. The interaction of MTEP with other NICE programmes is integral to its effectiveness and the means by which consistency is ensured across the different NICE programmes is described. The importance of the input of clinical experts from the cardiovascular professional community and the engagement by NICE with cardiovascular professional societies is highlighted as being fundamental to ensuring the quality of guidance outputs as well as to promoting their implementation and adoption.
Charlie Gard and the weight of parental rights to seek experimental treatment
Authors: Birchley Giles
Published: May 2018

The case of Charlie Gard, an infant with a genetic illness whose parents sought experimental treatment in the USA, brought important debates about the moral status of parents and children to the public eye. After setting out the facts of the case, this article considers some of these debates through the lens of parental rights. Parental rights are most commonly based on the promotion of a child’s welfare; however, in Charlie’s case, promotion of Charlie’s welfare cannot explain every fact of the case. Indeed, some seem most logically to extend from intrinsic parental rights, that is, parental rights that exist independent of welfare promotion. I observe that a strong claim for intrinsic parental rights can be built on arguments for genetic propriety and children’s limited personhood. Critique of these arguments suggests the scope of parental rights remains limited: property rights entail proper use; non-personhood includes only a small cohort of very young or seriously intellectually disabled children and the uniqueness of parental genetic connection is limited. Moreover, there are cogent arguments about parents’ competence to make judgements, and public interest arguments against allowing access to experimental treatment. Nevertheless, while arguments based on propriety may raise concerns about the attitude involved in envisioning children as property, I conclude that these arguments do appear to offer a prima facie case for a parental right to seek experimental treatment in certain limited circumstances.
Survey of ketolactia, determining the main predisposing management factors and consequences in Hungarian dairy herds by using a cow‐side milk test
Authors: Hejel Péter , Zechner Gerhard , Csorba Csaba , Könyves László
Published: May 2018

The aims of the survey were to determine the prevalence of ketosis in dairy herds by measuring the concentration of beta‐hydroxybutyrate (BHBA) in milk by Keto‐Test (Sanwa Kagaku Kenkyusho, Nagoya, Japan); risk factors and the relationship with postpartum diseases were investigated.

1667 early lactating (days in milk 0–75) cows were tested in 52 dairy herds in 2013 and 2014 years. In total, 29.3 per cent of samples were positive (BHBAMILK ≥100 µmol/l), including 3.7 per cent high positives (BHBAMILK ≥500 µmol/l). The prevalence was similar in herds with less than or more than 9000 kg milk yield (0.34 and 0.38, respectively, P=0.4); however, it was higher in the herds with more than 1000 cows than in smaller herds (<500 and 500–1000 cows) (0.46, P=0.03).

The BHBA level in milk was in a non‐linear positive relationship with parity (P=0.01), associated with retained placenta (P=0.0006), mastitis (P=0.02) and clinical ketosis (P<0.001).

The results confirm the high prevalence of ketolactia in Hungarian dairy herds and its links to herd‐related and cow‐related risk factors and diseases occurring commonly in fresh cows.