bluuebunny/crossref_metadata_2025 huggingface dataset:
The acute effect of beta‐guanidinopropionic acid versus creatine or placebo in healthy men (ABC‐Trial): A randomized controlled first‐in‐human trial
Authors: Karamat Fares A. , Horjus Deborah L. , Haan Yentl C. , van der Woude Lisa , Schaap Marianne C. , Oudman Inge , van Montfrans Gert A. , Nieuwland Rienk , Salomons Gajja S. , Clark Joseph F. , Brewster Lizzy M.
Published: August 2017

Aims

Increasing evidence indicates that the ATP‐generating enzyme creatine kinase (CK) is involved in hypertension. CK rapidly regenerates ATP from creatine phosphate and ADP. Recently, it has been shown that beta‐guanidinopropionic acid (GPA), a kidney‐synthesized creatine analogue and competitive CK inhibitor, reduced blood pressure in spontaneously hypertensive rats. To further develop the substance as a potential blood pressure‐lowering agent, we assessed the tolerability of a sub‐therapeutic GPA dose in healthy men.

Methods

In this active and placebo‐controlled, triple‐blind, single‐centre trial, we recruited 24 healthy men (18–50 years old, BMI 18.5–29.9 kg m−2) in the Netherlands. Participants were randomized (1:1:1) to one week daily oral administration of GPA 100 mg, creatine 5 g, or matching placebo. The primary outcome was the tolerability of GPA, in an intent‐to‐treat analysis.

Results

Twenty‐four randomized participants received the allocated intervention and 23 completed the study. One participant in the placebo arm dropped out for personal reasons. GPA was well tolerated, without serious or severe adverse events. No abnormalities were reported with GPA use in clinical safety parameters, including physical examination, laboratory studies, or 12‐Lead ECG. At day 8, mean plasma GPA was 213.88 (SE 0.07) in the GPA arm vs. 32.75 (0.00) nmol l−1 in the placebo arm, a mean difference of 181.13 (95% CI 26.53–335.72).

Conclusion

In this first‐in‐human trial, low‐dose GPA was safe and well‐tolerated when used during 1 week in healthy men. Subsequent studies should focus on human pharmacokinetic and pharmacodynamic assessments with different doses.
A systematic literature review of the use of Semantic Web technologies in formal education
Authors: Jensen Jesper
Published: August 2017

This paper presents a systematic literature review of research focused on use of Semantic Web technologies in formal educational contexts. Through systematic search, the review has identified 199 research articles, which are examined with the intention of identifying prevalent themes within the body of research within the field of formal educational use of Semantic Web technologies. The themes identified by the review are: (1) Semantic Web ontologies; (2) Efficient distribution, accessibility, retrieval, reuse and combination of educational resources; (3) Linked Data; (4) Semantic Web enhanced virtual learning environments and personalization of learning environments; (5) Semantic Web learning objects; (6) Evaluation, feedback and assessment; (7) Semantic Web services; (8) Pedagogical tools for teachers and students. Furthermore, this review seeks to examine how these themes and the use of Semantic Web technologies in formal education reflects on the ongoing discussion of how pedagogy and technology should interact. The outset of this discussion is a previous study by Dirckinck‐Holmfeld, which establishes that there is a tendency to emphasize technology over pedagogy in educational design and development.
Tracking sand‐fairways through a deformed turbidite system: the Numidian (Miocene) of Central Sicily, Italy
Authors: Pinter Patricia R. , Butler Robert W. H. , Hartley Adrian J. , Maniscalco Rosanna , Baldassini Niccolò , Di Stefano Agata
Published: August 2017

Understanding ancient deep‐water sedimentary systems that accumulated at complex plate boundaries requires confronting the stratigraphic record of deformed sedimentary successions by tracking sand‐fairways and identifying original relationships in later deformed sequences. Here, we investigate the Numidian turbidite system (early to mid‐Miocene) of Central‐East Sicily to explore a deep‐water sedimentary system deposited at an active thrust belt on the Central Mediterranean. Turbidites include multi‐metre thick‐bedded, ultra‐mature quartz sandstones that were sourced from North Africa and are now deformed and dismembered within the Apennine‐Maghrebian orogen. To date, much research has focused on the little‐deformed sections that sample discrete parts of the original turbidite pathways. Yet the bulk of these systems are represented by deformed successions and these have attracted little modern sedimentological and stratigraphic investigation. We present new data based on field mapping, sedimentological/structural fieldwork, and biostratigraphy (planktonic foraminifera and nannofossils) that focus on the Numidian turbidites of Central‐East Sicily. Thickness and facies variations, together with evidence of large‐scale sediment bypass and local substrate reworking, characterize the Numidian turbidites of the study area, consistent with a partially confined turbidite system. Our work demonstrates that the Numidian turbidite system accumulated across active structures and these provided tortuous, evolving corridors through which turbidity currents were routed, transporting coarse sand over many hundreds of km. These results provide insight on structurally confined turbidites in analogous tectonic settings and demonstrate the need to seek sedimentological and stratigraphic data from deformed and dismembered parts of deep‐water systems.
Coupling factors and exosomal packaging microRNAs involved in the regulation of bone remodelling
Authors: Zhu Sipin , Yao Felix , Qiu Heng , Zhang Ge , Xu Huazi , Xu Jiake
Published: August 2017

Bone remodelling is a continuous process by which bone resorption by osteoclasts is followed by bone formation by osteoblasts to maintain skeletal homeostasis. These two forces must be tightly coordinated not only quantitatively, but also in time and space, and its malfunction leads to diseases such as osteoporosis. Recent research focusing on the cross‐talk and coupling mechanisms associated with the sequential recruitment of osteoblasts to areas where osteoclasts have removed bone matrix have identified a number of osteogenic factors produced by the osteoclasts themselves. Osteoclast‐derived factors and exosomal‐containing microRNA (miRNA) can either enhance or inhibit osteoblast differentiation through paracrine and juxtacrine mechanisms, and therefore may have a central coupling role in bone formation. Entwined with angiocrine factors released by vessel‐specific endothelial cells and perivascular cells or pericytes, these factors play a critical role in angiogenesis–osteogenesis coupling essential in bone remodelling.
Complex genetic control of lung tumorigenesis in resistant mice strains
Authors: Dassano Alice , Pintarelli Giulia , Cotroneo Chiara E. , Pettinicchio Angela , Forcati Elena , De Cecco Loris , Borrego Andrea , Colombo Francesca , Dragani Tommaso A. , Manenti Giacomo
Published: August 2017

The SM/J mouse strain is resistant to chemically‐induced lung tumorigenesis despite having a haplotype, in the pulmonary adenoma susceptibility locus (Pas1) locus, that confers tumor susceptibility in other strains. To clarify this inconsistent genotype‐phenotype correlation, we crossed SM/J mice with another resistant strain and conducted genome‐wide linkage analysis in the (C57BL/6J × SM/J)F2 progeny exposed to urethane to induce lung tumors. Overall, >80% of F2 mice of both sexes developed from 1 to 20 lung tumors. Genotyping of 372 F2 mice for 744 informative non‐redundant SNPs dispersed over all autosomal chromosomes revealed four quantitative trait loci (QTLs) affecting lung tumor multiplicity, on chromosomes 3 (near rs13477379), 15 (rs6285067), 17 (rs33373629) and 18 (rs3706601), all with logarithm of the odds (LOD) scores >5. Four QTLs modulated total lung tumor volume, on chromosome 3 (rs13477379), 10 (rs13480702), 15 (rs6285067) and 17 (rs3682923), all with LOD scores >4. No QTL modulating lung tumor multiplicity or total volume was detected in Pas1 on chromosome 6. The present study demonstrates that the SM/J strain carries, at the Pas1 locus, the resistance allele: a finding that will facilitate identification of the Pas1 causal element. More generally, it demonstrates that lung tumorigenesis is under complex polygenic control even in a pedigree with low susceptibility to this neoplasia, suggesting that the genetics of lung tumorigenesis is much more complex than evidenced by the pulmonary adenoma susceptibility and resistance loci that have, so far, been mapped in a small number of crosses between a few inbred strains.
Mutation status of RAD51C,PALB2 and BRIP1 in 100 Japanese familial breast cancer cases without BRCA1 and BRCA2 mutations
Authors: Sato Katsutoshi , Koyasu Mio , Nomura Sachio , Sato Yuri , Kita Mizuho , Ashihara Yuumi , Adachi Yasue , Ohno Shinji , Iwase Takuji , Kitagawa Dai , Nakashima Eri , Yoshida Reiko , Miki Yoshio , Arai Masami
Published: August 2017

In addition to BRCA1 and BRCA2, RAD51C, PALB2 and BRIP1 are known as breast cancer susceptibility genes. However, the mutation status of these genes in Japanese familial breast cancer cases has not yet been evaluated. To this end, we analyzed the exon sequence and genomic rearrangement of RAD51C, PALB2 and BRIP1 in 100 Japanese patients diagnosed with familial breast and ovarian cancer and without BRCA1 and BRCA2 mutations. We detected a large deletion from exons 6 to 9 in RAD51C, 4 novel BRIP1 missense variants containing 3 novel non‐synonymous variants, c.89A>C, c.736A>G and c.2131A>G, and a splice donor site variant c.918+2T>C. No deleterious variant of PALB2 was detected. The results of pedigree analysis showed that the proband with a large deletion on RAD51C had a family history of both breast and ovarian cancer, and the families of probands with novel BRIP1 missense variants included a male patient with breast cancer or many patients with breast cancer within the second‐degree relatives. We showed that the mutation frequency of RAD51C in Japanese familial breast cancer cases was similar to that in Western countries and that the prevalence of deleterious mutation of PALB2 was possibly lower. Furthermore, our results suggested that BRIP1 mutation frequency in Japan might differ from that in Western countries.
Specific Preschool Executive Functions Predict Unique Aspects of Mathematics Development: A 3‐Year Longitudinal Study
Authors: Simanowski Stefanie , Krajewski Kristin
Published: August 2017

This study assessed the extent to which executive functions (EF), according to their factor structure in 5‐year‐olds (N = 244), influenced early quantity–number competencies, arithmetic fluency, and mathematics school achievement throughout first and second grades. A confirmatory factor analysis resulted in updating as a first, and inhibition and shifting as a combined second factor. In the structural equation model, updating significantly affected knowledge of the number word sequence, suggesting a facilitatory effect on basic encoding processes in numerical materials that can be learnt purely by rote. Shifting and inhibition significantly influenced quantity to number word linkages, indicating that these processes promote developing a profound understanding of numbers. These results show the supportive role of specific EF for specific aspects of a numerical foundation.
Role of handedness on forearm skin tissue dielectric constant (TDC) in relation to detection of early‐stage breast cancer‐related lymphedema
Authors: Mayrovitz Harvey N. , Fasen Madeline , Spagna Paige , Wong Jennifer
Published: August 2017

skin tissue dielectric constant (TDC) measurements help assess local skin water to detect incipient early‐stage lymphedema subsequent to breast cancer treatment‐related lymphedema. However, presurgery measurements are not always obtained and assessments for evolving lymphedema are only made after surgery. Thus, subsequent TDC assessments may be biased in an unknown way dependent on a patient's handedness in relation to the at‐risk arm. We investigated this issue by comparing TDC values in dominant and non‐dominant volar forearms of 31 left‐handed women and 31 right‐handed women (age range 24–84 years). Body fat and water percentages were assessed by bioimpedance at 50 KHz. Results showed that TDC values of dominant versus non‐dominant arms did not significantly differ for left‐handers or for right‐handers. There was also no statistically significant difference in absolute TDC values between left‐ and right‐handers or a statistically significant difference in dominant‐to‐non‐dominant arm ratios between left‐ and right‐handers. For the composite data set (N = 62), TDC values for dominant and non‐dominant arms were, respectively, 30·0 ± 4·6 and 29·6 ± 4·2 and the dominant‐to‐non‐dominant arm TDC ratio for combined left‐ and right‐handers was 1·015 ± 0·075. These results suggest that handedness is not a major factor when assessing lymphedema status in women who have previously been treated for breast cancer but for whom pretreatment TDCvalues have not been obtained. Moreover, these results suggest that threshold ratios of incipient subclinical unilateral lymphedema based on interarm TDC ratios apply independent of a patient's handedness for the site and tissue depths herein measured.
Feasibility study in teledermatopathology: An examination of the histopathologic features of mycosis fungoides and spongiotic dermatitis
Authors: Fertig Raymond M , Gaudi Sudeep , Cervantes Jessica , Maddy Austin , Sangueza Omar , Vu John , Ho Jonhan , Jukic Drazen M
Published: August 2017

Background

Digital pathology offers numerous advantages, allowing remote information sharing using whole slide imaging (WSI) to digitize an entire glass slide (GS) at high resolution, creating a digital slide (DS).

Methods

In this study, we examine the concordance in diagnoses made on 40 digital slides (DSs) vs traditional GSs in differentiating between spongiotic dermatitis (SD) and patch/plaque‐stage mycosis fungoides (MF).

Results

Greater interobserver concordance rate in final diagnosis of SD vs MF was observed with the utilization of DS (86.7%) compared with the utilization of GS (80%). Intraobserver concordance rate between the diagnoses rendered by a particular dermatopathologist on GS and DS was 86.7%. For all histopathological criteria, a correlation in the magnitudes of interobserver vs intraobserver discordances suggests that discordance between glass vs digital evaluation of these criteria may be largely expected subjective read variation independent of the media. Discordance in identification of histopathological features did not have a statistically significant link to discordance in diagnosis for 7 out of the 8 features.

Conclusions

The similarity between interobserver and intraobserver discordances suggests that WSI does not introduce additional barriers or variability to accurately identify histopathologic feature and to discriminate between MF and SD beyond interobserver variability.
Primary cutaneous acral CD8 positive T‐cell lymphoma with extra‐cutaneous involvement: A long‐standing case with an unexpected progression
Authors: Alberti‐Violetti Silvia , Fanoni Daniele , Provasi Matteo , Corti Laura , Venegoni Luigia , Berti Emilio
Published: August 2017

Primary cutaneous acral CD8+ T‐cell lymphoma (acral CD8+ TCL) is a new provisional entity characterized by acral skin lesions and an indolent course. We describe an extraordinary case characterized by relapsed nodules with CD8+ cytotoxic infiltrates on the left ear. After 35 years, the skin lesions spread to other acral sites, and a mass with the same histological features as the other skin lesions appeared on the nose. Multiple courses of chemotherapy led to stable disease. Histological examinations carried out at different times showed the gradual transformation of the neoplastic cells, with an increased proliferation index. Genomic analysis revealed losses in the regions harboring the genes involved in cell cycle control. This is the first case of an acral CD8+ TCL with a very long history of indolent nodular lesions progressing to extra‐cutaneous sites.
Protruding coronary stent detected by transesophageal echocardiography changes surgical procedure
Authors: Corda David M. , Dragstedt Carl , Allen Gary S. , Janelle Gregory M.
Published: August 2017

This case describes an unusual intraoperative transesophageal echocardiogram (TEE) finding of an unknown sinus of Valsalva mass in a patient undergoing an off‐pump coronary artery bypass procedure. The intraoperative TEE finding not only revealed a protruding right coronary ostial stent but also changed the surgical procedure to include an aortotomy that allowed successful removal of the stent. As interventional cardiologists begin exploring more techniques to manage difficult ostial lesions, this finding may be seen more commonly in the future. This case highlights how the use of routine TEE even in off‐pump coronary artery bypass procedures may be very beneficial.
Marx on the compatibility of freedom and necessity: A reply to David James
Authors: Kandiyali Jan
Published: August 2017

In a recent paper, David James argues for a new understanding of the compatibility of freedom and necessity in Marx's idea of a communist society. According to James, such compatibility has less to do with anything distinctive about the nature of labour and more to do with how communist producers organize the sphere of material production. In this paper, I argue that James provides a nuanced and plausible account of one part of Marx's story of the compatibility of freedom and necessity in communist society but that his account misses another, and, in my view, more fundamental part of the story. The part I have in mind centres on Marx's claim that communist producers achieve their freedom through the performance of necessary labour—by helping others to satisfy their needs. I argue that Marx is committed to a stronger claim than James wishes to make, namely, that freedom and necessity are not merely compatible but that participation in the realm of necessity is required for human freedom.
Family Profiles of Cohesion and Parenting Practices and Latino Youth Adjustment
Authors: Bámaca‐Colbert Mayra Y. , Gonzales‐Backen Melinda , Henry Carolyn S. , Kim Peter S.Y. , Roblyer Martha Zapata , Plunkett Scott W. , Sands Tovah
Published: August 2017

Using a sample of 279 (52% female) Latino youth in 9th grade (M = 14.57, SD = .56), we examined profiles of family cohesion and parenting practices and their relation to youth adjustment. The results of latent profile analyses revealed four family profiles: Engaged, Supportive, Intrusive, and Disengaged. Latino youth in the Supportive family profile showed most positive adjustment (highest self‐esteem and lowest depressive symptoms), followed by youth in the Engaged family profile. Youth in the Intrusive and Disengaged profiles showed the lowest levels of positive adjustment. The findings contribute to the current literature on family dynamics, family profiles, and youth psychological adjustment within specific ethnic groups.
Focal adhesions: a personal perspective on a half century of progress
Authors: Burridge Keith
Published: August 2017

Focal adhesions (FAs) are specialized sites within the cell where clustered integrin receptors interact with the extracellular matrix on the outside of cells and with the actin cytoskeleton on the inside. They provide strong adhesion to the matrix and transmit mechanical tension generated within cells across the plasma membrane to the external environment. Additionally, they act as scaffolds for many signaling pathways triggered by integrin engagement or mechanical force exerted on cells. Here I describe my personal perspective on FA research which I have witnessed since the initial discovery and description of FAs as electron dense regions of the ventral plasma nearly half a century ago.
Effect of environment's aggressiveness on the corrosion damage evolution and mechanical behavior of AA 2024‐T3
Authors: Vasco M. C. , Chamos A. N. , Pantelakis Sp. G.
Published: August 2017

The aim of this work is to contribute on establishing correlations between corrosion damage from accelerated laboratory corrosion tests of varying aggressiveness; by accounting for both, the metallographic features of corrosion damage and the mechanical properties of the corroded material. The work is based on the investigation of corrosion damage caused by the exposure of 2024‐T3 aluminum alloy to 3.5% NaCl solution, which is presently considered to properly represent in‐service exposure. Corrosion damage evolution was quantified for periods ranging between 500 and 3000 hours by evaluating pitting density, depth, and diameter. It was compared to available results of corrosion damage of the same alloy subjected to exfoliation corrosion test. Furthermore, the tensile properties of precorroded material in each solution were evaluated. The results allow the formulation of correlation functions between corrosion damage geometrical metallographic features from low‐ to high‐aggressiveness environment exposures. On the other hand, the degradation of tensile properties, and particularly of tensile ductility, is more pronounced in specimens exposed to higher corrosion rate environments, even when damage in both environments leads to equivalent metallographic features. This suggests significant differences in the underlying physical mechanisms of the damage accumulation process when the same material is exposed to different corrosive solutions. This work suggests the need to expand current corrosion damage interpretation, to account not only for geometrical metallographic features but also for mechanical properties of the affected material.
Constitutive relationship of polyolefin fibre–reinforced concrete: Experimental and numerical approaches to tensile and flexural behaviour
Authors: Enfedaque A. , Alberti M.G. , Gálvez J.C. , Beltrán M.
Published: August 2017

Flexural tensile tests are usually used to evaluate the suitability of fibre‐reinforced concrete (FRC) in structural applications. The constitutive relationships of FRC are derived from such tests by using several inverse analyses. Given that the structural design of FRC is based on the residual load‐bearing capacities obtained under flexural tests, the approach to analyse fracture behaviour by means of uniaxial tensile tests would mean use of more direct and reliable constitutive curves compared with those obtained by indirect means. The significance of this paper lies in the characterisation of polyolefin fibre–reinforced concrete (PFRC) not only by using fracture flexural results tests but also by comparing such results with the direct tensile behaviour of the material obtained from uniaxial tests. This comparison would both extend the knowledge of the PFRC mechanical properties and broaden the reliability of structural design by comparing the behaviour of PFRC under flexural and tensile stresses. Moreover, the suitability of an iterative method proposed by the authors for obtaining the constitutive relations of PFRC from flexural tests has been checked by performing a series of numerical simulations of the tensile tests performed. The differences in the properties obtained in the flexural tests and the tensile tests have been assessed. The experimental results gathered from the tensile tests have been accurately reproduced by using a cohesive crack approach with trilinear softening functions by the iterative inverse analysis proposed.
Use of the anion gap and intermittent hemodialysis following continuous hemodiafiltration in extremely high dose acute‐on‐chronic lithium poisoning: A case report
Authors: Komaru Yohei , Inokuchi Ryota , Ueda Yoshihiro , Nangaku Masaomi , Doi Kent
Published: August 2017

A 35‐year‐old woman intentionally took 40,000 mg of lithium carbonate, and she was transferred to our hospital with nausea, vomiting, and diarrhea. She was diagnosed as having bipolar disorder 10 years ago and was receiving oral lithium therapy. Blood test results on arrival were remarkable for a negative anion gap of −2.1 and later, the serum lithium level turned out to be as high as 15.4 mEq/L. Intubation was required because of disrupted consciousness, and continuous hemodiafiltration (CHDF) was immediately started in the intensive care unit to obtain constant removal of lithium. After adding intermittent hemodialysis (IHD) twice during the daytime to accelerate the lithium clearance, CHDF became unnecessary on day 4, and she was extubated on day 6 with complete recovery of consciousness. Close monitoring of the patient data showed recovery of the decreased anion gap as indicator of the serum lithium level reduction. On day 36, she was discharged without any complication and sequela. The current case highlighted the effective use of CHDF between IHD sessions to prevent the rebound elevation of lithium and the role of the anion gap as a surrogate marker of serum lithium concentration during the treatment.
Acute kidney injury in a postpartum woman with paroxysmal nocturnal hemoglobinuria: A case report and literature review
Authors: Nishimoto Masatoshi , Matsui Masaru , Tsushima Hideo , Tanabe Kaori , Tagawa Miho , Samejima Ken‐ich , Akai Yasuhiro , Saito Yoshihiko
Published: August 2017

Paroxysmal nocturnal hemoglobinuria is a rare clonal hematopoietic stem cell disorder characterized by intravascular hemolysis, hemoglobinuria, and inflammatory thrombotic state. Intravascular hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) can lead to acute and chronic renal injury through hemoglobin‐mediated toxicity. A 32‐year‐old pregnant woman with myelodysplastic syndrome was admitted to our hospital with severe preeclampsia. Shortly after an urgent caesarean section, she became obtunded and showed signs of acute kidney injury (AKI) with anuria, severe intravascular hemolysis, and hypermagnesemia. She was diagnosed with PNH with a positive Ham test and flow cytometry analysis. Renal magnetic resonance imaging revealed decreased signal intensity in the renal cortex due to hemosiderin deposition. Hemodialysis, plasma exchange, and administration of corticosteroids ameliorated her clinical condition and renal function. This case illustrates that careful management is required to prevent postpartum AKI in pregnant women with PNH.
Clinical significance of half‐lives of tumor markers α‐fetoprotein and des‐γ‐carboxy prothrombin after hepatectomy for hepatocellular carcinoma
Authors: Tsukamoto Masayo , Nitta Hidetoshi , Imai Katsunori , Higashi Takaaki , Nakagawa Shigeki , Okabe Hirohisa , Arima Kota , Kaida Takayoshi , Taki Katsunobu , Hashimoto Daisuke , Chikamoto Akira , Ishiko Takatoshi , Beppu Toru , Baba Hideo
Published: August 2017

Aim

The prognostic significance of the half‐lives (HLs) of α‐fetoprotein (AFP) and des‐γ‐carboxy prothrombin (DCP) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC) is unclear. We evaluated the HLs of AFP and DCP in a cohort of such patients.

Methods

This study included data on 202 patients with HCC who underwent curative hepatectomy and had preoperative AFP concentrations ≥100 ng/mL or DCP ≥200 mAU/mL. We calculated the HLs of AFP and DCP from their values just before and 1 month after hepatectomy. We identified three groups: a normalization group, tumor marker concentrations within normal range 1 month post‐hepatectomy; a long group, HL of AFP ≥7 days or DCP ≥4 days; and a short group, remaining patients. We evaluated associations between HL and prognosis.

Results

Three‐year recurrence‐free survival (RFS) in the normalization (n = 70), short (n = 71), and long groups (n = 61) was 41.3%, 46.0%, and 16.8%, respectively (P = 0.002). Five‐year overall survival (OS) of normalization, short, and long groups was 72.6, 70.6 and 43.8%, respectively (P = 0.002). Multivariate analysis revealed that long HL is an independent risk factor for poor RFS (hazard ratio [HR] 2.21, P = 0.0006) and poor OS (HR 2.70, P = 0.004). The extrahepatic recurrence rate was 21.3% (13/61) in the long group, which is higher than in the normalization group (8.6%, 6/70) (P = 0.04) and short group (9.9%, 7/71) (P = 0.07).

Conclusion

Post‐hepatectomy HLs of AFP and DCP are predictors of long‐term outcome in patients with HCC.
Clinicopathological analysis of 46 cases with CD4+ and/or CD56+ immature haematolymphoid malignancy: reappraisal of blastic plasmacytoid dendritic cell and related neoplasms
Authors: Suzuki Yuka , Kato Seiichi , Kohno Kei , Satou Akira , Eladl Ahmed E , Asano Naoko , Kono Michihiro , Kato Yuichi , Taniwaki Masafumi , Akiyama Masashi , Nakamura Shigeo
Published: August 2017

Aims

In this study, we aimed to investigate the clinicopathological features of CD4+ and/or CD56+ immature haematolymphoid malignancy (iHLM), including blastic plasmacytoid dendritic cell neoplasm (BPDCN).

Methods and results

We analysed the clinicopathological features of 46 patients diagnosed consecutively with CD4+/CD56+ iHLM. These cases were categorised into three groups based on their immunohistochemical expression of three plasmacytoid dendritic cell (pDC) markers [CD123, CD303 and T cell leukaemia/lymphoma (TCL1)]: cutaneous BPDCN (n = 35), non‐cutaneous BPDCN (n = 6) and non‐BPDCN‐type CD56+ neoplasms (n = 5). Compared to non‐cutaneous BPDCN, cutaneous BPDCN was associated with an older median age at onset (72 years versus 45 years, P < 0.05), and higher positivity for CD4 (P < 0.05), CD123 (P < 0.05) and 2–3 pDC markers (89% versus 50%, P = 0.05). Cutaneous BPDCN was divided into terminal deoxynucleotidyl transferase (TdT)+ and TdT− subgroups, which did not differ in prognosis, although TdT+ cases showed a lower median onset age (66 years versus 79 years, P < 0.05) and higher frequency of extracutaneous lesions (P < 0.05). Compared to the BPDCN groups, non‐BPDCN‐type CD56+ neoplasm cases showed higher cytoplasmic CD3 positivity (P < 0.05) and less frequent BCL‐2 expression (P < 0.05), and lacked cutaneous lesions. However, the survival curves overlapped. Notably, one case involved an unusual composite neoplasm, comprising CD56+ lymphoblastic lymphoma and mature CD56+ cytotoxic T cell lymphoma.

Conclusions

Our present data support the recognition of cutaneous BPDCN as a homogenous entity, in contrast to the non‐cutaneous form. Additional research is warranted to characterise non‐BPDCN‐type CD56+ neoplasms.
Outcomes, costs and stakeholders' perspectives associated with the incorporation of community pharmacy services into the National Health Insurance System in Thailand: a systematic review
Authors: Asayut Narong , Sookaneknun Phayom , Chaiyasong Surasak , Saramunee Kritsanee
Published: August 2017

Objectives

Identify costs, outcomes and stakeholders' perspectives associated with incorporation of community pharmacy services into the Thai National Health Insurance System and their values to all stakeholders.

Methods

Using a combination of search terms, a comprehensive literature search was performed using the Thai Journal Citation Index Centre, Health System Research Institute database, PubMed and references from recent reviews. Identified studies were published between January 2000 and December 2014. The review included publications in English and Thai on primary research undertaken in community pharmacies associated with the National Health Insurance System. Two independent authors performed study selection, data extraction and quality assessment.

Key findings

The literature search yielded 251 titles, with 18 satisfying the inclusion criteria. Clinical outcomes of community pharmacy services included control and reduction in blood pressure and blood sugar, improved adherence to medications, an increase in acceptance of interventions, and an increase in healthy behaviours. Thirty-three percentage of those at risk of diabetes and hypertension achieved normal blood sugar and blood pressure levels after being followed for 2–6 months by a community pharmacist. The cost of collaborative screening by community pharmacies and primary care units was US$ 4.5. Diabetes management costs were US$ 5.1–30.7. Community pharmacists reported high satisfaction rates. Stakeholders' perspectives revealed support for the community pharmacists' roles and the inclusion of community pharmacies as partners with the National Health Insurance System.

Conclusions

Community pharmacy services improved outcomes for diabetic and hypertensive patients. This review supports the feasibility of incorporating community pharmacies into the Thai National Health System.
Heat shock protein 70 from a thermotolerant Diptera species provides higher thermoresistance to Drosophila larvae than correspondent endogenous gene
Authors: Shilova V. Y. , Zatsepina O. G. , Garbuz D. G. , Funikov S. Y. , Zelentsova E. S. , Schostak N. G. , Kulikov A. M. , Evgen'ev M. B.
Published: August 2017

Heat shock proteins (Hsp70s) from two Diptera species that drastically differ in their heat shock response and longevity were investigated. Drosophila melanogaster is characterized by the absence of Hsp70 and other hsps under normal conditions and the dramatic induction of hsp synthesis after temperature elevation. The other Diptera species examined belongs to the Stratiomyidae family (Stratiomys singularior) and exhibits high levels of inducible Hsp70 under normal conditions coupled with a thermotolerant phenotype and much longer lifespan. To evaluate the impact of hsp70 genes on thermotolerance and longevity, we made use of a D. melanogaster strain that lacks all hsp70 genes. We introduced single copies of either S. singularior or D. melanogaster hsp70 into this strain and monitored the obtained transgenic flies in terms of thermotolerance and longevity. We developed transgenic strains containing the S. singularior hsp70 gene under control of a D. melanogaster hsp70 promoter. Although these adult flies did synthesize the corresponding mRNA after heat shock, they were not superior to the flies containing a single copy of D. melanogaster hsp70 in thermotolerance and longevity. By contrast, Stratiomyidae Hsp70 provided significantly higher thermotolerance at the larval stage in comparison with endogenous Hsp70.
Synthesis and growth mechanism of approximate spherical β‐Si3N4particles via carbothermal reduction‐nitridation method
Authors: Sun Si‐Yuan , Wang Qi , Ge Yi‐Yao , Tian Zhao‐Bo , Zhang Jie , Chen Ke‐Xin , Xie Zhi‐Peng
Published: August 2017

In this work, an efficient carbothermal reduction‐nitridation (CRN) strategy was rationally designed to directly synthesize β‐Si3N4powders with eminent dispersity and granularity uniformity. With the aid of CaO additive, the obtained β‐Si3N4particles were endowed with approximate spherical morphology and smooth surface. The size of β‐Si3N4particles could be regulated in submicro and microscale by altering N2pressures. More significantly, the underlying growth mechanism of the β‐Si3N4under elevated N2pressure was comprehensively analyzed and tentatively put forward. Benefiting from the remarkable merits, the as‐synthesized β‐Si3N4powders showed great potential for alternative fillers in the application of high thermal conductivity plastic packages.
How teachers integrate a math computer game: Professional development use, teaching practices, and student achievement
Authors: Callaghan M. N. , Long J. J. , van Es E. A. , Reich S. M. , Rutherford T.
Published: August 2017

As more attention is placed on designing digital educational games to align with schools' academic aims (e.g., Common Core), questions arise regarding how professional development (PD) may support teachers' using games for instruction and how such integration might impact students' achievement. This study seeks to (a) understand how teachers use PD resources (e.g., technology personnel and game‐use workshops) for integration; (b) determine how teachers integrate games into their instruction; and (c) examine how those teaching practices are associated with student achievement. This mixed method study used survey and interview responses from elementary school teachers (n = 863) with access to PD resources for implementing a math game intervention and standardized math‐test scores from their second‐ through sixth‐grade students (n = 10,715). Findings showed few teachers sought PD assistance for integration, but many desired such support. Some reported using integrative practices (i.e., referencing game and using game‐generated progress reports) to identify struggling students, whereas several found integration challenging. Teachers' reordering of game objectives to align with lessons and viewing of game‐based PD videos were associated with increased student math achievement in our OLS‐analysis. However, this result was no longer statistically significant within a school fixed‐effects model, suggesting school differences may influence how strongly teachers' practices are associated with student achievement.
Insulin‐producing cells derived from ‘induced pluripotent stem cells’ of patients with fulminant type 1 diabetes: Vulnerability to cytokine insults and increased expression of apoptosis‐related genes
Authors: Hosokawa Yoshiya , Toyoda Taro , Fukui Kenji , Baden Megu Yamaguchi , Funato Michinori , Kondo Yasushi , Sudo Tomomi , Iwahashi Hiromi , Kishida Marina , Okada Chihiro , Watanabe Akira , Asaka Isao , Osafune Kenji , Imagawa Akihisa , Shimomura Iichiro
Published: August 2017

Aims/Introduction

The present study was carried out to generate induced pluripotent stem cells (iPSCs) from patients with fulminant type 1 diabetes, and evaluate the cytokine‐induced apoptotic reactions of β‐like insulin‐producing cells differentiated from the iPSCs.

Materials and Methods

iPSCs were generated from fibroblasts of patients with fulminant type 1 diabetes by inducing six reprogramming factors. Insulin‐producing cells were differentiated from the iPSCs in vitro. The proportion of cleaved caspase‐3‐positive or terminal deoxynucleotidyl transferase 2′‐deoxyuridine, 5′‐triphosphate nick end labeling‐positive cells among insulin (INS)‐positive cells derived from fulminant type 1 diabetes iPSC and control human iPSC lines was evaluated under treatment with tumor necrosis factor‐α, interleukin‐1β and interferon‐γ. Ribonucleic acid sequencing was carried out to compare gene expressions in INS‐positive cells derived from fulminant type 1 diabetes iPSC and control human iPSC lines.

Results

Two iPSC clones were established from each of three patients with fulminant type 1 diabetes. The differentiation of insulin‐producing cells from fulminant type 1 diabetes iPSC was confirmed by immunofluorescence analysis and KCl‐induced C‐peptide secretion. After treatment with pro‐inflammatory cytokines, these INS‐positive cells showed higher expression of cleaved caspase‐3 than those derived from control human iPSCs. Altered expression levels of several apoptosis‐related genes were observed in INS‐positive cells derived from the fulminant type 1 diabetes iPSCs by ribonucleic acid sequencing.

Conclusions

We generated iPSCs from patients with fulminant type 1 diabetes and differentiated them into insulin‐producing cells. This in vitro disease model can be used to elucidate the disease mechanisms of fulminant type 1 diabetes.
Factors associated with greater benefit of a national reimbursement policy for blood glucose test strips in adult patients with type 1 diabetes: A prospective cohort study
Authors: Jin Sang‐Man , Baek Jong Ha , Suh Sunghwan , Jung Chang Hee , Lee Woo Je , Park Cheol‐Young , Yang Hae Kyung , Cho Jae Hyoung , Lee Byung‐Wan , Kim Jae Hyeon
Published: August 2017

Aims/Introduction

We aimed to identify factors independently associated with greater benefit of a national reimbursement policy for blood glucose test strips in adult patients with type 1 diabetes, in terms of glycemic control and the rate of severe hypoglycemia.

Materials and Methods

This was a prospective cohort study of 466 adult patients with type 1 diabetes from five tertiary referral hospitals who registered for a national reimbursement program for blood glucose strips and were then followed‐up for 12 months. Factors associated with a > 5% reduction in glycated hemoglobin (HbA1c) and decreased rate of severe hypoglycemia (SH) at 12 months from baseline were evaluated.

Results

At the end of the 12 months of follow up, 158 of 466 patients (33.9%) achieved >5% reduction in HbA1c, and 47 of 111 patients (42.3%) had a decreased rate of SH relative to baseline. Higher HbA1c (P < 0.001), lower total daily insulin dose at baseline (P = 0.048) and an increase in self‐monitoring of blood glucose (SMBG) frequency during follow up (P = 0.001) were independently associated with >5% reduction in HbA1c. A higher SMBG frequency (P < 0.001), higher rate of SH at baseline (P = 0.029) and lack of hypoglycemic unawareness (P = 0.044) were independently associated with an increase in the frequency of SMBG during follow up. Higher SMBG frequency at baseline (P < 0.001) was independently associated with a decreased rate of SH.

Conclusions

Several factors, including higher SMBG frequency at baseline, were independently associated with reduced HbA1c and a decreased rate of severe hypoglycemia, showing that patients with these characteristics derive the most benefit from reimbursement of blood glucose test strips.
Factors predicting the self‐evaluated health of hidradenitis suppurativa patients recruited from an outpatient clinic
Authors: Kjærsgaard Andersen R. , Theut Riis P. , Jemec G.B.E.
Published: August 2017

Objectives

In recent years, Hidradenitis suppurativa has received increased attention but still lack well‐defined, robust patient‐reported outcome measures. Such measures are likely to be influenced by contextual factors. We, therefore, aim to describe the association of biological and other factors with HS patient's self‐evaluated health as reflected by the EQ5D VAS score.

Methods

This cross‐sectional study measured basic information, Dermatology Life Quality Index, Major Depression Inventory and Euro‐QoL‐5D. Information obtained through questionnaires was used to create a model showing the relation between biological factors, questionnaire results and self‐evaluated health using the stepwise method for linear regression. Patients with HS (n = 805) registered at our department were invited to participate. A total of 503 (62.5%) patients replied to this survey. There was no difference in basic demographics between responders and non‐responders.

Results

Possible predictors for this study were DLQI, MDI, BMI, smoking, gender. A final model for correlation with self‐evaluated health was obtained. Significant predictors for the model were DLQI (P < 0.05), BMI points above 25 and active smoking (both: P < 0.01) and MDI (P < 0.001).

Conclusion

As this is a cross‐sectional study, it reveals several clinically relevant correlations. Smoking appears to correlate with the highest change in VAS score, but an MDI of 10 (lower than study average) or a BMI of 40 influences the results more. This study provides an assessment of how much BMI and smoking, in relation to other factors, correlate to the self‐evaluated health state of patients with HS. These may, therefore, be relevant contextual factors to the construction and interpretation of specific patient‐reported outcome measures. To improve QoL, we advocate smoking cessation and weight loss, and advice active screening for depression as over 10% of our patients qualify for a depressive diagnosis according to ICD‐10.
Fragrance contact allergens in 5588 cosmetic products identified through a novel smartphone application
Authors: Bennike N.H. , Oturai N.B. , Müller S. , Kirkeby C.S. , Jørgensen C. , Christensen A.B. , Zachariae C. , Johansen J.D.
Published: August 2017

Background

More than 25% of the adult European population suffers from contact allergy, with fragrance substances recognized as one of the main causes. Since 2005, 26 fragrance contact allergens have been mandatory to label in cosmetic products within the EU if present at 10 ppm or above in leave‐on and 100 ppm or above in wash‐off cosmetics.

Objective

To examine exposure, based on ingredient labelling, to the 26 fragrances in a sample of 5588 fragranced cosmetic products.

Methods

The investigated products were identified through a novel, non‐profit smartphone application (app), designed to provide information to consumers about chemical substances in cosmetic products. Products registered through the app between December 2015 and October 2016 were label checked according to International Nomenclature of Cosmetic Ingredients (INCI) for the presence of the 26 fragrance substances or the wording ‘fragrance/parfum/aroma’.

Results

The largest product categories investigated were ‘cream, lotion and oil’ (n = 1192), ‘shampoo and conditioner’ (n = 968) and ‘deodorants’ (n = 632). Among cosmetic products labelled to contain at least one of the 26 fragrances, 85.5% and 73.9% contained at least two and at least three of the 26 fragrances, respectively. Linalool (49.5%) and limonene (48.5%) were labelled most often among all investigated products. Hydroxyisohexyl 3‐cyclohexene carboxaldehyde (HICC/Lyral®) was found in 13.5% of deodorants. Six of the 26 fragrance substances were labelled on less than one per cent of all products, including the natural extracts Evernia furfuracea (tree moss) and Evernia prunastri (oak moss). A total of 329 (5.9%) products had one or more of the 26 fragrance substances labelled but did not have ‘parfum/fragrance/aroma’ listed on the label.

Conclusions

Consumers are widely exposed to, often multiple, well‐established fragrance contact allergens through various cosmetic products intended for daily use. Several fragrance substances that are common causes of contact allergy were rarely labelled in this large sample of cosmetic products.
Patients with psoriasis have different preferences for topical therapy, highlighting the importance of individualized treatment approaches: randomized phase IIIb PSO‐INSIGHTFUL study
Authors: Hong C‐H. , Papp K.A. , Lophaven K.W. , Skallerup P. , Philipp S.
Published: August 2017

Background

Poor adherence to topical therapy in psoriasis remains an issue; it is associated with poor clinical outcomes, reduced quality of life and increased costs. Treatment‐related factors leading to poor adherence include lack of efficacy, excessive time applying medication and poor cosmetic characteristics (e.g. slow absorption, greasiness).

Objective

To assess the topical treatment attributes that influence patient preference for fixed combination calcipotriol 50 μg/g (Cal) and betamethasone 0.5 mg/g as dipropionate (BD) foam vs. gel, as well as in comparison with the latest topical treatment (LTT) a patient received.

Methods

PSO‐INSIGHTFUL was a Phase IIIb, prospective, multicentre (Canada/Germany), open‐label, randomized, two‐arm crossover study in patients aged ≥18 years with mild‐to‐severe psoriasis (NCT02310646). Following a washout period of up to 4 weeks, patients were randomized 1 : 1 to once‐daily Cal/BD foam for 1 week, followed by Cal/BD gel for 1 week, or vice versa. Patients completed six questionnaires evaluating patient preferences.

Results

A total of 213 patients were randomized; 118 had received a topical treatment in the previous 3 months. Based on the Subject's Preference Assessment, 50% of patients preferred Cal/BD foam and 50% preferred Cal/BD gel. Based on the Topical Product Usability Questionnaire (TPUQ), overall mean scores were high for both Cal/BD foam and gel, and were often significantly in favour of both products compared with LTT. Greater differences between Cal/BD foam and gel vs. LTT occurred when the previous treatment was an ointment or cream. Cal/BD foam was generally preferred by younger patients (aged 18–39 years), whereas Cal/BD gel tended to be preferred by older patients (aged ≥40 years). Results from other questionnaires were aligned with the TPUQ.

Conclusions

Patients with psoriasis have diverse needs and different preferences for topical treatment. This knowledge may help prescribers to choose the right formulation for the right patient, potentially leading to improved adherence and better treatment outcomes.