bluuebunny/crossref_metadata_2025 huggingface dataset:
Rap1 binding and a lipid-dependent helix in talin F1 domain promote integrin activation in tandem
Authors: Gingras Alexandre R. , Lagarrigue Frederic , Cuevas Monica N. , Valadez Andrew J. , Zorovich Marcus , McLaughlin Wilma , Lopez-Ramirez Miguel Alejandro , Seban Nicolas , Ley Klaus , Kiosses William B. , Ginsberg Mark H.
Published: December 2018

Rap1 GTPases bind effectors, such as RIAM, to enable talin1 to induce integrin activation. In addition, Rap1 binds directly to the talin1 F0 domain (F0); however, this interaction makes a limited contribution to integrin activation in CHO cells or platelets. Here, we show that talin1 F1 domain contains a previously undetected Rap1 binding site of similar affinity to that in F0. A structure-guided point mutant (R118E) in F1, which blocks Rap1 binding, abolishes the capacity of Rap1 to potentiate talin1-induced integrin activation. The capacity of F1 to mediate Rap1-dependent integrin activation depends on a unique loop in F1 that transforms into an helix upon binding to membrane lipids. Basic membrane-facing residues of this helix are critical as charge reversal mutations led to dramatic suppression of talin1-dependent activation. Thus, a novel Rap1 binding site and a lipid-dependent helix in talin1 F1 work in tandem to enable a direct Rap1-talin1 interaction to cause integrin activation.

This work reveals that Rap1 GTPases bind directly to talin1 F1 domain and by ooperating with a unique lipid-dependent amphipathic helix in the F1 domain effects lin1-mediated integrin activation.
Mangrove forest structure and composition along urban gradients in Puerto Rico
Authors: Branoff Benjamin , Martinuzzi Sebastian
Published: December 2018

Urban forests are repeatedly characterized as distinct in composition and structure in comparison with their non-urban counterparts. This holds true for mangroves, although previous studies lack quantified representations of urbanness as well as any inclusion of hydrology or water chemistry, which are important influences on mangrove forest structure, composition, and function. This study uses LiDAR and ground-based measurements of mangroves within well quantified urban gradients in Puerto Rico to test for the relative importance of urbanization alongside flooding metrics and surface water chemistry in explaining observed patterns of forest structure and composition. In simple regression, urban metrics were the most powerful predictors of forest composition but not structure. Results show higher tree diversity but lower mangrove diversity in the most urban forests. Structural measurements, however, were best explained by flooding, surface water chemistry, and non-urban land cover metrics. Nitrogen concentrations best explained stem density and tree size, while flooding metrics best explained stand biomass and basal area, and surrounding vegetation cover best explained canopy cover and height metrics. In multiple regression, land cover and surface water chemistry were more important than flooding, with population density again being the most important variable in explaining mangrove forest diversity. Results show that urbanization is an important influence on mangrove composition and basal area, leading to higher tree diversity and lower basal area, consistent with patterns in terrestrial forests. But urban mangrove forests are also lower in mangrove diversity and tend to have representation only by Laguncularia racemosa. Nitrogen concentrations and surrounding vegetation cover, both of which are indirectly influenced by urbanization, were positively related to tree size and canopy cover and height, respectively. These tests suggest urbanization is an important influence on mangrove forest structure and composition, but that flooding and water chemistry must also be considered when managing these forests.
The FXR2P low complexity domain drives assembly of multiple fibril types with differing ribosome association in neurons
Authors: Stackpole Emily E , Akins Michael R , Ivshina Maria , Murthy Anastasia C , Fawzi Nicolas L , Fallon Justin R
Published: December 2018

RNA binding proteins (RBPs) typically function in higher order assemblages to regulate RNA localization and translation. The Fragile X homolog FXR2P is an RBP essential for formation of Fragile X granules, which associate with axonal mRNA and ribosomes in the intact brain. Here we performed an unbiased EGFP insertional mutagenesis screen to probe for FXR2P domains important for assembly into higher order structural states in neurons. Fifteen of the 18 unique in-frame FXR2PEGFP fusions tested formed cytosolic granules. However, EGFP insertion within a 23 amino acid region of the low complexity (LC) domain induced formation of distinct FXR2PEGFP fibrils (A and B) that were found in isolation or assembled into highly ordered bundles. Type A and B complexes exhibited different developmental timelines, ultrastructure and ribosome association with ribosomes absent from bundled Type B fibrils. The formation of both fibril types was dependent on an intact RNA binding domain. We conclude that formation of these higher order FXR2P assemblages with alternative structural and compositional states in neurons requires collaboration between the LC and RNA binding domains.
Beyond the dichotomy: Incarceration dosage and mental health*
Authors: Porter Lauren C. , DeMarco Laura M.
Published: December 2018

The findings from a growing body of research reveal that incarceration is detrimental for both physical and mental health. Incarceration, however, is typically conceptualized and operationalized as a dichotomy; individuals either have, or have not, been incarcerated. Considering that incarceration can range from one day to several years, a dichotomous measure may be overlooking important variations across lengths of exposure. In addition, most inmates are incarcerated more than once. In this study, we help to fill this gap by examining the relationship between incarceration dosage, measured as time served and number of spells, and mental health among a sample of young adults from the National Longitudinal Study of Youth 1997. By using fixed‐effects modeling, we find that the number of spells and the months incarcerated are positively related to mental health symptoms and the likelihood of depression. The association, however, is contingent on whether a respondent is currently or formerly incarcerated. Among current inmates, more time served is expected to improve mental health and the number of spells is unrelated to either outcome.
Analysis of the associated factors for severe weight loss after minimally invasive McKeown esophagectomy
Authors: Wang Peiyu , Li Yin , Sun Haibo , Zhang Ruixiang , Liu Xianben , Liu Shilei , Wang Zongfei , Zheng Yan , Yu Yongkui , Chen Xiankai , Li Haomiao , Zhang Jun , Liu Qi
Published: December 2018

Background

This study investigated the risk factors for severe weight loss (SWL) within one year after minimally invasive McKeown esophagectomy.

Methods

Esophageal cancer patients who underwent McKeown esophagectomy between January and July 2017 were prospectively enrolled. Preoperative body weight (PBW) was chosen as the initial body weight.

Results

Forty‐four patients were enrolled and successfully followed up for one year. Median weight loss was 7.4% (quartile: 5.3–8.1%) and 12.6% (quartile: 8.8–17.7%) four weeks and one year after surgery, respectively. Accelerated weight loss occurred during the first two weeks after discharge, with median weight loss of 5.6% (quartile: 4.2–7.1%). Multivariable analysis showed that age ≥ 70 years (odds ratio [OR] 7.65; P = 0.030), preoperative sarcopenia (OR 7.18; P = 0.030), the first surgery in the daily schedule (OR 6.87; P = 0.032) and vocal cord paralysis (OR 12.30; P = 0.046) were independent risk factors for short‐term (4 weeks) SWL (> 7.5% PBW), while an American Society of Anesthesiologists score of 3–4 (OR 6.58; P = 0.047), a high fat‐free mass (OR 21.91; P = 0.003), and vocal cord paralysis (OR 25.83; P = 0.017) were independent risk factors for long‐term (1 year) SWL (> 13.0% PBW) after esophagectomy. Postoperative symptoms of insomnia, appetite loss, dysphagia, eating difficulties, and taste issues were also related to SWL.

Conclusions

In esophageal cancer patients who have undergone esophagectomy, the first two weeks after hospital discharge is a key period for nutrition intervention. Patients with associated factors for SWL require postoperative nutrition support.
Asymmetrical subcortical plasticity entails cognitive progression in older individuals
Authors: Esteves Madalena , Moreira Pedro S. , Marques Paulo , Castanho Teresa C. , Magalhães Ricardo , Amorim Liliana , Portugal‐Nunes Carlos , Soares José M. , Coelho Ana , Almeida Armando , Santos Nadine C. , Sousa Nuno , Leite‐Almeida Hugo
Published: December 2018

Structural brain asymmetries have been associated with cognition. However, it is not known to what extent neuropsychological parameters and structural laterality covary with aging. Seventy‐five subjects drawn from a larger normal aging cohort were evaluated in terms of MRI and neuropsychological parameters at two moments (M1 and M2), 18 months apart. In this time frame, asymmetry as measured by structural laterality index (ΔLI) was stable regarding both direction and magnitude in all areas. However, a significantly higher dispersion for this variation was observed in subcortical over cortical areas. Subjects with extreme increase in rightward lateralization of the caudate revealed increased M1 to M2 Stroop interference scores, but also a worsening of general cognition (MMSE). In contrast, subjects showing extreme increase in leftward lateralization of the thalamus presented higher increase in Stroop interference scores. In conclusion, while a decline in cognitive function was observed in the entire sample, regional brain asymmetries were relatively stable. Neuropsychological trajectories were associated with laterality changes in subcortical regions.
Identification of programmed cell death 1 and its ligand in the testicular tissue of mice
Authors: Wang Li‐Ling , Li Zhi‐Hui , Duan Yong‐Gang , Yuan Shui‐Qiao , Mor Gil , Liao Ai‐Hua
Published: December 2018

Problem

This study aims to determine the expression and localization of programmed cell death 1 (PD‐1) and programmed cell death 1 ligand 1 (PD‐L1) in the testes of mice at different developmental stages.

Method of study

By means of RT‐qPCR, Western blot and immunofluorescence, the expression and localization of PD‐1 and PD‐L1 were detected in the testicular tissues of mice at different postnatal times: P7, P14, P21, P28, P35, and adulthood. Meanwhile, the level of soluble PD‐L1 (sPD‐L1) was evaluated by ELISA in the testicular interstitial fluid (IF) of the adult mice, culture supernatants of TM4 cell lines (Sertoli cells lines), and primary Sertoli cells at P14.

Results

Pd‐1 mRNA levels were unexpectedly low. From P7 to P21, there was limited PD‐1 protein detected while PD‐1 was evident at P28 and afterward at significantly higher levels than at P14 and P21 (P < 0.05). Despite being found in the interstitial area at P7, P14, and P21, PD‐1 was also detected in the germ cells of the seminiferous tubules after P28. Pd‐l1 mRNA exhibited age‐related changes, peaking at P21, while PD‐L1 protein was constitutively expressed at any stage, specifically localized in the nucleus of Sertoli cells. Moreover, the level of sPD‐L1 in IF was significantly higher than that in the culture supernatants of both TM4 and primary Sertoli cells at P14.

Conclusions

PD‐1 and PD‐L1 were present in the testicular tissue of adult mice. The expression and localization of PD‐1 fluctuated with age, and PD‐1 was mainly localized to advanced germ cells, suggesting that it may play a role in spermiogenesis. PD‐L1 was constitutively expressed in the nucleus of Sertoli cells, which could secrete sPD‐L1 into the testicular interstitial space and thus may be involved in testicular immune privilege.
Incidence of testicular tumor subtypes according to the updated WHO classification, North Rhine‐Westphalia, Germany, 2008–2013
Authors: Stang A. , Rusner C. , Trabert B. , Oosterhuis J. W. , McGlynn K. A. , Heidinger O.
Published: December 2018

Background

In 2016, the WHO introduced an updated classification for testicular tumors. The application of this updated classification to cancer registry data requires some recoding of tumors.

Objectives

The aim of this study was to provide up‐to‐date population‐based incidence estimates of subtypes of testicular germ cell tumors (TGCT) according to the updated classification.

Material and methods

We reviewed 2251 pathology reports (42.9%) out of 5252 testicular tumors at the cancer registry of North Rhine‐Westphalia for the years 2008–2013. We used population counts to estimate age‐standardized incidence rates per million person‐years (EUROSTAT revised European Standard Population).

Results

The application of the updated WHO classification resulted in a recoding of 8.9% of all testicular tumors. While the recodings have no influence on the incidence of seminomatous and non‐seminomatous TGCTs that include mixed TGCTs, they influence the incidence of individual histological types of seminomatous and non‐seminomatous TGCTs. Among the 4935 testicular germ cell tumors (TGCT), 23.7% were mixed TGCTs. Overall, 46.9% of all mixed TGCTs included seminoma and age‐standardized incidence rates were highest for the combination seminoma plus embryonal carcinoma (5.9 per million person‐years) and embryonal carcinoma plus teratoma (4.9 per million person‐years). The median age at diagnosis was higher for mixed TGCTs including seminoma (31 years) than those that did not include seminoma (28 years).

Discussion and conclusions

Population‐based incidence time trends for seminomatous and non‐seminomatous TGCTs that include mixed TGCTs are not distorted by the introduction of the WHO update. Trend distortions can only be expected if time trends of individual histological subtypes of the seminomatous and non‐seminomatous TGCTs are examined.
Protracted vacuum extraction and neonatal intracranial hemorrhage among infants born at term: a nationwide case‐control study
Authors: Åberg Katarina , Norman Mikael , Pettersson Karin , Järnbert‐Pettersson Hans , Ekéus Cecilia
Published: December 2018

Introduction

The association between vacuum extraction and intracranial hemorrhage has been debated. We sought to investigate the impact of protracted vacuum extraction on the risk for neonatal intracranial hemorrhage in term infants.

Material and methods

This nationwide case‐control study covered Swedish maternity wards from 1999 to 2013. All term, live‐born infants diagnosed with neonatal intracranial hemorrhage after vacuum‐assisted delivery were included as cases (n = 167). For each case, 3 vacuum‐delivered controls, without a diagnosis for intracranial hemorrhage, were selected (n = 546 controls). Conditional logistic regression analysis was used to study the association between protracted extraction (defined as vacuum duration > 15 min, > 6 pulls or > 2 cup detachments), and neonatal intracranial hemorrhage.

Results

Extractions exceeded 15 min among 33% of the cases, vs 5% of the controls. More than six pulls were used in 25% of the cases and in 4% of the controls, and more than two cup detachments occurred in 3.6% of the cases and in 0.6% of the controls. Compared with extractions adhering to safety recommendations, the odds for intracranial hemorrhage were nine‐fold (OR 8.91, 95%, CI 5.22‐15.20) among infants exposed to a protracted extraction. After adjustments for potential confounders, the OR decreased to 8.04 (95% CI 4.49‐14.38).

Conclusions

The strong association between protracted extraction and intracranial hemorrhage suggests that adherence to safety recommendations may reduce the risk for intracranial hemorrhage in infants delivered by vacuum extraction. However, safe limits for vacuum duration and number of pulls are still unknown and intracranial hemorrhage may occur even when performed in accordance with safety recommendations.
In‐hospital cost analysis of prostatic artery embolization compared with transurethral resection of the prostate: post hoc analysis of a randomized controlled trial
Authors: Müllhaupt Gautier , Hechelhammer Lukas , Engeler Daniel S. , Güsewell Sabine , Betschart Patrick , Zumstein Valentin , Kessler Thomas M. , Schmid Hans‐Peter , Mordasini Livio , Abt Dominik
Published: December 2018

Objectives

To perform a post hoc analysis of in‐hospital costs incurred in a randomized controlled trial comparing prostatic artery embolization (PAE) and transurethral resection of the prostate (TURP).

Patients and Methods

In‐hospital costs arising from PAE and TURP were calculated using detailed expenditure reports provided by the hospital accounts department. Total costs, including those arising from surgical and interventional procedures, consumables, personnel and accommodation, were analysed for all of the study participants and compared between PAE and TURP using descriptive analysis and two‐sided t‐tests, adjusted for unequal variance within groups (Welch t‐test).

Results

The mean total costs per patient (±sd) were higher for TURP, at €9137 ± 3301, than for PAE, at €8185 ± 1630. The mean difference of €952 was not statistically significant (P = 0.07). While the mean procedural costs were significantly higher for PAE (mean difference €623 [P = 0.009]), costs apart from the procedure were significantly lower for PAE, with a mean difference of €1627 (P < 0.001). Procedural costs of €1433 ± 552 for TURP were mainly incurred by anaesthesia, whereas €2590 ± 628 for medical supplies were the main cost factor for PAE.

Conclusions

Since in‐hospital costs are similar but PAE and TURP have different efficacy and safety profiles, the patient's clinical condition and expectations – rather than finances – should be taken into account when deciding between PAE and TURP.
Kazinol U inhibits melanogenesis through the inhibition of tyrosinase‐related proteins via AMP kinase activation
Authors: Lim Jihyun , Nam Sorim , Jeong Ji Hye , Kim Min Jung , Yang Young , Lee Myeong‐Sok , Lee Hee Gu , Ryu Jae‐Ha , Lim Jong‐Seok
Published: December 2018

Background and Purpose

Kazinol U is a prenylated flavan isolated from an extract of Broussonetia kazinoki Sieb (Moraceae). Kazinol U has shown cytoprotective effects against cytokine‐induced apoptotic cell death and induces AMP kinase (AMPK) activation through LKB1 activation. However, kazinol U has not been tested as a regulator of melanogenesis, although bark extract of B. kazinoki has been used as a cosmetic ingredient for skin conditioning.

Experimental Approach

We cultured mouse, human melanoma cells and normal human melanocytes to demonstrate anti‐melanogenic effects of kazinol U. A tyrosinase activity assay, Western blot, RT‐qPCR and a luciferase reporter gene assay were performed to determine the anti‐melanogenic mechanisms of kazinol U. We confirmed its effect on melanogenesis in vivo using zebrafish.

Key Results

Kazinol U inhibited the expression and activity of tyrosinase, the rate‐limiting enzyme in melanogenesis, and reduced tyrosinase expression and activity in response to cAMP‐inducing agents. Kazinol U reduced the expression of other melanogenic enzymes, such as tyrosinase‐related protein (Tyrp) 1 and Tyrp2, and down‐regulated microphthalmia‐associated transcription factor (MITF), the master regulator of the tyrosinase gene family. Moreover, kazinol U induced phosphorylation of AMPK and MAPK proteins, which are MITF inhibitors. It also exhibited anti‐melanogenic effects in zebrafish, a recently developed in vivo model.

Conclusions and Implications

Our findings suggest that kazinol U reduces melanogenesis via its inhibitory effect on MITF and its downstream target genes, tyrosinase, Tyrp1 and Tyrp2. This work may provide a basis for the application of kazinol U for the treatment of hyperpigmentation skin disorders.
Provenance analysis of detrital monazite, zircon and Cr‐spinel in the northern Tibetan Plateau: Implications for the Paleozoic tectonothermal history of the Altyn Tagh and Qimen Tagh Ranges
Authors: Zhu Wen , Wu Chaodong , Wang Jialin , Zhou Tianqi
Published: December 2018

Sediment provenance studies have proven to be an effective method to extract the sediment provenance and tectonic process information recorded by detrital minerals. In this contribution, we conducted detrital monazite and zircon U‐Pb geochronology and detrital Cr‐spinel major element chemistry analyses on samples from the Qaidam Basin to reconstruct the spatial and temporal evolution of the Altyn Tagh Range and the Qimen Tagh Range in the northern Tibetan Plateau. Based on the significant variation in [Th/U]N, [Gd/Lu]N and [Eu/Eu*]N and the U‐Pb ages of the monazite and zircon, the South Altyn Tagh subduction‐collision belt and the North Qimen Tagh Range were, respectively, the main provenances of the Ganchaigou section and the Dongchaishan‐Weitai section in the Qaidam Basin in the Cenozoic. Paleozoic peak metamorphism, retrograde granulite‐facies metamorphism and amphibolite‐facies metamorphism in the South Altyn Tagh subduction‐collision belt were well recorded by the detrital monazite. In comparison, the detrital zircon is a better indicator of igneous events than detrital monazite. Synthesizing the detrital monazite, zircon and Cr‐spinel data, we concluded that the South Altyn Tagh Ocean and Qimen Tagh Ocean existed in the early Paleozoic and that the Altyn Tagh terrane and Qimen Tagh terrane experienced different Paleozoic tectonothermal histories. The collision between the Qaidam terrane and the Azhong terrane occurred at ca. 500 Ma. The Middle Ordovician was the key period of transformation from the collision‐induced compressional environment to an extensional environment in the area of the South Altyn Tagh Range. In the early Paleozoic, the Qimen Tagh area was characterized by the subduction of oceanic crust.
Comparison of heat generation between guided and conventional implant surgery for single and sequential drilling protocols—An in vitro study
Authors: Frösch Leonie , Mukaddam Khaled , Filippi Andreas , Zitzmann Nicola U. , Kühl Sebastian
Published: December 2018

Objectives

The aim of this in vitro study was to compare the heat generation during guided osteotomy preparation (GOP) with that of a conventional approach (CA) for a single and sequential drilling protocol.

Methods

Temperature measurements were performed during standardized osteotomy preparations in polyurethane foam blocks with an infrared camera. The four groups included single and sequential drilling with and without the use of a surgical guide. In the first group (single CA) and the second group (single GOP), only the final drills diameters were applied once. In the third group (sequential CA) and the fourth group (sequential GOP), two to four drills with increasing diameters were applied. Guided and conventional as well as single and sequential drilling were compared using a one‐way ANOVA with Tukey post hoc test. The level of statistical significance was set at α = 0.05.

Results

Guided osteotomy preparation showed statistically significant higher temperatures than CA for the 2.2 mm, the 3.5 mm, and the 4.2 mm drill (p = 0.032, p = 0.005 and p < 0.001, respectively). Sequential drilling led to higher heat generation and longer duration of latent heat than single drilling. For all drilling procedures, the duration of heat exposure over critical temperature was less than 1 min, except for the sequential GOP drilling protocol with the 4.2 mm drill (76 s).

Conclusions

Guided drilling requires specific attention to heat development. When guided implant surgery is performed, a single drilling procedure could alleviate heat production compared to a sequential procedure.
Synchronous colorectal carcinoma: predisposing factors and characteristics
Authors: Chin C.‐C. , Kuo Y.‐H. , Chiang J.‐M.
Published: December 2018

Aim

Whether some diseases are related to the occurrence of synchronous colorectal carcinoma (sCRC) is unknown. Investigating the risk factors and presentation of sCRC could aid in the treatment of patients with colorectal cancer (CRC). The prognosis of sCRC compared with that of solitary CRC remains unclear.

Methods

A total of 17 093 CRC patients were recruited between 1st January 1995 and 31th December 2016. The risk factors of sCRC development were assessed using univariate and multivariate logistic regression. The effect of sCRC on survival was analysed using the multivariate Cox regression model.

Results

The prevalence of sCRC was 5.6% in this study. The independent risk factors of sCRC development were advanced age (P < 0.001), male sex (P < 0.001), hereditary cancer (P < 0.001), hypertension (P < 0.001) and liver cirrhosis (P = 0.024). Compared with solitary CRC, a higher number of patients with sCRC presented with an abnormal carcinoembryonic antigen (CEA) level (P = 0.011), anaemia (P < 0.001) and hypoalbuminemia (P < 0.001). Multivariate analysis revealed that sCRC was a significant factor for poor survival in patients at TNM Stage I [hazard ratio (HR) = 1.86; P < 0.001], Stage II (HR = 1.65; P < 0.001) and Stage III (HR = 1.40; P < 0.001).

Conclusions

In addition to hypertension and liver cirrhosis, other risk factors for sCRC were identified in this study. The prognosis of patients with sCRC was significantly worse than that of those with solitary CRC through TNM Stages I to III. Anaemia, abnormal CEA and hypoalbuminemia were more commonly seen in patients with sCRC.
Is there any role for thoracoscopy in the diagnosis of benign pleural effusions
Authors: Anevlavis Stavros , Varga Csaba , Nam Tse Hoi , Man Raymond Wong Chun , Demetriou Artemios , Jain Nitin , Lanfranco Anthony , Froudarakis Marios E.
Published: December 2018

Thoracoscopy in the endoscopy suite, has a high diagnostic yield of undiagnosed pleural effusions with minimal and mild complications. Whereas relatively minimal invasive techniques, such as thoracentesis, image‐guided pleural biopsy or blind pleural biopsy, can yield sufficient cell or tissue material to establish the diagnosis of the underlying condition, more definite invasive diagnostic and therapeutic procedure, such as thoracoscopy, may be required for accurate sampling and diagnosis, and further provide real‐time treatment options in same procedure. If thoracoscopy is considered the gold standard for the diagnosis is a fact in case. The current review aims to provide informations on thoracoscopy indications in benign pleural diseases according to up to date publications.
Molecular signatures and clinical outcomes of transplant glomerulopathy stratified by microvascular inflammation and donor‐specific antibody
Authors: Lubetzky Michelle , Hayde Nicole , Ó Broin Pilib , Ajaimy Maria , Bao Yi , Mohammed Omar , Schwartz Daniel , Pullman James , Akalin Enver
Published: December 2018

Background

We investigated clinical outcomes and molecular signatures of transplant glomerulopathy (TG) stratified by microvascular inflammation (MVI) and donor‐specific antibody (DSA) status.

Methods

We performed a retrospective review of 749 kidney transplant patients who received a for‐cause kidney biopsy from 2009 to 2014. We classified TG as MVI positive (MVI+) or MVI negative (MVI−), and with or without DSA. We obtained gene expression profiles for 44 biopsies by Affymetrix HuGene 1.0 ST expression arrays.

Results

A total of 100 patients had TG; 49 were MVI+, and 51 were MVI−. After a median post‐biopsy follow‐up of 2.08 years (range 0.43‐4.59), Kaplan‐Meier survival analysis demonstrated worse allograft survival in MVI+ TG patients compared with MVI− TG patients (P = 0.01), and time to graft failure was significantly shorter in MVI+ patients (1.08 ± 1.01 years vs 2.3 ± 1.8 years; P = 0.002). DSA status did not affect graft survival within MVI+ or MVI− groups. Analysis of pathogenesis‐based transcripts (PBT) showed that MVI+ TG biopsies had increased expression of gamma interferon and rejection (GRIT) and DSA‐associated transcripts (DSAST), as observed in antibody‐mediated rejection. MVI− TG biopsies had increased expression of cytotoxic and regulatory T cell‐ and B cell‐associated transcripts but not GRIT or DSAST. DSA status had no effect on expression of any PBTs studied in MVI− TG biopsies.

Conclusions

Graft survival in TG is significantly worse in the presence of MVI. Gene expression profiles of MVI+ TG resemble antibody‐mediated rejection while gene expression profiles of MVI− TG resemble cell‐mediated rejection regardless of DSA status.
Comparative effectiveness of exenatide once‐weekly versus liraglutide in routine clinical practice: A retrospective multicentre study and meta‐analysis of observational studies
Authors: Fadini Gian Paolo , Bonora Bendetta Maria , Lapolla Annunziata , Fattor Bruno , Morpurgo Paola Silvia , Simioni Natalino , Avogaro Angelo ,   for the DARWIN‐T2D Network
Published: December 2018

In this study, we retrospectively compared the effectiveness of exenatide once‐weekly (ExeOW) versus liraglutide in non‐insulin treated patients with type 2 diabetes followed under routine care. We also present a meta‐analysis of similar observational studies available in the literature. In our multicentre retrospective study, patients initiating ExeOW (n = 204) or liraglutide (n = 410) had similar baseline clinical characteristics. Change in HbA1c at 6 months was superimposable in the two groups (−0.7% ± 1.0%), and changes in body weight were also similar (ExeOW ‐2.2 ± 3.7 kg; liraglutide −2.5 ± 4.3 kg; p = 0.457). Discontinuation rates were numerically but not significantly lower for ExeOW versus liraglutide. Pooling these data with those of observational studies available in the literature yielded superimposable effects between the two groups for the change in HbA1c and body weight, with a higher risk of discontinuation (mainly based on pharmacy refill rates) for ExeOW. We conclude that, in patients under routine care, initiation of ExeOW provides similar benefits on HbA1c and body weight as initiation of liraglutide. These data help view the results of randomized controlled trials from the perspective of their application in routine clinical practice.
Policy strategies for economic development in Cuba: A simulation model analysis
Authors: Castellacci Fulvio , Dizyee Kanar
Published: December 2018

The economic reforms implemented in Cuba since 2008 do not adequately deal with the structural issues that hamper the country's economic development. The article presents a system dynamics model to investigate Cuba's development process, and a simulation analysis to compare different policy scenarios that may be realized in the future as economic reforms will continue. The results indicate that the most effective development policy would be to combine active public policies to enhance the research and development sector on the one hand, and to foster the emergence of an efficient private sector that will develop the capital infrastructure of the economy on the other.
Haploidentical transplantation using low‐dose alemtuzumab: Comparison with haploidentical transplantation using low‐dose thymoglobulin
Authors: Kako Shinichi , Gomyo Ayumi , Akahoshi Yu , Harada Naonori , Kameda Kazuaki , Ugai Tomotaka , Wada Hidenori , Ishihara Yuko , Kawamura Koji , Sakamoto Kana , Sato Miki , Terasako‐Saito Kiriko , Kimura Shun‐ichi , Kikuchi Misato , Nakasone Hideki , Kanda Junya , Kanda Yoshinobu
Published: December 2018

Objectives

To establish the optimal strategy for haploidentical hematopoietic stem cell transplantation (HSCT).

Methods

We performed a prospective study on haploidentical HSCT using low‐dose alemtuzumab. Alemtuzumab was added at 0.25 mg/kg for 2 days. The primary outcome measure was the survival rate with the engraftment of donor cells and without grade III‐IV acute graft‐vs‐host disease (GVHD) at 60 days after transplantation.

Results

Fourteen adult patients with advanced hematological disease were enrolled. The primary outcome measure was achieved in 86% of the patients. Six patients experienced relapse/progression. Non‐relapse death was observed in three patients, and all of them had a history of previous allogeneic HSCT. Overall survival and progression‐free survival rates at 1 year were 51% and 43%, respectively. Four patients were suspected to have herpes simplex virus infection and three had aseptic meningitis under the use of acyclovir at 200 mg. There were no deaths due to viral infection. Compared to those who underwent haploidentical HSCT using thymoglobulin, patients with alemtuzumab showed a slower recovery of CD8+ T‐cells and lower incidences of GVHD and EB virus reactivation.

Conclusions

Haploidentical HSCT using low‐dose alemtuzumab can be performed safely. We need to overcome the high relapse/progression rate in non‐remission patients.
Interaction of increasing ICU survival and admittance policies in patients with hematologic neoplasms: A single center experience with 304 patients
Authors: Kondakci Mustafa , Reinbach Marc C. , Germing Ulrich , Kobbe Guido , Fenk Roland , Schroeder Thomas , Quader Jasmin , Zeus Tobias , Rassaf Tienush , Haas Rainer
Published: December 2018

Objective

We evaluated the development of ICU survival of patients with hematopoietic malignancies and discussed changes in admittance policies.

Method

We compared 166 patients treated between 2009 and 2012 with 138 patients treated between 2013 and 2016. Patient characteristics and outcome were analyzed.

Results

ICU survival was 45.2% in the first group and 66.7% in the second (P < 0.0005). Infection (P = 0.033), invasive ventilation (IMV) (P = 0.014) and SOFA score at day 3 (SOFA‐48h) (P = 0.007) independently indicated worse ICU survival in the first group, IMV (P = 0.013) and SOFA‐48h (P = 0.019) in the second group. The second group showed lower frequencies of infection (P = 0.003), IMV (P < 0.0005), need for vasopressors (P < 0.0005) and RRT (P = 0.021) at ICU admittance than the first. Further, the accumulation of hyperkaliemia, acidosis, low bicarbonate, high lactate and hypotension showed worse ICU survival in both groups and was lower in second group.

Conclusion

ICU survival increased distinctly between 2009 and 2016. At ICU admittance, parameters showing severity of illness were less frequent in the second group. Our findings indicate general treatment improvements especially of infections and changes of admittance policies toward early ICU admittance during time.
Topic search filters: a systematic scoping review
Authors: Damarell Raechel A. , May Nikki , Hammond Sue , Sladek Ruth M. , Tieman Jennifer J.
Published: December 2018

Background

Searching for topics within large biomedical databases can be challenging, especially when topics are complex, diffuse, emerging or lack definitional clarity. Experimentally derived topic search filters offer a reliable solution to effective retrieval; however, their number and range of subject foci remain unknown.

Objectives

This systematic scoping review aims to identify and describe available experimentally developed topic search filters.

Methods

Reports on topic search filter development (1990‐) were sought using grey literature sources and 15 databases. Reports describing the conception and prospective development of a database‐specific topic search and including an objectively measured estimate of its performance (‘sensitivity’) were included.

Results

Fifty‐four reports met inclusion criteria. Data were extracted and thematically synthesised to describe the characteristics of 58 topic search filters.

Discussion

Topic search filters are proliferating and cover a wide range of subjects. Filter reports, however, often lack clear definitions of concepts and topic scope to guide users. Without standardised terminology, filters are challenging to find. Information specialists may benefit from a centralised topic filter repository and appraisal checklists to facilitate quality assessment.

Conclusion

Findings will help information specialists identify existing topic search filters and assist filter developers to build on current knowledge in the field.
Strengthen adhesion between zirconia and resin cement using different surface modifications
Authors: Akay Canan , Çakırbay Tanış Merve , Şen Murat , Akkaş Kavaklı Pınar
Published: December 2018

The aim of this research was to assess the influence of different surface modifications on the bond strength between resin cement and zirconia ceramics. Eighty‐four zirconium samples were prepared. Four different surface treatments were applied; nano‐alumina coating, 2 minutes gas‐phase fluorination, 50 μm alumina airborne‐particle abrasion, and 50 μm airborne‐particle abrasion + 2 minutes gas‐phase fluorination. Then specimens were bonded to resin cement. Half of the samples were then incubated in 37°C distilled water for 24 hours. The remaining samples were subjected to thermocycling for 5000 cycles. Shear‐bond strength testing was applied at a cross head speed of 5 mm/s. Two‐way ANOVA was used in comparison between groups. There is a significant difference between the groups with 5000 cycles and the groups with 24 hours of water cycling. The highest shear‐bond strength values were observed in the groups with airborne‐particle abrasion + 2 minutes fluorination (27.57 MPa) and nano‐alumina coating (26.45 MPa) which were not subjected to thermal cycling. Nano‐alumina coating of the zirconia surface and the 2 minutes gas‐phase fluorination method following airborne‐particle abrasion process increased bond strength between resin cement and zirconia.
Analytical strategies to identify and quantify organic admixtures in functionalized mineral model systems
Authors: Hahn Dominik , Sax Almuth , Quirmbach Peter , Faure Jean‐Michel , Benyahia Kamel , Wöhrmeyer Christoph , Parr Chris
Published: December 2018

This study describes an analytical approach to identify and quantify organic admixtures, which are increasingly being used in multifunctional additive systems, such as calcium aluminate cement‐based dry mix formulations. The investigations refer to a wide range of established organic admixtures used in high performance industrial concrete applications, such as flow agents, retarders, or organic plasticizers, which are added in dosages of up to 5% (to the mass of cement). Based on specific considerations, a consistent approach was outlined by combining the output of complementary analytical techniques. These analytical methods included Thermogravimetric Analysis and Differential Scanning Calorimetry coupled with Mass Spectrometry, in combination with Fourier Transform Infrared Spectroscopy and Morphologically Directed Raman Spectroscopy, as well as Total Carbon Analysis. Within the scope of the aforementioned studies, the applied methods were validated for stringent detection limits (LOD < 0.05%) and precision demands (SD 1% to 7% with R2 > 0.99).
The effects of extruded black rice flour on rheological and structural properties of wheat‐based dough and bread quality
Authors: Ma Jie , Kaori Fujita , Ma Lei , Gao Mengnan , Dong Chunxia , Wang Jiamin , Luan Guangzhong
Published: December 2018

Addition of raw black rice flour leads to deficient processability on bread making quality. One of the effective methods to modify the functional properties of black rice flour (BRF) composite dough is to extrude black rice flour (EBRF) before incorporation. This study investigated and compared the effect of BRF and EBRF addition level of 10%–50% on the rheology, microstructure of dough and bread quality. The rheological properties of composite dough were recorded by Mixolab, stress relaxation and tensile test. The substitution of EBRF presented higher water absorption but lower development time, protein weakening, starch gelatinization, starch gel stability and starch retrogradation than wheat flour dough. Both the BRF and EBRF dough presented solid‐like behaviour, while the EBRF dough showed more viscous, higher resistance and extensibility than BRF dough. The dough microstructure of dough was observed by SEM, and a more compact structure of EBRF dough could be seen than BRF dough. The incorporation of EBRF in bread quality presented higher specific volume, lower bake loss and firmness than BRF bread. These findings indicated the potential utilisation value of extruded black rice flour in bread making.
Delactosed permeate as a dairy processing co‐product with major potential value: a review
Authors: Oliveira Diana , Puri Ritika , Fenelon Mark A. , O'Mahony James A.
Published: December 2018

Delactosed permeate (DLP) is the co‐product generated during the separation of pre‐crystallised lactose from milk and whey permeates. DLP production has grown with the increased production of high protein content ingredients such as whey protein concentrates and isolates. Although DLP is nutritionally rich, with approximately 0.5–1.5, 68–70, 9–10 and 8–9 g/100 g dry matter of protein, total sugars, total mineral and organic acids, respectively, it is still currently underutilised, mostly for animal feed or energy production. There are a number of novel, promising and sustainable DLP‐derived food and non‐food applications which are the subject of current research. Therefore, there exists the opportunity to exploit this dairy co‐product in the development of new value‐added ingredients. In this comprehensive review, DLP production, processing challenges and potential applications are discussed, along with identification and assessment of selected strategies for the valorisation of DLP.
Effects of aleurone‐rich fraction on the hydration and rheological properties attributes of wheat dough
Authors: Li Xiaoya , Hu Honghai , Xu Fen , Liu Zhengquan , Zhang Liang , Zhang Hong
Published: December 2018

This study aimed to evaluate the effects of incorporation of aleurone‐rich fraction (ALF) on the hydration and rheological properties of wheat dough. Incorporation of ALF significantly increased water absorption (P < 0.05) and competition for water in dough was observed. Peak viscosity, through viscosity, and final viscosity decreased with the amount of ALF added (P < 0.05), whereas 20% ALF had stronger gel ability than whole‐wheat flour. Dynamic rheological experiments revealed ALF blend dough were more stable than whole‐wheat dough, which was in accord with the higher dough stability and strength observed in Mixolab. Scanning electron microscopy showed that disruption of gluten network with ALF incorporation, whereas 20% ALF showed better stability dough structure than the whole‐wheat dough. Considering those influences on dough properties, the 20% ALF seems to be a promising substitute for whole‐wheat flour to producing dietary fibre‐rich products.
Effect of the particle size of pear pomace on the quality of enriched layer and sponge cakes
Authors: Rocha‐Parra Andrés F. , Belorio Mayara , Ribotta Pablo D. , Ferrero Cristina , Gómez Manuel
Published: December 2018

Pear pomace (PP) is a by‐product of the fruit industry with a high content of fibre. Its potential as an ingredient at 15% or 30% level for sponge and layer cakes was investigated. Three PP powders with different particle sizes (fine, medium and coarse) were obtained. Batter microstructure, density and viscosity and cake specific volume, texture and colour were evaluated. When PP was added, less uniformity in bubble distribution was observed in batters, particularly at higher particle sizes. Cake specific volume significantly diminished with increasing amounts of PP. For sponge cakes, the decrease in specific volume was the highest for the finest particle size of PP. In general, increasing PP addition increased hardness and reduced elasticity, cohesiveness and resilience but the effect depended on the particle size. In general, better textural attributes were obtained with medium and coarse particle sizes. These results indicate that PP of an adequate particle size could be a promising fibre source for different cake formulations.
Estimation of uncertainty in flood forecasts—A comparison of methods
Authors: Boelee Leonore , Lumbroso Darren M. , Samuels Paul G. , Cloke Hannah L.
Published: December 2018

The scientific literature has many methods for estimating uncertainty, however, there is a lack of information about the characteristics, merits, and limitations of the individual methods, particularly for making decisions in practice. This paper provides an overview of the different uncertainty methods for flood forecasting that are reported in literature, concentrating on two established approaches defined as the ensemble and the statistical approach. Owing to the variety of flood forecasting and warning systems in operation, the question “which uncertainty method is most suitable for which application” is difficult to answer readily. The paper aims to assist practitioners in understanding how to match an uncertainty quantification method to their particular application using two flood forecasting system case studies in Belgium and Canada. These two specific applications of uncertainty estimation from the literature are compared, illustrating statistical and ensemble methods, and indicating the information and output that these two types of methods offer. The advantages, disadvantages and application of the two different types of method are identified. Although there is no one “best” uncertainty method to fit all forecasting systems, this review helps to explain the current commonly used methods from the available literature for the non‐specialist.
Home Time as a Patient‐Centered Outcome in Administrative Claims Data
Authors: Lee Hemin , Shi Sandra M. , Kim Dae Hyun
Published: December 2018

BACKGROUND

Home time, the number of days alive and spent out of hospital and skilled nursing facility, has been proposed as a patient‐centered outcome that can be readily calculated in administrative claims data.

OBJECTIVES

To compare home time against existing patient‐centered outcome measures.

DESIGN

Retrospective cohort study.

SETTING

Community.

PARTICIPANTS

A total of 4594 Medicare beneficiaries 65 years or older with complete survey and claims data in the Medicare Current Beneficiary Survey 2010 to 2011.

MEASUREMENTS

Home time was calculated from the 2011 claims data (range, 0‐365 days). The 1‐year incidence of patient‐centered outcomes (poor self‐rated health, mobility impairment, depression, limited social activity, and difficulty in self‐care) was measured. The minimum clinically important difference (MCID) was derived by contrasting the mean home time between those who experienced functional decline or death and those who did not.

RESULTS

The mean home time was 355.8 days (SD, 42.1 days); 84.1% had a home time of 365 days, and 5.7% had a home time of 336 days or fewer. The incidence of poor self‐rated health ranged from 2% (home time, 365 days) to 21% (home time, less than 337 days). Similarly, the corresponding incidence risks were 11% to 59% for mobility impairment, 5% to 19% for depression, 17% to 67% for limited social activity, and 13% to 68% for difficulty in self‐care. The risk of mobility impairment, depression, and difficulty in self‐care increased steeply after home time loss of 15 days or greater. The MCID of home time was 18.6 days.

CONCLUSION

A loss in home time is associated with decline in several patient‐centered outcome measures in community‐dwelling Medicare beneficiaries. These results provide empirical evidence to promote adoption of home time and its clinical interpretation for database studies of medical interventions. J Am Geriatr Soc 67:347–351, 2019.