bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive and sensitive biomarkers for thyroid dysfunctions during treatment with immune‐checkpoint inhibitors
Authors: Kurimoto Chiaki , Inaba Hidefumi , Ariyasu Hiroyuki , Iwakura Hiroshi , Ueda Yoko , Uraki Shinsuke , Takeshima Ken , Furukawa Yasushi , Morita Shuhei , Yamamoto Yuki , Yamashita Shimpei , Katsuda Masahiro , Hayata Atsushi , Akamatsu Hiroaki , Jinnin Masatoshi , Hara Isao , Yamaue Hiroki , Akamizu Takashi
Published: February 2020

Immune‐related adverse events (irAEs) are often seen during immune‐checkpoint inhibitor (ICI) treatment of various malignancies. Endocrine irAEs including thyroid dysfunctions are the most common irAEs, but their biomarkers remain unclear. In order to identify individuals who are susceptible to thyroid irAE for earlier diagnosis and appropriate follow‐up, the current study is aimed to investigate biomarkers of thyroid irAE. Herein, patients with advanced malignant diseases who received ICIs treatment were prospectively studied. Clinical and laboratory examination, thyroid function, and autoantibodies were evaluated at baseline, and every 4 wk after first treatment with ICIs. Cytokines/chemokines were measured at baseline and at 4 wk. In vivo effects of ICIs on experimental autoimmune thyroiditis were evaluated. Twenty‐six patients with malignant diseases who received ICIs treatment were enrolled in the study. Patients were divided into two groups: those who developed thyroid irAE, and those without irAEs. Comparing the two groups, early increase (≤4 wk) in serum thyroglobulin (Tg) levels and thyroid autoantibodies was seen in thyroid irAE (P < .05). Notably, higher levels of serum IL‐1β, IL‐2, and GM‐CSF at baseline, and early decrease of IL‐8, G‐CSF, and MCP‐1 were significantly associated in the development of thyroid irAE (P < .05). In vivo effects of anti‐PD‐1 antibody on deterioration of mice experimental thyroiditis were seen. In conclusion, early change in Tg, thyroid autoimmunity, and cytokine levels might indicate development of thyroid irAE. Pre‐existing thyroid autoimmunity might be involved with the development of thyroid irAE. Potential application of these factors as surrogate biomarkers for tumor therapy was indicated.
SPH3643: A novel cyclin‐dependent kinase 4/6 inhibitor with good anticancer efficacy and strong blood‐brain barrier permeability
Authors: Liao XueMei , Hong Yuan , Mao Yu , Chen Na , Wang Qian , Wang Zhe , Zhang LeDuo , Wang Li , Shi Chen , Shi WeiJun , Ge Hui , Li AnDi , Li Xin , Xia GuangXin , Liu YanJun
Published: February 2020

The cyclin‐dependent kinase (CDK)4/6‐cyclin D1‐Rb‐p16/ink4a pathway is responsible for regulating cell progression past the G1 restriction point during the cell cycle. The development of a majority of human tumors is associated with dysregulation of this pathway, resulting in increased cancer cell proliferation. Both CDK4 and CDK6, well‐validated cancer drug targets, function primarily as catalytic enzymes that mediate the phosphorylation of retinoblastoma protein (Rb). Here, we determined that SPH3643 is a novel potent antiproliferative agent that inhibits CDK4/6 kinase activity. In biochemical assays, SPH3643 showed more potent inhibition of both CDK4 and CDK6 than did 2 published CDK4/6 inhibitors, LY2835219 and palbociclib, and had better selectivity than LY2835219. Further in vitro study revealed that SPH3643 blocked Cdk/Rb signaling by inhibiting the phosphorylation of RbSer780 and arrested the MCF‐7 cancer cells at G0/G1 phase, resulting in marked inhibition of the proliferation of Rb‐positive cancer cell lines. In vivo SPH3643 treatment in mice bearing xenograft tumor models of breast cancer, colon cancer, acute myelocytic leukemia, and glioblastoma resulted in significant decreases in tumor growth. SPH3643 was able to particularly strongly inhibit glioblastoma (U87‐MG) cell growth in the brains of orthotopic carcinoma xenograft mice due to its high degree of intracerebral penetration and significant persistence in this setting. Together these results revealed that SPH3643 is a potent, orally active small‐molecule inhibitor of CDK4/6 with robust anticancer efficacy and a high degree of blood‐brain barrier permeability.
Omalizumab in the treatment of adult patients with mastocytosis: A systematic review
Authors: Jendoubi Fatma , Gaudenzio Nicolas , Gallini Adeline , Negretto Mathilde , Paul Carle , Bulai Livideanu Cristina
Published: February 2020

Background

Mastocytosis is associated with mast cell (MC) mediator‐related symptoms for which limited therapies are available.

Objective

Our aim was to assess the efficacy and safety of omalizumab in the treatment of MC mediator‐related symptoms in adult patients with mastocytosis.

Results

We identified one multi‐centre retrospective cohort study (39 patients), one retrospective cohort study (13 patients), 4 case series and 10 case reports. No published controlled randomized study was identified. We included 69 patients (13 patients with cutaneous mastocytosis and 56 with systemic mastocytosis). The mean age was 48 years. Omalizumab maintenance dose was 300 mg for the majority of patients. The mean duration of treatment was 17 months. Treatment led to a tolerability of venom immunotherapy and to a complete resolution of severe reactions in all patients with post‐honeybee sting anaphylaxis. Complete resolution of idiopathic anaphylaxis episodes was noted in 84% of the patients. Complete resolution of palpitations, gastrointestinal, cutaneous, neuropsychiatric, respiratory and musculoskeletal symptoms was observed at a rate of 43%, 29%, 27%, 11%, 9% and 0%, respectively. Efficacy was maintained for the entire duration of the treatment in all but four responders. Adverse events were reported for 13 patients.

Conclusions and Clinical Relevance

Omalizumab appears to prevent some life‐threatening reactions associated with mastocytosis and may be a good option to treat the associated symptoms. However, the evidence relied upon is observational, uncontrolled and from a small number of patients. A randomized controlled trial is needed to better understand the place of omalizumab in mastocytosis treatment.
Making sense of places: Belonging among “unaccompanied” young migrants in kinship care in a Swedish suburb
Authors: Moberg Stephenson Maria , Källström Åsa
Published: February 2020

For young people who have migrated unaccompanied by parents or other legal guardians, it is important to feel a sense of belonging. However, belonging is not fixed to one place. This study aims to explore how young migrants in kinship care in a Swedish suburb describe what different places mean to them and what these descriptions can tell us about their sense of belonging. In this study, semi‐structured interviews with 11 young migrants between 16 and 21 years of age who took part in a mentoring programme are analysed by thematic analysis. Our analysis reveals that (a) the young people described four “levels” of place as meaningful in different ways—their kinship homes, the local community, the country they currently inhabit, and the world and that (b) it was through the interrelationships between these levels that their described sense of belonging emerged. To counterbalance young migrants' uncertain future, social interventions are needed that can help them to meet other people and get wider social networks in order to gain a sense of belonging in the new country.
Consequences of epigenetic derepression in facioscapulohumeral muscular dystrophy
Authors: Greco Anna , Goossens Remko , van Engelen Baziel , van der Maarel Silvère M.
Published: February 2020

Facioscapulohumeral muscular dystrophy (FSHD), a common hereditary myopathy, is caused either by the contraction of the D4Z4 macrosatellite repeat at the distal end of chromosome 4q to a size of 1 to 10 repeat units (FSHD1) or by mutations in D4Z4 chromatin modifiers such as Structural Maintenance of Chromosomes Hinge Domain Containing 1 (FSHD2). These two genotypes share a phenotype characterized by progressive and often asymmetric muscle weakening and atrophy, and common epigenetic alterations of the D4Z4 repeat. All together, these epigenetic changes converge the two genetic forms into one disease and explain the derepression of the DUX4 gene, which is otherwise kept epigenetically silent in skeletal muscle. DUX4 is consistently transcriptionally upregulated in FSHD1 and FSHD2 skeletal muscle cells where it is believed to exercise a toxic effect. Here we provide a review of the recent literature describing the progress in understanding the complex genetic and epigenetic architecture of FSHD, with a focus on one of the consequences that these epigenetic changes inflict, the DUX4‐induced immune deregulation cascade. Moreover, we review the latest therapeutic strategies, with particular attention to the potential of epigenetic correction of the FSHD locus.
Pain relief and improvement in quality of life with 10 kHz SCS therapy: Summary of clinical evidence
Authors: Sayed Dawood , Kallewaard Jan Willem , Rotte Anand , Jameson Jessica , Caraway David
Published: February 2020

Objective

Chronic pain is a prevalent condition which has a significant effect on the lives of those it impacts. High‐frequency 10 kHz spinal cord stimulation (10 kHz SCS) has been shown to provide paresthesia‐free pain relief for a wide variety of pain indications. This article summarizes the current and emerging data as they relate to the clinical use of the therapy in various pain syndromes.

Methods

A literature search was conducted using the PubMed electronic database using keywords related to 10 kHz SCS. The database was queried from 2013 to May 2019. Articles reporting clinical studies that included human subjects permanently treated with 10 kHz SCS (Senza® system) were included in the review. Recent and relevant conference proceedings known to the authors were also included.

Results

The selected literature demonstrated significant evidence for the efficacy of 10 kHz SCS in treating chronic back and leg pain (CBLP), including a randomized, controlled trial as well as prospective and retrospective studies. One‐year follow‐up responder rates (pain relief ≥50%) ranged from 60% to 80%. Other studies and case series showed promising outcomes in specific conditions, including nonsurgical refractory back pain, neuropathic limb pain, complex regional pain syndrome, chronic widespread pain, chronic pelvic pain, and intractable headache. Subgroup analyses also pointed toward the potential of 10 kHz SCS being successful when low‐frequency SCS has failed. The vast majority of these studies reported improved quality of life (QOL) metrics and/or reduced opioid consumption.

Conclusions

Level I evidence already exists for the efficacy of 10 kHz SCS in treating CBLP, supported by real‐world clinical experience. Other studies demonstrate the potential of the therapy across a range of chronic pain etiologies, although larger confirmatory studies are recommended. Overall, the literature suggests that the therapy is associated with improved QOL as well as reduced opioid consumption.
Hidden risks in toys: A systematic review of pediatric toy contact dermatitis
Authors: Fenner Justine , Hadi Ali , Yeh Lindsey , Silverberg Nanette
Published: February 2020

Toys are a reflection of the compounds used frequently in manufacturing. Allergic contact dermatitis to potties, metal toys, and children's jewelry is well known, however, there is a broad range of skin risks in toys. With the objective to identify and publicize the associated risk of contact dermatitis in children's toys, we have searched the PubMed database from creation to September 9, 2019. Studies were eligible if they reported a new case of contact dermatitis secondary to interaction with a toy in patients from birth to 18 years of age. A toy was defined as something children interact with for entertainment during leisure time. In this review of the PubMed database we filtered by age and language which may have prevented us from detecting cases in adults that could be extrapolated to children. In addition, several articles were excluded based on title alone. A total of 1312 articles were identified and reviewed manually for inclusion criteria. Review of the articles found 25 original articles for consideration. Several toys were found to be associated with contact dermatitis. These included electronics, toy cars, costume jewelry, bicycles, sqwish balls, slime, Play‐Doh, and plasticine. Electronics such as video game controllers, cellphones, iPads, and computers were implicated. In conclusion, there is still an unmet need for observation of this segment of industry for labeling of contents and ongoing surveillance.
Season wise bike sharing demand analysis using random forest algorithm
Authors: V. E. Sathishkumar , Cho Yongyun
Published: February 2020

Rental bike sharing is an urban mobility model that is affordable and ecofriendly. The public bike sharing model is widely used in several cities across the world over the past decade. Because bike use is rising constantly, understanding the system demand in prediction is important to boost the operating system readiness. This article presents a prediction model to meet user demands and efficient operations for rental bikes using Random Forest (RF), which is a homogeneous ensemble method. The approach is carried out in Seoul, South Korea to predict the hourly use of rental bikes. RF is compared with Support Vector Machine with Radial Basis Function Kernel, k‐nearest neighbor and Classification and Regression Trees to verify RF supremacy in rental bike demand prediction. Performance Index measures the efficiency of RF compared to the other predictive models. Also, the variable importance analysis is performed to assess the most important characteristics during different seasons by creating a predictive model using RF for each season. The results show that the influence of variables changes depending on the seasons that suggest different operating conditions. RF models trained with yearly and seasonwise models show that bike sharing demand can be further improved by considering seasonal change.
Neural network prediction of bioleaching of metals from waste computer printed circuit boards using Levenberg‐Marquardt algorithm
Authors: Annamalai Mohan , Gurumurthy Kalaichelvan
Published: February 2020

The applicability of artificial neural network (ANN) to predict the bioleaching of metals using from computer printed circuit boards (CPCB) and the influence of process parameters were studied. The influence of process parameters initial pH (1.6‐2.4), pulp density (2%‐13%), and the initial volume of Inoculum (5%‐25%) were investigated on the rate of bioleaching of metals from CPCB. Network inputs were fed as initial pH, pulp density, and inoculum volume and with the extraction of Cu, Ag, and Au as output. The ANN was developed using the Levenberg‐Marquardt algorithm and trained for modeling and prediction. The most fitting architectures for Cu, Ag, and Au were [4‐5‐5‐2‐1], [4‐7‐5‐2‐1], [4‐7‐1‐1‐1] trained with Levenberg‐Marquardt algorithm, respectively. The R values were observed to be 0.996, 0.997, and 0.993 for Cu, Ag, and Au extraction predictions, respectively. The genetic algorithm model defined by ANN was used to achieve maximum extraction rates for Cu, Au, and Ag. The predicted data showed that there is a great capability of using ANN for the prediction of Cu, Ag, and Au extraction from CPCB through bioleaching process. Hence, the ANN model can be used to control the operational conditions for improved metals extraction through bioleaching.
L1 norm based pedestrian detection using video analytics technique
Authors: Selvaraj Anandamurugan , Selvaraj Jeeva , Maruthaiappan Sivabalakrishnan , Babu Gokulnath Chandra , Kumar Priyan Malarvizhi
Published: February 2020

Pedestrian detection from images of the visible spectrum is a high relevant area of research given its potential impact in the design of pedestrian protection systems. In general, detection is made with two different phases, feature extraction and classification. Also, features for detection of pedestrian are already are available such as optimal feature model. But still required is an improvement in detection by reducing the execution time and false positive. The proposed model has three different phases, that is, background subtraction, feature extraction, and classification. In spite of giving entire information into feature extraction, the system gives only a useful information (foreground image) by twin background model. Then the foreground image moves to the feature extraction and classifies the pedestrian. For feature extraction, histogram of orientation gradient (HOG) L1 normalization has been used. This will increase the detection accuracy and reduce the computation time of a process. In addition, false positive rate has been minimized.
Brentuximab vedotin in association with bendamustine in refractory or multiple relapsed Hodgkin lymphoma. A retrospective real‐world study
Authors: Iannitto Emilio , Romano Alessandra , Scalzulli Potito Rosario , Bonanno Vincenza , Scalone Renato , Chiarenza Annalisa , Pirosa Maria Cristina , Caruso Anastasia Laura , Minoia Carla , Mantuano Saverio , De Santis Gaetano , Salerno Marilena , Crescimanno Alessandra , Porretto Ferdinando , Li Gioi Felicina , Ricciuti Giuseppina , Greco Antonino , Pavone Enzo , Guarini Attilio , Tarantini Giuseppe , Mannina Donato , Consoli Ugo , Cascavilla Nicola , Di Raimondo Francesco , Musso Maurizio
Published: February 2020

Objective and Methods

In order to assess the efficacy of brentuximab vedotin (Bv) in combination with bendamustine (B) in multiple relapsed or refractory (RR) classic Hodgkin lymphoma (cHL), medical records of 47 patients treated with BvB in second relapse or beyond were reviewed.

Results

The median number of previous treatments was 2 (1‐4). Bv was given at 1.8 mg/kg on day 1 and bendamustine at 90 mg/m2 on days 1 and 2 of a 21‐day cycle. The median number of BvB cycles was 4 (2‐7), and all patients were evaluable for efficacy. The CR and OR rates were 49% and 79%, respectively; 67% of responding patients and 2 in stable disease proceeded to a SCT procedure. After a median follow‐up of 19 months (5‐47), median PFS was 18 months (95%CI: 23‐29), and the 2‐year OS was 72%. Significantly longer PFS and OS were observed in patients attaining a major clinical response to treatment and in those who received consolidation with SCT. Fifteen (32%) patients experienced severe (G > 2) toxicity. The main toxicities were neutropenia (23%), gastrointestinal (10%), peripheral sensory neuropathy (11%), and infection (4%).

Conclusion

Our real‐world results suggest that BvB is an effective third‐line rescue and bridge‐to‐transplant regimen for RR‐cHL patients.
Trait plasticity alters the range of possible coexistence conditions in a competition–colonisation trade‐off
Authors: Muthukrishnan Ranjan , Sullivan Lauren L. , Shaw Allison K. , Forester James D.
Published: February 2020

Most of the classical theory on species coexistence has been based on species‐level competitive trade‐offs. However, it is becoming apparent that plant species display high levels of trait plasticity. The implications of this plasticity are almost completely unknown for most coexistence theory. Here, we model a competition–colonisation trade‐off and incorporate trait plasticity to evaluate its effects on coexistence. Our simulations show that the classic competition–colonisation trade‐off is highly sensitive to environmental circumstances, and coexistence only occurs in narrow ranges of conditions. The inclusion of plasticity, which allows shifts in competitive hierarchies across the landscape, leads to coexistence across a much broader range of competitive and environmental conditions including disturbance levels, the magnitude of competitive differences between species, and landscape spatial patterning. Plasticity also increases the number of species that persist in simulations of multispecies assemblages. Plasticity may generally increase the robustness of coexistence mechanisms and be an important component of scaling coexistence theory to higher diversity communities.
Adjustments in fatty acid composition is a mechanism that can explain resilience to marine heatwaves and future ocean conditions in the habitat‐forming seaweed Phyllospora comosa (Labillardière) C.Agardh
Authors: Britton Damon , Schmid Matthias , Noisette Fanny , Havenhand Jonathan N. , Paine Ellie R. , McGraw Christina M. , Revill Andrew T. , Virtue Patti , Nichols Peter D. , Mundy Craig N. , Hurd Catriona L.
Published: February 2020

Marine heatwaves are extreme events that can have profound and lasting impacts on marine species. Field observations have shown seaweeds to be highly susceptible to marine heatwaves, but the physiological drivers of this susceptibility are poorly understood. Furthermore, the effects of marine heatwaves in conjunction with ocean warming and acidification are yet to be investigated. To address this knowledge gap, we conducted a laboratory culture experiment in which we tested the growth and physiological responses of Phyllospora comosa juveniles from the southern extent of its range (43–31°S) to marine heatwaves, ocean warming and acidification. We used a ‘collapsed factorial design’ in which marine heatwaves were superimposed on current (today's pH and temperature) and future (pH and temperature projected by 2100) ocean conditions. Responses were tested both during the heatwaves, and after a 7‐day recovery period. Heatwaves reduced net photosynthetic rates in both current and future conditions, while respiration rates were elevated under heatwaves in the current conditions only. Following the recovery period, there was little evidence of heatwaves having lasting negative effects on growth, photosynthesis or respiration. Exposure to heatwaves, future ocean conditions or both caused an increase in the degree of saturation of fatty acids. This adjustment may have counteracted negative effects of elevated temperatures by decreasing membrane fluidity, which increases at higher temperatures. Furthermore, P. comosa appeared to down‐regulate the energetically expensive carbon dioxide concentrating mechanism in the future conditions with a reduction in δ13C values detected in these treatments. Any saved energy arising from this down‐regulation was not invested in growth and was likely invested in the adjustment of fatty acid composition. This adjustment is a mechanism by which P. comosa and other seaweeds may tolerate the negative effects of ocean warming and marine heatwaves through benefits arising from ocean acidification.
Does gene flow balance the effect of habitat fragmentation in a population of the hermit beetleOsmoderma barnabita?
Authors: Melosik Iwona , Baraniak Edward , Przewoźny Marek , Grzegorczyk Tomasz , Rzepka Małgorzata
Published: February 2020

A fine‐scale spatial genetic structure is rarely analysed within insect populations, although such a structure influences the level of inbreeding and kin dynamics and can have implications for long‐term population persistence. A high level of genetic structure is expected in a divided population of the hermit beetleOsmoderma barnabitadue to its philopatry and habitat loss/fragmentation.

To assess the variability and population genetic structure, sex contributions to genetic variation, and gene flow, the beetles were collected in a fragmented forest (2920 ha) employing sex pheromone‐baited traps, georeferenced, and morphologically identified to species and sex; 187 sampled specimens were then evaluated using 10 microsatellite loci.

Based on our data, the population as a whole is characterised by low genetic diversity (He= 0.34) and a high level of inbreeding (FiAvg. = 0.31). Nevertheless, the level of differentiation between field subpopulations is low, indicating a high level of gene flow (a patchy model). This was evidenced by small pairwiseFSTestimates and slight differences inHo,He, and allelic richness, a lack of well‐defined boundaries between subpopulations, and relatively low relatedness among neighbouring female and male dyads.

Sex‐biased gene flow was evidenced from the analysis of isolation by distance (regression relatedness) but not from assignment tests.

Mating between close kin and recent colonisation from a small source are presented as a possible explanation for high inbreeding, low genetic diversity, and minimal population structure. Still, additional evidence is required to support this hypothesis. The results suggest that the population can be treated as a single management unit.
Nurses' perceptions of risks for occupational hazards in patient seclusion and restraint practices in psychiatric inpatient care: A focus group study
Authors: Varpula Jaakko , Välimäki Maritta , Lantta Tella , Berg Johanna , Lahti Mari
Published: February 2020

Seclusion and restraint are regularly used to manage patient aggression events in psychiatric inpatient care, despite occupational safety concerns. There is currently a lack of information on how nurses perceive the use of patient seclusion and restraint as a risk for occupational safety. The aim of this study is to describe the risks for occupational hazards in patient seclusion and mechanical restraint practices as well as ideas for improvement identified by nurses. A qualitative descriptive design was adopted, using focus groups comprising nurses (N = 32) working in psychiatric inpatient care. The data were analysed using inductive content analysis, and the results were reported using the consolidated criteria for reporting qualitative studies (COREQ). Four themes of risk for occupational hazards were identified: patient‐induced, staff‐induced, organization‐induced, and environment‐induced risks. One significant finding was that nurses described that their actions can strongly contribute to occupational hazards during seclusion and mechanical restraint practices. The nurses gave various ideas for how occupational safety could be improved during seclusion and mechanical restraint events, ideas involving staff, the organization, and environmental enhancements.
A pilot multi‐centre prospective randomised controlled trial of RECELL for the treatment of venous leg ulcers
Authors: Hayes Paul D. , Harding Keith G. , Johnson Susan M. , McCollum Charles , Téot Luc , Mercer Kevin , Russell David
Published: February 2020

Venous leg ulcers (VLUs) have a significant impact on approximately 3% of the adult population worldwide, with a mean NHS wound care cost of £7600 per VLU over 12 months. The standard care for VLUs is compression therapy, with a significant number of ulcers failing to heal with this treatment, especially with wound size being a risk factor for non‐healing. This multicentre, prospective, randomised trial evaluated the safety and effectiveness of autologous skin cell suspension (ASCS) combined with compression therapy compared with standard compression alone (Control) for the treatment of VLUs. Incidence of complete wound closure at 14 weeks, donor site closure, pain, Health‐Related Quality of Life (HRQoL), satisfaction, and safety were assessed in 52 patients. At Week 14, VLUs treated with ASCS + compression had a statistically greater decrease in ulcer area compared with the Control (8.94 cm2 versus 1.23 cm2, P = .0143). This finding was largely driven by ulcers >10 to 80 cm2 in size, as these ulcers had a higher mean percentage of reepithelialization at 14 weeks (ASCS + compression: 69.97% and Control: 11.07%, P = .0480). Additionally, subjects treated with ASCS + compression experienced a decrease in pain and an increase in HRQoL compared with the Control. This study indicates that application of ASCS + compression accelerates healing in large venous ulcers.
Giant permittivity up to 100 MHz in La and Nb co‐doped rutile TiO2 ceramics
Authors: Song Yuechan , Liu Peng , Guo Baochun , Cui Xiulei , Yang Wanmin
Published: February 2020

Dielectric spectroscopy was carried out for reduced and stoichiometric La0.0025Nb0.0025Ti0.995O2 ceramics synthesized by sintering in different atmospheres. A giant permittivity (~1 × 104) was obtained at a frequency of 100 MHz and temperature range from 170 to 350 K. Three dielectric relaxation mechanisms were observed within the temperature range of 10‐300 K via dielectric spectroscopy. A low temperature dipole relaxation peak (in the temperature range of 10‐30 K) in the spectra was identified to be associated with the giant permittivity specifically measured at 100 MHz. The origin of such giant permittivity was attributed to dipole orientation polarization. Hopping polaron and interfacial effect contributed to giant permittivity. After annealing treatment, all the relaxation contributions were weakened. Low dielectric loss was attributed to high resistance of grain and grain boundaries. Annealing in ambient conditions led to decreased relaxation times which gives the signature of decreased concentration of oxygen vacancies and Ti3+. Dipoles which were related to oxygen vacancies and Ti3+, resulted in giant permittivity up to 100 MHz.
Increasing number of authors in Cochrane reviews
Authors: Gülen Sengül , Fonnes Siv , Andresen Kristoffer , Rosenberg Jacob
Published: February 2020

Objective

To investigate authorship trends in Cochrane reviews from 1996 to 2018, and to examine if the authorship criteria from the International Committee of Medical Journal Editors (ICMJE) were met for Cochrane reviews with more than 15 authors based on the text in the section “Contributions of authors.”

Methods

The median number of authors per review was calculated, and authorship trends within each editorial group were analyzed. The section “Contributions of authors” was assessed about the first and second authorship criteria from the ICMJE for reviews with more than 15 authors.

Results

A total of 7447 Cochrane reviews were studied based on data from the Cochrane Database of Systematic Reviews. The median number of authors per Cochrane review was 3 in 1996 (IQR 2.5‐3, range 2‐3), 4 in 2007 (IQR 3‐5, range 1‐13), and 5 in 2018 (IQR 4‐7, range 2‐22). Within each editorial group, the total number of authors either increased (26/55, 47%) or was unchanged (29/55, 53%). Based on the text in “Contributions of authors,” 59% (16/27) of the reviews with more than 15 authors had authors that did not fulfil the ICMJE authorship criteria. However, the text in “Contributions of authors” was often difficult to interpret.

Conclusions

The number of authors per Cochrane review gradually increased from 1996 to 2018. The ICMJE authorship criteria were probably not met by all authors in more than half of the reviews with more than 15 authors.
Impact and Lessons From the Lifestyle Interventions and Independence for Elders (LIFE) Clinical Trials of Physical Activity to Prevent Mobility Disability
Authors: Pahor Marco , Guralnik Jack M. , Anton Stephen D. , Ambrosius Walter T. , Blair Steven N. , Church Timothy S. , Espeland Mark A. , Fielding Roger A. , Gill Thomas M. , Glynn Nancy W. , Groessl Erik J. , King Abby C. , Kritchevsky Stephen B. , Manini Todd M. , McDermott Mary M. , Miller Michael E. , Newman Anne B. , Williamson Jeff D.
Published: February 2020

BACKGROUND

Walking independently is basic to human functioning. The Lifestyle Interventions and Independence for Elders (LIFE) studies were developed to assess whether initiating physical activity could prevent major mobility disability (MMD) in sedentary older adults.

METHODS

We review the development and selected findings of the LIFE studies from 2000 through 2019, including the planning phase, the LIFE‐Pilot Study, and the LIFE Study.

RESULTS

The planning phase and the LIFE‐Pilot provided key information for the successful implementation of the LIFE Study. The LIFE Study, involving 1635 participants randomized at eight sites throughout the United States, showed that compared with health education, the physical activity program reduced the risk of the primary outcome of MMD (inability to walk 400 m: hazard ratio = 0.82; 95% confidence interval = 0.69‐0.98; P = .03), and that the intervention was cost‐effective. There were no significant effects on cognitive outcomes, cardiovascular events, or serious fall injuries. In addition, the LIFE studies provided relevant findings on a broad range of other outcomes, including health, frailty, behavioral outcomes, biomarkers, and imaging. To date, the LIFE studies have generated a legacy of 109 peer‐reviewed publications, 19 ancillary studies, and 38 independently funded grants and clinical trials, and advanced the development of 59 early career scientists. Data and biological samples of the LIFE Study are now publicly available from a repository sponsored by the National Institute on Aging (
https://agingresearchbiobank.nia.nih.gov).

CONCLUSIONS

The LIFE studies generated a wealth of important scientific findings and accelerated research in geriatrics and gerontology, benefiting the research community, trainees, clinicians, policy makers, and the general public. J Am Geriatr Soc 68:872–881, 2020
Cost‐Effectiveness of Pneumococcal Vaccination Policies and Uptake Programs in US Older Populations
Authors: Wateska Angela R. , Nowalk Mary Patricia , Lin Chyongchiou J. , Harrison Lee H. , Schaffner William , Zimmerman Richard K. , Smith Kenneth J.
Published: February 2020

BACKGROUND/OBJECTIVES

Recently revised vaccination recommendations for US adults, aged 65 years and older, include both 23‐valent pneumococcal polysaccharide vaccine (PPSV23) and 13‐valent pneumococcal conjugate vaccine (PCV13), with PCV13 now recommended for immunocompetent older people based on shared decision making. The public health impact and cost‐effectiveness of this recommendation or of pneumococcal vaccine uptake improvement interventions are unclear.

DESIGN

Markov decision analysis.

SETTING AND PARTICIPANTS

Hypothetical 65‐year‐old general and black population cohorts.

INTERVENTION

Current pneumococcal vaccination recommendations for US older people, an alternative policy omitting PCV13 in immunocompetent older people, and vaccine uptake improvement programs.

RESULTS

The current pneumococcal vaccination recommendation was the most effective strategy, but afforded slight public health benefits compared to an alternative (PPSV23 for all older people plus PCV13 for the immunocompromised) and cost greater than $750 000 per quality‐adjusted life‐year (QALY) gained in either population group with a vaccine uptake improvement program (absolute uptake increase = 12.3%; cost = $1.78/eligible patient) in place. The alternative strategy was more economically favorable, but cost greater than $100 000/QALY in either population, with or without an uptake intervention. Results were robust in sensitivity analyses; however, in black older people, the alternative strategy with an uptake program was most likely to be favored in probabilistic sensitivity analyses at a $150 000/QALY gained threshold.

CONCLUSION

Current pneumococcal vaccination recommendations for US older people are economically unfavorable compared to an alternative strategy omitting PCV13 in the immunocompetent. The alternative recommendation with an uptake improvement program may be economically reasonable in black population analyses and could be worth considering as a population‐wide recommendation if mitigating racial disparities is a priority. J Am Geriatr Soc 68:1271–1278, 2020.
Sibling Ill Health and Children's Educational Outcomes
Authors: Bortes Cristian , Strandh Mattias , Nilsson Karina
Published: February 2020

BACKGROUND

The presence of health problems in a child is known to be negatively associated with later academic achievement, but less is known about the educational outcomes for siblings of children in poor health. The study investigated how having a sibling with health problems affects a healthy sibling's academic achievement.

METHODS

We utilized medical and social microdata from Swedish administrative population registers. Our sample consisted of N = 115,106 individuals (51.3% boys) born in 1990 in Sweden. We compared children with ill siblings to children whose siblings did not have poor health. Siblings' hospital admissions and the academic achievements of the healthy sibling during their final year of compulsory education (at the age of 15‐16) were analyzed using linear and logistic regression in relation to individual health‐ and family‐related confounders.

RESULTS

Sibling hospitalization was significantly associated with lower overall grade points (β = −10.73, p < .001) and an increased odds ratio (OR) of ineligibility for upper secondary education (OR = 1.42, 95% confidence interval = 1.31‐1.52, p < .001).

CONCLUSIONS

School and health personnel should also consider the needs of healthy siblings during their work with children in poor health, because they too can be disadvantaged.
The Structure of Absorptive Capacity in Three Product Development Strategies
Authors: Skilton Paul F. , Bernardes Ednilson , Li Mei , Creek Steven A.
Published: February 2020

This study develops and tests theory about different forms of absorptive capacity that support radical, differentiation and imitation product development strategies. Absorptive capacity theory provides a generalized explanation for how firms exploit their embeddedness in relationships with buyers and suppliers. We develop and test theory that relates combinations of four components of absorptive capacity (R&D capability, product development capability, cooperative embeddedness, and competitive embeddedness) to success rates in three product development strategies. We used data from the American pharmaceutical industry to estimate generalized linear mixed models. Our results confirm known relationships between R&D capability, alliance network position, and the development of radically new products, but reveal different sets of factors that influence differentiation and imitation. We describe a previously undetected influence of competitive embeddedness on the development of radically new products, a contrasting absorptive capacity structure for generic product development, and a mixed structure for differentiated product development.
Unexpected long‐lasting anti‐HEV IgM positivity: Is HEV antigen a better serological marker for hepatitis E infection diagnosis?
Authors: Riveiro‐Barciela Mar , Rando‐Segura Ariadna , Barreira‐Díaz Ana , Bes Marta , P. Ruzo Sofía , Piron Maria , Quer Josep , Sauleda Silvia , Rodríguez‐Frías Francisco , Esteban Rafael , Buti María
Published: February 2020

Hepatitis E virus (HEV) is the leading cause of acute hepatitis worldwide. The minimum criterion for diagnosis of acute infection is detection of anti‐HEV antibodies, although there are scant data on IgM duration. Our aim was to assess the persistence of HEV markers after acute self‐limited hepatitis E. HEV serological tests (IgM by Mikrogen and Wantai and HEV‐Ag) and HEV RNA were carried out in two cohorts: (a) patients with prior acute hepatitis E (ALT >10 x ULN plus positive IgM ± HEV RNA) currently self‐limited and (b) 50 blood donors with positive HEV RNA. Among 25 cases of prior acute hepatitis E, after a median follow‐up of 34 months, all presented undetectable HEV RNA. However, anti‐HEV IgM remained detectable in 14 (56%) by Mikrogen, 6 (24%) by Wantai and none for HEV‐Ag. Anti‐HEV IgM tested positive in 80%‐100% within the second year and 17%‐42% over 3 years later, by Wantai and Mikrogen, respectively. Among HEV RNA‐positive donors, 12 (25%) tested positive for either IgM by Mikrogen or Wantai, 9 (18%) for both and 18 (36%) for HEV‐Ag. HEV‐Ag positivity was more likely as HEV RNA was higher (14% if <2.2 log IU/mL; 64% if RNA ≥ 3.7). Overall, HEV‐Ag performed best, with a positive predictive value of 100% and diagnostic accuracy of 57%. Anti‐HEV IgM exhibited unexpectedly long persistence after a self‐limited acute hepatitis E. HEV‐Ag had the best performance and could be especially useful in settings where HEV RNA is not available.
The association between etiology of hepatocellular carcinoma and race‐ethnicity in Florida
Authors: Pinheiro Paulo S. , Medina Heidy N. , Callahan Karen E. , Jones Patricia D. , Brown Clyde P. , Altekruse Sean F. , McGlynn Katherine A. , Kobetz Erin N.
Published: February 2020

Background and Aim

The incidence of hepatocellular carcinoma (HCC) has risen considerably in the US since 1980. The main causes include metabolic disorders (NAFLD, diabetes, obesity, metabolic syndrome), alcohol‐related disease (ALD) and hepatitis C and B virus infections (HCV, HBV). Etiology‐specific HCC incidence rates by detailed race‐ethnicity are needed to improve HCC control and prevention efforts.

Methods

All HCC cases diagnosed in Florida during 2014‐2015 were linked to statewide hospital discharge data to determine etiology. Age‐specific and age‐adjusted rates were used to assess the intersection between etiology and detailed racial‐ethnicities, including White, African American, Afro‐Caribbean, Asian, Cuban, Puerto Rican and Continental Hispanic (Mexican, South and Central American).

Results

Of 3666 HCC cases, 2594 matched with discharge data. HCV was the leading cause of HCC among men and women (50% and 43% respectively), followed by metabolic disorders (25% and 37%) and ALD (16% and 9%). Puerto Rican and African American men had the highest HCV‐HCC rates, 7.9 and 6.3 per 100 000 respectively. Age‐specific rates for HCV‐HCC peaked among baby boomers (those born in 1945‐1965). Metabolic‐HCC rates were highest among populations above age 70 and among Continental Hispanics. Afro‐Caribbean men had high rates of HBV‐HCC, whereas Puerto Rican men had high ALD‐HCC.

Conclusions

HCC etiology is associated with specific race/ethnicity. While HCV‐related HCC rates are projected to decrease soon, HCC will continue to affect Hispanics disproportionately, based on higher rates of metabolic‐HCC (and ALD‐HCC) among Continental Hispanics, who demographically represent 80% of all US Hispanics. Multifaceted approaches for HCC control and prevention are needed.
An effector of a necrotrophic fungal pathogen targets the calcium‐sensing receptor in chloroplasts to inhibit host resistance
Authors: Tang Liguang , Yang Guogen , Ma Ming , Liu Xiaofan , Li Bo , Xie Jiatao , Fu Yanping , Chen Tao , Yu Yang , Chen Weidong , Jiang Daohong , Cheng Jiasen
Published: February 2020

SsITL, a secretory protein of the necrotrophic phytopathogen Sclerotinia sclerotiorum, was previously reported to suppress host immunity at the early stages of infection. However, the molecular mechanism that SsITL uses to inhibit plant defence against S. sclerotiorum has not yet been elucidated. Here, we report that SsITL interacted with a chloroplast‐localized calcium‐sensing receptor, CAS, in chloroplasts. We found that CAS is a positive regulator of the salicylic acid signalling pathway in plant immunity to S. sclerotiorum and CAS‐mediated resistance against S. sclerotiorum depends on Ca2+ signalling. Furthermore, we showed that SsITL could interfere with the plant salicylic acid (SA) signalling pathway and SsITL‐expressing transgenic plants were more susceptible to S. sclerotiorum. However, truncated SsITLs (SsITL‐NT1 or SsITL‐CT1) that lost the ability to interact with CAS do not affect plant resistance to S. sclerotiorum. Taken together, our findings reveal that SsITL inhibits SA accumulation during the early stage of infection by interacting with CAS and then facilitating the infection by S. sclerotiorum.
Green leaf volatiles and jasmonic acid enhance susceptibility to anthracnose diseases caused by Colletotrichum graminicola in maize
Authors: Gorman Zachary , Christensen Shawn A. , Yan Yuanxin , He Yongming , Borrego Eli , Kolomiets Michael V.
Published: February 2020

Colletotrichum graminicola is a hemibiotrophic fungus that causes anthracnose leaf blight (ALB) and anthracnose stalk rot (ASR) in maize. Despite substantial economic losses caused by these diseases, the defence mechanisms against this pathogen remain poorly understood. Several hormones are suggested to aid in defence against C. graminicola, such as jasmonic acid (JA) and salicylic acid (SA), but supporting genetic evidence was not reported. Green leaf volatiles (GLVs) are a group of well‐characterized volatiles that induce JA biosynthesis in maize and are known to function in defence against necrotrophic pathogens. Information regarding the role of GLVs and JA in interactions with (hemi)biotrophic pathogens remains limited. To functionally elucidate GLVs and JA in defence against a hemibiotrophic pathogen, we tested GLV‐ and JA‐deficient mutants, lox10 and opr7 opr8, respectively, for resistance to ASR and ALB and profiled jasmonates and SA in their stalks and leaves throughout infection. Both mutants were resistant and generally displayed elevated levels of SA and low amounts of jasmonates, especially at early stages of infection. Pretreatment with GLVs restored susceptibility of lox10 mutants, but not opr7 opr8 mutants, which coincided with complete rescue of JA levels. Exogenous methyl jasmonate restored susceptibility in both mutants when applied before inoculation, whereas methyl salicylate did not induce further resistance in either of the mutants, but did induce mutant‐like resistance in the wild type. Collectively, this study reveals that GLVs and JA contribute to maize susceptibility to C. graminicola due to suppression of SA‐related defences.
Graduated nurses' experiences with baccalaureate thesis writing: A qualitative study
Authors: Aguayo‐González Mariela , Leyva‐Moral Juan M. , San Rafael Sabiniana , Fernandez Maria Isabel , Gómez‐Ibáñez Rebeca
Published: February 2020

This study explores the perceptions of newly graduated nurses regarding the baccalaureate thesis (BT) writing process. A qualitative approach with content analysis was adopted. Thirteen newly graduated nurses participated in the study. The inclusion criterion was having completed the BT during their university education as nurses within 3 years of the study. Information was obtained through semistructured interviews. Data collection began in June 2018 and ended in March 2019, once saturation of information was reached. Three major categories were identified: the beginning of the process, the advantages of Baccalaureate thesis writing, and the teacher's role. The participants expressed that their training focused on a synthetic and particular type of writing that is necessary for clinical scenarios but not suitable for scientific academic texts. Additionally, reflective diaries were described as a powerful writing practice during their studies. Participants conceive the realization of the baccalaureate thesis as a difficult process, especially as regards selecting, synthesizing, and writing about the available information, processes that they indicated generate anxiety. Academic writing skills should be specifically included in the nursing curriculum.