bluuebunny/crossref_metadata_2025 huggingface dataset:
Religious Service Attendance, Educational Attainment, and Hypertension at Baseline of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)
Authors: Varella Ana C , Benseñor Isabela M , Fonseca Maria J M , Griep Rosane H , Pereira Alexandre C , Lotufo Paulo A
Published: March 2020

Background

Some religious dimensions have been associated with different health-related outcomes over many years. Attending religious services is one of these dimensions that were associated with hypertension, with inconsistent results. And religious involvement seems to be closely influenced by sociodemographic factors, such as education. Therefore, this study aimed to investigate the association between religious service attendance and hypertension according to levels of education.

Methods

We analyzed baseline data of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Frequency of religious service attendance and presence of hypertension were assessed in all 15,105 participants at baseline. The analyses were stratified by two levels of education (less than high school and high school or more). Logistic regression models were used to obtain the association between religious service attendance and hypertension in both groups.

Results

For those with high school or more, attending religious services was positively associated with hypertension (adjusted odds ratio [OR] = 1.14, 95% confidence interval [CI] 1.02–1.28). In contrast, for those with less than high school, attending services was inversely associated with presence of hypertension (adjusted OR = 0.73, 95% CI 0.55–0.96).

Conclusions

There seems to be a paradox in the association of religious service attendance and hypertension depending on the level of education.
projectR: an R/Bioconductor package for transfer learning via PCA, NMF, correlation and clustering
Authors: Sharma Gaurav , Colantuoni Carlo , Goff Loyal A , Fertig Elana J , Stein-O’Brien Genevieve
Published: March 2020

Motivation

Dimension reduction techniques are widely used to interpret high-dimensional biological data. Features learned from these methods are used to discover both technical artifacts and novel biological phenomena. Such feature discovery is critically importent in analysis of large single-cell datasets, where lack of a ground truth limits validation and interpretation. Transfer learning (TL) can be used to relate the features learned from one source dataset to a new target dataset to perform biologically driven validation by evaluating their use in or association with additional sample annotations in that independent target dataset.

Results

We developed an R/Bioconductor package, projectR, to perform TL for analyses of genomics data via TL of clustering, correlation and factorization methods. We then demonstrate the utility TL for integrated data analysis with an example for spatial single-cell analysis.

Availability and implementation

projectR is available on Bioconductor and at https://github.com/genesofeve/projectR.

Contact

gsteinobrien@jhmi.edu or ejfertig@jhmi.edu

Supplementary information

Supplementary data are available at Bioinformatics online.
Functional effects of Tribbles homolog 2 in bovine ovarian granulosa cells†
Authors: Warma Aly , Ndiaye Kalidou
Published: March 2020

Tribbles homologs (TRIB) 1, 2, and 3 represent atypical members of the serine/threonine kinase superfamily. We previously identified TRIB2 as a differentially expressed gene in granulosa cells (GCs) of bovine preovulatory follicles. The current study aimed to further investigate TRIB2 regulation and study its function in the ovary. GCs were collected from follicles at different developmental stages: small antral follicles (SF), dominant follicles (DF) at day 5 of the estrous cycle, and hCG-induced ovulatory follicles (OFs). RT-qPCR analyses showed greater expression of TRIB2 in GC of DF as compared to OF and a significant downregulation of TRIB2 steady-state mRNA amounts by hCG/LH, starting at 6 h through 24 h post-hCG as compared to 0 h. Specific anti-TRIB2 polyclonal antibodies were generated and western blot analysis confirmed TRIB2 downregulation by hCG at the protein level. In vitro studies showed that FSH stimulates TRIB2 expression in GC. Inhibition of TRIB2 using CRISPR/Cas9 resulted in a significant increase in PCNA expression and an increase in steroidogenic enzyme CYP19A1 expression, while TRIB2 overexpression tended to decrease GC proliferation. TRIB2 inhibition also resulted in a decrease in transcription factors connective tissue growth factor (CTGF) and ankyrin repeat domain-containing protein 1 (ANKRD1) expression, while TRIB2 overexpression increased CTGF and ANKRD1. Additionally, western blot analyses showed reduction in ERK1/2 (MAPK3/1) and p38MAPK (MAPK14) phosphorylation levels following TRIB2 inhibition, while TRIB2 overexpression increased p-ERK1/2 and p-p38MAPK. These results provide evidence that TRIB2 modulates MAPK signaling in GC and that TRIB2 could act as a regulator of GC proliferation and function, which could affect steroidogenesis during follicular development.
Perceptions on community media for effective acculturation in Nigerian indigenous languages
Authors: Onwukwe Chimaobi
Published: March 2020

This study examined perceptions on the effectiveness, attendant challenges and remedies of community media for effective acculturation in Nigerian languages. The qualitative survey design was adopted with focus group discussions and key informant interviews of 50 purposively chosen informants. It was perceived that community media could serve as veritable platform for effective acculturation in Nigerian languages since they would engender the setting of acculturation in Nigerian languages as national objective or goal. It was further held that the strengths of community media for acculturation were in being goal-defined, ensuring local content and diversification. The study identified that as palatable as the proposal for community media for effective acculturation in Nigerian languages is, it would be fraught with some set-backs or challenges that were very much surmountable. Perceptions pointed towards transient nature of community media and funding as challenges as well as multibased funding as one remedy. Immediate establishment of community media for the purpose of acculturation in Nigerian languages was recommended.
General Principles of Law: The First Debate within the International Law Commission and the Sixth Committee
Authors: Vázquez-Bermúdez Marcelo , Crosato Alfredo
Published: March 2020

Continuing its work on the sources of international law, the International Law Commission decided, at its seventieth session, to include the topic “General principles of law” in its current programme of work. By taking up the topic, the Commission aims to shed light on various aspects of this source and provide guidance to States, international organizations, courts and tribunals and all others that may be called upon to deal with general principles of law. The present article provides an overview of the first debate on the topic that took place within the International Law Commission and the Sixth (Legal) Committee of the UN General Assembly in 2019, focusing on certain key issues that will be central to the treatment of the topic.
Living in a fragmented world: Birds in the Atlantic Forest
Authors: Pizo Marco A , Tonetti Vinicius R
Published: March 2020

The Atlantic Forest is the second largest tropical moist forest domain in South America after the Amazon, home to over 800 bird species (223 endemics or 27% of the avifauna). With only 28% of the original vegetation left, mostly fragmented and altered, the Atlantic Forest is a hotspot for bird conservation. We first introduce the extent, vegetation types, and exploitation history of the domain, and the composition and biogeographic affinities of its birds. We then provide an overview of the knowledge gathered so far on the ways Atlantic Forest birds thrive in the often-fragmented landscape, highlighting the landscape features that influence their occurrence and movement behavior. We end with the conservation issues affecting the Atlantic Forest birds and the actions hitherto taken to address them, including the establishment of conservation units, forest restoration, and rewilding.
Adult congenital diaphragmatic hernia with absent pericardium and liver heterotopia
Authors: Wang Xinyu , Chen Hezhong , Yang Lixin , Lu Chaojing
Published: March 2020

Adult congenital diaphragmatic hernia (CDH) with an absent pericardium and liver heterotopia is extremely rare, and had only been described in 1 patient. Here, we present another case of left-sided central CDH in a 40-year-old Chinese woman.
Use of amenable mortality indicators to evaluate the impact of financial crisis on health system performance in Greece
Authors: Zilidis Christos , Stuckler David , McKee Martin
Published: March 2020

Background

Greece experienced the largest reduction in its health care budget of any European country during the economic crisis of 2008–15. Here, we test the hypothesis that budget reductions worsened health system performance in Greece, using the concept of Amenable Mortality to capture deaths which should not occur in the presence of effective and timely health care.

Methods

Amenable mortality was calculated from national mortality statistics, using age-standardized deaths from 34 conditions amenable to medical intervention in Greece during 2000–16, with further analysis by sex, age, region and cause. Mortality rate ratios and their 95% CI were also computed. Interrupted time series analyses were performed to compare trends prior to austerity measures (2001–10) with those after (2011–16), adjusting for historical trends.

Results

Prior to austerity measures, amenable mortality rates were declining. After 2011, coinciding with the inception of budget reductions, the slope of decline diminished significantly. The average annual percent of change in standardized death rates was 2.65% in 2001–10, falling to 1.60% in 2011–6. In 10 of 34 conditions, the SDR increased significantly after the crisis onset, and in five more conditions the long-term decline reversed, to increasing after 2011. The age-specific mortality rates observed in 2011–16 were significantly higher than those expected at ages 0–4 and 65–74 but not significantly higher in all other age groups.

Conclusions

Health system performance in Greece worsened in association with austerity measures, leading to a deceleration of the decline in amenable mortality and increased mortality from several conditions amenable to medical interventions.
Methanobactin from methanotrophs: genetics, structure, function and potential applications
Authors: Semrau Jeremy D , DiSpirito Alan A , Obulisamy Parthiba Karthikeyan , Kang-Yun Christina S
Published: March 2020

Aerobic methane-oxidizing bacteria of the Alphaproteobacteria have been found to express a novel ribosomally synthesized post-translationally modified polypeptide (RiPP) termed methanobactin (MB). The primary function of MB in these microbes appears to be for copper uptake, but MB has been shown to have multiple capabilities, including oxidase, superoxide dismutase and hydrogen peroxide reductase activities, the ability to detoxify mercury species, as well as acting as an antimicrobial agent. Herein, we describe the diversity of known MBs as well as the genetics underlying MB biosynthesis. We further propose based on bioinformatics analyses that some methanotrophs may produce novel forms of MB that have yet to be characterized. We also discuss recent findings documenting that MBs play an important role in controlling copper availability to the broader microbial community, and as a result can strongly affect the activity of microbes that require copper for important enzymatic transformations, e.g. conversion of nitrous oxide to dinitrogen. Finally, we describe procedures for the detection/purification of MB, as well as potential medical and industrial applications of this intriguing RiPP.
Why Have Sleep Problems in Later-Midlife Grown Following the Great Recession? A Comparative Cohort Analysis
Authors: Bierman Alex
Published: March 2020

Objectives

This research compares three cohorts of individuals in their fifth decade of life and examines whether sleep problems are greater in cohorts following the Great Recession. We argue that these differences will occur because postrecession cohorts are exposed to more economic burdens that harm sleep. We also suggest that postrecession exposure to economic burdens will be amplified among women, leading to greater cross-cohort differences in sleep problems.

Method

Data were derived from the Health and Retirement Study, focusing on cohort surveys starting in 2004, 2010, and 2016 (N = 12,129). Structural equation models compared cohorts in latent levels of sleep problems and also examined whether economic burdens mediated cohort differences. Interactions tested whether cohort differences varied between men and women.

Results

The 2010 and 2016 cohorts had higher mean levels of sleep problems than the 2004 cohort. Greater postrecession exposure to economic burdens largely explained inter-cohort change in sleep problems, with this pattern stronger among women.

Discussion

Americans are approaching their senior years increasingly burdened by economic stressors that incur sleep problems. Practitioners and aging researchers should be prepared to address deleterious health consequences created by heightened sleep impairments.
The Proactive Shift in Managing an Older  Workforce 2009–2017: A Latent Class Analysis of Organizational Policies
Authors: Turek Konrad , Oude Mulders Jaap , Henkens Kène
Published: March 2020

Background and Objectives

Longitudinal perspectives on how organizations react to workforce aging are missing in the literature. In this study, we fill this gap and ask how organizations deal with older workers, how their approaches change over time, and in which sectors of the economy and types of organizations the changes were most profound.

Research Design and Methods

Data come from two large-scale employer surveys: 2009 (n = 1,077) and 2017 (n = 1,358), representative for the Netherlands. We use a three-step group-comparison latent class analysis combined with a multinomial logistic model.

Results

We found four clusters of organizations based on their practices regarding older workers—those trying to activate and develop their employees (active), focusing solely on exit measures (exit), implementing a combination of development, accommodating and exit measures (all), and practicing no age management (none). We find a major shift in employers’ approaches to aging workforces between 2009 and 2017, with strong decreases in those that offered no age management (47%–30%) and those focusing on exit measures (21%–6%), and an increase in active organizations (19%–52%). Active age management is no longer concentrated in large and developing organizations, but has become a standard human resources tool economy-wide.

Discussion and Implications

Overall, there is a long-term trend away from exit measures toward the application of proactive age management measures. More involvement of employers in retaining older adults in the workplace may signal a growing awareness of the changing demographic reality.
Presence of Influenza Virus on Touch Surfaces in Kindergartens and Primary Schools
Authors: Fong Min Whui , Leung Nancy H L , Xiao Jingyi , Chu Daniel K W , Cheng Samuel M S , So Hau Chi , Li Yuguo , Ip Dennis K M , Peiris J S Malik , Cowling Benjamin J
Published: March 2020

Backgrounds

Influenza virus can survive on some surfaces, facilitating indirect person-to-person transmission.

Methods

We collected swab samples weekly from commonly touched surfaces in 7 kindergartens and primary schools during the 2017/2018 winter influenza season in Hong Kong.

Results

We detected influenza virus ribonucleic acid (RNA) in 12 of 1352 samples (<1%) collected from 7 of 11 classrooms (5 to 2 × 106 RNA copies/mL). Viral RNA was more frequently recovered from communal items inside classrooms such as bookshelves and doorknobs.

Conclusions

Surface contamination indicates the potential role of fomites in influenza virus transmission in schools. Communal items inside classrooms may cause greater potential risks of transmission during influenza epidemics.
Pollution, Ability, and Gender-Specific Investment Responses to Shocks
Authors: Molina Teresa
Published: March 2020

This paper explores how labor market conditions drive gender differences in the human capital decisions of men and women. Specifically, I investigate how male and female schooling decisions respond to an exogenous change in cognitive ability. Using data from Mexico, I begin by documenting that in utero exposure to thermal inversions, which exacerbate air pollution, leads to lower cognitive ability in adulthood for both men and women. I then explore how male and female schooling decisions respond differentially to this cognitive shock: for women only, pollution exposure leads to reduced educational attainment and income. I show that this gender difference is explained by the fact that women disproportionately sort into white-collar jobs, where schooling and ability are more complementary than they are in blue-collar jobs.
WRKY10 transcriptional regulatory cascades in rice are involved in basal defense and Xa1-mediated resistance
Authors: Choi Naeyeoung , Im Jong Hee , Lee Eunhye , Lee Jinjeong , Choi Changhyun , Park Sang Ryeol , Hwang Duk-Ju
Published: March 2020

WRKY proteins play essential roles as negative or positive regulators of pathogen defense. This study explored the roles of different OsWRKY proteins in basal defense and Xa1-mediated resistance to Xanthomonas oryzae pv. oryzae (Xoo) infection in rice. Assays of disease in OsWRKY10KD and OsWRKY88KD lines following infection with an incompatible Xoo race, which induced Xa1-mediated resistance in wild-type plants, showed that OsWRKY10 and OsWRKY88 were positive regulators of Xa1-mediated resistance. OsWRKY10 also acted as a positive regulator in basal defense by directly or indirectly activating transcription of defense-related genes. OsWRKY10 activated the OsPR1a promoter by binding to specific WRKY binding sites. Two transcriptional regulatory cascades of OsWRKY10 were identified in basal defense and Xa1-mediated resistance. In the first transcriptional regulatory cascade, OsWRKY47 acted downstream of OsWRKY10 whereas OsWRKY51 acted upstream. OsWRKY10 activated OsPR1a in two distinct ways: by binding to its promoter and, at the same time, by indirect activation through OsWRKY47. In the second transcriptional regulatory cascade, OsWRKY47 acted downstream of OsWRKY10, and OsWRKY88 acted upstream. These OsWRKY10 transcriptional regulatory cascades played important roles in basal defense and Xa1-mediated resistance to enable the mounting of a rapid immune response against pathogens.
German-Jewish Esotericism: The Case of Meir Wiener’s Expressionist Kabbalah
Authors: Engel Amir
Published: March 2020

The fact that bizarre intellectual trends and teachings, like occultism, parapsychology, and neopaganism played an important role in modern German culture is thoroughly documented by scholars of German history. Experts on German-Jewish history, however, still tend to describe German-Jewish culture as one formed around the ideals of ‘Bildung’ and the Enlightenment. As a result, German-Jewish occultism, mysticism, and other non-Enlightenment texts and authors have received relatively little scholarly attention. The present article aims to help correct this bias by introducing a new framework for the study of German-Jewish culture, and by examining an all but forgotten case study: Meir Wiener and his work. After introducing the term ‘Western esotericism’, developed by scholars of religious studies, the article uses it to explore two of Meir Wiener’s strangest and virtually forgotten works. Wiener, it is shown, produced fantastically esoteric works in the context of German expressionism and Kabbalah studies, which better represent their time and place than scholars have thus far acknowledged.
Free Will and Luck: Compatibilism versus Incompatibilism
Authors: Mele Alfred R
Published: March 2020

Compatibilists about free will maintain that free will is compatible with determinism, and incompatibilists disagree. Incompatibilist believers in free will have been challenged to solve a problem that luck poses for them—the problem of present luck. This article articulates that challenge and then explores a novel compatibilist view recently proposed by Christian List. It is argued that List’s view, unlike standard compatibilist views, faces a very similar problem about luck.
Treatment of fibrillary glomerulonephritis with rituximab: a 12-month pilot study
Authors: Erickson Stephen B , Zand Ladan , Nasr Samih H , Alexander Mariam P , Leung Nelson , Drosou Maria Eleni , Fervenza Fernando C
Published: March 2020

Background

Fibrillary glomerulonephritis (FGN) is a rare type of glomerulonephritis with poor prognosis, with no known effective therapies available for treatment. The objective of the study was to evaluate the efficacy and safety of rituximab in treatment of patients with FGN and to investigate the effect of rituximab on DNAJB9 levels.

Methods

This was a pilot prospective clinical trial in which patients with idiopathic FGN were treated with two courses of rituximab (1 g each) 2 weeks apart at the beginning and then again at 6 months. Primary outcome was defined as preservation of kidney function at 12 months with stable or increased creatinine clearance. Secondary outcome was defined as achieving complete remission (CR) defined as proteinuria <300 mg/24 h or partial remission (PR) with proteinuria <3 g/24 h and at least 50% reduction in the proteinuria. DNAJB9 levels were also measured in the serum at baseline, 6 and 12 months.

Results

The creatinine clearance did not change significantly during this time, from 47.7 mL/min/1.73 m2 at baseline to 43.7 mL/min/1.73 m2 during follow-up (P = 0.15). Proteinuria declined from 4.43 (1.6–5.53) g/24 h at baseline to 1.9 (0.46–5.26) g/24 h at 12 months but did not reach significance (P = 0.06). None of the patients reached CR, and 3 of the 11 achieved PR. There was no change in the DNAJB9 levels following treatment with rituximab. The most common adverse event was nasal congestion, fatigue and muscle cramps.

Conclusions

Treatment of patients with two courses of rituximab over a span of 6 months was associated with stabilization of renal function but did not result in a significant change in proteinuria and with no change in the DNAJB9 levels.
A Sperm and Ovum Separately! Contra Marquis on Abortion and Contraception
Authors: Burkhardt Tim
Published: March 2020

Don Marquis argues that abortion is prima facie seriously wrong because it deprives the foetus of a valuable future. This paper argues that there is no morally relevant difference between the relations that foetuses stand in to valuable futures and those that gametes stand in to such futures. Therefore, Marquis’ account implies that contraception is prima facie seriously wrong. My argument for this conclusion has a significant advantage over existing criticisms of Marquis based on controversial accounts of personal identity. It shows that the problem with his account is not his view that identity across time is a matter of merely biological relations, but his investment of those relations with moral significance. This criticism has force no matter which account of personal identity is true.
A resazurin-based, nondestructive assay for monitoring cell proliferation during a scaffold-based 3D culture process
Authors: Gong Xianghui , Liang Zhuqing , Yang Yongxing , Liu Haifeng , Ji Jing , Fan Yubo
Published: March 2020

Development of viable cell estimation method without sacrificing proliferation and functions of cells cultured on regenerative biomaterials is essential for regenerative engineering. Cytotoxicity and depletion of resazurin are critical but often overlooked limitations that hindered applications of resazurin in viable cell estimation. The present work found that cytotoxicity and depletion of resazurin depended on cell concentration, resazurin concentration and resazurin incubation time. A simple strategy which only allowed cells to incubate with resazurin during each measurement was developed to eliminate negative effects of resazurin. This strategy was verified by monitoring proliferation of MC3T3-E1 preosteoblasts on poly(d,l-lactic acid) scaffold during a continuous 3D culture process for up to 21 days, comparing the accuracy with MTT assay which is a destructive assay with high sensitivity and accuracy and commonly used in regenerative engineering and comparing viability, proliferation and differentiation functions of MC3T3-E1, which were treated with/without this strategy for nondestructive evaluation. This method showed comparable linearity of standard curve and characteristics of growth curve to MTT assay. No major negative effects of this method on MC3T3-E1 viability and functions were found. Our work highlighted the importance of the concentration and incubation time of resazurin in designing application-specific nondestructive viability assay and would be helpful in improving the implanted medical devices as well as in regenerative engineering.
Exposure to Community-Based Violence on Social Media among Black Male Emerging Adults Involved with the Criminal Justice System
Authors: Motley Robert O , Chen Yu-Chih , Johnson Carnayla , Joe Sean
Published: March 2020

The prevalence of community-based violence (CBV) exposure among black American male emerging adults ages 18 to 25 with a history of involvement with the criminal justice system is a major public health concern. Although exposure (whether as victim or witness) to CBV is linked with negative outcomes, empirical research examining black men’s negative emotional responses to seeing videos of real-life incidents of CBV on social media is scant. To address these identified concerns and make recommendations for future research, the present study examines the relationship between seeing videos of CBV on social media and three types of negative emotional responses (that is, feeling sad, angry, and fearful) prior to incarceration among a sample of 101 black men detained in a midwestern jail. Social media use and seeing videos of CBV on social media were moderately high for study participants. Seeing a video involving police violence was significantly associated with an increase in the odds of feeling sad, angry, and fearful. Social media research is an emerging area that has the potential to advance our understanding of the impact of seeing social media videos of police violence on the well-being of black men and factors that mediate or moderate this relationship.
Nitrosative Stress and Lipid Homeostasis as a Mechanism for Zileuton Hepatotoxicity and Resistance in Genetically Sensitive Mice
Authors: You Dahea , Lyn-Cook Lascelles E , Gatti Daniel M , Bell Natalie , Mayeux Philip R , James Laura P , Mattes William B , Larson Gary J , Harrill Alison H
Published: March 2020

Zileuton is an orally active inhibitor of leukotriene synthesis for maintenance treatment of asthma, for which clinical usage has been associated with idiosyncratic liver injury. Mechanistic understanding of zileuton toxicity is hampered by the rarity of the cases and lack of an animal model. A promising model for mechanistic study of rare liver injury is the Diversity Outbred (J:DO) mouse population, with genetic variation similar to that found in humans. In this study, female DO mice were administered zileuton or vehicle daily for 7 days (i.g.). Serum liver enzymes were elevated in the zileuton group, with marked interindividual variability in response. Zileuton exposure-induced findings in susceptible DO mice included microvesicular fatty change, hepatocellular mitosis, and hepatocellular necrosis. Inducible nitric oxide synthase and nitrotyrosine abundance were increased in livers of animals with necrosis and those with fatty change, implicating nitrosative stress as a possible injury mechanism. Conversely, DO mice lacking adverse liver pathology following zileuton exposure experienced decreased hepatic concentrations of resistin and increased concentrations of insulin and leptin, providing potential clues into mechanisms of toxicity resistance. Transcriptome pathway analysis highlighted mitochondrial dysfunction and altered fatty acid oxidation as key molecular perturbations associated with zileuton exposure, and suggested that interindividual differences in cytochrome P450 metabolism, glutathione-mediated detoxification, and farnesoid X receptor signaling may contribute to zileuton-induced liver injury (ZILI). Taken together, DO mice provided a platform for investigating mechanisms of toxicity and resistance in context of ZILI which may lead to targeted therapeutic interventions.
Post-fire effects on development of leaves and secondary vascular tissues in Quercus pubescens
Authors: Gričar Jožica , Hafner Polona , Lavrič Martina , Ferlan Mitja , Ogrinc Nives , Krajnc Bor , Eler Klemen , Vodnik Dominik
Published: March 2020

An increased frequency of fire events on the Slovenian Karst is in line with future climate change scenarios for drought-prone environments worldwide. It is therefore of the utmost importance to better understand tree–fire–climate interactions for predicting the impact of changing environment on tree functioning. To this purpose, we studied the post-fire effects on leaf development, leaf carbon isotope composition (δ13C), radial growth patterns and the xylem and phloem anatomy in undamaged (H-trees) and fire-damaged trees (F-trees) of Quercus pubescens Willd. with good resprouting ability in spring 2017, the growing season after a rangeland fire in August 2016. We found that the fully developed canopy of F-trees reached only half of the leaf area index values measured in H-trees. Throughout the season, F-trees were characterized by higher water potential and stomatal conductivity and achieved higher photosynthetic rates compared to unburnt H-trees. The foliage of F-trees had more negative δ13C values than those of H-trees. This reflects that F-trees less frequently meet stomatal limitations due to reduced transpirational area and more favourable leaf-to-root ratio. In addition, the growth of leaves in F-trees relied more on the recent photosynthates than on reserves due to the fire disturbed starch accumulation in the previous season. Cambial production stopped 3 weeks later in F-trees, resulting in 60 and 22% wider xylem and phloem increments, respectively. A novel approach by including phloem anatomy in the analyses revealed that fire caused changes in conduit dimensions in the early phloem but not in the earlywood. However, premature formation of the tyloses in the earlywood vessels of the youngest two xylem increments in F-trees implies that xylem hydraulic integrity was also affected by heat. Analyses of secondary tissues showed that although xylem and phloem tissues are interlinked changes in their transport systems due to heat damage are not necessarily coordinated.
Treatment of immune checkpoint inhibitor-induced inflammatory arthritis
Authors: Jeurling Susanna , Cappelli Laura C.
Published: March 2020

Purpose of review

This review summarizes the current evidence on treatment strategies for inflammatory arthritis because of cancer treatment with immune checkpoint inhibitors (ICI), prognosis of ICI-induced arthritis, and management of patients with preexisting inflammatory arthritis receiving ICI therapy.

Recent findings

Inflammatory arthritis is the most common rheumatic immune-related adverse event observed in patients receiving ICI therapy. Most patients can successfully be treated with low doses of corticosteroids or conventional synthetic disease modifying anti-rheumatic drugs (DMARDs). A small minority will develop severe symptoms requiring biologic therapy including TNF inhibitors and IL-6 receptor inhibitors. Many cases of inflammatory arthritis will resolve with cessation of ICI therapy. Some patients will develop persistent arthritis despite discontinuation. Patients with preexisting inflammatory arthritis (e.g. rheumatoid arthritis) commonly flare on ICI therapy, but can usually be managed with corticosteroids.

Inflammatory arthritis following ICI therapy for cancer is relatively common and the practicing rheumatologist should be able to recognize and manage it in conjunction with Oncology. The majority of patients respond to corticosteroids, but some will need treatment with conventional synthetic or biologic DMARDs. Additional studies should investigate the effects of immunosuppression on tumor response and the use of ICI therapy in patients with preexisting autoimmune disease.
Effect of Flumazenil on Hypoactive Delirium in the ICU: A Double-Blind, Placebo-Controlled Pilot Study
Authors: Schomer Kendra J. , Duby Jeremiah J. , Firestone Rachelle L. , Louie Erin L. , Sebat Christian M. , Love Dawn M. , Cocanour Christine S. , Albertson Timothy E.
Published: March 2020

Objectives:

To determine whether the use of flumazenil reverses hypoactive delirium and increases delirium-free days in critically ill patients who were exposed to benzodiazepine therapy during the ICU admission.

Design:

This was a single-center, double-blinded, randomized placebo-controlled pilot study.

Setting:

Adult ICUs at a large academic medical center in the United States.

Patients:

Adult, critically ill patients with benzodiazepine exposure and hypoactive delirium based on the Confusion Assessment Method-ICU and Richmond Agitation Sedation Scale assessments were considered for enrollment.

Interventions:

Patients received a test dose of flumazenil starting at 0.1 mg intravenously and titrated up every 5 minutes by 0.1 mg increments up to a maximum total dose of 2 mg. Patients who demonstrated a Richmond Agitation Sedation Scale score increase of greater than 1 point were considered responders and randomized to flumazenil (0.05–0.3 mg/hr) or placebo infusion for up to 72 hours. Confusion Assessment Method-ICU scores were assessed twice daily for resolution of delirium.

Measurements and Main Results:

The trial was stopped early based on the observed size effect and power analysis. Twenty-two of the 25 patients responded to the flumazenil test dose (88%). The median number of delirium-free days alive without coma within 14 days of enrollment was similar between the two infusion groups (12.7 vs 9.2; p = 0.19). There was no difference in the probability of delirium resolution within the first 14 days with 90% versus 70% in the flumazenil and placebo groups, respectively (p = 0.2). There was no statistical difference (odds ratio, 0.17; 95% CI, 0.022–1.23; p = 0.079) in delirium- and coma-free days at the end of the study drug infusion. There was no difference between groups in ICU length of stay (7.8 ± 4.8 vs 7 ± 8; p = 0.74). No serious adverse events occurred.

Conclusions:

This study found that flumazenil test dose and infusion present a potential option for hypoactive delirium associated with benzodiazepine exposure; however, the possible benefit is unknown. Larger studies are warranted to further evaluate these findings.
Shared immunotherapeutic approaches in HIV and hepatitis B virus: combine and conquer
Authors: Maini Mala K. , Peppa Dimitra
Published: March 2020

Purpose of review

The aim of this study was to identify similarities, differences and lessons to be shared from recent progress in HIV and hepatitis B virus (HBV) immunotherapeutic approaches.

Recent findings

Immune dysregulation is a hallmark of both HIV and HBV infection, which have shared routes of transmission, with approximately 10% of HIV-positive patients worldwide being coinfected with HBV. Immune modulation therapies to orchestrate effective innate and adaptive immune responses are currently being sought as potential strategies towards a functional cure in both HIV and HBV infection. These are based on activating immunological mechanisms that would allow durable control by triggering innate immunity, reviving exhausted endogenous responses and/or generating new immune responses. Recent technological advances and increased appreciation of humoral responses in the control of HIV have generated renewed enthusiasm in the cure field.

For both HIV and HBV infection, a primary consideration with immunomodulatory therapies continues to be a balance between generating highly effective immune responses and mitigating any significant toxicity. A large arsenal of new approaches and ongoing research offer the opportunity to define the pathways that underpin chronic infection and move closer to a functional cure.
Global clinical experience of a long-term surgical mission trip
Authors: Barrera Rafael , Aronowitz Danielle , Badauoi Charles , Jarrin Patricia , Santoriello Lisa M. , Palacios Ivan , Grunauer Michelle , Snyder Dennis , Coppa Gene
Published: March 2020

Countless medical mission trips have traveled across the globe to provide health care, medical education, and social services to underserved populations in need. However, establishing sustainable health care initiatives in these remote locations has been challenging. Here we describe the successful strategies use by volunteers from the Medical Missions for Children (MMFC) and the Global Health Initiate of the Surgical Service Line of Northwell Health in our mission trips to Quito, Ecuador.
Local treatment of infectious and noninfectious intermediate, posterior, and panuveitis: current concepts and emerging therapeutics
Authors: Thomas Akshay S. , Lin Phoebe
Published: March 2020

Purpose of review

Local therapeutics play an important role in the management of infectious and noninfectious uveitis (NIU) as well as certain masquerade syndromes. This review highlights the established therapeutics and those under investigation for the management of uveitis.

Recent findings

An injectable long-acting fluocinolone acetonide insert was recently approved by the Food and Drug Administration for the treatment of NIU affecting the posterior segment. Intravitreal methotrexate, sirolimus, and anti-vascular endothelial growth factor (VEGF) agents are being evaluated for efficacy in NIU. Intravitreal foscarnet and ganciclovir are important adjuncts in the treatment of viral retinitis as are methotrexate and rituximab for the management of vitreoretinal lymphoma.

Local injectable steroids with greater durability are now available for NIU but comparative efficacy to other treatment modalities remains to be determined. Local steroid-sparing immunosuppressive agents are undergoing evaluation for efficacy in NIU as are anti-VEGF agents for uveitic macular edema. Local antivirals may improve outcomes in cases of viral retinitis. Local chemotherapeutics can help induce remission in vitreoretinal lymphoma.
The future of retinal imaging
Authors: Li Daniel Q. , Choudhry Netan
Published: March 2020

Purpose of review

This article reviews emerging technologies in retinal imaging, including their scientific background, clinical implications and future directions.

Recent findings

Fluorescence lifetime imaging ophthalmoscopy is a technology that will reveal biochemical and metabolic changes of the retina at the cellular level. Optical coherence tomography is evolving exponentially toward higher resolution, faster speed, increased portability and more cost effective. Adaptive optics scanning laser ophthalmoscopy fluorescein angiography will provide unprecedented detail of the retinal vasculature down to the level of capillaries, enabling earlier and more sensitive detection of retinal vascular diseases.

Continued developments in retinal imaging focus on improved resolution, faster speed and noninvasiveness, while providing new information on the structure–function relationship of the retina inclusive of metabolic activity at the cellular level.
Complete hemostasis achieved by factor XIII concentrate administration in a patient with bleeding after teeth extraction as a complication of aplastic anemia and chronic disseminated intravascular coagulation
Authors: Yamada Shinya , Okumura Hirokazu , Morishita Eriko , Asakura Hidesaku
Published: March 2020

Hemostatic treatment of disseminated intravascular coagulation (DIC) due to aortic aneurysm involves numerous difficulties. An 89-year-old man with aplastic anemia and chronic DIC developed periodontitis and loose teeth requiring extraction, after which hemostasis was difficult. Platelet concentrates and fresh-frozen plasma transfusions were ineffective, and there was a risk of hemorrhage; therefore, administration of anticoagulant agents for DIC was inappropriate. A decrease in factor XIII (FXIII) was discovered, and FXIII concentrate was administered, resulting in hemostasis together with wound healing. No complications were seen, but the following coagulation markers were found to decrease: fibrin degradation products, d-dimer, thrombin–antithrombin complex, and plasmin-α2 plasmin inhibitor complex. By 1 month after FXIII administration, FXIII had returned to the preadministration level, thus, the FXIII decrease was deduced to be have been due to DIC. These findings suggest that FXIII concentrate is useful for treating hemorrhage associated with DIC due to aortic aneurysm.
Changes in Pancreatic Endocrine Function and Morphology After Pancreaticoduodenectomy
Authors: Yoon Hye Jeong , Choi Jeong Sik , Shin Woo Young , Lee Keon-Young , Ahn Seung-Ik
Published: March 2020

Objectives

It is unclear whether the improved glucose metabolism in pancreas head cancer (PHC) patients after pancreaticoduodenectomy is due to the anatomical change or the relief of pancreatic duct obstruction.

Methods

We divided 170 patients into the PHC group (n = 54, 31.8%) and other pathology (non-PHC) group (n = 116, 68.2%). Glucose metabolic function was evaluated using the glucose tolerance index (GTI), and the pancreatic duct obstruction and dilatation was measured using the pancreatic atrophic index (PAI).

Results

The preoperative GTI was significantly higher in the PHC group (mean [standard deviation {SD}], 0.84 [1.16]) than in the non-PHC group (0.41 [SD, 0.59], P = 0.000). The postoperative GTI decreased significantly in the PHC group but remained unchanged in the non-PHC group. Similarly, the preoperative PAI was higher in the PHC group (0.32 [SD, 0.19]) than in the non-PHC group (0.13 [SD, 0.09], P = 0.000). The postoperative PAI decreased significantly in the PHC group, but not in the non-PHC group.

Conclusions

The impaired glucose metabolism in PHC can be caused by pancreatic duct obstruction. After pancreaticoduodenectomy, glucose metabolism is improved by the relief of pancreatic duct obstruction, and not by the anatomical change. The patients should be counseled accordingly.
Routine Chest Computed Tomography for Staging of Pancreatic Head Carcinoma
Authors: Leeuw Dianne , Pranger Bobby K. , de Jong Koert P. , Pennings Jan Pieter , de Meijer Vincent E. , Erdmann Joris I.
Published: March 2020

Objectives

The diagnostic value of routine chest computed tomography (CT) in addition to abdominal CT in workup for pancreatic head carcinoma is unclear. The aim of this study was to determine if routine chest CT revealed significant lesions that altered the management of patients with suspected pancreatic head carcinoma.

Methods

All Dutch pancreatic cancer centers were surveyed on the use of chest CT in preoperative staging. In addition, a single-center retrospective cohort study was performed including all patients referred with suspected pancreatic head malignancy without chest CT between 2005 and 2016. The primary end point was the proportion of patients in which chest CT revealed clinically significant lesions, leading to a change in management.

Results

In 7 of 18 Dutch pancreatic cancer centers (39%), a preoperative chest CT is not routinely performed. In the study cohort, 170 of 848 patients (20%) were referred without chest CT and underwent one by local protocol. Chest CT revealed new suspicious lesions in 17 patients (10%), of whom 6 had metastatic disease (3.5%).

Conclusions

Routine use of chest CT in diagnostic workup for pancreatic head carcinoma reveals clinically significant lesions in 10% of patients, being metastases in up to 4%.
Clinical Benefits of Telotristat Ethyl in Patients With Neuroendocrine Tumors and Low Bowel Movement Frequency
Authors: Benson Al B. , Strosberg Jonathan , Joish Vijay N. , Dharba Samyukta , Sapre Dipa , Lapuerta Pablo
Published: March 2020

Objectives

We evaluated carcinoid syndrome (CS) symptoms and the real-world effectiveness of telotristat ethyl (TE) among patients with ≤3 bowel movements (BM) per day.

Methods

Patients with CS initiating TE between March and November 2017 could participate in a nurse support program collecting demographic and CS symptom data before TE initiation (baseline) and during ≥1 monthly follow-up within 3 months. Symptoms for patients averaging ≤3 BM/d at baseline were evaluated using pre/post–Student t tests.

Results

Sixty-eight patients reported ≤3 BM/d at baseline. Symptom burden was high and similar to participants with higher daily BM frequency. After 3 months of TE, most patients reported stable or improved symptoms with significant improvements in urgency (88%; mean [SD], –13.2 [32.2]), stool consistency (88%; −1.3 [2.0]), BMs per day (81%; −0.2 [1.2]), abdominal pain (86%; −13.7 [25.8]), nausea (85%; −30.9 [35.7]), and daily flushing episodes (83%; −1.7 [4.4]; all except BMs per day, P < 0.05).

Conclusions

This analysis illustrates high CS symptom burden among patients with relatively low daily BM frequency. After initiating TE, patients reported significant improvements in urgency, stool consistency, abdominal pain, nausea, and flushing episodes. Clinicians and population health managers should consider CS symptom burden beyond daily BM frequency when evaluating treatment selection.
Neoadjuvant Capecitabine/Temozolomide for Locally Advanced or Metastatic Pancreatic Neuroendocrine Tumors
Authors: Squires Malcolm H. , Worth Patrick J. , Konda Bhavana , Shah Manisha H. , Dillhoff Mary E. , Abdel-Misih Sherif , Norton Jeffrey A. , Visser Brendan C. , Dua Monica , Pawlik Timothy M. , Schmidt Carl R. , Poultsides George , Cloyd Jordan M.
Published: March 2020

Objectives

The combination chemotherapy regimen capecitabine/temozolomide (CAPTEM) is efficacious for metastatic well-differentiated pancreatic neuroendocrine tumors (PNETs), but its role in the neoadjuvant setting has not been established.

Methods

The outcomes of all patients with locally advanced or resectable metastatic PNETs who were treated with neoadjuvant CAPTEM between 2009 and 2017 at 2 high-volume institutions were retrospectively reviewed.

Results

Thirty patients with locally advanced PNET (n = 10) or pancreatic neuroendocrine hepatic metastases (n = 20) received neoadjuvant CAPTEM. Thirteen patients (43%) exhibited partial radiographic response (PR), 16 (54%) had stable disease, and 1 (3%) developed progressive disease. Twenty-six (87%) patients underwent resection (pancreatectomy [n = 12], combined pancreatectomy and liver resection [n = 8], or major hepatectomy alone [n = 6]); 3 (18%) declined surgery despite radiographic PR, and 1 (3%) underwent aborted pancreatoduodenectomy. Median primary tumor size was 5.5 cm, and median Ki-67 index was 3.5%. Rates of PR were similar across tumor grades (P = 0.24). At median follow-up of 49 months, median progression-free survival was 28.2 months and 5-year overall survival was 63%.

Conclusions

Neoadjuvant CAPTEM is associated with favorable radiographic objective response rates for locally advanced or metastatic PNET and may facilitate selection of patients appropriate for surgical resection.