bluuebunny/crossref_metadata_2025 huggingface dataset:
Peptidorhamanomannan: A surface fungal glycoconjugate from Scedosporium aurantiacum and Scedosporium minutisporum and its recognition by macrophages
Authors: de Meirelles Jardel Vieira , Xisto Mariana Ingrid Dutra da Silva , Rollin-Pinheiro Rodrigo , Serrato Rodrigo Vassoler , Haido Rosa Maria Tavares , Barreto-Bergter Eliana
Published: August 2020

The genus Scedosporium is composed of clinically relevant fungal species, such as Scedosporium aurantiacum, Scedosporium apiospermum, and Scedosporium boydii. Surface molecules have been described that play crucial roles in fungi-macrophage interaction, and many of them are pathogen-associated molecular patterns (PAMPs). The present study aims to characterize peptidoglycans obtained from Scedosporium aurantiacum and Scedosporium minutisporum, a clinical and an environmental isolate, respectively, and compare their roles in pathogen-host interaction. Both molecules were characterized as peptidorhamnomannans (PRMs), similar to what has been already described for other Scedosporium species. Rabbit immune sera obtained by injecting whole cells from each species recognized both fungal cells and purified PRMs, suggesting that a cross-reaction occur between both fungi. Immunofluorescent microscopy revealed that PRMs are exposed on fungal surface. Prior incubation of purified molecules with immune sera before adding to cells led to loss of fluorescent, indicating that PRM is a major molecule recognized by immune sera. Fungi-macrophage interaction revealed that S. aurantiacum is able to survive more inside phagocytic cells than S. minutisporum, and PRM from both fungi plays a role in phagocytosis when the purified molecule is pre-incubated with macrophage. In addition, PRM induce nitric oxide release by macrophages. Our data indicate that PRM is an important PAMP exposed on fungal surface with the potential of immune modulation.
The stellar mass assembly of low-redshift, massive, central galaxies in SDSS and the TNG300 simulation
Authors: Jackson Thomas M , Pasquali A , Pacifici C , Engler C , Pillepich A , Grebel E K
Published: August 2020

The stellar mass assembly of galaxies can be affected by both secular and environmental processes. In this study, for the first time, we investigate the stellar mass assembly of $\sim 90\, 000$ low-redshift, central galaxies selected from SDSS group catalogues ($M_{\rm Stellar}\gtrsim 10^{9.5}\, \mathrm{M}_{\odot }$, $M_{\rm Halo}\gtrsim 10^{12}\, \mathrm{M}_{\odot }$) as a function of both stellar mass and halo mass. We use estimates of the times at which 10, 50, and 90 per cent of the stellar mass were assembled from photometric spectral energy distribution fitting, allowing a more complete investigation than single stellar ages alone. We consider trends in both stellar mass and halo mass simultaneously, finding dependences of all assembly times on both. We find that galaxies with higher stellar masses (at constant halo mass) have on average older lookback times, similar to previous studies of galaxy assembly. We also find that galaxies at higher halo mass (at constant stellar mass) have younger lookback times, possibly due to a larger reservoir of gas for star formation. An exception to this is a subsample with high stellar-to-halo mass ratios, which are likely massive, field spirals. We compare these observed trends to those predicted by the TNG300 simulation, finding good agreement overall as a function of either stellar mass or halo mass. However, some differences in the assembly times (of up to ∼3 Gyr) appear when considering both stellar mass and halo mass simultaneously, noticeably at intermediate stellar masses (MStellar ∼ 1011 M⊙). These discrepancies are possibly linked to the quenched fraction of galaxies and the kinetic mode active galactic nucleus feedback implemented in TNG300.
Extracellular vesicles engineered with valency-controlled DNA nanostructures deliver CRISPR/Cas9 system for gene therapy
Authors: Zhuang Jialang , Tan Jizhou , Wu Chenglin , Zhang Jie , Liu Ting , Fan Chunhai , Li Jiaping , Zhang Yuanqing
Published: August 2020

Extracellular vesicles (EVs) hold great promise for transporting CRISPR–Cas9 RNA-guided endonucleases (RNP) throughout the body. However, the cell-selective delivery of EVs is still a challenge. Here, we designed valency-controlled tetrahedral DNA nanostructures (TDNs) conjugated with DNA aptamer, and loaded the valency-controlled TDNs on EV surface via cholesterol anchoring for specific cell targeting. The targeting efficacy of different ratios of aptamer/cholesterol from 1:3 to 3:1 in TDNs on decorating EVs was investigated. TDNs with one aptamer and three cholesterol anchors (TDN1) efficiently facilitated the tumor-specific accumulation of the EVs in cultured HepG2 cells and human primary liver cancer-derived organoids, as well as xenograft tumor models. The intracellular delivery of RNP by TDN1-EVs successfully realized its subsequent genome editing, leading to the downregulation of GFP or WNT10B in specific cells. This system was ultimately applied to reduce the protein expression of WNT10B, which presented remarkable tumor growth inhibition in vitro, ex vivo and in vivo, and could be extended to other therapeutic targets. The present study provides a platform for the directional display of aptamer on surface labeling and the EVs-based Cas9 delivery, which provides a meaningful idea for future cell-selective gene editing.
39. CHARACTERIZING NOVEL INHIBITORS OF BRAIN METASTASIS-INITIATING CELLS
Authors: Kieliszek Agata , Venugopal Chitra , Bassey-Archibong Blessing , Aghaei Nikoo , Lam Fred , Singh Sheila
Published: August 2020

BACKGROUND

The incidence of brain metastases (BM) is tenfold higher than primary brain tumors. BM commonly originate from primary lung, breast, and melanoma tumors with a 90% mortality rate within one year of diagnosis. Current standard of care for BM includes surgical resection with concurrent chemoradiation, but does not extend median survival past 16 months, posing a large unmet need to identify novel therapies against BM.

METHODS

From a large in-house biobank of patient-derived BM cell lines, the Singh Lab has generated murine orthotopic patient-derived xenograft (PDX) models of lung, breast, and melanoma BM that recapitulate the stages of BM progression as seen in human patients. Using these three PDX models, we identified a population of “pre-metastatic” brain metastasis-initiating cells (BMICs) that are newly arrived in the brain but have yet to form detectable tumors. Pre-metastatic BMICs are not detectable in human patients but are important therapeutic targets with the potential to prevent BM in at-risk patients.

RESULTS

RNA sequencing of pre-metastatic BMICs from all three PDX primary tumor models with subsequent Connectivity Map analysis identified novel compounds that have the potential of killing all three types of BMICs. In particular, we identified two compounds that have selective killing of BMICs in vitro from all three primary tumor cohorts while sparing non-cancerous cells. We further characterized their ability to inhibit the self-renewal and proliferative properties of BMICs. Ongoing in vivo work will investigate the compounds’ preclinical utilities in preventing BM.

CONCLUSION

Identification of novel small molecules that target BMICs could prevent the formation of BM completely and dramatically improve the prognosis of at-risk cancer patients.
47. UNCOVERING A NOVEL ROLE FOR HLA-G IN BRAIN METASTASES
Authors: Bassey-Archibong Blessing , Aghaei Nikoo , Chokshi Chirayu , Kieliszek Agata , Tatari Nazanin , Mckenna Dillon , Singh Mohini , Subapanditha Minomi , Tokar Tomas , Jurisica Igor , Lam Fred , Lu Yu , Venugopal Chitra , Singh Sheila
Published: August 2020

Brain metastases (BM) are the most common brain tumour in adults and are ten times more likely to develop than primary brain tumours. More than 20% of patients with cancer will develop BM with the three most common sources being primary cancers of the lung, breast, and melanoma. Unfortunately, current treatment options for BM do not effectively eradicate BM, with a mere median overall survival time of 12 months in treated patients. This indicates the need for better and more effective therapies against BM. Using patient-derived cell lines established from surgically removed brain metastatic tumours of lung-, breast- and melanoma-BM patients, we generated patient-derived orthotopic murine xenograft (PDX) models of lung-, breast-, and melanoma-BM. From these PDX models, we isolated a rare population of stem-like brain metastasis initiating cells (BMICs) we termed “pre-metastatic”, that had traveled from their primary/orthotopic tumours and lodged in the brain but had not yet developed into mature BM. Transcriptomic analyses performed on pre-metastatic and non-pre-metastatic BMICs from lung, breast and melanoma PDX models of BM, identified a set of deregulated genes exclusive only to pre-metastatic BMICs. Further analysis revealed HLA-G as being commonly up-regulated only during the pre-metastatic stage of the lung-, breast-, and melanoma-BM cascade. In vitro and in vivo analyses demonstrated that HLA-G knock-down reduced the proliferation and survival of BMICs from all BM cohorts, and attenuated the establishment of mature brain metastatic tumours, implying a crucial role for HLA-G in the formation of BM. Developing a therapeutic strategy that targets HLA-G in BM may prove effective at completely eliminating brain metastatic cells at an early stage of the BM cascade, thereby turning a fatal disease into an eminently more treatable one.
61. EXPRESSION OF ANDROGEN RECEPTOR IN BREAST CANCER BRAIN METASTASIS
Authors: Qazi Maleeha , Jerzak Katarzyna , Nofech-Mozes Sharon
Published: August 2020

INTRODUCTION

Treatment options for women with breast cancer brain metastases (BrM) are generally limited to surgery and/or radiotherapy because most systemic therapies do not cross the blood-brain barrier. Androgen receptors (ARs) are frequently expressed in breast cancer and anti-androgenic therapies have been shown to penetrate the central nervous system. In this study, we analyzed the expression of AR in breast cancer BrM to identify patients who may benefit from anti-androgenic therapies.

METHODS

Consecutive BrM resected in our institution (July 1999-June 2013) were identified from the Anatomic Pathology departmental database. Cases that were signed out as breast origin given the available immunohistochemical profile and clinical history were included. A tissue microarray was constructed using 1 mm cores in triplicates and studied by immunohistochemistry for AR, ER, PR and HER2 (SP107, SP1, IE2, 4B5; Ventana Medical Systems, Tucson AZ, USA). HER2 gene amplification was determined by INFORM HER2 DNA and Chromosome 17 (both by Ventana Medical Systems, Tucson AZ, USA). Immunohistochemistry was used as a surrogate to determine intrinsic subtypes.

RESULTS

Among 61 breast cancer BrM with available tissue blocks, AR was expressed in 38 (62%) cases. Among BrMs of luminal A subtype (ER+, PR+/-, HER2-, Ki67<16%), 50% expressed AR (n=1/2). Within the luminal B subtype (ER+, PR+/-), all 15 HER2+ BrM expressed AR (100%), while only 50% of HER2- BrM expressed AR (n=8/16). Among 14 BrM of HER2+ subtype (ER-, PR-), 71% expressed AR (n=10/14). Only 30% of triple negative BrM (ER-, PR-, HER2-) were AR+ (n=4/14).

CONCLUSION

Almost two-thirds of breast cancer BrM expressed AR. HER2+ luminal B and HER2+ subtypes were most likely to be AR+, while only 30% of triple negative BrM were AR+. Our data suggests that certain subtypes of breast cancer BrM are more likely to be AR+ and could serve as a potential therapeutic target.
E-Cigarette Demand: Impact of Commodity Definitions and Test–Retest Reliability
Authors: Strickland Justin C , Vsevolozhskaya Olga A , Stoops William W
Published: August 2020

Introduction

Behavioral economic demand provides a multidimensional understanding of reinforcement. Commodity purchase tasks are an efficient method for measuring demand in human participants. One challenge in translating these procedures to electronic nicotine delivery systems (ENDS or e-cigarettes) is defining commodity units given the lack of standardization in the e-cigarette marketplace.

Aims and Methods

The purpose of this study was to directly compare methods of operationalizinge-cigarette purchases, puffs, cartridges, and mLs liquid, using a within-subject design. Participants (N = 132) reporting past week e-cigarette use were recruited using crowdsourcing. Purchase tasks were completed operationalizing e-cigarette units as puffs or cartridges at baseline and puffs or mLs liquid at a 3-month follow-up.

Results

Bivariate associations supported convergent and discriminant validity with the largest effect size correlations for intensity and elasticity observed for the puff version. Interaction models suggested that product preferences moderated the relationship between time-to-first use and cartridge demand with larger effect size correlations among persons reporting a preference for JUULs, but weaker relationships among persons reporting other device preferences. Puff intensity (rxx = .61) and elasticity (rxx = .62) showed good test–retest reliability for participants reporting stable consumption, but poor test–retest reliability for individuals with changed consumption levels (intensity rxx = −.08; elasticity rxx = −.10).

Conclusions

This study highlights the relevance of commodity definitions in the e-cigarette purchase task. Puffs as an experimental commodity may provide flexibility for studying e-cigarette demand in heterogenous or unknown populations, whereas more tailored or personalized approaches like cartridge or mL-based tasks will likely be helpful when studying known subgroups.

Implications

The commodity purchase task procedure is widely used for understanding cigarette and e-cigarette demand in nicotine dependence research. This study evaluates the importance of operational definitions of e-cigarette commodities in the purchase task (ie, puffs, cartridges, or mLs liquid). Puffs may provide a more flexible commodity unit when evaluating e-cigarette demand in general or heterogenous populations, whereas device-specific units may prove more valuable when studying populations with consistent and known product use.
Social Work Luminaries: Luminaries contributing to the founding of social work practice, policy, and research in the United States
Authors: Gutiérrez Lorraine M. , Davis Larry E. , Garvin Charles D.
Published: August 2020

Oxford Bibliographies in Social Work includes three articles describing the scholarly writings of a select group of deceased social workers who have been especially prominent and influential in the profession within the United States. The authors refer to these individuals as social work luminaries. These three articles can be used to identify the publications of prominent individuals who have been most influential in the development of social work. We identified these individuals by first reviewing the biographies of significant social workers from the Encyclopedia of Social Work, edited by Cynthia Franklin (Washington, DC: National Association of Social Workers Press, 2014), and obituaries collected by the Council on Social Work Education since the publication of the Encyclopedia of Social Work. From this list, the authors reviewed the biographical material and publications, selecting the most-prominent luminaries for each of the three articles. For each luminary, a brief biographical overview and one to five annotated citations of their most important publications are provided. Respectively, the three articles describe the publications of luminaries (1) who were involved in the founding and creation of the social work profession in the United States during the late 19th and early 20th centuries, (2) who subsequently contributed to the clarification and elaboration of social work practice and theory, and (3) who contributed to social work theory and scholarship in the late 20th and early 21st centuries. This article focuses on luminaries who contributed to the founding of the profession. They came to their work from different backgrounds and began the process of creating the field’s theoretical, ethical, and historical foundations. The earliest luminaries in this list contributed to the foundations of social work, with the later luminaries working on defining the field, its scope and functions, and its role in larger health and human services systems. These luminaries include those who established some of the first schools of social work in the nation. These bibliographies are ordered in chronological order on the basis of when the individual made his or her most substantial contributions to social work. These individuals and their work must be seen in the context of the eras in which they worked. The language they sometimes used could be viewed by some in the 2020s as archaic, patronizing, sexist, racist, or offensive. Some of their work may express views, such as eugenic policies, that are antithetical to the profession in the early 21st century. The authors think it imperative that those in the field recognize these historical trends and views in order to see how our field has evolved and also how it has always reflected the context and values in which it exists.
Halfway Houses
Authors: Conway Ayana , Ruffin Joshua R.
Published: August 2020

In 2016 there were a total of 4,537,100 individuals under community supervision in the United States, which equated to 1 in every 55 adults. This number included individuals who resided in halfway houses. Two-thirds of ex-offenders often recidivate within three years after being released from prison. Halfway houses have served many released and soon-to-be released prisoners, with the intention of rehabilitating and preparing them for successful reintegration back into society. Having undergone several name changes, halfway houses have been present for centuries within the United States. Since its creation, the halfway house has served as a bridge between imprisonment and society, where offenders are discharged to designated community residences before being released back into society. These centers serve people who do not need the confinement of an institution, yet are not ready for independent community living. Originally, these centers were created to serve as an alternative to incarceration for target populations within the United States. The goal was to help participants become law-abiding citizens through transitional housing, thus decreasing recidivism. Typically, halfway houses collaborate with nonprofit organizations, human service agencies, and other community services to provide education, counseling, 24-hour rehabilitative and residential services, and the like. These centers place an increased responsibility on the individual to determine how to balance life after incarceration. The term halfway houses emerged in the 1950s after being referred to as transitional housing years before, and most recently as offender reentry centers in some circles. They play a major role in the process of former inmates reentering society. Since the 1950s there has been an increased interest in these facilities and their utilization. They gained prominence in the 1960s and 1970s after the emergence of the concept of “residential continuum.” Determining whether such centers have a positive effect on offenders’ reintegration into the community remains deeply contested. Traditionally and contemporarily, halfway houses are not always welcomed in neighborhoods, as local community members often fear an increase in crime. Few studies have provided data on the impact halfway houses make on communities, however. While this remains a dilemma for scholars studying halfway houses and their impact on the larger community, there are publications that have laid the foundation for further research. The focus of this article is on halfway houses that provide transitional housing rather than those facilities that provide longer-term or indefinite residency.
Margaret Mead, Gregory Bateson, and Visual Anthropology
Authors: Jacknis Ira
Published: August 2020

The work of Margaret Mead (b. 1901–d. 1978) and Gregory Bateson (b. 1904–d. 1980) has proven to be critical in forming the subdiscipline of visual anthropology. In 1933 Mead met Bateson on the Sepik River, while both were engaged in ethnographic fieldwork in Papua New Guinea. Soon a couple (they married in 1936), they decided to travel to Bali with the explicit intention of pioneering the use of still photography and film as a basic ethnographic methodology. Before their collaboration Mead had studied with Franz Boas at Columbia University (PhD in 1929), and Bateson was a student of Alfred C. Haddon at Cambridge (MA in 1930). During their lives, neither held a tenured regular academic appointment, although both were active teachers and mentors. In their early and middle years, both worked in the field that came to be known as “culture and personality.” The couple worked together in Bali between January 1936 and March 1938. Following a comparative period of fieldwork among the Iatmul of New Guinea (April 1938–February 1939), they returned to Bali (February–March 1939), before returning to America. From their shared Balinese fieldwork they created a corpus of about 25,000 still photographs and 22,600 feet of 16 mm. film footage—and from the Iatmul of New Guinea, another 11,000 feet of film, and another 8,000 still photographs. From these materials, they produced two photographic ethnographies and seven edited films. These were perhaps the first cultural representations to use images, coupled with texts, as the primary vehicles for making ethnographic arguments and analyses. Although this transformed both visual anthropology and the discipline at large, it took many decades for their achievement to be recognized. Bateson and Mead, each in their own way, continued to advocate for the importance of visual representations in anthropology and related disciplines. After their divorce in 1950, Bateson continued his peripatetic professional career, often working collaboratively. His later work in psychiatry and the behavior of animals (otters, dolphins, and octopuses) found a place for visual documentation of non-verbal forms of communication. Except for her first fieldwork, in Samoa (1925), Mead never took her own photographs, instead collaborating with her ethnographic partners, especially two of her husbands, Reo Fortune and Gregory Bateson. More so than Bateson, in later life Mead was active in helping create the institutions of visual anthropology, through archives, conferences, publications, and teaching. Bateson and Mead’s visual anthropology has been influential throughout the scholarly world, but given the relatively large literature on the couple, this bibliography has been confined to works published in English.
‘Funk Money’: The End of Empires, The Expansion of Tax Havens, and Decolonization as an Economic and Financial Event*
Authors: Ogle Vanessa
Published: August 2020

This article explores the question of what happened to European assets in the process of decolonization. It argues that decolonization created a money panic of sorts that led white settlers, businessmen, and officials to seek to liquidate assets they owned and move funds out of the colonial world. Instead of being repatriated to metropolitan countries with high tax rates and exchange controls, money moved to tax havens. Decolonization thus provided an important share of early postwar tax haven business in a period when tax havens and offshore finance expanded during the 1950s and 1960s. In turn, the withdrawal of Euro-American investments from the decolonizing world set the stage for the politics of development and modernization in the coming decades. Ironically, the outflow of funds during decolonization and the subsequent return of some funds in restructured form as investments by multinational and other companies soon caused difficulties in newly independent developing countries. Companies soon found ways to rebook profits to have occurred in a tax haven rather than in the developing world, thus depriving low-income countries from tax revenue. The withdrawal of Euro-American investments from the colonial world during decolonization moreover had implications for the growth of portfolio investment, as funds removed from colonies were often invested through a tax haven onwards in US securities. All in all, decolonization was an economic and financial event that is only beginning to emerge in full detail.
Engineering a fluorescence biosensor for the herbicide glyphosate
Authors: N’Guetta Pierre-Emmanuel Y , Fink Maggie M , Rizk Shahir S
Published: August 2020

Glyphosate, the active ingredient in RoundUp, is the most widely used herbicide on the globe, and has recently been linked to an increased risk in non-Hodgkin’s lymphoma in exposed individuals. Therefore, detection and monitoring of glyphosate levels in water and soil is important for public safety. Here, we describe a biosensor for glyphosate based on an engineered Escherichia coli phosphonate-binding protein (PhnD). Mutations in the binding pocket were introduced to convert PhnD into a glyphosate-binding protein. A fluorescence group attached near the hinge of the protein was added to monitor binding of glyphosate and to determine its concentration in unknown samples. The resulting engineered biosensor can detect glyphosate in tap water and in soil samples treated with the herbicide at submicromolar concentrations, well below the limit for drinking water in the USA. Incorporating this biosensor in a device would allow rapid and continuous monitoring of glyphosate in water and soil samples.
Rehabilitation Interventions for Shoulder Dysfunction in Patients With Head and Neck Cancer: Systematic Review and Meta-Analysis
Authors: Almeida Kleicyane Aguiar Meireles , Rocha Aline Pereira , Carvas Nelson , Pinto Ana Carolina Pereira Nunes
Published: August 2020

Objective

Shoulder pain and dysfunction are highly prevalent after neck dissection in the treatment of head and neck cancer (HNC). They can lead to muscle weakness, limited range of motion, and shoulder tilt and pain, which can reduce patient functioning. The purpose of this study was to evaluate the effectiveness of rehabilitation interventions for shoulder dysfunction in patients with surgically treated HNC.

Methods

A search of principal databases (MEDLINE, Embase, CENTRAL, LILACS, IBECS, PEDro, and SciELO) was conducted, in addition to hand searches and a search of gray literature, for all randomized clinical trials (RCTs) published before February 2020. Two authors independently selected all relevant studies. The 7 RCTs fulfilling all inclusion and exclusion criteria were assessed for risk of bias and certainty of evidence using the Cochrane Collaboration risk-of-bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool, respectively.

Results

Moderate-certainty evidence suggests that progressive resistance training is better than conventional treatment for improving pain and dysfunction in patients with HNC (pooled data from 214 participants; mean difference = −5.92; 95% CI = −11.38 to −0.45). Low-certainty evidence (data from 2 RCTs with 106 participants that could not be combined) suggests that acupuncture seems to be more effective than conventional treatment.

Conclusions

Progressive resistance training is effective for improving shoulder pain and dysfunction in patients with HNC. Further high-quality RCTs are needed to examine the effectiveness of acupuncture for improving shoulder pain and dysfunction in these patients. Future studies with longer follow-up times are needed to clarify the effects of early postoperative intervention.

Impact

Clinicians can have confidence that progressive resistance training in patients with surgically treated HNC is effective.

Lay Summary

These study results show that people with head and neck cancer can benefit from gradually increased resistance training to reduce shoulder pain and improve function. This study will help researchers design clinical trials to determine whether treatments such as acupuncture and early physical therapy also could be effective in treating this population.
Effect of different aged cartilage ECM on chondrogenesis of BMSCs in vitro and in vivo
Authors: Wang Xiuyu , Lu Yan , Wang Wan , Wang Qiguang , Liang Jie , Fan Yujiang , Zhang Xingdong
Published: August 2020

Extracellular matrix (ECM)-based biomaterials are promising candidates in cartilage tissue engineering by simulating the native microenvironment to regulate the chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) without exogenous growth factors. The biological properties of ECM scaffolds are primarily depended on the original source, which would directly influence the chondrogenic effects of the ECM materials. Despite the expanding investigations on ECM scaffolds in recent years, the selection of optimized ECM materials in cartilage regeneration was less reported. In this study, we harvested and compared the articular cartilage ECM from newborn, juvenile and adult rabbits. The results demonstrated the significant differences in the mechanical strength, sulphated glycosaminoglycan and collagen contents of the different aged ECM, before and after decellularization. Consequently, different compositional and mechanical properties were shown in the three ECM-based collagen hydrogels, which exerted age-dependent chondrogenic inducibility. In general, both in vitro and in vivo results suggested that the newborn ECM promoted the most chondrogenesis of BMSCs but led to severe matrix calcification. In contrast, BMSCs synthesized the lowest amount of cartilaginous matrix with minimal calcification with adult ECM. The juvenile ECM achieved the best overall results in promoting chondrogenesis of BMSCs and preventing matrix calcification. Together, this study provides important information to our current knowledge in the design of future ECM-based biomaterials towards a successful repair of articular cartilage.
Anti-protein C antibodies and acquired protein C resistance in SLE: novel markers for thromboembolic events and disease activity?
Authors: Ramirez Giuseppe A , Mackie Ian , Nallamilli Susanna , Pires Tatiana , Moll Rachel , Pericleous Charis , Isenberg David A , Cohen Hannah , Efthymiou Maria
Published: August 2020

Objectives

Risk factors for thromboembolism in SLE are poorly understood. We hypothesized a possible role for protein C, based on its dual activity in inflammation and haemostasis and on the evidence of an association between acquired activated protein C (APC) resistance (APCR) and high-avidity anti-protein C antibodies (anti-PC) with a severe thrombotic phenotype in venous thrombosis APS patients.

Methods

In a cross-sectional study of 156 SLE patients, the presence and avidity of IgG anti-PC was established by in house-ELISA, and APCR to exogenous recombinant human APC (rhAPC) and Protac (which activates endogenous protein C) was assessed by thrombin generation-based assays. Associations with aPL profile, thrombotic history and disease activity (BILAG and SLEDAI-2K) were also established.

Results

Anti-PC were detected in 54.5% of patients and APCR in 59%. Anti-PC positivity was associated with APCR to both rhAPC (P <0.0001) and Protac (P =0.0001). High-avidity anti-PC, detected in 26.3% of SLE patients, were associated with APCR in patients with thrombosis only (P <0.05), and with the development of thrombosis over time (range: 0–52 years; P =0.014). High-avidity anti-PC levels correlated with SLEDAI-2K (P =0.033) and total BILAG (P =0.019); SLEDAI-2K correlated inversely with APCR to Protac (P =0.004).

Conclusion

Anti-PC occur in patients with SLE, independently of aPL profile, and are associated with APCR. High-avidity anti-PC are associated with thrombosis and with active disease and might prove a novel marker to monitor the risk of thrombosis and disease progression in SLE.
Serum cytokine levels associated with myocardial injury in systemic lupus erythematosus
Authors: du Toit Riëtte , Reuter Helmuth , Walzl Gerhard , Snyders Candice , Chegou Novel N , Herbst Phillip G , Doubell Anton F
Published: August 2020

Objectives

To identify cytokines, markers of endothelial activation [soluble vascular cell adhesion molecule-1 (sVCAM-1)] and myocyte strain [soluble ST2 (sST2)] associated with myocardial injury (MInj) in SLE, classified by cardiac magnetic resonance (CMR) criteria.

Methods

CMR was performed on patients with SLE, identifying stages of MInj (inflammation and necrosis or fibrosis). Data captured included: clinical assessment, laboratory and serological analyses, cytokine (IL-1β, IL-1Ra, IL-2, IL-6, IL-10, IL-17, IL-18, TNF-alpha), sVCAM-1 and sST2 levels. Cytokines were compared with regard to SLE features and evidence of CMR MInj. Predictors of CMR MInj were determined through regression analyses.

Results

Forty-one patients with high disease activity (SLEDAI-2K: 13; IQR: 3–17) were included. SLE features included: LN (n = 12), neurolupus (n = 6) and clinical lupus myocarditis (LM) (n = 6). Nineteen patients had CMR evidence of MInj. Patients with a SLEDAI-2K ≥ 12 had higher sVCAM-1 (P = 0.010) and sST2 (P = 0.032) levels. Neurolupus was associated with higher IL-1Ra (P = 0.038) and LN with lower IL-1Ra (P = 0.025) and sVCAM-1 (P = 0.036) levels. Higher IL-1Ra (P = 0.012), IL-17 (P = 0.045), IL-18 (P = 0.003), and sVCAM-1 (P = 0.062) levels were observed in patients with CMR MInj compared with those without. On multivariable logistic regression, IL-1Ra predicted CMR inflammation and fibrosis/necrosis (P < 0.005) while anti-Ro/SSA [odds ratio (OR): 1.197; P = 0.035] and the SLE damage index (OR: 4.064; P = 0.011) predicted fibrosis/necrosis.

Conclusion

This is a novel description of associations between cytokines and SLE MInj. IL-18 and IL-1Ra were significantly higher in patients with MInj. IL-1Ra independently predicted different stages of CMR MInj. Exploration of the role of these cytokines in the pathogenesis of SLE MInj may promote targeted therapies for LM.
Antidepressant and anticonvulsant prescription rates in patients with osteoarthritis: a population-based cohort study
Authors: van den Driest Jacoline J , Schiphof Dieuwke , de Wilde Marcel , Bindels Patrick J E , van der Lei Johan , Bierma-Zeinstra Sita M A
Published: August 2020

Objectives

There are signs that antidepressants and anticonvulsants are being prescribed more often for OA patients, despite limited evidence. Our objectives were to examine prescription rates and time trends for antidepressants and anticonvulsants in OA patients, to assess the percentage of long-term prescriptions, and to determine patient characteristics associated with antidepressant or anticonvulsant prescription.

Methods

A population-based cohort study was conducted using the Integrated Primary Care Information database. First, episodic and prevalent prescription rates for antidepressants (amitriptyline, nortriptyline and duloxetine) and anticonvulsants (gabapentinoids) in OA patients were calculated for the period 2008–17. Logistic regression was used to assess which patient characteristics were associated with prescriptions.

Results

In total, 164 292 OA patients were included. The prescription rates of amitriptyline, gabapentin and pregabalin increased over time. The increase in prescription rates for pregabalin was most pronounced. Episodic prescription rate increased from 7.1 to 13.9 per 1000 person-years between 2008 and 2017. Amitriptyline was prescribed most (15.1 episodic prescriptions per 1000 person-years in 2017). Prescription rates of nortriptyline and duloxetine remained stable at 3.0 and 2.0 episodic prescriptions per 1000 person-years, respectively. For ≤3% of patients with incident OA, medication was prescribed long-term (≥3 months). In general, all medication was prescribed more frequently for older patients (except duloxetine), women, patients with OA in ≥2 joints, patients with spinal OA and patients with musculoskeletal disorders.

Conclusion

Prescription rates of amitriptyline, gabapentin and pregabalin increased over time. Since there is little evidence to support prescription in OA, caution is necessary when prescribing.
Geolocation as a Digital Phenotyping Measure of Negative Symptoms and Functional Outcome
Authors: Raugh Ian M , James Sydney H , Gonzalez Cristina M , Chapman Hannah C , Cohen Alex S , Kirkpatrick Brian , Strauss Gregory P
Published: August 2020

Objective

Negative symptoms and functional outcome have traditionally been assessed using clinical rating scales, which rely on retrospective self-reports and have several inherent limitations that impact validity. These issues may be addressed with more objective digital phenotyping measures. In the current study, we evaluated the psychometric properties of a novel “passive” digital phenotyping method: geolocation.

Method

Participants included outpatients with schizophrenia or schizoaffective disorder (SZ: n = 44), outpatients with bipolar disorder (BD: n =19), and demographically matched healthy controls (CN: n = 42) who completed 6 days of “active” digital phenotyping assessments (eg, surveys) while geolocation was recorded.

Results

Results indicated that SZ patients show less activity than CN and BD, particularly, in their travel from home. Geolocation variables demonstrated convergent validity by small to medium correlations with negative symptoms and functional outcome measured via clinical rating scales, as well as active digital phenotyping behavioral indices of avolition, asociality, and anhedonia. Discriminant validity was supported by low correlations with positive symptoms, depression, and anxiety. Reliability was supported by good internal consistency and moderate stability across days.

Conclusions

These findings provide preliminary support for the reliability and validity of geolocation as an objective measure of negative symptoms and functional outcome. Geolocation offers enhanced precision and the ability to take a “big data” approach that facilitates sophisticated computational models. Near-continuous recordings and large numbers of samples may make geolocation a novel outcome measure for clinical trials due to enhanced power to detect treatment effects.
The Roman origin of the trust (juridical–linguistic peculiarities)
Authors: Gvelesiani Irina
Published: August 2020

The trust is a unique institution of the Anglo-American legal system. Its adaptable character facilitates its popularity in the European juridical arena. It is generally believed that the trust arose from legal institution use, which was created in the British law of the 13–14th centuries as a mode of transferring assets. However, the issue of the origin of the use/trust is still very debatable. The article deals with the question of the Roman origin of the use. The research is oriented to the juridical and linguistic peculiarities.
Effects of fatty acid profile of supplements on intake, performance, carcass traits, meat characteristics, and meat sensorial analysis of feedlot Bos indicus bulls offered a high-concentrate diet
Authors: Costa Carolina , Rizzieri Ramon , Melo Gabriel , Müller Leonardo , Estevan Daniela , Pacheco Rodrigo , Millen Danilo , Pereira Angélica , Zanatta Mariana , Cappellozza Bruno , Cervieri Rafael , Martins Cyntia , Arrigoni Mário
Published: August 2020

This experiment was designed to evaluate the effects of lipid source and fatty acid (FA) profile on intake, performance, carcass characteristics, expression of enzymes, and sensorial analysis of Bos indicus animals offered a high-concentrate diet. On day 0, 96 noncastrated animals were blocked by initial body weight (400 ± 19.3 kg), randomly allocated to 1 of 24 pens (4 animals/pen), and pens were randomly assigned to receive: 1) control: basal diet composed of whole cottonseed and corn germ as lipid substrates (CONT; n = 6), 2) calcium salts of fatty acids (CSFA) of soybean: CSFA of soybean oil as replacement for whole cottonseed and corn germ (calcium salts of soybean oil [CSSO]; n = 6), 3) CSFA-Blend: CSFA of palm, cottonseed, and soybean oil as replacement for whole cottonseed and corn germ (calcium salts of vegetable oils [CSVO]; n = 6), and 4) Mix: basal diet containing whole cottonseed, corn germ, and CSVO (MIXT; n = 6). Experiment lasted 108 d and performance, ultrasound measurements, as well as carcass characteristics were evaluated. Additionally, meat FA profile, expression of enzymes involved in lipid metabolism, and sensorial analysis were evaluated. No treatment effects were observed on performance variables, ultrasound, and carcass traits (P ≥ 0.22), whereas animals receiving CONT had a greater intake of C10:0, C16:0, C16:1 trans-9, C18:1 cis-9, C18:2, C18:3, total FA, monounsatured FA (MUFA), and polyunsaturated FA (PUFA) vs. CSSO and MIXT (P < 0.05). Conversely, intake ratios of saturated FA (SFA):MUFA and SFA:PUFA were all reduced for CONT vs. other treatments. Meat obtained from CONT animals had greater colorimetric (L*, a*, and b*) values vs. MIXT (P < 0.01). On meat FA profile, CONT increased C18:0 vs. supplementation with calcium salts (P < 0.02) and supplementation with CSSO yielded greater meat concentrations of C18:1 trans-10 and C18:2 CLA intermediates (P < 0.01). Expression of SREBP-1, SCD, and LPL was downregulated for CSSO (P < 0.05). For sensorial analysis, regular flavor was greater (P = 0.01) for CSSO vs. other treatments, but also greater aroma (P = 0.05) vs. CONT and CSVO. In summary, addition of different lipid sources with varying FA profiles into high-concentrate diets did not affect performance and carcass characteristics of B. indicus animals, but supplementation with calcium salts of soybean oil inhibited the mRNA expression of enzymes involved in lipid metabolism, whereas flavor and aroma were positively affected by this lipid source.
Early Life Exposure to Nicotine: Postnatal Metabolic, Neurobehavioral and Respiratory Outcomes and the Development of Childhood Cancers
Authors: Jamshed Laiba , Perono Genevieve A , Jamshed Shanza , Holloway Alison C
Published: August 2020

Cigarette smoking during pregnancy is associated with numerous obstetrical, fetal, and developmental complications, as well as an increased risk of adverse health consequences in the adult offspring. Nicotine replacement therapy and electronic nicotine delivery systems (e-cigarettes) have been developed as a pharmacotherapy for smoking cessation and are considered safer alternatives for women to smoke during pregnancy. The safety of nicotine replacement therapy use during pregnancy has been evaluated in a limited number of short-term human trials, but there is currently no information on the long-term effects of developmental nicotine exposure in humans. However, animal studies suggest that nicotine alone may be a key chemical responsible for many of the long-term effects associated with maternal cigarette smoking on the offspring and increases the risk of adverse neurobehavioral outcomes, dysmetabolism, respiratory illness, and cancer. This review will examine the long-term effects of fetal and neonatal nicotine exposure on postnatal health.
HLA DRB1*15:01-DQB1*06:02-Restricted Human CD4+ T Cells Are Selectively Activated With Amoxicillin-Peptide Adducts
Authors: Tailor Arun , Meng Xiaoli , Adair Kareena , Farrell John , Waddington James C , Daly Ann , Pirmohamed Munir , Dear Gordon , Park B Kevin , Naisbitt Dean J
Published: August 2020

Amoxicillin-clavulanate is the most common cause of idiosyncratic drug-induced liver injury (DILI). Drug-specific CD4+ T cells have been detected in patients with DILI, suggestive of an immune etiology. Furthermore, genetic associations including the human leucocyte antigen (HLA) DRB1*15:01-DQB1*06:02 haplotype influence susceptibility. Amoxicillin forms protein adducts that are postulated to activate T cells, by conjugating with lysine residues. However, a role for such adducts has not been described. This study aimed to (1) investigate whether amoxicillin-modified HLA-DRB1*15:01-DQB1*06:02 binding peptides selectively activate DILI patient T cells and (2) define the nature of the T-cell response with respective to antigen structure. Peptides carrying lysine residues for amoxicillin binding in positions (KP) 2-6 and anchors for the HLA-DRB1*15:01-DQB1*06:02 haplotype were designed. The amoxicillin-modified peptides were characterized by mass spectrometry prior to culturing with patient peripheral blood mononuclear cell. T-cell clones were then tested for specificity with amoxicillin, unmodified- and amoxicillin-modified peptides, and structural variants. Amoxicillin-modified KP-2 and KP-3 peptide-specific CD4+ clones proliferated and secreted interferon gamma (IFN-γ), interleukin (IL)-10, perforin and/or IL-17/IL-22 in a dose-dependent manner and displayed no cross-reactivity with amoxicillin, unmodified peptide or with positional derivatives. The T cells response was HLA class II restricted and the amoxicillin-modified peptides bound selectively to HLA-DRB1*15:01 and/or DQB1*06:02. To conclude, we show that amoxicillin-modified peptides bind to both components of the risk haplotype to stimulate DILI patient T cells and describe the importance of the position of nucleophilic lysine residue in the HLA binding peptide sequence.
Mitochondrial Epigenetics and Environmental Health: Making a Case for Endocrine Disrupting Chemicals
Authors: Zhou Zheng , Goodrich Jaclyn M , Strakovsky Rita S
Published: August 2020

Recent studies implicate mitochondrial dysfunction in the development and progression of numerous chronic diseases, which may be partially due to modifications in mitochondrial DNA (mtDNA). There is also mounting evidence that epigenetic modifications to mtDNA may be an additional layer of regulation that controls mitochondrial biogenesis and function. Several environmental factors (eg, smoking, air pollution) have been associated with altered mtDNA methylation in a handful of mechanistic studies and in observational human studies. However, little is understood about other environmental contaminants that induce mtDNA epigenetic changes. Numerous environmental toxicants are classified as endocrine disrupting chemicals (EDCs). Beyond their actions on hormonal pathways, EDC exposure is associated with elevated oxidative stress, which may occur through or result in mitochondrial dysfunction. Although only a few studies have assessed the impacts of EDCs on mtDNA methylation, the current review provides reasons to consider mtDNA epigenetic disruption as a mechanism of action of EDCs and reviews potential limitations related to currently available evidence. First, there is sufficient evidence that EDCs (including bisphenols and phthalates) directly target mitochondrial function, and more direct evidence is needed to connect this to mtDNA methylation. Second, these and other EDCs are potent modulators of nuclear DNA epigenetics, including DNA methylation and histone modifications. Finally, EDCs have been shown to disrupt several modulators of mtDNA methylation, including DNA methyltransferases and the mitochondrial transcription factor A/nuclear respiratory factor 1 pathway. Taken together, these studies highlight the need for future research evaluating mtDNA epigenetic disruption by EDCs and to detail specific mechanisms responsible for such disruptions.