bluuebunny/crossref_metadata_2025 huggingface dataset:
Autologous Non-Cultured Epidermal Cellular Grafting in the Surgical Treatment of Stable Vitiligo: The Skin Hospital Protocol
Authors: Doolan Brent J. , Weaich Michelle , Mamo Joanne , Gupta Monisha
Published: April 2021

Autologous non-cultured epidermal cellular grafting is the treatment of choice for patients with stable refractory vitiligo. Recently, studies have shown cost-effective alternatives for this procedure, superseding previous techniques that required large research facilities or expensive pre-packaged kits. We provide modifications to current techniques, including the use of individual Petri dishes to allow for processing larger skin grafts, hyfrecation instead of conventional manual dermabrasion of the recipient site to reduce scar formation as well as better margin delineation, and an intravenous giving set with a filter for improved filtration of the mixed cell population. These modifications facilitated sufficient skin repigmentation in a cost-effective outpatient setting.
Discriminative Ability for Adverse Outcomes After Hip Fracture Surgery: A Comparison of Three Commonly Used Comorbidity-Based Indices
Authors: Guo Junfei , Di Jun , Gao Xian , Zha Junpu , Wang Xiuli , Wang Zhiqian , Wang Qingxian , Hou Zhiyong , Zhang Yingze
Published: April 2021

Introduction: Preoperative risk assessment can predict adverse outcomes following hip fracture surgery, helping with decision-making and management strategies. Several risk adjustment models based on coded comorbidities such as Charlson Comorbidity Index (CCI), modified Elixhauser’s Comorbidity Measure (mECM), and modified frailty index (mFI-5) are currently prevalent for orthopedic patients, but there is no consensus regarding which is optimal. The primary purpose was to identify the risk factors of CCI, mECM, and mFI-5, as well as patient characteristics for predicting (1) 1-month, 3-month, 1-year, and 2-year mortality, (2) perioperative complications, and (3) extended length of stay (LOS) following hip fractured surgery. The secondary aim was to compare the best-performing comorbidity index combined with characteristics identified in terms of their discriminative ability for adverse outcomes. Methods: We retrospectively reviewed 3,379 consecutive patients presenting with intertrochanteric fractures at our Level I trauma center from 2013 to 2018. After eliminated by exclusion criteria, 2,241 patients undergoing hip fracture surgery by PFNA, with age ≥65 years, were included. Three main multivariate logistic regression models were constructed. Cox proportional hazards models were used to calculate hazard ratios for mortality. A base model included age, BMI, surgical delay, anesthesia type, hemoglobin record at admission, and American Society of Anesthesiologists grade (ASA) also was constructed and assessed. Results: Base model + mECM outperformed other models for the occurrence of major complications including severe complications, cardiac complications, and pulmonary complications [the area under the receiver operating characteristic curve (AUC), 0.647; 95% CI, 0.616–0.677; AUC, 0.637; 95% CI, 0.610–0.664; AUC, 0.679; 95% CI, 0.642–0.715, respectively], while base model + CCI provided better prediction of minor complications of neurological complications and hematological complications (AUC, 0.659; 95% CI, 0.609, 0.709; AUC, 0.658; 95% CI, 0.635, 0.680). In addition, BMI, surgical delay, anesthesia type, and ASA were found highly relevant to extended LOS. Age-group (with a 10-year interval) was indicated to be mostly associated with all-cause mortality with fully adjusted hazard ratio of 1.35 and 95% CI range 1.20–1.51. Conclusions: In comparison with mFI-5 and CCI, mECM so far may be the best comorbidity index combined with the base model for predicting major complications following hip fracture. The base model already achieved good discrimination for all-cause mortality and extended LOS, further addition of risk adjustment indices led to only 1% increase in the amount of variation explained.
Identifying the Lipidomic Effects of a Rare Loss-of-Function Deletion in
ANGPTL3
Authors: Blackburn Nicholas B. , Meikle Peter J. , Peralta Juan M. , Kumar Satish , Leandro Ana C. , Bellinger Melissa A. , Giles Corey , Huynh Kevin , Mahaney Michael C. , Göring Harald H.H. , VandeBerg John L. , Williams-Blangero Sarah , Glahn David C. , Duggirala Ravindranath , Blangero John , Michael Laura F. , Curran Joanne E.
Published: April 2021

Background:

The identification and understanding of therapeutic targets for atherosclerotic cardiovascular disease is of fundamental importance given its global health and economic burden. Inhibition of ANGPTL3 (angiopoietin-like 3) has demonstrated a cardioprotective effect, showing promise for atherosclerotic cardiovascular disease treatment, and is currently the focus of ongoing clinical trials. Here, we assessed the genetic basis of variation in ANGPTL3 levels in the San Antonio Family Heart Study.

Methods:

We assayed ANGPTL3 protein levels in ≈1000 Mexican Americans from extended pedigrees. By drawing upon existing plasma lipidome profiles and genomic data we conducted analyses to understand the genetic basis to variation in ANGPTL3 protein levels, and accordingly the correlation with the plasma lipidome.

Results:

In a variance components framework, we identified that variation in ANGPTL3 was significantly heritable (h
2
=0.33,
P
=1.31×10
−16
). To explore the genetic basis of this heritability, we conducted a genome-wide linkage scan and identified significant linkage (logarithm of odds =6.18) to a locus on chromosome 1 at 90 centimorgans, corresponding to the
ANGPTL3
gene location. In the genomes of 23 individuals from a single pedigree, we identified a loss-of-function variant, rs398122988 (N121Kfs*2), in
ANGPTL3
, that was significantly associated with lower ANGPTL3 levels (β=−1.69 SD units,
P
=3.367×10
−13
), and accounted for the linkage signal at this locus. Given the known role of ANGPTL3 as an inhibitor of endothelial and lipoprotein lipase, we explored the association of ANGPTL3 protein levels and rs398122988 with the plasma lipidome and related phenotypes, identifying novel associations with phosphatidylinositols.

Conclusions:

Variation in ANGPTL3 protein levels is heritable and under significant genetic control. Both ANGPTL3 levels and loss-of-function variants in
ANGPTL3
have significant associations with the plasma lipidome. These findings further our understanding of ANGPTL3 as a therapeutic target for atherosclerotic cardiovascular disease.
Dislocating Heidegger: Nietzsche’s Presence in Derrida’s Geschlecht III
Authors: Schwab Philipp
Published: April 2021

The paper discusses the question as to whether, and in which way, Nietzsche is present in Derrida’s readings of Heidegger in the Geschlecht texts, and in the newly edited Geschlecht III specifically. In order to unfold the background of this question, the first part turns to earlier texts from the 1960s and 1970s and shows that Nietzsche is a key figure in Derrida’s takes on Heidegger, especially as regards the issue of Heidegger’s “belonging” to metaphysics. The second part then addresses the Geschlecht texts and makes the case that, despite their brevity and seeming marginality, the remarks on Nietzsche, most of all in Geschlecht III, are indeed illuminating, in mainly two regards: on the one hand, they shed some light on how Derrida reads and “dislocates” Heidegger in these texts overall, and on the other hand, they contribute to the question of a “continuity” in Derrida’s relations to Heidegger.
Merleau-Ponty’s Lectures on Heidegger
Authors: Low Douglas
Published: April 2021

Merleau-Ponty’s late lecture course on Heidegger is primarily concerned with probing the possibility of a phenomenological ontology. Merleau-Ponty’s lectures provide a rather straightforward presentation of Heidegger’s later thought, without elaborate commentary or criticism. However, Merleau-Ponty does favor Heidegger’s later move toward an indirect expression of Being but does not think that he consistently maintains this view. By the time that we reach the end of Merleau-Ponty’s lecture course, we begin to see a number of differences between the two philosophers come into play, with Merleau-Ponty’s philosophy solving more problems than that of his German counterpart.
Archaeology’s Offerings to Jesuit History
Authors: Cobb Charles R.
Published: April 2021

The contributions to the thematic issue of this journal address archaeological approaches to Jesuit missionizing in three contexts in the colonial Americas: substantial missions that also served as plantations, missions lacking full-time clergy, and short-term outposts on the edges of colonial empires. By relying on evidence from the landscape, the built environment, and objects, these studies demonstrate that the Jesuit enterprise was not subservient to, or a simple accomplice of, European colonial ambitions. Instead, missionizing by all Christian orders was intertwined with an evolution of both secular and religious philosophies that gave rise to modernity.
Thomas Chalmers, David Nasmith, and the Origins of the City Mission Movement
Authors: Shaw Ian J.
Published: April 2021

The development of important models for urban mission took place in early nineteenth-century Glasgow. Thomas Chalmers’ work is widely known, but that of David Nasmith has been the subject of less study. This article explores the ideas shared by Chalmers and Nasmith, and their influence on the development of the city mission movement. Areas of common ground included the need for extensive domestic visitation, the mobilisation of the laity including a middle- class lay leadership, efficient organisation, emphasis on education, and discerning provision of charity. In the long term Chalmers struggled to recruit and retain sufficient volunteers to sustain his parochial urban mission scheme. However, Nasmith’s pan-evangelical scheme succeeded in attracting a steady stream of lay recruits to work as city missioners, as well as mission directors. Through their agency a significant attempt was made to reach those amongst the urban masses who had little or no church connection.
‘Personhood’ in the Old Testament? Who’s asking?
Authors: Sheriffs Deryck
Published: April 2021

This article examines the hermeneutical starting points, frames of reference and assumptions that are involved in investigating ‘personhood’ in the Old Testament. It samples texts from creation, the Jacob narrative, royal history, proverbial wisdom, and psalms with the emergence of our species, family dynamics, power politics and biblical spirituality in mind. The Old Testament offers us a colourful and holistic perspective on being human and relating to God without it being a handbook on biology, neuroscience or cognitive development.
One or two? A historical survey of an aspect of personhood
Authors: Hicks Peter
Published: April 2021

The article provides a rapid survey of concepts of human personhood over the last two and a half millennia, focussing particularly on the issue of dualism. It illustrates the variety of concepts of personhood, and the variety of types of dualism. The main thinkers touched on are the Presocratics, Buddha, Plato, Aristotle, Aquinas, Descartes, Hume and Kant, with a brief final section on developments in twentieth century psychology.
Approaching ‘personhood’ in the New Testament, with special reference to Ephesians
Authors: Turner Max
Published: April 2021

The article first examines general linguistic issues involved in speaking about personhood in the NT, and argues that it is not anachronistic to ask how the NT (or any other ancient document) relates to a modern linguistic stereotype of ‘personhood. In a second part, the article examines further the objects and method of such an inquiry. In part 3, we examine the more general NT contribution, and its Christological focus of the issues. Part 4 provides a relatively detailed analysis of personhood (alienated and reconciled) in Ephesians: the single NT writing that provides richest analysis of our theme. Part 5 briefly considers some implications of the dynamic/relational model of personhood elicited there to more modern questions about personhood in relation to foetal life and in the diminishments of old age.
The dignity of the human person: Towards an evangelical reading of the theology of personhood of Vatican II
Authors: de Chirico Leonardo
Published: April 2021

Present-day magisterial Roman Catholicism offers an interesting perspective on personhood. Recent interest in personhood has been fostered by Vatican II (1962-1965), especially the ‘Pastoral Constitution on the Church in the Modern World’ (Gaudium et spes) and the ‘Declaration on Religious Freedom’ (Dignitatis humanae). The anthropological thrust of Vatican II is particularly referred to the dignity of the human person, her mystery, and vocation. In all these aspects of personhood, the Church plays a fundamental role. In fact, the (Roman) Church is seen as safeguarding the dignity of the person , shedding light on the mystery of the person, and is the place where the person can fully accomplish his vocation. While the focus seems to be on the person, the Church is always in the background.
Honor, hospitality and haughtiness: the contention for leadership in 3 John
Authors: Campbell Barth L.
Published: April 2021

One of the most notorious leaders of the early Christian church was Diotrephes, who makes his appearance in 3 John. All that can be known of him with certainty is in that letter, where he is described as one ‘who loves to be first’ (v. 9 NIV). The Elder writes the letter of 3 John in order to defend his honor that Diotrephes has affronted, to uphold the honor of his emissaries (who have been barred from Diotrephes’ church), and to sustain the honor of those who have attempted to welcome the Christian missionaries from the Elder, but who have been put out of the church by the inhospitable Diotrephes. The best approach to this NT letter is by means of the ancient Mediterranean cultural code of honor, and through a rhetorical-critical analysis that is sensitive to that cultural value.
Jerusalem in history: the city of peace?
Authors: Riddell Peter
Published: April 2021

Jerusalem has great significance for all three Semitic faiths. In the case of Islam, Jerusalem’s rich past history is balanced by its future eschatological function. Islamic tradition looks not only to the city as the site of Muhammad’s ascension to Heaven but also to its role as the location for the final tribulation and judgement. In this context, contemporary conflicts between modern Israel and its Arab neighbours are interpreted by many Muslims as a fulfilment of prophecy. This poses important challenges for scholars engaged in research into Jerusalem’s past and present.
Puritan or enlightened? John Erskine and the transition of Scottish Evangelical theology
Authors: Yeager Jonathan
Published: April 2021

John Erskine was an eighteenth-century Scottish Evangelical who shared many of the theological beliefs of the Puritans while appropriating the techniques of the Enlightenment. He was thoroughly Calvinistic in affirming the total depravity of mankind, a denial of works and freewill in salvation, divine election and imputed righteousness. But, his method of preaching was more congenial to the Enlightenment since he abandoned the metaphysical speculations of the Puritans in favour of a simple, but clear message from the pulpit. He believed that the success of the Evangelical Revival depended on its leaders adopting these measures, so he became a leading propagator of books in order to enlighten his correspondents and assist them in making the gospel message more attractive in the current age.
Sistotremastrum limonadense sp. nov. from French Guiana
Authors: GRUHN GÉRALD , ALVARADO PABLO
Published: April 2021

A new species of Sistotremastrum J. Erikss. (Basidiomycota, Trechisporales) with (6-8)-spored basidia is described and supported by morphology and phylogenetic analyses based on ITS rDNA sequences.
Studies on type material from Kützing’s diatom collection IV: The basionym, author and type of Tetracyclus rupestre

Authors: WILLIAMS DAVID M. , SPAULDING SARAH A. , BISHOP IAN
Published: April 2021

While describing the species Tetracyclus hinziae I. Bishop & Spaulding (2015, p. 200), it was noticed that the basionym and type specimens of the similar species Tetracyclus rupestre  was unclear. This short note addresses those concerns.
Impacts of the North Atlantic Subtropical High on Daily Summer Precipitation over the Conterminous United States
Authors: Zorzetto Enrico , Li Laifang
Published: April 2021

By modulating the moisture flux from ocean to adjacent land, the North Atlantic Subtropical High (NASH) western ridge significantly influences summer-season total precipitation over the Conterminous United States (CONUS). However, its influence on the frequency and intensity of daily rainfall events over the CONUS remains unclear. Here we introduce a Bayesian statistical model to investigate the impacts of the NASH western ridge position on key statistics of daily-scale summer precipitation, including the intensity of rainfall events, the probability of precipitation occurrence, and the probability of extreme values. These statistical quantities play a key role in characterizing both the impact of wet extremes (e.g., the probability of floods) and dry extremes. By applying this model to historical rain gauge records (1948-2019) covering the entire CONUS, we find that the western ridge of the NASH influences the frequency of rainfall as well as the distribution of rainfall intensities over extended areas of the CONUS. In particular, we find that the NASH ridge also modulates the frequency of extreme rainfall, especially that over part of the Southeast and upper Midwest. Our analysis underlines the importance of including the NASH western ridge position as a predictor for key statistical rainfall properties to be used for hydrological applications. This result is especially relevant for projecting future changes in daily rainfall regimes over the CONUS based on the predicted strengthening of the NASH in a warming climate.
The Triglyceride-Glucose Index, a Predictor of Insulin Resistance, Is Associated With Subclinical Atherosclerosis
Authors: Baydar Onur , Kilic Alparslan , Okcuoglu John , Apaydin Ziya , Can Mehmet Mustafa
Published: April 2021

Insulin resistance is one of the most important risk factors that accelerate atherosclerosis. The goal of this study is to investigate the relationship between the triglyceride glucose (TyG) index and functional vessel disease measured using pulse wave velocity (PWV), in a nondiabetic asymptomatic Turkish population. Nondiabetic, healthy patients (n = 1095) with no previous history of coronary heart disease were enrolled. Functional vessel disease was detected by measuring PWV. The TyG index was calculated using the following equation: log [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The study population was divided into 2 groups based on their TyG index. The high TyG index group had higher PWV, corrected PWV, left ventricular mass index, body mass index, rates of hypertension, and was predominately male. Age, gender, blood urea nitrogen level, and TyG index were detected as independent risk factors of PWV in linear regression analysis. Triglyceride glucose index and age were also independent risk factors of the corrected PWV in logistic regression analysis. These findings show a relationship between TyG index and subclinical vessel disease, even in patients without a history of atherosclerotic cardiovascular disease or diabetes.
Language Difficulties in School-Age Children With Developmental Dyslexia
Authors: Price Kaitlyn M. , Wigg Karen G. , Misener Virginia L. , Clarke Antoine , Yeung Natalie , Blokland Kirsten , Wilkinson Margaret , Kerr Elizabeth N. , Guger Sharon L. , Lovett Maureen W. , Barr Cathy L.
Published: April 2021

Developmental dyslexia (DD) is a common reading disability, affecting 5% to 11% of children in North America. Children classified as having DD often have a history of early language delay (ELD) or language impairments. Nevertheless, studies have reported conflicting results as to the association between DD-ELD and the extent of current language difficulties in children with DD. To examine these relationships, we queried the parents of school-age children with reading difficulties on their child’s early and current language ability. Siblings were also examined. Children were directly assessed using quantitative tests of language and reading skills. To compare this study with the literature, we divided the sample ( N = 674) into three groups: DD, intermediate readers (IR), and skilled readers (SR). We found a significant association between DD and ELD, with parents of children in the DD/IR groups reporting their children put words together later than the SR group. We also found a significant association between DD and language difficulties, with children with low reading skills having low expressive/receptive language abilities. Finally, we identified early language predicted current language, which predicted reading skills. These data contribute to research indicating that children with DD experience language difficulties, suggesting early recognition may help identify reading problems.
Cervical Cancer: Assessment of Its Knowledge, Utilization of Services and Its Determinant Among Female Undergraduate Students in a Low Resource Setting
Authors: Anikwe Chidebe Christian , Osuagwu Philip Chidubem , Ikeoha Cyril Chijioke , Ikechukwu Dimejesi Okechukwu B , Okorochukwu Bartholomew Chukwunonye
Published: April 2021

Background

Cervical cancer is a preventable disease that contributes significantly to the death of women. This study is aimed at determining the level of knowledge and utilization of cervical cancer screening and its determinants among female undergraduates of Ebonyi State University.

Methods

A structured questionnaire was used for a cross-sectional survey of the study population between January 1 and March 3, 2018. The data were analyzed using IBM SPSS Statistics version 20. Data were represented with frequency table, simple percentage, mode, range, Chi square and pie chart. The level of significance is at P-value < 0.05.

Results

Majority (74.8%) of the respondents were aware of cervical cancer and it could be prevented (70.8%). More than three-fifths (68.30%) were informed via health workers, and 86.8% were aware that post-coital vaginal bleeding is a symptom. Less than half (49.8%) knew that HPV is the primary cause, and only 32.9% were aware of the HPV vaccine. One-quarter of the respondent were aware that early coitarche is a risk factor for cervical cancer. Only 41.8% of the women were aware of Pap smear, 9.2% had undergone screening, and 97.6% were willing to be screened. Marital status was the significant determinant of being screened while class level did not significantly influence uptake of cervical cancer screening. The most common reason (20.6%) for not being screened was lack of awareness of the test.

Conclusion

Our study population had a good knowledge of cervical cancer, but utilization of cervical cancer screening was poor. Awareness creation through the mass media and provision of affordable screening services can promote the use of cervical cancer screening in the study area.
Test–retest reliability and criterion-related validity of Shih–Hsu test of attention between people with and without schizophrenia
Authors: Shih Yi-Nuo , Hsu Jia-Lien , Wang Yi-Ching , Wu Chia-Chun , Liao Yin-huang
Published: April 2021

Introduction

The “Shih–Hsu Test of Attention” (SHTA) is an iPad-based attention assessment tool developed in recent years by occupational therapists and has acceptable criterion-related validity and high test–retest reliability in preliminary application. This research project explores the criterion-related validity and test–retest reliability of SHTA between people with and without schizophrenia.

Method

The participants were 76 adults with schizophrenia aged 20–64 years, and 66 adults without diagnosed mental illness aged 20–64 years were recruited in this study on a voluntary basis. Each participant was assessed twice. The participants completed both the SHTA and Chu’s Attention Test (CAT) in the first test and the SHTA after 3 weeks.

Findings

Analytical results indicate that the SHTA has satisfactory test–retest reliability (ICC = 0.67) and criterion-related validity (γ = 0.29, p < 0.05*) for adults with schizophrenia and has high test–retest reliability (ICC = 0.90) and criterion-related validity (γ = 0.25, p < 0.05*) for adults without diagnosed mental illness. The MDC% value for the subjects without diagnosed mental illness was 12.1%, indicating acceptable random measurement error.

Conclusion

Our preliminary findings show that the iPad-based attention assessment tool, SHTA, has satisfactory criterion-related validity and test–retest reliability, supporting the future application of SHTA as an attention assessment tool.
Strategies to Support LGBTQ+ Students in High Schools: What Did We Learn in Chicago Public Schools?
Authors: Jarpe-Ratner Elizabeth , Marshall Booker , Choudry Maham , Wishart Marisa , Reid Bianca , Perez Ernestina , Fagen Michael
Published: April 2021

In 2013, the Chicago Public Schools district received funding from the Division of Adolescent and School Health at the Centers for Disease Control and Prevention (CDC) to implement a series of strategies aimed to reduce HIV, STIs (sexually transmitted diseases), and related risk behaviors among students. One such set of strategies included “safe and supportive environments” (SSE), aimed to support lesbian, gay, bisexual, transgender, questioning, and other LGBTQ+ students. SSE strategies included professional development and technical assistance provided to K–12 school staff (teachers, administrators, social workers, etc.) to implement the following practices: support for transgender and gender nonconforming students in accordance with district guidelines, use of LGBTQ+ inclusive curricula, posting of signs and symbols of support, and creation of Genders and Sexualities Alliance student clubs. To monitor progress and performance, both quantitative and qualitative process measure data were collected. Quantitative data consisted of key metrics such as number of staff trained and surveillance data collected through school health profiles in collaboration with the CDC. Qualitative data were gathered to understand barriers and facilitators to implementation of SSE practices via interviews with 55 school staff members and four focus groups with 31 high school students. Results indicated an increased uptake of all SSE activities across the 5-year funding period. Findings also reveal additional needed supports, such as increased availability and offering of professional development for all staff, support for staff in engaging parents, and ensuring the LGBTQ+ inclusive sexual health education curriculum is experienced as such by students. Current work to address these needs is described.
Evaluation of Antioxidant, Antimicrobial and Potential Food Preserving Properties of Rubus Discolor (Rosaceae) Fruit Extracts
Authors: Veličković Ivona , Živković Jelena , Stojković Dejan , Sokovic Marina D. , Marin Petar D. , Grujić Slavica
Published: April 2021

The presented study was aimed at exploring the bioactive properties (antioxidant, antimicrobial and food preserving) and chemical composition of R. discolor fruits collected from 2 geographically distinct wild-growing populations and extracted by using different solvents (methanol, ethanol, acetone and water). The total phenol (TPC), flavonoid (TFC) and anthocyanin (TAC) content varied from 52.7 to 186.8 mg GAE/g, 3.5 to 7.0 mg QE/g and 11.1 to 28.2 mg/g dry weight (dw), respectively. HPLC-DAD analysis identified cyanidin-3-glucoside (Cy-3-Glu) as the dominant anthocyanin that ranged in concentration from 18.4 to 32.2 mg/g dw. The acetone extract revealed the highest antioxidant activity through the ferric reducing antioxidant power (FRAP), total reducing power (TRC) and ß-carotene bleaching in vitro methods. The examined extracts showed antimicrobial activity, being more effective against Gram-positive (G+) than Gram-negative (G-) bacteria. Furthermore, Candida glabrata was the most susceptible among the pathogenic yeasts. The ethanol fruit extract was the most active against Listeria monocytogenes and thus chosen for incorporation in yoghurt and further analyses regarding its food preserving properties, which confirmed its efficacy towards this food-borne pathogen. Additionally, panelists gave high marks to the novel product regarding color, taste, texture flavor and overall acceptance. The obtained results indicated that R. discolor fruit extracts exhibits notable bioactivity and might therefore be considered as a good platform for the development of new preparations to be used in the food industry.
Mechanisms of SARS‐CoV‐2‐induced lung vascular disease: potential role of complement
Authors: Stenmark Kurt R. , Frid Maria G. , Gerasimovskaya Evgenia , Zhang Hui , McCarthy Mary K. , Thurman Joshua M. , Morrison Thomas E.
Published: April 2021

The outbreak of COVID‐19 disease, caused by SARS‐CoV‐2 beta‐coronovirus, urges a focused search for the underlying mechanisms and treatment options. The lung is the major target organ of COVID‐19, wherein the primary cause of mortality is hypoxic respiratory failure, resulting from acute respiratory distress syndrome, with severe hypoxemia, often requiring assisted ventilation. While similar in some ways to acute respiratory distress syndrome secondary to other causes, lungs of some patients dying with COVID‐19 exhibit distinct features of vascular involvement, including severe endothelial injury and cell death via apoptosis and/or pyroptosis, widespread capillary inflammation, and thrombosis. Furthermore, the pulmonary pathology of COVID‐19 is characterized by focal inflammatory cell infiltration, impeding alveolar gas exchange resulting in areas of local tissue hypoxia, consistent with potential amplification of COVID‐19 pathogenicity by hypoxia. Vascular endothelial cells play essential roles in both innate and adaptive immune responses, and are considered to be “conditional innate immune cells” centrally participating in various inflammatory, immune pathologies. Activated endothelial cells produce cytokines/chemokines, dynamically recruit and activate inflammatory cells and platelets, and centrally participate in pro‐thrombotic processes (thrombotic microangiopathies). Initial reports presented pathological findings of localized direct infection of vascular endothelial cells with SARS‐CoV‐2, yet emerging evidence does not support direct infection of endothelial or other vascular wall cell and thus widespread endothelial cell dysfunction and inflammation may be better explained as secondary responses to epithelial cell infection and inflammation. Endothelial cells are also actively engaged in a cross‐talk with the complement system, the essential arm of innate immunity. Recent reports present evidence for complement deposition in SARS‐CoV‐2‐damaged lung microcirculation, further strengthening the idea that, in severe cases of COVID‐19, complement activation is an essential player, generating destructive hemorrhagic, capillaritis‐like tissue damage, clotting, and hyperinflammation. Thus, complement‐targeted therapies are actively in development. This review is intended to explore in detail these ideas.
Preclinical activity and determinants of response of the GPRC5DxCD3 bispecific antibody talquetamab in multiple myeloma
Authors: Verkleij Christie P. M. , Broekmans Marloes E. C. , van Duin Mark , Frerichs Kristine A. , Kuiper Rowan , de Jonge A. Vera , Kaiser Martin , Morgan Gareth , Axel Amy , Boominathan Rengasamy , Sendecki Jocelyn , Wong Amy , Verona Raluca I. , Sonneveld Pieter , Zweegman Sonja , Adams Homer C. , Mutis Tuna , van de Donk Niels W. C. J.
Published: April 2021

Cell surface expression levels of GPRC5D, an orphan G protein–coupled receptor, are significantly higher on multiple myeloma (MM) cells, compared with normal plasma cells or other immune cells, which renders it a promising target for immunotherapeutic strategies. The novel GPRC5D-targeting T-cell redirecting bispecific antibody, talquetamab, effectively kills GPRC5D+ MM cell lines in the presence of T cells from both healthy donors or heavily pretreated MM patients. In addition, talquetamab has potent anti-MM activity in bone marrow (BM) samples from 45 patients, including those with high-risk cytogenetic aberrations. There was no difference in talquetamab-mediated killing of MM cells from newly diagnosed, daratumumab-naïve relapsed/refractory (median of 3 prior therapies), and daratumumab-refractory (median of 6 prior therapies) MM patients. Tumor cell lysis was accompanied by T-cell activation and degranulation, as well as production of pro-inflammatory cytokines. High levels of GPRC5D and high effector:target ratio were associated with improved talquetamab-mediated lysis of MM cells, whereas an increased proportion of T cells expressing PD-1 or HLA-DR, and elevated regulatory T-cell (Treg) counts were associated with suboptimal killing. In cell line experiments, addition of Tregs to effector cells decreased MM cell lysis. Direct contact with bone marrow stromal cells also impaired the efficacy of talquetamab. Combination therapy with daratumumab or pomalidomide enhanced talquetamab-mediated lysis of primary MM cells in an additive fashion. In conclusion, we show that the GPRC5D-targeting T-cell redirecting bispecific antibody talquetamab is a promising novel antimyeloma agent. These results provide the preclinical rationale for ongoing studies with talquetamab in relapsed/refractory MM.
Correction to: Phytotoxin sorption to clay minerals
Authors: Schönsee Carina D. , Wettstein Felix E. , Bucheli Thomas D.
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
Efficacy and safety of apatinib in the treatment of osteosarcoma: a single-arm meta-analysis among Chinese patients
Authors: Yao Hui , Chen Xuyu , Tan Xiaodong
Published: April 2021

Background

Osteosarcoma is a relatively rare malignant tumor with a high incidence in young people. The development of tyrosine kinase inhibitors has brought the treatment of osteosarcoma into a new stage. Apatinib, a tyrosine kinase inhibitor specifically targeting VEGFR2, has been increasingly reported as a treatment for osteosarcoma with promising outcome parameters, but there has been no systematic analysis of the treatment of osteosarcoma by apatinib.

Methods

A single-arm meta-analysis was performed, and published literature from PubMed, Web of Science, Embase, Cochrane Library, CNKI and Wan Fang databases as of March 1, 2021 was systematically retrieved. Quality assessment is carried out in accordance with a 20 item checklist form prepared by the Institute of Health Economics (IHE). Double arcsine transformation is performed to stabilize the variance of the original ratio. When I2 > 50%, the random effect model is used to calculate the pooled parameters; otherwise, the fixed effect model is used. We conducted subgroup analysis according to age and apatinib dose.

Results

This meta-analysis included 11 studies of 356 Chinese patients with osteosarcoma. The pooled objective remission rate (ORR) of advanced or metastatic osteosarcoma treated by oral apatinib in Chinese patients was 0.27(95%CI = 0.18–0.38). The pooled disease control rate (DCR) was 0.57 (95%CI = 0.42–0.72). The pooled median progression-free survival (mPFS) and median total survival (mOS) were 5.18 months (95%CI = 4.03–6.33) and 10.87 months (95% CI = 9.40–12.33), respectively. More than 70% of adverse reactions were mild, the most common adverse reaction was hand-foot syndrome (HFMD), with an incidence of 0.46 (95%CI = 0.35–0.58), the second was hypertension, with an incidence of 0.40 (95%CI = 0.29–0.51).

Conclusions

The efficacy of apatinib in the treatment of osteosarcoma is competitive with current evidence, and it is worth noting that its low cost can significantly improve patient compliance and increase therapeutic value.
Healthcare professionals in research (HPiR) Facebook community: a survey of U.K. doctoral and postdoctoral healthcare professionals outside of medicine
Authors: Deane J. A. , Clunie G.
Published: April 2021

Background

Healthcare professionals outside of medicine (HCPs), including nurses, midwives and allied health professionals, are increasingly involved in research for patient benefit. Their challenge is to negotiate inter-professional or professionally isolated contexts. The aims of this study were to evaluate the ‘Healthcare Professionals in Research’ (HPiR) Facebook group (a self-directed and confidential peer support group for doctoral and postdoctoral HCPs) including engagement, the experiences of doctoral and postdoctoral HPiR members and to identify future career challenges using an on-line survey.

Methods

The HPiR Facebook group was launched in May 2019. Five HCP Community managers (CMs) were trained in on-line platform curation, moderation and screening. An on-line survey was designed to capture data from HPiR members. A purposive sampling approach was applied. Respondents were required to be doctoral and postdoctoral HCPs and a registered member of the HPiR group. Respondents represented a range of healthcare professions, 79 % of whom had over ten years clinical experience. Membership growth and engagement was analysed. Descriptive statistics were used to present numerical data. Qualitative data were analysed thematically.

Results

96 members were admitted to the group within the first month. All members were actively engaged with group content. 34/96 doctoral and postdoctoral HCPs completed the survey. Most members joined for networking (88 %) and peer support (82 %) purposes. Analysis of text responses showed difficulties in balancing a clinical academic career and highlighted the consequences of undefined clinical academic roles and pathways.

Conclusions

Doctoral and postdoctoral HCPs value the opportunities that HPiR provides for peer support and connection with fellow HCPs. HPiR has the potential to strengthen research capacity, support research skill development and drive change within the clinical academic community. Clinical academic roles and pathways need to be standardised. The creation of opportunities beyond doctoral studies is a priority.
Development of recombinase polymerase amplification assays for rapid and visual detection of canine distemper virus infecting giant panda
Authors: Huang Pei , Yu Yue , Meng Xianyong , Wang Tiecheng , Yan Feihu , Li Entao , Shi Zhikang , He Hongbin , Yang Songtao , Xia Xianzhu , Wang Jianzhong , Feng Na
Published: April 2021

Background

Canine distemper virus (CDV) is an enveloped negative-strand RNA virus that exhibits a high mutation rate and continuously expands the range of hosts. Notably, CDV has infected giant panda with spill over from viral reservoirs in canines. Giant pandas (Ailuropoda melanoleuca), especially captive pandas, are known to be susceptible to natural infection with CDV. The high fatality rate of CDV poses a serious threat to the safety of the giant panda population. However, vaccines or drugs for canine distemper in giant pandas have not been developed to date. Therefore, a rapid test that can achieve accurate onsite detection of CDV is important to enable the timely implementation of control measures. In this study, we established a nucleic acid visualization assay for targeting the CDV N gene by using combines reverse transcription recombinase polymerase amplification with a closed vertical flow visualization strip (RT-RPA-VF).

Results

The RT-RPA-VF assay does not require sophisticated equipment, and it was determined to provide rapid detection at 35 °C for 30 min, while the limit of detection was 5 × 101 copies/μl RNA transcripts and 100.5 TCID50 ml− 1 viruses. The results showed that the assay was high specific to CDV and had no cross-reactivity with other viruses infecting the giant panda. Compared with RT-qPCR, RT-RPA-VF assay had a sensitivity of 100% and a specificity of 100% in 29 clinical samples. The coincidence rate between RT-RPA-VF and RT-qPCR was 100% (kappa = 1), indicating that the RT-RPA-VF assay possessed good diagnostic performance on clinical samples.

Conclusions

The RT-RPA-VF provides a novel alternative for the simple, sensitive, and specific identification of CDV and showed great potential for point of care diagnostics for captive and wild giant panda.
Identification of an immune-related signature indicating the dedifferentiation of thyroid cells
Authors: Wang Xuemin , Peng Wen , Li Chunyan , Qin Rujia , Zhong Zhaoming , Sun Chuanzheng
Published: April 2021

Background

Immune cells account for a large proportion of the tumour microenvironment in anaplastic thyroid carcinomas (ATCs). However, the expression pattern of immune-related genes (IRGs) in ATCs is unclear. Our study aimed to identify an immune-related signature indicating the dedifferentiation of thyroid cells.

Methods

We compared the differences in thyroid differentiation score (TDS), infiltration of immune cells and enriched pathways between ATCs and papillary thyroid carcinomas (PTCs) or normal thyroid tissues in the Gene Expression Omnibus database. Univariate and multivariable Cox analyses were used to screen prognosis-associated IRGs in The Cancer Genome Atlas database. After constructing a risk score, we investigated its predictive value for differentiation and survival by applying receiver operating characteristic and Kaplan–Meier curves. We further explored its associations with important immune checkpoint molecules, infiltrating immune cells and response to immunotherapy.

Results

Compared with PTCs or normal thyroid tissues, ATCs exhibited lower TDS values and higher enrichment of immune cells and activation of the inflammatory response. The quantitative analyses and immunohistochemical staining validated that most ATC cell lines and ATC tissues had higher expression of MMP9 and lower expression of SDC2 than normal thyroid samples and PTC. Higher risk scores indicates dedifferentiation and a worse prognosis. Additionally, the risk score was positively correlated with the immune checkpoint molecules PDL1, CTLA4, IDO1, and HAVCR2 and infiltration of multiple immune cells. Importantly, we found that the samples with higher risk scores tended to have a better response to immunotherapy than those with lower scores.

Conclusion

Our findings indicate that the risk score may not only contribute to the determination of differentiation and prognosis of thyroid carcinomas but also help the prediction of immune cells infiltration and immunotherapy response.
A dual-targeting ruthenium nanodrug that inhibits primary tumor growth and lung metastasis via the PARP/ATM pathway
Authors: Lu Yu , Zhu Di , Gui Lin , Li Yuanming , Wang Wenjing , Liu Jiawang , Wang Yuji
Published: April 2021

Background

Many studies have found that ruthenium complexes possess unique biochemical characteristics and inhibit tumor growth or metastasis.

Results

Here, we report the novel dual-targeting ruthenium candidate 2b, which has both antitumor and antimetastatic properties and targets tumor sites through the enhanced permeability and retention (EPR) effect and transferrin/transferrin receptor (TF/TFR) interaction. The candidate 2b is composed of ruthenium-complexed carboline acid and four chloride ions. In vitro, 2b triggered DNA cleavage and thus blocked cell cycle progression and induced apoptosis via the PARP/ATM pathway. In vivo,2b inhibited not only Lewis lung cancer (LLC) tumor growth but also lung metastasis. We detected apoptosis and decreased CD31 expression in tumor tissues, and ruthenium accumulated in the primary tumor tissue of C57BL/6 mice implanted with LLC cells.

Conclusions

Thus, we conclude that 2b targets tumors, inhibits tumor growth and prevents lung metastasis.
Psychometric properties of the EORTC QLQ-C30 in Uganda
Authors: Naamala Allen , Eriksson Lars E. , Orem Jackson , Nalwadda Gorrette K. , Kabir Zarina Nahar , Wettergren Lena
Published: April 2021

Background

Self-reported measures play a crucial role in research, clinical practice and health assessment. Instruments used to assess self-reported health-related quality of life (HRQoL) need validation to ensure that they measure what they are intended to, detect true changes over time and differentiate between subjects. A generic instrument measuring HRQoL adapted for use among people living with cancer in Uganda is lacking; therefore, this study aimed to evaluate the psychometric properties of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 in patients with cancer in Uganda.

Methods

Adult patients with various types of cancer (n = 385) cared for at the Uganda Cancer Institute answered the EORTC QLQ-C30 in Luganda or English language, the two most spoken languages in the country. The two language versions were evaluated with regard to data quality (floor and ceiling effects and missing responses), reliability (internal consistency) and validity (construct, known-group and criterion). Construct validity was examined through confirmatory factor analysis (CFA). Mean scores were compared between groups differing in disease stage to assess known-group validity. Criterion validity was examined according to associations between two QLQ-C30 subscales (Global quality of life and Physical function) and the Karnofsky Performance Scale (KPS).

Results

Floor and ceiling effects were observed for several scales in the Luganda and English versions. All EORTC scales with the exception of Cognitive function (Luganda α = 0.66, English α = 0.50) had acceptable Cronbach’s alpha values (0.79–0.96). The CFA yielded good fit indices for both versions (RMSEA = 0.08, SRMR = 0.05 and CFI = 0.93). Known-group validity was demonstrated with statistically significant better HRQoL reported by patients with disease stages I–II compared to those in stages III–IV. Criterion validity was supported by positive correlations between KPS and the subscales Physical function (Luganda r = 0.75, English r = 0.76) and Global quality of life (Luganda r = 0.59, English r = 0.72).

Conclusion

The Luganda and English versions of the EORTC QLQ-C30 appear to be valid and reliable measures and can be recommended for use in clinical research to assess HRQoL in adult Ugandans with cancer. However, the cognitive scale did not reach acceptable internal consistency and needs further evaluation.
Equine pericardium: a versatile alternative reconstructive material in congenital cardiac surgery
Authors: Elassal Ahmed Abdelrahman , AL-Radi Osman Osama , Zaher Zaher Faisal , Dohain Ahmed Mohamed , Abdelmohsen Gaser Abdelmohsen , Mohamed Ragab Sayed , Fatani Mazin Adel , Abdelmotaleb Mohamed Esam , Noaman Nada Ahmed , Elmeligy Mahmoud Akl , Eldib Osama Saber
Published: April 2021

Background

Pericardial patches are often used for repair of congenital cardiac defects. The aim of this study was to describe our initial experience with the use of equine pericardium and its safety and advantages and disadvantages compared to bovine pericardium.

Methods

We designed a retrospective cohort study of 111 patients who were surgically treated for congenital heart disease between 2017 and 2020. Equine pericardium was used in 58 patients and bovine pericardium was used in 53 patients. Recorded variables included demographic data, preoperative cardiac pathology, site of patch insertion, morbidity and mortality.

Results

The overall survival rate was 94.5% and no deaths were related to patch insertion. None of our patients were reoperated on for patch related complications. Postoperative transcatheter intervention was needed in 2 patients (1.8%): one for dilatation of aortic arch stenosis after repair of hypoplastic left heart syndrome with equine pericardium and one for dilatation of pulmonary artery branches after repair of tetralogy of Fallot using bovine pericardium.

Conclusions

Equine pericardium is a safe patch material for reconstruction in congenital heart surgery. It may be preferable to bovine pericardium in cases requiring a complex shape or a pliable patch as in in arch reconstruction or for valve reconstruction.