bluuebunny/crossref_metadata_2025 huggingface dataset:
Degree of Agreement Between Infant Serum and Salivary Concentration of Leptin and Adiponectin and Its Association With Infants’ Feeding
Authors: Linares Ana M. , Rayens Mary Kay , Moylan Jennifer S. , Miller Craig S.
Published: November 2020

Background:

Leptin and adiponectin, two adipokines involved in glucose and lipid metabolism, have been linked to regulation of growth in early infancy, energy balance, and metabolic disorders in childhood. The aim of this study was to determine if concentrations of leptin and adiponectin could be measured reliably in infants’ saliva, to evaluate the degree of agreement with infant serum levels, and to explore their association with infant feeding status.

Methods:

A total of 34 infants were recruited after birth and followed for 20 weeks. After log-transformation of the values, a Bland-Altman graphical approach was used to summarize the direction of the difference between the serum and saliva values. Repeated measures mixed modeling was used to evaluate differences over time in these outcomes by feeding status.

Results:

Mean concentration of salivary leptin and adiponectin in infants was 3.7 ( SD = .8) ng/mL and 2.9 ( SD = 0.7) ng/mL, respectively. The degree of agreement between serum and saliva for log-transformed leptin and adiponectin values were relatively robust, albeit with a non-zero bias between the two methods, given that serum values were greater than corresponding saliva values for both adipokines in all infants. Each of the four repeated measures mixed models (one for each adipokine measure) had a significant main effect; however, the interaction between time and feeding status was not significant in any of the models.

Conclusion:

This study demonstrated that leptin and adiponectin can be measured in infant saliva, but in some cases leptin concentrations may be more difficult to detect.
Oral nomegestrol acetate and transdermal 17-beta-estradiol for preventing post-partum relapses in multiple sclerosis: The POPARTMUS study
Authors: Vukusic Sandra , Ionescu Iuliana , Cornu Catherine , Bossard Nadine , Durand-Dubief Françoise , Cotton François , Durelli Luca , Marignier Romain , Gignoux Laurence , Laplaud David-Axel , Moreau Thibault , Clavelou Pierre , De Seze Jérôme , Debouverie Marc , Brassat David , Pelletier Jean , Lebrun-Frenay Christine , Le Page Emmanuelle , Castelnovo Giovanni , Berger Eric , Hautecoeur Patrick , Heinzlef Olivier , Trojano Maria , Patti Francesco , Baulieu Etienne-Emile , Remontet Laurent , El-Etr Martine
Published: December 2020

Background:

Sex steroids could explain the course of multiple sclerosis (MS) in pregnancy.

Objective:

To compare the annualized relapse rate (ARR) 12 weeks post-partum in women treated with nomegestrol acetate (NOMAc) and 17-beta-estradiol (E2) versus placebo.

Methods:

POPARTMUS is a randomized, proof-of-concept trial in women with MS, receiving oral NOMAc 10 mg/day and transdermal estradiol 75 µg/week, or placebo.

Results:

Recruitment was stopped prematurely due to slow inclusions ( n = 202). No treatment effect was observed on ARR after 12 weeks (sex steroids = 0.90 (0.58–1.39), placebo = 0.97 (0.63–1.50) ( p = 0.79)).

Conclusion:

POPARTMUS failed showing efficacy of a NOMAc–E2 combination in preventing post-partum relapses.
Sharing travel related experiences on social media – Integrating social capital and face orientation
Authors: Kumar Thivashini B Jaya , Goh See-Kwong , Balaji M S
Published: November 2020

Tourists can share their travel experiences or related information freely through social media platforms. The purpose of this research is to explore the factors associated with sharing travel related experiences on social media by travellers in the context of social capital theory and person-context interaction theory. Data were collected among consumers in Malaysia using a structured survey; 423 responses were generated. The findings show that the social capital dimensions (social ties, trust, reciprocity and shared vision) positively impact sharing intention on social media while identification doesn’t impact the sharing intention. The results also partially support the hypothesis that protective face orientation negatively influences social capital dimensions and sharing intention while acquisitive face orientation positively influences them. The authors shed light on the construction of social capital dimensions and face orientation and the relative importance of the sharing intention on social media.
Distribution of sickness absence risk across different levels and patterns of drinking: findings from the Stockholm Public Health Cohort
Authors: Landberg Jonas , Ramstedt Mats
Published: November 2020

Aim:

This study estimated (i) the risk function between different indicators of alcohol use and long-term sickness absence, adjusting for possible confounding factors, (ii) whether the risk function between average volume of consumption and sickness absence is modified by heavy episodic drinking (HED), and (iii) to what extent the risk for sickness absence among abstainers is due to health selection bias.

Data and methods:

The study was based on data from the Stockholm Public Health Cohort 2006, with an analytical sample of 16,477 respondents aged 18–64 years. The outcome included register-based long-term (> 14 days) sickness absence. Negative binominal regression was used to estimate the association between sickness absence and average weekly volume of consumption, frequency of HED, and both in interaction.

Results:

Abstainers, chronic heavy drinkers and respondents with the highest frequency of HED had approximately two-fold higher rates of sickness absence relative to the reference groups, i.e., moderate drinkers and those with HED one to 6 times per year. Adjustment for confounding factors did not materially affect the shape of the risk function. After exclusion of abstainers with alcohol-related problems, or poor health, the estimates for abstainers became non-significant. Moderate drinkers with HED did not have significantly higher rates of sickness absence than moderate drinkers without HED.

Conclusions:

Our results suggest a significant association between alcohol use and sickness absence. There were indications that the U-shaped risk function may largely be due to health selection bias among abstainers. We found no indication of effect modification of HED on moderate drinking.
A comparative assessment of transfer accuracy of two indirect bonding techniques in patients undergoing fixed mechanotherapy: A randomised clinical trial
Authors: Chaudhary Vivek , Batra Puneet , Sharma Karan , Raghavan Sreevatsan , Gandhi Vikram , Srivastava Amit
Published: December 2020

Objectives

To assess the transfer accuracy of three-dimensional (3D) printed transfer trays and compare them with transfer trays made up of polyvinyl siloxane (PVS) for use in indirect bonding.

Design:

This was a two-arm parallel prospective randomised controlled trial.

Setting:

The trial was undertaken at the outpatient department of a dental college.

Participants:

A total of 30 patients (18 men, 12 women) were randomly allocated to two groups.

Methods:

The inclusion criteria included patients with permanent and fully erupted dentition (age range = 17–24 years), Angles class I malocclusion with crowding <3 mm requiring non-extraction treatment, good oral hygiene and no previous history of orthodontic treatment. Blinding was applicable only for outcome assessment. Indirect bonding was performed by the primary investigator for both the groups. Digital images of the pre-transfer and post-transfer brackets were obtained by means of an intra-oral scanner and compared using software. Superimpositions of pre- and post-transfer images were done to determine the transfer error for linear and angular variables for all tooth types.

Results:

A total of 600 teeth were bonded, 300 each for both groups. Statistically significant differences were observed in all dimension between the two groups, with 3D-printed trays being more accurate than PVS trays except in the vertical dimension ( P < 0.05). The prevalence of clinically unacceptable transfer errors revealed that most of the transfer errors were in the vertical dimensions for 3D-printed trays.

Conclusion:

3D-printed trays are more accurate than PVS trays except for transfers in vertical dimension.
Remembering love: Memory work of orphaned children in the Philippine drug war
Authors: Ofreneo Mira Alexis , Canoy Nico , Martinez Luz Maria , Fortin Pacita , Mendoza Merlie , Yusingco Mara Patricia , Aquino Michaela Grace
Published: November 2020

The “war on drugs” in the Philippines has left a generation of Filipino orphaned children in deep grief and social disarray. Using feminist memory work as critical methodology and intervention design, this study examines accounts of 56 orphaned children and how they exercise agency embedded in the collective remembering of a traumatic past (i.e. rooted in painful memories of tokhang or community police operations) and to identify social structures that marginalize their present and future lifeworld.

Findings

Findings show three overarching themes namely: (1) reclaiming stripped agency in the loss and injustice of the past, (2) holding on to crippled agency in the sadness and insecurity of the present, and (3) carrying on with agency to hope for healing and justice in a reimagined future.

Applications

Insights and recommendations to critical praxis of social work in light of an ongoing drug war are further discussed which include strengthening civil societies and intersectoral collaborations, integrating specific social provisions for tokhang survivors in the creation of a national orphan policy, and using digital memorialization. Guided by enacting ethics and politics of caring for and with the marginalized, social workers working alongside expanded communities of care are called to remember love despite traumatic pains and to restore homes for orphaned children in the midst of state insecurity.
Reflections on the contribution of Muhammad Anwar to the study of sociology and racial politics
Authors: Abbas Tahir
Published: December 2020

Muhammad Anwar passed away on 11 June 2019, at the age of 75 after 50 years of research and policy development in the area of race and ethnic studies. In this article, I explore his numerous contributions, including his important work, The Myth of Return: Pakistanis in Britain, published in 1979. His interest in politics and, in particular, participation, and representation within it, led to Race and Elections, published in 1994. His subsequent works on identifying the intergenerational differences among British Pakistanis, who also happen to represent a significant proportion of British Muslims, developed into his final major book, Between Cultures, published in 1998. I explore the nature of his contribution, the impact that it had in the field of race and ethnic studies, and the research openings generated for other scholars to expand on his social anthropological and sociological emphasis on better understanding the experiences of racial and ethnic minorities and the need to better develop policies to alleviate ethnic and racial disadvantage.
Serum miR-185 Is a Diagnostic and Prognostic Biomarker for Non-Small Cell Lung Cancer
Authors: Liu Jinghao , Han Yueting , Liu Xingyu , Wei Sen
Published: November 2020

Objective:

MicroRNAs (miRNAs) have been found to play important roles in the development of non-small cell lung carcinoma (NSCLC). The aim of this study was to analyze the expression and clinical value of serum miR-185 in NSCLC.

Methods:

Serum miR-185 levels were detected in 146 NSCLC patients, 50 patients with carcinoma in situ, 25 patients with non-malignant lung diseases (NMLD), and 80 healthy controls using quantitative reverse transcription PCR. The correlation between serum miR-185 level and clinical status of NSCLC was explored.

Results:

The results revealed that serum miR-185 expression was progressively decreased in healthy controls, patients with NMLD, patients with carcinoma in situ and NSCLC patients. In addition, compared to carcinoembryonic antigen (CEA), serum miR-185 demonstrated better diagnostic accuracy for discriminating patients with carcinoma from healthy controls, NSCLC patients from healthy controls and NSCLC patients from patients with carcinoma in situ. In addition, serum miR-185 levels were significantly elevated in post-treated samples compared to the pre-treated samples. Moreover, reduced serum miR-185 was closely associated with unfavorable clinicopathological parameters and worse survival. Univariate and multivariate cox regression analysis confirmed that serum miR-185 was an independent prognostic indicator for NSCLC.

Conclusions:

Collectively, our findings have demonstrated that serum miR-185 might serve as a promising and robust biomarker for the early detection and prognosis prediction of NSCLC.
miR-518a-3p Suppresses Triple-Negative Breast Cancer Invasion and Migration Through Regulation of TMEM2
Authors: Gan Lin , Yang Huachao , Xiong Zhifeng , Yang Zailiang , Wang Ting , Lyu Gang
Published: November 2020

MicroRNAs (miRNAs) are emerging as critical mediators in tumors, including triple-negative breast cancer (TNBC). The role of miR-518a-3p in TNBC was investigated to identify potential therapeutic target. Data from KM Plotter database ( www.kmplot.com ) showed that high miR-518a-3p expression was significantly associated with overall survival of patients with TNBC ( p = 0.04). The expression of miR-518a-3p was dysregulated in TNBC cells. Functional assays revealed that over-expression of miR-518a-3p inhibited cell invasion and migration of TNBC. Additionally, miR-518a-3p could target TMEM2 (transmembrane protein 2), and decreased protein and mRNA expression of TMEM2 in TNBC cells. Knockdown of TMEM2 suppressed cell invasion and migration through inhibiting phospho (p)-JAK1 (Janus kinase 1) and p-STAT (signal transducer and activator of transcription protein) 1/2. Moreover, over-expression of TMEM2 counteracted the suppressive effect of miR-518a-3p on TNBC invasion and migration through promoting the levels of p-JAK1 and p-STAT1/2. In conclusion, miR-518a-3p negatively regulates the JAK/STAT pathway via targeting TMEM2 and suppresses invasion and migration in TNBC, suggesting that miR-518a-3p may be a potential therapeutic target in TNBC.
Store-operated calcium entry: Pivotal roles in renal physiology and pathophysiology
Authors: Chaudhari Sarika , Mallet Robert T , Shotorbani Parisa Y , Tao Yu , Ma Rong
Published: November 2020

Research conducted over the last two decades has dramatically advanced the understanding of store-operated calcium channels (SOCC) and their impact on renal function. Kidneys contain many types of cells, including those specialized for glomerular filtration (fenestrated capillary endothelium, podocytes), water and solute transport (tubular epithelium), and regulation of glomerular filtration and renal blood flow (vascular smooth muscle cells, mesangial cells). The highly integrated function of these myriad cells effects renal control of blood pressure, extracellular fluid volume and osmolality, electrolyte balance, and acid–base homeostasis. Many of these cells are regulated by Ca2+signaling. Recent evidence demonstrates that SOCCs are major Ca2+entry portals in several renal cell types. SOCC is activated by depletion of Ca2+stores in the sarco/endoplasmic reticulum, which communicates with plasma membrane SOCC via the Ca2+sensor Stromal Interaction Molecule 1 (STIM1). Orai1 is recognized as the main pore-forming subunit of SOCC in the plasma membrane. Orai proteins alone can form highly Ca2+selective SOCC channels. Also, members of the Transient Receptor Potential Canonical (TRPC) channel family are proposed to form heteromeric complexes with Orai1 subunits, forming SOCC with low Ca2+selectivity. Recently, Ca2+entry through SOCC, known as store-operated Ca2+entry (SOCE), was identified in glomerular mesangial cells, tubular epithelium, and renovascular smooth muscle cells. The physiological and pathological relevance and the characterization of SOCC complexes in those cells are still unclear. In this review, we summarize the current knowledge of SOCC and their roles in renal glomerular, tubular and vascular cells, including studies from our laboratory, emphasizing SOCE regulation of fibrotic protein deposition. Understanding the diverse roles of SOCE in different renal cell types is essential, as SOCC and its signaling pathways are emerging targets for treatment of SOCE-related diseases.
Pre-Operative CT-Based Planning Integrated With Intra-Operative Navigation in Reverse Shoulder Arthroplasty: Data Acquisition and Analysis Protocol, and Preliminary Results of Navigated Versus Conventional Surgery
Authors: Moreschini Fabio , Colasanti Giovanni Battista , Cataldi Carlo , Mannelli Lorenzo , Mondanelli Nicola , Giannotti Stefano
Published: November 2020

Reverse total shoulder arthroplasty (RSA) successfully restores shoulder function in different conditions. Glenoid baseplate fixation and positioning seem to be the most important factors influencing RSA survival. When scapular anatomy is distorted (eccentric osteoarthrirtis, rotator cuff arthropathy), optimal baseplate positioning and secure screw purchase can be challenging. The aim of this study was to evaluate whether CT-based pre-operative planning, integrated with intra-operative navigation could improve glenoid baseplate fixation and positioning by increasing screw length, reducing number of screws required to obtain fixation and increasing the use of augmented baseplate to gain the desired positioning. Twenty patients who underwent navigated RSA were compared retrospectively with 20 patients operated on with a conventional technique. All the procedures were performed by the same surgeon, using the same implant. Mean screw length was significantly longer in the navigation group (35.5 ± 4.4 mm vs 29.9 ± 3.6 mm; p = .001). Significant higher rate of optimal fixation using 2 screws only (17 vs 3 cases, p = .019) and higher rate of augmented baseplate usage (13 vs 4 cases, p = .009) was also present in the navigation group. Pre-operative CT-based planning integrated with intra-operative navigation can improve glenoid component positioning and fixation, possibly leading to an improvement of RSA survival.
The Effect of MicroRNA-Mediated Exercise on Delaying Sarcopenia in Elderly Individuals
Authors: Xie Wen-Qing , Men Chen , He Miao , Li Yu-sheng , Lv Shan
Published: November 2020

Sarcopenia is often regarded as an early sign of weakness and is the core element of muscle weakness in elderly individuals. Sarcopenia is closely related to the reduction of exercise, and elderly individuals often suffer from decreased muscle mass and function due to a lack of exercise. At present, studies have confirmed that resistance and aerobic exercise are related to muscle mass, strength and fiber type and to the activation and proliferation of muscle stem cells (MuSCs). Increasing evidence shows that microRNAs (miRNAs) play an important role in exercise-related changes in the quantity, composition and function of skeletal muscle. At the cellular level, miRNAs have been shown to regulate the proliferation and differentiation of muscle cells. In addition, miRNAs are related to the composition and transformation of muscle fibers and involved in the transition of MuSCs from the resting state to the activated state. Therefore, exercise may delay sarcopenia in elderly individuals by regulating miRNAs in skeletal muscle. In future miRNA-focused treatment strategies, these studies will provide valuable information for the formulation of exercise methods and will provide useful and targeted exercise programs for elderly individuals with sarcopenia.
Technical aspects of combined intrasaccular and endoluminal flow diversion
Authors: White Timothy G , Shah Kevin , Turpin Justin , Link Thomas , Dehdashti Amir R , Katz Jeffrey M , Woo Henry H
Published: November 2020

Introduction

The concurrent use of endoluminal flow diversion with coils is a viable option when treating complex or large aneurysms. Alternatives to coil embolization as an adjunctive treatment are currently limited. The Food and Drug Administration recently approved the Woven EndoBridge (WEB) device (Microvention, Aliso Viejo, California) as an intrasaccular flow diverter for wide-neck bifurcation aneurysms. We present the technical aspects of combined WEB device plus endoluminal flow diversion for the treatment of complex wide-necked intracranial aneurysms.

Methods

A retrospective chart review of all patients treated via intrasaccular flow diversion at a single institution over the last 12 months was performed.

Results

In total, seven patients underwent treatment of eight aneurysms via combined intrasaccular and endoluminal flow diversion. Of the seven patients, six were treated in a single setting. The most common aneurysm location was the posterior communicating artery. The majority of the aneurysms required steam shaping of the Via deployment catheter to place the WEB device orthogonally to the aneurysm dome. There were no complications.

Conclusions

We believe this is one of the first series reporting the combined use of the WEB device and endoluminal flow diversion for the treatment of intracranial aneurysms. This series demonstrates that the concurrent use of the WEB device with endoluminal flow diversion is safe for achieving immediate aneurysm treatment and may enhance the long-term durability in complex aneurysms.
Unjustifiably Irresponsible: The Effects of Social Roles on Attributions of Intent
Authors: Rowe Stephen J. , Vonasch Andrew J. , Turp Michael-John
Published: November 2020

How do people’s social roles change others’ perceptions of their intentions to cause harm? Three preregistered vignette-based experiments ( N = 788) manipulated the social role of someone causing harm and measured how intentional people thought the harm was. Results indicate that people judge harmful consequences as intentional when they think the actor unjustifiably caused harm. Social roles were shown to alter intention judgments by making people responsible for preventing harm (thereby rendering the harm as an intentional neglect of one’s responsibilities) or for causing the harm (thereby excusing it as an unintentional byproduct of the role). Additionally, Experiment 3 conceptually replicated and moderated the side-effect effect —revealing that people think harmful side effects are intentional when the harm is unjustified but not when a role’s responsibility justifies it. We discuss the importance of social information—including roles—in how people judge others’ intentions.
Recognition and attunement in migration research
Authors: Conradson David
Published: November 2020

This commentary reflects upon Miriam Tedeschi’s (2021) use of Gilbert Simondon’s work to examine the lived experience of irregular migrants in Finland. It considers what Simondon’s ideas illuminate as well as what they appear to leave relatively unexamined. If we are to understand the lived experience of irregular migrants, it is argued that we need theoretical resources that more fully foreground social and political processes of welcome/unwelcome, recognition/disregard and hospitality/hostility. To the extent that Simondon’s work supports only a generalised consideration of such matters, it might usefully be supplemented by perspectives that address them in more depth. In this regard, it is suggested that postcolonial and critical geographical scholarship could enable fuller recognition of and attunement to the complex lived experience of irregular migrants.
Migration ethics in pandemic times
Authors: Collins Francis L
Published: November 2020

Geographical approaches to studying migration have recently been substantially enlivened by the introduction of social theory from a range of traditions – poststructural, feminist, new materialist, and postcolonial, amongst others. Tedeschi’s introduction of Gilbert Simondon’s notions of individuation, affect, and ethics offers an interesting and important addition to this growing movement to reconceptualising migration. In this commentary, I reflect on the potential of Tedeschi’s approach in relation to the COVID-19 pandemic and its implications for border control and migration. I argue that while the focus on indivdiuation and individual-environment articulations is valuable, Tedeschi’s argument also problematically sets aside collective individuation, affect, and ethics as well as their potential for addressing precarity. Here lies the risk for reconceptualising migration studies – that researchers aim for ever more granular accounts of migration but perhaps lose sight of the politics and ethics of transforming systems and circumstances in ways that enhance migrant lives.
Self-reported psychological distress among caregivers of patients with cancer: Findings from a health facility-based study in Vietnam 2019
Authors: Long Nguyen Xuan , Phung Tran Thi , Ngoc Nguyen Bao , Linh Dao Thi Dieu , Anh Ta Nhat , Lan Nguyen Thi Mai , Thang Nguyen Thi , Trang Vu Thu , Hung Nguyen Viet , Thuong Nguyen Hiep , Hieu Nguyen Van , Minh Hoang Van
Published: December 2020

In Vietnam, little is elucidated in scientific literatures about the mental health of caregivers of people with cancer. We conducted a cross-sectional study to report the situation and correlates of self-reported psychological distress among caregivers of cancer patients in Vietnam in 2019. Multiple logistic and linear regression analyses were performed. A total of 16.5% of the study participants had psychological distress. Respondent’s mean score of negative emotion was 7.6 ± 2. Educational level and type of support were significantly associated with having psychological distress among caregivers. Gender, occupation, financial difficulty, treatment belief and social support significantly correlated to psychological distress level of caregivers.
Protecting the Well-Being of Medical Residents and Faculty Physicians During the COVID-19 Pandemic: Making the Case for Accessible, Comprehensive Wellness Resources
Authors: Ey Sydney , Soller Marie , Moffit Mary
Published: December 2020

Accounts of frontline health care workers experiencing distress in the midst of the COVID-19 pandemic highlight the need for accessible psychological support for them. Prior to the pandemic, medical residents and physicians often experienced difficulty receiving counseling due to concerns about confidentiality, stigma, cost, time, and reportability to licensure/credentialing bodies. Since 2004, the OHSU Resident and Faculty Wellness Program (RFWP) team has sought to reduce these barriers by providing on-site free, confidential, individual counseling and medication management. Utilization of this program is high with over 500 physicians a year seeking care; 38% of all OHSU residents/fellows and 7% of all faculty eligible for our services participated in 2019-20. In the present essay, we describe how our model of care for trainees and faculty was a key wellness resource during COVID-19.

Similar to other accounts of lower help-seeking by health professionals initially during the pandemic, we experienced a slight downturn in utilization rates during the initial weeks of when the pandemic struck our area, but quickly returned to normal and exceeded prior levels. All appointments shifted to telehealth visits and a number of physicians expressed gratitude for the opportunity to talk through concerns and strengthen coping. A number of physicians requested medication consultations to address severe insomnia, anxiety, and depression. We hope that being present in our physicians’ lives when they are exposed to COVID-related stress or trauma will keep them safe, help them cope with difficult experiences and losses, and ultimately facilitate both recovery and post-traumatic growth.
Rapid Diagnosis of Invasive Aspergillosis and Active Hepatitis-B Virus Co-Infection in a HIV-1 Infected Patient Using Cell Free DNA Sequencing
Authors: Roy Moni , Kim Joseph Y. , Lin Rone-Chun
Published: November 2020

Multiple simultaneous opportunistic infections in Human Immunodeficiency virus-1/Acquired immunodeficiency syndrome (HIV-1/AIDS) is a known and dreaded occurrence that often leads to poor outcomes. We present a case of disseminated aspergillosis and active Hepatitis-B virus (HBV) infection in such a host, where cell free DNA (cfDNA) next generation sequencing (NGS) of plasma was used to expedite diagnosis. Bronchoscopy was avoided and treatment was started expeditiously. In this case report we discuss the interpretation of the cfDNA NGS, and its potential role for early diagnosis and avoidance of invasive testing.
Transient expansion of TP53 mutated clones in polycythemia vera patients treated with idasanutlin
Authors: Marcellino Bridget K. , Farnoud Noushin , Cassinat Bruno , Lu Min , Verger Emanuelle , McGovern Erin , Patel Minal , Medina-Martinez Juan , Levine Max Fine , Arango Ossa Juanes E. , Zhou Yangyu , Kosiorek Heidi , Mehrotra Meenakshi , Houldsworth Jane , Dueck Amylou , Rossi Michael , Mascarenhas John , Kiladjian Jean-Jacques , Rampal Raajit K. , Hoffman Ronald
Published: December 2020

Activation of the P53 pathway through inhibition of MDM2 using nutlins has shown clinical promise in the treatment of solid tumors and hematologic malignancies. There is concern, however, that nutlin therapy might stimulate the emergence or expansion of TP53-mutated subclones. We recently published the results of a phase 1 trial of idasanutlin in patients with polycythemia vera (PV) that revealed tolerability and clinical activity. Here, we present data indicating that idasanutlin therapy is associated with expansion of TP53 mutant subclones. End-of-study sequencing of patients found that 5 patients in this trial harbored 12 TP53 mutations; however, only 1 patient had been previously identified as having a TP53 mutation at baseline. To identify the origin of these mutations, further analysis of raw sequencing data of baseline samples was performed and revealed that a subset of these mutations was present at baseline and expanded during treatment with idasanutlin. Follow-up samples were obtained from 4 of 5 patients in this cohort, and we observed that after cessation of idasanutlin, the variant allele frequency (VAF) of 8 of 9 TP53 mutations decreased. Furthermore, disease progression to myelofibrosis or myeloproliferative neoplasm blast phase was not observed in any of these patients after 19- to 32-month observation. These data suggest that idasanutlin treatment may promote transient TP53 mutant clonal expansion. A larger study geared toward high-resolution detection of low VAF mutations is required to explore whether patients acquire de novo TP53 mutations after idasanutlin therapy.
Che-1/AATF-induced transcriptionally active chromatin promotes cell proliferation in multiple myeloma
Authors: Bruno Tiziana , De Nicola Francesca , Corleone Giacomo , Catena Valeria , Goeman Frauke , Pallocca Matteo , Sorino Cristina , Bossi Gianluca , Amadio Bruno , Cigliana Giovanni , Ricciardi Maria Rosaria , Petrucci Maria Teresa , Spugnini Enrico Pierluigi , Baldi Alfonso , Cioce Mario , Cortese Giancarlo , Mattei Elisabetta , Merola Roberta , Gianelli Umberto , Baldini Luca , Pisani Francesco , Gumenyuk Svitlana , Mengarelli Andrea , Höpker Katja , Benzing Thomas , Vincenzi Bruno , Floridi Aristide , Passananti Claudio , Blandino Giovanni , Iezzi Simona , Fanciulli Maurizio
Published: December 2020

Multiple myeloma (MM) is a hematologic malignancy produced by a clonal expansion of plasma cells and characterized by abnormal production and secretion of monoclonal antibodies. This pathology exhibits an enormous heterogeneity resulting not only from genetic alterations but also from several epigenetic dysregulations. Here we provide evidence that Che-1/AATF (Che-1), an interactor of RNA polymerase II, promotes MM proliferation by affecting chromatin structure and sustaining global gene expression. We found that Che-1 depletion leads to a reduction of “active chromatin” by inducing a global decrease of histone acetylation. In this context, Che-1 directly interacts with histones and displaces histone deacetylase class I members from them. Strikingly, transgenic mice expressing human Che-1 in plasma cells develop MM with clinical features resembling those observed in the human disease. Finally, Che-1 downregulation decreases BRD4 chromatin accumulation to further sensitize MM cells to bromodomain and external domain inhibitors. These findings identify Che-1 as a promising target for MM therapy, alone or in combination with bromodomain and external domain inhibitors.
Mesenchymal stromal cells in hematopoietic cell transplantation
Authors: Burnham Andre J. , Daley-Bauer Lisa P. , Horwitz Edwin M.
Published: December 2020

Mesenchymal stromal cells (MSCs) are widely recognized to possess potent immunomodulatory activity, as well as to stimulate repair and regeneration of diseased or damaged tissue. These fundamental properties suggest important applications in hematopoietic cell transplantation. Although the mechanisms of therapeutic activity in vivo are yet to be fully elucidated, MSCs seem to suppress lymphocytes by paracrine mechanisms, including secreted mediators and metabolic modulators. Most recently, host macrophage engulfment of apoptotic MSCs has emerged as an important contributor to the immune suppressive microenvironment. Although bone marrow–derived MSCs are the most commonly studied, the tissue source of MSCs may be a critical determinant of immunomodulatory function. The key application of MSC therapy in hematopoietic cell transplantation is to prevent or treat graft-versus-host disease (GVHD). The pathogenesis of GVHD reveals multiple potential targets. Moreover, the recently proposed concept of tissue tolerance suggests a new possible mechanism of MSC therapy for GVHD. Beyond GVHD, MSCs may facilitate hematopoietic stem cell engraftment, which could gain greater importance with increasing use of haploidentical transplantation. Despite many challenges and much doubt, commercial MSC products for pediatric steroid-refractory GVHD have been licensed in Japan, conditionally licensed in Canada and New Zealand, and have been recommended for approval by an FDA Advisory Committee in the United States. Here, we review key historical data in the context of the most salient recent findings to present the current state of MSCs as adjunct cell therapy in hematopoietic cell transplantation.
Renal outcome in patients with newly diagnosed multiple myeloma: results from the UK NCRI Myeloma XI trial
Authors: Rana Ritika , Cockwell Paul , Drayson Mark , Cook Mark , Pratt Guy , Cairns David A. , Pawlyn Charlotte , Jackson Graham , Davies Faith , Morgan Gareth , Pinney Jennifer Helen
Published: December 2020

Renal injury is a common complication of multiple myeloma (MM) and is associated with adverse outcome. Despite this, the natural history of renal injury in patients with MM remains uncertain especially in the context of intensive therapy and novel therapies. To address the lack of data, we evaluated the renal function of 2334 patients from the UK National Cancer Research Institute Myeloma XI trial at baseline and at 12 months to assess renal function over time and the factors associated with change. Patients who had severe acute kidney injury or a requirement for dialysis were excluded. At 12 months of the 1450 evaluable patients planned for autologous transplantation; 204 (14%) patients had a decline in estimated glomerular filtration rate (eGFR) ≥25% from baseline, 341 (23.5%) had an improvement and 905 (62%) had no significant change in eGFR. Renal outcome at 12 months for the 884 evaluable patients who were not planned for transplant was similar. Improved renal function was more likely if patients were <70 years old, male, had an average eGFR <60 mL per minute per 1.73 m2 and a higher baseline free light chain level >1000 mg/L, and/or a free light chain response of >90%. It did not correlate with monoclonal–protein response, transplantation, or use of a bortezomib-based regimen. We show that with current therapies the proportion of patients who have a significant decline in renal function in the first 12 months is small. The greatest relative improvement in eGFR is seen in patients with high free light chain at baseline and a high light chain response. This trial was registered at http://www.isrctn.com as #49407852.
Follicular lymphoma t(14;18)-negative is genetically a heterogeneous disease
Authors: Nann Dominik , Ramis-Zaldivar Joan Enric , Müller Inga , Gonzalez-Farre Blanca , Schmidt Janine , Egan Caoimhe , Salmeron-Villalobos Julia , Clot Guillem , Mattern Sven , Otto Franziska , Mankel Barbara , Colomer Dolors , Balagué Olga , Szablewski Vanessa , Lome-Maldonado Carmen , Leoncini Lorenzo , Dojcinov Stefan , Chott Andreas , Copie-Bergman Christiane , Bonzheim Irina , Fend Falko , Jaffe Elaine S. , Campo Elias , Salaverria Itziar , Quintanilla-Martinez Leticia
Published: December 2020

Fifty-five cases of t(14;18)− follicular lymphoma (FL) were genetically characterized by targeted sequencing and copy number (CN) arrays. t(14;18)− FL predominated in women (M/F 1:2); patients often presented during early clinical stages (71%), and had excellent prognoses. Overall, t(14;18)− FL displayed CN alterations (CNAs) and gene mutations carried by conventional t(14;18)+ FL (cFL), but with different frequencies. The most frequently mutated gene was STAT6 (57%) followed by CREBBP (49%), TNFRSF14 (39%), and KMT2D (27%). t(14;18)− FL showed significantly more STAT6 mutations and lacked MYD88, NOTCH2, MEF2B, and MAP2K1 mutations compared with cFL, nodal marginal zone lymphoma (NMZL), and pediatric-type FL (PTFL). We identified 2 molecular clusters. Cluster A was characterized by TNFRSF14 mutations/1p36 alterations (96%) and frequent mutations in epigenetic regulators, with recurrent loss of 6q21-24 sharing many features with cFL. Cluster B showed few genetic alterations; however, a subgroup with STAT6 mutations concurrent with CREBBP mutations/16p alterations without TNFRSF14 and EZH2 mutations was noted (65%). These 2 molecular clusters did not distinguish cases by inguinal localization, growth pattern, or presence of STAT6 mutations. BCL6 rearrangements were demonstrated in 10 of 45 (22%) cases and did not cluster together. Cases with predominantly inguinal presentation (20 of 50; 40%) had a higher frequency of diffuse growth pattern, STAT6 mutations, CD23 expression, and a lower number of CNAs, in comparison with noninguinal cases (5.1 vs 9.1 alterations per case; P < .05). STAT6 mutations showed a positive correlation with CD23 expression (P < .001). In summary, t(14;18)− FL is genetically a heterogeneous disorder with features that differ from cFL, NMZL, and PTFL.
Early detection of steroid-induced femoral head necrosis using 99mTc-Cys-Annexin V-based apoptosis imaging in a rabbit model
Authors: Wang Xiaolong , Li Jianbo , Man Da , Liu Rui , Zhao Jianmin
Published: December 2020

Background

At present, the early diagnosis of femoral head necrosis mainly relies on Magnetic resonance imaging (MRI), and most early patients are difficult to make an accurate diagnosis. Therefore, to investigate the early diagnostic value of99mTc-Cys-Annexin V Single-photon emission computed tomography (SPECT) imaging were compared with MRI in rabbit models of steroid-induced femoral head necrosis.

Methods

The animal model of steroid-induced femoral head necrosis (SIFHN) was established in 5-month-old healthy New Zealand white rabbits by injecting horse serum into ear vein and methylprednisolone into gluteal muscle, the purpose of modeling is to simulate the actual clinical situation of SIFNH.99mTc-Cys-Annexin V SPECT imaging and MRI were performed at 2nd week, 4th week, and 6th week after modeling. After that, histopathology was used to verify the success of modeling. Apoptosis was detected by transmission electron microscopy (TEM) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL).

Results

At 2 weeks after the injection of hormone,99mTc-Cys-Annexin V SPECT image showed abnormal radioactive uptake in the bilateral femoral head. And over time, the radioactivity concentration was more obvious, and the ratio of T/NT (target tissue/non-target tissues, which is the ratio of femoral head and the ipsilateral femoral shaft) was gradually increased. In the99mTc-Cys-Annexin V SPECT imaging at each time point, T/NT ratio of the model group was significantly higher than that of the control group (P < 0.01); at 4 weeks after the injection of hormone, MRI showed an abnormal signal of osteonecrosis. At 2, 4, and 6 weeks after hormone injection, apoptosis was observed by TUNEL and TEM.

Conclusions

99mTc-Cys-Annexin V SPECT imaging can diagnose steroid-induced femoral head necrosis earlier than MRI, and has potential application value for non-invasively detecting early and even ultra-early stage of femoral head necrosis.
Efficient Preparation of Nanoparticle-Reinforced Nickel-based Composite Coating with Highly Preferred (220) Orientation
Authors: Ji Renjie , Jin Hui , Liu Yonghong , Dong Tiancong , Zhang Fan , Zhao Lilong , Wu Xinlei , Sun Qiang , Liu Peng , Dong Hang , Ma Chi , Li Dege , Cai Baoping
Published: December 2020

Nanoparticle-reinforced metal matrix composite coatings have significant potential in mechanical part surface strengthening owing their excellent mechanical properties. This paper reports a phenomenon in which the grain orientation gradually evolves to (220) as the deposition current density increases when preparing nanoparticle-reinforced nickel-based composite coatings through jet electrodeposition (JED). During the preparation of the Ni-SiC composite coatings, the deposition current density increased from 180 A/dm2 to 220 A/dm2, and TC(220) gradually increase from 41.4% to 97.7%. With an increase of TC(220), the self-corrosion potential increases from −0.575 to −0.477 V, the corrosion current density decreases from 9.52 μA/cm2 to 2.76 μA/cm2, the diameter of the corrosion pits that after 10 days of immersion in a 3.5 wt% NaCl solution decreases from 278–944 nm to 153–260 nm, and the adhesion of the coating increases from 24.9 N to 61.6 N. Compared a conventional electrodeposition (CED), the Ni-SiC composite coating using JED has the advantages of a smooth surface morphology, high corrosion resistance, and strong adhesion, which are more obvious with an increase in TC(220).
Comparison of two ASC-derived therapeutics in an in vitro OA model: secretome versus extracellular vesicles
Authors: Giannasi Chiara , Niada Stefania , Magagnotti Cinzia , Ragni Enrico , Andolfo Annapaola , Brini Anna Teresa
Published: December 2020

Background

In the last years, several clinical trials have proved the safety and efficacy of adipose-derived stem/stromal cells (ASC) in contrasting osteoarthritis (OA). Since ASC act mainly through paracrine mechanisms, their secretome (conditioned medium, CM) represents a promising therapeutic alternative. ASC-CM is a complex cocktail of proteins, nucleic acids, and lipids released as soluble factors and/or conveyed into extracellular vesicles (EV). Here, we investigate its therapeutic potential in an in vitro model of OA.

Methods

Human articular chondrocytes (CH) were induced towards an OA phenotype by 10 ng/ml TNFα in the presence of either ASC-CM or EV, both deriving from 5 × 105 cells, to evaluate the effect on hypertrophic, catabolic, and inflammatory markers.

Results

Given the same number of donor cells, our data reveal a higher therapeutic potential of ASC-CM compared to EV alone that was confirmed by its enrichment in chondroprotective factors among which TIMP-1 and -2 stand out. In details, only ASC-CM significantly decreased MMP activity (22% and 29% after 3 and 6 days) and PGE2 expression (up to 40% at day 6) boosted by the inflammatory cytokine. Conversely, both treatments down-modulated of ~ 30% the hypertrophic marker COL10A1.

Conclusions

These biological and molecular evidences of ASC-CM beneficial action on CH with an induced OA phenotype may lay the basis for its future clinical translation as a cell-free therapeutic in the management of OA.
The impact of health information technology on prescribing errors in hospitals: a systematic review and behaviour change technique analysis
Authors: Devin Joan , Cleary Brian J. , Cullinan Shane
Published: December 2020

Background

Health information technology (HIT) is known to reduce prescribing errors but may also cause new types of technology-generated errors (TGE) related to data entry, duplicate prescribing, and prescriber alert fatigue. It is unclear which component behaviour change techniques (BCTs) contribute to the effectiveness of prescribing HIT implementations and optimisation. This study aimed to (i) quantitatively assess the HIT that reduces prescribing errors in hospitals and (ii) identify the BCTs associated with effective interventions.

Methods

Articles were identified using CINAHL, EMBASE, MEDLINE, and Web of Science to May 2020. Eligible studies compared prescribing HIT with paper-order entry and examined prescribing error rates. Studies were excluded if prescribing error rates could not be extracted, if HIT use was non-compulsory or designed for one class of medication. The Newcastle-Ottawa scale was used to assess study quality. The review was reported in accordance with the PRISMA and SWiM guidelines. Odds ratios (OR) with 95% confidence intervals (CI) were calculated across the studies. Descriptive statistics were used to summarise effect estimates. Two researchers examined studies for BCTs using a validated taxonomy. Effectiveness ratios (ER) were used to determine the potential impact of individual BCTs.

Results

Thirty-five studies of variable risk of bias and limited intervention reporting were included. TGE were identified in 31 studies. Compared with paper-order entry, prescribing HIT of varying sophistication was associated with decreased rates of prescribing errors (median OR 0.24, IQR 0.03–0.57). Ten BCTs were present in at least two successful interventions and may be effective components of prescribing HIT implementation and optimisation including prescriber involvement in system design, clinical colleagues as trainers, modification of HIT in response to feedback, direct observation of prescriber workflow, monitoring of electronic orders to detect errors, and system alerts that prompt the prescriber.

Conclusions

Prescribing HIT is associated with a reduction in prescribing errors in a variety of hospital settings. Poor reporting of intervention delivery and content limited the BCT analysis. More detailed reporting may have identified additional effective intervention components. Effective BCTs may be considered in the design and development of prescribing HIT and in the reporting and evaluation of future studies in this area.