bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of eye tracking for a decision support application
Authors: Visweswaran Shyam , King Andrew J , Tajgardoon Mohammadamin , Calzoni Luca , Clermont Gilles , Hochheiser Harry , Cooper Gregory F
Published: August 2021

Eye tracking is used widely to investigate attention and cognitive processes while performing tasks in electronic medical record (EMR) systems. We explored a novel application of eye tracking to collect training data for a machine learning-based clinical decision support tool that predicts which patient data are likely to be relevant for a clinical task. Specifically, we investigated in a laboratory setting the accuracy of eye tracking compared to manual annotation for inferring which patient data in the EMR are judged to be relevant by physicians. We evaluated several methods for processing gaze points that were recorded using a low-cost eye-tracking device. Our results show that eye tracking achieves accuracy and precision of 69% and 53%, respectively compared to manual annotation and are promising for machine learning. The methods for processing gaze points and scripts that we developed offer a first step in developing novel uses for eye tracking for clinical decision support.
Effective use of biosensors for high-throughput library screening for metabolite production
Authors: Kaczmarek Jennifer A , Prather Kristala L J
Published: August 2021

The development of fast and affordable microbial production from recombinant pathways is a challenging endeavor, with targeted improvements difficult to predict due to the complex nature of living systems. To address the limitations in biosynthetic pathways, much work has been done to generate large libraries of various genetic parts (promoters, RBSs, enzymes, etc.) to discover library members that bring about significantly improved levels of metabolite production. To evaluate these large libraries, high throughput approaches are necessary, such as those that rely on biosensors. There are various modes of operation to apply biosensors to library screens that are available at different scales of throughput. The effectiveness of each biosensor-based method is dependent on the pathway or strain to which it is applied, and all approaches have strengths and weaknesses to be carefully considered for any high throughput library screen. In this review, we discuss the various approaches used in biosensor screening for improved metabolite production, focusing on transcription factor-based biosensors.
Mechanistic investigation of synergistic interaction of tocopherol succinate with a quinoline-based inhibitor of mammalian target of rapamycin
Authors: Behera Chittaranjan , Kour Jaspreet , Banjare Nagma , Verma Praveen K , Chashoo Gousia , Sawant Sanghapal D , Gupta Prem N
Published: August 2021

Objectives

Cancer monotherapy is associated with various limitations; therefore, combination chemotherapy is widely explored for optimum drug efficacy. In this study, 4-(N-Phenyl-N′-substituted benzenesulfonyl)-6-(4-hydroxyphenyl) quinoline-based mammalian target of rapamycin (mTOR) inhibitor (IIIM-4Q) was investigated in combination with tocopherol succinate (TOS), and the mechanism of cytotoxicity was elucidated.

Methods

The cytotoxic potential of IIIM-4Q and TOS was evaluated in five cell lines. Further, to understand the mechanism of cytotoxicity of IIIM-4Q, TOS and their combination, various studies including morphological analysis using scanning electron microscopy and 6-diamidino-2-phenylindole (DAPI) staining, estimation of reactive oxygen species (ROS) level, measurement of mitochondrial membrane potential (MMP), in-vitro cell migration assay, Western blotting and staining with acridine orange (AO) for autophagy detection were performed.

Key findings

Investigated combination was synergistic in nature and exhibited greater oxidative stress and mitochondrial dysfunction in pancreatic cancer cells. The migration potential of MIA PaCa-2 cells was significantly mitigated under the influence of this combination, and morphological changes such as chromatin condensation and nuclear blebbing were observed. Also, poly (adenosine diphosphate-ribose) polymerase cleavage and caspase-3 activation were observed in IIIM-4Q and TOS combination-treated cells.

Conclusions

The investigated combination synergistically inhibited proliferation of MIA PaCa-2 cells through simultaneous induction of autophagy followed by apoptosis, and this combination demonstrated potential for further translational studies.
The Renfrew Unified Treatment for Eating Disorders and Comorbidity
Authors: Thompson-Brenner Heather , Smith Melanie , Brooks Gayle E. , Berman Rebecca , Kaloudis Angela , Espel-Huynh Hallie , Ross Franklin Dee , Boswell James
Published: August 2021

This treatment is designed to address eating disorders along with other emotional problems that individuals with eating disorders also commonly experience. Eating disorders are related to emotional functioning in many important ways. First, negative emotions—and the desire to avoid or control negative emotions—have been shown repeatedly to be related to the development of eating disorders, as well as most other emotional disorders, for many people. Depression and anxiety are known risk factors for the development of an eating disorder. Research also shows that emotional events—such as feeling sadness, feeling anxiety, or feeling stress—are often the immediate triggers for eating disorder symptoms. Furthermore, having an eating disorder is a difficult emotional experience, and many people develop depression and anxiety in reaction to their eating disorder symptoms. Therefore, emotions often create the context in which eating disorders develop, emotions are a part of what drives eating disorder symptoms on a daily level, and emotional experience become worse as a result of having an eating disorder. This Unified Treatment (UT) manual, like the Unified Protocol (UP) manual, is cohesive, with a continuous focus on the relationship between the interventions/concepts included in each module and the overall goal of reducing emotion avoidance and promoting emotion regulation.
Motivation and Regular Eating
Authors: Thompson-Brenner Heather , Smith Melanie , Brooks Gayle , Franklin Dee Ross , Espel-Huynh Hallie , Boswell James F.
Published: August 2021

During the session covered in this chapter, clients will learn about the importance of motivation. High motivation can lead to treatment engagement and treatment commitment. To this end, clients participate in a decisional balance activity to explore the costs and benefits of changing, as well as the costs and benefits of remaining the same. Next, clients will set specific treatment goals they hope to achieve during treatment as well as develop manageable steps to reach treatment goals. Regular eating—loosely defined as three meals and two or three snacks per day, spaced at regular intervals throughout the day—is an important goal to include early in the treatment of eating disorders. Some clients may have treatment teams in which a different team member (e.g., nutritionist/dietitian) is responsible for addressing the goal of regular eating. If not, regular eating can be addressed as one of the goals within this treatment. To that end, Form 4.1: Regular Eating Food Log is introduced in this session.
Tracking Emotions over Time (the “ARC”)
Authors: Thompson-Brenner Heather , Smith Melanie , Brooks Gayle , Franklin Dee Ross , Espel-Huynh Hallie , Boswell James F.
Published: August 2021

The primary goal for this session is for clients to explore and learn how emotional experiences unfold. This allows clients to learn from their emotional experiences and how these experiences can influence their later behaviors and emotions. During this session, clients learn the steps that unfold over time in emotions: antecedent (A, what happened before), response (R, which includes thoughts, physical sensations, and behaviors/urges), and consequence (C, what happens after). Clients learn to look for patterns in their emotional triggers. They also learn to explore short- and long-term consequences of their emotional responses. Form 8.1: The ARC of Emotional Experiences is introduced.
Core Beliefs
Authors: Thompson-Brenner Heather , Smith Melanie , Brooks Gayle , Franklin Dee Ross , Espel-Huynh Hallie , Boswell James F.
Published: August 2021

During this session, clients learn about core beliefs, which are powerful beliefs that exist deep within our brains and influence how we think. They are at the root, or the core, of our automatic thoughts about ourselves, and they can be positive or negative. In this chapter, clients learn what core beliefs are and where they come from—specifically, they can come from repetitive early experiences, or from a single formative, highly emotional experience. They will also learn about the relationship between negative core beliefs and negative automatic thoughts—specifically, that negative core beliefs, though usually outside of awareness, influence or shape automatic thoughts. Clients are taught the downward arrow technique to identify their own negative core beliefs.
Using Dynamic Personality Theories, Cognitive Neuroscience, and mHealth to Uncover the Process of Post-Traumatic Personality Change in Women with Breast Cancer
Authors: Baez Lara M. , Antoni Michael H. , Heller Aaron S.
Published: August 2021

This chapter discusses the promise of new longitudinal methods for collecting psychological and behavioral data to examine the extent to which post-traumatic growth is possible. These methods include weekly in-the-moment self-reports of functioning as individuals go about their everyday lives via mobile health methods, in addition to retrospective self-reports of character. To examine the potential of such methodologies, the chapter uses the example case of whether and to what extent post-traumatic growth should be expected in women who experience breast cancer diagnosis. This research represents a promising way to move in a direction for uncovering post-traumatic growth. Breast cancer diagnosis and treatment are potent stressors for the individual. This may be particularly so for younger patients (<40 years) where the disease can be more aggressive, with a higher potential for lost years of life. Yet women differ greatly in their responses to diagnosis and treatment. Some cultivate new relationships, experience psychological growth, and act more prosocially and altruistically. Some evidence suggests that certain types of character growth in response to stressful life events may be associated with better psychological and physiological outcomes after the event is over. However, there are limited prospective longitudinal data to indicate which specific character traits primarily change in response to life challenges and which are most associated with changes in actual behavior. This chapter discusses how the implementation of multiple methods will better allow researchers to characterize the trajectories of character traits and actions following adversity.
Emotions and Positive Personality Change in Syrian-Origin Young Adults Who Have Recently Resettled in the Netherlands
Authors: Laceulle Odilia M. , Alajak Kinan , Alisic Eva , Al Sawaf Zeina , Rahim Haza F. , Zonneveld Renée , Chung Joanne M.
Published: August 2021

Around the world, the number of people who seek or have refugee status continues to increase. Despite the adverse experiences and challenges that many people who seek or have refugee status encounter, adversity is thought to promote growth in resilience, kindness, and humility. Little is known about how such positive personality development occurs, but one potential pathway is through emotions. Exposure to adversity may trigger a range of emotional experiences such as sorrow, guilt, trepidation, nostalgia, compassion, gratitude, and love. These emotional experiences, in turn, may drive personality change. Karakter is a 13-month longitudinal study examining how emotional experiences in everyday life may contribute to the link between adversity and personality change in Syrian-origin young adults who have recently resettled in the Netherlands. In this project, the authors join a growing literature examining positive development and specifically whether positive personality change follows adversity in individuals who seek or have refugee status. The results should provide much needed information that can help people with refugee backgrounds thrive and also help change the way they are perceived by receiving cultures.
Considering Characteristics of Events in Research on Post-Traumatic Growth
Authors: Luhmann Maike , Fassbender Ina
Published: August 2021

Why do some events lead to growth in character strengths and others do not? Past research has addressed this question using a typological approach where adversities are grouped into different types or categories (e.g., daily stressor vs. clinical trauma). This approach has practical and theoretical limitations. In this chapter, the authors propose a conceptual model that incorporates a dimensional approach to examining how and why adverse events differ in their impact on character strengths. This conceptual model identifies 10 dimensions of event characteristics (e.g., external control, negative valence). They also explore the association among these event characteristics and character growth with a focus on five central research questions: (1) Which characteristics of adverse events are generally associated with character growth? (2) Which characteristics of adverse events are generally associated with declines in character strengths? (3) Are specific characteristics of adverse events associated with growth in specific character strengths? (4) Does the perception of event characteristics change over time? (5) Is the association between adversity and character strengths bidirectional?
Case Example 2
Authors: Newins Amie R. , Wilson Laura C.
Published: August 2021

While some disclosures of sexual assault are expected, such as when a client is presenting for services to address problems resulting from sexual assault, other disclosures are not expected. Therefore, clinicians must be prepared for when these disclosures do occur. In this chapter, two case examples are presented—one in which an unanticipated disclosure occurs during an intake evaluation and one in which an unanticipated disclosure occurs during the course of therapy. The authors provide recommendations on how to handle these disclosures, including how to assess whether further discussion of the sexual assault is necessary and how to handle possible disruptions to the therapy plan when disclosures occur.
Flexibility within Fidelity
Authors: Kendall Philip C.
Published: August 2021

This book explores empirically supported treatments (ESTs), which can be implemented with integrity and flexibility. There is a consensus, in the field of mental health disorder treatment research, that ESTs have favorable outcomes that are supported by data, and that the outcomes are typically better than other approaches. There is also a consensus that some of the manuals and books that describe ESTs are formulaic, possibly rigid, and that many if not most are likely insensitive to individual patient needs/presentations. With the separate consensuses that ESTs are preferred and that EST materials are stiff, there is a need for accurate communication and reconciliation between the two groups. The book focuses on specific ESTs for identified problem areas amongst adults and children/adolescents, including anxiety disorders, substance use, insomnia, post-traumatic stress disorder (PTSD), pain management, and depression. It deals with the specific treatment components that are required to maintain fidelity and the features of the EST which can be applied with flexibility, making for a client-focused implementation. The book also provides clinical discussions and examples of how to implement the EST program across client presentations.
Introduction
Authors: Kendall Philip C.
Published: August 2021

Do research findings apply to an individual case? Although the answer is yes, we are tempted to think that an individual case, for whatever reason, is somehow an exception (we fall prey to a cognitive processing error). We can be flexible when applying an empirically supported treatment (EST). Research findings typically carry more weight than the “features” of the individual. Take the client’s features into account and apply the known-to-be-effective treatment with flexibility... flexibility within fidelity.
Cognitive Behavioral Therapy for Social Anxiety Disorder
Authors: Butler Rachel M. , O’Day Emily B. , Heimberg Richard G.
Published: August 2021

This chapter discusses the efficacy of cognitive behavioral therapy (CBT) for the treatment of social anxiety disorder (SAD). SAD is a mental health condition marked by impairment and distress across a number of social situations. Manual-based, workbook-driven protocols for CBT for SAD hold promise for promoting evidence-based practice across clinical settings. Not only does the protocol offer a structured framework to guide therapists through therapy sessions, but it also provides clients with their own set of resources to bolster what is learned in the therapy room and bring it into their daily lives. These materials emphasize the importance of a person-centered approach to treatment that can be applied flexibly and adapted to the needs of the individual client. Although key components of the treatment are required for fidelity, there is substantial flexibility built into the structure of the protocol and each component, including the number of treatment sessions, the approach to cognitive restructuring, the content of the fear and avoidance hierarchy, the focus of exposure exercises conducted in session and as homework assignments, as well as how comorbid psychological disorders are addressed.
Flexible Principles for the Treatment of Adult Worry
Authors: Sewart Amy R. , Craske Michelle G.
Published: August 2021

This chapter outlines various empirically supported cognitive-behavioral strategies driven by current understanding of worry-related mechanisms that may be implemented in the treatment of chronic worry. Excessive and uncontrollable worry is reliably observed across anxiety disorders, and it is most evident in generalized anxiety disorder (GAD), of which it is the cardinal symptom. At present, achieving treatment fidelity for cognitive behavioral therapy (CBT) for excessive worry requires cognitive restructuring—wherein targets can range from challenging overestimation of likelihood, severity of negative outcomes, or metacognitive beliefs about worry—and exposure, either in vivo or imaginal, as a means to provide extinction learning around feared outcomes involving uncertainty or aversive emotional experiences. It also requires behavioral experimentation through which worry-related cognitions are tested and challenged through “real-life” experiences, which may involve stimulus control/worry postponement; explicit removal of safety behaviors throughout all components of treatment; and incorporation of strategies to enhance problem orientation. Using a case formulation-driven approach, these elements can be flexibly applied in a systematic, responsive, and data-driven manner to target the deficits present in the individual.
Post-Traumatic Stress Disorder Treatment with Adults
Authors: Sloan Colleen A. , Litwack Scott , Sloan Denise M.
Published: August 2021

This chapter describes the theoretical models behind evidence-based post-traumatic stress disorder (PTSD) treatments and the importance of adhering to the model of PTSD treatment when making adaptations to treatment protocols. We review modifications that might be made for both exposure-based and cognitive-based treatment approaches, rooted in their respective underlying theories. We also describe modifications to the delivery of treatment (e.g., number and duration of treatment sessions, method of treatment delivery, and location where treatment is delivered). Throughout the chapter, we emphasize that decisions regarding modifications should aim to foster mechanisms of change, based on theoretical models, and implemented to maximize treatment outcomes.
Being Flexible While Maintaining Fidelity in Cognitive Behavioral Therapy of Depression
Authors: Strunk Daniel R. , Adler Mandel Abby , Ezawa Iony D.
Published: August 2021

Cognitive Therapy or Cognitive Behavioral Therapy (CBT) for depression is a well-studied, research-supported treatment. Contrary to common misconceptions about manual-based treatments, CBT can be provided with considerable flexibility. As the first manual-based treatment to be developed, it is remarkable that it is so principle-based and flexible. There is flexibility in focusing on the goals and topics of importance to clients. Therapists have discretion in determining how much to use various CBT strategies and determining how they might be used to meet the diverse needs of clients with depression. Because of the flexibility of CBT, therapists also have many options for determining what approach to use when a client does not initially respond well to an intervention. To ensure that CBT offers the therapeutic benefits that have been identified and supported in clinical trials, the treatment also needs to be provided with fidelity to the manual. Despite their limitations, observer ratings of competence remain the standard for ensuring that CBT is provided with fidelity.
Being Flexible While Maintaining Fidelity for Medical Patients
Authors: Reichman Mira , Grunberg Victoria A. , Doorley James D. , Bakhshaie Jafar , Lester Ethan G. , Mace Ryan A. , Vranceanu Ana-Maria
Published: August 2021

For health psychologists, flexibility within fidelity is required to address the individual patient factors resulting from the dual physical and psychosocial comorbidities that characterize medical populations, and the contextual factors arising from the complexities of medical settings and multidisciplinary medical teams. This chapter presents a model for flexibility within fidelity for medical populations, addressing flexibility both in the delivery of treatments to patients (i.e., patient-centered flexibility) and in collaborations with multidisciplinary medical teams (i.e., team-based flexibility). We provide examples from our clinical research to illustrate how flexibility within fidelity can be employed for medical patients and offer recommendations to health psychology researchers and providers for exercising thoughtful clinical decision-making in the delivery of evidence-based interventions.
Goodness of Fit
Authors: Otte Suzanne , Bratiotis Christiana , Steketee Gail
Published: August 2021

Disorder (HD) is a complex mental health problem defined by an overabundance of clutter, difficulty with organization and discarding, and problems regulating acquisition. This chapter describes the features of HD, evidence-based intervention approaches and outcomes, and the elements of a manualized treatment approach with emphasis on flexible delivery to meet clients’ needs. Opportunities to flexibly implement cognitive and behavioral treatments (CBT) for HD include modification of assessment methods, the order of therapy components, treatment timing and focus, responsiveness to client comorbidity and context, consideration of treatment planning, and approaches to increasing motivation and building skills. Also covered are supports for cognitive and behavioral changes in acquisition/organizing/discarding, assessing the appropriateness of a home cleanout, and determining “flexibility within fidelity” (Kendall & Frank, 2018) for group HD treatments and online interventions.
Inferring properties of neutron stars born in short gamma-ray bursts with a plerion-like X-ray plateau
Authors: Strang L C , Melatos A , Sarin N , Lasky P D
Published: August 2021

Time-resolved spectra of six short gamma-ray bursts (sGRBs), measured by the Swift telescope, are used to estimate the parameters of a plerion-like model of the X-ray afterglow. The unshrouded, optically thin component of the afterglow is modelled as emanating from an expanding bubble of relativistic, shock-accelerated electrons fuelled by a central object. The electrons are injected with a power-law distribution and cool mainly by synchrotron losses. We compute posteriors for model parameters describing the central engine (e.g. spin frequency at birth, magnetic field strength) and shock acceleration (e.g. power-law index, minimum injection energy). It is found that the central engine is compatible with a millisecond magnetar, and the shock physics is compatible with what occurs in Galactic supernova remnants, assuming standard magnetic field models for the magnetar wind. Separately, we allow the magnetic field to vary arbitrarily and infer that it is roughly constant and lower in magnitude than the wind-borne extension of the inferred magnetar field. This may be due to the expansion history of the bubble, or the magnetization of the circumstellar environment of the sGRB progenitor.
A dynamical analysis of the Taurid Complex: evidence for past orbital convergences
Authors: Egal A , Wiegert P , Brown P G , Spurný P , Borovička J , Valsecchi G B
Published: August 2021

The goal of this work is to determine if the dynamics of individual Taurid Complex (TC) objects are consistent with the formation of the complex via fragmentation of a larger body, or if the current orbital affinities between the TC members result from other dynamical processes. To this end, the orbital similarity through the time of comet 2P/Encke, 51 near-Earth asteroids (NEAs), and 16 Taurid fireballs was explored. Clones of each body were numerically simulated backwards in time, and epochs when significant fractions of the clones of any two bodies approached each other with both a low Minimum Orbit Intersection Distance and small relative velocity were identified. Only 12 pairs of bodies in our sample show such an association in the past 20 000 yr, primarily circa 3200 BCE. These include 2P/Encke and NEAs 2004 TG10, 2005 TF50, 2005 UR, 2015 TX24, and several Southern Taurid fireballs. We find this orbital convergence to be compatible with the fragmentation of a large parent body 5000–6000 yr ago, resulting in the separation of 2P/Encke and several NEAs associated with the TC, as well as some larger meteoroids now recorded in the Taurid stream. However, the influence of purely dynamical processes may offer an alternative explanation for this orbital rapprochement without requiring a common origin between these objects. In order to discriminate between these two hypotheses, future spectral surveys of the TC asteroids are required.
SpecHap: a diploid phasing algorithm based on spectral graph theory
Authors: YU Yonghan , Chen Lingxi , Miao Xinyao , Li Shuai Cheng
Published: August 2021

Haplotype phasing plays an important role in understanding the genetic data of diploid eukaryotic organisms. Different sequencing technologies (such as next-generation sequencing or third-generation sequencing) produce various genetic data that require haplotype assembly. Although multiple diploid haplotype phasing algorithms exist, only a few will work equally well across all sequencing technologies. In this work, we propose SpecHap, a novel haplotype assembly tool that leverages spectral graph theory. On both in silico and whole-genome sequencing datasets, SpecHap consumed less memory and required less CPU time, yet achieved comparable accuracy with state-of-art methods across all the test instances, which comprises sequencing data from next-generation sequencing, linked-reads, high-throughput chromosome conformation capture, PacBio single-molecule real-time, and Oxford Nanopore long-reads. Furthermore, SpecHap successfully phased an individual Ambystoma mexicanum, a species with gigantic diploid genomes, within 6 CPU hours and 945MB peak memory usage, while other tools failed to yield results either due to memory overflow (40GB) or time limit exceeded (5 days). Our results demonstrated that SpecHap is scalable, efficient, and accurate for diploid phasing across many sequencing platforms.
Data-Driven Residency Training: A Scoping Review of Educational Interventions for Neurosurgery Residency Programs
Authors: Kelly Patrick D , Yengo-Kahn Aaron M , Roth Steven G , Zuckerman Scott L , Chitale Rohan V , Wellons John C , Chambless Lola B
Published: August 2021

BACKGROUND

Neurosurgery residency programs are tasked with imparting large volumes of both clinical knowledge and technical skill to trainees in limited time. Many investigators have described local practices, which may offer evidence-based interventions in neurosurgical residency education, but this literature has not been systematically reviewed.

OBJECTIVE

To perform a scoping review of educational practices in neurosurgery, which are supported by quantitative, peer-reviewed research.

METHODS

A scoping review of the literature was performed. PubMed, Embase, and Web of Science databases were queried for articles describing educational interventions for neurosurgery residents, which included a quantitative assessment of the effect on resident performance.

RESULTS

From an initial set of 1785 unique articles, 29 studies were ultimately screened and included. Studies were into the following 6 topics: (1) didactics and curricula (n = 13), (2) nontechnical skills (n = 6), (3) wellness and burnout (n = 4), (4) assessment and feedback (n = 2), (5) mentorship and career development (n = 2), and (6) research (n = 2). Individual study results were described.

CONCLUSION

Several educational interventions in neurosurgical training are supported by quantitative evidence. Methodological shortcomings are prevalent among studies of education, particularly in the selection of meaningful outcome measures. A summary of evidence-based considerations is provided for current and future program directors.
Embodied design using augmented reality: the case of the gradient
Authors: Bos Rogier , Doorman Michiel , Drijvers Paul , Shvarts Anna
Published: August 2021

We study the augmented reality sandbox (ARSB) as an embodied learning environment to foster meaning making in the context of bivariable calculus. We present the case of Tiago, a first-year bachelor chemistry student, performing a series of tasks based on embodied design, including perception-based, action-based and incorporation-based tasks. Tiago’s work demonstrates the affordances of the ARSB, e.g. to trace a height line and to manipulate plastic planes either with or without feedback from projected height lines. Tiago’s reasoning about mathematical concepts, e.g. the parameters in a plane equation and the gradient vector, is supported by perceptual structures that he discovers during these embodied tasks. We distinguished two ways in which ARSB affordances were used in the learning sequence. In perception-based and action-based tasks, the affordances of the ARSB were immediately available and intensively involved in the interaction. In incorporation tasks, on the contrary, a critical affordance was deliberately removed and the student was able to reproduce its functionality without technology.
Effect of titanium dioxide nanoparticles on DNA methylation of human peripheral blood mononuclear cells
Authors: Malakootian Mohammad , Nasiri Alireza , Osornio-Vargas Alvaro R , Faraji Maryam
Published: August 2021

The aim of the current study was to investigate the effect of well-characterized TiO2 nanoparticles on DNA methylation of peripheral blood mononuclear cells (PBMCs) in vitro. Maximum non-toxic concentration of nanoparticles for PBMCs was determined by MTT assay. The effect of TiO2 nanoparticles at concentrations of 25–100 μg/ml on DNA methylation of PBMCs was investigated by measuring the %5-mC alterations through an ELISA assay. The physicochemical analysis showed that the TiO2 nanoparticles were crystalline, pure and in the anatase phase. Peaks related to Ti-O tensile vibrations were observed in the range of 1510 cm−1. The size of nanoparticles was in the range of 39–74 nm with an average hydrodynamic diameter of 43.82 nm. According to the results of the MTT test, 100 μg/ml was found to be maximum non-toxic concentration. The %5-mC in treated PBMCs revealed that TiO2 nanoparticles could lead to DNA hypomethylation in PBMCs. The %5-mC difference compared with the negative control was found to be 2.07 ± 1.02% (P = 0.03). The difference of %5-mC between the 25 and 100 μg/ml concentration of nanoparticles was statistically significant (P = 0.02). The results of the current study show that the TiO2 nanoparticles cause DNA hypomethylation in PBMCs in a dose-response manner. Therefore, it is recommended to evaluate the effects of cytotoxicity and epigenotoxicity of commonly used nanoparticles before their use.
Changes in Pain Sensitivity and Conditioned Pain Modulation During Recovery From Whiplash-associated Disorders
Authors: Christensen Steffan W.M. , Bellosta-López Pablo , Doménech-García Víctor , Herrero Pablo , Palsson Thorvaldur S.
Published: August 2021

Objective:

The objective of this study was to investigate the pain-sensory profile of patients with whiplash-associated disorders (WADs) prior and post 2 weeks of standardized rehabilitation and after a 6-month follow-up.

Materials and Methods:

Twenty-two WAD participants (grade II; 14 women) and 22 sex-matched and age-matched healthy pain-free controls were enrolled. Pressure pain thresholds (PPTs) were assessed at local and distal muscles. Conditioned pain modulation (CPM) of PPTs was assessed using cuff pressure around the upper arm. Referred area of pain following supra-threshold pressure stimulation of the infraspinatus muscle was recorded on a body chart. Psychometric variables (pain intensity, area of perceived pain, pain catastrophizing, kinesiophobia, sleep problems, and depression level) were assessed. WAD group additionally completed the Neck Disability Index.

Results:

The WAD group demonstrated lower local PPTs compared with controls at all time points (P<0.05) and lower distal PPTs at baseline and at 2 weeks when compared with 6 months (within-group) (P<0.05). The WAD group had a reduced CPM response and larger induced referred pain areas compared with controls (P<0.05), while no within-group changes were observed at any time point. The WAD group reported higher pain intensity and perceived area of pain compared with controls at all time points (P<0.05) and a mean Neck Disability Index score of 41% at baseline, 16% at 2 weeks, and 4% at 6 months. Furthermore, the WAD group reported improvements in all other psychometric variables (P<0.05), although only pain catastrophizing levels were comparable to controls at 2 weeks.

Discussion:

PPTs but not CPM improved in the WAD group and were comparable to controls following 2 weeks following standardized rehabilitation, indicating that normalization of CPM may not be required to recover from WAD.
Evaluation of the Premature Infant Pain Profile-Revised (PIPP-R) e-Learning Module
Authors: Campbell-Yeo Marsha , Carrier Leah , Benoit Britney , Kim Theresa , Bueno Mariana , Rao Megha , Riahi Shirine , Stevens Bonnie
Published: August 2021

Background

Electronic health (e-health) learning is a potential avenue to educate health professionals about accurately using infant pain assessment tools, although little is known about the impact of e-health interventions on clinical competence.

Purpose:

To evaluate whether an e-health learning module for teaching the accurate use of the Premature Infant Pain Profile-Revised (PIPP-R) pain assessment tool results in immediate and sustained competency to assess infant pain.

Methods:

Neonatal intensive care unit (NICU) nurses who participated in a larger study across 2 tertiary NICUs in Canada examining the implementation and clinical utility of the PIPP-R e-learning module completed 2 follow-up evaluations at 1 week and 3 months. Participants were asked to view a video recording of an infant undergoing a painful procedure and to assess the infant's pain intensity response using the PIPP-R measure. Immediate and sustained competency was assessed via interrater consensus of participant-reported PIPP-R scores compared with those of an experienced trained coder.

Results:

Of the 25 eligible nurses, 22 completed 1-week and 3-month follow-up evaluations. At the 1-week follow-up, 84% of nurses scored the video accurately compared with 50% at 3 months. Behavioral pain indicators were more likely to be scored incorrectly than physiological indicators.

Implications for Practice:

Follow-up training after completion of the initial e-learning module training may improve competency related to the clinical use of the PIPP-R tool to assess infant pain over time.

Implications for Research:

Additional study regarding the need and timing of e-health training to optimize sustained competency in infant pain assessment is warranted.
Hip Displacement in MECP2 Disorders: Prevalence and Risk Factors
Authors: Kanashvili Bidzina , Rogers Kenneth J. , Shrader Michael Wade , Miller Freeman , Dabney Kirk W. , Howard Jason J.
Published: August 2021

Background:

Methyl-CpG binding protein 2 (MECP2) disorders, including Rett syndrome and MECP2 duplication syndrome, are typified by profound intellectual disability, spasticity, and decline in gross motor function. Unlike scoliosis, linked to disease severity, little has been reported regarding the hip. The aim of this study was to report the prevalence and risk factors of hip displacement (HD) in MECP2 disorders.

Methods:

This was a retrospective, comparative study. Children with a genetically confirmed MECP2 disorder were included. The primary outcome measure was the prevalence of HD (migration percentage>30%). Secondary outcomes included age at HD onset, ambulatory status, presence of clinically relevant scoliosis, genetic severity, presence of seizures, and associated comorbidities. Analysis of proportions of categorical variables was performed using χ2 testing (P=0.05).

Results:

Fifty-six patients (54 Rett syndrome and 2 MECP2 duplication syndrome), diagnosed at 6.6 (SD: 4.7) years, met the inclusion criteria. The prevalence of HD was 36% [onset, 7.7 (SD: 3.8) y]. Risk factors for HD were nonwalker status (P=0.04), scoliosis (P=0.001), and refractory epilepsy (P=0.04).

Conclusions:

The prevalence of HD in MECP2 disorders is comparable to cerebral palsy, associated with proxy measures of disease severity. These results can be used to develop hip surveillance programs for MECP2 disorders, allowing for timely management.

Level of Evidence:

Level III.
Efficacy of Antibiotics in Supracondylar Fractures
Authors: Bhatt Etasha , Ridley Taylor J. , Kruckeberg Bradley , Quanbeck Zachary , Quanbeck Deborah S. , Schiffern Alison
Published: August 2021

Background:

Controversy exists surrounding antibiotic use in the setting of pediatric supracondylar humerus fractures treated with closed reduction and percutaneous Kirschner wire (K-wire) fixation. While the reported incidence of infection in the literature is low, surgeons frequently administer preoperative antibiotics. The purpose of this study was to retrospectively review preoperative antibiotic use and incidence of infection in children with supracondylar humerus fractures treated with closed reduction and K-wire fixation. It was hypothesized that antibiotic administration will not affect the incidence of infection following this procedure.

Methods:

We performed a retrospective review of 1053 patients with supracondylar humerus fractures treated with closed reduction and K-wire fixation at 3 institutions between 2006 and 2016. Patient demographics, antibiotic administration and follow-up data were reviewed in 905 patients.

Results:

Of 905 patients, 755 patients received preoperative antibiotics and 150 patients did not. The incidence of infection was 2.5% (n=22) in the group that received preoperative antibiotics and 2.0% in the group that did not receive antibiotics with an overall incidence of infection of 2.4%. The difference between groups did not reach significance (P>0.5). The majority of infections were treated with oral antibiotics with or without early pin removal. Four patients, all in the preoperative antibiotic group, required surgical debridement and intravenous antibiotics.

Conclusions:

Retrospective review of the incidence of infection in closed reduction and percutaneous pinning of supracondylar humerus fractures found no difference between patients who received preoperative antibiotics and those who did not receive preoperative antibiotics.

Level of Evidence:

Level III—therapeutic.
Feasibility of Magnetic Resonance Angiography in Patients With Legg-Calvé-Perthes Disease
Authors: Moreno Grangeiro Patricia , Rodrigues João C. , de Angeli Luiz R.A. , Leão Filho Hilton , Montenegro Nei B. , Guarniero Roberto , Dempsey Molly , Kim Harry K.W.
Published: August 2021

Background:

The etiology of Legg-Calvé-Perthes disease (LCPD) remains unknown; however, interruption of medial circumflex femoral artery (MCFA) supply to the femoral head is the key pathogenic factor. The main purpose of this study is to determine the feasibility of using magnetic resonance angiography (MRA) to evaluate the course of the MCFA in the normal and affected hips of patients with unilateral LCPD.

Methods:

We analyzed 24 patients with unilateral LCPD using a time-resolved imaging of contrast kinetics magnetic resonance angiography (TRICKS-MRA). The course of the MCFA was divided into 4 segments in the coronal plane and in 3 segments in the axial plane, based on its location with respect to the femoral neck. The visibility of each segment was studied in the normal and affected sides. The segments were defined as not visible when no contrast was seen within the vessel lumen or visible when the lumen was partially or completely visualized with contrast. The statistical analysis was done using the χ2 test.

Results:

TRICKS-MRA provided well-defined images of the first 2 segments of the MCFA on both the normal and affected sides of patients with LCPD (P=1). In half of the patients, the third segment was also visible using TRICKS-MRA on both sides (P=1). The fourth segment of the MCFA, which was the ascending lateral epiphyseal segment, was not visible on either side (P=0.49). No significant difference was found between the normal and affected hips in terms of visibility of the 4 segments of the MCFA using TRICKS-MRA. Anastomosis of the MCFA with the inferior gluteal artery was found in 3 hips (2 hips with LCPD and 1 normal hip).

Conclusions:

TRICKS-MRA provides well-defined images of the arterial supply to the proximal femoral epiphysis in children with LCPD, presenting a noninvasive and radiation-free alternative to conventional angiography. However, the TRICKS-MRA method used did not allow visualization of the ascending lateral epiphyseal segment of MCFA in the affected and the contralateral normal side. We believe that further advancement of this noninvasive imaging technique may open new opportunities for research aimed at evaluating the vascular supply of the femoral head in children.

Level of Evidence:

Level IV—case-control study.
Complete pathological response with diabetic ketoacidosis to the combination of sintilimab and anlotinib in an unresectable hepatocellular carcinoma patient: a case report
Authors: Fu Lingli , Chen Ping , Wang Shijie , Liu Wenmin , Chen Zubing , Chen Hongbin , Fu Zhenming
Published: August 2021

Most hepatocellular carcinoma (HCC) patients have dismal prognoses because they are already in the advanced stage at the time of initial diagnosis and are unable to undergo upfront surgery. Recent studies of immune checkpoint inhibitors (ICIs) and antiangiogenic agents (AAAs) have shown encouraging results for unresectable HCC (uHCC). Here, we report a patient with uHCC who was treated with a combination of anlotinib and sintilimab (sintilimab 200 mg, intravenous glucose tolerance test, q21d and anlotinib 12 mg, orally, d1–14, q21d), an analog of the combination of lenvatinib and pembrolizumab with much lower cost. The patient with recurrent uHCC was downstaged to resectable disease by the combination therapy. After eight cycles of treatment with anlotinib and sintilimab, the patient underwent a second operation. The histology of the resected mass revealed a major and almost complete pathological response. However, this patient was diagnosed with type I diabetes mellitus with ketoacidosis after nearly 10 cycles of combination treatment with anlotinib and sintilimab. Active follow-ups revealed no signs of local recurrence or distant failure. In conclusion, this case report demonstrated that the combination of anlotinib and sintilimab, one of the strategies combining ICIs with AAAs, showed promising efficacy in the treatment of uHCC patients.
Persistent response of an ovarian cancer patient after a short-term single-agent immunotherapy: a case report
Authors: Sun Shaoxing , Sun Wenjie , Xiang Qingming , Yang Chunxu , Chen Min , Mei Zijie , Yang Hui , Zeng Zihang , Cao Hong , Tian Yueli , Zhang Gong , Qiu Hui
Published: August 2021

Epithelial ovarian cancer is extremely difficult to treat due to its high recurrence rate and acquired tolerance to chemotherapy. Immune checkpoint inhibitors (ICIs) are expected to be promising solutions for treatment failure. However, the low response rate to a single ICI agent was demonstrated in approximately all published clinical trials. Surprisingly patients with complete response were also noticed as an anecdote. Proper indicators of treatment response were urgently required. Programmed death- ligand 1 expression levels in the tumor tissues provide relatively limited discrimination. Tumor mutation burden (TMB) serves as a more reliable parameter. Here we presented an ovarian cancer case with multiple gene mutations and high TMB, who benefited from a short-term treatment of pembrolizumab and experienced a long-lasting complete response of 2 years till now. The patient was irradiated in the pelvic before pembrolizumab. Our study demonstrated that ICIs might provide survival benefits for ovarian cancer with high TMB and that pelvic radiation might have synergistical effects with immunotherapy.
Viral, inflammatory, and reservoir characteristics of posttreatment controllers
Authors: McMahon James , Lewin Sharon R. , Rasmussen Thomas A.
Published: August 2021

Purpose of review

To provide an overview of studies to date that have identified posttreatment controllers (PTCs) and to explore current evidence around clinical characteristics, immune effector function, and inflammatory and viral reservoir characteristics that may underlie the control mechanism.

Recent findings

PTCs are broadly defined as individuals capable of maintaining control of HIV replication after cessation of antiretroviral therapy (ART). While starting ART early after HIV infection is associated with PTC, genetic disposition or CD8+ T-cell function do not appear to explain this phenomenon, but these features have not been exhaustively analyzed in PTCs. A lower frequency of latently infected cells prior to stopping ART has been associated with achieving PTC, including a lower level of intact HIV DNA, but more studies are needed to map the genetic location, epigenetic characteristics, and tissue distribution of the intact HIV reservoir in PTCs.

Current studies are small and heterogeneous and there is a significant need to agree on a uniform definition of PTC. Many aspects of PTC are still unexplored including whether specific features of genetic disposition, immune effector functions, and/or viral reservoir characteristics play a role in PTC. A large multisite international cohort study could aide in providing the important insights needed to fully understand PTC.