bluuebunny/crossref_metadata_2025 huggingface dataset:
Why scientists, academic institutions, and investors fail in bringing more products to the bedside: the Active Compass model for overcoming the innovation paradox
Authors: Ilan Yaron
Published: February 2021

The vast majority of good science and excellent ideas do not translate into products. Many good products that have the potential to assist in diagnosis and therapy do not mature into everyday care. This often becomes a source of frustration for innovators, academic institutions, companies both small and large, and investors. The “innovation paradox” , wherein excellent ideas and good science fail to reach the bedside, is a major challenge. This study presents the Active Compass model as a way to overcome this obstacle. The model is designed to assist projects at early stages by redirecting and reshaping them in a way that increases their chances of reaching the markets. The model is based on the use of next-generation translational research and on creating differentiators at the early stages of development. The proposed model’s implementation by innovators, scientists, technology transfer offices, academic institutions, analysts, and investors can help move forward high-potential projects to improve the quality of life and alleviate the burdens of disease.
Women’s empowerment for abortion and family planning decision making among marginalized women in Nepal: a mixed method study
Authors: KC Heera , Shrestha Mangala , Pokharel Nirmala , Niraula Surya Raj , Pyakurel Prajjwal , Parajuli Surya Bahadur
Published: February 2021

Background

Women’s empowerment is multidimensional. Women’s education, employment, income, reproductive healthcare decision making, household level decision making and social status are vital for women’s empowerment. Nepal is committed to achieving women empowerment and gender equality, which directly affects the reproductive health issues. This can be achieved by addressing the issues of the poor and marginalized communities. In this context, we aimed to find the association of women’s empowerment with abortion and family planning decision making among marginalized women in Nepal.

Methods

A cross sectional study was conducted at selected municipalities of Morang district of Nepal from February 2017 to March 2018. A mixed method approach was used, where 316 married marginalized women of reproductive age (15–49 years) and 15 key informant interviews from representative healthcare providers and local leaders were taken. From key informants, data were analysed using the thematic framework method. Findings obtained from two separate analyses were drawn together and meta inferences were made.

Results

Women’s empowerment was above average, at 50.6%. Current use of modern contraceptives were more among below average empowerment groups (p 0.041, OR 0.593 C.I. 0.36–0.98). We could not find any statistically significant differences among levels of women’s empowerment, including those women with abortion knowledge (p 0.549); family planning knowledge (p 0.495) and women’s decision for future use of modern contraceptives (p 0.977). Most key informants reported that unsafe abortion was practiced.

Conclusions

Women’s empowerment has no direct role for family planning and abortion decision making at marginalized communities of Morang district of Nepal. However, different governmental and non-governmental organizations influence woman for seeking health care services and family planning in rural community of Nepal irrespective of empowerment status.
Immersive augmented reality system for the training of pattern classification control with a myoelectric prosthesis
Authors: Boschmann Alexander , Neuhaus Dorothee , Vogt Sarah , Kaltschmidt Christian , Platzner Marco , Dosen Strahinja
Published: February 2021

Background

Hand amputation can have a truly debilitating impact on the life of the affected person. A multifunctional myoelectric prosthesis controlled using pattern classification can be used to restore some of the lost motor abilities. However, learning to control an advanced prosthesis can be a challenging task, but virtual and augmented reality (AR) provide means to create an engaging and motivating training.

Methods

In this study, we present a novel training framework that integrates virtual elements within a real scene (AR) while allowing the view from the first-person perspective. The framework was evaluated in 13 able-bodied subjects and a limb-deficient person divided into intervention (IG) and control (CG) groups. The IG received training by performing simulated clothespin task and both groups conducted a pre- and posttest with a real prosthesis. When training with the AR, the subjects received visual feedback on the generated grasping force. The main outcome measure was the number of pins that were successfully transferred within 20 min (task duration), while the number of dropped and broken pins were also registered. The participants were asked to score the difficulty of the real task (posttest), fun-factor and motivation, as well as the utility of the feedback.

Results

The performance (median/interquartile range) consistently increased during the training sessions (4/3 to 22/4). While the results were similar for the two groups in the pretest, the performance improved in the posttest only in IG. In addition, the subjects in IG transferred significantly more pins (28/10.5 versus 14.5/11), and dropped (1/2.5 versus 3.5/2) and broke (5/3.8 versus 14.5/9) significantly fewer pins in the posttest compared to CG. The participants in IG assigned (mean ± std) significantly lower scores to the difficulty compared to CG (5.2 ± 1.9 versus 7.1 ± 0.9), and they highly rated the fun factor (8.7 ± 1.3) and usefulness of feedback (8.5 ± 1.7).

Conclusion

The results demonstrated that the proposed AR system allows for the transfer of skills from the simulated to the real task while providing a positive user experience. The present study demonstrates the effectiveness and flexibility of the proposed AR framework. Importantly, the developed system is open source and available for download and further development.
Correction to: Micronized sacchachitin promotes satellite cell proliferation through TAK1-JNK-AP-1 signaling pathway predominantly by TLR2 activation
Authors: Wu Meng–Huang , Lin Chuang–Yu , Hou Chun–Yin , Sheu Ming–Thau , Chang Hsi
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Sulthiame impairs mitochondrial function in vitro and may trigger onset of visual loss in Leber hereditary optic neuropathy
Authors: Reinert Marie-Christine , Pacheu-Grau David , Catarino Claudia B. , Klopstock Thomas , Ohlenbusch Andreas , Schittkowski Michael , Wilichowski Ekkehard , Rehling Peter , Brockmann Knut
Published: February 2021

Background

Leber hereditary optic neuropathy (LHON) is the most common mitochondrial disorder and characterized by acute or subacute painless visual loss. Environmental factors reported to trigger visual loss in LHON mutation carriers include smoking, heavy intake of alcohol, raised intraocular pressure, and some drugs, including several carbonic anhydrase inhibitors. The antiepileptic drug sulthiame (STM) is effective especially in focal seizures, particularly in benign epilepsy of childhood with centrotemporal spikes, and widely used in pediatric epileptology. STM is a sulfonamide derivate and an inhibitor of mammalian carbonic anhydrase isoforms I–XIV.

Results

We describe two unrelated patients, an 8-year-old girl and an 11-year-old boy, with cryptogenic focal epilepsy, who suffered binocular (subject #1) or monocular (subject #2) visual loss in close temporal connection with starting antiepileptic pharmacotherapy with STM. In both subjects, visual loss was due to LHON. We used real-time respirometry in fibroblasts derived from LHON patients carrying the same mitochondrial mutations as our two subjects to investigate the effect of STM on oxidative phosphorylation. Oxygen consumption rate in fibroblasts from a healthy control was not impaired by STM compared with a vehicle control. In contrast, fibroblasts carrying the m.14484T>C or the m.3460G>A LHON mutation displayed a drastic reduction of the respiration rate when treated with STM compared to vehicle control.

Conclusions

Our observations point to a causal relationship between STM treatment and onset or worsening of visual failure in two subjects with LHON rather than pure coincidence. We conclude that antiepileptic medication with STM may pose a risk for visual loss in LHON mutation carriers and should be avoided in these patients.
Experience of health care at a reference centre as reported by patients and parents of children with rare conditions
Authors: Hytiris Monica , Johnston Daisy , Mullen Shannon , Smyth Arlene , Dougan Elizabeth , Rodie Martina , Ahmed S. Faisal
Published: February 2021

Background

Whilst diagnostic pathways for children with rare conditions have shown marked improvement, concerns remain about the care children with rare conditions receive at the level of the health care provider. There is, therefore, a need to improve our understanding of the health care received and explore the development of benchmarks that can be regularly monitored.

Methods

Patients and parents with rare conditions at a tertiary children’s hospital were approached to complete a questionnaire-based survey that enquired on their experience of clinical care. The survey explored six key themes: diagnosis; provision of information; availability of support; satisfaction with healthcare team; awareness and support for life-limiting conditions; and participation in research.

Results

130 questionnaires were completed on behalf of 134 patients between 2018 and 2020. Of these, 114 (85%) had received a formal diagnosis, 5 (4%) had a suspected diagnosis and 15 (11%) were undiagnosed. Of the 114 who had received a diagnosis, 24 (20%) were diagnosed within 6 months of developing symptoms, and 22 (20%) within 1–3 years. Seventy patients (53%) reported that they were given little or no information around the time of diagnosis, whilst 81 (63%) felt they were currently well supported, mostly from family members, followed by friends, hospital services, school, other community based healthcare services and lastly, primary care. Of the 127 who were asked, 88 (69%) reported a consistent team of healthcare professionals taking overall responsibility for their care, 86 (67%) felt part of the team, 74 (58%) were satisfied with the level of knowledge of the professionals, and 86 (68%) knew who to contact regarding their condition. Of the 91 who were asked, 23 (25%) were aware their child had a life limiting condition, but only 4 (17%) were receiving specialist support for this. Of 17 who were asked about research, 4 (24%) were actively participating in research, whilst the remainder were all willing to participate in future research.

Conclusions

The survey provides a unique insight into the experience of patients and parents within a specialist centre and the benchmarks that it has revealed can be used for future improvement in services.
The Matthews correlation coefficient (MCC) is more reliable than balanced accuracy, bookmaker informedness, and markedness in two-class confusion matrix evaluation
Authors: Chicco Davide , Tötsch Niklas , Jurman Giuseppe
Published: February 2021

Evaluating binary classifications is a pivotal task in statistics and machine learning, because it can influence decisions in multiple areas, including for example prognosis or therapies of patients in critical conditions. The scientific community has not agreed on a general-purpose statistical indicator for evaluating two-class confusion matrices (having true positives, true negatives, false positives, and false negatives) yet, even if advantages of the Matthews correlation coefficient (MCC) over accuracy and F1 score have already been shown.In this manuscript, we reaffirm that MCC is a robust metric that summarizes the classifier performance in a single value, if positive and negative cases are of equal importance. We compare MCC to other metrics which value positive and negative cases equally: balanced accuracy (BA), bookmaker informedness (BM), and markedness (MK). We explain the mathematical relationships between MCC and these indicators, then show some use cases and a bioinformatics scenario where these metrics disagree and where MCC generates a more informative response.Additionally, we describe three exceptions where BM can be more appropriate: analyzing classifications where dataset prevalence is unrepresentative, comparing classifiers on different datasets, and assessing the random guessing level of a classifier. Except in these cases, we believe that MCC is the most informative among the single metrics discussed, and suggest it as standard measure for scientists of all fields. A Matthews correlation coefficient close to +1, in fact, means having high values for all the other confusion matrix metrics. The same cannot be said for balanced accuracy, markedness, bookmaker informedness, accuracy and F1 score.
Clinical challenges in interpreting multiple pathogenic mutations in single patients
Authors: Slaught Christa , Berry Elizabeth G. , Bacik Lindsay , Skalet Alison H. , Anadiotis George , Tuohy Therese , Leachman Sancy A.
Published: February 2021

Background

In the past two decades, genetic testing for cancer risk assessment has entered mainstream clinical practice due to the availability of low-cost panels of multiple cancer-associated genes. However, the clinical value of multiple-gene panels for cancer susceptibility is not well established, especially in cases where panel testing identifies more than one pathogenic variant. The risk for specific malignancies as a result of a mutated gene is complex and likely influenced by superimposed modifier variants and/or environmental effects. Recent data suggests that the combination of multiple pathogenic variants may be fewer than reported by chance, suggesting that some mutation combinations may be detrimental. Management of patients with “incidentally” discovered mutations can be particularly challenging, especially when established guidelines call for radical procedures (e.g. total gastrectomy in CDH1) in patients and families without a classic clinical history concerning for that cancer predisposition syndrome.

Case presentation

We present two cases, one of an individual and one of a family, with multiple pathogenic mutations detected by multi-gene panel testing to highlight challenges practitioners face in counseling patients about pathogenic variants and determining preventive and therapeutic interventions.

Conclusions

Ongoing investigation is needed to improve our understanding of inherited susceptibility to disease in general and cancer predisposition syndromes, as this information has the potential to lead to the development of more precise and patient-specific counseling and surveillance strategies. The real-world adoption of new or improved technologies into clinical practice frequently requires medical decision-making in the absence of established understanding of gene-gene interactions. In the meantime, practitioners must be prepared to apply a rationale based on currently available knowledge to clinical decision-making. Current practice is evolving to rely heavily on clinical concordance with personal and family history in making specific therapeutic decisions.
Impact of post-diagnosis weight change on survival outcomes in Black and White breast cancer patients
Authors: Shang Lihua , Hattori Masaya , Fleming Gini , Jaskowiak Nora , Hedeker Donald , Olopade Olufunmilayo I. , Huo Dezheng
Published: February 2021

Purpose

To evaluate weight change patterns over time following the diagnosis of breast cancer and to examine the association of post-diagnosis weight change and survival outcomes in Black and White patients.

Methods

The study included 2888 women diagnosed with non-metastatic breast cancer in 2000–2017 in Chicago. Longitudinal repeated measures of weight and height were collected, along with a questionnaire survey including questions on body size. Multilevel mixed-effects models were used to examine changes in body mass index (BMI). Delayed entry Cox proportional hazards models were used to investigate the impacts of changing slope of BMI on survival outcomes.

Results

At diagnosis, most patients were overweight or obese with a mean BMI of 27.5 kg/m2 and 31.5 kg/m2 for Blacks and Whites, respectively. Notably, about 45% of the patients had cachexia before death and substantial weight loss started about 30 months before death. In multivariable-adjusted analyses, compared to stable weight, BMI loss (> 0.5 kg/m2/year) showed greater than 2-fold increased risk in overall survival (hazard ratio [HR] = 2.60, 95% CI 1.88–3.59), breast cancer-specific survival (HR = 3.05, 95% CI 1.91–4.86), and disease-free survival (HR = 2.12, 95% CI 1.52–2.96). The associations were not modified by race, age at diagnosis, and pre-diagnostic weight. BMI gain (> 0.5 kg/m2/year) was also related to worse survival, but the effect was weak (HR = 1.60, 95% CI 1.10–2.33 for overall survival).

Conclusion

BMI loss is a strong predictor of worse breast cancer outcomes. Growing prevalence of obesity may hide diagnosis of cancer cachexia, which can occur in a large proportion of breast cancer patients long before death.
Barriers impacting the POINT pragmatic trial: the unavoidable overlap between research and intervention procedures in “real-world” research
Authors: Dir Allyson L. , Watson Dennis P. , Zhiss Matthew , Taylor Lisa , Bray Bethany C. , McGuire Alan
Published: February 2021

Background

This manuscript provides a research update to the ongoing pragmatic trial of Project POINT (Planned Outreach, Intervention, Naloxone, and Treatment), an emergency department-based peer recovery coaching intervention for linking patients with opioid use disorder to evidence-based treatment. The research team has encountered a number of challenges related to the “real-world” study setting since the trial began. Using an implementation science lens, we sought to identify and describe barriers impacting both the intervention and research protocols of the POINT study, which are often intertwined in pragmatic trials due to the focus on external validity.

Method

Qualitative data were collected from 3 peer recovery coaches, 2 peer recovery coach supervisors, and 3 members of the research team. Questions and deductive qualitative analysis were guided by the Consolidated Framework for Implementation Research (CFIR).

Results

Nine unique barriers were noted, with 5 of these barriers impacting intervention and research protocol implementation simultaneously. These simultaneous barriers were timing of intervention delivery, ineffective communication with emergency department staff, lack of privacy in the emergency department, the fast-paced emergency department setting, and patient’s limited resources. Together, these barriers represent the intervention characteristics, inner setting, and outer setting domains of the CFIR.

Conclusion

Results highlight the utility of employing an implementation science framework to assess implementation issues in pragmatic trials and how this approach might be used as a quality assurance mechanism given the considerable overlap that exists between research and intervention protocols in real-world trial settings. Previously undocumented changes to the trial design that have been made as a result of the identified barriers are discussed.
Prevalence of traumatic brain injury among the guests at a low-barrier homeless shelter
Authors: Ang Nicholas Benjamin , Wasserman Jason Adam
Published: February 2021

Objective

This study aimed at determining the prevalence of traumatic brain injuries (TBI) among guests staying at a low-barrier homeless shelter who represent an especially vulnerable subset of individuals experiencing homelessness.

Results

A total of 21 out of 35 shelter guests participated in the survey. We found that 17 (81.0%) had experienced at least one traumatic brain injury in their lifetime and 15 (71.3%) had TBI associated with loss of consciousness. In addition, 7 (33.3%) of the participants had experienced TBIs rated as moderate to severe. Of the participants with head trauma history, 16 (94.1%) experienced their injury before their first onset of homelessness. Compared to both the general population and the broader population of individuals experiencing homelessness, those in this sample were significantly more likely to experience TBI (95% CI 0.0000:0.2857; p < 0.001 and 95% CI 0.3333:0.7619; p < 0.015, respectively) and significantly more likely to experience severe TBI (95% CI 0.0000:0.09524; p < 0.001).
Whole-genome sequencing data of Kazakh individuals
Authors: Kairov Ulykbek , Molkenov Askhat , Rakhimova Saule , Kozhamkulov Ulan , Sharip Aigul , Karabayev Daniyar , Daniyarov Asset , H.Lee Joseph , D.Terwilliger Joseph , Akilzhanova Ainur , Zhumadilov Zhaxybay
Published: February 2021

Objectives

Kazakhstan is a Central Asian crossroad of European and Asian populations situated along the way of the Great Silk Way. The territory of Kazakhstan has historically been inhabited by nomadic tribes and today is the multi-ethnic country with the dominant Kazakh ethnic group. We sequenced and analyzed the whole-genomes of five ethnic healthy Kazakh individuals with high coverage using next-generation sequencing platform. This whole-genome sequence data of healthy Kazakh individuals can be a valuable reference for biomedical studies investigating disease associations and population-wide genomic studies of ethnically diverse Central Asian region.

Data description

Blood samples have been collected from five ethnic healthy Kazakh individuals living in Kazakhstan. The genomic DNA was extracted from blood and sequenced. Sequencing was performed on Illumina HiSeq2000 next-generation sequencing platform. We sequenced and analyzed the whole-genomes of ethnic Kazakh individuals with the coverage ranging from 26 to 32X. Ranging from 98.85 to 99.58% base pairs were totally mapped and aligned on the human reference genome GRCh37 hg19. Het/Hom and Ts/Tv ratios for each whole genome ranged from 1.35 to 1.49 and from 2.07 to 2.08, respectively. Sequencing data are available in the National Center for Biotechnology Information SRA database under the accession number PRJNA374772.
An unusual case of multiple hepatic and pulmonary abscesses caused by Aggregatibacter aphrophilus in a young man: a case report
Authors: Sumer Johannes , Haller Sabine , Sawatzki Mikael , Kellner Jan , Boggian Katia
Published: February 2021

Background

Aggregatibacter aphrophilus, formerly known as Haemophilus aphrophilus, belongs to the HACEK organisms, a group of pathogens classically associated with infectious endocarditis. A. aphrophilus is a rarely found pathogen, though abscess formation in various organs has been described, typically due to spread from an infected heart valve. Here we describe the unusual case of multiple hepatic abscesses caused by A. aphrophilus.

Case presentation

A 33-year-old Caucasian man presented at our hospital with fever and malaise, elevated inflammatory markers, and liver enzymes. Imaging was compatible with multiple liver and pulmonary abscesses, without evidence of endocarditis. Cultures of blood and liver abscess material remained without growth. Polymerase chain reaction finally revealed Aggregatibacter aphrophilus in the liver tissue. The patient recovered fully within 6 weeks of doxycycline treatment.

Conclusions

There are only a few case descriptions of liver abscesses caused by A. aphrophilus. As a ubiquitous organism in the gastrointestinal tract, A. aphrophilus may reach the liver via the portal venous system, as well as through hematogenous spread from the oropharynx. HACEK organisms are notoriously difficult to grow on culture, which highlights the diagnostic importance of eubacterial PCR.
Enhanced cell survival and therapeutic benefits of IL-10-expressing multipotent mesenchymal stromal cells for muscular dystrophy
Authors: Nitahara-Kasahara Yuko , Kuraoka Mutsuki , Oda Yuki , Hayashita-Kinoh Hiromi , Takeda Shin’ichi , Okada Takashi
Published: February 2021

Background

Multipotent mesenchymal stromal cells (MSCs) are potentially therapeutic for muscle disease because they can accumulate at the sites of injury and act as immunosuppressants. MSCs are attractive candidates for cell-based strategies that target diseases with chronic inflammation, such as Duchenne muscular disease (DMD). We focused on the anti-inflammatory properties of IL-10 and hypothesized that IL-10 could increase the typically low survival of MSCs by exerting a paracrine effect after transplantation.

Methods

We developed a continuous IL-10 expression system of MSCs using an adeno-associated virus (AAV) vector. To investigate the potential benefits of IL-10 expressing AAV vector-transduced MSCs (IL-10-MSCs), we examined the cell survival rates in the skeletal muscles after intramuscular injection into mice and dogs. Systemic treatment with IL-10-MSCs derived from dental pulp (DPSCs) was comprehensively analyzed using the canine X-linked muscular dystrophy model in Japan (CXMDJ), which has a severe phenotype similar to that of DMD patients.

Results

In vivo bioluminescence imaging analysis revealed higher retention of IL-10-MSCs injected into the hindlimb muscle of mice. In the muscles of dogs, myofiber-like tissue was formed after the stable engraftment of IL-10-MSCs. Repeated systemic administration of IL-10-DPSCs into the CXMDJmodel resulted in long-term engraftment of cells and slightly increased the serum levels of IL-10. IL-10-hDPSCs showed significantly reduced expression of pro-inflammatory MCP-1 and upregulation of stromal-derived factor-1 (SDF-1). MRI and histopathology of the hDPSC-treated CXMDJindicated the regulation of inflammation in the muscles, but not myogenic differentiation from treated cells. hDPSC-treated CXMDJshowed improved running capability and recovery in tetanic force with concomitant increase in physical activity. Serum creatine kinase levels, which increased immediately after exercise, were suppressed in IL-10-hDPSC-treated CXMDJ.

Conclusions

In case of local injection, IL-10-MSCs could maintain the long-term engraftment status and facilitate associated tissue repair. In case of repeated systemic administration, IL-10-MSCs facilitated the long-term retention of the cells in the skeletal muscle and also protected muscles from physical damage-induced injury, which improved muscle dysfunction in DMD. We can conclude that the local and systemic administration of IL-10-producing MSCs offers potential benefits for DMD therapy through the beneficial paracrine effects of IL-10 involving SDF-1.
New onset diabetes mellitus and cardiovascular events in Korean patients with acute myocardial infarction receiving high-intensity statins
Authors:   KAMIR-NIH Investigators, Choi Jah Yeon , Choi Cheol Ung , Choi Byoung Geol , Park Yoonjee , Kang Dong Oh , Jang Won Young , Kim Woohyeun , Na Jin Oh , Kim Jin Won , Kim Eung Ju , Rha Seung-Woon , Park Chang Gyu , Seo Hong Seog , Jeong Myung Ho , Chae Sung-Chull , Seong In-Whan , Yoon Chang-Hwan , Cha Kwang Soo , Oh Seok Kyu
Published: February 2021

Background

High-intensity statin therapy is typically used in patients with acute myocardial infarction (AMI) for secondary prevention. However, there have been consistent concerns regarding its association with diabetes mellitus. We investigated the effect of high-intensity atorvastatin and rosuvastatin on new-onset diabetes mellitus (NODM) and cardiovascular outcomes over a 3-year follow-up period.

Methods

Data from the Korea Acute Myocardial Infarction Registry were collected from November 2011 to October 2015, and 13,104 patients with AMI were enrolled from major cardiovascular centers. Among them, 2221 patients without diabetes who had been administered with high-intensity atorvastatin (40–80 mg) and rosuvastatin (20 mg) were investigated. The atorvastatin and rosuvastatin groups were evaluated for the incidence of NODM and major adverse cardiac events (MACE) including death, myocardial infarction, and revascularization cases in the following 3 years.

Results

Baseline characteristics were comparable between the two groups. Event-free survival rate of NODM was not significantly different between the atorvastatin and rosuvastatin groups (92.5% vs. 90.8%, respectively; Log-rank P-value = 0.550). The event-free survival rate of MACE was also not significantly different between atorvastatin and rosuvastatin groups (89.0% vs. 89.6%, respectively; Log rank P-value = 0.662). Multivariate Cox analysis revealed that statin type was not a prognostic factor in the development of NODM and MACE.

Conclusions

Administering high-intensity atorvastatin and rosuvastatin in patients with AMI produced comparable effects on NODM and clinical outcomes, suggesting their clinical equivalence in secondary prevention.
Correction to: Combating an invisible enemy: the American military response to global pandemics
Authors: Dutton Lauren K. , Rhee Peter C. , Shin Alexander Y. , Ehrlichman Richard J. , Shemin Richard J.
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Eye tracking metrics and leader’s behavioral performance during a post-partum hemorrhage high-fidelity simulated scenario
Authors: Capogna Emanuele , Capogna Giorgio , Raccis Denise , Salvi Francesco , Velardo Matteo , Del Vecchio Angelica
Published: February 2021

Background

The use of eye tracking in the simulated setting can help improve our understanding of what sources of information clinicians are using as they deliver routine patient care.

The aim of this simulation study was to observe the differences, if any, between the eye tracking patterns of leaders who performed best in a simulated postpartum hemorrhage (PPH) high-fidelity scenario, in comparison with those who performed worst.

Methods

Forty anesthesia trainees from the University of Catania Medical School were divided into eight teams, to enact four times the same scenario of a patient with postpartum hemorrhage following vaginal delivery.

Trainees who were assigned the leader’s role wore the eye tracking glasses during the scenario, and their behavioral skills were evaluated by two observers, who reviewed the video recordings of the scenarios using a standardized checklist. The leader’s eye tracking metrics, extracted from 27 selected areas of interest (AOI), were recorded by a Tobii Pro Glasses 50 Hz wearable wireless eye tracker. Team performance was evaluated using a PPH checklist.

After completion of the study, the leaders were divided into two groups, based on the scores they had received (High-Performance Leader group, HPL, and Low-Performance Leader group, LPL).

Results

In the HPL group, the duration and number of fixations were greater, and the distribution of gaze was uniformly distributed among the various members of the team as compared with the LPL group (with the exception of the participant who performed the role of the obstetrician).

The HPL group also looked both at the patient’s face and established eye contact with their team members more often and for longer (P < .05). The team performance (PPH checklist) score was greater in the HPL group (P < .001).

The LPL group had more and/or longer fixations of technical areas of interest (P < .05).

Conclusions

Our findings suggest that the leaders who perform the best distribute their gaze across all members of their team and establish direct eye contact. They also look longer at the patient’s face and dwell less on areas that are more relevant to technical skills. In addition, the teams led by these best performing leaders fulfilled their clinical task better. The information provided by the eye behaviors of “better-performing physicians” may lay the foundation for the future development of both the assessment process and the educational tools used in simulation.

Trial Registration

Clinical.Trial.Gov ID n. NCT04395963.
Effect of NEuroplasticity-Principles-based SEnsory-Rehabilitation (NEPSER) on sensori-motor recovery in stroke: study protocol for a randomized controlled trial
Authors: Arya Kamal Narayan , Pandian Shanta , Agarwal G. G. , Chaudhary Neera , Joshi Akshay Kumar
Published: February 2021

Introduction

Up to 2/3rd of the stroke subjects may experience impairment in any of the somatosensory modalities such as light touch, proprioception, and stereognosis. The sensory recovery is strongly associated with the level of motor recovery. Very negligible sensory-based interventions have been developed and found to be evident in enhancing the sensory deficit and associated motor recovery. The possible factor for the ineffectiveness of these sensory interventions could be lack of the neuroscientific basis in formulation of the program. Thus, the objective of the study is to determine the effectiveness of a neuralplasticity-principles-based sensory-rehabilitation protocol on motor and sensory recovery, and disability of the post-stroke hemiparetic subjects.

Methods

We propose to recruit 122 poststroke subjects in a randomized controlled, assessor blinded trial to be conducted in a rehabilitation-institute. The key eligibility criteria is age between 20 to 80 years, hemiparesis (right or left), ischemic or hemorrhagic stroke, 1 to 12 months poststroke, and impairment in any of the sensory modalities. The participants in the experimental group will receiveNEuroplasticity-Principles-basedSEnsory-Rehabilitation (NEPSER) protocol comprising active, repetitive, and meaningful training of the specific sensory modalities utilizing visuo-perceptual, cognitive, motor, and functional tasks will be imparted for 8 weeks, 5 sessions / week, each of 2 h. The control subjects will undergo only standard rehabilitation based on neurophysiological, biomechanical, and rehabilitative approaches. All the participants will be assessed for motor (Fugl-Meyer assessment, upper extremity section) and sensory recovery [Nottingham Sensory assessment (Erasmus MC modification of the revised version)] at baseline, 8-week, and 12-week follow-up. The Semmes weinstein monofilament, two-point discrimination test and modified rankin scale (disability) will be applied as secondary measures. A repeated-measures 2-way ANOVA will be used to estimate difference for the post intervention and follow-up scores between the groups.

Perspective

The proposed study will lead to development of a novel rehabilitation protocol that will not only enhance the sensory recovery but also the motor and functional recovery. This may reduce the impact of stroke disability and enhance the quality of life.

Trial registration

The trial has been registered under Clinical Trial Registry of India (CTRI) asCTRI/2019/09/021442on 30th September 2019.
Evaluation of neurobehavioral activities of ethanolic extract of Psidium guajava Linn leaves in mice model
Authors: Biswas Sonchita , Mondol Debashish , Jodder Protic , Sana Samiron , Saleh Md. Abu , Tarafdar Amit Kumar , Islam Farhana
Published: February 2021

Background

The complementary and alternative medicines have particular importance in treating various comorbid conditions including anxiety and depression which prevalence will be raised to the second highest risk of morbidity, triggering a noteworthy socioeconomic burden. Ethanolic extract of leaves of Psidium guajava Linn (EEPG) was investigated to evaluate the anxiolytic and anti-depressant activity into two different doses (200 mg/kg and 400 mg/kg of body weight) on Swiss Albino male mice utilizing experimental paradigms of anxiety and depression. The extract was also subjected to phytochemical screening.

Results

Phytochemicals screening showed the presence of numerous types of active constituents in extract, for example, flavonoids, alkaloids, terpenoids, and steroids. The experimental results revealed that in case of anxiolytic activity tests, a statistical significant (p < 0.05 vs group I) effect is observed in EPMT model, hole cross model, light and dark model in both doses, whereas in hole-board model, marble burying model tests, a statistical considerable effect is observed only at the dose of 400 mg/kg although at the dose of 200 mg/kg, anxiolytic effect is also expressed and in case of anti-depressant activity test, the statistical significant effect is observed only at the dose of 400 mg/kg. All the results are comparable with the effect of standard drugs used.

Conclusions

Taken together, the present research work evidences the anxiolytic and anti-depressant effects of EEPG, but further investigation needed to find out the underlying mechanism of action and to isolate and purify the specific components that are responsible for aforementioned activities.
Efficacy of platelet-rich plasma injection in comparison to physical therapy for treatment of chronic partial supraspinatus tear
Authors: Serya Sarah Saad Mohamed Ahmed , Neseem Nanis Onsy , Shaat Reham M. , Nour.A. Khaled , Senna Mohammad K.
Published: February 2021

Background

Supraspinatus tendon is a part of the rotator cuff of the shoulder, partial or full-thickness tear can affect the tendon secondary to trauma or repeated microtrauma. The aim of the present study is to evaluate the efficacy of platelet-rich plasma (PRP) injection in comparison to physical therapy for treatment of chronic partial supraspinatus tears.

Results

At the beginning of the study, there were no significant differences between both groups in all parameters: (a) PRP injection had significantly improved the visual analog scale (VAS), disabilities of arm, shoulder and hand scale (DASH) and shoulder range of motion (ROM) but not size of tear at 6 and 12 weeks post-injection in comparison to baseline recordings; (b) physical therapy had significantly improved VAS, DASH but not shoulder ROM nor size of tear at 6 and 12 weeks post-injection in comparison to baseline recordings; and (c) PRP injection was superior to physical therapy in the improvement of VAS, shoulder ROM, and DASH score.

Conclusion

The US-guided PRP injection is superior to physical therapy in improving pain, ROM, and function in treatment of partial thickness tear of supraspinatus tendon.
Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up
Authors: Piccart Martine , Procter Marion , Fumagalli Debora , de Azambuja Evandro , Clark Emma , Ewer Michael S. , Restuccia Eleonora , Jerusalem Guy , Dent Susan , Reaby Linda , Bonnefoi Hervé , Krop Ian , Liu Tsang-Wu , Pieńkowski Tadeusz , Toi Masakazu , Wilcken Nicholas , Andersson Michael , Im Young-Hyuck , Tseng Ling Ming , Lueck Hans-Joachim , Colleoni Marco , Monturus Estefania , Sicoe Mihaela , Guillaume Sébastien , Bines José , Gelber Richard D. , Viale Giuseppe , Thomssen Christoph ,   for the APHINITY Steering Committee and Investigators
Published: February 2021

PURPOSE

APHINITY, at 45 months median follow-up, showed that pertuzumab added to adjuvant trastuzumab and chemotherapy significantly improved invasive disease–free survival (IDFS) (hazard ratio 0.81 [95% CI, 0.66 to 1.00], P = .045) for patients with early human epidermal growth factor receptor 2 (HER2)–positive breast cancer (BC), specifically those with node-positive or hormone receptor (HR)–negative disease. We now report the preplanned second interim overall survival (OS) and descriptive updated IDFS analysis with 74 months median follow-up.

METHODS

After surgery and central HER2-positive confirmation, 4,805 patients with node-positive or high-risk node-negative BC were randomly assigned (1:1) to either 1-year pertuzumab or placebo added to standard adjuvant chemotherapy and 1-year trastuzumab.

RESULTS

This interim OS analysis comparing pertuzumab versus placebo did not reach the P = .0012 level required for statistical significance ( P = .17, hazard ratio 0.85). Six-year OS were 95% versus 94% with 125 deaths (5.2%) versus 147 (6.1%), respectively. IDFS analysis based on 508 events (intent-to-treat population) showed a hazard ratio of 0.76 (95% CI, 0.64 to 0.91) and 6-year IDFS of 91% and 88% for pertuzumab and placebo groups, respectively. The node-positive cohort continues to derive clear IDFS benefit from pertuzumab (hazard ratio 0.72 [95% CI, 0.59 to 0.87]), 6-year IDFS being 88% and 83%, respectively. Benefit was not seen in the node-negative cohort. In a subset analysis, IDFS benefit from pertuzumab showed a hazard ratio of 0.73 (95% CI, 0.59 to 0.92) for HR-positive disease and a hazard ratio of 0.83 (95% CI, 0.63 to 1.10) for HR-negative disease. Primary cardiac events remain < 1% in both the treatment groups. No new safety signals were seen.

CONCLUSION

This analysis confirms the IDFS benefit from adding pertuzumab to standard adjuvant therapy for patients with node-positive HER2-positive early BC. Longer follow-up is needed to fully assess OS benefit.
Unmet Care Needs and Financial Hardship in Patients With Metastatic Non–Small-Cell Lung Cancer on Immunotherapy or Chemoimmunotherapy in Clinical Practice
Authors: McLouth Laurie E. , Nightingale Chandylen L. , Levine Beverly J. , Burris Jessica L. , McDougall Jean A. , Lycan Thomas W. , Gabbard Jennifer , Ruiz Jimmy , Farris Michael , Blackstock Arthur W. , Grant Stefan C. , Petty W. Jeffrey , Weaver Kathryn E.
Published: February 2021

PURPOSE:

Immunotherapy or chemoimmunotherapy is now standard treatment for most patients with metastatic non–small-cell lung cancer (mNSCLC), yet patient supportive care needs (SCNs) on immunotherapy are not well defined. This study characterized the SCNs and financial hardship of patients with mNSCLC treated with immunotherapy or chemoimmunotherapy and examined the relationship between patient and caregiver cancer-related employment reductions and patient financial hardship.

METHODS:

Patients with mNSCLC on immunotherapy or chemoimmunotherapy from a single academic medical center completed the SCNs Survey-34, items indexing material, psychological, and behavioral financial hardship, and the Comprehensive Score for Financial Toxicity. Univariate and bivariate analyses examined care needs, financial hardship, and impact of cancer-related employment reductions on patient financial hardship.

RESULTS:

Sixty patients (40% male; 75% White, mean age = 62.5 years, 57% on immunotherapy alone) participated. Fifty-five percent reported unmet needs in physical or daily living and psychological domains. Financial hardship was common (33% material, 63% psychological, and 57% behavioral). Fifty-two percent reported hardship in at least two domains. Forty percent reported a caregiver cancer-related employment reduction. Caregiver employment reduction was related to patient financial hardship (68% of those reporting caregiver employment reduction reported at least two domains of hardship v 40% of those without reduction, P = .03) and patient financial distress (mean Comprehensive Score for Financial Toxicity = 19.6 among those with caregiver employment reduction v 26.8 without, P = .01).

CONCLUSION:

Patients with mNSCLC treated with immunotherapy or chemoimmunotherapy report multiple unmet care needs and financial hardship. Psychological, functional, financial, and caregiver concerns merit assessment and intervention in this population.
Importance of Adipose Tissue NAD+ Biology in Regulating Metabolic Flexibility
Authors: Franczyk Michael P , Qi Nathan , Stromsdorfer Kelly L , Li Chengcheng , Yamaguchi Shintaro , Itoh Hiroshi , Yoshino Mihoko , Sasaki Yo , Brookheart Rita T , Finck Brian N , DeBosch Brian J , Klein Samuel , Yoshino Jun
Published: February 2021

Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme that regulates cellular energy metabolism in many cell types. The major purpose of the present study was to test the hypothesis that NAD+ in white adipose tissue (WAT) is a regulator of whole-body metabolic flexibility in response to changes in insulin sensitivity and with respect to substrate availability and use during feeding and fasting conditions. To this end, we first evaluated the relationship between WAT NAD+ concentration and metabolic flexibility in mice and humans. We found that WAT NAD+ concentration was increased in mice after calorie restriction and exercise, 2 enhancers of metabolic flexibility. Bariatric surgery-induced 20% weight loss increased plasma adiponectin concentration, skeletal muscle insulin sensitivity, and WAT NAD+ concentration in people with obesity. We next analyzed adipocyte-specific nicotinamide phosphoribosyltransferase (Nampt) knockout (ANKO) mice, which have markedly decreased NAD+ concentrations in WAT. ANKO mice oxidized more glucose during the light period and after fasting than control mice. In contrast, the normal postprandial stimulation of glucose oxidation and suppression of fat oxidation were impaired in ANKO mice. Data obtained from RNA-sequencing of WAT suggest that loss of NAMPT increases inflammation, and impairs insulin sensitivity, glucose oxidation, lipolysis, branched-chain amino acid catabolism, and mitochondrial function in WAT, which are features of metabolic inflexibility. These results demonstrate a novel function of WAT NAMPT-mediated NAD+ biosynthesis in regulating whole-body metabolic flexibility, and provide new insights into the role of adipose tissue NAD+ biology in metabolic health.
Do aquatic ectotherms perform better under hypoxia after warm acclimation?
Authors: Collins Michael , Truebano Manuela , Verberk Wilco C. E. P. , Spicer John I.
Published: February 2021

Aquatic animals increasingly encounter environmental hypoxia due to climate-related warming and/or eutrophication. Although acute warming typically reduces performance under hypoxia, the ability of organisms to modulate hypoxic performance via thermal acclimation is less understood. Here, we review the literature and ask whether hypoxic performance of aquatic ectotherms improves following warm acclimation. Interpretation of thermal acclimation effects is limited by reliance on data from experiments that are not designed to directly test for beneficial or detrimental effects on hypoxic performance. Most studies have tested hypoxic responses exclusively at test temperatures matching organisms' acclimation temperatures, precluding the possibility of distinguishing between acclimation and acute thermal effects. Only a few studies have applied appropriate methodology to identify beneficial thermal acclimation effects on hypoxic performance, i.e. acclimation to different temperatures prior to determining hypoxic responses at standardised test temperatures. These studies reveal that acute warming predominantly impairs hypoxic performance, whereas warm acclimation tends to be either beneficial or have no effect. If this generalises, we predict that warm-acclimated individuals in some species should outperform non-acclimated individuals under hypoxia. However, acclimation seems to only partially offset acute warming effects; therefore, aquatic ectotherms will probably display overall reduced hypoxic performance in the long term. Drawing on the appropriate methodology, future studies can quantify the ability of organisms to modulate hypoxic performance via (reversible) thermal acclimation and unravel the underlying mechanisms. Testing whether developmental acclimation and multigenerational effects allow for a more complete compensation is essential to allow us to predict species' resilience to chronically warmer, hypoxic environments.
Myxoid glioneuronal tumour – report of three cases of a new tumour in a typical location and review of literature
Authors: Narvaez Eduardo de Oliveira , Inada Bruno Shigueo Yonekuro , de Almeida Paulo Ricardo Sousa Frota , Freitas Leonardo Furtado , Soldatelli Matheus Dorigatti , Costa Danilo Manuel Cerqueira , Marussi Victor Hugo Rocha , Campos Christiane Siqueira , Vitorino Araujo João Luiz , Carrete Junior Henrique , Amaral Lázaro Luis Faria do
Published: February 2021

Formerly called dysembryoplastic neuroepithelial tumour (DNET) of the septum pellucidum, myxoid glioneuronal tumour (MGT) was recently recognized as a distinct entity. We report three cases of presumed MGT with typical location and image features.