bluuebunny/crossref_metadata_2025 huggingface dataset:
A Framework for Developing Antiracist Medical Educators and Practitioner–Scholars
Authors: Sotto-Santiago Sylk , Poll-Hunter Norma , Trice Traci , Buenconsejo-Lum Lee , Golden Sherita , Howell Joy , Jacobs Nicole , Lee Winona , Mason Hyacinth , Ogunyemi Dotun , Crespo Waleska , Lamba Sangeeta
Published: September 2021

With an increasing awareness of the disparate impact of COVID-19 on historically marginalized populations and acts of violence on Black communities in 2020, academic health centers across the United States have been prioritizing antiracism strategies. Often, medical students and residents have been educated in the concepts of equity and antiracism and are ready to tackle these issues in practice. However, faculty are not prepared to respond to or integrate antiracism topics into the curriculum. Leaders in faculty affairs, education, diversity, and other departments are seeking tools, frameworks, expertise, and programs that are best suited to meet this imminent faculty development need.

In response to these demands for guidance, the authors came together to explore best practices, common competencies, and frameworks related to antiracism education. The focus of their work was preparing faculty to foster antiracist learning environments at traditionally predominantly White medical schools. In this Scholarly Perspective, the authors describe their collaborative work to define racism and antiracism education; propose a framework for antiracism education for faculty development; and outline key elements to successfully build faculty capacity in providing antiracism education.

The proposed framework highlights the interplay between individual learning and growth and the systemic and institutional changes needed to advance antiracist policies and practices. The key elements of the framework include building foundational awareness, expanding foundational knowledge on antiracism, embedding antiracism education into practice, and dismantling oppressive structures and measuring progress. The authors list considerations for program planning and provide examples of current work from their institutions. The proposed strategies aim to support all faculty and enable them to learn, work, and educate others in an antiracist learning environment.
Growth of surgically confirmed leiomyomas in postmenopausal women: analysis of the influencing factors
Authors: Shen Minghong , Duan Hua , Chang Yanan , Wang Sha
Published: September 2021

Objectives:

The aim of this study was to examine the growth of uterine leiomyomas in postmenopausal women and evaluate the influencing factors associated with fibroid growth.

Methods:

We retrospectively analyzed the medical records of postmenopausal women with fibroids between 2015 and 2020. All women received at least 2 transvaginal ultrasound examinations within a 6-month interval. All fibroids were verified via surgery. The postoperative pathology of all tumors was uterine fibroid. We calculated the fibroid volume using the ellipsoid volume formula and evaluated the growth rate of fibroids within 6 months simultaneously. Univariable analysis and a linear mixed-effects model were used to assess the factors influencing fibroid growth.

Results:

A total of 102 postmenopausal women with a total of 132 fibroids were assessed. The median growth rate of surgically confirmed fibroids in postmenopausal women was 12.9% every 6 months (from −61.4% to 184.1%). Obesity was associated with fibroid growth (P < 0.05). Notably, the estimated growth rates of fibroids in obese and overweight women were 26.6% (95% confidence interval [CI]: 2.3-50.9) and 15.9% (95% CI: 0.4-31.4) higher than those in women of normal weight, respectively. The growth of fibroids varied by the initial tumor size (P < 0.05). The estimated growth rate of larger fibroids (≥5.0 cm diameter) was reduced 30.0% (95% CI: −52.4 to −7.5) compared with that of small fibroids (<3.0 cm diameter).

Conclusions:

Uterine fibroids continually grow in some postmenopausal women. Obesity and small fibroids (<3.0 cm diameter) may contribute to higher growth rates of fibroids.
Massive hemorrhage after resection of uterine endocervical polyp and endometrial polyps with hysteroscopic tissue removal system
Authors: Takasaki Kazuki , Henmi Hirofumi , Ikeda Utako , Sakuhara Yusuke , Endo Toshiaki
Published: September 2021

Rationale:

Hysteroscopic tissue removal system has clinical benefits of short operation time, high total resection rate, and high patient acceptability. It has been reported to be as safe as electrosurgical resection with fewer complications. We report a case of massive hemorrhage after resection of endocervical polyp and endometrial polyps with TruClear, hysteroscopic morcellator.

Patient concerns:

A 47-year-old woman visited our hospital with vaginal discomfort. Diagnosis: Based on the hysteroscopic findings and imaging findings, endocervical polyp and multiple endometrial polyps were diagnosed.

Interventions:

Hysteroscopic resection with TruClear was performed. Thirteen hours after the surgery, massive hemorrhage from uterus was observed. Imaging examination revealed bleeding from left uterine artery and uterine artery embolization was performed.

Outcomes:

After uterine artery embolization, bleeding stopped, and further hospitalization course was uneventful. Pathological diagnosis was endocervical polyp and endometrial polyps with no malignant findings.

Lessons:

Hysteroscopic tissue removal has several clinical benefits. However, our case report shows that there is a possibility of significant hemorrhage associated with hysteroscopic tissue removal system.
Diversity, Equity, and Inclusion in Nursing
Authors: Morrison Valerie , Hauch Rodney R. , Perez Edith , Bates Melissa , Sepe Paulette , Dans Maricon
Published: September 2021

The promotion of diversity, equity, and inclusion (DEI) in nursing is a topic of renewed importance, given the civil unrest following the death of George Floyd and identified disparities in health and health outcomes during the COVID-19 pandemic. Despite its progress, the nursing profession continues to struggle with recruiting and retaining a workforce that represents the cultural diversity of the patient population. The authors completed a review of the literature on DEI in nursing and found a scarcity of studies, and that a limitation exists due to the strength of the evidence examined. This article aims to provide a review of the literature on DEI in nursing, outcomes and strategies associated with organizational DEI efforts, and knowledge on how the American Nurses Credentialing Center Pathway to Excellence® Designation Program framework supports DEI initiatives. The authors further provided recommendations for nurse leaders and a checklist of proposed questions for assessing commitment, culture, and structural empowerment initiatives toward a more diverse, equitable, and inclusive organization.
Self-Care Efficacy–Mediated Associations Between Healthcare Provider-Patient Communication and Psychological Distress Among Patients With Gastrointestinal Cancers
Authors: Chen Yongfeng , Chen Yanrong , Zhang Liyuan , Li Jilian , Bai Jinbing
Published: September 2021

Background

Both healthcare provider-patient communication and self-care efficacy affect psychological distress, which is prevalent among patients with gastrointestinal (GI) cancers. It is essential to explore the underlying mechanism among them to relieve psychological distress.

Objective

The aim of this study was to examine whether self-care efficacy mediated the association between healthcare provider-patient communication and psychological distress among patients with GI cancers.

Methods

A cross-sectional study was conducted between March 2018 and May 2019 in China. In total, 219 patients with GI cancers were recruited before discharge from chemotherapy. Healthcare provider-patient communication was assessed by the revised Physician-Patient Communication Scale; patient self-care efficacy was assessed by the Strategies Used by People to Promote Health; and psychological distress was assessed by the Distress Thermometer and the Hospital Anxiety and Depression Scale. Mediation analyses were conducted to examine the mediating effect of self-care efficacy on the association between healthcare provider-patient communication and psychological distress.

Results

A total of 54.34% of patients experienced psychological distress. Patients reported a mean score of 89.93 (SD, 13.81) for healthcare provider-patient communication and 93.91 (SD, 23.39) for self-care efficacy. Self-care efficacy completely mediated the association between healthcare provider-patient communication and psychological distress, and communication outcome was the only domain that significantly influenced self-care efficacy.

Conclusion

Psychological distress is prevalent among patients with GI cancers. Healthcare provider-patient communication, especially communication outcome, promoted patients’ self-care efficacy to reduce psychological distress.

Implications for Practice

Healthcare providers should design interventions to improve communication outcomes and eventually increase self-care efficacy to relieve psychological distress among patients with GI cancers.
Florid Foreign Body-type Giant Cell Response to Keratin Is Associated With Improved Overall Survival in Patients Receiving Preoperative Therapy for Esophageal Squamous Cell Carcinoma
Authors: Chen Wei , Zhao Lei , Agoston Agoston , White Abby , Mazzola Emanuele , Boyle Patrick J. , Deshpande Vikram , Hornick Jason L. , Bueno Raphael , Bass Adam J. , Enzinger Peter , Mamon Harvey , Redston Mark , Patil Deepa T.
Published: September 2021

While most resection specimens from patients with neoadjuvantly treated esophageal squamous cell carcinoma show therapy-related changes in the form of inflammation and fibrosis, others harbor a florid foreign body-type giant cell response to keratin debris. The purpose of our study was to perform a detailed clinicopathologic analysis of these histologic types of treatment responses and correlate these findings with patient outcome. Clinical and pathologic parameters from 110 esophagogastrectomies were recorded and analyzed. Two main types of histologic responses were observed: inflammatory-predominant response (59%) and florid foreign body-type giant cell response to keratin (41%). Irrespective of cG, cTNM, and amount of residual cancer, florid foreign body-type giant cell reaction was predominantly noted deep within the esophageal wall, while the inflammatory response was restricted to the mucosa, submucosa, and inner half of muscularis propria. Patients with foreign body-type giant cell response showed significantly better overall survival compared with the inflammatory response group (log-rank test P=0.015). Florid foreign body-type giant cell response was the only factor associated with improved survival in a multivariable analysis for overall survival (hazard ratio=0.5; 95% confidence interval=0.3-1.0; P=0.038), but not in the model for disease-specific survival, whereas ypTNM stage II was the only significant risk factor for disease-specific survival in multivariable analysis (hazard ratio=3.4; 95% confidence interval=1.0-11.2; P=0.047). Our results suggest that in addition to the College of American Pathologists Tumor Regression Score and ypTNM stage, subtype of histologic response to therapy may represent another prognostic marker for neoadjuvantly treated esophageal squamous cell carcinoma.
Stress and Resilience Among Healthcare Workers During the COVID-19 Pandemic
Authors: Liljestrand Rebecca , Martin Sarah
Published: September 2021

The COVID-19 pandemic has caused a significant increase in stress for frontline healthcare workers, including rehabilitation workers. Contributing factors include disrupted workflows, heavier workloads, increased time restraints, and fear of contracting/passing the virus. Prolonged high stress levels can produce adverse health outcomes when unaddressed. Resilience can mitigate the negative effects of prolonged stress. Four healthcare workers relate their experiences from the frontlines of the pandemic, discussing their strategies to build resilience and maintain health. Highlighted strategies include mindfulness (the purposeful act of paying attention to the present moment without judgment), gratitude (the practice of being grateful for the positive things in life), self-care (the maintenance of a healthy lifestyle using physical, psychological, and emotional tools), and social support (the sense of belonging that comes from being cared for and valued). These strategies reduce negative outcomes produced by elevated stress levels and promote resilience in frontline healthcare workers.
Choledochoduodenostomy Versus Hepaticogastrostomy in Endoscopic Ultrasound-guided Drainage for Malignant Biliary Obstruction: A Meta-analysis and Systematic Review
Authors: Mao Kejie , Hu Binbin , Sun Feng , Wan Kaiming
Published: September 2021

Objectives:

This study aimed to estimate the safety and efficacy of endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) and endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) for malignant biliary obstruction.

Methods:

We conducted a literature search using PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. Studies that compared EUS-CDS and EUS-HGS were included in this study.

Results:

Thirteen studies were eligible for inclusion. The technical [odds ratio (OR): 0.95; 95% confidence interval (CI): 0.51-1.74) and clinical (OR: 1.13; 95%CI: 0.66-1.94) success rates of EUS-CDS were comparable to those of EUS-HGS. However, EUS-CDS had less reintervention (OR: 0.31; 95%CI: 0.16-0.63) and stent obstruction (OR: 0.48; 95%CI: 0.21-0.94) than EUS-HGS. Both groups had similar adverse events (OR: 1.00; 95%CI: 0.70-1.43) and overall survival (hazard ratio: 1.07; 95%CI: 0.58-1.97).

Conclusions:

EUS-CDS and EUS-HGS have comparable technical and clinical success rates, adverse events, and overall survival. However, EUS-CDS has less reintervention and stent obstruction.
Eco-friendly fluorimetric approaches for the simultaneous estimation of the co-administered ternary mixture: etoposide, moxifloxacin and nalbuphine
Authors: Tolba M. M. , Belal F. , Salim M. M.
Published: September 2021

Antineoplastic drugs, etoposide (ETO), are widely used in leukaemia. A patient with leukaemia has a relative infection with pneumonia treated by fluoroquinolones as moxifloxacin HCL (MOX). Because opioid analgesic as nalbuphine HCL (NAL) does not have a ceiling dose, it is used to manage the distasteful sensory in leukaemia. Consequently, green methods for synchronous spectrofluorimetric quantification of a ternary mixture of ETO, MOX and NAL were developed. Thefirst approachrelies simply on the estimation of MOX at 371 nm by conventional synchronous fluorimetric technique (Δλof 60 nm). Thesecond approachdepends on applying the first derivative synchronous fluorimetric technique (Δλof 60 nm) for simultaneous estimation of ETO and NAL at 257 and 273 nm, respectively. A good linear correlation was obtained in the ranges of 0.04–0.40, 0.10–1.00 and 0.50–5.00 µg ml−1for MOX, ETO and NAL, respectively. Moreover, the proposed approaches were successfully applied for the estimation of the studied drugs in the pharmaceutical dosage forms. Additionally, the synchronous assessment of ETO, MOX and NAL in the spiked human urine was successfully attained by the facile protein precipitation technique. The mean % recoveries in spiked human urine were 99.49, 98.07 and 98.48 for MOX, ETO and NAL, respectively.
Decreased Immune Response to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases Treated with Anti TNFα
Authors: Edelman-Klapper Hadar , Zittan Eran , Shitrit Ariella Bar-Gil , Rabinowitz Keren Masha , Goren Idan , Avni-Biron Irit , Ollech Jacob E. , Lichtenstein Lev , Banai-Eran Hagar , Yanai Henit , Snir Yifat , Pauker Maor H. , Friedenberg Adi , Levy-Barda Adva , Segal Arie , Broitman Yelena , Maoz Eran , Ovadia Baruch , Golan Maya Aharoni , Shachar Eyal , Ben-Horin Shomron , Perets Tsachi-Tsadok , Eliakim Rami , Goren Sophy , Navon Michal , Krugliak Noy , Werbner Michal , Alter Joel , Dessau Moshe , Gal-Tanamy Meital , Freund Natalia T. , Cohen Dani , Dotan Iris
Published: August 2021

Background

Patients with inflammatory bowel diseases (IBD), specifically those treated with anti-tumor necrosis factor (TNF)α biologics are at high risk for vaccine preventable infections. Their ability to mount adequate vaccine responses is unclear.

Aim

to assess immune responses to mRNA-COVID-19 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared to healthy controls (HC).

Methods

Prospective, controlled, multi-center Israeli study. Subjects enrolled received two BNT162b2 (Pfizer/BioNTech) doses. Anti-spike (S) antibodies levels and functional activity, anti-TNFα levels and adverse events (AEs) were detected longitudinaly.

Results

Overall 258 subjects: 185 IBD (67 treated with anti-TNFα), and 73 HC. After the first vaccine dose all HC were seropositive, while some patients with IBD, regardless of treatment, remained seronegative. After the second dose all subjects were seropositive, however anti-S levels were significantly lower in anti-TNFα treated compared to untreated patients, and HC (p<0.001; p<0.001, respectively). Neutralizing and inhibitory functions were both lower in anti-TNFα treated compared to untreated patients, and HC (p<0.03; p<0.0001, respectively). Anti-TNFα drug levels and vaccine responses did not affect anti-S levels. Infection rate (∼2%) and AEs were comparable in all groups. IBD activity did not change in response to BNT162b2.

Conclusions

In this prospective study in patients with IBD stratified according to treatment all patients mounted an immune response to two doses of BNT162b2. However, its magnitude was significantly lower in patients treated with anti-TNFα, regardless of administration timing and drug levels. Vaccine was safe. As vaccine immune response longevity in this group may be limited, vaccine booster dose should be considered.
Community-Based Culturally Tailored Education Programs for Black Adults with Cardiovascular Disease, Diabetes, Hypertension, and Stroke: A Systematic Review Protocol
Authors: Fulton Joseph Hawkins , Singh Hardeep , Pakkal Oya , Uleryk Elizabeth M , Nelson Michelle LA
Published: August 2021

Background

Chronic conditions and stroke disproportionately affect Black adults in communities all around the world due patterns of systemic racism, disparities in care, and lack of resources. To address unequal care received by Black communities, a shift to community-based programs that deliver culturally-tailored programs to meet the needs of the communities they serve, including Black adults who tend to have reduced access to postacute services, may give an alternative to a healthcare model which reinforces health inequities. However, community-based culturally-tailored programs (CBCT) are relatively understudied but show promise to improve the delivery of services to marginalized communities. The objectives of this review are to: (i) determine key program characteristics and outcomes of CBCT programs that are designed to improve health outcomes in Black adults with cardiovascular disease, hypertension, diabetes, or stroke and (ii) identify which of the five categories of culturally appropriate programs from Kreuter and colleagues have been used to implement CBCT programs.

Methods

This is a protocol for a systematic review that will search MEDLINE, EMBASE, and CINAHL databases to identify community-based culturally-tailored programs for Black adults with cardiovascular disease, hypertension, diabetes, or stroke.

Discussion

Health inequities have disproportionately impacted Black communities and will continue to persist if adjustments are not prioritized within healthcare to provide services, care, and programs meant to address the specific barriers to better health experienced. Many interventions meant to improve the health outcomes of marginalized groups are created with little input from target communities, leading to interventions that may not address the specific barriers contributing to poor health outcomes and are designed and implemented from an outsider’s perspective. The inclusion of community members allows for a deeper understanding of the issues facing the community and provides an opportunity to incorporate cultural values to potentially increase the efficacy, tailoring the intervention to distinct communities. An alternative to current healthcare interventions must be explored to reduce the health gap experienced by Black adults.

Trial registration

PROSPERO CRD42021245772
How soon should patients be eligible for differentiated service delivery models for antiretroviral treatment? Evidence from Zambia
Authors: Jamieson Lise , Rosen Sydney , Phiri Bevis , Grimsrud Anna , Mwansa Muya , Shakwelele Hilda , Haimbe Prudence , Mwenechanya Mpande M , Lumano-Mulenga Priscilla , Chimboma Innocent , Nichols Brooke E
Published: August 2021

Introduction

Attrition from HIV treatment is high during patients’ first 6 months after antiretroviral therapy (ART) initiation and patients with less than 6 months on ART are systematically excluded from most differentiated service delivery (DSD) models, which are intended to reduce attrition. Despite eligibility criteria requiring greater than 6 months on ART, some patients enroll earlier. Using routinely-collected medical record data in Zambia, we compared loss to follow-up (LTFU) among patients enrolling in DSD models early (<6 months on ART) to LTFU among those who enrolled according to guidelines (≥6 months on ART) in order to assess whether the ART experience eligibility criterion is necessary.

Methods

We extracted data from electronic medical records for adults (≥15 years) who initiated ART between 01/01/2019 and 31/12/2019 and evaluated LTFU, defined as >90 days late for last scheduled medication pickup, at 18 months for “early enrollers” (DSD enrolment after <6 months on ART) and “established enrollers” (DSD enrolment after ≥6 months on ART). We used a log-binomial model to compare LTFU risk between groups, adjusting for age, sex, urban/rural status, ART refill interval and DSD model.

Results

For 6,340 early enrollers and 25,857 established enrollers there were no important differences between the groups in sex (61% female), age (median 37 years), or setting (65% urban). ART refill intervals were longer for established vs early enrollers (72% vs 55% were given 4–6-month refills). LTFU at 18 months was 3% (192/6,340) for early enrollers and 5% (24,646/25,857) for established enrollers. Early enrollers were 41% less likely to be LTFU than established patients (adjusted risk ratio [95% confidence interval] 0.59 [0.50-0.68]).

Conclusions

Patients enrolled in DSD models in Zambia with < 6 months on ART were more likely to be retained in care than patients referred after they were established on ART. A limitation of the analysis is that early enrollers may have been selected for DSD participation due to providers’ and patients’ expectations about future retention. Offering DSD model entry to at least some ART patients <6 months after ART initiation may help address high attrition during the early treatment period.
Cognitive functioning in anxiety and depression: Results from the ALSPAC cohort
Authors: Suddell Steph , Mahedy Liam , Skirrow Caroline , Penton-Voak Ian S. , Munafò Marcus R. , Wootton Robyn E.
Published: August 2021

Background

Understanding the nature of cognitive deficits in anxiety and depression may identify intervention targets and help prevent functional decline. This study used observational and genetic methods to investigate the association of anxiety and depression with emotion recognition, response inhibition, and working memory, in young adulthood.

Methods

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a large prospective birth cohort study. Participants completed regular postal questionnaires and in-clinic assessments, starting from September 6, 1990. Data collection is ongoing. Linear regression was used to assess 1) cross-sectional associations between anxiety, depression, and cognition at age 24 (n = 2,187) and 2) prospective associations between anxiety and depression at age 18 and cognition at age 24 (n = 1,855). Mendelian randomization analyses were conducted to assess causal pathways between anxiety, depression, and cognition.

Results

Primary analyses were conducted on 3,087 participants following multiple imputation. There was evidence for anxiety being associated with a decreased recognition of happiness (b = -0.27, 95% CI -0.54 to 0.01, p = .045), and depression being associated with an increased recognition of sadness (b = 0.35, 95% CI 0.07 to 0.64, p = .016). Anxiety was negatively associated with working memory (b = -0.14, 95% CI -0.24 to 0.04, p = .005), but no association was found for depression (b = 0.06, 95% CI -0.05 to 0.16, p = .284). There was no evidence for any association with response inhibition. Results from Mendelian randomization analyses were inconclusive, likely due to low statistical power.

Conclusions

There was little evidence that anxiety and depression are associated with significant impairments in executive functioning. However, both anxiety and depression were associated with altered emotion recognition. This may inform the development of interventions that target psychosocial functioning.
Microenvironmental correlates of immune checkpoint inhibitor response in human melanoma brain metastases revealed by T cell receptor and single-cell RNA sequencing
Authors: Alvarez-Breckenridge Christopher A. , Markson Samuel C. , Stocking Jackson H. , Nayyar Naema , Lastrapes Matthew , Strickland Matthew R. , Kim Albert E. , de Sauvage Magali , Dahal Ashish , Larson Juliana M , Mora Joana L. , Navia Andrew W. , Kuter Benjamin M. , Gill Corey M. , Bertalan Mia Solana , Shaw Brian , Kaplan Alexander , Subramanian Megha , Jain Aarushi , Kumar Swaminathan , Danish Husain , White Michael , Shahid Osmaan , Pauken Kristen E. , Miller Brian C. , Frederick Dennie T. , Herbert Christine , Shaw McKenzie , Martinez-Lage Maria , Frosch Matthew P. , Wang Nancy , Gerstner Elizabeth R. , Nahed Brian V. , Curry William T. , Carter Bob S. , Cahill Daniel P. , Boland Genevieve Marie , Izar Benjamin , Davies Michael , Sharpe Arlene , Suvà Mario L. , Sullivan Ryan J. , Brastianos Priscilla K. , Carter Scott L.
Published: August 2021

Melanoma-derived brain metastases (MBM) represent an unmet clinical need due to central nervous system (CNS) progression as a frequent, end-stage site of disease. Immune checkpoint inhibition (ICI) represents a clinical opportunity against MBM; however, the MBM tumor microenvironment (TME) has not been fully elucidated in the context of ICI. To dissect unique MBM-TME elements and correlates of MBM-ICI response, we collected 32 fresh MBM and performed single cell RNA sequencing of the MBM-TME and T cell receptor clonotyping on T cells from MBM and matched blood and extracranial lesions. We observed myeloid phenotypic heterogeneity, most notably multiple distinct neutrophil states including an IL-8 expressing population that correlated with malignant cell epithelial-to-mesenchymal transition. Additionally, we observe significant relationships between intracranial T cell phenotypes and the distribution of T cell clonotypes intracranially and peripherally. We found that the phenotype, clonotype, and overall number of MBM-infiltrating T cells were associated with response to ICI, suggesting that ICI-responsive MBMs interact with peripheral blood in a manner similar to extracranial lesions. These data demonstrate unique features of the MBM-TME, which may represent potential targets to improve clinical outcomes for patients with MBM.
Fiscore Package: Effective Protein Structural Data Visualisation and Exploration
Authors: Kanapeckaite Auste
Published: August 2021

The lack of bioinformatics tools to quickly assess protein conformational and topological features motivated to create an integrative and user-friendly R package. Moreover, the Fiscore package implements a pipeline for Gaussian mixture modelling making such machine learning methods readily accessible to non-experts. This is especially important since probabilistic machine learning techniques can help with a better interpretation of complex biological phenomena when it is necessary to elucidate various structural features that might play a role in protein function. Thus, Fiscore builds on the mathematical formulation of protein physicochemical properties that can aid in drug discovery, target evaluation, or relational database building. In addition, the package provides interactive environments to explore various features of interest. Finally, one of the goals of this package was to engage structural bioinformaticians and develop more robust R tools that could help researchers not necessarily specialising in this field. Package Fiscore (v.0.1.3) is distributed via CRAN and Github.
Synergistic Enzyme Mixtures to Realize Near-Complete Depolymerization in Biodegradable Polymer/Additive Blends
Authors: DelRe Christopher , Chang Boyce , Jayapurna Ivan , Hall Aaron , Wang Ariel , Zolkin Kyle , Xu Ting
Published: August 2021

Embedding catalysts inside of plastics affords accelerated chemical modification with programmable latency and pathways. Nanoscopically embedded enzymes can lead to near complete degradation of polyesters via chain-end mediated processive depolymerization. The overall degradation rate and pathways have a strong dependence on the morphology of semi-crystalline polyesters. Yet, most studies to date focus on pristine polymers instead of mixtures with additives and other components despite their nearly universal uses in plastic production. Here, additives are introduced to purposely change the morphology of polycaprolactone (PCL) by increasing the bending and twisting of crystalline lamellae. These morphological changes immobilize chain-ends preferentially at the crystalline/amorphous interfaces and limit chain-end accessibility by the embedded processive enzyme. This chain end redistribution reduces the polymer-to-monomer conversion from >95% to less than 50%, causing formation of highly crystalline plastic pieces including microplastics. By synergizing both random chain scission and processive depolymerization, it is feasible to navigate morphological changes in polymer/additive blends and to achieve near complete depolymerization. The random scission enzymes in the amorphous domains create new chain ends that are subsequently bound and depolymerized by processive enzymes. Present studies further highlight the importance to consider host polymer morphological effects on the reactions catalyzed by embedded catalytic species.
Biological research in Papua New Guinea: a publication activity analysis
Authors: Novotny Vojtech , Toko Pagi
Published: August 2021

The Nature Index and the Web of Science databases are used to analyse the publication patterns in life sciences in Papua New Guinea, aiming to identify the ways of improving the country’s research output.
Amphetamine alters an EEG marker of reward processing in humans and mice
Authors: Cavanagh James F. , Olguin Sarah , Talledo Jo A , Kotz Juliana E. , Roberts Benjamin Z. , Nungaray John A , Sprock Joyce , Gregg David , Bhakta Savita G. , Light Gregory A. , Swerdlow Neal R. , Young Jared W. , Brigman Jonathan L.
Published: August 2021

The bench-to-bedside development of pro-cognitive therapeutics for psychiatric disorders has been mired by translational failures. This is in part due to the absence of pharmacologically-sensitive cognitive biomarkers common to humans and rodents. Here, we describe a cross-species translational marker of reward processing that is sensitive to the dopamine agonist, d-amphetamine. Motivated by human electroencephalographic (EEG) findings, we recently reported that frontal midline delta-band power is also an electrophysiological biomarker of reward surprise in mice. In the current series of experiments, we determined the impact of parametric doses of d-amphetamine on this reward-related EEG response from humans (n=23) and mice (n=28) performing a probabilistic learning task. In humans, d-amphetamine (placebo, 10 mg, 20 mg) boosted the Reward Positivity event-related potential (ERP) component as well as the spectral delta-band representations of this signal. In mice, d-amphetamine (placebo, 0.1 mg/kg, 0.3 mg/kg, 1.0 mg/kg) boosted both reward and punishment ERP features, yet there was no modulation of spectral activities. In sum, the present results confirm the role of dopamine in the generation of the Reward Positivity in humans, and paves the way towards a pharmacologically valid biomarker of reward sensitivity across species.
Plucking a string or playing a G? Choice type impacts human reinforcement learning
Authors: Rmus Milena , Zou Amy , Collins Anne G.E.
Published: August 2021

In reinforcement learning (RL) experiments, participants learn to make rewarding choices in response to different stimuli; RL models use outcomes to estimate stimulus-response values which change incrementally. RL models consider any response type indiscriminately, ranging from more concretely defined motor choices (e.g. pressing a key with the index finger), to more general choices that can be executed in a number of ways (e.g. getting dinner at the restaurant). But does the learning process vary as a function of the choice type? In Experiment 1, we show that it does: participants were slower and less accurate in learning correct choices of a general format compared to learning more concrete, motor actions. Using computational modeling, we show that two mechanisms contribute to this. First, there was evidence of irrelevant credit assignment: the values of motor actions interfered with the values of other choice dimensions, resulting in more incorrect choices when the correct response is not defined by a single motor action; second, information integration for relevant general choices was slower. In Experiment 2, we replicated and further extended the findings from Experiment 1, by showing that slowed learning was attributable to weaker working memory use, rather than slowed RL learning. In both experiments we ruled out the explanation that the difference in performance between two condition types was driven by difficulty/different levels of complexity. We conclude that defining a more abstract choice space used by multiple learning systems for credit assignment recruits executive resources, limiting how much such processes then contribute to fast learning.
Fractionation of neural reward processing into independent components by novel decoding principle
Authors: Xiang Shitong , Jia Tianye , Xie Chao , Zhu Zhichao , Cheng Wei , Schumann Gunter , Robbins Trevor W. , Feng Jianfeng
Published: August 2021

How to retrieve latent neurobehavioral processes from complex neurobiological signals is an important yet unresolved challenge. Here, we develop a novel approach, orthogonal-Decoding multi-Cognitive Processes (DeCoP), to reveal underlying latent neurobehavioral processing and show that its performance is superior to traditional non-orthogonal decoding in terms of both false inference and robustness. Processing value and salience information are two fundamental but mutually confounded pathways of reward reinforcement essential for decision making. During reward/punishment anticipation, we applied DeCoP to decode brain-wide responses into spatially overlapping, yet functionally independent, evaluation and readiness processes, which are modulated differentially by meso-limbic vs nigro-striatal dopamine systems. Using DeCoP, we further demonstrated that most brain regions only encoded abstract information but not the exact input, except for dACC and insula. Furthermore, our novel analytical principle could be applied generally to decode multiple latent neurobehavioral processes and thus advance both the design and hypothesis testing for cognitive tasks.
Tensor-decomposition–based unsupervised feature extraction in single-cell multiomics data analysis
Authors: Taguchi Y-h. , Turki Turki
Published: August 2021

Analysis of single-cell multiomics datasets is a novel topic and is considerably challenging because such datasets contain a large number of features with numerous missing values. In this study, we implemented a recently proposed tensor-decomposition (TD)–based unsupervised feature extraction (FE) technique to address this difficult problem. The technique can successfully integrate single-cell multiomics data composed of gene expression, DNA methylation, and accessibility. Although the last two have large dimensions, as many as ten million, containing only a few percentages of non-zero values, TD-based unsupervised FE can integrate three omics datasets without filling missing values. Together with UMAP, which is used frequently when embedding single-cell measurements into two-dimensional space, TD-based unsupervised FE can produce two-dimensional embedding coincident with classification when integrating single-cell omics datasets. Genes selected based on TD-based unsupervised FE were also significantly related to reasonable biological roles.
Brain Activation in Chronic Nonspecific Low Back Pain : A Systematic review and ALE Meta-analysis
Authors: Hazra Sandipan , Sahu Samantak , Nayak Prasun Priya , Sarkar Koushik , Srikumar V , Handa Gita
Published: August 2021

Pain, a protective mechanism turns into a pathologic response when it becomes chronic. Recent evidences are pointing towards neuroplastic brain changes as the primary factor for the persisting pain in chronic nonspecific low back pain (cLBP). To summarise the previous fMRI studies, a coordinate-based ALE meta-analysis of resting functional brain imaging studies is carried out to identify the clusters activated in the brain in cLBP.

Literature survey: ‘PubMed’, ‘Scopus’ and ‘Sleuth’ were searched for studies with resting functional whole-brain imaging in cLBP. Till October 2020; 258, 238, and 7 studies were found respectively after search. The activity pattern was documented in ‘without stimulation’ and ‘with stimulation’ groups. The risk of bias was assessed by Joanna Briggs Institute critical appraisal checklist for analytical cross-section studies. Total seven (224 cLBP patients, 110 activation foci) and six studies (106 cLBP patients, 66 activation foci) were selected among 277 studies for metanalysis in the ‘without stimulation’ and ‘with stimulation’ group respectively. In the ‘without stimulation’ group 8 statistically significant clusters were found. The clusters are distributed in the prefrontal cortex, primary somatosensory cortex, and primary motor cortex, anterior cingulate cortex, insular cortex, putamen, claustrum, amygdala, and associated white matters in both hemispheres. On the other group, 3 statistically significant clusters were found in the frontal cortex, Parietal cortex, and Insula. In the ‘with stimulation’ group, significant lateralization was observed and most of the clusters were in the right hemisphere. The white matter involvement was more in the ‘with stimulation’ group (78.62% Vs 38.21%). The statistically significant clusters found in this study indicate a probable imbalance in GABAergic modulation of brain circuit and dysfunction in descending pain modulation system. This disparity in pain neuro-matrix is the source of spontaneous and persisting pain in cLBP.
Best templates outperform homology models in predicting the impact of mutations on protein stability
Authors: Pak Marina A. , Ivankov Dmitry N.
Published: August 2021

Motivation

Prediction of protein stability change upon mutation (ΔΔG) is crucial for facilitating protein engineering and understanding of protein folding principles. Robust prediction of protein folding free energy change requires the knowledge of protein three-dimensional (3D) structure. Unfortunately, protein 3D structure is not always available. In this case, one can still predict the protein stability change by constructing a homology model of the protein; however, the accuracy of homology model-based ΔΔG predictions is unknown. The perspectives of using 3D structures of the best templates are also unclear.

Results

To investigate these questions, we used the most popular and accurate publicly available tools: FoldX for stability change prediction and I-Tasser for homology modeling. We found that both homology models and best templates worsen the ΔΔG prediction, with best templates performing 1.5 times better than homology models. For AlphaFold models, we also found that the best templates seem to outperform protein models. Our findings imply using the 3D structures of the best templates for ΔΔG prediction if the 3D protein structure is unavailable.

Contact

d.ivankov@skoltech.ru
Oral Glucosamine Ameliorates Aggravated Neurological Phenotype in Mucopolysaccharidosis III Type C Mouse Model Expressing Misfolded HGSNAT Variant
Authors: Pan Xuefang , Taherzadeh Mahsa , Bose Poulomee , Heon-Roberts Rachel , Nguyen Annie L. A. , Xu TianMeng , Pará Camila , Yamanaka Yojiro , Priestman David A. , Platt Frances M. , Khan Shaukat , Fnu Nidhi , Tomatsu Shunji , Morales Carlos R. , Pshezhetsky Alexey V.
Published: August 2021

Objective

Over 55% of mucopolysaccharidosis IIIC (MPS IIIC) patients have at least one allelic missense variant responsible for misfolding of heparan sulfate acetyl-CoA:α-glucosaminide N- acetyltransferase (HGSNAT). These variants are potentially treatable with pharmacological chaperones, such as a competitive HGSNAT inhibitor, glucosamine. Since the constitutive HGSNAT knockout mice, we generated previously cannot be used to test such strategyin vivo,we generated a novel model, theHgsnatP304Lstrain, expressing misfolded mutant HGSNAT with human missense mutation Pro311Leu (Pro304Leu in the mouse enzyme).

Results

HgsnatP304Lmice present deficits in short-term (novel object recognition test) and working/spatial (Y-maze test) memory at 4 months of age, 2-4 months earlier than previously described gene-targetedHgsnat-Geomice, which lack HGSNAT protein.HgsnatP304Lmice also show increased severity of synaptic deficits in CA1 neurons, and accelerated course of CNS pathology including neuronal storage of heparan sulfate, accumulation of misfolded proteins, increase of simple gangliosides, and neuroinflammation as compared withHgsnat-Geomice. Expression of misfolded human Pro311Leu HGSNAT protein in cultured hippocampalHgsnat- Geoneurons aggravated reduction of synaptic proteins. Memory deficits and majority of pathological changes in the brain were rescued in mice receiving daily doses of oral glucosamine.

Interpretation

Altogether, our data for the first time demonstrate dominant-negative effects of the misfolded HGSNAT Pro304Leu variant and show that these effects are treatable by oral administration of glucosamine, suggesting that patients, affected with missense mutations preventing normal folding of the enzyme, could benefit from chaperone therapy.
Hi-C-LSTM: Learning representations of chromatin contacts using a recurrent neural network identifies genomic drivers of conformation
Authors: Dsouza Kevin B. , Maslova Alexandra , Al-Jibury Ediem , Merkenschlager Matthias , Bhargava Vijay K. , Libbrecht Maxwell W.
Published: August 2021

Despite the availability of chromatin conformation capture experiments, understanding the relationship between regulatory elements and conformation remains a challenge. We propose Hi-C-LSTM, a method that produces low-dimensional latent representations that summarize intra-chromosomal Hi-C contacts via a recurrent long short-term memory (LSTM) neural network model. We find that these representations contain all the information needed to recreate the original Hi-C matrix with high accuracy, outperforming existing methods. These representations enable the identification of a variety of conformation-defining genomic elements, including nuclear compartments and conformation-related transcription factors. They furthermore enable in-silico perturbation experiments that measure the influence of cis-regulatory elements on conformation.
The Practical Haplotype Graph, a platform for storing and using pangenomes for imputation
Authors: Bradbury PJ , Casstevens T , Jensen SE , Johnson LC , Miller ZR , Monier B , Romay MC , Song B , Buckler ES
Published: August 2021

Motivation

Pangenomes provide novel insights for population and quantitative genetics, genomics, and breeding not available from studying a single reference genome. Instead, a species is better represented by a pangenome or collection of genomes. Unfortunately, managing and using pangenomes for genomically diverse species is computationally and practically challenging. We developed a trellis graph representation anchored to the reference genome that represents most pangenomes well and can be used to impute complete genomes from low density sequence or variant data.

Results

The Practical Haplotype Graph (PHG) is a pangenome pipeline, database (PostGRES & SQLite), data model (Java, Kotlin, or R), and Breeding API (BrAPI) web service. The PHG has already been able to accurately represent diversity in four major crops including maize, one of the most genomically diverse species, with up to 1000-fold data compression. Using simulated data, we show that, at even 0.1X coverage, with appropriate reads and sequence alignment, imputation results in extremely accurate haplotype reconstruction. The PHG is a platform and environment for the understanding and application of genomic diversity.

Availability

All resources listed here are freely available. The PHG Docker used to generate the simulation results ishttps://hub.docker.com/as maizegenetics/phg:0.0.27. PHG source code is athttps://bitbucket.org/bucklerlab/practicalhaplotypegraph/src/master/. The code used for the analysis of simulated data is athttps://bitbucket.org/bucklerlab/phg-manuscript/src/master/. The PHG database of NAM parent haplotypes is in the CyVerse data store (https://de.cyverse.org/de/) and named /iplant/home/shared/panzea/panGenome/PHG_db_maize/phg_v5Assemblies_20200608.db.

Contact

pjb39@cornell.edu
MS-driven metabolic alterations are recapitulated in iPSC-derived astrocytes
Authors: Ghirotto Bruno , Oliveira Danyllo F. , Cipelli Marcella , Basso Paulo J. , de Lima Jean , Breda Cristiane N. S. , Ribeiro Henrique C. , Silva Camille C. C. , Hiyane Meire I. , Caldini Elia G. , Sussulini Alessandra , Kowaltowski Alicia J. , Oliveira Enedina M. L. , Zatz Mayana , Câmara Niels O. S.
Published: August 2021

Objective

Astrocytes play a significant role in the pathology of Multiple Sclerosis (MS). Nevertheless, for ethical reasons, most of the studies in these cells were performed on the Experimental Autoimmune Encephalomyelitis model. As there are significant differences between human and mouse cells, we aimed here to better characterize astrocytes from patients with MS (PwMS), focusing mainly on mitochondrial function and cell metabolism.

Methods

We obtained and characterized induced pluripotent stem cell (iPSC)-derived astrocytes from three PwMS and three unaffected controls and performed functional assays including electron microscopy, flow cytometry, cytokine measurement, gene expression, in situ respiration, and metabolomics.

Results

We detected several differences in MS astrocytes including: (i) enrichment of genes associated with mitophagy and neurodegeneration, (ii) increased mitochondrial fission and decreased mitochondrial to nuclear DNA ratio, indicating disruption of mitochondrial content, (iii) increased production of superoxide and MS-related proinflammatory chemokines, (iv) increased electron transport capacity and proton leak, in line with the increased oxidative stress, and (v) a distinct metabolic profile, with a deficiency in amino acid catabolism and increased sphingolipid metabolism, which have already been linked to MS.

Interpretation

To our knowledge, this is the first study thoroughly describing the metabolic profile of iPSC-derived astrocytes from PwMS, and validating this model as a powerful tool to study disease mechanisms and to perform non-invasive drug targeting assays in vitro. Our findings recapitulate several disease features described in patients and provide new mechanistic insights into the metabolic rewiring of astrocytes in MS, which could be targeted in future therapeutic studies.