bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of a comprehensive intervention focused on hospitalized patients with HIV by an existing stewardship program: successes and lessons learned
Authors: Roshdy Danya , McCarter Maggie , Meredith Jacqueline , Jaffa Rupal , Hammer Katie , Santevecchi Barbara , Rozario Nigel , Campbell Jamie , Leonard Michael , Polk Christopher
Published: April 2021

Background:

Several national organizations have advocated for inpatient antiretroviral stewardship to prevent the consequences of medication-related errors. This study aimed to evaluate the impact of a stewardship initiative on outcomes in people with HIV (PWH).

Methods:

A pharmacist-led audit and review of adult patients admitted with an ICD-10 code for HIV was implemented to an existing antimicrobial stewardship program. A quasi-experimental, retrospective cohort study was conducted comparing PWH admitted during pre- and post-intervention periods. Rates of antiretroviral therapy (ART)-related errors and infectious diseases (ID) consultation with linkage to care were evaluated through selection of a random sample of patients receiving ART in each period. Length of stay (LOS) and mortality were assessed by analyzing all admissions in the post-intervention period. Clinical outcomes including LOS, 30-day all-cause hospital readmission, and in-hospital and 30-day mortality in the post-intervention group were stratified by patients not on ART, on ART at admission, and started on ART as a result of the intervention.

Results:

A total of 100 patients in the pre-intervention period and 103 patients in the post-intervention period were included to assess ART-related errors and linkage to care. A reduction in errors (70.0 versus 25.7%, p < 0.001) and increased linkage to care (19.0 versus 39.6%, p < 0.01) were demonstrated. Of 389 admissions during the post-intervention period, 30-day mortality rates were similar between PWH on ART at admission and those initiated on ART during admission (5% versus 8%, respectively), but less than those not on ART (21%). A longer LOS was observed in the patients started on ART during admission (5 days if ART started during admission versus 3 days if not started during admission, p < 0.01).

Conclusions:

This interdisciplinary intervention was successful in reducing inpatient ART-related errors and increasing ID consultation with linkage to care among PWH.
A rare case of testicular mixed germ cell tumour with adrenal metastasis
Authors: Theivendrampillai Shenthiuiyan , Lockyer Richard , Wheater Matthew , Veryard Leon , King Alexander
Published: April 2021

Testicular cancer commonly affects younger men, with testicular germ cell tumours comprising the vast majority of cases. They are classified into either seminomatous or non-seminomatous germ cell tumours, with mixed germ cell tumours treated as non-seminomas.

In the following case report, we describe the clinical course and management of a 38-year-old male patient who presented with a right unilateral testicular mixed germ cell tumour, predominantly seminoma that had metastasized to the adrenal gland. This pattern of spread is indeed a rare occurrence. It also highlights the significance of the current diagnostic and management protocol and the benefits of using positron emission tomography as a diagnostic tool.

Level of evidence: 4
The vulnerability of consumers with disabilities: The benefits of taking time into account
Authors: Beudaert Anthony , Nau Jean-Philippe
Published: April 2021

In a society faced with rapid social acceleration, time is a central issue for consumers, especially when they are disabled. This qualitative research therefore proposes to study the way in which time contributes to the vulnerability of these particular consumers. To do this, we consider consumers as being caught up in different embedded, stratified temporalities that need to be synchronised. The analysis of 51 interviews conducted with people with motor or hearing impairments reveals a vulnerability fuelled by problematic individual temporal experiences and by a lack of synchronisation with the time of others and/or with the time of society. These findings contribute to the literature by shedding light on the complex articulation between individual, interpersonal and structural factors at the origin of vulnerability. Managerial recommendations are then formulated in order to help consumers reappropriate their time.
The design of Lil’Flo, a socially assistive robot for upper extremity motor assessment and rehabilitation in the community via telepresence
Authors: Sobrepera Michael J , Lee Vera G , Johnson Michelle J
Published: April 2021

Introduction

We present Lil’Flo, a socially assistive robotic telerehabilitation system for deployment in the community. As shortages in rehabilitation professionals increase, especially in rural areas, there is a growing need to deliver care in the communities where patients live, work, learn, and play. Traditional telepresence, while useful, fails to deliver the rich interactions and data needed for motor rehabilitation and assessment.

Methods

We designed Lil’Flo, targeted towards pediatric patients with cerebral palsy and brachial plexus injuries using results from prior usability studies. The system combines traditional telepresence and computer vision with a humanoid, who can play games with patients and guide them in a present and engaging way under the supervision of a remote clinician. We surveyed 13 rehabilitation clinicians in a virtual usability test to evaluate the system.

Results

The system is more portable, extensible, and cheaper than our prior iteration, with an expressive humanoid. The virtual usability testing shows that clinicians believe Lil’Flo could be deployed in rural and elder care facilities and is more capable of remote stretching, strength building, and motor assessments than traditional video only telepresence.

Conclusions

Lil’Flo represents a novel approach to delivering rehabilitation care in the community while maintaining the clinician-patient connection.
The Role of Regulatory Capital and Ownership Structure in Bank Liquidity Creation: Evidence From Emerging Asian Economies
Authors: Kayani Ghulam Mujtaba , Akhtar Yasmeen , Yiguo Chen , Yousaf Tahir , Shahzad Syed Jawad Hussain
Published: April 2021

We examine the effect of regulatory capital and ownership structure on banks’ liquidity creation in emerging Asian economies. We find a positive association between regulatory capital and bank liquidity creation, which is consistent with the risk-absorption hypothesis. Bank size has a positive relation with liquidity creation, implying that large banks have more capacity to create liquidity as they enjoy more of the safety net provided by lenders of last resort in the event of crisis, the advantage of reputational benefit, and easier access to external market funding. The negative effect of the bank funding structure is that, as the subordinate debt is typically uninsured, higher funding costs lead banks to reduce liquidity creation. The results imply that an increase in interest rates worsens liquidity creation. For ownership structure, the results show the significance of the impact of ownership concentration on liquidity creation. Banking institutions having higher equity and higher concentration ownership leads to improved liquidity creation.
To We or Not to We: Corpus-Based Research on First-Person Pronoun Use in Abstracts and Conclusions
Authors: Wang Shih-ping , Tseng Wen-Ta , Johanson Robert
Published: April 2021

A growing trend exists for authors to employ a more informal writing style that uses “we” in academic writing to acknowledge one’s stance and engagement. However, few studies have compared the ways in which the first-person pronoun “we” is used in the abstracts and conclusions of empirical papers. To address this lacuna in the literature, this study conducted a systematic corpus analysis of the use of “we” in the abstracts and conclusions of 400 articles collected from eight leading electrical and electronic (EE) engineering journals. The abstracts and conclusions were extracted to form two subcorpora, and an integrated framework was applied to analyze and seek to explain how we-clusters and we-collocations were employed. Results revealed whether authors’ use of first-person pronouns partially depends on a journal policy. The trend of using “we” showed that a yearly increase occurred in the frequency of “we” in EE journal papers, as well as the existence of three “we-use” types in the article conclusions and abstracts: exclusive, inclusive, and ambiguous. Other possible “we-use” alternatives such as “I” and other personal pronouns were used very rarely—if at all—in either section. These findings also suggest that the present tense was used more in article abstracts, but the present perfect tense was the most preferred tense in article conclusions. Both research and pedagogical implications are proffered and critically discussed.
Can Higher Education Ameliorate Racial/Ethnic Disadvantage? An Analysis of the Wage Assimilation of College-Educated Hispanic Americans
Authors: Wang Sharron Xuanren , Sakamoto Arthur
Published: April 2021

Hispanics are the largest minority group in the United States, but quantitative research on the various components of this population has not received extensive investigation. College-educated Hispanics have been particularly neglected due to exaggerated and negative stereotypes. This present study uses data from the 2010 National Survey of College Graduates to investigate wage attainments among college-educated Hispanics. Hispanic Americans are categorized based on their place of birth and age in which they entered the U.S. education system. Results indicate that native-born and foreign-born Hispanic women who have at least a college degree have reached approximate wage parity with comparable native-born non-Hispanic White women. By contrast, native-born Hispanic men face a 10% wage penalty relative to comparable native-born non-Hispanic White men. In addition, foreign-born Hispanic men who immigrated as adults and obtained their college degree outside of the United States face larger wage penalties that are augmented by a lack of citizenship. Theoretical and empirical implications are discussed.
Coordinated Interactions of Sustainable Urbanization Dimensions: Case Study in Hunan, China
Authors: Geng Yuqing , Zhang Han
Published: April 2021

Within the sustainable urbanization framework, two dimensions, namely, social urbanization and environmental urbanization, have complex coordinated interactions. To better understand the coordinated interaction status between the two dimensions of sustainable urbanization, an empirical study was carried out in the 14 cities of Hunan Province, China, from 2011 to 2019. This study establishes an integrated measurement framework, uses the coupling coordination degree model, information entropy weight analysis approach, and the Technique for Order Preference by Similarity to an Ideal Solution method to analyze the development degrees and coordinated interaction degrees of the two dimensions. The results show that the quality and efficiency of leisure facilities and water use have the greatest impacts on the coordinated interactions between the two dimensions. Besides, the development degrees of social urbanization and environmental urbanization are not consistent. What is more, the spatial noncorrelation of the coordinated interaction status demonstrates that the “high-quality development” tactics aiming to promote balanced development of dimensions among cities in China is feasible. Furthermore, corresponding suggestions are proposed, providing references for governments’ planning and decision-making processes.
Effect of human articular chondroprogenitor derived conditioned media on chondrogenic potential of bone marrow derived mesenchymal stromal cells
Authors: Vinod Elizabeth , Padmaja Kawin , Kachroo Upasana
Published: April 2021

Background:

Current research in cartilage repair is focusing on the use of soluble factors released by cells during expansion, either as stand-alone therapy or as conditioned media (CM) supplements to optimize cellular phenotype for in-vivo transplantation. The present study aimed at utilizing spent media from cultured human articular cartilage derived chondroprogenitors and assessing their influence on bone marrow mesenchymal stem cell (BM-MSC) growth and phenotype.

Methodology:

CM was collected from passage 2 chondroprogenitors and evaluated for latent TGFβ1 levels. Passage 3 BM-MSCs were divided into two groups and cultured with either a) standard expansion medium (EM-group) or b) EM supplemented with 50% CM (CCM-group). At sub-confluence both groups were assessed for population doubling, migration assay, cell surface markers, gene expression for chondrogenic and hypertrophy markers. Additionally, pellet cultures were subjected to chondrogenic differentiation and analyzed by Alcian blue stain.

Results:

On analysis of proliferation and migration, CCM-group showed comparable results to EM in terms of population doubling and cell movement toward scratched area. Similarly, use of spent medium did not affect the surface protein or gene expression profile of BM-MSCs with similar flow cytometric and mRNA results seen in both groups. Glycosaminoglycan deposition (Alcian blue) was seen in the CCM-group, comparable to the EM-group.

Conclusion:

This preliminary report provided valuable information on the influence of unfractionated CCM on BM-MSC characteristics which may be further optimized for cartilage regeneration by the use of purified components such as exosomes, micro-vesicles, and concentrated trophic factors in future.
Mediating Role of Job Satisfaction on Turnover Intentions and Job Mismatch Among Millennial Employees in Bengaluru
Authors: Chavadi Chandan A. , Sirothiya Monika , M R Vishwanatha
Published: April 2021

The millennials have become the largest cohort in the workforce, and their retention has become challenging for policymakers and organizations. Millennials are career-oriented and are ready to switch jobs if there is a mismatch in skills and job requirement. The purpose of this study is to investigate the mediating role of job satisfaction on turnover intention and job mismatch among millennial employees in Bengaluru. The study consists of 247 millennial employees from different industries of Bengaluru. Statistical tools such as SPSS 20, AMOS 20, and Sobel-Z test have been used for analysis. It is found from our research study that job mismatch is having a positive relationship with turnover intention, while job satisfaction is having a negative relationship with turnover intention. The relation between job mismatch and job satisfaction is negative. The findings demonstrated that job satisfaction partially mediated the relationships between job mismatch and turnover intentions. It was concluded from the study that millennials consider personal growth as the major factor, which influences their job satisfaction. This study is of practical importance as it impacts organizational practices (specifically human resource management practices).
Patient-Reported Outcome Measurements (PROMs) After Discharge From the Emergency Department: A Cross-Sectional Study
Authors: Menditto Vincenzo G , Maraldo Antonello , Barbadoro Pamela , Maccaroni Roberto , Salvi Aldo , D’Errico Marcello M , Marasca Stefano
Published: April 2021

Background:

The purpose of a patient-reported outcome (PRO) is to elicit the perspectives of patients and translate them into a reliable measurement questionnaire.

Objectives:

The objective of this cross-sectional study was to detect a set of PROs and PRO measurements (PROMs) about patients with isolated trauma of the limbs receiving emergency department (ED) care.

Methods:

A survey was performed in the ED using a questionnaire among the enrolled patients to identify which proposed outcomes were perceived as important by the patients according to their expectations.

Results:

Ninety-six consecutive patients were conveniently enrolled. For each item of the questionnaire, the percentage of patients who agreed to perceive it important were calculated. Three items were perceived important by almost 85% of the patients: getting an x-ray (91%; 95% CI: 88%-98%), obtaining a written therapy (94%; 95% CI: 87%-97%), and feeling the physicians’ and nurses’ empathy (97%; 95% CI: 91%-99%). The ED system was able to satisfy 2 of the 3 agreed PROs in at least 85% of the cases: getting an x-ray (97%; 95% CI: 91%-99%) and obtaining a written therapy (97%; 95% CI: 91%-99%). Moreover, in 30/96 patients (31%; 95% CI: 22%-41%), all the PROs were satisfied, and in 75/96 patients (78%; 95% CI: 69%-85%), all agreed PROs were satisfied.

Conclusions:

Our study shows an example of core of PROs proposed by the ED physicians and agreed by the patients. Moreover, we presented a set of PROMs which could be used to measure the quality of an ED.
Efficacy and Safety Considerations With Second-Generation Antipsychotics as Adjunctive Analgesics: A Review of Literature
Authors: Coronado Belinda , Dunn Jacob , Veronin Michael A. , Reinert Justin P.
Published: April 2021

Objective: To determine the efficacy and safety of second-generation antipsychotics (SGAs) as adjunctive analgesics. Data Sources: A comprehensive literature review was conducted between August 2020 and January 2021 on PubMed, Scopus, and ProQuest Central. Study Selection and Data Extraction: Keyword and Boolean phrase searches using the following terminology were conducted: “Quetiapine” OR “Risperidone” OR “Olanzapine” OR “Ziprasidone” AND “Analgesia” NOT “Psychosis” NOT “Psych.” Articles that involved human adult patients who received any of the SGAs mentioned in the searching filter with an opioid were included. Articles that described pediatrics, pregnant women, patients who received any of these agents for treatment of psychosis and articles that were not in English, or readily translatable to English, were excluded. Data Synthesis: Three articles were selected for inclusion in this review, with 2 articles detailing reports with olanzapine and 1 article describing a randomized, controlled trial with extended-release quetiapine. Both olanzapine and quetiapine were able to decrease pain scores on the numeric rating scale, indicating a reduction pain experienced, and additionally reduced opioid craving behavior in patients. Depression scores and quality-of-life indicators improved with quetiapine, though those metrics were not studied with olanzapine. Conclusions: Select SGAs, specifically extended-release quetiapine and olanzapine, may serve as an appropriate adjunctive analgesic choice in select patients. Further research is required in a clinical setting to determine the exact role of this drug class in pain management.
SAPHYR: Swiss Atlas of Physical Properties of Rocks: the continental crust in a database
Authors: Zappone Alba , Kissling Eduard
Published: April 2021

The Swiss Atlas of Physical Properties of Rocks (SAPHYR) project aims at centralize, uniform, and digitize dispersed and often hardly accessible laboratory data on physical properties of rocks from Switzerland and surrounding regions. The goal of SAPHYR is to make the quality-controlled and homogenized data digitally accessible to an open public, including industrial, engineering, land and resource planning companies as well as governmental and academic institutions, or simply common people interested in rock physics. The physical properties, derived from pre-existing literature or newly measured, are density, porosity and permeability as well as seismic, magnetic, thermal and electrical properties. The data were collected on samples either from outcrops or from tunnels and boreholes. At present, data from literature have been collected extensively for density, porosity, seismic and thermal properties. In the past years, effort has been placed especially on collecting samples and measuring the physical properties of rock types that were poorly documented in literature. A workflow for quality control on reliability and completeness of the data was established. We made the attempt to quantify the variability and the uncertainty of the data. The database has been recently transferred to the Federal Office of Topography swisstopo with the aim to develop the necessary tools to query the database and open it to the public. Laboratory measurements are continuously collected, therefore the database is ongoing and in continuous development. The spatial distribution of the physical properties can be visualized as maps using simple GIS tools. Here the distribution of bulk density and velocity at room conditions are presented as examples of data representation; the methodology to produce these maps is described in detail. Moreover we also present an exemplification of the use of specific datasets, for which pressure and temperatures derivatives are available, to develop crustal models.
Genotype-driven therapeutic developments in Parkinson’s disease
Authors: Prasuhn Jannik , Brüggemann Norbert
Published: April 2021

Background

Remarkable advances have been reached in the understanding of the genetic basis of Parkinson’s disease (PD), with the identification of monogenic causes (mPD) and a plethora of gene loci leading to an increased risk for idiopathic PD. The expanding knowledge and subsequent identification of genetic contributions fosters the understanding of molecular mechanisms leading to disease development and progression. Distinct pathways involved in mitochondrial dysfunction, oxidative stress, and lysosomal function have been identified and open a unique window of opportunity for individualized treatment approaches. These genetic findings have led to an imminent progress towards pathophysiology-targeted clinical trials and potentially disease-modifying treatments in the future.

Main body of the manuscript

In this review article we will summarize known genetic contributors to the pathophysiology of Parkinson’s disease, the molecular mechanisms leading to disease development, and discuss challenges and opportunities in clinical trial designs.

Conclusions

The future success of clinical trials in PD is mainly dependent on reliable biomarker development and extensive genetic testing to identify genetic cases. Whether genotype-dependent stratification of study participants will extend the potential application of new drugs will be one major challenge in conceptualizing clinical trials. However, the latest developments in genotype-driven treatments will pave the road to individualized pathophysiology-based therapies in the future.
Rule-based classification and mapping of ecosystem services with data on the integrity of forest ecosystems
Authors: Schlutow Angela , Schröder Winfried
Published: April 2021

Background

The state of ecosystems influences their services for humans. Therefore, the European Union aims to assess and map ecosystem conditions and ecosystem services at the level of the Union and the Member States to implement maintenance or protection measures, if necessary.This paper examines the relationship between forest ecosystem conditions and ecosystem services at the national level, using Germany as an example. The aim is to create a methodology that allows users to understand and predict how the potential supply of selected ecosystem services might change over time under the influence of climate change and atmospheric nitrogen deposition, and that is reproducible, unlike previous approaches. To this end, the methodology was operationalised in a quantitative and rule-based manner.

Methods and results

The multitude of forest ecosystem types were grouped into 78 classes according to the degree of similarity of their ecological characteristics that influence the provision of ecosystem services. Thereby, ecoclimatic, soil hydrological and nutrient balance characteristics and 12 potential ecosystem service capacities were taken into account. Three potential ecosystem services were quantified for representatives of the ecosystem type classes. The ecosystem service classification was mapped for all of Germany.

Conclusions

The methodology presented enables a transparent and thus a reproducible classification of current and future ecosystem services
Correction to: Galectins from Onchocerca ochengi and O. volvulus and their immune recognition by Wistar rats, Gudali zebu cattle and human hosts
Authors: Ngwasiri Ngwafu Nancy , Brattig Norbert W. , Ndjonka Dieudonné , Liebau Eva , Paguem Archile , Leusder Dustin , Kingsley Manchang Tanyi , Eisenbarth Albert , Renz Alfons , Daniel Achukwi Mbunkah
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
COVID-19: challenges faced by Nepalese migrants living in Japan
Authors: Bhandari Divya , Kotera Yasuhiro , Ozaki Akihiko , Abeysinghe Sudeepa , Kosaka Makoto , Tanimoto Tetsuya
Published: April 2021

Background

Worldwide, COVID-19 has exacerbated the vulnerability of migrants, impacting many facets of their lives. Nepalese make up one of the largest groups of migrants residing in Japan. Crises, such as the ongoing COVID-19 pandemic could disproportionately affect migrants from low- and middle-income countries like Nepal, widening health and economic inequalities. An in-depth, comprehensive assessment is needed to appraise the diverse problems they encounter. Drawing upon qualitative interviews, this study aimed to identify challenges faced by Nepalese migrants in Japan as a consequence of the COVID-19 pandemic and to discuss their needs to counter these challenges.

Methods

This qualitative study employed an interpretivist approach to appraise the first-hand experience of Nepalese migrants living in Japan. Fourteen participants (8 males and 6 females, aged 21 to 47 years old) were recruited to participate in semi-structured in-depth telephone interviews (45–60 min) regarding: (a) their perceived current physical and mental health, (b) problems faced as a result of the COVID-19 pandemic, and (c) perception of available and necessary support structures. Purposive and snowball sampling techniques were used to recruit the participants. Interviews were recorded, transcribed, and thematically analyzed.

Results

Six themes were identified: 1) experiencing psychosomatic symptoms, 2) adoption of new healthy behaviors, 3) financial hardship, 4) family concerns, 5) reflections on discrimination and 6) reflections of existing support and expectations of support systems. The findings of our study illustrate the specific impact of COVID-19 among Nepalese migrants regarding their unstable employment conditions, perceived lack of social support, possible obligation to send money home, difficulty in accessing services due to the language barrier, and a lack of effective governmental support from Nepal. Pandemic-related adversity has negatively impacted migrants’ mental well-being, exacerbating their vulnerability.

Conclusions

Comprehensive and timely support should be provided to the vulnerable migrant population. Effective coordination among relevant parties in both countries, including the governments concerned, should be facilitated.
Association between food insecurity and access to a mental health professional: cross-sectional analysis of NHANES 2007–2014
Authors: Burruss Nina Camille , Girgis Marina , Green Karen Elizabeth , Lu Lingyi , Palakshappa Deepak
Published: April 2021

Background

To determine if individuals with food insecurity (FI) were less likely to have seen a mental health professional (MHP) within the past year than individuals without FI.

Methods

This is a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) conducted in the United States between 2007 and 2014. All participants 20 years of age or older were eligible for this study. We excluded participants who were pregnant, missing FI data, or missing data from the Patient Health Questionnaire (PHQ-9). The primary outcome was self-reported contact with a MHP in the past 12 months. We used multivariable logistic regression models to test the association between FI and contact with a MHP, controlling for all demographic and clinical covariates.

Results

Of the 19,789 participants, 13.9% were food insecure and 8.1% had major depressive disorder (MDD). In bivariate analysis, participants with FI were significantly more likely to have MDD (5.3% vs 2.8%, p < 0.0001) and to have been seen by a MHP in the preceding 12 months (14.0% vs 6.9%, p < 0.0001). In multivariable models, adults with FI had higher odds of having seen a MHP (OR = 1.32, CI: 1.07, 1.64).

Conclusions

This study demonstrates that individuals with FI were significantly more likely to have seen a MHP in the preceding 12 months compared to individuals without FI. Given the growing interest in addressing unmet social needs in healthcare settings, this data suggests that visits with MHPs may be a valuable opportunity to screen for and intervene on FI.
The impact of distance cataract surgical wet laboratory training on cataract surgical competency of ophthalmology residents
Authors: Geary Amelia , Wen Qing , Adrianzén Rosa , Congdon Nathan , Janani R. , Haddad Danny , Timbo Clare Szalay , Khalifa Yousuf M.
Published: April 2021

Background

This study assessed the impact of distance cataract surgical wet laboratory training on surgical competency of ophthalmology residents at a tertiary-level ophthalmic training center in Trujillo, Peru.

Methods

Three five-week distance wet lab courses were administered through Cybersight, Orbis International’s telemedicine platform. Weekly lectures and demonstrations addressed specific steps in phacoemulsification surgery. Each lecture had two accompanying wet lab assignments, which residents completed and recorded in their institution’s wet lab and uploaded to Cybersight for grading. Competency was assessed through anonymous grading of pre- and post-training surgical simulation videos, masked as to which occurred before and after training, using a standardized competency rubric adapted from the Ophthalmology Surgical Competency Assessment Rubric (OSCAR, scale of 0–32). Day one best-corrected post-operative visual acuity (BVCA) was assessed in the operative eye on the initial consecutive 4–6 surgeries conducted by the residents as per the norms of their residency training. An anonymous post-training satisfaction survey was administered to trainees’.

Results

In total, 21 ophthalmic residents participated in the courses, submitting a total of 210 surgical videos. Trainees’ average competency score increased 6.95 points (95%CI [4.28, 9.62], SD = 5.01, p < 0.0001, two sample t-test) from 19.3 (95%CI [17.2, 21.5], SD = 4.04) to 26.3 (95%CI [24.2, 28.3], SD = 3.93). Visual acuity for 92% of post-training resident surgeries (n = 100) was ≥20/60, meeting the World Health Organization’s criterion for good quality.

Conclusions

Structured distance wet lab courses in phacoemulsification resulted in significantly improved cataract surgical skills. This model could be applicable to locations where there are obstacles to traditional in-person training, such as the current COVID-19 pandemic.
Regulation of circulating CTRP-2/CTRP-9 and GDF-8/GDF-15 by intralipids and insulin in healthy control and polycystic ovary syndrome women following chronic exercise training
Authors: Jerobin Jayakumar , Ramanjaneya Manjunath , Bettahi Ilham , Parammal Raihanath , Siveen Kodappully Sivaraman , Alkasem Meis , Aye Myint , Sathyapalan Thozhukat , Skarulis Monica , Atkin Stephen L. , Abou-Samra Abdul Badi
Published: April 2021

Background

Polycystic ovary syndrome (PCOS) is associated with obesity, diabetes, and insulin resistance. The circulating C1Q/TNF-related proteins (CTRP-2, CTRP-9) and growth differentiation factors (GDF-8, GDF-15) contribute to glucose and lipid homeostasis. The effects of intralipids and insulin infusion on CTRP-2, CTRP-9, GDF-8 and GDF-15 in PCOS and control subjects before and after chronic exercise training were examined.

Methods

Ten PCOS and nine healthy subjects were studied at baseline status and after moderate-intensity chronic exercise training (1 h exercise, 3 times per week, 8 weeks). All participants were infused with 1.5 mL/min of saline or intralipids (20%) for 5 h, and during the last 2 h of saline or intralipids infusion hyperinsulinemic-euglycemic clamp (HIEC) was performed. CTRP-2, CTRP-9, GDF-8 and GDF-15 levels were measured at 0, 3 and 5 h.

Results

Intralipids dramatically increased CTRP-2 levels in PCOS (P = 0.02) and control (P = 0.004) subjects, which was not affected by insulin infusion or by exercise. Intralipids alone had no effects on CTRP-9, GDF-8, or GDF-15. Insulin increased the levels of GDF-15 in control subjects (P = 0.05) during the saline study and in PCOS subjects (P = 0.04) during the intralipid infusion. Insulin suppressed CTRP9 levels during the intralipid study in both PCOS (P = 0.04) and control (P = 0.01) subjects. Exercise significantly reduced fasting GDF-8 levels in PCOS (P = 0.03) and control (P = 0.04) subjects; however, intralipids infusion after chronic exercise training increased GDF-8 levels in both PCOS (P = 0.003) and control (P = 0.05) subjects and insulin infusion during intralipid infusion reduced the rise of GDF-8 levels.

Conclusion

This study showed that exogenous lipids modulate CTRP-2, which might have a physiological role in lipid metabolism. Since chronic exercise training reduced fasting GDF-8 levels; GDF-8 might have a role in humoral adaptation to exercise. GDF-15 and CTRP-9 levels are responsive to insulin, and thus they may play a role in insulin responses.
Effect of antibiotic-induced intestinal dysbacteriosis on bronchopulmonary dysplasia and related mechanisms
Authors: Ran Xiao , He Yu , Ai Qing , Shi Yuan
Published: April 2021

Background

Modification of the gut microbiota by antibiotics may influence the disease susceptibility and immunological responses. Infants in the neonatal intensive care unit (NICU) subjected to frequent antibiotics and oxygen therapies, which may give rise to local and systemic inflammatory reactions and progression of bronchopulmonary dysplasia (BPD). This study aimed to investigate the role of intestinal dysbacteriosis by antibiotic therapy before hyperoxia exposure in the progression of BPD.

Methods

Mice had been exposed to hyperoxia (85% O2) since postnatal day 3 until day 16 for the BPD model establishment, treated with antibiotics from postnatal day 2 until day 8. Treated mice and appropriate controls were harvested on postnatal day 2 or 10 for 16S rRNA gene sequencing, or postnatal day 17 for assessment of alveolar morphometry and macrophages differentiation.

Results

Antibiotic-induced intestinal dysbacteriosis before hyperoxia exposure gave rise to deterioration of BPD evidenced by reduced survival rates and alveolarization. Moreover, antibiotic-induced intestinal dysbacteriosis resulted in increased M1 macrophage maker (iNOS) and decreased M2 macrophage maker (Arg-1) levels in lung homogenates.

Conclusion

Broad-spectrum antibiotic-induced intestinal dysbacteriosis may participate in BPD pathogenesis via alteration of the macrophage polarization status. Manipulating the gut microbiota may potentially intervene the therapy of BPD.
Human Huntington’s disease pluripotent stem cell-derived microglia develop normally but are abnormally hyper-reactive and release elevated levels of reactive oxygen species
Authors: O’Regan Grace C. , Farag Sahar H. , Casey Caroline S. , Wood-Kaczmar Alison , Pocock Jennifer M. , Tabrizi Sarah J. , Andre Ralph
Published: April 2021

Background

Neuroinflammation may contribute to the pathogenesis of Huntington’s disease, given evidence of activated microglia and elevated levels of inflammatory molecules in disease gene carriers, even those many years from symptom onset. We have shown previously that monocytes from Huntington’s disease patients are hyper-reactive to stimulation in a manner dependent on their autonomous expression of the disease-causing mutant HTT protein. To date, however, whether human microglia are similarly hyper-responsive in a cell-autonomous manner has not been determined.

Methods

Microglial-like cells were derived from human pluripotent stem cells (PSCs) expressing mutant HTT containing varying polyglutamine lengths. These included lines that are otherwise isogenic, such that any observed differences can be attributed with certainty to the disease mutation itself. Analyses by quantitative PCR and immunofluorescence microscopy respectively of key genes and protein markers were undertaken to determine whether Huntington’s disease PSCs differentiated normally to a microglial fate. The resultant cultures and their supernatants were then assessed by various biochemical assays and multiplex ELISAs for viability and responses to stimulation, including the release of pro-inflammatory cytokines and reactive oxygen species. Conditioned media were applied to PSC-derived striatal neurons, and vice versa, to determine the effects that the secretomes of each cell type might have on the other.

Results

Human PSCs generated microglia successfully irrespective of the expression of mutant HTT. These cells, however, were hyper-reactive to stimulation in the production of pro-inflammatory cytokines such as IL-6 and TNFα. They also released elevated levels of reactive oxygen species that have neurotoxic potential. Accompanying such phenotypes, human Huntington’s disease PSC-derived microglia showed increased levels of apoptosis and were more susceptible to exogenous stress. Such stress appeared to be induced by supernatants from human PSC-derived striatal neurons expressing mutant HTT with a long polyglutamine tract.

Conclusions

These studies show, for the first time, that human Huntington’s disease PSC-derived microglia are hyper-reactive due to their autonomous expression of mutant HTT. This provides a cellular basis for the contribution that neuroinflammation might make to Huntington’s disease pathogenesis.
Age-dependency of terminal ileum tissue resident memory T cell responsiveness profiles to S. Typhi following oral Ty21a immunization in humans
Authors: Booth Jayaum S. , Goldberg Eric , Patil Seema A. , Barnes Robin S. , Greenwald Bruce D. , Sztein Marcelo B.
Published: April 2021

Background

The impact of aging on the immune system is unequivocal and results in an altered immune status termed immunosenescence. In humans, the mechanisms of immunosenescence have been examined almost exclusively in blood. However, most immune cells are present in tissue compartments and exhibit differential cell (e.g., memory T cells -TM) subset distributions. Thus, it is crucial to understand immunosenescence in tissues, especially those that are exposed to pathogens (e.g., intestine). Using a human model of oral live attenuated typhoid vaccine, Ty21a, we investigated the effect of aging on terminal ileum (TI) tissue resident memory T (TRM) cells. TRMprovide immediate adaptive effector immune responsiveness at the infection site. However, it is unknown whether aging impacts TRMS. Typhi-responsive cells at the site of infection (e.g., TI). Here, we determined the effect of aging on the induction of TIS.Typhi-responsive TRMsubsets elicited by Ty21a immunization.

Results

We observed that aging impacts the frequencies of TI-lamina propria mononuclear cells (LPMC) TMand TRMin both Ty21a-vaccinated and control groups. In unvaccinated volunteers, the frequencies of LPMC CD103- CD4+ TRMdisplayed a positive correlation with age whilst the CD4/CD8 ratio in LPMC displayed a negative correlation with age.We observed that elderly volunteers have weakerS.Typhi-specific mucosal immune responses following Ty21a immunization compared to adults. For example, CD103+ CD4+ TRMshowed reduced IL-17A production, while CD103- CD4+ TRMexhibited lower levels of IL-17A and IL-2 in the elderly than in adults following Ty21a immunization. Similar results were observed in LPMC CD8+ TRMand CD103- CD8+ T cell subsets. A comparison of multifunctional (MF) profiles of both CD4+ and CD8+ TRMsubsets between elderly and adults also showed significant differences in the quality and quantity of elicited single (S) and MF responses.

Conclusions

Aging influences tissue resident TMS. Typhi-specific responses in the terminal ileum following oral Ty21a-immunization. This study is the first to provide insights in the generation of local vaccine-specific responses in the elderly population and highlights the importance of evaluating tissue immune responses in the context of infection and aging.

Trial registration

This study was approved by the Institutional Review Board and registered on ClinicalTrials.gov (identifierNCT03970304, Registered 29 May 2019 - Retrospectively registered).
Exploring mechanisms of ventricular enlargement in idiopathic normal pressure hydrocephalus: a role of cerebrospinal fluid dynamics and motile cilia
Authors: Yamada Shigeki , Ishikawa Masatsune , Nozaki Kazuhiko
Published: April 2021

Idiopathic normal pressure hydrocephalus (iNPH) is considered an age-dependent chronic communicating hydrocephalus associated with cerebrospinal fluid (CSF) malabsorption; however, the aetiology of ventricular enlargement in iNPH has not yet been elucidated. There is accumulating evidence that support the hypothesis that various alterations in CSF dynamics contribute to ventricle dilatation in iNPH. This review focuses on CSF dynamics associated with ventriculomegaly and summarises the current literature based on three potential aetiology factors: genetic, environmental and hydrodynamic. The majority of gene mutations that cause communicating hydrocephalus were associated with an abnormal structure or dysfunction of motile cilia on the ventricular ependymal cells. Aging, alcohol consumption, sleep apnoea, diabetes and hypertension are candidates for the risk of developing iNPH, although there is no prospective cohort study to investigate the risk factors for iNPH. Alcohol intake may be associated with the dysfunction of ependymal cilia and sustained high CSF sugar concentration due to uncontrolled diabetes increases the fluid viscosity which in turn increases the shear stress on the ventricular wall surface. Sleep apnoea, diabetes and hypertension are known to be associated with the impairment of CSF and interstitial fluid exchange. Oscillatory shear stress to the ventricle wall surfaces is considerably increased by reciprocating bidirectional CSF movements in iNPH. Increased oscillatory shear stress impedes normal cilia beating, leading to motile cilia shedding from the ependymal cells. At the lack of ciliary protection, the ventricular wall is directly exposed to increased oscillatory shear stress. Additionally, increased oscillatory shear stress may be involved in activating the flow-mediated dilation signalling of the ventricular wall. In conclusion, as the CSF stroke volume at the cerebral aqueduct increases, the oscillatory shear stress increases, promoting motor cilia shedding and loss of ependymal cell coverage. These are considered to be the leading causes of ventricular enlargement in iNPH.
Identifying potential treatment effect modifiers of the effectiveness of chiropractic care to infants with colic through prespecified secondary analyses of a randomised controlled trial
Authors: Holm Lise Vilstrup , Vach Werner , Jarbøl Dorte Ejg , Christensen Henrik Wulff , Søndergaard Jens , Hestbæk Lise
Published: April 2021

Background

A recent trial identified large variation in effect of chiropractic care for infantile colic. Thus, identification of possible effect modifiers could potentially enhance the clinical reasoning to select infants with excessive crying for chiropractic care. Therefore, the aim of this study is to identify potential treatment effect modifiers which might influence the effect of chiropractic care for excessive crying in infancy.

Methods

Design: Prespecified secondary analyses of data from a randomised controlled trial. The analyses are partly confirmative and partly exploratory.

Setting: Four chiropractic clinics in Denmark.

Participants: Infants aged 2–14 weeks with unexplained excessive crying. Of the 200 infants randomised (1:1), 103 were assigned to a chiropractic care group and 97 to a control group.

Intervention: Infants in the intervention group received chiropractic care for 2 weeks, while the control group was not treated.

Main analyses: The outcome was change in daily hours of crying. Fifteen baseline variables and 6 general variables were selected as potential effect modifiers, and indices based on these were constructed. Factor analyses, latent class analyses and prognosis were used to construct other potentially modifying variables. Finally, an attempt at defining a new index aiming at optimal prediction of the treatment effect was made. The predictive value for all resulting variables were examined by considering the difference in mean change in crying time between the two treatment groups, stratified by the values of the candidate variables, i.e. interaction analyses.

Results

None of the predefined items or indices were shown to be useful in identifying colicky infants with potentially larger gain from manual therapy. However, more baseline hours of crying (p = 0.029), short duration of symptoms (p = 0.061) and young age (p = 0.089) were all associated with an increased effect on the outcome of hours of crying.

Conclusion

Musculoskeletal indicators were not shown to be predictive of an increased benefit for colicky infants from chiropractic treatment. However, increased benefit was associated with early treatment and a high level of baseline crying, suggesting that the most severely affected infants have the greatest potential of benefiting from manual therapy. This finding requires validation by future studies.

Trial registration

Clinical TrialsNCT02595515, registered 2 November 2015.
The multi-domain responder index: a novel analysis tool to capture a broader assessment of clinical benefit in heterogeneous complex rare diseases
Authors: Tandon P. K. , Kakkis Emil D.
Published: April 2021

In traditional clinical trial design, efficacy is typically assessed using a single primary endpoint in a randomized controlled trial to detect an expected treatment effect of a therapy in a narrowly selected patient population. This accepted paradigm is based on clinical evaluations that may not actually capture the breadth of the impact of a disease, which is especially true in the setting of complex, multisystem, rare diseases with small, extremely heterogeneous patient populations. The multi-domain responder index (MDRI) is a novel approach that accommodates complex and heterogeneous disease manifestations and evaluates a broad array of clinical disease without impairing the power or rigor of a study to fully understand a treatment. The MDRI sums the scores corresponding to clinically significant thresholds of change for each component domain in each individual patient, capturing the mean clinically meaningful change across multiple domains within individuals. This novel approach combines and then sums the results of independent domain endpoint responder analyses into one responder score to provide a broad basis for the assessment of efficacy. The impact of a treatment across multiple, physiologically independent domains, can be assessed clinically, reducing the adverse impact of heterogeneity on trial outcomes and allowing eligibility criteria to enroll a wider range of patients, ultimately resulting in efficacy and safety assessments of a therapy across a broad group of heterogeneous patients in rare disease programs.

Trial registration The following studies are referenced within this manuscript (CLINICALTRIALS.GOV registration numbers): NCT00912925; NCT00146770; NCT00067470; NCT00104234; NCT00069641; NCT02230566; NCT02377921; NCT02432144.