bluuebunny/crossref_metadata_2025 huggingface dataset:
Externalization of Speech When Listening With Hearing Aids
Authors: Best Virginia , Roverud Elin
Published: February 2024

Subjective reports indicate that hearing aids can disrupt sound externalization and/or reduce the perceived distance of sounds. Here we conducted an experiment to explore this phenomenon and to quantify how frequently it occurs for different hearing-aid styles. Of particular interest were the effects of microphone position (behind the ear vs. in the ear) and dome type (closed vs. open). Participants were young adults with normal hearing or with bilateral hearing loss, who were fitted with hearing aids that allowed variations in the microphone position and the dome type. They were seated in a large sound-treated booth and presented with monosyllabic words from loudspeakers at a distance of 1.5 m. Their task was to rate the perceived externalization of each word using a rating scale that ranged from 10 (at the loudspeaker in front) to 0 (in the head) to −10 (behind the listener). On average, compared to unaided listening, hearing aids tended to reduce perceived distance and lead to more in-the-head responses. This was especially true for closed domes in combination with behind-the-ear microphones. The behavioral data along with acoustical recordings made in the ear canals of a manikin suggest that increased low-frequency ear-canal levels (with closed domes) and ambiguous spatial cues (with behind-the-ear microphones) may both contribute to breakdowns of externalization.
Validating Parallel-Forms Tests for Assessing Anesthesia Resident Knowledge
Authors: Lee Allison J. , Goodman Stephanie R. , Bauer Melissa E. B. , Minehart Rebecca D. , Banks Shawn , Chen Yi , Landau Ruth L. , Chatterji Madhabi
Published: February 2024

We created a serious game to teach first year anesthesiology (CA-1) residents to perform general anesthesia for cesarean delivery. We aimed to investigate resident knowledge gains after playing the game and having received one of 2 modalities of debriefing. We report on the development and validation of scores from parallel test forms for criterion-referenced interpretations of resident knowledge. The test forms were intended for use as pre- and posttests for the experiment. Validation of instruments measuring the study's primary outcome was considered essential for adding rigor to the planned experiment, to be able to trust the study's results. Parallel, multiple-choice test forms development steps included: (1) assessment purpose and population specification; (2) content domain specification and writing/selection of items; (3) content validation by experts of paired items by topic and cognitive level; and (4) empirical validation of scores from the parallel test forms using Classical Test Theory (CTT) techniques. Field testing involved online administration of 52 shuffled items from both test forms to 24 CA-1's, 21 second-year anesthesiology (CA-2) residents, 2 fellows, 1 attending anesthesiologist, and 1 of unknown rank at 3 US institutions. Items from each form yielded near-normal score distributions, with similar medians, ranges, and standard deviations. Evaluations of CTT item difficulty (item p values) and discrimination (D) indices indicated that most items met assumptions of criterion-referenced test design, separating experienced from novice residents. Experienced residents performed better on overall domain scores than novices ( P < .05). Kuder-Richardson Formula 20 (KR-20) reliability estimates of both test forms were above the acceptability cut of .70, and parallel forms reliability estimate was high at .86, indicating results were consistent with theoretical expectations. Total scores of parallel test forms demonstrated item-level validity, strong internal consistency and parallel forms reliability, suggesting sufficient robustness for knowledge outcomes assessments of CA-1 residents.
Study of Electrical and Mechanical Properties of Polypyrrole-Coated Three-Dimensional Spacer Fabric
Authors: Luo Juan , Chen Si , Shi Da-Wei
Published: February 2024

In this study, the liquid phase oxidative polymerization method was utilized to prepare polypyrrole conductive three-dimensional spacer fabrics. By controlling pyrrole solution, oxidant FeCl3 solution, dopant p-toluene sulfonic acid concentration and reaction time, the optimal process for the preparation of conductive spacer fabrics was obtained. This led to the best preparation process of polypyrrole-coated three-dimensional spacer conductive fabric (polypyrrole/three-dimensional spacer fabrics) being obtained. The results showed that the conductive properties of polypyrrole/three-dimensional spacer fabrics were the best when 0.10 mol/L pyrrole, 0.40 mol/L oxidant FeCl3 solution, and 0.40 mol/L dopant p-toluene sulfonic acid were prepared within a 2-h reaction time. The properties of polypyrrole/three-dimensional spacer fabrics were analyzed using the results from surface resistance, Fourier transform-infrared spectroscopy, mechanical properties, and stability tests. The results showed that polypyrrole was well attached to the three-dimensional spacer fabric surface, and the concentration of polypyrrole in the fabric exhibited an inverse correlation with changes in surface resistance. The mechanical properties of polypyrrole/three-dimensional spacer fabrics after treatment exhibit superior performance, with consistent changes in the meridional and zonal electrical properties during tensile testing and can maintain excellent long-term electrical stability in atmospheric environments.
Impact of Bariatric Surgery on Treatment Burden and Progression of Diabetic Retinopathy
Authors: Allen Ariana , Patel Hemal , Stinnett Sandra S. , Rosdahl Jullia A. , Schuman Stefanie
Published: February 2024

Purpose: To assess the severity, progression, and treatment burden of diabetic retinopathy (DR) in patients after bariatric surgery compared with controls. Methods: A retrospective cohort study was performed of patients with type 2 diabetes and DR seen at the Duke Eye Center between 2014 and 2023. Clinical data included hemoglobin A1c (HbA1c), diagnostic stage of DR, diabetic macular edema (DME) or vitreous hemorrhage (VH), visual acuity (VA), and treatment burden at baseline and follow-up. Generalized estimating equation analysis was used to account for the correlation between 2 eyes of the same patient. Results: Sixteen patients who had bariatric surgery were matched by age, sex, and duration of diabetes with 60 control patients managed medically during the same time period. The HbA1c level, severity of DR, presence of DME or VH, VA, and treatment burden were not significantly different (all P > .05) at the baseline examination. On average, patients were followed for 6 years. The HbA1c level at the follow-up was significantly lower in the bariatric surgery group (6.4% vs 8.5%; P < .001). At the follow-up, the treatment burden was reduced in the bariatric surgery group compared with the control group ( P = .04). There was a clear trend toward reduced progression of DR and treatment burden in the bariatric surgery group over the follow-up. Conclusions: Bariatric surgery may improve glycemic control, stabilize DR progression, and reduce the treatment burden, which may have a significant impact on quality of life for patients with DR.
Sustainability and impossible worlds
Authors: Menga Filippo , Vanolo Alberto
Published: February 2024

This paper mobilises the idea of impossible worlds to conceptualise and explore inconsistent and illogical visions and ways of living sustainably. Specifically, the paper focuses on an understanding of sustainability based on classic Kantian universalistic ethics (suppose everyone did the same) and relative feelings of responsibility and guilt for the environment. By mobilising three vignettes, the paper argues that impossibility is present in current environmental thinking, and narratives of impossibility have an emotional and political role in shaping popular discourses concerning environmentalism and responsibility. It suggests that exploring glitches, impossibilities, contradictions and inconsistencies may contribute to understanding the role of personal guilt in sustainability narratives, and potentially trigger change.
EOLinPLACE: an international research project to reform the way dying places are classified and understood
Authors: Namukwaya Elizabeth , de Sousa Andrea Bruno , Lopes Sílvia , Touwen Dorothea Petra , van der Steen Jenny Theodora , Bélanger Emmanuelle , Brooks Joanna , Yghemonos Stecy , Sehmi Kawaldip , Gomes Barbara
Published: February 2024

Background:

Whenever possible, a person should die where they feel it is the right place to be. There is substantial global variation in home death percentages but it is unclear whether these differences reflect preferences, and there are major limitations in how the place of death is classified and compared across countries.

Objectives:

EOLinPLACE is an international interdisciplinary research project funded by the European Research Council aiming to create a solid base for a ground-breaking international classification tool that will enable the mapping of preferred and actual places towards death.

Design:

Mixed-methods observational research.

Methods and analysis:

We combine classic methods of developing health classifications with a bottom-up participatory research approach, working with international organizations representing patients and informal carers [International Alliance of Patients’ Organizations (IAPO) and Eurocarers]. First, we will conduct an international comparative analysis of existing classification systems and routinely collected death certificate data on place of death. Secondly, we will conduct a mixed-methods study (ethnography followed by longitudinal quantitative study) in four countries (the Netherlands, Portugal, Uganda and the United States), to compare the preferences and experiences of patients with life-threatening conditions and their families. Thirdly, based on the generated evidence, we will build a contemporary classification of dying places; assess its content validity through focus groups with patients, carers and other stakeholders; and evaluate it in a psychometric study to examine construct validity, reliability, responsiveness, data quality and interpretability.

Ethics:

Approved by the ethics committee of the University of Coimbra, Faculty of Medicine (CE-068-2022) and committees in each of the participating countries.

Discussion:

The findings will provide a deeper understanding of the diversity in individual end-of-life pathways. They will enable key developments such as measurement of progress towards achievement of preferences when care can be planned. The project will open new directions in how to care for the dying.

Trial registration:

Research Registry UIN 9213.
Consequences of consequence models: The impact of economies of scale on seismic loss estimates
Authors: Banihashemi MirAmir , Miliziano Alessandra , Zsarnóczay Ádám , Wiebe Lydell , Filiatrault Andre
Published: February 2024

The detailed evaluation of expected losses and damage experienced by structural and nonstructural components is a fundamental part of performance-based seismic design and assessment. The FEMA P-58 methodology represents the state of the art in this area. Increasing interest in improving structural performance and community resilience has led to widespread adoption of this methodology and the library of component models published with it. This study focuses on the modeling of economies of scale for repair cost calculation and specifically highlights the lack of a definition for aggregate damage, a quantity with considerable influence on the component repair costs. The article illustrates the highly variable and often substantial impact of damage aggregation that can alter total repair costs by more than 25%. Four so-called edge cases representing different damage aggregation methods are introduced to investigate which components experience large differences in their repair costs and under what circumstances. A three-step evaluation strategy is proposed that allows engineers to quickly evaluate the potential impact of damage aggregation on a specific performance assessment. This helps users of currently available assessment tools to recognize and communicate this uncertainty even when the tools they use only support one particular damage aggregation method. A case study of a 9-story building illustrates the proposed strategy and the impact of this ambiguity on the performance of a realistic structure. The article concludes with concrete recommendations toward the development of a more sophisticated model for repair consequence calculation.
microRNAs in exhaled breath condensate for diagnosis of lung cancer in a resource-limited setting: a concise review
Authors: Rai Divyanjali , Pattnaik Bijay , Bangaru Sunil , Tak Jaya , Kumari Jyoti , Verma Umashankar , Vadala Rohit , Yadav Geetika , Dhaliwal Rupinder Singh , Kumar Sunil , Kumar Rakesh , Jain Deepali , Luthra Kalpana , Chosdol Kunzang , Palanichamy Jayanth Kumar , Khan Maroof Ahmad , Surendranath Addagalla , Mittal Saurabh , Tiwari Pawan , Hadda Vijay , Madan Karan , Agrawal Anurag , Guleria Randeep , Mohan Anant
Published: February 2024

Lung cancer is one of the common cancers globally with high mortality and poor prognosis. Most cases of lung cancer are diagnosed at an advanced stage due to limited diagnostic resources. Screening modalities, such as sputum cytology and annual chest radiographs, have not proved sensitive enough to impact mortality. In recent years, annual low-dose computed tomography has emerged as a potential screening tool for early lung cancer detection, but it may not be a feasible option for developing countries. In this context, exhaled breath condensate (EBC) analysis has been evaluated recently as a noninvasive tool for lung cancer diagnosis. The breath biomarkers also have the advantage of differentiating various types and stages of lung cancer. Recent studies have focused more on microRNAs (miRNAs) as they play a key role in tumourigenesis by regulating the cell cycle, metastasis and angiogenesis. In this review, we have consolidated the current published literature suggesting the utility of miRNAs in EBC for the detection of lung cancer.
Malignant pleural disease
Authors: Piggott Laura M. , Hayes Conor , Greene John , Fitzgerald Deirdre B.
Published: February 2024

Malignant pleural disease represents a growing healthcare burden. Malignant pleural effusion affects approximately 1 million people globally per year, causes disabling breathlessness and indicates a shortened life expectancy. Timely diagnosis is imperative to relieve symptoms and optimise quality of life, and should give consideration to individual patient factors. This review aims to provide an overview of epidemiology, pathogenesis and suggested diagnostic pathways in malignant pleural disease, to outline management options for malignant pleural effusion and malignant pleural mesothelioma, highlighting the need for a holistic approach, and to discuss potential challenges including non-expandable lung and septated effusions.
Chronic cough: is the end nigh?
Authors: Hirons Barnaby , Turner Richard , Cho Peter S.P. , Birring Surinder S.
Published: February 2024

Chronic cough (lasting more than 8 weeks) is a common condition with substantial psychosocial impact. Despite huge efforts following robust guidelines, chronic cough in many patients remains refractory or unexplained (RU-CC). Recent insights support a significant role for cough hypersensitivity in RU-CC, including neuropathophysiological evidence from inhalational cough challenge testing, functional magnetic resonance imaging, and airway nerve biopsy. Along with improved approaches to measuring cough, this knowledge has developed in tandem with repurposing neuromodulator medications, including gabapentin, and evidence for non-pharmacological treatments. Most significantly, there is now a pipeline for novel classes of drugs specifically for chronic cough. The P2X3 receptor antagonist gefapixant is the first such drug to be approved in Europe. However, challenges persist. The field of chronic cough needs more robust epidemiological data, enhanced diagnostic tools, further well-designed clinical trials accounting for the effects of placebo, and treatments with minimal side-effects. Addressing these challenges are novel chronic cough registries, improved International Classification of Diseases (10th revision) coding, genetic testing options and further mechanistic studies. This Viewpoint article discusses these facets and considers how, whilst the end of chronic cough may not be imminent for all patients, the evolving landscape looks increasingly optimistic.
Integrated physiological, metabolomic, and transcriptomic analyses elucidate the regulation mechanisms of lignin synthesis under osmotic stress in alfalfa leaf (Medicago sativa L.)
Authors: Yang Jing , Yi Jiangnan , Ma Shihai , Wang Yafang , Song Jiaxing , Li Shuo , Feng Yueyan , Sun Haoyang , Gao Cai , Yang Rongchen , Li Zhongxing , Cao Yuman , Yang Peizhi
Published: February 2024

Alfalfa, an essential forage crop known for its high yield, nutritional value, and strong adaptability, has been widely cultivated worldwide. The yield and quality of alfalfa are frequently jeopardized due to environmental degradation. Lignin, a constituent of the cell wall, enhances plant resistance to abiotic stress, which often causes osmotic stress in plant cells. However, how lignin responds to osmotic stress in leaves remains unclear. This study explored the effects of osmotic stress on lignin accumulation and the contents of intermediate metabolites involved in lignin synthesis in alfalfa leaves. Osmotic stress caused an increase in lignin accumulation and the alteration of core enzyme activities and gene expression in the phenylpropanoid pathway. We identified five hub genes (CSE, CCR, CADa, CADb, and POD) and thirty edge genes (including WRKYs, MYBs, and UBPs) by integrating transcriptome and metabolome analyses. In addition, ABA and ethylene signaling induced by osmotic stress regulated lignin biosynthesis in a contradictory way. These findings contribute to a new theoretical foundation for the breeding of high-quality and resistant alfalfa varieties.
Standards of care and determinants of women’s satisfaction with delivery services in Nepal: a multi-perspective analysis using data from a health facility-based survey
Authors: Tuladhar Sabita , Delius Maria , Siebeck Matthias , Oberhauser Cornelia , Paudel Deepak , Rehfuess Eva
Published: February 2024

Background

Compliance with standards of care is required for sustained improvement in the quality of delivery services. It thus represents a key challenge to improving maternal survival and meeting the Sustainable Development Goal (SDG) target of reducing the maternal mortality ratio to 70 deaths per 100,000 live births. This study examines the extent to which normal low-risk health facility deliveries in Nepal meet the standards of quality of care and assesses the effect of the standards of quality of care and various contextual factors on women’s satisfaction with the services they receive.

Methods

Drawing on the 2021 Nepal Health Facility Survey, the sample comprised 320 women who used health facilities for normal, low-risk delivery services. A weighted one-sample t-test was applied to examine the proportion of deliveries meeting the eight standards of care. Women’s overall satisfaction level was computed from seven satisfaction variables measured on a Likert scale, using principal component analysis. The composite measure was then dichotomized. Binary logistic regression was used to analyze the determinants of women’s satisfaction with delivery care services.

Results

Deliveries complying with the eight standards of care and its 53 indicators varied widely; output indicators were more frequently met than input indicators. Of the eight standards of care, the “functional referral system” performed highest (92.0%), while “competent, motivated human resources” performed the least (52.4%). Women who were attended by a provider when they called for support (AOR: 5.29; CI: 1.18, 23.64), who delivered in health facilities that displayed health statistics (AOR 3.16; CI: 1.87, 5.33), who experienced caring behaviors from providers (AOR: 2.59; CI: 1.06, 6.30) and who enjoyed audio-visual privacy (AOR 2.13; CI: 1.04, 4.38) had higher satisfaction levels compared to their counterparts. The implementation of the Maternity Incentive Scheme and presence of a maternal waiting room in health facilities, however, were associated with lower satisfaction levels.

Conclusions

Nepal performed moderately well in meeting the standards of care for normal, low-risk deliveries. To meet the SDG target Nepal must accelerate progress. It needs to focus on people-centered quality improvement to routinely assess the standards of care, mobilize available resources, improve coordination among the three tiers of government, and implement high-impact programs.
The mistreatment of women during maternity care and its association with the maternal continuum of care in health facilities
Authors: Kasaye Habtamu , Scarf Vanessa , Sheehy Annabel , Baird Kathleen
Published: February 2024

Background

Mistreatment of childbearing women continues despite global attention to respectful care. In Ethiopia, although there have been reports of mistreatment of women during maternity care, the influence of this mistreatment on the continuum of maternity care remains unclear. In this paper, we report the prevalence of mistreatment of women from various dimensions, factors related to mistreatment and also its association to the continuum of maternity care in health facilities.

Methods

We conducted an institution-based cross-sectional survey among women who gave birth within three months before the data collection period in Western Ethiopia. A total of 760 women participated in a survey conducted face-to-face at five health facilities during child immunization visits. Using a validated survey tool, we assessed mistreatment in four categories and employed a mixed-effects logistic regression model to identify its predictors and its association with the continuum of maternity care, presenting results as adjusted odds ratios (AORs) with their 95% confidence intervals (CIs).

Results

Over a third of women (37.4%) experienced interpersonal abuse, 29.9% received substandard care, 50.9% had poor interactions with healthcare providers, and 6.2% faced health system constraints. The odds of mistreatment were higher among women from the lowest economic status, gave birth vaginally and those who encountered complications during pregnancy or birth, while having a companion of choice during maternity care was associated to reduced odds of mistreatment by 42% (AOR = 0.58, 95% CI: [0.42–0.81]). Women who experienced physical abuse, verbal abuse, stigma, or discrimination during maternity care had a significantly reduced likelihood of completing the continuum of care, with their odds decreased by half compared to those who did not face such interpersonal abuse (AOR = 0.49, 95% CI: [0.29–0.83]).

Conclusions

Mistreatment of women was found to be a pervasive problem that extends beyond labour and birth, it negatively affects upon maternal continuum of care. Addressing this issue requires an effort to prevent mistreatment through attitude and value transformation trainings. Such interventions should align with a system level actions, including enforcing respectful care as a competency, enhancing health centre functionality, improving the referral system, and influencing communities to demand respectful care.
A 12-year follow up survey of childhood blindness at schools for the blind in Cambodia
Authors: Rogerson Thomas , Ath Sith Sam , Meng Ngy , Casson Robert
Published: February 2024

Background

Cambodia is a low-income country in South East Asia with a population of 15.5 million people of whom 4.9 million (38%) are under the age of 16. The causes of childhood blindness in Cambodia have not been investigated since the first survey of schools for the blind done in 2009 by our group. Given the large demographic and economic shifts in Cambodia since 2009 it is important to determine if these causes have changed in order to ensure intervention programmes are appropriately targeted. The purpose of the present study is to investigate the prevalence of causes of childhood blindness at schools for the blind in Cambodia.

Methods

Students between the ages of 5 and 16 years who were attending schools for the blind in Cambodia were examined by a consultant paediatric ophthalmologist and had clinical photographs taken. Distance visual acuity was measured using a logMAR tumbling E chart and the WHO definitions of blindness and severe visual impairment were used. The examining ophthalmologist recorded the anatomical site and aetiology of vision loss using the WHO Prevention of Blindness eye examination record for children. Collected data were compared to a previous survey from 2009.

Results

Data from 73 students were included for analysis. The most common anatomical location of abnormality causing vision loss was the cornea (n = 20, 33.9%) followed by the lens and retina (n = 11, 18.64% each). Hereditary factors (n = 29, 49.15%) and childhood diseases (n = 27, 45.76%) were the most common aetiological causes of childhood blindness. The majority (71.19%) of childhood blindness was avoidable. The present study did not demonstrate 0a significant difference in the causes of childhood blindness compared to 2009.

Conclusions

Corneal pathologies continue to represent the most common cause of vision loss amongst the surveyed population and the majority of causes of childhood blindness continue to be avoidable. These findings will facilitate the development of evidence-based targeted interventional programmes in Cambodia.
Review of brachytherapy clinical trials: a cross-sectional analysis of ClinicalTrials.gov
Authors: Chen David , Parsa Rod , Chauhan Kabir , Lukovic Jelena , Han Kathy , Taggar Amandeep , Raman Srinivas
Published: February 2024

Introduction

Characterizing the landscape of clinical trials including brachytherapy can provide an overview of the current status and research trends which may guide further areas of investigation.

Method

We queried 449,849 clinical trials from the ClinicalTrials.gov registry using brachytherapy-related keywords from 1980 to 2023, yielding 245 multi-arm and 201 single-arm, brachytherapy trials. Multi-arm and single-arm brachytherapy trials were compared using 12 trial protocol elements.

Results

The number of trials including brachytherapy has increased over time, with over 60% of trials registered in 2010 onwards. The majority of clinical trials were Phase 2 or 3, evaluated both safety and efficacy, and were funded by academic sponsors. The most common tumor sites evaluated in brachytherapy clinical trials include prostate, cervix, liver, endometrium, and breast.

Conclusion

There remains continued interest in clinical trials including brachytherapy focused on evaluation of novel delivery systems, treatment planning, and new indications. More brachytherapy clinical trials are needed to define the optimal clinical utilization and advance prospective research in this field.
Interfractional variation in whole-breast VMAT irradiation: a dosimetric study with complementary SGRT and CBCT patient setup
Authors: Mankinen M. , Virén T. , Seppälä J. , Koivumäki T.
Published: February 2024

Background

The dosimetric effect of setup uncertainty and tissue deformations in left-sided whole-breast irradiation with complementary surface-guided radiotherapy (SGRT) and cone-beam computed tomography (CBCT) setup was evaluated.

Method

Treatment courses of 40.05 Gy prescribed dose in 15 fractions were simulated for 29 patients by calculating the dose on deformed CT images, that were based on daily CBCT images, and deforming and accumulating the dose onto the planning CT image. Variability in clinical target volume (CTV) position and shape was assessed as the 95% Hausdorff distance (HD95) between the planning CTV and deformed CTV structures. DVH metrics were evaluated between the planned and simulated cumulative dose distributions using two treatment techniques: tangential volumetric modulated arc therapy (tVMAT) and conventional 3D-conformal radiotherapy (3D-CRT).

Results

Based on the HD95 values, the variations in CTV shape and position were enclosed by the 5 mm CTV-PTV margin in 85% of treatment fractions using complementary CBCT and SGRT setup. A residual error of 8.6 mm was observed between the initial SGRT setup and CBCT setup. The median CTV V95% coverage was 98.1% (range 93.1–99.8%) with tVMAT and 98.2% (range 84.5–99.7%) with 3D-CRT techniques with CBCT setup. With the initial SGRT-only setup, the corresponding coverages were 96.3% (range 92.6–99.4%) and 96.6% (range 84.2–99.4%), respectively. However, a considerable bias in vertical residual error between initial SGRT setup and CBCT setup was observed. Clinically relevant changes between the planned and cumulative doses to organs-at-risk (OARs) were not observed.

Conclusions

The CTV-to-PTV margin should not be reduced below 5 mm even with daily CBCT setup. Both tVMAT and 3D-CRT techniques were robust in terms of dose coverage to the target and OARs. Based on the shifts between setup methods, CBCT setup is recommended as a complementary method with SGRT.
CSF protein ratios with enhanced potential to reflect Alzheimer’s disease pathology and neurodegeneration
Authors: Mravinacová Sára , Alanko Vilma , Bergström Sofia , Bridel Claire , Pijnenburg Yolande , Hagman Göran , Kivipelto Miia , Teunissen Charlotte , Nilsson Peter , Matton Anna , Månberg Anna
Published: February 2024

Background

Amyloid and tau aggregates are considered to cause neurodegeneration and consequently cognitive decline in individuals with Alzheimer’s disease (AD). Here, we explore the potential of cerebrospinal fluid (CSF) proteins to reflect AD pathology and cognitive decline, aiming to identify potential biomarkers for monitoring outcomes of disease-modifying therapies targeting these aggregates.

Method

We used a multiplex antibody-based suspension bead array to measure the levels of 49 proteins in CSF from the Swedish GEDOC memory clinic cohort at the Karolinska University Hospital. The cohort comprised 148 amyloid- and tau-negative individuals (A-T-) and 65 amyloid- and tau-positive individuals (A+T+). An independent sample set of 26 A-T- and 26 A+T+ individuals from the Amsterdam Dementia Cohort was used for validation. The measured proteins were clustered based on their correlation to CSF amyloid beta peptides, tau and NfL levels. Further, we used support vector machine modelling to identify protein pairs, matched based on their cluster origin, that reflect AD pathology and cognitive decline with improved performance compared to single proteins.

Results

The protein-clustering revealed 11 proteins strongly correlated to t-tau and p-tau (tau-associated group), including mainly synaptic proteins previously found elevated in AD such as NRGN, GAP43 and SNCB. Another 16 proteins showed predominant correlation with Aβ42 (amyloid-associated group), including PTPRN2, NCAN and CHL1. Support vector machine modelling revealed that proteins from the two groups combined in pairs discriminated A-T- from A+T+ individuals with higher accuracy compared to single proteins, as well as compared to protein pairs composed of proteins originating from the same group. Moreover, combining the proteins from different groups in ratios (tau-associated protein/amyloid-associated protein) significantly increased their correlation to cognitive decline measured with cognitive scores. The results were validated in an independent cohort.

Conclusions

Combining brain-derived proteins in pairs largely enhanced their capacity to discriminate between AD pathology-affected and unaffected individuals and increased their correlation to cognitive decline, potentially due to adjustment of inter-individual variability. With these results, we highlight the potential of protein pairs to monitor neurodegeneration and thereby possibly the efficacy of AD disease-modifying therapies.
Increased bronchiolitis burden and severity after the pandemic: a national multicentric study
Authors: Ghirardo Sergio , Ullmann Nicola , Zago Alessandro , Ghezzi Michele , Minute Marta , Madini Barbara , D’Auria Enza , Basile Cecilia , Castelletti Francesca , Chironi Federica , Capodiferro Agata , Andrenacci Beatrice , Risso Francesco Maria , Aversa Salvatore , Dotta Laura , Coretti Antonella , Vittucci Anna Chiara , Badolato Raffaele , Amaddeo Alessandro , Barbi Egidio , Cutrera Renato
Published: February 2024

Background

The coronavirus 2019 (COVID-19) related containment measures led to the disruption of all virus distribution. Bronchiolitis-related hospitalizations shrank during 2020–2021, rebounding to pre-pandemic numbers the following year. This study aims to describe the trend in bronchiolitis-related hospitalization this year, focusing on severity and viral epidemiology.

Methods

We conducted a retrospective investigation collecting clinical records data from all infants hospitalized for bronchiolitis during winter (1st September-31th March) from September 2018 to March 2023 in six Italian hospitals. No trial registration was necessary according to authorization no.9/2014 of the Italian law.

Results

Nine hundred fifty-three infants were hospitalized for bronchiolitis this last winter, 563 in 2021–2022, 34 in 2020–2021, 395 in 2019–2020 and 483 in 2018–2019. The mean length of stay was significantly longer this year compared to all previous years (mean 7.2 ± 6 days in 2022–2023), compared to 5.7 ± 4 in 2021–2022, 5.3 ± 4 in 2020–2021, 6.4 ± 5 in 2019–2020 and 5.5 ± 4 in 2018–2019 (p < 0.001), respectively. More patients required mechanical ventilation this winter 38 (4%), compared to 6 (1%) in 2021–2022, 0 in 2020–2021, 11 (2%) in 2019–2020 and 6 (1%) in 2018–2019 (p < 0.05), respectively. High-flow nasal cannula and non-invasive respiratory supports were statistically more common last winter (p = 0.001 or less). RSV prevalence and distribution did not differ this winter, but coinfections were more prevalent 307 (42%), 138 (31%) in 2021–2022, 1 (33%) in 2020–2021, 68 (23%) in 2019–2020, 61 (28%) in 2018–2019 (p = 0.001).

Conclusions

This study shows a growth of nearly 70% in hospitalisations for bronchiolitis, and an increase in invasive respiratory support and coinfections, suggesting a more severe disease course this winter compared to the last five years.
An immunoinformatics and structural vaccinology approach to design a novel and potent multi-epitope base vaccine targeting Zika virus
Authors: Hakami Mohammed Ageeli
Published: February 2024

Zika virus is an infectious virus, that belongs to Flaviviridae family, which is transferred to humans through mosquito vectors and severely threatens human health; but, apart from available resources, no effective and secure vaccine is present against Zika virus, to prevent such infections. In current study, we employed structural vaccinology approach to design an epitope-based vaccine against Zika virus, which is biocompatible, and secure and might trigger an adaptive and innate immune response by using computational approaches. We first retrieved the protein sequence from National Center for Biotechnology Information (NCBI) database and carried out for BLAST P. After BLAST P, predicted protein sequences were shortlisted and checked for allergic features and antigenic properties. Final sequence of Zika virus, with accession number (APO40588.1) was selected based on high antigenic score and non-allergenicity. Final protein sequence used various computational approaches including antigenicity testing, toxicity evaluation, allergenicity, and conservancy assessment to identify superior B-cell and T-cell epitopes. Two B-cell epitopes, five MHC-six MHC-II epitopes and I were used to construct an immunogenic multi-epitope-based vaccine by using suitable linkers. A 50S ribosomal protein was added at N terminal to improve the immunogenicity of vaccine. In molecular docking, strong interactions were presented between constructed vaccine and Toll-like receptor 9 (− 1100.6 kcal/mol), suggesting their possible relevance in the immunological response to vaccine. The molecular dynamics simulations ensure the dynamic and structural stability of constructed vaccine. The results of C-immune simulation revealed that constructed vaccine activate B and T lymphocytes which induce high level of antibodies and cytokines to combat Zika infection. The constructed vaccine is an effective biomarker with non-sensitization, nontoxicity; nonallergic, good immunogenicity, and antigenicity, however, experimental assays are required to verify the results of present study.
Early signs of myocardial systolic dysfunction in patients with type 2 diabetes are strongly associated with myocardial microvascular dysfunction independent of myocardial fibrosis: a prospective cohort study
Authors: Bojer Annemie S. , Sørensen Martin H. , Madsen Stine H. , Broadbent David A. , Plein Sven , Gæde Peter , Madsen Per L.
Published: February 2024

Background

Patients with diabetes demonstrate early left ventricular systolic dysfunction. Notably reduced global longitudinal strain (GLS) is related to poor outcomes, the underlying pathophysiology is however still not clearly understood. We hypothesized that pathophysiologic changes with microvascular dysfunction and interstitial fibrosis contribute to reduced strain.

Methods

211 patients with type 2 diabetes and 25 control subjects underwent comprehensive cardiovascular phenotyping by magnetic resonance imaging. Myocardial blood flow (MBF), perfusion reserve (MPR), extracellular volume (ECV), and 3D feature tracking GLS and global circumferential (GCS) and radial strain (GRS) were quantified.

Results

Patients (median age 57 [IQR 50, 67] years, 70% males) had a median diabetes duration of 12 [IQR 6, 18] years. Compared to control subjects GLS, GCS, and GRS were reduced in the total diabetes cohort, and GLS was also reduced in the sub-group of patients without diabetic complications compared to control subjects (controls − 13.9 ± 2.0%, total cohort − 11.6 ± 3.0%; subgroup − 12.3 ± 2.6%, all p < 0.05). Reduced GLS, but not GCS or GRS, was associated with classic diabetes complications of albuminuria (UACR ≥ 30 mg/g) [β (95% CI) 1.09 (0.22–1.96)] and autonomic neuropathy [β (95% CI) 1.43 (0.54–2.31)] but GLS was not associated with retinopathy or peripheral neuropathy. Independently of ECV, a 10% increase in MBF at stress and MPR was associated with higher GLS [multivariable regression adjusted for age, sex, hypertension, smoking, and ECV: MBF stress (β (95% CI) − 0.2 (− 0.3 to − 0.08), MPR (β (95% CI) − 0.5 (− 0.8 to − 0.3), p < 0.001 for both]. A 10% increase in ECV was associated with a decrease in GLS in univariable [β (95% CI) 0.6 (0.2 to 1.1)] and multivariable regression, but this was abolished when adjusted for MPR [multivariable regression adjusted for age, sex, hypertension, smoking, and MPR (β (95% CI) 0.1 (− 0.3 to 0.6)]. On the receiver operating characteristics curve, GLS showed a moderate ability to discriminate a significantly lowered stress MBF (AUC 0.72) and MPR (AUC 0.73).

Conclusions

Myocardial microvascular dysfunction was independent of ECV, a biomarker of myocardial fibrosis, associated with GLS. Further, 3D GLS could be a potential screening tool for myocardial microvascular dysfunction. Future directions should focus on confirming these results in longitudinal and/or interventional studies.
Impact of dexamethasone in severe COVID-19-induced acute kidney injury: a multicenter cohort study
Authors: Rubin Sébastien , Orieux Arthur , Prezelin-Reydit Mathilde , Garric Antoine , Picard Yoann , Mellati Nouchan , Le Gall Lisa , Dewitte Antoine , Prevel Renaud , Gruson Didier , Louis Guillaume , Boyer Alexandre ,   for the Groupe Recherche Rein Réanimation (G3R)
Published: February 2024

Background

Acute kidney injury (AKI) in intensive care unit (ICU) patients with severe COVID-19 is common (> 50%). A specific inflammatory process has been suggested in the pathogenesis of AKI, which could be improved by dexamethasone (DXM). In a small monocenter study (n = 100 patients), we reported a potential protective effect of DXM on the risk of AKI. This study aimed to investigate the preventive impact of DXM on AKI in a multicenter study of patients with severe COVID-19.

Methods

We conducted a multicenter study in three French ICUs from March 2020 to August 2021. All patients admitted to ICU for severe COVID-19 were included. Individuals with preexistent AKI or DXM administration before admission to ICU were excluded. While never used during the first wave, DXM was used subsequently at ICU entry, providing two treatment groups. Multivariate Cause-specific Cox models taking into account changes in ICU practices over time, were utilized to determine the association between DXM and occurrence of AKI.

Results

Seven hundred and ninety-eight patients were included. Mean age was 62.6 ± 12.1 years, 402/798 (50%) patients had hypertension, and 46/798 (6%) had previous chronic kidney disease. Median SOFA was 4 [3–6] and 420/798 (53%) required invasive mechanical ventilation. ICU mortality was 208/798 (26%). AKI was present in 598/798 (75%) patients: 266/598 (38%), 163/598 (27%), and 210/598 (35%) had, respectively, AKI KDIGO 1, 2, 3, and 61/598 (10%) patients required renal replacement therapy. Patients receiving DXM had a significantly decreased hazard of AKI occurrence compared to patients without DXM (HR 0.67; 95CI 0.55–0.81). These results were consistent in analyses that (1) excluded patients with DXM administration to AKI onset delay of less than 12 h, (2) incorporating the different ‘waves’ of the COVID-19 pandemic.

Conclusions

DXM was associated with a decrease in the risk of AKI in severe COVID-19 patients admitted to ICU. This supports the hypothesis that the inflammatory injury of AKI may be preventable.
Orthodontic camouflage treatment for a patient with bilateral cleft lip and palate, bilateral crossbite, and microdontic maxillary lateral incisors
Authors: Cheng Lanxin , Xia Kai , Sun Wentian , Yu Liyuan , Zhao Zhihe , Liu Jun
Published: February 2024

Cleft lip and palate is a congenital craniofacial anomaly that affects the lip and oral cavity. The management and orthodontic treatment of this anomaly is important but challenging. This article reports the successful treatment of a patient with bilateral cleft lip and palate, Class III malocclusion, bilateral crossbite, crowding and microdontic maxillary lateral incisors. One mandible incisor was extracted, and three miniscrew anchorages were utilized to distalize the maxillary left dental arch and retract the mandibular arch. After treatment, ideal occlusion and a better profile were established, and long-term stability was confirmed by a 4-year follow-up. This article represents a successful attempt of orthodontic camouflage treatment of severe dentofacial discrepancy, as an important part of the series treatment of cleft lip and palate, to provide some insight into the clinical field.
A comprehensive review on ecology, life cycle and use of Tecoma stans (bignoneaceae)
Authors: Singh Simrat , Miller Chad Thomas , Singh Parminder , Sharma Rishu , Rana Nepu , Dhakad Ashok Kumar , Dubey Rajesh Kumar
Published: February 2024

Tecoma stans is a widely distributed tall ornamental shrub in the plains of Indian subcontinent and is considered an invasive species across Argentina, Australia, South Africa, Pacific Islands and tropical regions of Asia. Besides having an ornamental significance, T. stans has been extensively investigated for its pharmaceutical applications as a source of bioactive compounds. In addition, the shrub is cultivated commercially as a potted flowering plant. We believe that T. stans, being a hardy, invasive and aggressively growing species, holds a considerable potential and a promising solution for re-greening waste and degraded lands outside its invasive range, due to its wider adaptability and drought tolerant characteristics. The shrub is an excellent source of pollen and nectar, that attracts diverse insect-pollinators and several species of birds. The prudent plantation of this shrub has the potential to restore the ecology of barren landscapes, that can change its perspective of ‘being invasive’ to ‘being ecologically healthy’ across the tropical, semi-arid and subtropical regions worldwide. This paper reviews the current updates on ecology, life cycle including morphology, plant growth characteristics, flowering phenology, reproductive biology, breeding system and fruiting of T. stans. In addition, details on insect-pollinator diversity and natural regeneration potential have also been discussed, besides highlighting its therapeutic and landscape use.
Impact of ChatGPT on ESL students’ academic writing skills: a mixed methods intervention study
Authors: Mahapatra Santosh
Published: February 2024

This paper presents a study on the impact of ChatGPT as a formative feedback tool on the writing skills of undergraduate ESL students. Since artificial intelligence-driven automated writing evaluation tools positively impact students’ writing, ChatGPT, a generative artificial intelligence-propelled tool, can be expected to have a more substantial positive impact. However, very little empirical evidence regarding the impact of ChatGPT on writing is available. The current mixed methods intervention study tried to address this gap. Data were collected from tertiary level ESL students through three tests and as many focus group discussions. The findings indicate a significant positive impact of ChatGPT on students' academic writing skills, and students’ perceptions of the impact were also overwhelmingly positive. The study strengthens and advances theories of feedback as a dialogic tool and ChatGPT as a reliable writing tool, and has practical implications. With proper student training, ChatGPT can be a good feedback tool in large-size writing classes. Future researchers can investigate the impact of ChatGPT on various specific genres and micro aspects of writing.