bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility of conducting a cohort randomized controlled trial assessing the effectiveness of a nurse-led package of care for knee pain
Authors: Fuller Amy , Hall Michelle , Nomikos Polykarpos Angelos , Millar Bonnie , Ogollah Reuben , Valdes Ana , Greenhaff Paul , das Nair Roshan , Doherty Michael , Walsh David A , Abhishek Abhishek
Published: August 2023

Objective

To evaluate the feasibility of conducting a cohort randomized controlled trial (RCT) of a nurse-led package of care for knee pain and determining a treatment sequence for use in a future trial.

Methods

This study was an open-label, three-arm, single-centre, mixed-methods, feasibility cohort RCT. Adults aged ≥40 years with moderate-to-severe knee pain for ≥3 months were eligible. Participants were randomized into group A (non-pharmacological treatment first), group B (pharmacological treatment first), or group C (usual care). The intervention was delivered over 26 weeks. Outcomes were dropout rate, recruitment rate, intervention fidelity, ability to collect outcome data, and treatment acceptability.

Results

Seventeen participants were randomized and enrolled into each of groups A and B (5.2% recruitment rate), and 174 participants were randomized to group C. The participant characteristics at randomization were comparable across the three arms. Coronavirus disease (COVID-19) paused the study from March–November 2020. Participants enrolled in groups A and B before March 2020 were withdrawn at the restart. Of the 20 participants enrolled after the restart, 18 completed the study (10% dropout). The nurse reported delivering most aspects of the intervention with high fidelity. The participants viewed the package of care as structured, supportive and holistic, they learnt about self-managing knee pain, and they could engage with and follow the non-pharmacological treatment. Most found the non-pharmacological treatment more useful than the pharmacological treatment, preferring to receive it before or alongside analgesia. Many self-report questionnaires were not fully completed.

Conclusion

The nurse-led package of care for knee pain was acceptable, with low dropout, although the cohort RCT design may not be feasible for a definitive trial.

Trial registration

ClinicalTrials.gov, https://clinicaltrials.gov, NCT03670706.
The Combined Role of Subsidy and Discussion Intervention in the Demand for a Stigmatized Product
Authors: Shrestha Vinish , Shrestha Rashesh
Published: August 2023

This paper studies the joint role of subsidization and group discussion intervention in increasing the demand for sanitary pads—a product that is widely available but demand for which may be curtailed due to the psychological cost associated with menstrual stigmatization. The study deploys a field experiment in Nepal to randomly allocate discount coupons of various values so that participants face exogenous variation in the effective price of sanitary pads. In addition, a randomly selected group of women in the sample participate in menstrual-health-related group discussion intervention. The findings suggest that an increase in subsidy level increases the probability of adoption across both groups of women—those receiving only a subsidy and those participating in the discussion intervention coupled with a subsidy. Also, women participating in the discussion intervention have a higher adoption rate. The effects of group discussion intervention are concentrated among women with high psychological cost, whose purchase decisions are more likely to be affected by societal stigma. The results suggest that combining a subsidy with group discussion could provide a cost-effective strategy to increase the adoption of health technology, the demand for which is constrained by social norms.
Plasmapheresis Versus Intravenous Immunoglobulin in Patients With Autoimmune Neuromuscular and Neuro-immunological Conditions
Authors: Zubair Adeel S. , Rethana Melissa , Ma Anthony , McAlpine Lindsay S. , Abulaban Ahmad , Munro Bailey Sheldon , Patwa Huned S. , Nowak Richard J. , Roy Bhaskar
Published: August 2023

Objectives:

Plasmapheresis (PLEX) and intravenous immunoglobulin (IVIg) are commonly used to treat autoimmune neuromuscular disorders, including myasthenia gravis, acute inflammatory demyelinating polyradiculoneuropathy, chronic inflammatory demyelinating polyradiculoneuropathy, and other autoimmune neurological disorders. The side effect profiles of these therapies vary, and concern has been raised regarding the safety of PLEX in the elderly population. In this study, we have examined the pattern of PLEX and IVIg use for autoimmune neurological disorders at a single facility and in a national database, focusing on the complications in elderly patients.

Methods:

We performed a retrospective chart review of adult patients at our institution receiving PLEX or IVIg for any autoimmune neuromuscular or neuro-immunological disease. Next, we analyzed the National Inpatient Sample database to confirm the trend in IVIg and PLEX use from 2012 to 2018 for a set of neuromuscular and neuro-immunological primary diagnoses.

Results:

IVIg was overall favored over PLEX. The adverse effects were similar among elderly patients (age ≥65 years) compared with younger patients (<65 years) in our institution, even after adequate matching of patients based on age, sex, and medical history. We examined the National Inpatient Sample dataset and noted increasingly higher frequency of IVIg use, consistent with the findings from our institution or facility.

Conclusions:

Both PLEX and IVIg are safe therapeutic choices in adult patients with autoimmune neuromuscular disorders and other neuro-immunological diseases and can be safely administered in the appropriate clinical setting.
Association of senescence-associated secretory phenotype proteins with ovarian reserve among middle-aged/older women
Authors: Shin Ji-Won , Park Hyun Tae , Choe Seung-Ah , Jeon Ok Hee
Published: August 2023

Objective

This study aimed to examine the association of circulating senescence-associated secretory phenotype proteins, secreted by senescent cells, with indicators of women's ovarian reserve.

Methods

This secondary analysis of cross-sectional baseline survey data was undertaken by the Korean Genome and Epidemiology Study Cardiovascular Disease Association Study. A total of 223 women (aged 40-82 y), without any history of oophorectomy, hysterectomy, or other medical conditions that could lower the ovarian reserve, were enrolled in this analysis. Chronological age (years), menopausal status, and serum anti-müllerian hormone (ng/mL) level were used to assess the associations among biological aging, accelerated menopausal aging, and ovarian reserve.

Results

Of the 223 women participants (53.4 ± 11.0 y), 147 (46.4 ± 3.9 y) and 76 (67.0 ± 6.9 y) were premenopausal and postmenopausal, respectively. Serum levels of senescence-associated secretory phenotype proteins were generally higher in postmenopausal, than in premenopausal, women. In the analyses adjusted for chronological age and body mass index, 17 senescence-associated secretory phenotype proteins were associated with menopausal status. However, in premenopausal women, no association trends with the level of anti-müllerian hormone were detected for a total of 28 senescence-associated secretory phenotype proteins.

Conclusions

In a cohort of middle-aged/older women, the level of circulating senescence-associated secretory phenotype proteins indicated chronological age and menopausal status. Yet, serum levels of senescence-associated secretory phenotype protein potentially have limited predictive value for ascertaining ovarian reserve in premenopausal women.
Novel approach to Behçet's disease in the era of biologic agents
Authors: Khieu Chansathya , Chanthan David
Published: August 2023

Purpose

This review aims to provide better understanding of modern modalities to investigate ocular symptoms of Behçet's disease in order to achieve appropriate management protocols and reduce irreversible visual loss.

Relevant findings

Current methods of diagnosing intraocular involvement in Behçet's disease gives clue to early diagnosis. In addition to standard ocular examination and fluorescein angiography, new noninvasive methods include ocular coherence tomography (OCT) and OCT angiography provide early detection of macular and retinal involvement that can be treated early to improve the prognosis.

Over the last decade, new multimodal imagings are becoming more accessible; therefore, rapid diagnosis can be made. In addition to newer approved biologic agents, ocular Behçet's disease is seen to be in better controlled with fewer complications.
Efficacy of teprotumumab therapy in patients with long-duration thyroid eye disease
Authors: Subramanian Prem S. , Cho Raymond I. , Kahana Alon
Published: August 2023

Purpose of review

Teprotumumab, an inhibitor of the insulin-like growth factor 1 receptor (IGF-1R), was approved by the US Food and Drug Administration in January 2020 for the treatment of thyroid eye disease (TED). The clinical trials leading to its approval enrolled patients with recent disease onset and significant inflammatory symptoms and signs. Subsequent real-world teprotumumab use in patients with longer duration of disease also may be effective, and there have been several publications reporting on experience in these patient groups.

Recent findings

TED results in disfiguring changes such as ocular proptosis and affects visual function by altering extraocular muscle function, leading to diplopia. Compressive optic neuropathy also may occur, and disease manifestations may persist for years. Teprotumumab treatment in cases of TED in which prior interventions (medical or surgical) had failed, or in treatment-naïve patients whose disease had been stable for years, has been reported to improve both clinical signs and symptoms (proptosis, diplopia) and to reduce the pathologic orbital changes as assessed by orbital imaging.

Teprotumumab may be an appropriate treatment for TED regardless of disease duration and irrespective of the presence or absence of markers of active inflammation within the orbit.
Surveying Early Intervention Providers to Identify Opportunities for Workforce Support to Strengthen Family-Centered Care
Authors: Griffith Shayl F. , Magariño Loreen S. , Martínez Pedraza Frances D. , Frazier Stacy L. , Berkovits Michelle D. , Bagner Daniel M.
Published: August 2023

Traditional provider-to-child models of early intervention (EI) service provision have been increasingly replaced by service guidelines that promote a broader family-centered approach to support improvement in the child's primary area of delay. These guidelines include working directly with caregivers and addressing needs of the family that might impact a caregivers' capacity to engage in developmentally supportive interactions with children (e.g., caregiver distress). Knowledge of provider skills, practices, and attitudes would inform efforts to broaden and enhance practice in line with these guidelines. Within an academic-community partnership to support EI, we surveyed 88 providers in Miami and Boston about their usual practice, perceptions of their skills, general attitudes toward evidence-based practices, and interest in specific training opportunities. Findings indicated that providers spent more time working directly with children than caregivers. Providers reported high interest in training to manage caregiver distress, support preschool readiness, and align work with family culture. Negative overall attitudes toward using evidence-based interventions and provider exhaustion were related to less interest in obtaining training in culturally responsive practice. Exhaustion also related to less interest in training on other topics that represent a broadened scope of care, including building warm parent–child relationships. Findings are informing efforts to design EI training opportunities to improve parent–provider relations, enhance parent–child interactions, and reduce caregiver stress.
A Framework for the Design of Inclusive Community-Based Early Childhood Intervention Programs
Authors: Guralnick Michael J.
Published: August 2023

In this article, a framework for the creation of a fully inclusive and comprehensive early childhood intervention system is described. Although aspirational at this time, the potential for developmental science, intervention science, and implementation science to be integrated to maximize the effectiveness of early intervention systems is presented in the context of the Developmental Systems Approach. This framework guides a practice model emphasizing a family-centered problem-solving process that focuses on supporting well-characterized family patterns of interaction that contribute to children's development. Discussed as well is the ability of such an integrated system to be compatible with and incorporate principles and practices from a human rights perspective; all designed to support family and child goals. The transformational potential of this framework for organizing inclusive community-based early childhood programs is considered.
A simulated pedagogical intervention to educate nurse practitioner students about human trafficking
Authors: Valdes Beatriz , Salani Deborah , Falcon Ashley , McKay Mary , Arrojo Michelle , Quintana Amauri , DeSantis Joseph P.
Published: August 2023

Human trafficking (HT) affects an estimated 40.3 million people globally with 24.9 million people affected in forced labor and 4.8 million in forced sexual exploitation. An estimated 18,000 people are trafficked yearly into the United States. Reports suggest that between 63% and 87% of trafficked persons were seen by health care professionals and were unrecognized while in captivity. The authors designed and implemented an innovative pedagogical intervention for nurse practitioner (NP) students using a 10-min simulation-based education encounter with a standardized patient depicting a potential sex or labor HT clinical presentation. Results demonstrated that simulation-based education is a feasible way to provide HT education to NP students. It is imperative that future NPs receive education/training about HT to recognize potential victims and promote access to appropriate resources.
Chronic daily respiratory care needs in people with cystic fibrosis treated with highly effective cystic fibrosis transmembrane conductance regulator modulators
Authors: Wajda Katherine E. , Roesch Erica A. , Gifford Alex H.
Published: August 2023

Purpose of review

Cystic fibrosis is a genetic disease that increases risk of death from respiratory failure because of impairment in mucociliary clearance. Complex daily care regimens including medications and airway clearance techniques (ACTs) aim to preserve lung function and alleviate symptoms for people with cystic fibrosis (pwCF). The success of highly effective modulator therapy (HEMT) permits evaluation of treatment simplification. In this review, we evaluate adjustments made in daily respiratory care among pwCF taking HEMT and the feasibility of treatment simplification.

Recent findings

Treatment simplification has been identified as a top priority among pwCF, with recent studies showing pwCF are willing to sacrifice mild to moderate amounts of lung function and longevity to reduce treatment burden. Retrospective studies have shown that patients taking HEMT with better baseline lung function have lower adherence to and prescription of inhaled medications. A randomized, controlled trial found that short-term discontinuation of dornase alfa or hypertonic saline was clinically noninferior to continuation of these medications. Major knowledge gaps remain about withdrawing ACTs.

This review highlights trials evaluating the feasibility of treatment simplification among pwCF taking HEMT. More data is needed to evaluate approaches to simplification in this phenotypically diverse patient population.
Ménière's disease is a disorder of the inner ear
Authors: Ahmad Jumah G. , Lin Kenny F.
Published: August 2023

Purpose of review

Ménière's disease is a disorder characterized by recurrent episodes of vertigo, hearing loss, tinnitus, and pressure in the ear. Its pathogenesis and optimal management continue to be the subject of ongoing debate. Although it is classically believed to be a primary disorder of the inner ear, some clinicians have hypothesized that it is a form of vestibular migraine.

Recent findings

Evidence supporting vestibular migraine in the differential of Ménière's disease includes overlap of symptoms, high prevalence of migraines in patients with Ménière's disease, and the efficacy of migraine treatments for symptoms of Ménière's disease in some patients. However, there is far more evidence to support Ménière's disease as a disorder of the inner ear, including genetic and histologic changes of hydrops, imaging studies showing hydropic changes, predominance of low-frequency hearing loss, clinical efficacy of treatments targeted at inflammatory change/hydrops, and clinical efficacy of ablating the vestibular end-organ.

Although there is conflicting evidence regarding the cause and treatment of Ménière's disease, current evidence favors it as a disorder of the inner ear. Further research is needed to fully understand the mechanisms of Ménière's disease and how to improve diagnosis and treatment outcomes.
Implementing a Disease-specific Multidisciplinary Team and Order Set for Hemophagocytic Lymphohistiocytosis in a Pediatric Hospital
Authors: Rousset Meaghan , Orr Kaci , Gartstein Evelyn , Anthony Aly , Brady Steven , Rios Ana , Guirola Ricardo , Perez Maria , Eames Gretchen , Howrey Richard , Trinkman Heidi , Chaimowitz Natalia , Diaz Maranda , Ray Anish
Published: August 2023

Objective:

To improve outcomes of hemophagocytic lymphohistiocytosis (HLH), prompt recognition and treatment are necessary. A HLH multidisciplinary team was implemented at our institution, and we established an electronic order set to foster uniformity in the diagnostic approach. The goal of this study is to capture the impact of this diagnostic tool.

Methods:

This is a retrospective study analyzing the utilization of a HLH-specific order set since time of implementation in June 2019 through December 2022. The trends in the utilization of the order set by providers were analyzed to evaluate the awareness and effectiveness of this tool.

Results:

The order set was utilized 50 times, most commonly by hematology/oncology (50%) and infectious disease (26%). Utilization by providers on newly presenting patients included 4 times in the year 2019, 12 times in 2020, 16 times in 2021, and 18 times in 2022. Utilization was associated with the diagnosis of HLH in 9 patients (18%).

Conclusion:

Implementation of an HLH-specific order set facilitated a systematic method to approach patients with suspected HLH. The utilization of the order set displayed an upward trend over time, indicating support of this tool among these providers. This tool can increase awareness and early identification of HLH.
The disease burden of respiratory syncytial virus in Infants
Authors: Munro Alasdair P.S. , Martinón-Torres Federico , Drysdale Simon B. , Faust Saul N.
Published: August 2023

Purpose of review

To describe the current global burden of respiratory syncytial virus (RSV) in infants and its implications for morbidity, health resources and economic costs.

Recent findings

New prophylactic therapies are on the horizon for RSV in the form of long-acting monoclonal antibodies suitable for healthy infants and maternal immunizations.

Despite being responsible for significant global infant morbidity and mortality, until recently there have been no effective therapeutics available for healthy infants to protect them from RSV. Several new drugs are likely to be available within the next few years which could help relieve a huge burden on healthcare systems over the coming winters.
Three-Dimensional Digital Technology: A Powerful Assistant for the Reconstruction of Complex Craniofacial Deformities
Authors: Huang Qinghua , Chen Zhewei , Li Binghang , Yang Bin
Published: August 2023

Three-dimensional digital technology has been widely applied in craniofacial surgeries, particularly in conventional procedures such as facial contouring and orthognathic surgery. To some extent, the process has already been standardized. As to reconstruction surgeries of complex craniofacial deformity, however, surgical plans need to be patient-specific. Traditionally, individualized surgical treatment largely relies on the surgeon’s clinical experience. The application of digital technology mainly focuses on preoperative planning and postoperative evaluation of surgical outcomes rather than intraoperative patient-specific implants or osteotomy guides. For patients with complex craniofacial deformities, requirements for accurate 3-dimensional digital technology can be much higher. This study presents a favorable surgical reconstruction of the severe craniofacial deformity using 3-dimensional digital technology, providing references for craniofacial surgeons, which could be beneficial to clinical practice and treatment efficacy.
Observation of viscous liquid flow in tobacco substrate during heating using optical coherence tomography
Authors: Pratiwi Tiara N. , Iwai Toshiaki , Nakaya Iori , Lenggoro I. Wuled
Published: August 2023

The present study used optical coherence tomography (OCT) to monitor the dynamics of a highly viscous liquid in a porous tobacco substrate during heating. The OCT technique was integrated with a specially designed heating chamber and an air pump for measuring. Two transitional points in the liquid behaviours at different temperatures were estimated using OCT and statistical analysis of the attenuation coefficient. The first point, ‘A’, shows the time approximation at which the penetration-dominant zone transitions into the evaporation-dominant zone. The second point, ‘B’, indicates the time approximation at which rapid evaporation of free liquid transitions into slow evaporation of trapped and bound liquid. This analytical system is an alternative for tracking liquid transport in porous biomass during heating.
Marsupial position on life-history continua and the potential contribution of life-history traits to population growth
Authors: Ferreira Mariana Silva , Dickman Christopher R. , Fisher Diana O. , Figueiredo Marcos de Souza Lima , Vieira Marcus Vinícius
Published: August 2023

Previous studies have suggested that mammal life history varies along the fast–slow continuum and that, in eutherians, this continuum is linked to variation in the potential contribution of survival and reproduction to population growth rate (
λ
). Fast eutherians mature early, have large litters and short lifespans, and exhibit high potential contribution of age at first reproduction and fertility to
λ
, while slow eutherians show high potential contribution of survival to
λ
. However, marsupials have typically been overlooked in comparative tests of mammalian life-history evolution. Here, we tested whether the eutherian life-history pattern extends to marsupials, and show that marsupial life-history trade-offs are organized along two major axes: (i) the reproductive output and dispersion axis, and (ii) the fast–slow continuum, with an additional association between adult survival and body mass. Life-history traits that potentially drive changes in
λ
are similar in eutherians and marsupials with slow life histories, but differ in fast marsupials; age at first reproduction is the most important trait contributing to
λ
and fertility contributes little. Marsupials have slower life histories than eutherians, and differences between these clades may derive from their contrasting reproductive modes; marsupials have slower development, growth and metabolism than eutherians of equivalent size.
Non-pharmaceutical interventions for COVID-19: a systematic review on environmental control measures
Authors: Madhusudanan Anagha , Iddon Christopher , Cevik Muge , Naismith James H. , Fitzgerald Shaun
Published: August 2023

The purpose of this review was to identify the effectiveness of environmental control (EC) non-pharmaceutical interventions (NPIs) in reducing transmission of SARS-CoV-2 through conducting a systematic review. EC NPIs considered in this review are room ventilation, air filtration/cleaning, room occupancy, surface disinfection, barrier devices,CO2monitoring and one-way-systems. Systematic searches of databases from Web of Science, Medline, EMBASE, preprint servers MedRxiv and BioRxiv were conducted in order to identify studies reported between 1 January 2020 and 1 December 2022. All articles reporting on the effectiveness of ventilation, air filtration/cleaning, room occupancy, surface disinfection, barrier devices,CO2monitoring and one-way systems in reducing transmission of SARS-CoV-2 were retrieved and screened. In total, 13 971 articles were identified for screening. The initial title and abstract screening identified 1328 articles for full text review. Overall, 19 references provided evidence for the effectiveness of NPIs: 12 reported on ventilation, 4 on air cleaning devices, 5 on surface disinfection, 6 on room occupancy and 1 on screens/barriers. No studies were found that considered the effectiveness ofCO2monitoring or the implementation of one-way systems. Many of these studies were assessed to have critical risk of bias in at least one domain, largely due to confounding factors that could have affected the measured outcomes. As a result, there is low confidence in the findings. Evidence suggests that EC NPIs of ventilation, air cleaning devices and reduction in room-occupancy may have a role in reducing transmission in certain settings. However, the evidence was usually of low or very low quality and certainty, and hence the level of confidence ascribed to this conclusion is low. Based on the evidence found, it was not possible to draw any specific conclusions regarding the effectiveness of surface disinfection and the use of barrier devices. From these results, we further conclude that community agreed standards for well-designed epidemiological studies with low risk of bias are needed. Implementation of such standards would enable more confident assessment in the future of the effectiveness of EC NPIs in reducing transmission of SARS-CoV-2 and other pathogens in real-world settings.

This article is part of the theme issue ‘The effectiveness of non-pharmaceutical interventions on the COVID-19 pandemic: the evidence’.
Pontibacterium sinense sp. nov., a nitrate-reducing and thiosulphate-oxidizing bacterium, isolated from coastal sediment
Authors: Chen Rui-Ying , Chen Rui-Jie , Lu De-Chen , Gong Ya , Du Zong-Jun
Published: August 2023

A novel bacterial strain, N1Y112T, was isolated from coastal sediment collected in Weihai, PR China. This Gram-stain-negative, facultatively anaerobic, motile rod-shaped bacterium exhibited the ability to oxidize thiosulphate to sulphate and reduce nitrate to ammonia through its Sox system and nitrate reduction pathway, respectively. The strain grew at 20–35 °C (optimum, 28 °C), pH 6.0–10.0 (optimum, pH 7.5) and in the presence of 1.0–5.0 % (w/v) NaCl (optimum, 3.0 %). Major fatty acids present in the strain included summed feature 8 (comprising C18 : 1
 ω7c and/or C18 : 1
 ω6c), summed feature 3 (comprising C16 : 1
 ω7c and/or C16 : 1
 ω6c) and C16 : 0. Its polar lipid profile consisted of one phosphatidylethanolamine, two unknown aminolipids, one aminophosphoglycolipid, one diphosphatidylglycerol, one phosphatidylglycerol, two unknown phospholipids and two unknown lipids. Strain N1Y112T contained ubiquinone-7 and ubiquinone-8 as isoprenoid quinones, with a genomic G+C content of 50.6 mol%. Based on phylogenetic analysis, strain N1Y112T clustered with

Pontibacterium granulatum

JCM 30316T being its closest relative at 97.1 % 16S rRNA gene sequence similarity. The average nucleotide identity and digital DNA–DNA hybridization values were 77.1 and 20.7 %, respectively, which suggest significant differences between genomes of N1Y112T and

P. granulatum

JCM 30316T. Based on the findings from its phenotypic, genotypic and phylogenetic analyses, N1Y112T is considered to represent a novel species of the genus

Pontibacterium

, for which the name Pontibacterium sinense sp. nov. is proposed. The type strain is N1Y112T (=KCTC 72927T=MCCC 1H00429T).
Comparison of logistic regression with regularized machine learning methods for the prediction of tuberculosis disease in people living with HIV: cross-sectional hospital-based study in Kisumu County, Kenya
Authors: Orwa James , Oduor Patience , Okelloh Douglas , Gethi Dickson , Agaya Janet , Okumu Albert , Wandiga Steve
Published: August 2023

Background

Tuberculosis (TB) is a major public health concern, particularly among people living with the Human immunodeficiency Virus (PLWH). Accurate prediction of TB disease in this population is crucial for early diagnosis and effective treatment. Logistic regression and regularized machine learning methods have been used to predict TB, but their comparative performance in HIV patients remains unclear. The study aims to compare the predictive performance of logistic regression with that of regularized machine learning methods for TB disease in HIV patients.

Methods

Retrospective analysis of data from HIV patients diagnosed with TB in three hospitals in Kisumu County (JOOTRH, Kisumu sub-county hospital, Lumumba health center) between [dates]. Logistic regression, Lasso, Ridge, Elastic net regression were used to develop predictive models for TB disease. Model performance was evaluated using accuracy, and area under the receiver operating characteristic curve (AUC-ROC).

Results

Of the 927 PLWH included in the study, 107 (12.6%) were diagnosed with TB. Being in WHO disease stage III/IV (aOR: 7.13; 95%CI: 3.86-13.33) and having a cough in the last 4 weeks (aOR: 2.34;95%CI: 1.43-3.89) were significant associated with the TB. Logistic regression achieved accuracy of 0.868, and AUC-ROC of 0.744. Elastic net regression also showed good predictive performance with accuracy, and AUC-ROC values of 0.874 and 0.762, respectively.

Conclusions

Our results suggest that logistic regression, Lasso, Ridge regression, and Elastic net can all be effective methods for predicting TB disease in HIV patients. These findings may have important implications for the development of accurate and reliable models for TB prediction in HIV patients.
The Clinical Effectiveness of One-Dose HPV Vaccine: A meta-analysis of 902,368 vaccinated women
Authors: Setiawan Didik , Nurulita Nunuk Aries , Khoirunnisa Sudewi Mukaromah , Postma Maarten J
Published: August 2023

Introduction

Although the effectiveness of the HPV vaccine has been comprehensively described, adherence to dosing and limited budget is one of the causes of delay in HPV vaccination implementation in a country. A one-dose HPV vaccine could possibly solve those issues since several studies show promising results.

Areas covered

This is a systematic review and meta-analysis focusing on the effectiveness of the one-dose HPV vaccine compared to two- and three doses of vaccination. We focused on clinical effectiveness, including prevention of HPV16, HPV18, and hrHPV infection, HSIL or ASC-H incidence, and CIN II/III incidence.

Expert opinion

Our review showed that a one-dose HPV vaccine could potentially be as effective as two-or three doses since it offers immunogenic protection up to 8 years follow up and also prevention on infection and pre-cancers incidence. However, more studies and an extended duration of existing studies are required in order to provide robust evidence of this recommendation.
Natural Language Processing for Adjudication of Heart Failure Hospitalizations in a Multi-Center Clinical Trial
Authors: Cunningham Jonathan W. , Singh Pulkit , Reeder Christopher , Claggett Brian , Marti-Castellote Pablo M. , Lau Emily S. , Khurshid Shaan , Batra Puneet , Lubitz Steven A. , Maddah Mahnaz , Philippakis Anthony , Desai Akshay S. , Ellinor Patrick T. , Vardeny Orly , Solomon Scott D. , Ho Jennifer E.
Published: August 2023

Background

The gold standard for outcome adjudication in clinical trials is chart review by a physician clinical events committee (CEC), which requires substantial time and expertise. Automated adjudication by natural language processing (NLP) may offer a more resource-efficient alternative. We previously showed that the Community Care Cohort Project (C3PO) NLP model adjudicates heart failure (HF) hospitalizations accurately within one healthcare system.

Methods

This study externally validated the C3PO NLP model against CEC adjudication in the INVESTED trial. INVESTED compared influenza vaccination formulations in 5260 patients with cardiovascular disease at 157 North American sites. A central CEC adjudicated the cause of hospitalizations from medical records. We applied the C3PO NLP model to medical records from 4060 INVESTED hospitalizations and evaluated agreement between the NLP and final consensus CEC HF adjudications. We then fine-tuned the C3PO NLP model (C3PO+INVESTED) and trained ade novomodel using half the INVESTED hospitalizations, and evaluated these models in the other half. NLP performance was benchmarked to CEC reviewer inter-rater reproducibility.

Results

1074 hospitalizations (26%) were adjudicated as HF by the CEC. There was high agreement between the C3PO NLP and CEC HF adjudications (agreement 87%, kappa statistic 0.69). C3PO NLP model sensitivity was 94% and specificity was 84%. The fine-tuned C3PO andde novoNLP models demonstrated agreement of 93% and kappa of 0.82 and 0.83, respectively. CEC reviewer inter-rater reproducibility was 94% (kappa 0.85).

Conclusion

Our NLP model developed within a single healthcare system accurately identified HF events relative to the gold-standard CEC in an external multi-center clinical trial. Fine-tuning the model improved agreement and approximated human reproducibility. NLP may improve the efficiency of future multi-center clinical trials by accurately identifying clinical events at scale.
Evaluating the Safety Profile of the CoronaVac in Adult and Elderly populations: A Phase IV Prospective Observational Study in Brazil
Authors:   Monica Akissue de Camargo Teixeira Cintra, Fernandes Eder Gatti , Infante Vanessa , Loch Ana Paula , Ragiotto Lucas , Braga Patrícia Emília , Salomão Maria da Graça , Lucchesi Maria Beatriz Bastos , de Oliveira Mayra Martho Moura , Gattás Vera Lúcia , da Silva Anderson Soares , Villas Boas Paulo José Fortes , Lopes Marta Heloisa , Moreira José , Boulos Fernanda Castro ,   CFV-01-IB study group
Published: August 2023

Objective

This Phase IV prospective observational study aimed to evaluate the safety and monitor adverse events following immunization (AEFI) associated with CoronaVac, an inactivated SARS-CoV-2 vaccine, in Brazilian adult (18-59 years) and elderly (≥60 years) populations.

Methods

Participants (n=538; 487 adults and 51 elderly) were enrolled from three public health services in São Paulo, Brazil. A two-dose vaccination regimen, administered 14 days apart, was used. The study assessed Adverse Reactions (AR) necessitating medical attention within seven days post-vaccination dose and monitored AEFI for a period of 42 days. Safety was monitored through a review of participant diary cards, telephone contacts, and on-site study visits.

Results

Among adults, the most frequently reported local AR after the first and second dose was pain (256[52.6%] and 129 [29.5], respectively), while the most common systemic reaction was a headache (158[34.5%] and 51 [11.6%], respectively). Most local and systemic solicited ARs were of Grade 1 or 2, with these reactions being more prevalent in adults after the first dose. One serious adverse event possibly related to the vaccine was reported among adults, but there were no fatalities. Nine adult participants experienced adverse events of special interest, which included five cases of Covid-19.

Conclusion

CoronaVac demonstrated safety and tolerability in the observed population. Ongoing post-marketing surveillance is crucial for the identification of rare adverse events and further affirmation of the vaccine’s safety profile.
Jumping between Turtles, Fishes, and a Frog: The Unexpected Horizontal Transfer of a DNA Transposon
Authors: Hassan Nozhat T. , Galbraith James D. , Adelson David L.
Published: August 2023

Horizontal transfer of transposable elements (HTT) has been reported across many species and the impact of such events on genome structure and function has been well described. However, few studies have focused on reptilian genomes, especially HTT events in Testudines (turtles). Here, we investigated the repetitive content ofMalaclemys terrapin terrapin(Diamondback turtle) and found a high similarity hAT-6 DNA transposon shared between other turtle species, ray-finned fishes, and a frog. hAT-6 was notably absent in taxa closely related to turtles, such as crocodiles and birds. Successful invasion of DNA transposons into new genomes requires the conservation of specific residues in the encoded transposase, and through structural analysis, these residues were identified indicating retention of functional transposition activity. We document a rare and recent HTT event of a DNA transposon between turtles which are known to have a low genomic evolutionary rate and ancient repeats.
Serum metabolomics improve risk stratification for incident heart failure
Authors: Oexner Rafael R. , Ahn Hyunchan , Theofilatos Konstantinos , Shah Ravi A. , Schmitt Robin , Chowienczyk Philip , Zoccarato Anna , Shah Ajay M.
Published: August 2023

Background and Aims

Prediction and early detection of heart failure (HF) is crucial to mitigate its impact on quality of life, survival, and healthcare expenditure. In this study, we explored the predictive value of serum metabolomics (168 metabolites detected by proton nuclear magnetic resonance (1H-NMR) spectroscopy) for incident HF.

Methods

We leveraged data of 68,311 individuals and > 0.8 million person-years of follow-up from the UK Biobank (UKB) cohort to assess individual metabolite associations and to train models to predict HF risk in individuals not previously considered at risk. Specifically, we (I) fitted per-metabolite COX proportional hazards (COX-PH) models to assess individual metabolite associations and (II) trained and internally validated elastic net (EN) models to predict incident HF using the serum metabolome. We benchmarked discriminative capacities against a comprehensive, well-validated clinical risk score (Pooled Cohort Equations to Prevent HF, PCP-HF1).

Results

During median follow-up of ≈ 12.3 years, several metabolites showed independent association with incident HF (90/168 adjusting for age and sex, 48/168 adjusting for PCP-HF; false discovery rate (FDR)-controlled P < 0.01). Performance-optimized risk models effectively retained key predictors representing highly correlated clusters (≈ 80 % feature reduction). The addition of metabolomics to PCP-HF improved predictive performance (Harrel’s C: 0.768 vs. 0.755.; continuous net reclassification improvement (NRI) = 0.287; relative integrated discrimination improvement (IDI): 17.47 %). Simplified models including age, sex and metabolomics performed almost as well as PCP-HF (Harrel’s C: 0.745 vs. 0.755, continuous NRI: 0.097, relative IDI: 13.445 %). Risk and survival stratification was improved by the integration of metabolomics.

Conclusions

The assessment of serum metabolomics improves incident HF risk prediction. Scores based simply on age, sex and metabolomics exhibit similar predictive power to clinically-based models, potentially offering a cost- and time-effective, standardizable, and scalable single-domain alternative to more complex clinical scores.
Antibody Neutralization of Emerging SARS-CoV-2: EG.5.1 and XBC.1.6
Authors: Wang Qian , Guo Yicheng , Zhang Richard M. , Ho Jerren , Mohri Hiroshi , Valdez Riccardo , Manthei David M. , Gordon Aubree , Liu Lihong , Ho David D.
Published: August 2023

SARS-CoV-2 variants EG.5.1 and XBC.1.6 have recently emerged, attracting increased attention due to their rapid expansion globally and in Australia, respectively. EG.5.1 evolved from Omicron subvariant XBB.1.9, harboring additional Q52H and F456L spike substitutions. The F456L mutation is located within the epitopes of many class-1 monoclonal antibodies (mAbs) directed to the receptor-binding domain (RBD), raising concerns about further antibody evasion. XBC.1.6, a descendant of a Delta-BA.2 recombinant, carries 15 additional spike mutations. The extent to which antibody evasion contributes to the growth advantage of XBC.1.6 in Australia remains to be determined. To assess the antibody evasion properties of the emergent variants, we conducted pseudovirus neutralization assays using sera from individuals who received three doses of COVID-19 mRNA monovalent vaccines plus one dose of a BA.5 bivalent vaccine, as well as from patients with BQ or XBB breakthrough infection. The assays were also performed using a panel of 14 mAbs that retained neutralizing activity against prior XBB subvariants. Our data suggested that EG.5.1 was slightly but significantly more resistant (< 2-fold) to neutralization by BQ and XBB breakthrough sera than XBB.1.16, which is known to be antigenically similar to XBB.1.5. Moreover, the F456L mutation in EG.5.1 conferred heightened resistance to certain RBD class-1 mAbs. In contrast, XBC.1.6 was more sensitive to neutralization by sera and mAbs than the XBB subvariants. Notably, XBB breakthrough sera retained only weak neutralization activity against XBB subvariants. In summary, EG.5.1 and XBC.1.6 exhibited distinct antibody evasion properties. The recent global expansion of EG.5.1 might be attributable, in part, to its enhanced neutralization resistance. That XBB breakthrough infections did not elicit a robust antibody neutralization response against XBB subvariants is indicative of immunological imprinting. The high prevalence of XBC.1.6 in Australia is not due to enhanced antibody evasion.
Enhancing t-SNE Performance for Biological Sequencing Data through Kernel Selection
Authors: Chourasia Prakash , Murad Taslim , Ali Sarwan , Patterson Murray
Published: August 2023

The genetic code for many different proteins can be found in biological sequencing data, which offers vital insight into the genetic evolution of viruses. While machine learning approaches are becoming increasingly popular for many “Big Data” situations, they have made little progress in comprehending the nature of such data. One such area is the t-distributed Stochastic Neighbour Embedding (t-SNE), a generalpurpose approach used to represent high dimensional data in low dimensional (LD) space while preserving similarity between data points. Traditionally, the Gaussian kernel is used with t-SNE. However, since the Gaussian kernel is not data-dependent, it determines each local bandwidth based on one local point only. This makes it computationally expensive, hence limited in scalability. Moreover, it can misrepresent some structures in the data. An alternative is to use the isolation kernel, which is a data-dependent method. However, it has a single parameter to tune in computing the kernel. Although the isolation kernel yields better performance in terms of scalability and preserving the similarity in LD space, it may still not perform optimally in some cases. This paper presents a perspective on improving the performance of t-SNE and argues that kernel selection could impact this performance. We use 9 different kernels to evaluate their impact on the performance of t-SNE, using SARS-CoV-2 “spike” protein sequences. With three different embedding methods, we show that the cosine similarity kernel gives the best results and enhances the performance of t-SNE.
Metastable Intermediates Identified in Epithelial to Mesenchymal Transition are Regulated by G-Quadruplex DNA Structures
Authors: King Jessica J. , Evans Cameron W. , Kadolsky Ulrich D. , Norret Marck , Iqbal Munir , Mercé Clémentine , Bhatia Sugandha , Gregory Philip A. , Thompson Erik W. , Saxena Alka , Iyer K. Swaminathan , Smith Nicole M.
Published: August 2023

Cancer is a heterogenous disease, with multiple cellular subpopulations present within a single tumour mass that differ genetically and morphologically, and thus respond differently to chemotherapeutics. Epithelial-to-Mesenchymal transition (EMT) has been shown to play a role in tumour heterogeneity. Single-cell sequencing is critical to identify cell-type-specific transcriptomic differences with multiplexing methods increasing experimental scope with reduced cost. Cell hashing with barcoded antibodies is commonly used to multiplex samples but is limited to samples expressing target antigens. Antigen-independent methods of barcoding cells, such as barcoded lipid-anchors, have gained traction but present substantial populations that cannot be unambiguously demultiplexed. Herein we report a multiplexed single-cell transfection-enabled cell hashing sequencing (scTECH-seq) platform, which uses antigen-independent endocytic uptake to barcode cells, resulting in efficient, uniform barcoding with high cell recovery. We apply this methodology to identify distinct metastable cell states in human mammary cells undergoing EMT and show that stabilisation of G-quadruplex DNA has the potential to inhibit EMT.
Identifying LasR quorum sensors with improved signal specificity by mapping the sequence-function landscape
Authors: Zeng Min , Sarker Biprodev , Rondthaler Stephen N. , Vu Vanessa , Andrews Lauren B.
Published: August 2023

Programmable intercellular signaling using components of naturally-occurring quorum sensing can allow for coordinated functions to be engineered in microbial consortia. LuxR-type transcriptional regulators are widely used for this purpose and are activated by homoserine lactone (HSL) signals. However, they often suffer from imperfect molecular discrimination of structurally similar HSLs, causing misregulation within engineered consortia containing multiple HSL signals. Here, we studied one such example, the regulator LasR fromPseudomonas aeruginosa. We elucidated its sequence-function relationship for ligand specificity using targeted protein engineering and multiplexed high-throughput biosensor screening. A pooled combinatorial saturation mutagenesis library (9,486 LasR DNA sequences) was created by mutating six residues in LasR’s β5 sheet with single, double, or triple amino acid substitutions. Sort-seq assays were performed in parallel using cognate and non-cognate HSLs to quantify each corresponding sensor’s response to each HSL signal, which identified hundreds of highly specific variants. Sensor variants identified were individually assayed and exhibited up to 60.6-fold (p= 0.0013) improved relative activation by the cognate signal compared to the wildtype. Interestingly, we uncovered prevalent mutational epistasis and previously unidentified residues contributing to signal specificity. The resulting sensors with negligible signal crosstalk could be broadly applied to engineer bacteria consortia.