bluuebunny/crossref_metadata_2025 huggingface dataset:
Study protocol for a randomized controlled trial of the NEIVATECH virtual reality system to improve visual function in children with anisometropic amblyopia
Authors: Leal Vega L. , Piñero D. P. , Hernández Rodríguez C. J. , Molina Martín A. , Morales-Quezada L. , Vallelado Álvarez A. I. , Arenillas Lara J. F. , Coco Martín M. B.
Published: June 2022

Background

Interest in developing alternative methods for the treatment of amblyopia has long been a topic of interest among clinicians and researchers, as prescribed occlusion and penalization therapies do not always provide an effective response and are associated with a high risk of recurrence and non-compliance. Here, we present the protocol of a small-scale RCT to evaluate the safety and clinical efficacy of a novel VR-based system designed to provide binocular vision training to children with anisometropic amblyopia.

Methods

We aim to recruit a total of 60 children with anisometropic amblyopia aged 5-17 years with no previous treatment for amblyopia other than refractive correction from the pediatric ophthalmology units of the University Clinical Hospital of Valladolid and the Vithas Medimar International Hospital of Alicante. Children who meet the eligibility criteria and consent to participate will be randomly assigned to a three-month intervention group of 18 half-hour in-office therapy sessions with the NEIVATECH system (group A) or to a parallel group receiving 2 hours of conventional patching per day at home for the same period of time (group B). Assessments of visual function will be carried out before the intervention and at 1, 2 and 3 months, with changes in distance BCVA being the primary outcome measure to be considered. Patient safety, compliance, satisfaction and acceptance to treatment will also be assessed after therapy as other valuable outcome measures. In addition, a rsfMRI scan will be performed on a subgroup of 5 patients from each group at the pre-intervention visit and at the post-intervention visit to test the effects of both therapies on neural plasticity in the visual cortex.

Discussion

The NEIVATECH system has been conceived as a serious game designed to provide binocular vision training to anisometropic amblyopic children by complementing the concepts of perceptual learning, dichoptic training and gamification in an immersive VR environment. We hope that this novel approach may lead to greater improvements in vision performance than those provided so far by conventional patching in anisometropic amblyopic children.

Trial registration

This protocol was registered with ClinicalTrials.gov (NCT04819386) on 29 March 2021.
OCT biomarkers related to subthreshold micropulse laser treatment effect in central serous chorioretinopathy
Authors: Zheng Fang , He Jingliang , Su Zhitao , Liu Ye , Xu Yufeng , Liu Lei , Ye Panpan
Published: June 2022

Background

To identify the OCT biomarkers related to the anatomical outcomes in eyes with central serous chorioretinopathy (CSCR) after subthreshold micropulse laser (SML) treatment.

Methods

Patients with CSCR underwent SML were enrolled in this retrospective study. Only patients who underwent enhanced depth imaging optical coherence tomography (EDI-OCT) examination before and after SML were selected. Patients were divided into two groups based on whether subretinal fluid (SRF) absorbed or not after SML. Group 1 was the SRF resolved group, and Group 2 was the SRF non-resolved group. Factors including age and gender, duration of symptoms, CSCR history, the height of SRF at baseline, retinal pigment epithelium (RPE) /inner choroid alterations, as well as subfoveal choroidal thickness (SFCT) of the affected eye and the fellow eye before and after SML were recorded and compared between two groups. Longitudinal change of SFCT of a subgroup of patients were analyzed.

Results

A total of 58 eyes of 58 patients were involved in this study. SRF of 31 eyes got completely absorbed, and SRF of 27 eyes was retained after SML. Logistic regression analysis revealed baseline SFCT of the affected eye (OR = 1.007, 95% CI: 1.001–1.012, P = 0.019) and RPE/inner choroid alterations (OR = 25.229, 95% CI: 2.890–220.281, P = 0.004) were correlated with SML efficacy. Thirty-three eyes of 33 patients were enrolled in the subgroup analysis. A significant difference of SFCT changes between two groups were demonstrated (P = 0.001). The difference of SFCT between baseline and three months after SML was also related to SRF resolution (OR = 0.952, 95% CI: 0.915–0.990, P = 0.014).

Conclusion

Baseline SFCT, change of SFCT at 3-month after treatment, and RPE/inner choroid alterations were the OCT biomarkers related to SRF resolution after SML treatment.
Compound heterozygous variations in IARS1 cause recurrent liver failure and growth retardation in a Chinese patient: a case report
Authors: Zou Ting-Ting , Sun Hua-Qin , Zhu Yu , He Tian-Tian , Ling Wen-Wu , Zhu Hong-Mei , Lin Zi-Yuan , Liu Yan-Yan , Liu Shan-Ling , Wang He , Zhang Xue-Mei
Published: June 2022

Background

Aminoacyl-tRNA synthetases (ARSs) are enzymes responsible for attaching amino acids to tRNA, which enables protein synthesis. Mutations in isoleucyl-tRNA synthetase (IARS1) have recently been reported to be a genetic cause for growth retardation, intellectual disability, muscular hypotonia, and infantile hepatopathy (GRIDHH).

Case presentation

In this study, we reported an additional case of compound heterozygous missense variations c.701 T > C (p.L234P) and c.1555C > T (p.R519C) in IARS1, which were identified using medical exome sequencing; c.701 T > C (p.L234P) was a novel variant, and c.1555C > T (p.R519C) was found in GnomAD. Unlike other reported patients, this individual presented prominently with recurrent liver failure, which led to her death at an early age of 19 months. She also had significant growth retardation, muscular hypotonia, chubby and flabby face, recurrent loose stools, and abnormal brain computed tomography (CT), while zinc deficiency and hearing loss were not present. Studies in zebrafish embryo modeling recapitulated some of the key phenotypic traits in embryo development, neurodevelopment, liver development, and myogenesis, demonstrating that these variations caused a loss of gene function in IARS1.

Conclusions

We have found a novel mutation point c.701 T > C (p.L234P) in IARS1. Compound heterozygous mutations of c.701 T > C (p.L234P) and c.1555C > T (p.R519C) in IARS1 are pathogenic, which can cause GRIDHH in child.
Changes in self-harm- and violence-related urgent psychiatric consultation in the emergency department during the different stages of the COVID-19 pandemic
Authors: Liu Chun-Hao , Chen Po-Cheng , Chen Jian-Hong , Yeh Chung-Cheng
Published: June 2022

Background

The coronavirus disease 2019 pandemic significantly affected emergency department (ED) visits and urgent psychiatric consultation (UPC) seeking behavior in EDs. Our study explored the changes in UPCs during and after the pandemic peak.

Methods

This retrospective observational study evaluated UPCs in the ED of a referral medical center in Taiwan, where treated both physical and psychiatric complaints. We defined the COVID-19 pandemic peak period as calendar week 4–18, 2020. The corresponding baseline as calendar week 4–18, 2019, and the slack period as week 4–18, 2021. The total number of UPCs, patient demographic data such as sex and age of the patients seen, the referral system (whether police or emergency medical service [EMS] or other sources), and the chief complaint (self-harm or violence) were recorded.

Results

Compared with the baseline period, a significant decline in UPCs was observed in the pandemic peak period, and a rebound was observed in the slack period, with the median [IQR] Q1, Q3 values of 22 [18, 26], 12 [10, 17]), and 16 [15, 23], respectively. We observed significantly few men (34.9% vs 45.2%) and less violence (10.2% vs 17.6%) in the peak period compared with in the baseline period, but no significant difference was found compared with the slack period. Throughout the pandemic, younger patients (41.8 ± 17.4 in 2019, 39.2 ± 18.5 [p = 0.121] in 2020, and 35.6 ± 17.2 [p < 0.001] in 2021), higher proportions of police/EMS referral (38.7% in 2019, 41.9% [p = 0.473] in 2020, and 51.9% [p = 0.001] in 2021) and self-harm–related complaints (57% in 2019, 62.4% [p = 0.233] in 2020, and 64.9% [p = 0.049] in 2021) was noted among UPC seekers during the pandemic. However, the proportion of violence-related UPCs (17.6% in 2019, 10.2% [p = 0.023] in 2020, and 12.3% [p = 0.072] in 2021) declined.

Conclusions

This study found that UPCs changed throughout the pandemic. This result raises the concern that mental health needs are masked during the pandemic.
Safety and efficacy of vacuum bottle plus catheter for drainage of iatrogenic pneumothorax
Authors: Chen Shih-Yu , Kuo Yao-Wen , Ho Chao-Chi , Wu Huey-Dong , Wang Hao-Chien
Published: June 2022

Background

Iatrogenic pneumothorax is common after thoracic procedures. For patients with pneumothorax larger than 15%, simple aspiration is suggested. Although vacuum bottle plus non-tunneled catheter drainage has been performed in many institutions, its safety and efficacy remain to be assessed.

Methods

Through this prospective cohort study (NCT03724721), we evaluated the safety and efficacy of vacuum bottle plus non-tunneled catheter drainage. Patients older than 20 years old who developed post-procedural pneumothorax were enrolled. A non-tunneled catheter was placed at the intersection of the midclavicular line and the second intercostal space. A 3-way stopcock, a drainage set, and a digital pressure gauge were connected. The stopcock was manipulated to connect the pleural space to the pressure gauge for measurement of end-expiration intrapleural pressure or to the vacuum bottle for air drainage. The rate of successful drainage, the end-expiration intrapleural pressure before, during, and after the procedure and the duration of hospitalization were recorded.

Results

From August 2018 to February 2020, 21 patients underwent vacuum bottle plus catheter drainage (intervention group) and 31 patients received conservative treatment (control group). The end-expiration intrapleural pressure of all patients remained less than − 20 cmH2O during drainage. No procedure related complication was observed. Large pneumothorax (≥ 15%) was associated with higher risk of persistent air leak (Odds ratio 12, 95% CI 1.2–569.7). Vacuum bottle assisted air drainage yielded shorter event-free duration than that of conservative treatment (2 days vs 5 days [interquartile range 1–4 days vs 3–7 days], p < .05). Vacuum bottle assisted air drainage also help identifying patients with persistent pneumothorax and necessitate the subsequent management. The event-free duration of persistent air leak in the intervention group was also comparable with that of conservative treatment (5 days vs 5 days [interquartile range 5–8 days vs 3–7 days], p = .45).

Conclusions

Vacuum bottle plus catheter drainage of iatrogenic pneumothorax is a safe and efficient procedure. It may be considered as an alternative management of stable post-procedural pneumothorax with size larger than 15%.

Trial registration The study protocol was approved by the Research Ethics Committee of National Taiwan University Hospital (No. 201805105DINA) on 6th August, 2018. The first participant was enrolled on 23rd August, 2018 after Research Ethics Committee approval. This clinical trial complete registration at U.S. National Library of Medicine clinicaltrials.gov with identifier NCT03724721 and URL: https://clinicaltrials.gov/ct2/show/NCT03724721 on 30th October, 2018.
Modelling vulnerability: qualitative study of the Balint process for medical students
Authors: Ng Lillian , Seu Chris , Cullum Sarah
Published: June 2022

Background

Health professionals in training may be overwhelmed by the emotional dimensions of their work. Balint groups have been proposed as an intervention to support students to process emotional aspects their encounters with patients. The aim of this study was to explore medical students’ emotional experiences of a Balint group during their psychiatry attachment.

Methods

Medical students completing a six week clinical attachment in psychiatry took part in weekly Balint group sessions. Five sessions were audio-recorded, transcribed and coded by members of the research team and an independent researcher co-coded all transcripts. Themes were discussed and refined over three rounds of coding.

Results

Four themes were identified: the Balint process as a container to enable vulnerability; becoming attuned to clinical and professional encounters; an evolving sense of identity within the medical hierarchy; and, the need for self-preservation to retain empathy for others.

Conclusion

The Balint structure provides medical students with a secure and emotionally resonant experience. Medical students’ engagement with the Balint process, even over a relatively short time period, teaches them how to reflect on difficult emotions associated with clinical encounters. Early exposure during a psychiatry placement may benefit students in terms of understanding relationship dynamics and the need for self-integration and lifelong reflection over the course of their medical career.
Decision algorithm for when to use the ICD-11 3-part model for healthcare harms
Authors: Eastwood Cathy A. , Khair Shahreen , Southern Danielle A.
Published: June 2022

Accurate data collection of healthcare-related adverse events provides a foundation for quality and health system improvement. The International Classification of Diseases for Mortality and Morbidity Statistics, 11th revision (ICD-11 MMS) includes new codes to identify harm or injury and the events or actions leading to the adverse events. However, it is difficult to choose the correct codes without in-depth understanding of which event may be classified as an injury or harm. A 3-part model will be available in the ICD-11 MMS to cluster the codes for the harm or injury that occurred, the causal factors, and the mode (mechanism) involved. While field testing coding of adverse events, our team developed a decision tree (algorithm), which guides when to use the 3-part model. The decision tree now resides in the ICD-11 Reference Guide. This paper is part of a special ICD-11 paper series and outlines the steps used in the decision-tree (algorithm) and provides examples to help understand the process.

While it may take coders some time to gain experience to use the 3-part model and decision-tree, the ICD-11 Reference Guide and this paper can be helpful resources to help clarify the process.
Daily surgery caseload prediction: towards improving operating theatre efficiency
Authors: Hassanzadeh Hamed , Boyle Justin , Khanna Sankalp , Biki Barbara , Syed Faraz
Published: June 2022

Background

In many hospitals, operating theatres are not used to their full potential due to the dynamic nature of demand and the complexity of theatre scheduling. Theatre inefficiencies may lead to access block and delays in treating patients requiring critical care. This study aims to employ operating theatre data to provide decision support for improved theatre management.

Method

Historical observations are used to predict long-term daily surgery caseload in various levels of granularity, from emergency versus elective surgeries to clinical specialty-level demands. A statistical modelling and a machine learning-based approach are developed to estimate daily surgery demand. The statistical model predicts daily demands based on historical observations through weekly rolling windows and calendar variables. The machine learning approach, based on regression algorithms, learns from a combination of temporal and sequential features. A de-identified data extract of elective and emergency surgeries at a major 783-bed metropolitan hospital over four years was used. The first three years of data were used as historical observations for training the models. The models were then evaluated on the final year of data.

Results

Daily counts of overall surgery at a hospital-level could be predicted with approximately 90% accuracy, though smaller subgroups of daily demands by medical specialty are less predictable. Predictions were generated on a daily basis a year in advance with consistent predictive performance across the forecast horizon.

Conclusion

Predicting operating theatre demand is a viable component in theatre management, enabling hospitals to provide services as efficiently and effectively as possible to obtain the best health outcomes. Due to its consistent predictive performance over various forecasting ranges, this approach can inform both short-term staffing choices as well as long-term strategic planning.
Healthcare service utilization patterns and patient experience in persons with spinal cord injury: a comparison across 22 countries
Authors: Bychkovska Olena , Tederko Piotr , Engkasan Julia Patrick , Hajjioui Abderrazak , Gemperli Armin
Published: June 2022

Background

Persons with spinal cord injury frequently visit numerous clinical settings. Such all-around experience of the system may serve as a comprehensive experience indicator. This study compared the patient experience of persons with chronic SCI in relation to healthcare service utilization patterns in 22 countries, hypothesizing that primary-care oriented patterns would offer a better experience.

Methods

This study was based on International Spinal Cord Injury Survey with 12,588 participants across 22 countries worldwide. Utilization patterns/clusters were identified by cluster analysis and experience score – by the partial credit model. The association between healthcare utilization and experience at the provider and cluster level was explored by regression analysis.

Results

The highest share of visits was to primary care physicians (18%) and rehabilitation physicians (16%). Utilization patterns had diverse orientations: from primary care to specialized and from inpatient to outpatient. The experience was reported as very good and good across different dimensions: 84% reported respectful treatment; 81% – clear explanations; 77% – involvement in decision making; 65% – satisfaction with care. The average experience score (0–100) was 64, highest – 74 (Brazil) and the lowest – 52 (Japan, South Korea). Service utilization at provider and at cluster levels were associated with patient experience, but no utilization pattern resulted in uniformly better patient experience.

Conclusion

While there are distinct patterns between countries on how persons with chronic SCI navigate the healthcare system, we found that different utilization patterns led to similar patient experience. The observed difference in patient experience is likely determined by other contextual factors than service utilization.
Self-care interventions for sexual and reproductive health in humanitarian and fragile settings: a scoping review
Authors: Dawson Angela , Tappis Hannah , Tran Nguyen Toan
Published: June 2022

Background

Self-care is the ability of individuals, families, and communities to promote health, prevent disease, maintain health, and manage illness and disability with or without a health care provider. In resource-constrained settings with disrupted sexual and reproductive health (SRH) service coverage and access, SRH self-care could play a critical role. Despite SRH conditions being among the leading causes of mortality and morbidity among women of reproductive age in humanitarian and fragile settings, there are currently no reviews of self-care interventions in these contexts to guide policy and practice.

Methods

We undertook a scoping review to identify the design, implementation, and outcomes of self-care interventions for SRH in humanitarian and fragile settings. We defined settings of interest as locations with appeals for international humanitarian assistance or identified as fragile and conflict-affected situations by the World Bank. SRH self-care interventions were described according to those aligned with the Minimum Initial Services Package for Reproductive Health in Crises. We searched six databases for records using keywords guided by the PRISMA statement. The findings of each included paper were analysed using an a priori framework to identify information concerning effectiveness, acceptability and feasibility of the self-care intervention, places where self-care interventions were accessed and factors relating to the environment that enabled the delivery and uptake of the interventions.

Results

We identified 25 publications on SRH self-care implemented in humanitarian and fragile settings including ten publications on maternal and newborn health, nine on HIV/STI interventions, two on contraception, two on safe abortion care, one on gender-based violence, and one on health service provider perspectives on multiple interventions. Overall, the findings show that well-supported self-care interventions have the potential to increase access to quality SRH for crisis-affected communities. However, descriptions of interventions, study settings, and factors impacting implementation offer limited insight into how practical considerations for SRH self-care interventions differ in stable, fragile, and crisis-affected settings.

Conclusion

It is time to invest in self-care implementation research in humanitarian settings to inform policies and practices that are adapted to the needs of crisis-affected communities and tailored to the specific health system challenges encountered in such contexts.
Observational study of population genomic screening for variants associated with endocrine tumor syndromes in a large, healthcare-based cohort
Authors: Savatt Juliann M. , Ortiz Nicole M. , Thone Gretchen M. , McDonald Whitney S. , Kelly Melissa A. , Berry Alexander S. F. , Alvi Madiha M. , Hallquist Miranda L. G. , Malinowski Jennifer , Purdy Nicholas C. , Williams Marc S. , Sturm Amy C. , Buchanan Adam H.
Published: June 2022

Background

In current care, patients’ personal and self-reported family histories are primarily used to determine whether genetic testing for hereditary endocrine tumor syndromes (ETS) is indicated. Population genomic screening for other conditions has increased ascertainment of individuals with pathogenic/likely pathogenic (P/LP) variants, leading to improved management and earlier diagnoses. It is unknown whether such benefits occur when screening broader populations for P/LP ETS variants. This manuscript assesses clinical utility outcomes of a large, unselected, healthcare-based genomic screening program by describing personal and family history of syndrome-related features, risk management behaviors after result disclosure, and rates of relevant post-disclosure diagnoses in patient-participants with P/LP ETS variants.

Methods

Observational study of individuals informed of a P/LP variant inMEN1,RET,SDHAF2,SDHB,SDHC,SDHD, orVHLthrough Geisinger’s MyCode Community Health Initiative between June 2016 and October 2019. Electronic health records (EHRs) of participants were evaluated for a report of pre-disclosure personal and self-reported family histories and post-disclosure risk management and diagnoses.

Results

P/LP variants in genes of interest were identified in 199 of 130,490 (1 in 656) adult Geisinger MyCode patient-participants, 80 of which were disclosed during the study period. Eighty-one percent (n= 65) did not have prior evidence of the result in their EHR and, because they were identified via MyCode, were included in further analyses. Five participants identified via MyCode (8%) had a personal history of syndrome-related features; 16 (25%) had a positive self-reported family history. Time from result disclosure to EHR review was a median of 0.7 years. Post-disclosure, 36 (55.4%) completed a recommended risk management behavior; 11 (17%) were diagnosed with a syndrome-related neoplasm after completing a risk management intervention.

Conclusions

Broader screening for pathogenic/likely pathogenic variants associated with endocrine tumor syndromes enables detection of at-risk individuals, leads to the uptake of risk management, and facilitates relevant diagnoses. Further research will be necessary to continue to determine the clinical utility of screening diverse, unselected populations for such variants.
A cross-sectional questionnaire survey on knowledge of anti-protozoal drug use and resistance among AHPs in Kwara State, Nigeria
Authors: Elelu Nusirat , Agene Grace , Sanusi Fatima , Al-Mustapha Ahmad Ibrahim
Published: June 2022

Antimicrobial resistance is a global public health crisis. However, there is a paucity of data on anti-protozoal resistance (APR), especially in animals. Hence, we assessed the knowledge of prudent antiprotozoal drug usage (APU) and resistance among animal health practitioners (AHPs) in Kwara State, Nigeria.

A cross-sectional survey of 435 AHPs was performed in Kwara State from the 5th of March to the 31st of July 2020 using a structured and validated questionnaire. We used logistic regression analysis to identify socio-demographic factors that are associated with the satisfactory perception of prudent APU and good knowledge of APR among AHPs.

Our findings showed that 80.2% (n = 349) of the AHPs in Kwara state had a good knowledge of APR with a mean knowledge score of 5.8 ± 1.2. In the same vein, 75.6% (n = 329) of the AHPs had a satisfactory perception of prudent APU with a mean score of 3.84 ± 1.21. Only 10.1% of the AHPs had observed treatment failures after the use of anti-protozoal drugs. Most of the AHPs (75.6%) believed that APR poses a significant threat to animal production and health globally. Logistic regression analysis showed that female AHPs were more likely (OR: 2.17; 95% CI: 0.91, 5.20;p < 0.005) to have better knowledge of APR than their male counterparts. AHPs with tertiary education were likely (OR: 2.77; 95% CI: 0.96, 4.99;p < 0.05) to be more knowledgeable about APR and have satisfactory perceptions of APU (OR: 1.57; 95% CI: 1.16, 2.99;p = 0.07) respectively. Finally, veterinarians were 3.76 times (95% CI:1.26, 9.25;p < 0.001) more likely to have good knowledge of APR and better perceptions of APU (OR: 3.28; 95% CI: 1.89, 5.68;p < 0.001) than other AHPs respectively.

To control antimicrobial resistance, continuous training of AHPs especially para-veterinary officers is essential to update their knowledge on prudent antimicrobial usage and prevent the emergence of resistant protozoan parasites.
A microfluidic paper analytical device using capture aptamers for the detection of PfLDH in blood matrices
Authors: Ogunmolasuyi Adewoyin Martin , Fogel Ronen , Hoppe Heinrich , Goldring Dean , Limson Janice
Published: June 2022

Background

The prevalence and death rate arising from malaria infection, and emergence of other diseases showing similar symptoms to malaria require the development of malaria-specific and sensitive devices for its diagnosis. To address this, the design and fabrication of low-cost, rapid, paper-based analytical devices (µPAD) using surface-immobilized aptamers to detect the presence of a recombinant malarial biomarker—Plasmodium falciparum lactate dehydrogenase (rPfLDH)—is reported in this study.

Methods

Test zones on paper surfaces were created by covalently immobilizing streptavidin to the paper, subsequently attaching biotinylated aptamers to streptavidin. Aptamers selectively bound rPfLDH. The measurement of captured rPfLDH enzyme activity served as the means of detecting this biomarker. Enzyme activity across three replicate sensors was digitally quantified using the colorimetric Malstat assay.

Results

Screening of several different aptamers reported in the literature showed that aptamers rLDH7 and 2008s immobilized in this manner specifically recognised and captured PfLDH. Using rLDH7, the sensitivity of the µPAD sensor was evaluated and the µPAD sensor was applied for preferential detection of rPfLDH, both in buffered solutions of the protein and in spiked serum and red blood cell lysate samples. In buffered solutions, the test zone of the µPAD sensor exhibited a KD of 24 ± 11 nM and an empirical limit of detection of 17 nM, respectively, a limit similar to commercial antibody-based sensors exposed to rPfLDH. The specific recognition of 133 nM rPfLDH in undiluted serum and blood samples was demonstrated by the µPAD.

Conclusion

The reported µPAD demonstrates the potential of integrating aptamers into paper-based malarial rapid diagnostic tests.

Graphical Abstract
Outdoor biting and pyrethroid resistance as potential drivers of persistent malaria transmission in Zanzibar
Authors: Musiba Revocatus M. , Tarimo Brian B. , Monroe April , Msaky Dickson , Ngowo Halfan , Mihayo Kimberly , Limwagu Alex , Chilla Godlove T. , Shubis Gasper K. , Ibrahim Ahmada , Greer George , Mcha Juma H. , Haji Khamis A. , Abbas Faiza B. , Ali Abdullah , Okumu Fredros O. , Kiware Samson S.
Published: June 2022

Background

Low-level of malaria transmission persist in Zanzibar despite high coverage of core vector control interventions. This study was carried out in hot-spot sites to better understand entomological factors that may contribute to residual malaria transmission in Zanzibar.

Methods

A total of 135 households were randomly selected from six sites and consented to participate with 20–25 households per site. Mosquito vector surveillance was carried out indoors and outdoors from 6:00 pm–7:00 am using miniaturized double net trap (DN-Mini™). Additional collections were done indoors using mouth aspirators to retrieve resting mosquitoes from wall and ceiling surfaces, and outdoors using resting bucket and pit traps. All collected mosquitoes were morphologically and genetically (PCR) analysed in the laboratory. All collected anopheline and blood-fed mosquitoes were analysed for sporozoite infection and blood meal host preferences by Circumsporozoite Protein ELISA and blood meal ELISA, respectively. The differences between indoor and outdoor mosquito biting rates were analysed using generalized linear mixed models. Levels of resistance to commonly used insecticides were quantified by WHO susceptibility tests.

Results

Out of 704 malaria vectors collected across 135 households, PCR analysis shows that 98.60% were Anopheles arabiensis, 0.6% Anopheles merus and 0.6% Anopheles gambiae sensu stricto. Sporozoite ELISA analysis indicates that all mosquitoes were negative for the malaria parasite. The results show that more An. arabiensis were collected outdoor (~ 85%) compared to indoor (~ 15%). Furthermore, large numbers of An. arabiensis were caught in outdoor resting sites, where the pit trap (67.2%) collected more mosquitoes compared to the outdoor DN-Mini trap (32.8%). Nearly two-thirds (60.7%) of blood-fed mosquitoes had obtained blood meals from non-human hosts. Mosquitoes displayed non-uniform susceptibility status and resistance intensity among the tested insecticides across the study sites to all WHO recommended insecticides across the study sites.

Conclusion

This study suggests that in contexts such as Zanzibar, testing of novel techniques to complement indoor protection and targeting outdoor biting and/or resting mosquitoes, may be warranted to complement existing interventions and contribute to malaria elimination efforts. The study highlights the need to implement novel interventions and/or adaptations of strategies that can target outdoors biting mosquitoes.
Comparison of two malaria multiplex immunoassays that enable quantification of malaria antigens
Authors: Jang Ihn Kyung , Jiménez Alfons , Rashid Andrew , Barney Rebecca , Golden Allison , Ding Xavier C. , Domingo Gonzalo J. , Mayor Alfredo
Published: June 2022

Background

Immunoassay platforms that simultaneously detect malaria antigens including histidine-rich protein 2 (HRP2)/HRP3 and Plasmodium lactate dehydrogenase (pLDH), are useful epidemiological tools for rapid diagnostic test evaluation. This study presents the comparative evaluation of two multiplex platforms in identifying Plasmodium falciparum with presence or absence of HRP2/HRP3 expression as being indicative of hrp2/hrp3 deletions and other Plasmodium species. Moreover, correlation between the malaria antigen measurements performed at these platforms is assessed after calibrating with either assay standards or international standards and the cross-reactivity among Plasmodium species is examined.

Methods

A 77-member panel of specimens composed of the World Health Organization (WHO) international Plasmodium antigen standards, cultured parasites for P. falciparum and Plasmodium knowlesi, and clinical specimens with mono-infections for P. falciparum, Plasmodium vivax, and Plasmodium malariae was generated as both whole blood and dried blood spot (DBS) specimens. Assays for HRP2, P. falciparum–specific pLDH (PfLDH), P. vivax–specific pLDH (PvLDH), and all human Plasmodium species Pan malaria pLDH (PanLDH) on the Human Malaria Array Q-Plex and the xMAP platforms were evaluated with these panels.

Results

The xMAP showed a higher percent positive agreement for identification of hrp2-deleted P. falciparum and Plasmodium species in whole blood and DBS than the Q-Plex. For whole blood samples, there was a highly positive correlation between the two platforms for PfLDH (Pearson r = 0.9926) and PvLDH (r = 0. 9792), moderate positive correlation for HRP2 (r = 0.7432), and poor correlation for PanLDH (r = 0.6139). In Pearson correlation analysis between the two platforms on the DBS, the same assays were r = 0.9828, r = 0.7679, r = 0.6432, and r = 0.8957, respectively. The xMAP HRP2 assay appeared to cross-react with HRP3, while the Q-Plex did not. The Q-Plex PfLDH assay cross-reacted with P. malariae, while the xMAP did not. For both platforms, P. knowlesi was detected on the PvLDH assay. The WHO international standards allowed normalization across both platforms on their HRP2, PfLDH, and PvLDH assays in whole blood and DBS.

Conclusions

Q-Plex and xMAP show good agreement for identification of P. falciparum mutants with hrp2/hrp3 deletions, and other Plasmodium species. Quantitative results from both platforms, normalized into international units for HRP2, PfLDH, and PvLDH, showed good agreement and should allow comparison and analysis of results generated by either platform.
Trajectories of socioeconomic inequality in early child development: a cohort analysis
Authors: Houweling Tanja A. J. , Oude Groeniger Joost , Jansen Pauline W. , van Lier Pol , Horoz Nil , Buil Marieke , van Lenthe Frank J.
Published: June 2022

Background

Addressing socioeconomic inequalities in early child development (ECD) is key to reducing the intergenerational transmission of health inequalities. Yet, little is known about how socioeconomic inequalities in ECD develop over the course of childhood. Our study aimed to describe how inequalities in ECD by maternal education develop from infancy to middle childhood.

Methods

We used data from Generation R, a prospective population-based cohort study in The Netherlands. Language skills were measured at ages 1, 1.5, 2, 3, and 4 years, using the Minnesota Child Development Inventory. Socioemotional (i.e. internalizing and externalizing) problems were measured at ages 1.5, 3, 5 and 9 years using the Child Behavior Checklist. We estimated inequalities in language skills and socioemotional problems across the above-mentioned ages, using linear mixed models with standardized scores at each wave. We used maternal education as indicator of socioeconomic position.

Results

Children of less educated mothers had more reported internalizing (B = 0.72, 95%CI = 0.51;0.95) and externalizing (B = 0.25, 95%CI = 0.10;0.40) problems at age 1.5 years, but better (caregiver reported) language skills at 1 year (B = 0.50, 95%CI = 0.36;0.64) than children of high educated mothers. Inequalities in internalizing and externalizing problems decreased over time. Inequalities in language scores reversed at age 2, and by the time children were 4 years old, children of less educated mothers had substantially lower language skills than children of high educated mothers (B = -0.38, 95%CI = -0.61;-0.15).

Conclusions

Trajectories of socioeconomic inequality in ECD differ by developmental domain: whereas inequalities in socioemotional development decreased over time, inequalities increased for language development. Children of less educated mothers are at a language disadvantage even before entering primary education, providing further evidence that early interventions are needed.
3D printed hydrogel scaffolds combining glutathione depletion-induced ferroptosis and photothermia-augmented chemodynamic therapy for efficiently inhibiting postoperative tumor recurrence
Authors: Dang Wentao , Chen Wei-Chih , Ju Enguo , Xu Yanteng , Li Kai , Wang Haixia , Wang Kun , Lv Shixian , Shao Dan , Tao Yu , Li Mingqiang
Published: June 2022

Surgical resection to achieve tumor-free margins represents a difficult clinical scenario for patients with hepatocellular carcinoma. While post-surgical treatments such as chemotherapy and radiotherapy can decrease the risk of cancer recurrence and metastasis, growing concerns about the complications and side effects have promoted the development of implantable systems for locoregional treatment. Herein, 3D printed hydrogel scaffolds (designed as Gel-SA-CuO) were developed by incorporating one agent with multifunctional performance into implantable devices to simplify the fabrication process for efficiently inhibiting postoperative tumor recurrence. CuO nanoparticles can be effectively controlled and sustained released during the biodegradation of hydrogel scaffolds. Notably, the released CuO nanoparticles not only function as the reservoir for releasing Cu2+ to produce intracellular reactive oxygen species (ROS) but also serve as photothermal agent to generate heat. Remarkably, the heat generated by photothermal conversion of CuO nanoparticles further promotes the efficiency of Fenton-like reaction. Additionally, ferroptosis can be induced through Cu2+-mediated GSH depletion via the inactivation of GPX4. By implanting hydrogel scaffolds in the resection site, efficient inhibition of tumor recurrence after primary resection can be achieved in vivo. Therefore, this study may pave the way for the development of advanced multifunctional implantable platform for eliminating postoperative relapsable cancers.

Graphical Abstract
Nanoparticle classification, physicochemical properties, characterization, and applications: a comprehensive review for biologists
Authors: Joudeh Nadeem , Linke Dirk
Published: June 2022

Interest in nanomaterials and especially nanoparticles has exploded in the past decades primarily due to their novel or enhanced physical and chemical properties compared to bulk material. These extraordinary properties have created a multitude of innovative applications in the fields of medicine and pharma, electronics, agriculture, chemical catalysis, food industry, and many others. More recently, nanoparticles are also being synthesized ‘biologically’ through the use of plant- or microorganism-mediated processes, as an environmentally friendly alternative to the expensive, energy-intensive, and potentially toxic physical and chemical synthesis methods. This transdisciplinary approach to nanoparticle synthesis requires that biologists and biotechnologists understand and learn to use the complex methodology needed to properly characterize these processes. This review targets a bio-oriented audience and summarizes the physico–chemical properties of nanoparticles, and methods used for their characterization. It highlights why nanomaterials are different compared to micro- or bulk materials. We try to provide a comprehensive overview of the different classes of nanoparticles and their novel or enhanced physicochemical properties including mechanical, thermal, magnetic, electronic, optical, and catalytic properties. A comprehensive list of the common methods and techniques used for the characterization and analysis of these properties is presented together with a large list of examples for biogenic nanoparticles that have been previously synthesized and characterized, including their application in the fields of medicine, electronics, agriculture, and food production. We hope that this makes the many different methods more accessible to the readers, and to help with identifying the proper methodology for any given nanoscience problem.
PDGFB targeting biodegradable FePt alloy assembly for MRI guided starvation-enhancing chemodynamic therapy of cancer
Authors: Zhang Caiyun , Leng Zhiguo , Wang Yinfeng , Ran Lang , Qin Xia , Xin Huan , Xu Xiaotong , Zhang Guilong , Xu Zhaowei
Published: June 2022

The application of chemodynamic therapy (CDT) for cancer is a serious challenge owing to the low efficiency of the Fenton catalyst and insufficient H2O2 expression in cells. Herein, we fabricated a PDGFB targeting, biodegradable FePt alloy assembly for magnetic resonance imaging (MRI)-guided chemotherapy and starving-enhanced chemodynamic therapy for cancer using PDGFB targeting, pH-sensitive liposome-coated FePt alloys, and GOx (pLFePt-GOx). We found that the Fenton-catalytic activity of FePt alloys was far stronger than that of traditional ultrasmall iron oxide nanoparticle (UION). Upon entry into cancer cells, pLFePt-GOx nanoliposomes degraded into many tiny FePt alloys and released GOx owing to the weakly acidic nature of the tumor microenvironment (TME). The released GOx-mediated glucose consumption not only caused a starvation status but also increased the level of cellular H2O2 and acidity, promoting Fenton reaction by FePt alloys and resulting in an increase in reactive oxygen species (ROS) accumulation in cells, which ultimately realized starving-enhanced chemodynamic process for killing tumor cells. The anticancer mechanism of pLFePt-GOx involved ROS-mediated apoptosis and ferroptosis, and glucose depletion-mediated starvation death. In the in vivo assay, the systemic delivery of pLFePt-GOx showed excellent antitumor activity with low biological toxicity and significantly enhanced T2-weighted magnetic resonance imaging (MRI) signal of the tumor, indicating that pLFePt-GOx can serve as a highly efficient theranostic tool for cancer. This work thus describes an effective, novel multi-modal cancer theranostic system.
Stability of SF-36 profiles between 2007 and 2016: A study of 27,302 patients surgically treated for lumbar spine diseases
Authors: Joelson Anders , Sigmundsson Freyr Gauti , Karlsson Jan
Published: June 2022

Background

Previous studies have shown that patients with different lumbar spine diseases report different SF-36 profiles, but data on the stability of the SF-36 profiles are limited. The primary aim of the current study was to evaluate the stability of the SF-36 profile for lumbar spine diseases.

Methods

Patients, surgically treated between 2007 and 2016 for three lumbar spine diseases, lumbar spinal stenosis (LSS) with degenerative spondylolisthesis (DS), LSS without DS, and lumbar disk herniations (LDH), were identified in the Swedish spine register. Preoperative and 1 year postoperative SF-36 data for a total of 27,302 procedures were available for analysis. The stability of the SF-36 profiles over the 10-year period was evaluated using graphical exploration, linear regression, difference in means, and 95% confidence intervals. The responsiveness of the SF-36 domains to surgical treatment was evaluated using the standardized response mean (SRM).

Results

LSS and LDH have different SF-36 profiles. LSS with DS and LSS without DS have similar SF-36 profiles. The preoperative and the 1 year postoperative SF-36 profiles were stable from 2007 to 2016 for all three diagnoses. There were no major changes in the effect size of change (SRM) during the study period for all three diagnoses. For LSS with DS, the number of fusions peaked in 2010 and then decreased. The postoperative SF-36 profiles for LSS with DS were unaffected by changes in surgical treatment trends.

Conclusions

Patients with lumbar spinal stenosis and lumbar disk herniations have different SF-36 profiles. Concomitant degenerative spondylolisthesis had no impact on the SF-36 profile of lumbar spinal stenosis. Adding fusion to the decompression did not alter the postoperative SF-36 profile of lumbar spinal stenosis. The SF-36 health profiles are stable from a 10 years perspective.
Automated whole-slide images assessment of immune infiltration in resected non-small-cell lung cancer: towards better risk-stratification
Authors: Lin Huan , Pan Xipeng , Feng Zhengyun , Yan Lixu , Hua Junjie , Liang Yanting , Han Chu , Xu Zeyan , Wang Yumeng , Wu Lin , Cui Yanfen , Huang Xiaomei , Shi Zhenwei , Chen Xin , Chen Xiaobo , Zhang Qingling , Liang Changhong , Zhao Ke , Li Zhenhui , Liu Zaiyi
Published: June 2022

Background

High immune infiltration is associated with favourable prognosis in patients with non-small-cell lung cancer (NSCLC), but an automated workflow for characterizing immune infiltration, with high validity and reliability, remains to be developed.

Methods

We performed a multicentre retrospective study of patients with completely resected NSCLC. We developed an image analysis workflow for automatically evaluating the density of CD3+ and CD8+ T-cells in the tumour regions on immunohistochemistry (IHC)-stained whole-slide images (WSIs), and proposed an immune scoring system “I-score” based on the automated assessed cell density.

Results

A discovery cohort (n = 145) and a validation cohort (n = 180) were used to assess the prognostic value of the I-score for disease-free survival (DFS). The I-score (two-category) was an independent prognostic factor after adjusting for other clinicopathologic factors. Compared with a low I-score (two-category), a high I-score was associated with significantly superior DFS in the discovery cohort (adjusted hazard ratio [HR], 0.54; 95% confidence interval [CI] 0.33–0.86; P = 0.010) and validation cohort (adjusted HR, 0.57; 95% CI 0.36–0.92; P = 0.022). The I-score improved the prognostic stratification when integrating it into the Cox proportional hazard regression models with other risk factors (discovery cohort, C-index 0.742 vs. 0.728; validation cohort, C-index 0.695 vs. 0.685).

Conclusion

This automated workflow and immune scoring system would advance the clinical application of immune microenvironment evaluation and support the clinical decision making for patients with resected NSCLC.