bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of a multicomponent communication training to involve older people in decisions to DEPRESCRIBE cardiometabolic medication in primary care (CO-DEPRESCRIBE): protocol for a cluster randomized controlled trial with embedded process and economic evaluation
Authors: Stuijt Peter J.C. , Heringa Mette , van Dijk Liset , Faber Adrianne , Burgers Jako S. , Feenstra Talitha L. , Taxis Katja , Denig Petra
Published: June 2024

Background

Deprescribing of medication for cardiovascular risk factors and diabetes has been incorporated in clinical guidelines but proves to be difficult to implement in primary care. Training of healthcare providers is needed to enhance deprescribing in eligible patients. This study will examine the effects of a blended training program aimed at initiating and conducting constructive deprescribing consultations with patients.

Methods

A cluster-randomized trial will be conducted in which local pharmacy-general practice teams in the Netherlands will be randomized to conducting clinical medication reviews with patients as usual (control) or after receiving the CO-DEPRESCRIBE training program (intervention). People of 75 years and older using specific cardiometabolic medication (diabetes drugs, antihypertensives, statins) and eligible for a medication review will be included. The CO-DEPRESCRIBE intervention is based on previous work and applies models for patient-centered communication and shared decision making. It consists of 5 training modules with supportive tools. The primary outcome is the percentage of patients with at least 1 cardiometabolic medication deintensified. Secondary outcomes include patient involvement in decision making, healthcare provider communication skills, health/medication-related outcomes, attitudes towards deprescribing, medication regimen complexity and health-related quality of life. Additional safety and cost parameters will be collected. It is estimated that 167 patients per study arm are needed in the final intention-to-treat analysis using a mixed effects model. Taking loss to follow-up into account, 40 teams are asked to recruit 10 patients each. A baseline and 6-months follow-up assessment, a process evaluation, and a cost-effectiveness analysis will be conducted.

Discussion

The hypothesis is that the training program will lead to more proactive and patient-centered deprescribing of cardiometabolic medication. By a comprehensive evaluation, an increase in knowledge needed for sustainable implementation of deprescribing in primary care is expected.

Trial registration

The study is registered at ClinicalTrials.gov (identifier: NCT05507177).
Evaluation of upper limb perception after stroke with the new Affected Limb Perception Questionnaire (ALPQ): a study protocol
Authors: Konik Stéphanie , Beaud Valérie , Fellrath Julia , Martinelli Isabella , Guanziroli Eleonora , Molteni Franco , Bassolino Michela , Serino Andrea
Published: June 2024

Background

Following a stroke, patients may suffer from alterations in the perception of their own body due to an acquired deficit in body representations. While such changes may impact their quality of life as well as recovery, they are not systematically assessed in clinical practice. This study aims at providing a better understanding of the rate, evolution, and impact on recovery of upper limb (UL) body perceptions (BPs) alterations following stroke. In addition, we will investigate associations among BPs alterations items, their associations with the sensorimotor functions, UL activity, damages in brain structure and connectivity.

Methods

We developed a new tool named ALPQ (for Affected Limb Perception Questionnaire) to address the present study objectives. It assesses subjective alterations in the perception of the affected UL following stroke, by measuring several dimensions, namely: anosognosia for hemiplegia, anosodiaphoria for hemiplegia, hemiasomatognosia, somatoparaphrenia, personification of the affected limb, illusion of modification of physical characteristics (temperature, weight, length), illusory movements, super- or undernumerary limb, UL disconnection, misoplegia, and involuntary movement. This study combines a cross-sectional and longitudinal design. The completed data sample will include a minimum of 60 acute and 100 sub-acute stroke patients. When possible, patients are followed up to the chronic stage. Complementary evaluations are administered to assess patients’ sensorimotor and cognitive functions as well as UL activity, and brain lesions will be analysed.

Discussion

This study will provide a better understanding of BPs alterations following stroke: their rate and evolution, as well as their associations with sensorimotor deficit, cognitive profile and UL activity, brain lesions and recovery. Ultimately, the results could support the personalization of rehabilitation strategy according to patients’ UL perception to maximize their recovery.

Study registration

The protocol for this study has been pre-registered on the Open Science Framework on July the 7th, 2021: https://osf.io/p6v7f.
Comparison of cognitive performance in first-episode drug-naïve schizophrenia, bipolar II disorder, and major depressive disorder patients after treatment
Authors: Tang Chaohua , Huang Wei , Tan Yukang , Liu Yiliang , Zheng Guangen , Li Bin , Chen Wensheng , Yang Yu , Xu Guohong , Li Xiaoling , Xu Caixia , Xie Guojun , Liang Jiaquan
Published: June 2024

Background

Cognitive impairment is a recognized fundamental deficit in individuals diagnosed with schizophrenia (SZ), bipolar II disorder (BD II), and major depressive disorder (MDD), among other psychiatric disorders. However, limited research has compared cognitive function among first-episode drug-naïve individuals with SZ, BD II, or MDD.

Methods

This study aimed to address this gap by assessing the cognitive performance of 235 participants (40 healthy controls, 58 SZ patients, 72 BD II patients, and 65 MDD patients) using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) before and after 12 weeks of treatment in SZ, BD II, and MDD patients. To clarify, the healthy controls only underwent RBANS testing at baseline, whereas the patient groups were assessed before and after treatment. The severity of symptoms in SZ patients was measured using the Positive and Negative Syndrome Scale (PANSS), and depression in BD II and MDD patients was assessed using the Hamilton Depression Scale-24 items (HAMD-24 items).

Results

Two hundred participants completed the 12-week treatment period, with 35 participants dropping out due to various reasons. This group included 49 SZ patients, 58 BD II patients, and 53 MDD patients. Among SZ patients, significant improvements in immediate and delayed memory were observed after 12 weeks of treatment compared to their initial scores. Similarly, BD II patients showed significant improvement in immediate and delayed memory following treatment. However, there were no significant differences in RBANS scores for MDD patients after 12 weeks of treatment.

Conclusions

In conclusion, the findings of this study suggest that individuals with BD II and SZ may share similar deficits in cognitive domains. It is important to note that standardized clinical treatment may have varying degrees of effectiveness in improving cognitive function in patients with BD II and SZ, which could potentially alleviate cognitive dysfunction.
Real-world predictors of changes in fear of COVID-19 in the Japanese general population: a large-scale internet-based cohort study with 20,712 participants
Authors: Tokumitsu Keita , Sugawara Norio , Tabuchi Takahiro , Yasui-Furukori Norio
Published: June 2024

Background

Coronavirus disease 2019 (COVID-19) is a respiratory infection that considerably impacts both physical and mental health. In particular, the prolonged nature of psychological issues associated with COVID-19 has become a concern. However, evidence based on longitudinal studies investigating the changes in fear of COVID-19 has been limited, posing a public health challenge.

Methods

We investigated the predictors of changes in the Fear of COVID-19 Scale (FCV-19S) scores in the general Japanese population using data from a large-scale internet-based cohort study.

Results

We included 20,712 study participants (mean age = 51.1 years, percentage of males = 49.9%). The baseline FCV-19S score for the research participants was 17.0, and one year later, the FCV-19S score decreased to 15.8. The predictors of increase in FCV-19S scores were older age, male sex, COVID-19 requiring oxygen therapy, higher baseline FCV-19S total score, severe psychological distress, never married, worsening subjective health status, a greater number of COVID-19 vaccinations, a history of alcohol dependency, and living with family members. Conversely, the predictors of decrease in FCV-19S scores included habitual alcohol intake, COVID-19 not requiring oxygen therapy and a higher household income. Our study was an internet-based survey focused on residents of Japan, which raises the possibility of selection bias and makes it unclear whether the findings can be extrapolated to other countries and cultures.

Conclusion

During the observation period, the FCV-19S scores significantly decreased. Severe COVID-19 requiring oxygen therapy within one year of baseline was the most impactful predictor of an increase in FCV-19S score. On the other hand, mild COVID-19 not requiring oxygen therapy was a predictor of a decrease in FCV-19S scores. Therefore, we believe that it is necessary to adopt individualized approaches stratified by the severity of the infection when addressing the fear of COVID-19.
Hepatitis B discrimination: global responses requiring global data
Authors: Freeland Catherine , Qureshi Anousha , Wallace Jack , Kabagambe Kenneth , Desalegn Hailemichael , Munoz Chris , Lee Dee , Owusu-Ansah Theobald , Adda Danjuma , Ndow Gibril , Yousif Sarra , Abdalla Hala , Kheir Omer , Tu Thomas , Cohen Chari
Published: June 2024

Over 250 million individuals live with chronic hepatitis B (CHB) infection worldwide. A significant proportion of these people often face discrimination defined as the unjust, unfair, or prejudicial treatment of a person on the grounds of their hepatitis B status. Hepatitis B related discrimination has not been widely documented in the literature. This study aims to describe the lived experience of discrimination, document its impact, and shed light on its consequences. A hepatitis B discrimination registry was launched to record self-reported discrimination associated with hepatitis B. The registry included brief demographic questions (age, gender, country of origin), discrimination-specific questions (where, when, and how discrimination occurred), and open-ended questions to detail specific experiences. The registry was distributed to hepatitis B patient/people-focused listservs, social media networks, and community-based organizations around the globe. Descriptive data were analyzed including comparative analysis by country and type of discrimination occurring along with qualitative data (open-ended responses) which were analyzed using thematic analysis techniques A total of 569 individuals responded to the survey between May 2021 and December 2023. Individuals identified as residing in the Philippines (34%; N = 194), Nigeria (11%; N = 60), Pakistan (8%; N = 45), India (6%, N = 34), Uganda (5%; N = 31), the United States of America (4%, N = 26), Ghana (3%; N = 15), Ethiopia (2%; N = 14), and other countries in smaller number with a total of 65 countries reported discrimination at least by one individual. Of these, 461 individuals shared details about their experiences of discrimination with most relating to restrictions on access to work visas, followed by in-country hepatitis B-related employment restrictions, educational-based discrimination, discrimination within the community and health facilities, and the emotional impact of hepatitis B discrimination. This is the largest primary collection of hepatitis B-associated discrimination events and highlights how hepatitis B discrimination clearly has a significant impact on individuals’ lives and limits economic opportunities regardless of physical symptoms. Such impacts likely act as barriers to diagnosis and engagement in care, so need to be addressed to achieve the global hepatitis B elimination goals. The data highlight a need for global, national responses and more systematic responses to discrimination experienced by people with hepatitis B.
Dental and dental hygienist trainee satisfaction with their veterans affairs clinical training experiences during the COVID-19 pandemic
Authors: Northcraft Heather , Bai Jia , Griffin Anne R. , Dobalian Aram
Published: June 2024

Background

The COVID-19 pandemic rapidly altered dental practice, training, and education. This study investigates the pandemic’s impacts on the clinical training experiences of dental and dental hygienist trainees at the US Department of Veterans Affairs (VA).

Methods

Using data from post-doctoral general practice dentists, dental specialists, and dental hygienist trainees who completed the VA Trainee Satisfaction Survey before and during COVID-19, we performed logistic regression and thematic content analyses to determine whether COVID-19 was associated with training satisfaction and likelihood of considering future VA employment.

Results

While post-doctoral dentist and dental specialty trainees did not report significant differences, dental hygienist trainees reported increased overall satisfaction and an increased likelihood to consider future VA employment during the pandemic compared to before the pandemic. Similar reasons for dissatisfaction were identified for both the pre-pandemic and pandemic groups.

Conclusions

Research outside VA indicates the pandemic’s association with trainees’ intentions to leave health profession education programs. Our results suggest the likely existence of factors that could lead to positive changes for at least some portion of the dental workforce. Future studies should explore those potential factors as some may be replicable in other settings or may apply to other health professions.
Resilience and adaptation: a mixed-methods exploration of COVID-19’s influence on neonatal residency education in China
Authors: Liu Weiqin , Wei Hong , Wang Chunyi , Hua Ziyu
Published: June 2024

Background

This study aimed to assess the impact of the pandemic of the coronavirus disease 2019 (COVID-19) on neonatology residency training in a tertiary children’s hospital in Chongqing, located in southwest China. Specifically, the study encompassed the effects on residents’ education, lived experiences, well-being, and the quality of neonatal care delivered. As higher educational institutions adapt to the post-COVID-19 era after the pandemic disruption, it is imperative that educational designers/academics learn from their experiences and challenges in curriculum design and delivery, ensuring quality and relevance in education.

Methods

This study employed a mixed-methods approach to investigate the influence of the COVID-19 pandemic on neonatology residency training at a tertiary children’s hospital in Chongqing. The first phase surveyed residents’ perceptions and experiences of their clinical education and well-being during the crisis. The second phase compared the quality of neonatal care between the pre-pandemic and pandemic periods.

Results

The survey of 123 neonatology residents examines the effects of COVID-19 on their learning, training, and mental health. The survey showed that most residents adapted well to the situation. Still, some faced challenges in their clinical education and experiences, such as reduced clinical exposure and opportunities to see rare diseases and conditions. A retrospective analysis of clinical data revealed that 7,151 neonates were admitted to the neonatology department during the study period. There was a 27.6% decrease in neonatal admissions during COVID-19, with more premature births and transfers. Residents conducted fewer clinical procedures but managed more complex cases. During COVID, hospital stays and costs were higher, but antibiotic use was lower. Although the case-mix index (CMI) score increased during the pandemic (1.25 vs. 1.18, p < 0.05), there was no significant difference in the rates of readmission within 7 days or poor prognosis.

Conclusions

Despite reduced clinical exposure, the quality of neonatal care was maintained through innovative training methods that enhanced comprehensive residency programs. The study suggested that neonatology residency education remained effective and resilient during the crisis. Exceptional health professional education is vital to train qualified physicians and enhance healthcare systems for future challenges.
Chronic pain in children and young people with cerebral palsy: a narrative review of challenges, advances, and future directions
Authors: Harvey Adrienne , Smith Nadine , Smith Meredith , Ostojic Katarina , Berryman Carolyn
Published: June 2024

Background

Cerebral palsy (CP), the most common physical disability of childhood, is often accompanied by a range of comorbidities including pain. Pain is highly prevalent in children and young people with CP, yet has been poorly understood, inaccurately assessed, and inadequately managed in this vulnerable population. This narrative review presents recent research advances for understanding and managing pain in children and young people with CP, focusing on chronic pain, and highlights future research directions.

Main body

Pain prevalence rates in CP vary due to different methodologies of studies. Recent systematic reviews report up to 85% of children experience pain; higher in older children, females, and those with dyskinesia and greater motor impairment. Research examining the lived experience perspectives of children and their families demonstrate that even those with mild motor impairments have pain, children want to self-report pain where possible to feel heard and believed, and management approaches should be individualized. Notably, many children with cognitive and communication impairments can self-report their pain if adjustments are provided and they are given a chance. Past inadequacies of pain assessment in CP relate to a focus on pain intensity and frequency with little focus on pain interference and coping, a lack of tools appropriate for the CP population, and an assumption that many children with cognitive and/or communication limitations are unable to self-report. Recent systematic reviews have identified the most reliable and valid assessment tools for assessing chronic pain. Many were not developed for people with CP and, in their current form, are not appropriate for the spectrum of physical, communication, and cognitive limitations seen. Recently, consensus and co-design in partnership with people with lived experience and clinicians have identified tools appropriate for use in CP considering the biopsychosocial framework. Modifications to tools are underway to ensure feasibility and applicability for the spectrum of abilities seen.

Conclusion

Recent research advances have improved our understanding of the prevalence, characteristics and lived experience of chronic pain, and refined assessment methods in children and young people with CP. However, the very limited evidence for effective and novel management of chronic pain in this population is where research should now focus.
TMPRSS2 is a tumor suppressor and its downregulation promotes antitumor immunity and immunotherapy response in lung adenocarcinoma
Authors: Liu Zhixian , Lu Qiqi , Zhang Zhilan , Feng Qiushi , Wang Xiaosheng
Published: June 2024

Background

TMPRSS2, a key molecule for SARS-CoV-2 invading human host cells, has an association with cancer. However, its association with lung cancer remains insufficiently unexplored.

Methods

In five bulk transcriptomics datasets, one single‐cell RNA sequencing (scRNA-seq) dataset and one proteomics dataset for lung adenocarcinoma (LUAD), we explored associations between TMPRSS2 expression and immune signatures, tumor progression phenotypes, genomic features, and clinical prognosis in LUAD by the bioinformatics approach. Furthermore, we performed experimental validation of the bioinformatics findings.

Results

TMPRSS2 expression levels correlated negatively with the enrichment levels of both immune-stimulatory and immune-inhibitory signatures, while they correlated positively with the ratios of immune-stimulatory/immune-inhibitory signatures. It indicated that TMPRSS2 levels had a stronger negative correlation with immune-inhibitory than with immune-stimulatory signatures. TMPRSS2 downregulation correlated with increased proliferation, stemness, genomic instability, tumor progression, and worse survival in LUAD. We further validated that TMPRSS2 was downregulated with tumor progression in the LUAD cohort we collected from Jiangsu Cancer Hospital, China. In vitro and in vivo experiments verified the association of TMPRSS2 deficiency with increased tumor cell proliferation and invasion and antitumor immunity in LUAD. Moreover, in vivo experiments demonstrated that TMPRSS2-knockdown tumors were more sensitive to BMS-1, an inhibitor of PD-1/PD-L1.

Conclusions

TMPRSS2 is a tumor suppressor, while its downregulation is a positive biomarker of immunotherapy in LUAD. Our data provide a potential link between lung cancer and pneumonia caused by SARS-CoV-2 infection.
PSMD14 is a novel prognostic marker and therapeutic target in osteosarcoma
Authors: Lai Jiabin , Kong Weike , Fu Qiangchang , Jiang Zhaochang , Sun Bohao , Ye Xin , Kong Jing , Wei Shumei , Jiang Lifeng
Published: June 2024

Background

Osteosarcoma is a bone tumor that is characterized by high malignancy and a high mortality rate, and that originates from primitive osteoblastic mesenchymal cells and is most common in rapidly growing long bones. PSMD14, also known as RPN11 or POH1, is a member of the JAMM isopeptidase family, which is able to remove the substrate protein ubiquitination label, thereby regulating the stability and function of the substrate protein. In this study, we explored the expression and potential biological significance of the PSMD14 deubiquitinating enzyme in osteosarcoma.

Methods

Immunohistochemical methods were used to detect the expression of PSMD14 in biopsies of 91 osteosarcoma patients, and the specimens were classified into high and low PSMD14 expression groups. The correlation between PSMD14 expression and clinical indicators and prognosis was compared.SiRNA was used to downregulate PSMD14 in two osteosarcoma cell lines (HOS and SJSA-1), and the effects of downregulation of PSMD14 on the viability, proliferation, and invasion ability of osteosarcoma cells were analyzed.

Results

We identified significant differences in recurrence, metastasis, and survival time of the osteosarcoma patients on the basis of PSMD14 expression. High expression of PSMD14 in osteosarcoma patients was associated with a low survival rate and high risk of metastasis and recurrence. Down-regulation of PSMD14 inhibited the viability, proliferation, and invasiveness of osteosarcoma cell lines.

Conclusions

PSMD14 may be a new prognostic marker and therapeutic target for osteosarcoma.
Extracellular vesicle-delivered hsa_circ_0090081 regulated by EIF4A3 enhances gastric cancer tumorigenesis
Authors: Mou Yanjie , Lv Kun
Published: June 2024

Background

Circular RNA (circRNA) and extracellular vesicles (EVs) in tumors are crucial for the malignant phenotype of tumor cells. Nevertheless, the mechanisms and clinical effects of EV-delivered hsa_circ_0090081 in gastric cancer (GC) are unclear. This study aimed to reveal the effect of eukaryotic translation initiation factor 4A3 (EIF4A3)-mediated hsa_circ_0090081 expression and EV-delivered hsa_circ_0090081 on GC progression.

Methods

qRT-PCR was conducted to clarify hsa_circ_0090081 and EIF4A3 levels in GC tissues. Transmission electronic microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting identified the EVs isolated from GC cells by ultracentrifugation. The roles of hsa_circ_0090081, EIF4A3, and EV-delivered hsa_circ_0090081 in GC cells were analyzed using Transwell, EdU, and CCK-8 assays. The regulatory role between EIF4A3 and hsa_circ_0090081 was investigated using RIP, qRT-PCR, and Pearson’s analysis.

Results

Our study showed that hsa_circ_0090081 and EIF4A3 were highly expressed in GC, and hsa_circ_0090081 was associated with poor prognosis. Data revealed that hsa_circ_0090081 inhibition restrained GC cell proliferation, invasion, and migration. Additionally, EIF4A3 could bind to the pre-mRNA of PHEX (linear form of hsa_circ_0090081) to enhance hsa_circ_0090081 expression in GC cells. Moreover, EIF4A3 overexpression nullified the malignant phenotypic suppression caused by hsa_circ_0090081 silencing in GC cells. Furthermore, EVs secreted by GC cells delivered hsa_circ_0090081 to facilitate the malignant progression of targeted GC cells.

Conclusion

This study showed that hsa_circ_0090081 was enhanced by EIF4A3 to play a promotive role in GC development. The results may help understand the mechanism of EIF4A3 and EV-delivered hsa_circ_0090081 and offer a valuable GC therapeutic target.
A novel variant in the SLCO2A1 gene in a Chinese patient with chronic gastroenteropathy and primary hypertrophic osteoarthropathy
Authors: Dai Yimin , He Miao , Xu Hui , Tan Bei , Zhou Weixun , Liu Wei , Wang Qiang , Huang Jingyi , Shang Qing , Liu Yaping , Li Yue
Published: June 2024

Background

Chronic enteropathy associated with SLCO2A1 gene (CEAS) results from loss-of-function variants in SLCO2A1, which encodes the prostaglandin transporter (PGT). CEAS follows an autosomal recessive inheritance pattern. To date, approximate 30 pathogenic variants have been reported in CEAS.

Methods

We performed whole exome sequencing (WES) to screen for potential pathogenic variants in a patient suspected of having CEAS, and confirmed a variant in SLCO2A1 using Sanger sequencing. We established an in vitro minigene model to compare splicing between wild type (WT) and mutant transcripts. Quantitative polymerase chain reaction (qPCR) was used to evaluate SLCO2A1 transcription in the stomach and colon tissues from the patient and a healthy control (HC). The transcripts were further cloned and sequenced.

Results

The patient had a novel, homozygous, recessive c.929A > G variant in exon 7 of SLCO2A1, which has not been previously reported in CEAS or PHO. This variant altered splicing, resulting in an exon 7‐truncated transcript lacking 16 bases. No normal transcript was detected in the patient’s stomach or colon tissue. qPCR also showed significantly decreased SLCO2A1 transcription compared to HC.

Conclusion

A previously unreported variant caused defective SLCO2A1 splicing and reduced mRNA levels in a patient with CEAS and PHO. This research enhances understanding of CEAS and PHO pathophysiology and aids genetic counseling and diagnosis.
Cognitive potential of children and adolescents with CHARGE syndrome and deafblindness
Authors: Skei Lynn , Skei Sigmund , Hartshorne Timothy , Landrø Nils Inge
Published: June 2024

Background

The present study aimed to test the hypothesis stating that the cognitive potential of individuals with deafblindness is equal to those without a deafblind condition, an assumption that until now has been empirically unsubstantiated within the field of deafblindness.

Methods

To explore the assumption, 15 children and adolescents with CHARGE underwent cognitive assessment with WISC-V using a sequential two-level assessment design. The 1st level involved standardized test conditions. The 2nd level was designed as a continuation of the performances obtained from the 1st level and involved accommodations to compensate for sensory motor impairment. Statistical procedures involved the sample as a whole and when divided into two subgroups: (i) participants with CHARGE without deafblindness; (ii) participants with CHARGE and deafblindness using the 1st level scores as base line.

Results

Although results showed significantly lower scores in the deafblind subgroup with standardized procedures, they approximated the others after accommodating for their sensory deficits. This positive increase proved significant.

Conclusion

Findings supported the assumption of equal cognitive potential of individuals with and without deafblindness. Results indicated that the children and adolescents with deafblindness had most effect of the accommodations, enabling them to approximate the results of the subgroup without deafblindness. These gains were attributed enhanced accessibility endorsed by the accommodations and represented the participants latent cognitive dispositions only realized under certain circumstances.
Spatial and temporal analysis on the impact of ultra-low volume indoor insecticide spraying on Aedes aegypti household density
Authors: Kawiecki Anna B. , Morrison Amy C. , Barker Christopher M.
Published: June 2024

Background

Aedes aegypti is the primary mosquito vector for several arboviruses, such as dengue, chikungunya and Zika viruses, which cause frequent outbreaks of human disease in tropical and subtropical regions. Control of these outbreaks relies on vector control, commonly in the form of insecticide sprays that target adult female mosquitoes. However, the spatial coverage and frequency of sprays needed to optimize effectiveness are unclear. In this study, we characterize the effect of ultra-low-volume (ULV) indoor spraying of pyrethroid insecticides on Ae. aegypti abundance within households. We also evaluate the effects of spray events during recent time periods or in neighboring households. Improved understanding of the duration and distance of the impact of a spray intervention on Ae. aegypti populations can inform vector control interventions, in addition to modeling efforts that contrast vector control strategies.

Methods

This project analyzes data from two large-scale experiments that involved six cycles of indoor pyrethroid spray applications in 2 years in the Amazonian city of Iquitos, Peru. We developed spatial multi-level models to disentangle the reduction in Ae. aegypti abundance that resulted from (i) recent ULV treatment within households and (ii) ULV treatment of adjacent or nearby households. We compared fits of models across a range of candidate weighting schemes for the spray effect, based on different temporal and spatial decay functions to understand lagged ULV effects.

Results

Our results suggested that the reduction of Ae. aegypti in a household was mainly due to spray events occurring within the same household, with no additional effect of sprays that occurred in neighboring households. Effectiveness of a spray intervention should be measured based on time since the most recent spray event, as we found no cumulative effect of sequential sprays. Based on our model, we estimated the spray effect is reduced by 50% approximately 28 days after the spray event.

Conclusions

The reduction of Ae. aegypti in a household was mainly determined by the number of days since the last spray intervention in that same household, highlighting the importance of spray coverage in high-risk areas with a spray frequency determined by local viral transmission dynamics.

Graphical abstract
Quantifying sustainability in the agri-food system: a comprehensive methodological framework and expert consensus approach
Authors: Castillo-Díaz Francisco José , Belmonte-Ureña Luis J. , López-Serrano María José , Camacho-Ferre Francisco
Published: June 2024

Assessing the economic, social, and environmental sustainability of food production is imperative for aligning with the Sustainable Development Goals (SDGs) of the 2030 Agenda and adhering to evolving regulatory and strategic frameworks. The absence of a standardized methodology for quantifying sustainability in the agri-food system value chain necessitates the development of an effective approach. This study proposes a comprehensive methodological framework for quantifying the sustainability of agriculture, livestock, and the agri-food industry. The proposed methodology is based on the consensus achieved by a panel of experts using the Delphi methodology. The study emphasizes the identification of activities requiring corrective measures to enhance sustainability within the circular economy principles. The proposed model incorporates 70 indicators, with a particular emphasis on environmental indicators, aligning with the consensus of the expert panel. The resulting composite indicator and the accompanying battery of indicators provide a nuanced understanding of agribusiness sustainability. The study's findings underscore the need for prioritizing environmental considerations in evaluating agribusiness sustainability. The proposed model facilitates the formulation of actionable plans to enhance the viability of agribusinesses, enabling their adaptation to the evolving social and political landscape. This adaptation is crucial in meeting the contemporary demand for a reduction in the environmental footprint associated with food production and transformation. The developed methodology contributes to the harmonization of sustainability assessment practices, fostering a more comprehensive and standardized approach across the agri-food sector.
Ethical implications of defining longstanding anorexia nervosa
Authors: Voswinkel Marthe M. , Hanegraaff Simone M. , Mares Suzanne H.W. , Wezenberg Elke , van Delden Johannes J.M. , van Elburg Annemarie A.
Published: June 2024

The label severe and enduring anorexia nervosa (SE-AN) is widely used in the literature on longstanding anorexia nervosa (AN). However, the process of constructing the criteria and the use of the label SE-AN has ethical implications that have not been taken into account. Through combining existing literature and lived experience perspective, this paper addresses to what extent the current criteria do and do not reflect the lived experience. Arguments are presented on why the process of constructing the criteria for SE-AN and the application of the label can be both identified as, and give rise to, epistemic injustice. Epistemic injustice is an injustice that is done to a person as an individual with the capacity of acquiring and sharing knowledge. This type of injustice can occur at any stage of an interaction between people in which knowledge is shared with one another. The paper concludes by giving suggestions on how to pursue epistemic justice in the process of defining longstanding AN.
Seasonal migrations of the European sea bass (Dicentrarchus labrax L.) in UK and surrounding waters
Authors: Wright Serena , Griffiths Christopher A. , Bendall Victoria , Righton David , Hyder Kieran , Hunter Ewan
Published: June 2024

The movements and behaviour of mature European sea bass (Dicentrarchus labrax L.) in UK waters have not been studied extensively since a series of mark-recapture experiments during the 1970s, 80s and 90s. To better understand the timing and extent of seasonal migrations, 171 mature sea bass > 42 cm were internally tagged with floated electronic tags programmed to record temperature and depth, and released in the English Channel, in the southern North Sea and in the Irish Sea. Among the 48 tags returned to date, sea bass were at liberty for 370 ± 337 days and were recovered 172 ± 200 km from their respective release locations. Most tags were recovered from beaches (54%), or via the fishery (44%). A comparison of the reconstructed tracks from returned electronic tags with the recapture locations of 237 mark-recapture returns (6.5%) from 3615 sea bass released between 1970 and 2020 showed strong overlap. Seasonal movements between shallow areas (Q2–Q3) and deeper spawning areas (Q4–Q1) were accompanied by elevated vertical swimming speeds and average water temperatures of 8.5 °C in the English Channel and Irish Sea, but lower temperatures in the North Sea. Movements between the Celtic Sea/Irish Sea and the North Sea and vice versa demonstrate high levels of connectivity in UK waters. We demonstrate that a proportion of sea bass remained resident within the North Sea throughout the year, with a strong suggestion that spawning might be occurring. These data have significant implications for the future sustainable management of sea bass stocks in UK and surrounding waters.
Low-flow time and outcomes in hypothermic cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation: a secondary analysis of a multi-center retrospective cohort study
Authors: Shoji Kosuke , Ohbe Hiroyuki , Matsuyama Tasuku , Inoue Akihiko , Hifumi Toru , Sakamoto Tetsuya , Kuroda Yasuhiro , Kushimoto Shigeki ,   the SAVE-J II study group, Sawano Hirotaka , Egawa Yuko , Kato Shunichi , Sugiyama Kazuhiro , Bunya Naofumi , Kasai Takehiko , Ijuin Shinichi , Nakayama Shinichi , Kanda Jun , Kanou Seiya , Takiguchi Toru , Yokobori Shoji , Takada Hiroaki , Inoue Kazushige , Takeuchi Ichiro , Honzawa Hiroshi , Kobayashi Makoto , Hamagami Tomohiro , Takayama Wataru , Otomo Yasuhiro , Maekawa Kunihiko , Shimizu Takafumi , Nara Satoshi , Nasu Michitaka , Takahashi Kuniko , Hagiwara Yoshihiro , Fukuda Reo , Ogura Takayuki , Shiraishi Shinichiro , Zushi Ryosuke , Otani Norio , Kikuchi Migaku , Watanabe Kazuhiro , Nakagami Takuo , Shoko Tomohisa , Kitamura Nobuya , Otani Takayuki , Matsuoka Yoshinori , Sakuraya Masaaki , Arimoto Hideki , Homma Koichiro , Naito Hiromichi , Nakao Shunichiro , Okazaki Tomoya , Tahara Yoshio , Okamoto Hiroshi , Kunikata Jun , Yokoi Hideto
Published: June 2024

Background

In out-of-hospital cardiac arrest (OHCA) patients with extracorporeal cardiopulmonary resuscitation (ECPR), the association between low-flow time and outcomes in accidental hypothermia (AH) patients compared to those of patients without AH has not been fully investigated.

Methods

This was a secondary analysis of the retrospective multicenter registry in Japan. We enrolled patients aged ≥ 18 years who had been admitted to the emergency department for OHCA and had undergone ECPR between January, 2013 and December, 2018. AH was defined as an arrival body temperature below 32 °C. The primary outcome was survival to discharge. Cubic spline analyses were performed to assess the non-linear associations between low-flow time and outcomes stratified by the presence of AH. We also analyzed the interaction between low-flow time and the presence of AH.

Results

Of 1252 eligible patients, 105 (8.4%) and 1147 (91.6%) were in the AH and non-AH groups, respectively. Median low-flow time was 60 (47–79) min in the AH group and 51 (42–62) min in the non-AH group. The survival discharge rates in the AH and non-AH groups were 44.8% and 25.4%, respectively. The cubic spline analyses showed that survival discharge rate remained constant regardless of low-flow time in the AH group. Conversely, a decreasing trend was identified in the survival discharge rate with longer low-flow time in the non-AH group. The interaction analysis revealed a significant interaction between low-flow time and AH in survival discharge rate (p for interaction = 0.048).

Conclusions

OHCA patients with arrival body temperature < 32 °C who had received ECPR had relatively good survival outcomes regardless of low-flow time, in contrast to those of patients without AH.
Histogram analysis of multiple diffusion models for predicting advanced non-small cell lung cancer response to chemoimmunotherapy
Authors: Zheng Yu , Zhou Liang , Huang Wenjing , Han Na , Zhang Jing
Published: June 2024

Background

There is an urgent need to find a reliable and effective imaging method to evaluate the therapeutic efficacy of immunochemotherapy in advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the capability of intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) histogram analysis based on different region of interest (ROI) selection methods for predicting treatment response to chemoimmunotherapy in advanced NSCLC.

Methods

Seventy-two stage III or IV NSCLC patients who received chemoimmunotherapy were enrolled in this study. IVIM and DKI were performed before treatment. The patients were classified as responders group and non-responders group according to the Response Evaluation Criteria in Solid Tumors 1.1. The histogram parameters of ADC, Dslow, Dfast, f, Dk and K were measured using whole tumor volume ROI and single slice ROI analysis methods. Variables with statistical differences would be included in stepwise logistic regression analysis to determine independent parameters, by which the combined model was also established. And the receiver operating characteristic curve (ROC) were used to evaluate the prediction performance of histogram parameters and the combined model.

Results

ADC, Dslow, Dk histogram metrics were significantly lower in the responders group than in the non-responders group, while the histogram parameters of f were significantly higher in the responders group than in the non-responders group (all P < 0.05). The mean value of each parameter was better than or equivalent to other histogram metrics, where the mean value of f obtained from whole tumor and single slice both had the highest AUC (AUC = 0.886 and 0.812, respectively) compared to other single parameters. The combined model improved the diagnostic efficiency with an AUC of 0.968 (whole tumor) and 0.893 (single slice), respectively.

Conclusions

Whole tumor volume ROI demonstrated better diagnostic ability than single slice ROI analysis, which indicated whole tumor histogram analysis of IVIM and DKI hold greater potential than single slice ROI analysis to be a promising tool of predicting therapeutic response to chemoimmunotherapy in advanced NSCLC at initial state.
Sinus irrigation as an adjunctive therapy for odontogenic maxillary sinusitis — an in-depth analysis
Authors: Jaiswal M. Shriya , Ha Gyu-Bong , Hwang Ji-Young , Lee Ja-Young , Hwang Dae-Seok
Published: June 2024

Background

Odontogenic maxillary sinusitis (OMS) is widely acknowledged in both the dentistry and otolaryngology fields. Recently, iatrogenic odontogenic maxillary sinusitis cases can be encountered frequently. The purpose of this study was to evaluate the effect of intraoral sinus irrigation using the small lateral window approach in patients with odontogenic maxillary sinusitis by comparing pre- and postoperative volumetric measurement of CBCT and symptoms.

We surveyed 21 patients who visited the Oral and Maxillofacial Surgery Department at PNUDH from 2016 to 2022. All the patients’ information was extracted from an electronic database. The patients with a follow-up period of 2 months or more were included. The three-dimensional volumetric measurement was performed using the ImageJ program (National Institute of Health, University of Wisconsin).

Results

Among 21 patients, 16 (76.1%) were male, and 5 (23%) were female. The most common type of surgery was general anesthesia (16 cases) in which oroantral fistula was present in 7 cases. In the causes of maxillary sinusitis, there were seven implant-related patients, five patients of tooth extraction, seven patients of bone grafting, and two patients in other groups. Radiographic opacity decreased by 40.15% after sinus irrigation especially in bone graft and tooth extraction cases. Clinically, symptoms improved in 17 patients (80.9%).

Conclusion

By this study, it can be concluded that maxillary sinus irrigation using the small lateral window approach is a clinically and radiologically effective treatment method for odontogenic maxillary sinusitis.
Leveraging Patient Engagement Through Collaboration for Improved Global Health Outcomes in Sarcoma
Authors: Evans Denisse , Rothschild Sara , Tordella Carol , Chacón Matías
Published: June 2024

In the dynamic landscape of oncology, collaborative efforts between the medical community and patient advocacy groups are pivotal in shaping standards of care and advancing research. Nowhere is this collaboration more evident than in sarcoma, a group of rare cancers posing unique challenges to diagnosis, management, and treatment, which profoundly affect patient outcomes. Here, we explore the vital role of patient-centric collaboration in improving global health outcomes in sarcoma, emphasizing the transformative power of collective action and shared expertise. Challenges in sarcoma care, including diagnostic complexities, disparities in access to care, and genomic tumor heterogeneity, underscore the urgent need for collaborative solutions. Initiatives like the Sarcoma European and Latin American Network (SELNET) and The Life Raft Group (LRG) exemplify successful models of collaborative research and patient advocacy, driving advancements in diagnosis, treatment, and disease understanding. Stakeholders across disciplines are uniting to improve sarcoma care and outcomes through the development of clinical practice guidelines, continuous medical education, patient registries, virtual tumor boards, and consortium-driven research endeavors, all of which foster the growth of global collaborative groups. The success of these collaborative efforts serves as a model for other rare diseases, highlighting the potential of collective action to drive progress and innovation in health care.
Molecular characterization and biomarker identification in pediatric B-cell acute lymphoblastic leukemia.
Authors: Du Yu , Zhang Xiankai , Sun Ming , Yang Li , Long Fei , Qi Shanshan , Luo Linlin , Wang Chenxuan , Lv Xiaoyan , Wu Xiaoying , Zhu Liuqing , Ou Qiuxiang , Xiong Hao
Published: June 2024

6524

Background: B-cell acute lymphoblastic leukemia (B-ALL) is the most prevalent hematologic malignancy in children and a leading cause of mortality. Despite high cure rates, the management of B-ALL remains challenging due to its high heterogeneity and propensity for relapse. This study aimed to delineate molecular features of pediatric B-ALL and explore the clinical utility of circulating tumor DNA (ctDNA) as a biomarker in B-ALL. Methods: The study analyzed 146 primary pediatric B-ALL patients who were diagnosed from August 2020 to April 2023 and received systemic chemotherapy in Wuhan Children's Hospital. Baseline bone marrow (BM) and plasma samples were collected for next-generation sequencing (NGS) to profile the mutational landscape. BM samples collected on day 19 of the treatment were utilized for minimal residual disease (MRD) testing to assess treatment efficacy. Transcriptomic profiling of baseline BM samples was performed via bulk RNA sequencing. Fisher's exact test and the Wilcoxon rank sum test were utilized to compare categorical and continuous variables between groups, respectively. A two‐tailed P-value<0.05 was considered statistically significant unless indicated otherwise. Results: Transcriptomic analysis revealed that 86.3% of patients (126 out of 146) could be categorized into 13 distinct molecular subtypes, with hyperdiploidy emerging as the predominant subtype. Baseline BM NGS identified gene fusions in 61% of patients, including 37 novel fusions previously unreported in B-ALL. Specifically, the KMT2A-TRIM29 novel fusion was detected and validated in a male child diagnosed with the KMT2A-rearranged subtype. Despite initially responding well to therapy, the patient experienced disease progression after a year, indicating a poor prognosis. We also found that elevated mutant counts and maximum-variant-allele-frequency (maxVAF) in baseline BM were associated with significantly poorer response to chemotherapy ( P=0.0012 and 0.028, respectively). Additionally, MRD-negative patients exhibited upregulated expression of immune-related pathways ( P<0.01) and increased CD8+ T cell infiltration ( P=0.047), indicating a more active immune microenvironment in better responding tumors. Baseline plasma ctDNA, which exhibited high mutational concordance with paired baseline BM samples, also demonstrated significant associations with chemotherapy efficacy, highlighting its potential as a non-invasive tool for disease monitoring and treatment outcome prediction. Conclusions: This study elucidated novel gene fusions and potential biomarkers for treatment response in pediatric B-ALL. Importantly, both baseline plasma ctDNA and BM samples offer promising prognostic insights into chemotherapy responses, paving the way for non-invasive monitoring strategies in the management of pediatric B-ALL.