bluuebunny/crossref_metadata_2025 huggingface dataset:
New equations of fibre reinforced polymers-concrete bond strength and bond-slip law based on mesoscale simulations
Authors: Li Ya-Qi , Yang Zhenjun
Published: June 2023

The bond behaviour between fibre reinforced polymers (FRP) and concrete plays a critical role in FRP-strengthened concrete structures. Most existing equations of bond strength and bond-slip laws ignore the heterogeneous nature of concrete, resulting in considerable disparities with experimental data. In this study, the mesoscale finite element modelling approach developed and validated previously is applied in extensive Monte Carlo simulations (MCS) of FRP-concrete bonded joints with various concrete compressive strength and coarse aggregate fractions ( AF). Based on the MCS results, AF-dependent empirical equations for the bond strength and the interfacial bond-slip law are proposed and validated against 101 FRP-concrete joint tests under single-shear loading. The consideration of AF leads to closer predictions of bond strength and force-displacement curves to the test data than the widely-accepted Chen and Teng’s bond-strength model and Lu et al.’s bond-slip law.
Phantom array and stroboscopic effect visibility under combinations of TLM parameters
Authors: Miller NJ , Rodriguez-Feo Bermudez E , Irvin L , Tan J
Published: June 2023

Solid-state light sources can be more prone to larger temporal light modulation (TLM) than conventional sources. TLM visibility depends on wave shape, frequency, modulation depth and duty cycle, and is affected by the sensitivity of the observer. TLM can be visible well above the critical flicker fusion frequency, when there is relative movement between the observer’s eyes and light source, lighted space or moving objects in the field of view. This human subjects experiment explored visibility of the stroboscopic effect (SE) versus the phantom array effect (PAE) with targeted tasks under 74 TLM waveforms. The results showed the SE visibility peaks between 90 Hz and 120 Hz, while the PAE visibility peaks between 500 Hz and 1000 Hz. The phantom array is visible to sensitive participants at 6000 Hz. Both effects are more visible under rectangular versus sinusoidal TLM, higher modulation, and when duty cycles are 10% or 30% versus 50%. Higher sensitivity participants, differentiated using the Leiden Visual Sensitivity Scale, rated TLM waveforms as more visible, especially those inherently harder to see. This work lays a foundation for a PAE metric and guides driver and dimmer designers toward electronic circuits that minimize the visibility of TLM in LED products.
Cognitive Impairments After Stroke Do Not Attenuate Explicit Visuomotor Adaptation in Reaching and Savings With the Unaffected Arm
Authors: Binyamin-Netser Reut , Goldhamer Noy , Avni Inbar , Ressel Zviely Adva , Shmuelof Lior
Published: June 2023

Background

Accumulating evidence suggests that motor performance is affected by the cognitive control abilities of the subject. Performance in motor tasks in populations with cognitive deficits such as older adults and subjects with stroke is therefore expected to deteriorate. The goal of this study is to investigate the relationship between cognitive impairments and motor control and learning impairments in a visuomotor adaptation task in subjects with stroke.

Methods

Twenty-seven post-stroke, 31 age matched controls, and 30 young control subjects completed a sensorimotor adaptation task composed of 2 adaptation blocks separated by a washout block. Explicit learning was assessed by cueing subjects to suppress their strategy. Cognitive assessment was conducted using the Montreal Cognitive Assessment (MoCA) and a verbal learning test. Subjects with stroke performed the task with their unaffected arm.

Results

Despite the cognitive deterioration, the adaptation and savings of the stroke group and age matched controls were comparable. Adaptation and savings were smaller with respect to the young subjects. Savings was associated with a significant improvement in the explicit component across blocks. Finally, the explicit enhancement between blocks was significantly correlated with the MoCA scores in the stroke group and with the results of the verbal learning test in the young controls.

Conclusion

The lack of stroke-induced attenuation on adaptation, despite a correlation between cognitive abilities and explicit learning in adaptation, suggests that subjects with stroke have enough cognitive resources to support sensorimotor adaptation. The availability of cognitive resources for motor learning following brain damage could be utilized in the rehabilitation process.
Study on the forming fracture of the crash box with extruded Al6060-T6 profile
Authors: Ma Seungchan , Choi Young
Published: June 2023

This study was performed to analyze the forming fracture of crash box with extruded Al6060-T6 profile. Deep drawing test was performed to evaluate the formability of the extruded profile. For the various specimens, deep drawing tests were repeated to measure the maximum stroke at which fracture did not occur. The finite element analysis for the deep drawing tests was performed to calculate the principal strain through the obtained maximum stroke. The forming limit diagram for the design of the concave forming shape was calculated through the obtained principal strains with the FEA. The forming shape was optimized by using the design variables and FLD by using the FEA. The design variables are the central curvature, the lateral curvature, and the forming depth. The tools were made with the optimizing model and the crash box has been formed without fracture.
Color and NICU Design
Authors: Shepley Mardelle McCuskey , Ames Rebecca L. , Lin Connie Y.
Published: June 2023

Purpose:

The appropriate use of color in healthcare settings has been a topic of interest for designers and researchers, and the need for evidence-based standards evident. The purpose of this article is to summarize recent research on color as applicable to neonatal intensive care units and to propose standards for color in these settings.

Background:

Research on this topic is limited due to difficulties associated with constructing research protocols, challenges in setting parameters for the independent variable (color), and the need to simultaneously address infants, families, and caregivers.

Methods:

For our literature review, the following research question was developed: Does the use of color in the design of the neonatal intensive care units (NICUs) impact health outcomes in newborn infants, families, and/or staff? Using Arksey and O’Malley’s framework for conducting a structured literature review, we (1) identified the research question, (2) identified relevant studies, (3) selected studies, and (4) collated and summarized the results. Only four papers were found regarding NICUs, so the search was expanded to include related healthcare and authors reporting on best practice.

Results:

Overall, the primary research focused on behavioral or physiological outcomes including the role of wayfinding and art, the impact of lighting on color, and tools for evaluating the impact of color. Best practice recommendations sometimes reflected the primary research but occasionally provided contradictory advice.

Conclusions:

Based on the reviewed literature, five topics are addressed: palette malleability; the use of the primary colors, blue, red, and yellow; and the relationship between light and color.
Exhaled volatile organic compounds associated with risk factors for obstructive pulmonary diseases: a systematic review
Authors: Shahbazi Khamas Shahriyar , Alizadeh Bahmani Amir Hossein , Vijverberg Susanne J.H. , Brinkman Paul , Maitland-van der Zee Anke H.
Published: June 2023

Background

Asthma and COPD are among the most common respiratory diseases. To improve the early detection of exacerbations and the clinical course of asthma and COPD new biomarkers are needed. The development of noninvasive metabolomics of exhaled air into a point-of-care tool is an appealing option. However, risk factors for obstructive pulmonary diseases can potentially introduce confounding markers due to altered volatile organic compound (VOC) patterns being linked to these risk factors instead of the disease. We conducted a systematic review and presented a comprehensive list of VOCs associated with these risk factors.

Methods

A PRISMA-oriented systematic search was conducted across PubMed, Embase and Cochrane Libraries between 2000 and 2022. Full-length studies evaluating VOCs in exhaled breath were included. A narrative synthesis of the data was conducted, and the Newcastle–Ottawa Scale was used to assess the quality of included studies.

Results

The search yielded 2209 records and, based on the inclusion/exclusion criteria, 24 articles were included in the qualitative synthesis. In total, 232 individual VOCs associated with risk factors for obstructive pulmonary diseases were found; 58 compounds were reported more than once and 12 were reported as potential markers of asthma and/or COPD in other studies. Critical appraisal found that the identified studies were methodologically heterogeneous and had a variable risk of bias.

Conclusion

We identified a series of exhaled VOCs associated with risk factors for asthma and/or COPD. Identification of these VOCs is necessary for the further development of exhaled metabolites-based point-of-care tests in these obstructive pulmonary diseases.
Tuberculosis medicines for children in Europe: an unmet medical need
Authors: Cherchi Antonio , Vaz Alexandra , Coelho Ana , Fregonese Laura , Thirstrup Steffen
Published: June 2023

The availability of first-line medicines for the treatment of drug-susceptible tuberculosis (TB) is inconsistent across European countries. This is particularly worrisome for child-friendly medicines. There are reported examples of physicians being forced to adapt and/or combine formulations intended for adults to treat children with TB. Reduced compliance, unknown effects on treatment outcomes and unpredictable toxicity are potential consequences of resorting to these suboptimal treatment options. Furthermore, the use of these alternatives may increase the risk of drug-resistant TB. This study analysed the availability and use of TB medicines in the European Union (EU)/European Economic Area, with a particular focus on child-friendly formulations. We sought to carry out a full review of the situation by means of a survey involving the EU regulatory network. Countries were asked to confirm marketing status of anti-drug-susceptible-TB medicines, ways used to overcome their absence in their territory and the general difficulties they face to treat children with TB. Results confirmed that rifampicin suspension is the only child-friendly formulation available in Europe, approved in just 10 member states. Overall, 24 countries out of 30 considered the lack of adequate drug-susceptible TB medicines an unmet medical need. To overcome this, countries confirmed that they resort to importation or use adapted formulations. The joint forces of European institutions and pharmaceutical industry are crucial for the development of paediatric formulations and contribute to better compliance and health outcomes.
How economic weights translate into genetic and phenotypic progress, and vice versa
Authors: Simianer Henner , Heise Johannes , Rensing Stefan , Pook Torsten , Geibel Johannes , Reimer Christian
Published: June 2023

Background

This paper highlights the relationships between economic weights, genetic progress, and phenotypic progress in genomic breeding programs that aim at generating genetic progress in complex, i.e., multi-trait, breeding objectives via a combination of estimated breeding values for different trait complexes.

Results

Based on classical selection index theory in combination with quantitative genetic models, we provide a methodological framework for calculating expected genetic and phenotypic progress for all components of a complex breeding objective. We further provide an approach to study the sensitivity of the system to modifications, e.g. to changes in the economic weights. We propose a novel approach to derive the covariance structure of the stochastic errors of estimated breeding values from the observed correlations of estimated breeding values. We define ‘realized economic weights’ as those weights that would coincide with the observed composition of the genetic trend and show, how they can be calculated. The suggested methodology is illustrated with an index that aims at achieving a breeding goal composed of six trait complexes, that was applied in German Holstein cattle breeding until 2021.

Conclusions

Based on the presented results, the main conclusions are (i) the composition of the observed genetic progress matches the expectations well, with predictions being slightly better when the covariance of estimation errors is taken into account; (ii) the composition of the expected phenotypic trend deviates significantly from the expected genetic trend due to the differences in trait heritabilities; and (iii) the realized economic weights derived from the observed genetic trend deviate substantially from the predefined ones, in one case even with a reversed sign. Further results highlight the implications of the change to a modified breeding goal based on the example of a new index comprising eight, partly new, trait complexes, which is used since 2021 in the German Holstein breeding program. The proposed framework and the analytical tools and software provided will be useful to define more rational and generally accepted breeding objectives in the future.
Remote cerebellar hemorrhage following repeated lumbar punctures
Authors: Wang Hai-Yang , Hu Zerui , Han Jinming , Wang Dongsen , Wu Qingjian
Published: June 2023

Background

Remote cerebellar hemorrhage (RCH) is a rare complication in neurosurgery. No case of RCH secondary to repeated lumbar punctures (LPs) has been previously reported.

Case presentation

A 49-year-old man presented with impaired consciousness following persistent fever. Cerebrospinal fluid examination showed high opening pressure, elevated white blood cells, increased protein level, and decreased glucose level, resulting in a diagnosis of bacterial meningoencephalitis. Treatment with repeated LPs and intrathecal injection of ceftriaxone resulted in an improvement in neurological symptoms. However, on day 31 of treatment, brain magnetic resonance image (MRI) showed streaky bleeding in bilateral cerebellum (zebra sign), leading to a diagnosis of RCH. Close observation and repeated brain MRI imaging without specific treatments led to the absorption of bilateral cerebellar hemorrhage, and the patient was discharged with improved neurological symptoms. Repeated brain MRI scans one month after discharge showed that bilateral cerebellar hemorrhage had improved, and had disappeared one year after discharge.

Conclusion

We reported a rare occurrence of LPs-induced RCH presenting as isolated bilateral inferior cerebellar hemorrhage. Clinicians should be vigilant of the risk factors for RCH, closely monitoring patients' clinical symptoms and neuroimaging findings to determine the need for specialized treatment. Furthermore, this case highlights the importance of ensuring the safety of LPs and managing any potential complications appropriately.
Log odds of positive lymph nodes as a novel prognostic predictor for gastric cancer: a systematic review and meta-analysis
Authors: Li Yiding , Wu Guiling , Liu Jinqiang , Zhang Yujie , Yang Wanli , Wang Xiaoqian , Duan Lili , Niu Liaoran , Chen Junfeng , Zhou Wei , Han Weili , Wang Jing , Zhong Helun , Ji Gang , Fan Daiming , Hong Liu
Published: June 2023

Background

We conducted a systematic review and meta-analysis to summarize the predictive and prognostic ability of the log odds of positive lymph nodes (LODDS) staging system and compare it with pathological N (pN) classification and the ratio-based lymph node system (rN) for the overall survival (OS) of gastric cancer (GC).

Methods

Through a systematic review till March 7, 2022, we identified population-based studies that reported the prognostic effects of LODDS in patients with GC. We compare the predictive effectiveness of the LODDS staging system with that of the rN and pN classification systems for the OS of GC.

Results

Twelve studies comprising 20,312 patients were included in this systematic review and meta-analysis. The results showed that LODDS1, LODDS2, LODDS3, and LODDS4 in GC patients were correlated with poor OS compared with LODDS0 (LODDS1 vs. LODDS0: HR = 1.62, 95% CI (1.42, 1.85); LODDS2 vs. LODDS0: HR = 2.47, 95% CI (2.02, 3.03); LODDS3 vs. LODDS0: HR = 3.15, 95% CI (2.50, 3.97); LODDS4 vs. LODDS0: HR = 4.55, 95% CI (3.29, 6.29)). Additionally, significant differences in survival were observed among patients with different LODDS classifications (all P-values were < 0.001) with the same rN and pN classifications. Meanwhile, for patients with different pN or rN classifications with the same LODDS classification, prognosis was highly similar.

Conclusion

The findings show that LODDS is correlated with the prognosis of GC patients and is superior to the pN and rN classifications for prognostic assessment.
BMI and perceived weight on suicide attempts in Korean adolescents: findings from the Korea Youth Risk Behavior Survey (KYRBS) 2020 to 2021
Authors: Kim Byungmi , Kim Hyo-Seon , Park Sunhee , Kwon Jeoung A
Published: June 2023

Background

Suicide is a leading cause of death in South Korea (hereafter ‘Korea’), and there is evidence that body weight and perceived weight affecting suicide have a significant effect on suicidal behavior in adolescence. This study investigated the association between body mass index (BMI), perceived weight, and suicide attempts in adolescents.

Methods

We included nationally representative data for a total of 106,320 students in our final analysis. We calculated and stratified BMI (underweight, normal weight, overweight) to determine the correlation between BMI and suicide attempts. We stratified the participants into three groups (perceived as underweight, normal weight, and overweight) for subjective body weight perception to analyze the relationship between subjective body weight perception and suicide attempts. We further analyzed the combination of BMI and subjective body weight perception to determine the relationship between suicide attempts and distorted subjective weight perception.

Results

Compared with perceiving oneself as having a normal weight, the odds ratios (ORs) for suicide attempts were significantly increased in the group perceiving themselves as overweight. In addition, those who perceived themselves as overweight but were underweight according to their BMI were at significantly increased risk of suicide attempts relative to those who perceived themselves as about the right weight.

Conclusions

There was a significant association with suicide attempts in the underweight and perceived overweight group. This shows the importance of combining BMI and perceived weight when examining the relationship between weight and suicide attempts in adolescents.
The importance of developing palliative care quality indicators for the prison setting: why now, and next steps
Authors: Schaefer Isabelle , Heneka Nicole , DiGiacomo Michelle , Panozzo Stacey , Phillips Jane L.
Published: June 2023

Palliative care is increasingly important in the prison setting, but information about the quality and accessibility of this care is extremely limited. Developing and implementing standardised quality indicators will provide transparency, accountability, and a platform for quality improvement at both local and national levels.
Children with palliative care needs in Papua New Guinea, and perspectives from their parents and health care workers: a qualitative study
Authors: Watch Villa , Anga Gwenda , Kilalang Cornelia , Pulsan Francis , Vince John D , Duke Trevor
Published: June 2023

Introduction

The World Health Organisation defines paediatric palliative care (PPC) as caring for the child’s body, mind, and spirit, and giving support to the family. In life-limiting conditions it is important that palliative support can be provided even when curative attempts are being utilised. In Papua New Guinea, as in other low- and middle-income countries there is a lack of services and training on PPC. This study aims to describe the characteristics of children with palliative care needs and to assess the perspectives of their parents and health care workers.

Methods

A descriptive qualitative study was carried out over 5 months in 2022 at the Port Moresby General Hospital children’s wards. Clinical information was gathered from the admission charts of children with life threatening and life limiting conditions and a recorded interview was carried out with the children’s parents. A focus group interview with 10 experienced nurses caring for these children was video recorded. The recorded interviews were subjected to thematic analysis.

Results

Twenty children and their parents were included in this study. Nine had a cancer diagnosis and 11 had a chronic progressive condition. The common clinical characteristics of children with palliative care needs were pain (n = 9) and shortness of breath (n = 9), and most children had more than one symptom. Several themes were identified in the parent interviews. Most parents could not name their child’s diagnosis, but they were able to correctly describe their child’s condition using their own terms. Most parents felt involved in their child’s management and were satisfied with the care provided. Parents were psychologically affected by their child’s situation but were hopeful that God and the medicines would heal their child. Ten nurses were involved in a focus-group interview. Most nurses’ understanding of palliative care was from experience not from formal training, but most felt confident in identifying the physical, emotional, and spiritual needs of the children. Understanding of analgesia was limited, as was the availability of appropriate medications included in the WHO Analgesic Ladder.

Conclusion

There is a need for a systematic approach to palliative care in Papua New Guinea. Palliative care can be integrated into an overall approach to quality of paediatric care. It is relevant to a broad section of children with severe chronic or malignant conditions and can be carried out with limited resources. It does require some resources, further training and education, and increased provision of basic drugs for symptom control.
The relationship of PrEP beliefs to perceived personal, interpersonal and structural benefits and barriers to PrEP use in women who inject drugs
Authors: Paulus Kirsten , Kelly Patrick J.A. , Brajuha Jesse , D’Avanzo Paul , Dauria Emily F. , Trainor Aurora , Alrez Annabelle , Bass Sarah Bauerle
Published: June 2023

Background

Women who inject drugs (WWID) have significant biological, behavioral, and gender-based barriers to accessing HIV prevention services, including Pre-Exposure Prophylaxis (PrEP) medication. Little is known about how beliefs about PrEP impact both perceived barriers and benefits of PrEP use and how they may be related to the decision-making process.

Methods

Surveys were conducted with 100 female clients of a large syringe services program in Philadelphia, Pennsylvania. The sample was categorized into three groups based on mean PrEP beliefs scores using terciles: accurate beliefs, moderately accurate beliefs, and inaccurate beliefs. Oneway ANOVA tests were used to compare groups by perceived benefits and barriers to PrEP, drug use stigma, healthcare beliefs, patient self-advocacy, and intention to use PrEP.

Results

Participants had a mean age of 39 years (SD 9.00), 66% reported being White, 74% finished high school, and 80% reported having been homeless within the past 6 months. Those with the most accurate PrEP beliefs reported highest intent to use PrEP and were more likely to agree that benefits of PrEP included it preventing HIV and helping them “feel in charge”. Those with inaccurate beliefs were more likely to strongly agree that barriers, such as fear of reprisal from a partner, potential theft, or feeling they “might get HIV anyway”, were reasons not to use PrEP.

Conclusions

Results indicate perceived personal, interpersonal and structural barriers to PrEP use are associated with accuracy of beliefs is, pointing to important intervention targets to increase uptake among WWID.
Moderators of the cost-effectiveness of transdiagnostic CBT for anxiety disorders over an 8-month time horizon using a net-benefit regression framework
Authors: Chapdelaine Alexandra , Vasiliadis Helen-Maria , Provencher Martin D. , Norton Peter J. , Roberge Pasquale
Published: June 2023

Background

Access to evidence-based psychological treatment is a concern in many parts of the globe due to government-level financial constraints and patient-level barriers. Transdiagnostic cognitive behavioural therapy (tCBT) is an effective treatment approach that uses a single protocol for anxiety disorders which could enhance the dissemination of evidence-based psychotherapy. In a context of limited resources, the study of treatment moderators can allow to identify subgroups for which the cost-effectiveness of an intervention differs, information that could impact decision-making. So far, there has been no economic evaluation of tCBT for different subpopulations. The objectives of this study, using the net-benefit regression framework, were to explore clinical and sociodemographic factors as potential moderators of the cost-effectiveness of tCBT compared to treatment-as-usual (TAU).

Methods

This is a secondary data analysis of a pragmatic randomized controlled trial opposing tCBT added to TAU (n = 117) to TAU only (n = 114). Data on costs from the health system and the limited societal perspectives, as well as anxiety-free days, an effectiveness measure based on the Beck Anxiety Inventory, were collected over an 8-month time horizon and used to derive individual net-benefits. The net-benefit regression framework was used to assess moderators of the cost-effectiveness of tCBT + TAU as opposed to TAU alone. Variables of sociodemographic and clinical nature were assessed.

Results

Results showed that the number of comorbid anxiety disorders significantly moderated the cost-effectiveness of tCBT + TAU compared to TAU from the limited societal perspective.

Conclusions

The number of comorbid anxiety disorders was identified as a moderator affecting the cost-effectiveness of tCBT + TAU compared to TAU from the limited societal perspective. More research is needed to strengthen the case of tCBT from an economic standpoint for large-scale dissemination.

Trial registration

ClinicalTrials.gov: NCT02811458, 23/06/2016
Which value aspects are relevant for the evaluation of medical devices? Exploring stakeholders’ views through a Web-Delphi process
Authors: Freitas Liliana , Vieira Ana C. L. , Oliveira Mónica D. , Monteiro Helena , Bana e Costa Carlos A.
Published: June 2023

Background

Implementation and uptake of health technology assessment for evaluating medical devices require including aspects that different stakeholders consider relevant, beyond cost and effectiveness. However, the involvement of stakeholders in sharing their views still needs to be improved.

Objective

This article explores the relevance of distinct value aspects for evaluating different types of medical devices according to stakeholders' views.

Methods

Thirty-four value aspects collected through literature review and expert validation were the input for a 2-round Web-Delphi process. In the Web-Delphi, a panel of participants from five stakeholders’ groups (healthcare professionals, buyers and policymakers, academics, industry, and patients and citizens) judged the relevance of each aspect, by assigning a relevance-level (‘Critical’, ‘Fundamental’, ‘Complementary’, or ‘Irrelevant’), for two types of medical devices separately: ‘Implantable’ and ‘In vitro tests based on biomarkers’. Opinions were analysed at the panel and group level, and similarities across devices were identified.

Results

One hundred thirty-four participants completed the process. No aspects were considered ‘Irrelevant’, neither for the panel nor for stakeholder groups, in both types of devices. The panel considered effectiveness and safety-related aspects ‘Critical’ (e.g., ‘Adverse events for the patient’), and costs-related aspects ‘Fundamental’ (e.g., ‘Cost of the medical device’). Several additional aspects not included in existing frameworks’ literature, e.g., related to environmental impact and devices’ usage by the healthcare professional, were deemed as relevant by the panel. A moderate to substantial agreement across and within groups was observed.

Conclusion

Different stakeholders agree on the relevance of including multiple aspects in medical devices’ evaluation. This study produces key information to inform the development of frameworks for valuing medical devices, and to guide evidence collection.
Current and prospective strategies for advancing the targeted delivery of CRISPR/Cas system via extracellular vesicles
Authors: Huang Xiaowen , Li Aifang , Xu Peng , Yu Yangfan , Li Shuxuan , Hu Lina , Feng Shuying
Published: June 2023

Extracellular vesicles (EVs) have emerged as a promising platform for gene delivery owing to their natural properties and phenomenal functions, being able to circumvent the significant challenges associated with toxicity, problematic biocompatibility, and immunogenicity of the standard approaches. These features are of particularly interest for targeted delivery of the emerging clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) systems. However, the current efficiency of EV-meditated transport of CRISPR/Cas components remains insufficient due to numerous exogenous and endogenous barriers. Here, we comprehensively reviewed the current status of EV-based CRISPR/Cas delivery systems. In particular, we explored various strategies and methodologies available to potentially improve the loading capacity, safety, stability, targeting, and tracking for EV-based CRISPR/Cas system delivery. Additionally, we hypothesise the future avenues for the development of EV-based delivery systems that could pave the way for novel clinically valuable gene delivery approaches, and may potentially bridge the gap between gene editing technologies and the laboratory/clinical application of gene therapies.

Graphical Abstract
Aging and chronic inflammation: highlights from a multidisciplinary workshop
Authors: Saavedra Danay , Añé-Kourí Ana Laura , Barzilai Nir , Caruso Calogero , Cho Kyung-Hyun , Fontana Luigi , Franceschi Claudio , Frasca Daniela , Ledón Nuris , Niedernhofer Laura J. , Pereira Karla , Robbins Paul D. , Silva Alexa , Suarez Gisela M. , Berghe Wim Vanden , von Zglinicki Thomas , Pawelec Graham , Lage Agustín
Published: June 2023

Aging is a gradual, continuous series of natural changes in biological, physiological, immunological, environmental, psychological, behavioral, and social processes. Aging entails changes in the immune system characterized by a decrease in thymic output of naïve lymphocytes, an accumulated chronic antigenic stress notably caused by chronic infections such as cytomegalovirus (CMV), and immune cell senescence with acquisition of an inflammatory senescence-associated secretory phenotype (SASP). For this reason, and due to the SASP originating from other tissues, aging is commonly accompanied by low-grade chronic inflammation, termed “inflammaging”. After decades of accumulating evidence regarding age-related processes and chronic inflammation, the domain now appears mature enough to allow an integrative reinterpretation of old data. Here, we provide an overview of the topics discussed in a recent workshop “Aging and Chronic Inflammation” to which many of the major players in the field contributed. We highlight advances in systematic measurement and interpretation of biological markers of aging, as well as their implications for human health and longevity and the interventions that can be envisaged to maintain or improve immune function in older people.
Combined pelvic and acetabular injuries: clinical features and treatment strategies of a unique injury pattern
Authors: Li Renjie , Zhao Peishuai , Guan Jianzhong , Wang Xiaopan , Liu Leyu , Wu Min
Published: June 2023

Background

To explore the clinical characteristics of patients with unstable pelvic fractures combined with acetabular fractures and to discuss the treatment strategies for such patients to help guide treatment.

Methods

We retrospectively assessed 24 patients admitted to our hospital from June 2018 to June 2022 with unstable pelvic fractures combined with acetabular fractures, including 15 male patients and 9 female patients with a mean age of 44.8 years. According to the Tile pelvic fracture classification, 15 cases were type B, and 9 cases were type C. The acetabular fractures were classified using the Letournel–Judet classification. There were 8 transverse fractures, 4 transverse and posterior wall fractures, 3 anterior and posterior hemitransverse fractures, 6 both-column fractures, 2 T-shaped fractures and 1 anterior column fracture. We recorded the cause of the patient's injury and vital signs on admission and assessed the patient's treatment strategy and prognosis.

Results

All patients completed the surgery successfully, and the follow-up ranged from 6 to 42 months, with a mean of 23 months. The healing time for pelvic fractures ranged from 11 to 21 weeks, with a mean of 14.8 weeks, and the postoperative displacement of the posterior pelvic ring ranged from 1.2 to 9.0 mm, with a mean of 3.5 mm. The final clinical outcome at follow-up was evaluated using the Majeed scale: excellent in 11 cases, good in 10 cases and fair in 3 cases; the excellent rate was 87.5%. The time to healing of the acetabular fracture ranged from 13 to 25 weeks, with a mean of 15.9 weeks, and the postoperative displacement of the acetabular fracture ranged from 0.6 to 5.2 mm, with a mean of 1.9 mm. Hip function was assessed at the final follow-up using a modified Merle D’ Aubigné and Postel scale: there were 9 excellent, 11 good and 4 acceptable scores; an excellent rate of 83.3% was achieved.

Conclusion

Patients with unstable pelvic fractures combined with acetabular fractures suffer severe trauma and complex mechanisms of injury. Treatment needs to be individualized, taking into account the patient's physiological status, fracture classification and degree of displacement.
What does receiving autism diagnosis in adulthood look like? Stakeholders’ experiences and inputs
Authors: Ghanouni Parisa , Seaker Liam
Published: June 2023

Introduction

The age of diagnosis is crucial for optimal health outcomes; however, some individuals with Autism Spectrum Disorder (ASD) may not be diagnosed until adulthood. Limited information is available about the lived experience of receiving a diagnosis during adulthood. Thus, we aimed to investigate stakeholders’ experiences about the ASD diagnosis during adulthood.

Method

We interviewed 18 individuals including 13 adults with ASD who had received a late diagnosis during adulthood and 5 parents of individuals with ASD from various Canadian provinces.

Results

Using a thematic analysis, three main themes emerged: (a) noticing differences and similarities, (b) hindering elements to diagnosis, and (c) emotional response to diagnostic odyssey.

Conclusion

This study adds to the literature about experiences of receiving ASD diagnosis in adulthood. Given the impact of diagnosis on individuals, it is important to minimize the barriers to ensure individuals who require ASD-related supports can access them in a timely and effective manner. This study highlights the importance of receiving an ASD diagnosis and facilitates positive health outcomes. The findings from the current study can be used to guide adult diagnostic processes and practices to help make ASD diagnosis more accessible.
Long-term evaluation of viability of microfilariae and intravenously transplanted adult Dirofilaria immitis in microfilaremic dogs treated with low-dose, short- and long-treatment regimens of doxycycline and ivermectin
Authors: McCall John Wilson , Mansour Abdelmoneim , DiCosty Utami , Fricks Crystal , McCall Scott , Dzimianski Michael Timothy , Carson Ben
Published: June 2023

Background

Microfilarial (mf) counts were monitored over 21.3 months for any rebound that might occur in counts, and adulticidal efficacy was assessed following administration of low dosage with short- and long-treatment regimens of doxycycline and ivermectin to heartworm-microfilaremic dogs.

Methods

Twelve heartworm-naïve beagles infected with 10 pairs of adult Dirofilaria immitis by intravenous transplantation were randomly allocated to three groups of four dogs. All treatments started on day 0. On day 0, Group 1 (short-treatment regimen) received doxycycline orally at 10 mg/kg once daily for 30 days plus ivermectin orally (minimum, 6 mcg/kg) on days 0 and 30. Group 2 (long-treatment regimen) received doxycycline orally at 10 mg/kg once daily until individual dogs became mf-negative (72–98 days) and ivermectin every other week until individual dogs became mf-negative (6–7 doses). Group 3 was the untreated control. Mf counts and antigen (Ag) tests were conducted. Dogs were necropsied for recovery and enumeration of heartworms on day 647.

Results

Day −1 mean mf counts were 15,613, 23,950, and 15,513 mf/ml for groups 1, 2, and 3, respectively. Mean counts for Groups 1 and 2 declined until days 239 and 97, respectively, when all were negative. Group 3 had high mf counts throughout the study. There was not a rebound in mf counts in any of the treated dogs after they became amicrofilaremic. All dogs in group 1 and group 3 were Ag-positive throughout the study and had at least one live female worm at necropsy. All dogs in treated Group 2 were positive for Ag through day 154, but were antigen-negative on days 644 and 647, as all had only male worms. Mean live adult worm recoveries for Groups 1, 2, and 3 were 6.8 (range, 5–8), 3.3 (range, 1–6), and 16.0 (range, 14–17), respectively, with a percent reduction in adult worm counts of 57.5% for Group 1 and 79.3% for Group 2.

Conclusions

These data lend support to the use of the American Heartworm Society Canine Guidelines for adulticide therapy recommending the initiation of doxycycline plus a macrocyclic lactone (ML) at the time of the heartworm-positive diagnosis.

Graphical Abstract
Contribution of CKD to mortality in middle-aged and elderly people with diabetes: the China Health and Retirement Longitudinal Study
Authors: Liao Xihong , Shi Ke , Zhang Yumeng , Huang Xiaoxu , Wang Ning , Zhang Ling , Zhao Xiaohuan
Published: June 2023

Background

The contribution of chronic kidney disease (CKD) to mortality in diabetic patients is unclear. This study aimed to explore the association between diabetics with CKD and mortality in middle-aged and elderly people of different ages.

Methods

Data were obtained from the China Health and Retirement Longitudinal Study, including 1,715 diabetic individuals, 13.1% of whom also had CKD. Diabetes and CKD were assessed by combining the physical measurements and self-reports. We fitted Cox proportional hazards regression models to examine the effect of diabetics with CKD on mortality in middle-aged and elderly people. The risk factors for death were further predicted based on age stratification.

Results

The mortality rate of diabetic patients with CKD (29.3%) was increased as compared to that of diabetic patients without CKD (12.4%). Diabetics with CKD were at a higher risk of all-cause mortality than those without CKD, with a hazard ratio of 1.921 (95% CI: 1.438, 2.566). Additionally, for participants 45 to 67 years of age, the hazard ratio was 2.530 (95% CI: 1.624, 3.943).

Conclusions

Our findings suggested that, for diabetics, CKD was a chronic stressor that led to death in middle-aged and elderly people, especially among participants aged 45 to 67 years.
Ventilation dynamics using a portable device coupled to the six-minute walk test in people with long-COVID syndrome: a preliminary study
Authors: Oliveira Jéssica Gabriela Messias , Campos Renan Pereira , Azevedo Beatriz Luiza Pinheiro Alves , de Alegria Samantha Gomes , Litrento Patrícia Frascari , Mafort Thiago Thomaz , Lopes Agnaldo José
Published: June 2023

Objective

To investigated the dynamic ventilatory responses and their influence on functional exercise capacity in patients with long-COVID-19 syndrome (LCS).

Results

Sixteen LCS patients were subjected to resting lung function (spirometry and respiratory oscillometry-RO) and cardiopulmonary performance to exercise (Spiropalm®-equipped six-minute walk test-6MWT and cardiopulmonary exercise test-CPX). At rest, spirometry showed a normal, restrictive and obstructive pattern in 87.5%, 6.25% and 6.25% of participants, respectively. At rest, RO showed increased resonance frequency, increased integrated low-frequency reactance and increased difference between resistance at 4–20 Hz (R4-R20) in 43.7%, 50%, and 31.2% of participants, respectively. The median of six-minute walking distance (DTC6) was 434 (386–478) m, which corresponds to a value of 83% (78–97%) of predicted. Dynamic hyperinflation (DH) and reduced breathing reserve (BR) were detected in 62.5% and 12.5% of participants, respectively. At CPX, the median peak oxygen uptake (VO2peak) was 19 (14–37) ml/kg/min. There was a significant correlation of 6MWD with both R4-R20 (rs=-0.499, P = 0.039) and VO2peak (rs=0.628, P = 0.009). Our results indicate that DH and low BR are contributors to poor exercise performance, which is associated with peripheral airway disease. These are promising results considering that they were achieved with simple, portable ventilatory and metabolic systems.
The anticancer effect of recombinant LukS-PV protein and silver nanoparticles loaded with this protein
Authors: Haghighatafshar Hafizeh , Golestani Eimani Bahram , Moazamian Elham , Amani Jafar
Published: June 2023

LukS-PV is a component of Panton-Valentine leucocidin (PVL) and is secreted by Staphylococcus aureus. Silver nanoparticles exhibit considerable potential as anticancer agents and drug delivery systems. Drug delivery is a way to deliver medicinal combinations to achieve a beneficial therapeutic effect. In the current study, recombinant LukS-PV protein-loaded silver nanoparticles were prepared and their cytotoxicity effect was analyzed on human breast cancer cells and human normal embryonic kidneys cells by MTT assay. Apoptosis was investigated by staining with Annexin V/propidium iodide. The recombinant LukS-PV protein-loaded silver nanoparticles showed dose‐dependent cytotoxicity and induced apoptosis in the MCF7 cells and had a lesser effect on HEK293 cells. After 24 h exposure to the recombinant LukS-PV protein-loaded silver nanoparticles (IC50), Annexin V-FITC/PI FCM revealed that 33.2% of MCF7 cells were apoptotic. In conclusion, recombinant LukS-PV protein-loaded silver nanoparticles probably cannot be a better alternative for the targeted healing approaches to cancer therapies. Hence, it is suggested that silver nanoparticles could be utilized as a delivery system for releasing toxins into cancer cells.
The genomic signature of resistance to platinum-containing neoadjuvant therapy based on single-cell data
Authors: Sui Qihai , Hu Zhengyang , Jin Xing , Bian Yunyi , Liang Jiaqi , Zhang Huan , Yang Huiqiang , Lin Zongwu , Wang Qun , Zhan Cheng , Chen Zhencong
Published: June 2023

Background

Neoadjuvant chemotherapy (NACT) becomes the first-line option for advanced tumors, while patients who are not sensitive to it may not benefit. Therefore, it is important to screen patients suitable for NACT.

Methods

Single-cell data of lung adenocarcinoma (LUAD) and esophageal squamous carcinoma (ESCC) before and after cisplatin-containing (CDDP) NACT and cisplatin IC50 data of tumor cell lines were analyzed to establish a CDDP neoadjuvant chemotherapy score (NCS). Differential analysis, GO, KEGG, GSVA and logistic regression models were performed by R. Survival analysis were applied to public databases. siRNA knockdown in A549, PC9, TE1 cell lines, qRT-PCR, western-blot, cck8 and EdU experiments were used for further verification in vitro.

Results

485 genes were expressed differentially in tumor cells before and after neoadjuvant treatment for LUAD and ESCC. After combining the CDDP-associated genes, 12 genes, CAV2, PHLDA1, DUSP23, VDAC3, DSG2, SPINT2, SPATS2L, IGFBP3, CD9, ALCAM, PRSS23, PERP, were obtained and formed the NCS score. The higher the score, the more sensitive the patients were to CDDP-NACT. The NCS divided LUAD and ESCC into two groups. Based on differentially expressed genes, a model was constructed to predict the high and low NCS. CAV2, PHLDA1, ALCAM, CD9, IGBP3 and VDAC3 were significantly associated with prognosis. Finally, we demonstrated that the knockdown of CAV2, PHLDA1 and VDAC3 in A549, PC9 and TE1 significantly increased the sensitivity to cisplatin.

Conclusions

NCS scores and related predictive models for CDDP-NACT were developed and validated to assist in selecting patients who might benefit from it.
Color difference for shade determination with visual and instrumental methods: a systematic review and meta-analysis
Authors: Morsy Noha , Holiel Ahmed A.
Published: June 2023

Background

Shade determination is a critical step for the fabrication of a satisfactory restoration. Visual shade selection with conventional shade guides is subjective and influenced by variables related to light, observer, and object. Shade selection devices have been introduced to provide subjective and quantitative shade values. This systematic review and meta-analysis aimed to compare the color difference for shade selection with visual and instrumental methods.

Methods

An initial search was conducted on databases (MEDLINE via PubMed, Scopus, and Web of Science) in addition to a manual search through references of identified articles. Studies comparing the accuracy of visual and instrumental shade selection based on ΔΕ were included in data synthesis. Mean differences (MDs) and 95% confidence intervals (CIs) were calculated to estimate the effect size for global and subgroup meta-analysis using the inverse variance weighted method and random-effects model (P ˂ 0.05). Results were presented as forest plots.

Results

The authors identified 1776 articles from the initial search. Seven in vivo studies were included in the qualitative analysis of which six studies were included in the meta-analysis. For the global meta-analysis, the pooled mean (95% CI) was − 1.10 (− 1.92, − 0.27). Test for overall effect showed that instrumental methods were significantly more accurate than visual methods with significantly less ΔΕ (P = 0.009). Test for subgroup difference showed that the type of instrumental shade selection method used had a significant effect on accuracy (P ˂ 0.001). Instrumental methods including spectrophotometer, digital camera, and smartphone showed significantly better accuracy compared with visual shade selection (P ˂ 0.05). The greatest mean difference was found between the smartphone and visual method with a mean (95% CI) of − 2.98 (− 3.37, − 2.59) with P ˂ 0.001 followed by digital camera and spectrophotometer. There was no significant difference in accuracy between IOS and visual shade selection (P = 1.00).

Conclusions

Instrumental shade selection with a spectrophotometer, digital camera, and smartphone showed significantly better shade matching compared with a conventional shade guide, whereas IOS did not improve the shade matching significantly compared with shade guides.

Review registration

PROSPERO CRD42022356545