bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation contexts and strategies for alternative peripherally inserted central catheter material and design selection: A qualitative exploration using CFIR/ERIC approach
Authors: August Deanne , Walker Rachel M. , Gibson Victoria , Marsh Nicole , Kleidon Tricia M. , Delaforce Alana , Mihalopoulous Claire , Ullman Amanda , Keogh Samantha
Published: July 2024

Aim

To explore the implementation contexts and strategies that influence the uptake and selection of alternative peripherally inserted central catheter (PICC) materials and design.

Design

Qualitative evaluation of end user perspectives within a randomized control trial of different PICC materials and design.

Methods

Semi‐structured interviews with key stakeholders were undertaken via an adapted, rapid‐analytic approach using the Consolidated Framework for Implementation Research. Outcomes were mapped against the Expert Recommendations for Implementing Change (ERIC) tool for strategies to guide innovation in PICC practice.

Results

Participants (n = 23) represented a combination of users and inserters/purchasers, from adult and paediatric settings. Dominant themes included intervention characteristics (intervention source), inner setting (structural characteristics) and individuals involved (self‐efficacy). Strategies emerging to support a change from ERIC mapping (n = 16) included promotion of intervention adaptability, inclusion of staff and consumer perspectives and sufficient funding. Implementation contexts such as inner setting and individuals involved equally impacted PICC success and implementation effectiveness and enabled a greater understanding of barriers and facilitators to intervention implementation in this trial.

Conclusion

Trial evidence is important, but healthcare decision‐making requires consideration of local contexts especially resourcing. Implementation contexts for Australian healthcare settings include a practical, strategic toolkit for the implementation of alternative PICC materials and designs.

Reporting Method

This study adhered to COREQ guidelines.

Patient or Public Contribution

No patient or public contribution.
Exploring the implementation of national health and social care standards in Ireland: A qualitative descriptive study
Authors: Kelly Yvonne , O'Rourke Niamh , Flynn Rachel , Hegarty Josephine , Keyes Laura M.
Published: July 2024

Background

National health and social care standards are complex, quality improvement interventions. Standards typically describe a process and/or outcome of safe, quality, person‐centred care according to best evidence. Currently, there are 11 national standards that apply to diverse services in Ireland including residential centres, acute hospitals and rehabilitation and community inpatient healthcare services. A better understanding of contextual factors influencing implementation will inform decision‐making when selecting implementation strategies to enhance the implementation of standards.

Aim

To explore experiences of implementing national health and social care standards and secondly, to identify enablers and barriers to implementation with stakeholders from across multiple levels of the health system.

Design

A qualitative descriptive study.

Methods

We conducted six focus groups and eight individual interviews from October to November 2021 with stakeholders at system level (n = 14), organizational level (n = 14) and individual level (n = 10). Focus groups and interviews were audio‐recorded, transcribed verbatim and analysed using reflexive thematic analysis.

Results

Six themes were generated; (1) Top‐down, bottom‐up, a team approach: everybody together, we are all involved, we are all responsible, (2) Support tools: accessible tools and bite‐size material pertaining to standards will support us to implement standards, (3) Empower with knowledge: increase awareness and understanding of standards, make them relatable in practice so we can make sense of them, (4) A system‐wide malaise: we do not have the bandwidth to implement standards, (5) Follow the leader: we need a lead person at every level to inspire implementation, (6) A bi‐directional influence: we know inspections drive quality improvements but we still feel trepidation around inspection outcomes.

Conclusion

Key enablers identified related to teamwork, support tools, leadership and inspections. Key barriers related to workforce issues, a lack of awareness of standards and fear of inspection outcomes. Our findings can be incorporated into strategies to support implementation of standards, ultimately for the benefit of service‐users.

Implications for Practice

The enablers and barriers described in this study reflect the importance of organizational factors in the implementation of standards. Interdisciplinary teams can infer from these findings, which enablers and barriers apply to their own context. These findings can inform decision‐making when selecting strategies that can be effective in supporting the implementation of standards.

Reporting Method

We have adhered to the Standards for Reporting Qualitative Research (SRQR) guidelines.

Patient or Public Contribution

No patient or public contribution.
Adaptation, Experimentation or Conservation? The Use of Differentiated Implementation Under the Energy Efficiency Directive
Authors: Hoppe Alexander , Hübner Michael , Princen Sebastiaan , Svec Martin
Published: July 2024

In this article, we introduce an innovative theoretical framework to analyse the use of differentiated implementation in the implementation process of European Union (EU) Directives. We identify rationales for offering flexibility in EU Directives as well as motives for policy‐makers to make use of the discretion. We analyse patterns and drivers of differentiated implementation under the Energy Efficiency Directive (EED) in four member states in order to assess whether practices of differentiated implementation conform to the rationales for offering flexibility. We show that member states mainly use the flexibility offered to retain existing policies. In addition, the EED led to some mutual learning based on experimentation, although this effect is limited. Whilst the EED offered a high potential for mutual learning, the member states did not use this opportunity. Overall, the implementation of the EED offers mixed evidence for the use of differentiated implementation to support differentiation.
Characteristics of children with a psychiatric disorder in 1999, 2004 and 2017: an analysis of the national child mental health surveys of England
Authors: Armitage Jessica M. , Newlove‐Delgado Tamsin , Ford Tamsin , McManus Sally , Collishaw Stephan
Published: July 2024

Background

While research has described the profile of children with poor mental health, little is known about whether this profile and their needs have changed over time. Our aim was to investigate whether levels of difficulties and functional impact faced by children with a psychiatric disorder have changed over time, and whether sociodemographic and family correlates have changed.

Methods

Samples were three national probability surveys undertaken in England in 1999, 2004 and 2017 including children aged 5–15 years. Psychiatric disorders were assessed using the Development and Well‐Being Assessment (DAWBA), a standardised multi‐informant diagnostic tool based on the tenth International Classification of Diseases (ICD‐10). The impact and difficulties of having a disorder (emotional, behavioural or hyperkinetic) were compared over time using total difficulty and impact scores from the Strengths and Difficulties Questionnaire (SDQ). Analyses explored the impact of having any disorder, as well as for each disorder separately. Regression analyses compared associations between disorders and sociodemographic factors over time.

Results

Parent‐ and adolescent‐reported total SDQ difficulty and impact scores increased between 1999 and 2017 for children and adolescents with disorders. No differences were noted when using teacher ratings. No differences in total SDQ difficulty score were found for children without a disorder. Comparison of sociodemographic correlates across the surveys over time revealed that ethnic minority status, living in rented accommodation and being in the lowest income quintile had a weaker association with disorder in 2017 compared to 1999.

Conclusions

Our study reveals a concerning trend; children with a disorder in 2017 experienced more severe difficulties and greater impact on functioning at school, home and in their daily lives, compared to children with a disorder in earlier decades. Research is needed to identify and understand factors that may explain the changing nature and level of need among children with a disorder.
Beyond the classic players: Mas‐related G protein‐coupled receptor member X2 role in pruritus and skin diseases
Authors: Kumar Mukesh , Choi Ye Gi , Wong Trevor , Li Philip H. , Chow Billy K. C.
Published: July 2024

Chronic spontaneous urticaria (CSU), atopic dermatitis (AD), psoriasis and rosacea are highly prevalent inflammatory skin conditions which impose a significant burden on patients' quality of life. Their pathophysiology is likely multifactorial, involving genetic, immune and environmental factors. Recent advancements in the field have demonstrated the key role of mast cells (MC) in the pathophysiology of these conditions. The Mas‐related G protein‐coupled receptor X2 (MRGPRX2) has emerged as a promising non‐IgE‐mediated MC activation receptor. MRGPRX2 is predominately expressed on MC and activated by endogenous and exogenous ligands, leading to MC degranulation and release of various pro‐inflammatory mediators. Mounting evidence on the presence of endogenous MRGPRX2 agonists (substance P, cortistatin‐14, LL37, PAMP‐12 and VIP) and its high expression among patients with CSU, AD, rosacea, psoriasis and chronic pruritus emphasizes the pathogenic role of MRGPRX2 in these conditions. Despite the currently available treatments, there remains a pressing need for novel drug targets and treatment options for these chronic inflammatory skin conditions. Here, we reviewed the pathogenic role of MRGPRX2 and its potential as a novel therapeutic target and provided an update on future research directions.
Esophageal cancer mortality disparities between Black and White adults in the United States, 1999–2020: insights from CDC‐WONDER
Authors: Pan Chun‐Wei , Wang Yichen , Abboud Yazan , Dominguez Alejandro Nieto , Lo Chun‐Han , Pang Maoyin
Published: July 2024

Background and Aim

Esophageal cancer significantly contributes to US cancer mortality, with notable racial disparities. This study aims to provide updated esophageal cancer mortality trends among Black and White adults from 1999 to 2020.

Methods

CDC‐WONDER was used to identify Black and White adults in the United States from 1999 to 2020. We calculated age‐standardized mortality rates, absolute rate differences, and rate ratios to compare the mortality differences between these populations.

Results

From 1999 to 2020 in the United States, there were 303 267 esophageal cancer deaths, with significant racial disparities. The age‐adjusted mortality rate for Black adults fell from 6.52 to 2.62 per 100 000, while for White adults, it declined from 4.19 to 3.97 per 100 000, narrowing the racial mortality gap. Gender‐wise, the study showed a decrease in the mortality rate from 3.31 to 2.29 per 100 000 in Black women, but an increase from 1.52 to 1.99 per 100 000 in White women. Among young men, the rate dropped in Black men from 12.82 to 6.26 per 100 000 but rose in White men from 9.90 to 10.57 per 100 000. Regionally, Black adults in the Midwest and South initially had higher mortality rates than Whites, but this gap reduced over time. By 2020, Black men had lower mortality rates across all regions.

Conclusions

Over the last two decades, age‐adjusted esophageal cancer mortality decreased in Black adults but stabilized in White adults, reflecting distinct cancer trends and risk factors. The study highlights the importance of tailored public health strategies for healthcare access and risk factor management.
Hepatic‐specific Pgc‐1α ablation drives fibrosis in a MASH model
Authors: Arconzo Maria , Piccinin Elena , Pasculli Emanuela , Cariello Marica , Loiseau Nicolas , Bertrand‐Michel Justine , Guillou Hervé , Matrella Maria L. , Villani Gaetano , Moschetta Antonio
Published: July 2024

Background & Aims

Metabolic dysfunction‐associated steatohepatitis (MASH) is a growing cause of chronic liver disease, characterized by fat accumulation, inflammation and fibrosis, which development depends on mitochondrial dysfunction and oxidative stress. Highly expressed in the liver during fasting, peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α) regulates mitochondrial and oxidative metabolism. Given the relevant role of mitochondrial function in MASH, we investigated the relationship between PGC‐1α and steatohepatitis.

Methods

We measured the hepatic expression of Pgc‐1α in both MASH patients and wild‐type mice fed a western diet (WD) inducing steatosis and fibrosis. We then generated a pure C57BL6/J strain loss of function mouse model in which Pgc‐1α is selectively deleted in the liver and we fed these mice with a WD supplemented with sugar water that accurately mimics human MASH.

Results

We observed that the hepatic expression of Pgc‐1α is strongly reduced in MASH, in both humans and mice. Moreover, the hepatic ablation of Pgc‐1α promotes a considerable reduction of the hepatic mitochondrial respiratory capacity, setting up a bioenergetic harmful environment for liver diseases. Indeed, the lack of Pgc‐1α decreases mitochondrial function and increases inflammation, fibrosis and oxidative stress in the scenario of MASH. Intriguingly, this profibrotic phenotype is not linked with obesity, insulin resistance and lipid disbalance.

Conclusions

In a MASH model the hepatic ablation of Pgc‐1α drives fibrosis independently from lipid and glucose metabolism. These results add a novel mechanistic piece to the puzzle of the specific and crucial role of mitochondrial function in MASH development.
Horizontally transferred mitochondrial DNA tracts become circular by microhomology‐mediated repair pathways
Authors: Roulet M. Emilia , Ceriotti Luis Federico , Gatica‐Soria Leonardo , Sanchez‐Puerta M. Virginia
Published: July 2024

The holoparasitic plant Lophophytum mirabile exhibits remarkable levels of mitochondrial horizontal gene transfer (HGT). Gathering comparative data from other individuals and host plants can provide insights into the HGT process.

We sequenced the mitochondrial genome (mtDNA) from individuals of two species of Lophophytum and from mimosoid hosts. We applied a stringent phylogenomic approach to elucidate the origin of the whole mtDNAs, estimate the timing of the transfers, and understand the molecular mechanisms involved.

Ancestral and recent HGT events replaced and enlarged the multichromosomal mtDNA of Lophophytum spp., with the foreign DNA ascending to 74%. A total of 14 foreign mitochondrial chromosomes originated from continuous regions in the host mtDNA flanked by short direct repeats. These foreign tracts are circularized by microhomology‐mediated repair pathways and replicate independently until they are lost or they eventually recombine with other chromosomes. The foreign noncoding chromosomes are variably present in the population and likely evolve by genetic drift.

We present the ‘circle‐mediated HGT’ model in which foreign mitochondrial DNA tracts become circular and are maintained as plasmid‐like molecules. This model challenges the conventional belief that foreign DNA must be integrated into the recipient genome for successful HGT.
Leptin is a potential biomarker of childhood obesity and an indicator of the effectiveness of weight‐loss interventions
Authors: Al Zein Mohammad , Akomolafe Aishat Funmilayo , Mahmood Fathima R. , Khrayzat Ali , Sahebkar Amirhossein , Pintus Gianfranco , Kobeissy Firas , Eid Ali H.
Published: July 2024

Childhood obesity represents a significant public health concern, imposing a substantial burden on the healthcare system. Furthermore, weight‐loss programs often exhibit reduced effectiveness in adults who have a history of childhood obesity. Therefore, early intervention against childhood obesity is imperative. Presently, the primary method for diagnosing childhood obesity relies on body mass index (BMI), yet this approach has inherent limitations. Leptin, a satiety hormone produced by adipocytes, holds promise as a superior tool for predicting both childhood and subsequent adulthood obesity. In this review, we elucidate the tools employed for assessing obesity in children, delve into the biological functions of leptin, and examine the factors governing its expression. Additionally, we discuss maternal and infantile leptin levels as predictors of childhood obesity. By exploring the relationship between leptin levels and weight loss, we present leptin as a potential indicator of the effectiveness of obesity interventions.
Leveraging normative power in co‐production to redress power imbalances
Authors: Chen Yaru , Croft Charlotte , Currie Graeme
Published: July 2024

In this article, we explore how less dominant actors, service users in our case, utilize different types of power to influence more dominant professional groups during processes of co‐production. Drawing on semi‐structured interviews with 48 service users involved in healthcare improvement research, we illuminate the crucial role of normative power during processes of co‐production. In contrast to extant co‐production literature, which largely focuses on structural or resource power, we show how normative power is created by service users to leverage influence over more dominant actors. We highlight the relationship between structural, resource, and normative power during processes of co‐production, extending understandings of the dynamic nature of co‐production and generating implications for public involvement policy and practice.
Public health nurses leaving remote islands: An investigation into the turnover rate of remote island PHNs in Japan
Authors: Hirata Mako , Otsuka Kazunori
Published: July 2024

Introduction

This study investigated the number of public health nurses (PHNs) and the turnover rates of PHNs working in small municipal administrations on remote islands throughout Japan.

Methods

A questionnaire survey was administered on 359 remote islands, each with a population of less than 5000, including islands connected to the Japanese mainland by a bridge or road. The survey questionnaire asked about the number of PHNs stationed on the remote islands, their length of service, the number of retirees, and the ages of those who had retired.

Results

Of the 353 islands which responded, 30 islands had a total of 77 PHNs. Of those 30 islands, 29 were isolated islands that were not connected to the mainland by a bridge or road. The turnover rate of PHNs on the 29 islands was 13.3%.

Conclusion

The turnover rate of 13.3% for PHNs on remote islands (with no bridge or road) with a population of less than 5000 was higher than the 7.9% turnover rate for PHNs in municipalities of equal size. To maintain the quality of life of island residents, preventing PHNs from leaving their jobs is an important challenge.
The efficacy of long‐term psoralen plus ultraviolet A and low‐dose interferon‐a combination therapy in mycosis fungoides: A literature review
Authors: Şanlı Hatice , Yıldızhan İncilay Kalay , Gündüz Kaan , Akay Bengü Nisa
Published: July 2024

Background/Purpose

Interferon (IFN)‐a is often used in combination with psoralen plus ultraviolet A (PUVA) in patients with mycosis fungoides (MF) refractory to skin—targeted therapies in early or advanced stages. The main objective is to evaluate the effectiveness of combined PUVA and low‐dose IFN‐α‐2a therapy in patients with early‐ and advanced‐stage MF.

Methods

Sixty‐eight patients who received a combination of PUVA twice or thrice a week and INF‐a 3 MU thrice a week for at least 3 months were reviewed retrospectively. The treatment response was evaluated as complete remission (CR), partial remission, stable disease, or progression.

Results

At the initiation, the majority of patients (66.2%) had early‐stage disease. In 27.9% of cases, this was the initial treatment administered following the diagnosis of MF. The median duration of combination therapy was 11 months. Complete remission was achieved in 45.6% of the patients with an overall response rate of 60.3%. The mean duration of response was 5 months. Complete remission was statistically significantly higher in early‐stage patients (p < .05). No statistically significant correlation was observed between CR and gender, histopathological features, or laboratory parameters. In patients with CR, 80% experienced relapse, significantly higher in early‐stage patients (p < .05). However, there was no significant difference in disease‐free survival between early and advanced stages (p > .05).

Conclusions

The study results indicated that PUVA + low‐dose INF‐a combination therapy was more effective in the early stage than in the advanced stage. Additionally, there was a high relapse rate after the cessation of treatment in patients who achieved CR.
A footloose capital model of economic development
Authors: Tabuchi Takatoshi , Wang Congcong , Zhu Xiwei
Published: July 2024

We present a footloose capital model in a two‐country economy and the manufacturing and natural resource sectors with heterogeneous manufacturing firms to analyze the impacts of trade liberalization and technological progress on the net capital flows, net export, and social welfare. Our main analytical result is that a lagged country initially experiences capital outflow due to the high technological gap in the manufacturing sector with increasing returns to scale, then capital inflow due to the home market effect. This corresponds with the fact that China was a net importer of manufactured goods initially, and became a net exporter recently. These results are consistent with the data obtained after the reform and opening‐up policy in 1978.
The rising incidence of feline and cat‐transmitted sporotrichosis in Latin America
Authors: Santos Mariana Tibúrcio , Nascimento Luiz Fernando de Jesus , Barbosa Ana Andrea Teixeira , Martins Maira Pompeu , Tunon Gabriel Isaias Lee , Santos Patrícia Oliveira Meira , Dantas‐Torres Filipe , Dolabella Silvio Santana
Published: July 2024

Introduction

Sporotrichosis is a subcutaneous mycosis caused by different species of thermodimorphic fungi belonging to the genus Sporothrix. These fungi may affect a wide range of warm‐blooded animals, including humans, dogs and, mainly, cats.

Methods

In this article, we conducted a narrative literature review about the status of feline and cat‐transmitted sporotrichosis in Latin American countries, with emphasis on Brazil.

Results

From a global perspective, Latin America is one of the main foci of human and feline sporotrichosis. In humans, the disease has been reported in several countries, with endemic transmission occurring in Brazil, Colombia, Costa Rica, Guatemala, Mexico and Uruguay. Sporothrix brasiliensis is the most common species identified in human cases in Brazil, whereas Sporothrix schenckii predominates in other countries.

Conclusion

Domestic cats are the main source of infection in the zoonotic transmission cycle of sporotrichosis in Latin America. Cases of feline sporotrichosis have been reported in several countries, including Argentina, Brazil, Chile, Colombia, Mexico, Panama, Paraguay and Peru.
Memory Retention and Cultural Resonance: Exploring the Impact of Ephemeral Digital Narratives
Authors: Maran Aishwarya , Raj J. Michael
Published: July 2024

The accelerating progress of the digital landscape has led to the rise of consumption of content that is short-lived and fast-paced. In this context, social media platforms such as Instagram and Snapchat have become predominant for their effective use of temporary digital content that lasts for a brief period (usually 24 hours) before disappearing. Ephemerality has become the zeitgeist of the 21st century. In a world where immediacy and instant gratification are highly valued, the pattern of consumption of digital media is also aligned to such quick snippets of information rather than watching a long video. This paradigm shift is redefining how people perceive time and memory in the digital age. This preliminary study analyses the effect of such ephemeral digital narratives on the memory retention of consumers and also explores the implications of such content on cultural and collective memory. A sample of 100 participants ranging from the age of 18-35 years, were exposed to curated ephemeral content from Instagram and Snapchat for seven days. Participants were exposed to different media types, presentation styles, and cognitive demands. Daily surveys examined their memory retention using various question formats. The study examined ten hypotheses using Analysis of Variance (ANOVA) to determine how media type (video, image, both), presentation style (visual, verbal/textual, both), cognitive processing demands (shallow, deep processing), and question format affect recall effectiveness.
Mitigation of electronic crosstalk interference in graphene transistor biosensors
Authors: Deshmukh Rahul , Wright Alexander James , Jamalzadeh Moeid , Nasralla Hashem Hassan , Riedo Elisa , Shahrjerdi Davood
Published: July 2024

The need for higher sensitivity and parallel detection of multiple biological targets drives the research on electronic biosensing platforms based on two-dimensional (2D) materials. However, signal fidelity from individual sensors may be compromised due to the existing nonidealities of 2D electronic devices. Here, we use graphene field effect transistors (gFETs) as a model system to investigate a multisensor device architecture. We identify two potential sources of crosstalk interference between sensors in such a platform: resistive interference through shared gFET channels and capacitive coupling through the shared device substrate. Having illustrated these sources of interference, we offer solutions to mitigate them for ensuring the fidelity of the biosensor signal. This study provides important practical insights for researchers working on 2D biosensor platforms.
Developing Close, Trusting Coach–Athlete Relationships With High-Performance Adolescent Tennis Players
Authors: Papich Mikaela C. , Bloom Gordon A. , Dohme Lea-Cathrin
Published: July 2024

The purpose of this study was to understand why and how experienced tennis coaches developed quality relationships with their high-performance adolescent athletes that prioritized athletes’ needs and well-being. Five highly regarded Canadian tennis coaches of internationally ranked adolescent players engaged in two semistructured interviews and three story completion tasks. The data were analyzed using reflexive thematic analysis. Findings outlined that coaches unanimously believed establishing a close, trusting relationship with their adolescent athletes was fundamental to creating a caring environment in which empathy for athletes’ athletic, academic, and personal demands could be demonstrated. Coaches also described the difficulties of navigating these close relationships in a climate that is under severe scrutiny because of athlete maltreatment allegations. Examples of coaching behaviors that fostered closeness and maintained athlete safety included demonstrating care towards athletes’ social, emotional, academic, and athletic challenges, encouraging dialogue in which athletes expressed their wants and needs, and involving parents to help maintain transparency regarding the establishment of closeness. Uniquely, this study provides practical suggestions for how coaches can nurture closeness while promoting safe environments that prioritize athletes’ welfare.
Computational synthesis of locomotive soft robots by topology optimization
Authors: Kobayashi Hiroki , Gholami Farzad , Montgomery S. Macrae , Tanaka Masato , Yue Liang , Yuhn Changyoung , Sato Yuki , Kawamoto Atsushi , Qi H. Jerry , Nomura Tsuyoshi
Published: July 2024

Locomotive soft robots (SoRos) have gained prominence due to their adaptability. Traditional locomotive SoRo design is based on limb structures inspired by biological organisms and requires human intervention. Evolutionary robotics, designed using evolutionary algorithms (EAs), have shown potential for automatic design. However, EA-based methods face the challenge of high computational cost when considering multiphysics in locomotion, including materials, actuations, and interactions with environments. Here, we present a design approach for pneumatic SoRos that integrates gradient-based topology optimization with multiphysics material point method (MPM) simulations. This approach starts with a simple initial shape (a cube with a central cavity). The topology optimization with MPM then automatically and iteratively designs the SoRo shape. We design two SoRos, one for walking and one for climbing. These SoRos are 3D printed and exhibit the same locomotion features as in the simulations. This study presents an efficient strategy for designing SoRos, demonstrating that a purely mathematical process can produce limb-like structures seen in biological organisms.
Robust parahydrogen-induced polarization at high concentrations
Authors: Dagys Laurynas , Korzeczek Martin C. , Parker Anna J. , Eills James , Blanchard John W. , Bengs Christian , Levitt Malcolm H. , Knecht Stephan , Schwartz Ilai , Plenio Martin B.
Published: July 2024

Parahydrogen-induced polarization (PHIP) is a potent technique for generating target molecules with high nuclear spin polarization. The PHIP process involves a chemical reaction between parahydrogen and a target molecule, followed by the transformation of nuclear singlet spin order into magnetization of a designated target nucleus through magnetic field manipulations. Although the singlet-to-magnetization polarization transfer process works effectively at moderate concentrations, it is observed to become much less efficient at high molar polarization, defined as the product of polarization and concentration. This strong dependence on the molar polarization is attributed to interference due to the field produced by the sample magnetization during polarization transfer, which leads to complex dynamics and can severely affect the scalability of the technique. We address this challenge with a pulse sequence that suppresses the influence of the distant dipolar field, while simultaneously achieving singlet-to-magnetization polarization transfer to the desired target spins, free from restrictions on the molar polarization.
A water-resistant, ultrathin, conformable organic photodetector for vital sign monitoring
Authors: Du Baocai , Xiong Sixing , Sun Lulu , Tagawa Yusaku , Inoue Daishi , Hashizume Daisuke , Wang Wenqing , Guo Ruiqi , Yokota Tomoyuki , Wang Shuxu , Ishida Yasuhiro , Lee Sunghoon , Fukuda Kenjiro , Someya Takao
Published: July 2024

Ultrathin flexible photodetectors can be conformably integrated with the human body, offering promising advancements for emerging skin-interfaced sensors. However, the susceptibility to degradation in ambient and particularly in aqueous environments hinders their practical application. Here, we report a 3.2-micrometer-thick water-resistant organic photodetector capable of reliably monitoring vital sign while submerged underwater. Embedding the organic photoactive layer in an adhesive elastomer matrix induces multidimensional hybrid phase separation, enabling high adhesiveness of the photoactive layer on both the top and bottom surfaces with maintained charge transport. This improves the water-immersion stability of the photoactive layer and ensures the robust sealing of interfaces within the device, notably suppressing fluid ingression in aqueous environments. Consequently, our fabricated ultrathin organic photodetector demonstrates stability in deionized water or cell nutrient media over extended periods, high detectivity, and resilience to cyclic mechanical deformation. We also showcase its potential for vital sign monitoring while submerged underwater.
Bilateral Back Extensor Exosuit for multidimensional assistance and prevention of spinal injuries
Authors: In Kim Jae , Choi Jaeyoun , Kim Junhyung , Song Junkyung , Park Jaebum , Park Yong-Lae
Published: July 2024

Lumbar spine injuries resulting from heavy or repetitive lifting remain a prevalent concern in workplaces. Back-support devices have been developed to mitigate these injuries by aiding workers during lifting tasks. However, existing devices often fall short in providing multidimensional force assistance for asymmetric lifting, an essential feature for practical workplace use. In addition, validation of device safety across the entire human spine has been lacking. This paper introduces the Bilateral Back Extensor Exosuit (BBEX), a robotic back-support device designed to address both functionality and safety concerns. The design of the BBEX draws inspiration from the anatomical characteristics of the human spine and back extensor muscles. Using a multi–degree-of-freedom architecture and serially connected linear actuators, the device’s components are strategically arranged to closely mimic the biomechanics of the human spine and back extensor muscles. To establish the efficacy and safety of the BBEX, a series of experiments with human participants was conducted. Eleven healthy male participants engaged in symmetric and asymmetric lifting tasks while wearing the BBEX. The results confirm the ability of the BBEX to provide effective multidimensional force assistance. Moreover, comprehensive safety validation was achieved through analyses of muscle fatigue in the upper and the lower erector spinae muscles, as well as mechanical loading on spinal joints during both lifting scenarios. By seamlessly integrating functionality inspired by human biomechanics with a focus on safety, this study offers a promising solution to address the persistent challenge of preventing lumbar spine injuries in demanding work environments.
Improving vaccine equity by increasing vaccine thermostability
Authors: Hare Jonathan , Hesselink Renske , Bongers Alexander , Blakeley Paul , Riggall Giovanna
Published: July 2024

The development, manufacture, and deployment of new vaccine technologies to combat SARS-CoV-2 enabled an unparalleled rapid response to the emerging health threat. However, the unequal global distribution of these vaccines highlighted a major gap in existing thermotolerance profiles and cold chain infrastructure that needs to be addressed to maximize their global health impact.
E3 ligase RNF2 inhibits porcine circovirus type 3 replication by targeting its capsid protein for ubiquitination-dependent degradation
Authors: Wang Dedong , Zhao Jie , Yang Xiaoyu , Ji Ying , Yu Ju , Li Zhaoyang , Shi Yongyan , Guo Jinshuo , Zhou Jianwei , Hou Lei , Liu Jue
Published: July 2024

Porcine circovirus type 3 (PCV3) is closely associated with various diseases, such as the porcine dermatitis, nephropathy syndrome, and multisystemic clinicopathological diseases. PCV3-associated diseases are increasingly recognized as severe diseases in the global swine industry. Ring finger protein 2 (RNF2), an E3 ubiquitin ligase exclusively located in the nucleus, contributes to various biological processes. This ligase interacts with the PCV3 Cap. However, its role in PCV3 replication remains unclear. This study confirmed that the nuclear localization signal domain of the Cap and the RNF2 N-terminal RING domain facilitate the interaction between the Cap and RNF2. Furthermore, RNF2 promoted the binding of K48-linked polyubiquitination chains to lysine at positions 139 and 140 (K139 and K140) of the PCV3 Cap, thereby degrading the Cap. RNF2 knockdown and overexpression increased or decreased PCV3 replication, respectively. Moreover, the RING domain-deleted RNF2 mutant eliminated the RNF2-induced degradation of the PCV3 Cap and RNF2-mediated inhibition of viral replication. This indicates that both processes were associated with its E3 ligase activity. Our findings demonstrate that RNF2 can interact with and degrade the PCV3 Cap via its N-terminal RING domain in a ubiquitination-dependent manner, thereby inhibiting PCV3 replication.

IMPORTANCE

Porcine circovirus type 3 is a recently described pathogen that is prevalent worldwide, causing substantial economic losses to the swine industry. However, the mechanisms through which host proteins regulate its replication remain unclear. Here, we demonstrate that ring finger protein 2 inhibits porcine circovirus type 3 replication by interacting with and degrading the Cap of this pathogen in a ubiquitination-dependent manner, requiring its N-terminal RING domain. Ring finger protein 2-mediated degradation of the Cap relies on its E3 ligase activity and the simultaneous existence of K139 and K140 within the Cap. These findings reveal the mechanism by which this protein interacts with and degrades the Cap to inhibit porcine circovirus type 3 replication. This consequently provides novel insights into porcine circovirus type 3 pathogenesis and facilitates the development of preventative measures against this pathogen.
Prediction of differential Gag versus Env responses to a mosaic HIV-1 vaccine regimen by HLA class I alleles
Authors: Nelson George W. , van Duijn Janine , Yuki Yuko , Pau Maria G. , Tomaka Frank , Lavreys Ludo , DeRosa Steven C. , McElrath M. Juliana , Kirk Gregory D. , Michael Nelson L. , Haas David W. , Deeks Steven G. , Wolinsky Steven , Walker Bruce , Barouch Dan H. , Stieh Daniel , Carrington Mary
Published: July 2024

HLA
class I variation has the strongest effect genome-wide on outcome after HIV infection, and as such, an understanding of the impact of
HLA
polymorphism on response to HIV vaccination may inform vaccine design. We sought
HLA
associations with HIV-directed immunogenicity in the phase 1/2a APPROACH vaccine trial, which tested vaccine regimens containing mosaic inserts in Ad26 and MVA vectors, with or without a trimeric gp140 protein. While there were no
HLA
allelic associations with the overall cellular immune response to the vaccine assessed by ELISpot (Gag, Pol, and Env combined), significant associations with differential response to Gag compared to Env antigens were observed. Notably,
HLA
class I alleles known to associate with disease susceptibility in HIV natural history cohorts are associated with stronger Env-directed responses, whereas protective alleles are associated with stronger Gag-directed responses. Mean viral loads determined for each
HLA
allele in untreated individuals correlated negatively with the strength of the Gag response minus the Env response in Black vaccinees based on both ELISpot and CD8
+
T cell ICS responses. As the association of T cell responses to conserved Gag epitopes with lower viral load in untreated individuals is well established, our data raise the possibility that the Ad26.Mos.HIV vaccine may induce more effective cellular responses in those with HLA alleles that confer improved virologic control in untreated HIV infection.

IMPORTANCE

No vaccine tested to date has shown sufficient efficacy against HIV infection. A vaccine that induces robust responses in one individual may fail to do so in another individual due to variation in HLA class I genes, loci central to the immune response. Extensive data have shown the strong effect of HLA variation on outcome after HIV infection, but very little is known about the effect of such variation on HIV vaccine success. Here, we identify a link between the effect of HLA variation on HIV disease outcome and immune responses to an HIV vaccine. HLA variants associated with better HIV control after infection also induce stronger responses against the HIV Gag protein relative to the Env protein after vaccination. Given the virologic control conferred by responses to Gag in natural history of HIV infection, these data suggest that HLA alleles conferring protection after HIV infection may also support a more effective cellular response to HIV vaccination.
Aptamer-associated colorimetric reverse transcription loop-mediated isothermal amplification assay for detection of dengue virus
Authors: Arruda Vitória de Oliveira , Filho Luiz Ricardo Goulart , Neves Adriana Freitas
Published: July 2024

Current diagnostic methods for dengue, such as serological tests, have limitations in terms of cross-reactivity with other viruses. To address this issue, we explored the potential of combining the loop-mediated isothermal amplification (LAMP) technique with the affinity of aptamers to develop point-of-care testing. In this study, we utilized 60 serum samples. An aptamer capable of binding to the dengue virus was employed as a platform for capturing genetic material, and its performance was compared to a commercial kit. Dengue virus was detected through RT-PCR and colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP), allowing visual observation of the results without the need for equipment. In the context of the aptamer LAMP assay, our analysis revealed the detection of the dengue virus in 38 out of 60 samples, with 95% sensitivity and 100% specificity compared to RT-PCR and/or APTA-RT-PCR. Importantly, we observed no cross-reaction when assessing samples positive for the zika virus, underscoring the assay’s selectivity. This innovative aptameric capture of the viral RNA in combination with the RT-LAMP (APTA-RT-LAMP) method has the potential to offer valuable molecular insights into neglected infectious diseases in a simpler and faster manner.

IMPORTANCE

Dengue is a neglected tropical disease of significant epidemiological importance in tropical and subtropical countries. Current diagnostics for this infection present challenges, such as cross-reactivity in serological tests. Finding ways to enhance the diagnosis of this disease is crucial, given the absence of specific treatments. An accurate, simple, and effective diagnosis contributes to the improved management of infected individuals. In this context, our work combines molecular biology techniques, such as isothermal loop amplification, with aptamers to detect the dengue virus in biological samples. Our method produces colorimetric results based on a color change, with outcomes available in less than 2 hours. Moreover, it requires simpler equipment compared to molecular PCR tests.
Persistent Müllerian duct syndrome (PMDS) presenting as bilateral cryptorchidism and left-sided inguinal hernia
Authors: Adke Shrishail , Khot Chandrasekhar I , Thakkar Hemangini
Published: July 2024

PMDS (persistent Müllerian duct syndrome) is a rare disorder of sex development characterised by the presence of Müllerian duct remnants in a phenotypically male individual with a 46XY karyotype. Radiological investigations play a crucial role in diagnosing and characterising this condition. Ultrasound and MRI are the modalities of choice. They help to non-invasively localise the gonads and Müllerian duct derivatives. Broadly, PMDS has two anatomical variants: male type and female type. The case report presented here does not fit into these classically described variants and can be called a variant of the female type. There is a risk of infertility and malignant transformation of undescended testis and Müllerian duct derivatives in cases of PMDS. Hence, management is focused on preventing these risks. Surgical intervention involves orchidopexy, removal of Müllerian duct derivatives and inguinal hernia repair.
Lomustine overdose in a patient with diffuse glioma: symptoms, management and outcome
Authors: Heggebø Liv Cathrine , Blakstad Hanne , Eriksson Marlena Christina , Brandal Petter
Published: July 2024

A male patient started PCV chemotherapy (a combination of procarbazine, lomustine and vincristine) for a recurrent oligodendroglioma grade 2. Unfortunately, our patient took an unintended overdose of lomustine during the first PCV course: instead of 160 mg absolute dose of lomustine on day 1 only, he consumed 160 mg absolute dose of lomustine for seven consecutive days to a total dose of 1120 mg. Pancytopenia became evident after 24 days, and several months of severe myelosuppression, infections, reduced general condition, and nutrition difficulties followed. Fortunately, our patient with time recovered his bone marrow function. However, the patient’s quality of life was reduced for a long time and several lessons were learnt: oral and written information on chemotherapy is essential, but not always sufficient to ensure the correct dosing of patient-administered chemotherapy. Oral chemotherapeutics should be delivered as a single-dose supply or be administered by experienced health personnel.
Three-dimensional printing for complex cardiac reoperations: optimising Gerbode defect repairs
Authors: Khan Fazal W , Chopko Trevor C , Maltais Simon , Stulak John
Published: July 2024

Cardiac fistulas present diagnostical and therapeutical challenges due to their variability in size, shape and pathway. Three-dimensional printing is increasingly used to provide a tactile representation that aids in preoperative planning and patient education. We present the case of a female in her 60s who developed a fistula between the left ventricle, right atrium and coronary sinus 2 years after bioprosthetic valve replacement. We used three-dimensional modelling to better understand her cardiac anatomy and optimise our surgical approach. She was discharged home without deficit following an uneventful postoperative course. Three-dimensional printing can improve patient care through tangible demonstration, preoperative planning and trainee education.
Parkinson’s disease psychosis associated with accelerated multidomain cognitive decline
Authors: Pisani Sara , Gosse Luca , Aarsland Dag , Ray Chaudhuri K , Ballard Clive , Ffytche Dominic , Velayudhan Latha , Bhattacharyya Sagnik
Published: July 2024

Background

Cognitive deficits are associated with poor quality of life and increased risk of development of dementia in patients with Parkinson’s disease (PD) psychosis. The trajectory of cognitive decline in PD psychosis remains however unclear.

Objective

We examined this using data from the Parkinson’s Progression Markers Initiative study.

Methods

We analysed data from patients with drug-naïve PD (n=676) and healthy controls (HC, n=187) over 5 years, and examined all cognitive measures assessed at each time point. We classified patients with PD into those who developed psychosis over the course of the study (PDP) and those without psychosis throughout (PDnP) using the Movement Disorders Society Unified Parkinson’s Disease Rating Scale part I hallucinations/psychosis item. We used linear mixed-effect models with restricted maximum likelihood. Age, sex, ethnicity, education and neuropsychiatric and PD-specific symptoms were entered as covariates of interest.

Findings

There were no baseline cognitive differences between PD patient groups. There were differences in cognitive performance between PD and HC across the majority of the assessments.Patients with PDP exhibited greater cognitive decline over 5 years compared with PDnP across most domains even after controlling for sociodemographics, depression, sleepiness, rapid eye movement sleep behaviour disorder and motor symptom severity (immediate recall, b=−0.288, p=0.003; delayed recall, b=−0.146, p=0.003; global cognition, Montreal Cognitive Assessment, b=−0.206, p<0.001; visuospatial, b=−0.178, p=0.012; semantic fluency, b=−0.704, p=0.002; processing speed, b=−0.337, p=0.029).

Conclusions

Patients with PD psychosis exhibited decline in semantic aspects of language, processing speed, global cognition, visuospatial abilities and memory, regardless of sociodemographic characteristics, neuropsychiatric and motor symptoms. These cognitive domains, particularly semantic aspects of language may therefore play an important role in PD psychosis and warrant further investigation.

Trial registration number

NCT01141023.