bluuebunny/crossref_metadata_2025 huggingface dataset:
Decentralized discrete adaptive sliding mode control for interconnected nonlinear systems
Authors: Znidi Aicha , Dehri Khadija , Nouri Ahmed Said
Published: October 2023

This article presents a study on controlling a class of large-scale systems composed of interconnected subsystems. The systems are represented by discrete block-oriented models with unknown parameters. This article proposes a novel adaptive sliding mode control strategy to address the tracking control problem and minimize the impact of interconnection. This approach leverages the robustness of sliding mode control against unmodeled dynamics and disturbances with the advantages of adaptive control. To adapt the system’s parameters, a recursive parametric estimation algorithm using least-squares techniques is employed. The proposed method offers benefits such as robustness against parameter uncertainties, handling of nonlinearities, improved tracking accuracy, and reduced chattering phenomena. The effectiveness of the method is demonstrated through the evaluation of two simulation examples.
Professional Development Effects on Early Intervention Providers’ Implementation of Home Visiting Practices
Authors: Harrington Jennifer F. , Snyder Patricia , Reichow Brian , Sun Shujia
Published: October 2023

A non-concurrent multiple baseline design across four early intervention providers was used to examine functional relations between job-embedded professional development (PD), including practice-based coaching (PBC), and providers’ fidelity of implementation of home visiting practices for embedded intervention. Four providers with one to two caregivers and their toddler with disabilities or developmental delays participated. The primary dependent measure was the number of essential home visiting practices providers implemented with fidelity. Results from visual analyses showed a functional relation between job-embedded PD and the number of essential home visiting practices implemented with fidelity for three of four providers. Provider and caregiver social validity data indicated PD and home visiting practices and embedded intervention were appropriate, feasible, and useful. Results provide promising evidence for job-embedded PD, including PBC, to support providers’ fidelity of implementation of home visiting practices for embedded intervention. Implications for future research and practice are discussed.
Model-based trade-off curves to support the set-based concurrent engineering of highly innovative projects
Authors: Silvestre De Oliveira Mayara , Fidelis Peixer Guilherme , Forcellini Fernando Antônio , Riso Barbosa Jader , Lozano Cadena Jaime Andrés
Published: October 2023

The literature acknowledges the advantages of Set-Based Concurrent Engineering (SBCE), but there is a lack of models for its adoption and documented cases of its implementation, mostly on products with consolidated technology, which raises the possibility of expanding SBCE for highly innovative products. These projects often have extensive resource limitations, leading to computational tools and mathematical modelling as fundamental sources of information. This paper proposes a method for model-based Trade-off Curves (ToC) generation to support SBCE. We adopted it to develop a magnetic air conditioner. The use of model-based ToC enabled the narrowing of the design space and monitoring of the design parameters and performance metrics and enabled SBCE adoption in the design process. The main contributions of this research are presenting the state-of-the-art in ToC generation and application, proposing the model, and demonstrating SBCE in highly innovative projects, while its importance lies in the opportunity to further disseminate SBCE to different development environments.
The MoXFo initiative – study design: Considerations related to study design and methodology in exercise research for people with multiple sclerosis
Authors: Dalgas Ulrik , Riemenschneider Morten , Gold Stefan M , Kalron Alon , Beckerman Heleen , de Groot Vincent , Dennett Rachel , Edwards Thomas , Pilutti Lara A , Freeman Jenny
Published: October 2023

Background:

Exercise as a subset of physical activity is a cornerstone in the management of multiple sclerosis (MS) based on its pleiotropic effects, but continued progression of the field requires better future designs and methodologies.

Objectives:

This paper outlines the work of the ‘Study design and methodology’ group of the MoXFo (moving exercise research forward) initiative, and addresses critical aspects and future directions when defining the research question of interest, and subsequently, designing the study and exercise intervention in MS patients.

Methods:

The work is based on the formation of an international expert panel formed within the MoXFo initiative. We provide a structured and concise synthesis of exercise-specific MS research challenges and considerations when designing randomized controlled trials (RCTs).

Results:

Challenges and considerations are presented using the Patient population, Intervention, Comparator, Outcomes, Timing, Setting (PICOTS) framework, thereby forming a new and specific MS exercise PICOTS framework.

Conclusion:

We propose that researchers should carefully consider and align all elements of this MS exercise PICOTS framework when developing future research questions and study designs, ultimately improving the quality of new exercise studies in people with MS.
European integration and political party logos: A ‘visual Europeanization’?
Authors: Casiraghi Matteo CM , Cusumano Eugenio , Chryssogelos Angelos
Published: October 2023

European integration scholars have paid little attention to the visual dimension of Europeanization. We fill this gap by analysing how European Union integration reshapes political parties’ most visible symbols: their logos. We examine 579 party logos in Central, Eastern and Southern Europe before and after countries became European Union members, obtained the status of candidates or joined the European neighbourhood policy. Our difference-in-differences models show that European Union integration corresponds to a decrease in extremist and nationalist symbols as well as national flag colours. This ‘visual Europeanization’ process, prompted by population ecology and rebranding, cannot be solely explained by democratization or economic growth. Our analysis considers potential mechanisms that explain this correlation, including Europarty membership and normative diffusion, and discusses implications for the Europeanization literature.
Stigma Toward Substance Dependence: Causes, Consequences, and Potential Interventions
Authors: Krendl Anne C. , Perry Brea L.
Published: October 2023

Substance dependence is a prevalent and urgent public health problem. In 2021, 60 million Americans reported abusing alcohol within the month prior to being surveyed, and nearly 20 million Americans reported using illegal drugs (e.g., heroin) or prescription drugs (e.g., opioids) for nonmedical reasons in the year before. Drug-involved overdose rates have been steadily increasing over the past 20 years. This increase has been primarily driven by opioid and stimulant use. Despite its prevalence, drug dependence is one of the most stigmatized health conditions. Stigma has myriad negative consequences for its targets, including limiting their access to employment and housing, disrupting interpersonal relationships, harming physical and mental health, and reducing help-seeking. However, because research on stigma toward people with substance use disorders (SUDs) is relatively sparse compared with research on stigma toward other mental illnesses, the field lacks a comprehensive understanding of the causes and consequences of SUD stigma. Moreover, it remains unclear how, if at all, these factors differ from other types of mental illness stigma. The goal of this review is to take stock of the literature on SUD stigma, providing a clear set of foundational principles and a blueprint for future research and translational activity.
A Shared Intentionality Account of Uniquely Human Social Bonding
Authors: Wolf Wouter , Tomasello Michael
Published: October 2023

Many mechanisms of social bonding are common to all primates, but humans seemingly have developed some that are unique to the species. These involve various kinds of interactive experiences—from taking a walk together to having a conversation—whose common feature is the triadic sharing of experience. Current theories of social bonding have no explanation for why humans should have these unique bonding mechanisms. Here we propose a shared intentionality account of uniquely human social bonding. Humans evolved to participate with others in unique forms of cooperative and communicative activities that both depend on and create shared experience. Sharing experience in these activities causes partners to feel closer because it allows them to assess their partner’s cooperative competence and motivation toward them and because the shared representations created during such interactions make subsequent cooperative interactions easier and more effective.
An α, β-unsaturated ketone alkylation and efficient reduction protocol for the synthesis of 3α-hydroxy-3β-methyl-4,4-dimethyl-5α-21-bromo-19-nor-pregnan-20-one
Authors: Zhang Mingguang , Wang Wenlong , Guo Cheng , Jiang Chunhuan
Published: October 2023

Alkyl-substituted testosterone derivatives are promising platforms for new drug discovery in medicinal chemistry. This approach provides a simple and efficient method for introducing an alkyl substituent to steroids at the C-4 position. In this study, the novel compound 3α-hydroxy-3β-methyl-4,4-dimethyl-5α-21-bromo-19-nor-pregnan-20-one is synthesized from 19-nor-testosterone. The protocol involves methylation of the dienolate, reduction of the alkene, the Grignard reaction of the carbonyl group, a Wittig reaction, hydroboration with BH3, the oxidation and bromination with a 49% overall yield. For the methylation and reduction steps, the effects of the base, solvent, and reactant ratio on the conversion and yield are investigated. The structures of the synthesized compounds are determined by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) (electrospray ionization (ESI)).
Optimal defense resource allocation against cyber-attacks in distributed generation systems
Authors: Mo Huadong , Xiao Xun , Sansavini Giovanni , Dong Daoyi
Published: October 2023

The deployment of advanced information and communication technologies necessitates considering new security threats, such as distributed denial of service attacks and malware, which can fault power generators and feeders and exacerbate power outages in distributed generation systems (DGS). Existing cyber-security studies fail to validate the attacker–defender game model between operators and hackers or provide a DGS model that accounts for realistic characteristics and operations. Furthermore, current game models may be infeasible for large-scale systems and are not robust against uncertainties owing to the use of metaheuristic algorithms. To overcome these gaps, this study quantified the result of a game using the contest success function and estimated the parameters of this function based on real-world evidence: the dataset of cyber crime incidents from Advisen, US. The DGS management was optimized using the power flow model considering the scenario-based uncertainty stemming from cyber-attacks. A three-stage attack+defend–defend–attack framework is proposed to optimize attack–defense resource allocation using the cooperative game and [Formula: see text]-subgradient method. The results for IEEE 4, 13, 34, 123 and 342 test node feeders show that the proposed framework is applicable to large-scale systems and robust to various types of cyber-attacks. The proposed model and algorithms further enhance the DGS performance under uncertainties by protecting the entire grid or only critical nodes according to the defenders’ objectives.
Traumatic brachial plexus injuries: a national review of epidemiology in the Scottish population over a 10-year period
Authors: Warwick Catherine E. , Hems Tim
Published: October 2023

A study was undertaken to establish the incidence and types of traumatic brachial plexus injury in the Scottish population over a 10-year period between 2011 and 2020, using a prospectively compiled database. There were 425 injuries, of which 328 were infraclavicular and 97 were supraclavicular. Infraclavicular injury associated with anterior shoulder dislocation was the most common subtype ( n = 166). The most common mechanism of injury was fall from standing height ( n = 160). In total, 45 operations were performed for supraclavicular and 89 for infraclavicular injuries, with 54 requiring nerve repairs with grafts, transfers or suture. The incidence was 0.8/100,000 per year, with numbers of infraclavicular injuries increasing. The majority were low-energy infraclavicular injuries, not requiring surgery. Supraclavicular injuries were less common but associated with high-energy trauma and likely to require nerve repair. This study gives information on epidemiology and resource requirement for brachial plexus injuries in this defined population, which is likely to be representative of Western European countries with similar demographics.

Level of evidence

III
Postoperative deviation in Wassel types II and III radial polydactyly: a retrospective analysis of 73 thumbs
Authors: Inaba Naoto , Takagi Takehiko , Seki Atsuhito , Takayama Shinichiro
Published: October 2023

This study examined the relationship between osteochondral stability and postoperative deviation at the interphalangeal (IP) joint in Wassel types II and III radial polydactyly. Cases with cartilaginous fusion between the radial distal phalanx and the proximal phalanx were classified as type IIB, while the remaining cases were categorized as type IIA. In conventional surgery, the cartilage was routinely resected on the radial aspect of the proximal phalangeal head, while in the modified procedure, this was preserved to avoid postoperative radial deviation. Postoperatively, there was no significant difference between both procedures in type IIA thumbs regarding IP joint deviation, whereas in type IIB/III thumbs, IP joint deviation was significantly higher in the conventional group (mean 19° [SD 16°]) compared to the modified group (mean 0.8° [SD 4.9°]). Surgeons should exercise caution against excessive cartilage excision to preserve osteochondral stability during procedures, especially for type IIB and III radial polydactylies.

Level of evidence: IV
Medical malpractice litigation following humeral fractures in the United States
Authors: Megalla Martinus , Zaifman Jay M , Grace Zachary T , Imam Nareena , Kohan Eitan M , Alberta Frank G
Published: October 2023

Background

The purpose of this study is to characterize malpractice claims against orthopedic surgeons treating humeral fractures and determine factors associated with plaintiff verdicts and settlements.

Methods

The Westlaw legal database was queried for all cases involving humeral fractures. Patient demographics, causes cited for litigation, case outcomes, and indemnity payments were collected to determine common factors that lead plaintiffs to pursue legal action.

Results

Fifty-seven cases were identified that met inclusion criteria. The mean plaintiff age was 52.5 years with 61% female. The most common category of negligence was treatment error, which occurred in 29 claims (51%). The most common types of damages incurred were functional limitation (40%), nerve injury (32%), and malunion/nonunion (26%). Overall, 42 cases (74%) resulted in a defense verdict. Four cases (7%) resulted in settlements and 11 cases (19%) resulted in plaintiff verdicts. Cases that resulted in plaintiff verdicts or settlements were treated with intramedullary nails more often than those with defense verdicts (27% vs. 4.8%, p = 0.036).

Discussion

These findings highlight the importance of effective communication with patients regarding treatment modalities, risks and benefits, and prognosis of their injury.

Level of evidence

IV; Case Series using Large Database; Epidemiology Study
Costal Cartilage Graft Repair Osteochondral Defect in a Mouse Model
Authors: Pang Yidan , Ma Yiyang , Zheng Kaiwen , Zhu Siyuan , Sui Hongyu , Ren Hao , Liu Kang , Li Wei , Huang Yigang , Du Dajiang , Gao Junjie , Zhang Changqing
Published: October 2023

Objective

Osteochondral defects develop into osteoarthritis without intervention. Costal cartilage can be utilized as an alternative source for repairing osteochondral defect. Our previous clinical study has shown the successful osteochondral repair by costal cartilage graft with integration into host bone bed. In this study, we investigate how cartilaginous graft adapt to osteochondral environment and the mechanism of bone-cartilage interface formation.

Design

Costal cartilage grafting was performed in C57BL/6J mice and full-thickness osteochondral defect was made as control. 3D optical profiles and micro-CT were applied to evaluate the reconstruction of articular cartilage surface and subchondral bone as well as gait analysis to evaluate articular function. Histological staining was performed at 2, 4, and 8 weeks after surgery. Moreover, costal cartilage from transgenic mice with fluorescent markers were transplanted into wild-type mice to observe the in vivo changes of costal chondrocytes.

Results

At 8 weeks after surgery, 3D optical profiles and micro-CT showed that in the graft group, the articular surface and subchondral bone were well preserved. Gait analysis and International Cartilage Repair Society (ICRS) score evaluation showed a good recovery of joint function and histological repair in the graft group. Safranin O staining showed the gradual integration of graft and host tissue. Costal cartilage from transgenic mice with fluorescent markers showed that donor-derived costal chondrocytes turned into osteocytes in the subchondral area of host femur.

Conclusion

Costal cartilage grafting shows both functional and histological repair of osteochondral defect in mice. Graft-derived costal chondrocytes differentiate into osteocytes and contribute to endochondral ossification.
The Renewal of the Webcomic in the Era of Platformization: The Case of 9Gag on Instagram
Authors: Hernández María Abellán , Bautista Pavel Sidorenko
Published: October 2023

This article addresses the place that the webcomic occupies as valuable content within the repertoire of consumable options in digital social media platforms. For the new digital generations, these new media spaces of light entertainment are spaces of encounter and interaction. Taking as a case study the Instagram profile of 9Gag, this article analyzes the level of engagement of 9Gag audiences with the webcomics published in that profile during the year 2022. The hypothesis defended in this text is to consider that these new spaces of consumption and interaction between users and content are especially relevant when considering the reach that the webcomic has as a format or content of interest for younger audiences. The results obtained after the data analysis show, even considering its possible exploratory nature of the study, that the webcomic is an attractive content for centennial audiences, although its formal and discursive concreteness remains far from the linguistic innovations that the digital comic promoted in its first manifestations.
The Effect of L2 Self-Guides and Autonomous Motivation on L2 Motivated Behavior
Authors: Kim Hyang-il
Published: October 2023

The present study is aimed at examining the links between L2 self-guides and self-determination theory (SDT). 429 Korean university students participated in the study and their responses to the questionnaires on L2 self-guides in the 2 × 2 model and autonomous motivation of SDT were analyzed. The results show that, first, promotion focused L2 self-guides were found to share some characteristics with autonomous motivation, that is, intrinsic motivation and identified motivation. Second, these two types of motivation appeared to have stronger predictor values for motivated learning behavior than L2 self-guides with a promotion focus. Lastly, these L2 self-guides’ relationship with motivated behavior was found to be completely mediated by autonomous motivation. This indicates that when considering the relationship between students’ L2 self-guides and their motivated effort, autonomous motivation should be taken into account.
Risk factors for delayed sputum conversion: A qualitative case study from the person-in-charge of TB program’s perspectives
Authors: Wardani Dyah Wulan Sumekar Rengganis , Pramesona Bayu Anggileo , Septiana Trisya , Soemarwoto Retno Ariza Soeprihatini
Published: October 2023

Background:

One of the indicators to determine the success of TB treatment is the conversion of sputum from smear positive to negative. However, several factors can lead to this failure of sputum conversion.

Objectives:

To investigate the risk factors for delayed sputum conversion from the person-in-charge (PIC) of the TB program’s perspective.

Design and methods:

This qualitative case study was conducted on September 7th, 2022. Thirty-one PICs of the TB program from 31 public health centers ( Puskesmas) in Bandar Lampung, Indonesia, were recruited purposively. All participants were grouped into three FGDs. Developed semi-structured interview questions were used for data collection. Thematic analysis was used to synthesize and cross-reference emerging topics.

Results:

Three themes emerged in our study: (1) individual factors with the sub-themes of medication adherence, education, initial laboratory examination, comorbid disease, nutrition, and lifestyle; (2) environmental factors with the sub-themes of types of support, sources of support, environmental conditions and stigma; and (3) health service factors with the sub-theme of access to health service facilities.

Conclusions:

Problems related to TB management are not only the individual's responsibility but need to strengthen support from the environment and health services.
Nicotine as an Environmental Toxin: Implications for Children's Health
Authors: Gatzke-Kopp Lisa M. , Rice Danielle R.
Published: October 2023

Despite significant declines in population smoking rates and effective policies to ban smoking in public places, environmental exposure to nicotine remains prevalent among children. Environmental smoke exposure affects children's respiratory, immune, and metabolic health but is also implicated in children's cognitive and behavioral development. Nicotine's chemical properties mimic naturally occurring chemicals in the brain. When nicotine is present during brain development (prenatally through the first five years of life), it alters developmental processes that affect systems involved in cognitive control, impulsivity, and sensitivity to rewarding substances, increasing risks for obesity. Because nicotine is the specific toxin underlying these outcomes, vaping is unlikely to be a safer alternative. Given the rise in vaping among young adults generally, and pregnant women specifically, this exposure represents a public health concern that warrants additional attention. Policies including modernized public health messaging and routine screening could reduce children's inadvertent exposure.
Anti-Racism Efforts in Healthcare: A Selective Review From a Social Cognitive Perspective
Authors: Brondolo Elizabeth , Kaur Amandeep , Seavey Rebecca , Flores Melissa ,   the Collaborative Health Integration Research Program (CHIRP) DEI Writing Group 3
Published: October 2023

Health effects of structural racism occur on cultural and institutional levels and potentiate racism on an interpersonal level. Consequently, efforts to mitigate the health effects of racism may require intervention on all levels. The effectiveness of these approaches may depend partly on the degree to which they address the underlying patterns of social cognition, shaping social norms and influencing thoughts, feelings, and expectations about oneself, one's relationships with others, and interactions with the healthcare system. This paper aims to evaluate the current approaches to addressing structural racism (via racism and health statements and training programs in diversity, equity, and inclusion or cultural competence). These interventions work to shift social cognition, and consequently, shape social behavior in the healthcare context. Our goal is to identify ways to maximize the potential of these approaches to address social cognition to guide efforts to achieve a more inclusive and equitable healthcare system.
Developmental Neuroscience Informs Policy Related to Migrant and Refugee Children's Mental Health
Authors: Kribakaran Sahana , Cohodes Emily M. , Gee Dylan G.
Published: October 2023

Migrant and refugee children commonly experience traumatic events and stressful conditions along their migration journeys. Migration-related trauma can have persisting effects on children's mental health. Developmental neuroscience suggests neural mechanisms that connect these experiences to mental health conditions such as post-traumatic stress disorder. This research review, focused on migrant families emigrating from Mexico, Central America, and Haiti and bound for the United States, first overviews the nature of trauma exposure faced by migrant families and next delineates potential neurobiological mechanisms underlying the effects of migration-related trauma on youth mental health. Finally, detailed policy recommendations relate to (1) providing mental health care, (2) addressing chronic stressors in the context of daily life, and (3) preventing migration-related trauma.
Research on Gene–Environment Interplay Over Time in Diverse Populations to Inform Public Health Initiatives
Authors: Elam Kit K.
Published: October 2023

Differences in individual genetic predisposition are associated with adaptive and maladaptive behavior. Also, the interplay between genetic predisposition and one's social and contextual environments can work together to influence behavior. This gene–environment interplay can change across development and vary across different racial and ethnic populations. Genetically informed developmental research in diverse populations can enhance understanding of the etiology, risk, and prevention of public health issues. Advancing and translating this research can help identify social and contextual risk factors, as well as protective mechanisms, during specific developmental periods and across diverse populations. This approach can inform public health strategies in promoting health behaviors.
Toward Removing Barriers in the Evaluation, Diagnosis, and Care of Individuals With Cerebral Visual Impairments
Authors: Lueck Amanda , Harpster Karen , Hartmann Elizabeth , Tracy Helen St Clair , Jones Monika , Legge Richard , Kran Barry , Ravenscroft John , Bauer Corinna M.
Published: October 2023

Cerebral visual impairment (CVI) is a leading cause of pediatric visual impairment worldwide. Despite the ramifications on multiple developmental domains and quality of life factors, substantial barriers remain for evaluation, diagnosis, treatment, and education of this growing population of children and adults. At the root is a lack of consensus on the definition and diagnostic criteria of CVI and a narrow ocular/acuity-based classification of visual impairment. This article covers four main issues that need to be urgently addressed to make strides toward removing current barriers. These challenges highlight the need for policy change at multiple levels to help ensure that individuals with CVI will have access to appropriate (re)habilitation and education services regardless of their acuity or visual function. Suggested solutions include the implementation of a globally accepted definition of CVI and increased multidisciplinary training programs. These will support international efforts to develop and implement quantitative interdisciplinary assessment methods, identify meaningful and effective intervention approaches, and monitor long-term outcomes for those with CVI. Additionally, sensitive and specific markers can be identified for differentiating CVI from other related developmental conditions, such as autism spectrum disorder and developmental coordination disorder. Ultimately, these proposed changes will lead toward improved quality of life for individuals with CVI and their caregivers.
Testosterone, Sex, and Sport
Authors: Casto Kathleen V. , Carré Justin M.
Published: October 2023

Recent policies banning or limiting the participation of transgender and intersex women from the women's category of sport have called upon the science of testosterone to justify exclusion and define eligibility criteria. Scientific evidence supports a male advantage in sport, substantial sex differences in circulating testosterone, permanent effects on physiology from its long-term exposure, and a dose-dependent sporting advantage to its exogenous use. Yet, evidence connecting these findings has major gaps. Notably, no direct evidence shows that transgender and intersex women have a systematic sport advantage or that testosterone is the causal link. A brief review covers the relevant societal context, the science of testosterone, and the existing data used to support policies of exclusion. Key complexities, gaps in knowledge, and related ethical concerns all point to the need for more rigorous research.
Experiences of Implementing Rooming-in Practice for First-Time Mothers in a Postpartum Care Center
Authors: Wu Hsiao-Ling , Lu Der-Fa , Tsay Pei-Kwei
Published: October 2023

Introduction

Practices promoted by the Baby-Friendly Hospital Initiative have become a part of the current mainstream postpartum infant care. However, adherence to rooming-in practice by health-care facilities is lower than that of other steps under this initiative.

Objective

The aim of this study was to investigate the experiences in implementing the rooming-in policy among first-time mothers at a postpartum center.

Methods

The present study is a qualitative research conducted using the descriptive phenomenological method. This study was performed at a postpartum care center in Southern Taiwan between August 2018 and December 2018. Semi-structured interviews were conducted with 20 postpartum mothers during their postpartum care center stay.

Results

Based on interview data, this study identified three main themes about implementing full-time rooming-in experiences: (a) against the rule of taking plenty of rest during the postpartum period, (b) negative experiences and myths regarding implementing rooming-in experience, and (c) postpartum care centers service content affect first-time mothers’ willingness to implement rooming-in.

Conclusions

In postpartum care centers, first-time mothers’ willingness to implement full-time rooming-in significantly decreases due to the effects of the “doing-the-month” culture, postpartum physical recovery status, stress of the rooming-in experience, myths regarding rooming-in practice, trusting professional neonate care services more than own care, and attitude toward payment for services.
Fibroblast growth factor 10 reverses cigarette smoke- and elastase-induced emphysema and pulmonary hypertension in mice
Authors: Hadzic Stefan , Wu Cheng-Yu , Gredic Marija , Pak Oleg , Loku Edma , Kraut Simone , Kojonazarov Baktybek , Wilhelm Jochen , Brosien Monika , Bednorz Mariola , Seimetz Michael , Günther Andreas , Kosanovic Djuro , Sommer Natascha , Warburton David , Li Xiaokun , Grimminger Friedrich , Ghofrani Hossein A. , Schermuly Ralph T. , Seeger Werner , El Agha Elie , Bellusci Saverio , Weissmann Norbert
Published: October 2023

Background

COPD is an incurable disease and a leading cause of death worldwide. In mice, fibroblast growth factor (FGF)10 is essential for lung morphogenesis, and in humans, polymorphisms in the humanFGF10gene correlate with an increased susceptibility to develop COPD.

Methods

We analysed FGF10 signalling in human lung sections and isolated cells from healthy donor, smoker and COPD lungs. The development of emphysema and PH was investigated inFgf10+/−andFgfr2b+/−(FGF receptor 2b) mice upon chronic exposure to cigarette smoke. In addition, we overexpressed FGF10 in mice following elastase- or cigarette smoke-induced emphysema and pulmonary hypertension (PH).

Results

We found impaired FGF10 expression in human lung alveolar walls and in primary interstitial COPD lung fibroblasts. In contrast, FGF10 expression was increased in large pulmonary vessels in COPD lungs. Consequently, we identified impaired FGF10 signalling in alveolar walls as an integral part of the pathomechanism that leads to emphysema and PH development: mice with impaired FGF10 signalling (Fgf10+/−andFgfr2b+/−) spontaneously developed lung emphysema, PH and other typical pathomechanistic features that generally arise in response to cigarette smoke exposure.

Conclusion

In a therapeutic approach, FGF10 overexpression successfully restored lung alveolar and vascular structure in mice with established cigarette smoke- and elastase-induced emphysema and PH. FGF10 treatment triggered an initial increase in the number of alveolar type 2 cells that gradually returned to the basal level when the FGF10-mediated repair process progressed. Therefore, the application of recombinant FGF10 or stimulation of the downstream signalling cascade might represent a novel therapeutic strategy in the future.
Utility of rehabilitation prior to bronchoscopic lung volume reduction:post hocanalysis of the VENT trial
Authors: Brock Judith Maria , Kontogianni Konstantina , Sciurba Frank C. , Criner Gerard J. , Herth Felix
Published: October 2023

Background and objective

Rehabilitation programmes are a valuable treatment modality for patients with COPD to increase exercise capacity and quality of life. The utility of pulmonary rehabilitation prior to bronchoscopic lung volume reduction (BLVR) is unclear.

Methods

We performed apost hocanalysis of the Valve for Emphysema Palliation Trial (VENT) trial, the first multicentre randomised trial comparing the safety and efficacy of BLVR. Patients completed a pulmonary rehabilitation programme prior to BLVR over 6–10 weeks and maintained by daily practice, consisting of endurance training, strength training and upper/lower limb exercise. Lung function and exercise parameters (6-min walk distance (6MWD)) were assessed before and after rehabilitation and we tried to identify predictors for pulmonary rehabilitation benefit.

Results

Lung function and exercise capacity of 403 patients (mean±sdage 63.3±7.4 years, 37.5% female, mean±sdforced expiratory volume in 1 s 30.1±7.6 L) were analysed. Exercise capacity significantly improved from 331.6±98.8 m to 345.6±95.3 m (p<0.001) in 6-min walk testing (6MWT), with 40.3% showing clinically meaningful improvements. Patients also experienced less dyspnoea after 6MWT, while pulmonary function parameters did not change significantly overall. Patients with lower exercise capacity at screening (6MWD <250 m) benefited more from pulmonary rehabilitation. The indication and prerequisites for BLVR were still present in all patients after pulmonary rehabilitation.

Conclusion

The national mandatory requirements for rehabilitation prior to BLVR, which apply to all COPD patients, should be reconsidered and specified for COPD patients who really benefit.
The role of red ginseng in men’s reproductive health: a literature review
Authors: Wang Hao , Zhang Jiwei , Ma Dongyue , Zhao Ziwei , Yan Bin , Wang Fu
Published: October 2023

Background

Red ginseng (RG) is a traditional herb commonly used in China, Korea, and other East Asian countries. Recently, it has demonstrated a better clinical value in men’s reproductive health (MRH). The present review aimed to examine the effects of RG treatment on MRH.

Results

Overall, 42 articles related to RG application in MRH were reviewed, of which 31 were animal experiments and 11 were clinical studies. Furthermore, this review analyzed the use of RG in some male reproductive diseases in clinical trials and determined the associated mechanisms of action. The mechanism of action of RG in MRH may be related to oxidative stress, regulation of sex hormones and spermatogenesis-related proteins, and anti-inflammation.

Conclusions

The application of RG for the treatment of male infertility, erectile dysfunction, and prostate diseases has the potential to contribute to MRH.
Deep learning, radiomics and radiogenomics applications in the digital breast tomosynthesis: a systematic review
Authors: Hussain Sadam , Lafarga-Osuna Yareth , Ali Mansoor , Naseem Usman , Ahmed Masroor , Tamez-Peña Jose Gerardo
Published: October 2023

Background

Recent advancements in computing power and state-of-the-art algorithms have helped in more accessible and accurate diagnosis of numerous diseases. In addition, the development of de novo areas in imaging science, such as radiomics and radiogenomics, have been adding more to personalize healthcare to stratify patients better. These techniques associate imaging phenotypes with the related disease genes. Various imaging modalities have been used for years to diagnose breast cancer. Nonetheless, digital breast tomosynthesis (DBT), a state-of-the-art technique, has produced promising results comparatively. DBT, a 3D mammography, is replacing conventional 2D mammography rapidly. This technological advancement is key to AI algorithms for accurately interpreting medical images.

Objective and methods

This paper presents a comprehensive review of deep learning (DL), radiomics and radiogenomics in breast image analysis. This review focuses on DBT, its extracted synthetic mammography (SM), and full-field digital mammography (FFDM). Furthermore, this survey provides systematic knowledge about DL, radiomics, and radiogenomics for beginners and advanced-level researchers.

Results

A total of 500 articles were identified, with 30 studies included as the set criteria. Parallel benchmarking of radiomics, radiogenomics, and DL models applied to the DBT images could allow clinicians and researchers alike to have greater awareness as they consider clinical deployment or development of new models. This review provides a comprehensive guide to understanding the current state of early breast cancer detection using DBT images.

Conclusion

Using this survey, investigators with various backgrounds can easily seek interdisciplinary science and new DL, radiomics, and radiogenomics directions towards DBT.
Telomere and subtelomere high polymorphism might contribute to the specificity of homologous recognition and pairing during meiosis in barley in the context of breeding
Authors: Serrano-León I. M. , Prieto P. , Aguilar M.
Published: October 2023

Barley (Hordeum vulgare) is one of the most popular cereal crops globally. Although it is a diploid species, (2n = 2x = 14) the study of its genome organization is necessary in the framework of plant breeding since barley is often used in crosses with other cereals like wheat to provide them with advantageous characters. We already have an extensive knowledge on different stages of the meiosis, the cell division to generate the gametes in species with sexual reproduction, such as the formation of the synaptonemal complex, recombination, and chromosome segregation. But meiosis really starts with the identification of homologous chromosomes and pairing initiation, and it is still unclear how chromosomes exactly choose a partner to appropriately pair for additional recombination and segregation. In this work we present an exhaustive molecular analysis of both telomeres and subtelomeres of barley chromosome arms 2H-L, 3H-L and 5H-L. As expected, the analysis of multiple features, including transposable elements, repeats, GC content, predicted CpG islands, recombination hotspots, G4 quadruplexes, genes and targeted sequence motifs for key DNA-binding proteins, revealed a high degree of variability both in telomeres and subtelomeres. The molecular basis for the specificity of homologous recognition and pairing occurring in the early chromosomal interactions at the start of meiosis in barley may be provided by these polymorphisms. A more relevant role of telomeres and most distal part of subtelomeres is suggested.
Transcriptome analysis reveals a lncRNA-miRNA-mRNA regulatory network in OsRpp30-mediated disease resistance in rice
Authors: Li Minghua , Li Wei , Zhao Meixia , Li Zhiqiang , Wang Guo-Liang , Liu Wende , Liang Chun
Published: October 2023

Background

Long non-coding RNAs (lncRNAs) play critical roles in various biological processes in plants. Extensive studies utilizing high-throughput RNA sequencing have revealed that many lncRNAs are involved in plant disease resistance. Oryza sativa RNase P protein 30 (OsRpp30) has been identified as a positive regulator of rice immunity against fungal and bacterial pathogens. Nevertheless, the specific functions of lncRNAs in relation to OsRpp30-mediated disease resistance in rice remain elusive.

Results

We conducted a comprehensive analysis of lncRNAs, miRNAs, and mRNAs expression patterns in wild type (WT), OsRpp30 overexpression (OsRpp30-OE), and OsRpp30 knockout (OsRpp30-KO) rice plants. In total, we identified 91 differentially expressed lncRNAs (DElncRNAs), 1671 differentially expressed mRNAs (DEmRNAs), and 41 differentially expressed miRNAs (DEmiRNAs) across the different rice lines. To gain further insights, we investigated the interaction between DElncRNAs and DEmRNAs, leading to the discovery of 10 trans- and 27 cis-targeting pairs specific to the OsRpp30-OE and OsRpp30-KO samples. In addition, we constructed a competing endogenous RNA (ceRNA) network comprising differentially expressed lncRNAs, miRNAs, and mRNAs to elucidate their intricate interplay in rice disease resistance. The ceRNA network analysis uncovered a set of gene targets regulated by lncRNAs and miRNAs, which were found to be involved in pathogen recognition, hormone pathways, transcription factor activation, and other biological processes related to plant immunity.

Conclusions

Our study provides a comprehensive expression profiling of lncRNAs, miRNAs, and mRNAs in a collection of defense mutants in rice. To decipher the putative functional significance of lncRNAs, we constructed trans- and cis-targeting networks involving differentially expressed lncRNAs and mRNAs, as well as a ceRNA network incorporating differentially expressed lncRNAs, miRNAs, and mRNAs. Together, the findings from this study provide compelling evidence supporting the pivotal roles of lncRNAs in OsRpp30-mediated disease resistance in rice.
Paralemnalia thyrsoides-associated fungi: phylogenetic diversity, cytotoxic potential, metabolomic profiling and docking analysis
Authors: Taher Mohie el-dien Radwa , Mahmoud Basma Khalaf , Abdelwahab Miada F. , Khedr Amgad I. M. , Kamel Mohamed Salah , Yahia Ramadan , Mohamed Nada M. , Zawily Amr El , Kamel Eman S. , Salem Aliasger K , Abdelmohsen Usama Ramadan , Fouad Mostafa A.
Published: October 2023

Background

Cancer continues to be one of the biggest causes of death that affects human health. Chemical resistance is still a problem in conventional cancer treatments. Fortunately, numerous natural compounds originating from different microbes, including fungi, possess cytotoxic characteristics that are now well known. This study aims to investigate the anticancer prospects of five fungal strains that were cultivated and isolated from the Red Sea soft coral Paralemnalia thyrsoides. The in vitro cytotoxic potential of the ethyl acetate extracts of the different five isolates were evaluated using MTS assay against four cancer cell lines; A549, CT-26, MDA-MB-231, and U87. Metabolomics profiling of the different extracts using LC-HR-ESI-MS, besides molecular docking studies for the dereplicated compounds were performed to unveil the chemical profile and the cytotoxic mechanism of the soft coral associated fungi.

Results

The five isolated fungal strains were identified as Penicillium griseofulvum (RD1), Cladosporium sphaerospermum (RD2), Cladosporium liminiforme (RD3), Penicillium chrysogenum (RD4), and Epicoccum nigrum (RD5). The in vitro study showed that the ethyl acetate extract of RD4 exhibited the strongest cytotoxic potency against three cancer cell lines A549, CT-26 and MDA-MB-231 with IC50 values of 1.45 ± 8.54, 1.58 ± 6.55 and 1.39 ± 2.0 µg/mL, respectively, also, RD3 revealed selective cytotoxic potency against A549 with IC50 value of 6.99 ± 3.47 µg/mL. Docking study of 32 compounds dereplicated from the metabolomics profiling demonstrated a promising binding conformation with EGFR tyrosine kinase that resembled its co-crystallized ligand albeit with better binding energy score.

Conclusion

Our results highlight the importance of soft coral-associated fungi as a promising source for anticancer metabolites for future drug discovery.
Elimination of blaKPC−2-mediated carbapenem resistance in Escherichia coli by CRISPR-Cas9 system
Authors: Tao Shuan , Chen Huimin , Li Na , Fang Yewei , Zhang He , Xu Yao , Chen Luyan , Liang Wei
Published: October 2023

Objective

The purpose of this study is to re-sensitive bacteria to carbapenemases and reduce the transmission of the blaKPC−2 gene by curing the blaKPC−2-harboring plasmid of carbapenem-resistant using the CRISPR-Cas9 system.

Methods

The single guide RNA (sgRNA) specifically targeted to the blaKPC−2 gene was designed and cloned into plasmid pCas9. The recombinant plasmid pCas9-sgRNA(blaKPC−2) was transformed into Escherichia coli (E.coli) carrying pET24-blaKPC−2. The elimination efficiency in strains was evaluated by polymerase chain reaction (PCR) and quantitative real-time PCR (qPCR). Susceptibility testing was performed by broth microdilution assay and by E-test strips (bioMérieux, France) to detect changes in bacterial drug resistance phenotype after drug resistance plasmid clearance.

Results

In the present study, we constructed a specific prokaryotic CRISPR-Cas9 system plasmid targeting cleavage of the blaKPC−2 gene. PCR and qPCR results indicated that prokaryotic CRISPR-Cas9 plasmid transforming drug-resistant bacteria can efficiently clear blaKPC−2-harboring plasmids. In addition, the drug susceptibility test results showed that the bacterial resistance to imipenem was significantly reduced and allowed the resistant model bacteria to restore susceptibility to antibiotics after the blaKPC−2-containing drug-resistant plasmid was specifically cleaved by the CRISPR-Cas system.

Conclusion

In conclusion, our study demonstrated that the one plasmid-mediated CRISPR-Cas9 system can be used as a novel tool to remove resistance plasmids and re-sensitize the recipient bacteria to antibiotics. This strategy provided a great potential to counteract the ever-worsening spread of the blaKPC−2 gene among bacterial pathogens and laid the foundation for subsequent research using the CRISPR-Cas9 system as adjuvant antibiotic therapy.