bluuebunny/crossref_metadata_2025 huggingface dataset:
Acceptability of a Text Message‐Based Mobile Health Intervention to Promote Physical Activity in Cardiac Rehabilitation Enrollees: A Qualitative Substudy of Participant Perspectives
Authors: Atluri Namratha , Mishra Sonali R. , Anderson Theresa , Stevens Rachel , Edwards Angel , Luff Evan , Nallamothu Brahmajee K. , Golbus Jessica R.
Published: January 2024

Background

Mobile health (mHealth) interventions have the potential to deliver longitudinal support to users outside of episodic clinical encounters. We performed a qualitative substudy to assess the acceptability of a text message‐based mHealth intervention designed to increase and sustain physical activity in cardiac rehabilitation enrollees.

Methods and Results

Semistructured interviews were conducted with intervention arm participants of a randomized controlled trial delivered to low‐ and moderate‐risk cardiac rehabilitation enrollees. Interviews explored participants' interaction with the mobile application, reflections on tailored text messages, integration with cardiac rehabilitation, and opportunities for improvement. Transcripts were thematically analyzed using an iteratively developed codebook. Sample size consisted of 17 participants with mean age of 65.7 (SD 8.2) years; 29% were women, 29% had low functional capacity, and 12% were non‐White. Four themes emerged from interviews: engagement, health impact, personalization, and future directions. Participants engaged meaningfully with the mHealth intervention, finding it beneficial in promoting increased physical activity. However, participants desired greater personalization to their individual health goals, fitness levels, and real‐time environment. Generally, those with lower functional capacity and less experience with exercise were more likely to view the intervention positively. Finally, participants identified future directions for the intervention including better incorporation of exercise physiologists and social support systems.

Conclusions

Cardiac rehabilitation enrollees viewed a text message‐based mHealth intervention favorably, suggesting the potentially high usefulness of mHealth technologies in this population. Addressing participant‐identified needs on increased user customization and inclusion of clinical and social support is crucial to enhancing the effectiveness of future mHealth interventions.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04587882.
Cocreative Interaction: Somax2 and the REACH Project
Authors: Assayag Gérard , Bonnasse-Gahot Laurent , Borg Joakim
Published: January 2024

Somax2 is an artificial intelligence (AI)-based multiagent system for human–machine “coimprovisation” that generates stylistically coherent streams while continuously listening and adapting to musicians or other agents. The model on which it is based can be used with little configuration to interact with humans in full autonomy, but it also allows fine real-time control of its generative processes and interaction strategies, closer in this case to a “smart” digital instrument. An offspring of the Omax system, conceived at the Institut de Recherche et Coordination Acoustique/Musique (IRCAM), the Somax2 environment is part of the European Research Council Raising Cocreativity in Cyber–Human Musicianship (REACH) project, which studies distributed creativity as a general template for symbiotic interaction between humans and digital systems. It fosters mixed musical reality involving cocreative AI agents. The REACH project puts forward the idea that cocreativity in cyber–human systems results from the emergence of complex joint behavior, produced by interaction and featuring cross-learning mechanisms. Somax2 is a first step toward this ideal, and already shows life-size achievements. This article describes Somax2 extensively, from its theoretical model to its system architecture, through its listening and learning strategies, representation spaces, and interaction policies.
Pair-List Interpretation in Multiple Sluicing in Mandarin Chinese
Authors: Bai Xue , Takahashi Daiko
Published: January 2024

Among the proposals for multiple sluicing in Mandarin Chinese is what we call the multiclausal analysis, which posits that it involves conjoined single wh-questions. In this squib, we examine the analysis through the possibility of a pair-list interpretation for multiply sluiced clauses. We conclude that the multiclausal analysis alone is not sufficient to fully explicate the relevant phenomenon.
The challenge of assessing academic books: The U.K. and Lithuanian cases through the ISBN lens
Authors: Dagienė Eleonora
Published: January 2024

Books are an important output in many fields of research. However, they pose a significant challenge for research assessment systems, partly because of the limited availability of information to support the assessment of books. To inform book assessment practices, I present a systematic examination of the ISBN Manual and the Global Register of Publishers (GRP). I evaluate the extent to which these two sources can be used to determine the genre and publisher of a book as well as the country in which a book was issued. My analysis focuses on books submitted to the research assessment systems in Lithuania and the United Kingdom from 2008 to 2020. I show how the ISBN Manual captures the complex interactions between publishers, their imprints, and other organizations active in academic publishing, revealing the pitfalls of measuring books’ quality by their publisher’s prestige. The results also indicate that the ISBN standard provides no basis for the book genres mandated by research assessment systems in some countries. Finally, I demonstrate how the ISBN Manual and metadata accumulated in the GRP are convenient tools for designers of research assessment systems and are suitable for identifying ISBN registrants and performing bibliometric analysis.
Effect of Cu on microstructure and properties of Co2CrFeNiMnCux high-entropy alloy coatings prepared by laser cladding
Authors: Hu Pingjiu , Zhu Qingjun , Peng Zhongbo , Duan Jizhou
Published: January 2024

High-entropy alloy coatings (HEACs) of Co2CrFeNiMnCu x ( x = 0, 0.25, 0.5, 0.75, 1.0, 1.25) were fabricated on Q235 steel surfaces by laser cladding. A portion of the HEACs ( x = 0, 0.5 and 1.25) displayed a dual-phase FCC structure, while the remaining portion ( x = 0.25, 0.75 and 1.0) exhibited a single-phase FCC structure. Furthermore, as the Cu content increased, the grain size of the coatings became finer and elongated. Due to the unique processing technology of laser cladding, the HEACs exhibited a hardness gradient from the top to the substrates. Cu segregated within the crystal and accumulated near the grain boundaries. The primary mechanism for protecting the steel substrate through coatings was passive films protection. Remarkably, the coatings demonstrated better anti-corrosion properties when the Cu content was 0.25, with a charge transfer resistance of 9.528 × 104 Ω cm2, corrosion potential of −0.387 V and corrosion current density of 3.125 × 10−7 A/cm2.
Antinuclear antibody–associated autoimmune cytopenia in childhood is a risk factor for systemic lupus erythematosus
Authors: Granel Jérôme , Fernandes Helder , Bader-Meunier Brigitte , Guth Amandine , Richer Olivier , Pillet Pascal , Leverger Guy , Ducassou Stéphane , Fahd Mony , Pasquet Marlène , Garnier Nathalie , Barlogis Vincent , Guitton Corinne , Jeziorski Eric , Thomas Caroline , Bayart Sophie , Cheikh Nathalie , Paillard Catherine , Abou Chahla Wadih , Chastagner Pascal , Neven Bénédicte , Millot Frédéric , Lejeune Julien , Li-Thiao Te Valérie , Armari-Alla Corinne , Briandet Claire , Carausu Liana , Deparis Marianna , Piguet Christophe , Benadiba Joy , Marie-Cardine Aude , Stephan Jean-Louis , Pellier Isabelle , Pluchart Claire , Doré Eric , Michaux Katell , Héritier Sébastien , Leblanc Thierry , Aladjidi Nathalie
Published: January 2024

Autoimmune cytopenia (AIC) in children may be associated with positive antinuclear antibodies (ANA) and may progress to systemic lupus erythematosus (SLE). We evaluated the risk of progression to SLE of childhood-onset ANA-associated AIC. In the French national prospective OBS’CEREVANCE cohort, the long-term outcome of children with ANA-associated AIC (ANA titer ≥1/160) and a subgroup of children who developed SLE were described. ANA were positive in 355 of 1803 (20%) children with AIC. With a median follow-up of 5.8 (range, 0.1-29.6) years, 79 of 355 (22%) patients developed SLE at a median age of 14.5 (1.1-21.4) years; 20% of chronic immune thrombocytopenic purpura, 19% of autoimmune hemolytic anemia, and 45% of Evans syndrome. None of the patients with ANA-negative test developed SLE. Severe manifestations of SLE were observed in 21 patients, and 2 patients died. In multivariate analysis including patients with positive ANA within the first 3 months after AIC diagnosis, age >10 years at AIC diagnosis (relative risk [RR], 3.67; 95% confidence interval [CI], 1.18-11.4; P = .024) and ANA titer >1/160 (RR, 5.28; 95% CI, 1.20-23.17; P = .027) were associated with the occurrence of SLE after AIC diagnosis. ANA-associated AIC is a risk factor for progression to SLE, especially in children with an initial ANA titer >1/160 and an age >10 years at AIC diagnosis. ANA screening should be recommended in children with AIC, and patients with ANA should be monitored long-term for SLE, with special attention to the transition period. This trial was registered at www.ClinicalTrials.gov as #NCT05937828.
Bulging Distortion of Austenitic Stainless Steel Sheet on the Partially Penetrated Side of Non-Penetration Lap Laser Welding Joint
Authors: Yao Chengwu , Liu Enze , Ni Jiaming , Nie Binying
Published: January 2024

Non-penetration laser welding of lap joints in austenitic stainless steel sheets is commonly preferred in fields where the surface quality is of utmost importance. However, the application of non-penetration welded austenitic stainless steel parts is limited owing to the micro bulging distortion that occurs on the back surface of the partial penetration side. In this paper, non-penetration lap laser welding experiments, were conducted on galvanized and SUS304 austenitic stainless steel plates using a fiber laser, to investigate the mechanism of bulging distortion. A comparative experiment of DC01 galvanized steel-Q235 carbon steel lap laser welding was carried out, and the deflection and distortion profile of partially penetrated side of the sheets were measured using a non-contact laser interferometer. In addition, the cold-rolled SUS304 was subjected to heat holding at different temperatures and water quenching after bending to characterize its microstructure under tensile and compressive stress. The results show that, during the heating stage of the thermal cycle of laser lap welding, the partial penetration side of the SUS304 steel sheet generates compressive stress, which extrudes the material in the heat-affected zone to the outside of the back of the SUS304 steel sheet, thereby forming a bulge. The findings of these experiments can be of great value for controlling the distortion of the partial penetrated side of austenitic stainless steel sheet during laser non-penetration lap welding.
Identification of two major QTLs for pod shell thickness in peanut (Arachis hypogaea L.) using BSA-seq analysis
Authors: Liu Hongfei , Zheng Zheng , Sun Ziqi , Qi Feiyan , Wang Juan , Wang Mengmeng , Dong Wenzhao , Cui Kailu , Zhao Mingbo , Wang Xiao , Zhang Meng , Wu Xiaohui , Wu Yue , Luo Dandan , Huang Bingyan , Zhang Zhongxin , Cao Gangqiang , Zhang Xinyou
Published: January 2024

Background

Pod shell thickness (PST) is an important agronomic trait of peanut because it affects the ability of shells to resist pest infestations and pathogen attacks, while also influencing the peanut shelling process. However, very few studies have explored the genetic basis of PST.

Results

An F2 segregating population derived from a cross between the thick-shelled cultivar Yueyou 18 (YY18) and the thin-shelled cultivar Weihua 8 (WH8) was used to identify the quantitative trait loci (QTLs) for PST. On the basis of a bulked segregant analysis sequencing (BSA-seq), four QTLs were preliminarily mapped to chromosomes 3, 8, 13, and 18. Using the genome resequencing data of YY18 and WH8, 22 kompetitive allele-specific PCR (KASP) markers were designed for the genotyping of the F2 population. Two major QTLs (qPSTA08 and qPSTA18) were identified and finely mapped, with qPSTA08 detected on chromosome 8 (0.69-Mb physical genomic region) and qPSTA18 detected on chromosome 18 (0.15-Mb physical genomic region). Moreover, qPSTA08 and qPSTA18 explained 31.1–32.3% and 16.7–16.8% of the phenotypic variation, respectively. Fifteen genes were detected in the two candidate regions, including three genes with nonsynonymous mutations in the exon region. Two molecular markers (Tif2_A08_31713024 and Tif2_A18_7198124) that were developed for the two major QTL regions effectively distinguished between thick-shelled and thin-shelled materials. Subsequently, the two markers were validated in four F2:3 lines selected.

Conclusions

The QTLs identified and molecular markers developed in this study may lay the foundation for breeding cultivars with a shell thickness suitable for mechanized peanut shelling.
Outcomes of a novel algorithm for levator muscle plication surgery in congenital blepharoptosis
Authors: Kotb Ahmed N , Salamah Moustafa A. , Khalil Ahmad S. , Dessouky Reem Amir Kamal
Published: January 2024

Aim

to assess the outcomes of a novel algorithm for the calculation of the amount levator muscle plication in congenital blepharoptosis surgery.

Methods

this retrospective comparative study included 34 patients with congenital ptosis subjected to levator muscle plication surgery during the period from October 2021 to November 2022. They were divided into two groups. Group A: the amount of levator muscle plication was calculated by a traditional formula [(amount of ptosis x 3) + 9 mm in cases with good levator function or (amount of ptosis x 3) + 11 mm in cases with fair levator function]. Group B: the amount of levator muscle plication was calculated by a novel nomogram [the result of the traditional formula was modified by subtracting 4 mm if the calculated amount was ≥ 15 mm or subtracting 3 mm if the calculated amount was < 15 mm]. Demographic data, baseline ptosis characteristics and postoperative results at 1st week, 1st month, 3rd month and 6th month were compared between the groups. Primary outcome measure was postoperative Marginal Reflex Distance (MRD1). Secondary outcome measures were lid contour, lid crease and any reported complications.

Results

Group A included 20 eyes of 18 patients while Group B included 20 eyes of 16 patients. The mean amount of levator muscle plication was 16.98 ± 2.44 mm and 13.48 ± 2.42 mm in group A and group B respectively. The difference between the two groups was highly statistically significant (p < 0.001). Mean MRD1 at the 1st postoperative week was 4.95 ± 0.37 mm in group A and 4.08 ± 0.64 mm in group B. This difference was highly statistically significant (P < 0.001). Overcorrection was seen in 8 (40%) eyes in group A and 1 (5%) eye in group B. The difference was statistically significant between the two groups (p = 0.008). Undercorrection was seen in only 1 (5%) eye in group B. No other complications were reported. Surgical success was achieved in 12 (60%) eyes in group A versus 18 (90%) eyes in group B. The difference between the two groups was statistically significant (p = 0.03).

Conclusion

our novel nomogram for the calculation of the amount levator muscle plication in congenital blepharoptosis surgery is effective in achieving a satisfactory postoperative MRD1.
Clinical manifestations and EEG findings in children infected with COVID-19 and exhibiting neurological symptoms
Authors: Yang Yue , Yu Tao , Yang Jie , Luo Jia , Liu Xuan , Mu Chong , Wang Xiaochuan , Deng Yao , Luo Rong
Published: January 2024

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection has many neurological manifestations, and its effects on the nervous system are increasingly recognized. There has been no systematic analysis of electroencephalography (EEG) characteristics in children exhibiting neurological symptoms of Coronavirus disease 2019 (COVID-19). The primary aim of this study was to describe the EEG characteristics caused by COVID-19 infection in children who were showing neurological symptoms and to assess the relationship between COVID-19-related EEG changes and clinical features in these children. Method: This study included 125 pediatric patients infected with SARS-CoV2 and showing neurological symptoms, and their continuous EEG was recorded. In addition, the demographic and clinical characteristics of these patients were analyzed and the correlation between the two was investigated. Results: Abnormal EEG findings were detected in 31.20% (N = 39) of the patients. Abnormal discharges (43.59%) were the most common EEG abnormalities, followed by background abnormalities (41.03%). The proportion of patients diagnosed with febrile seizure was higher in the normal EEG group than in the abnormal EEG group (P = 0.002), while the opposite was true for epilepsy and encephalitis/encephalopathy (P = 0.016 and P = 0.003, respectively). The independent associated factors of abnormal EEG were age and total length of stay (P < 0.001 and P = 0.003, respectively). Non-specific EEG abnormalities were found in COVID-19-related encephalitis/encephalopathy. Conclusion: Our study corroborated that a small group of pediatric patients infected by COVID-19 and showing neurological symptoms may exhibit abnormal EEG. This study could help improve the understanding of clinical and EEG characteristics in children with COVID-19 and inform triage policies in other hospitals during the COVID-19 pandemic.
Myths and common misbeliefs about cervical cancer causation among Palestinian women: a national cross-sectional study
Authors: Elshami Mohamedraed , Abukmail Hanan , Thalji Mariam , Al-Slaibi Ibrahim , Alser Mohammed , Radaydeh Afnan , Alfuqaha Alaa , Khader Salma , Khatib Lana , Fannoun Nour , Ahmad Bisan , Kassab Lina , Khrishi Hiba , Elhussaini Deniz , Abed Nour , Nammari Aya , Abdallah Tumodir , Alqudwa Zaina , Idais Shahd , Tanbouz Ghaid , Hajajreh Ma’alem , Selmiyh Hala Abu , Abo-Hajouj Zakia , Hebi Haya , Zamel Manar , Skaik Refqa Najeeb , Hammoud Lama , Rjoub Saba , Ayesh Hadeel , Rjoub Toqa , Zakout Rawan , Alser Amany , Albarqi Shurouq I. , Abu-El-Noor Nasser , Bottcher Bettina
Published: January 2024

Background

Cervical cancer (CC) myths and beliefs can negatively impact women's preventive behaviors, including vaccination against human papillomavirus and having regular screening tests. This study aimed to examine awareness of Palestinian women about myths related to CC causation and investigated factors associated with good awareness.

Methods

A national cross-sectional study was conducted to recruit adult Palestinian women from hospitals, primary healthcare facilities, and public areas in 11 Palestinian governorates. A translated-into-Arabic version of the Cancer Awareness Measure-Mythical Causes Scale was used to collect data. Awareness level was determined based on the number of CC myths around CC causation recognized to be incorrect: poor (0–4), fair (5–9), and good (10–13).

Results

A total of 7058 questionnaires were included. Myths unrelated to food were more commonly recognized as incorrect compared to those related to food. The most recognized food-unrelated myth was ‘having a physical trauma’ (n = 3714, 52.6%), whereas the least recognized was ‘using mobile phones’ (n = 2238, 31.7%). The most recognized food-related myth was ‘drinking from plastic bottles’ (n = 2708, 38.4%), whereas the least recognized was ‘eating food containing additives’ (n = 1118, 15.8%).

Only 575 participants (8.1%) displayed good awareness and promptly recognized at least 10 out of 13 myths around CC causation as incorrect. Factors associated with lower likelihood of displaying good awareness of myths around CC causation included living in the West Bank and Jerusalem, being married, widowed or divorced, knowing someone with cancer, and visiting hospitals or primary healthcare centers.

Conclusions

A very small proportion of Palestinian women recognized 10 or more myths around CC causes as incorrect. Initiatives addressing CC myths are needed in the Palestinian community.
Exploring barriers to using modern contraceptives and accessing safe abortion care in women who terminated unintended pregnancies in Southern Ethiopia
Authors: Woldetsadik Mahlet A. , Yoseph Yeshihareg , Degu Mekonnen
Published: January 2024

Background

Unsafe abortion is a major medical and public health problem in Ethiopia and contributes significantly to abortion-related morbidity and mortality in the country. We explored women’s experiences with modern contraceptives and identified barriers to accessing safe abortion care and other sexual and reproductive health services.

Methods

We recruited participants from six health clinics and a public hospital in southern Ethiopia. We conducted one-on-one interviews with 34 women aged 18–49 years who sought abortion care within the past twelve months of the study. Interviews were recorded, transcribed verbatim, translated to English, and imported into Dedoose software. We analysed the data using a directed content analysis.

Results

Our findings show prevailing belief among participants that contraceptives caused infertility, abnormalities in subsequent pregnancies, and other side effects. Some of the women suggested that medical or unsafe abortions were a better alternative to using modern contraceptives for terminating unplanned pregnancies. Barriers to accessing safe abortion care included costs of services, lack of privacy, and fear of judgment from providers. Women who had negative experiences with providers were more likely to seek unsafe abortion the second time around.

Conclusion

Providers need to address women’s concerns about using modern contraceptives, educate their clients about the best ways to prevent unwanted pregnancies, and provide non-judgemental services. In addition, comprehensive counselling services that include contraceptive counselling should be made available to women before, during, and after abortion care. Finally, providers should strive to be facilitators of, not barriers to, safe abortion care.
USP5 facilitates bladder cancer progression by stabilizing the c-Jun protein
Authors: Zhang Hui-hui , Zhang An-qi , Peng Peng , Huang Liang , Liu Cai-ying , Nie Xin-rui , Hou De-fu , Zhang Xia , Li Shang-ze
Published: January 2024

Background

Bladder cancer is the second most common genitourinary malignancy worldwide. The death rate of bladder cancer has increased every year. However, the molecular mechanism of bladder cancer is not sufficiently studied. Deubiquitinating enzymes (DUBs) play an important role in carcinogenesis. Several studies have demonstrated that USP5 associated with malignancy and pathological progression in hepatocellular carcinoma, colorectal and non-small cell lung cancer. However, the role of USP5 in bladder cancer need to be explored.

Methods

The USP5 expression was analysed using the web server GEPIA. To explore USP5 function in bladder cancer, we constructed USP5-knockout cell lines in T24 cells. A FLAG-USP5 (WT USP5) plasmid and a plasmid FLAG-USP5 C335A (catalytic-inactive mutant) used to overexpress USP5 in EJ cells. CCK8, colony formation, transwell and scratch assays were used to assess cell viability, proliferation and migration. RNA sequencing (RNA-seq) and dual-luciferase reporter assays were performed to screen the pathway. Coimmunoprecipitation and immunofluorescence were used to explore the interaction between USP5 and c-Jun. Cycloheximide (CHX) chase assays were performed to establish the effect of USP5 on c-Jun stability. Xenograft mouse model was used to study the role of USP5 in bladder cancer.

Results

USP5 expression is increased in bladder cancer patients. Genetic ablation of USP5 markedly inhibited bladder cancer cell proliferation, viability, and migration both in vitro and in vivo. RNA-seq and luciferase pathway screening showed that USP5 activated JNK signalling, and we identified the interaction between USP5 and c-Jun. USP5 was found to activate c-Jun by inhibiting its ubiquitination.

Conclusions

Our results show that high USP5 expression promotes bladder cancer progression by stabilizing c-Jun and that USP5 is a potential therapeutic target in bladder cancer.
Improving economic access to healthy diets in first nations communities in high-income, colonised countries: a systematic scoping review
Authors: Lee Amanda J. , Herron Lisa-Maree , Rainow Stephan , Wells Lisa , Kenny Ingrid , Kenny Leon , Wells Imogen , Kavanagh Margaret , Bryce Suzanne , Balmer Liza
Published: January 2024

Background

Affordability of healthy food is a key determinant of the diet-related health of First Nations Peoples. This systematic scoping review was commissioned by the Ngaanyatjarra Pitjantjatjara Yankunytjatjara Women’s Council (NPYWC) in Central Australia to identify interventions to improve economic access to healthy food in First Nations communities in selected high-income, colonised countries.

Methods

Eight databases and 22 websites were searched to identify studies of interventions and policies to improve economic access to healthy food in First Nations communities in Australia, Canada, the United States or New Zealand from 1996 to May 2022. Data from full text of articles meeting inclusion criteria were extracted to a spreadsheet. Results were collated by descriptive synthesis. Findings were examined with members of the NPYWC Anangu research team at a co-design workshop.

Results

Thirty-five publications met criteria for inclusion, mostly set in Australia (37%) or the US (31%). Interventions (n = 21) were broadly categorised as price discounts on healthy food sold in communities (n = 7); direct subsidies to retail stores, suppliers and producers (n = 2); free healthy food and/or food vouchers provided to community members (n = 7); increased financial support to community members (n = 1); and other government strategies (n = 4).

Promising initiatives were: providing a box of food and vouchers for fresh produce; prescriptions for fresh produce; provision/promotion of subsidised healthy meals and snacks in community stores; direct funds transfer for food for children; offering discounted healthy foods from a mobile van; and programs increasing access to traditional foods. Providing subsidies directly to retail stores, suppliers and producers was least effective.

Identified enablers of effective programs included community co-design and empowerment; optimal promotion of the program; and targeting a wide range of healthy foods, particularly traditional foods where possible. Common barriers in the least successful programs included inadequate study duration; inadequate subsidies; lack of supporting resources and infrastructure for cooking, food preparation and storage; and imposition of the program on communities.

Conclusions

The review identified 21 initiatives aimed at increasing affordability of healthy foods in First Nations communities, of which six were deemed promising. Five reflected the voices and experiences of members of the NPYWC Anangu research team and will be considered by communities for trial in Central Australia. Findings also highlight potential approaches to improve economic access to healthy foods in First Nations communities in other high-income colonised countries.

Trial registration

PROSPERO CRD42022328326.
Intracellular delivery of Parkin-RING0-based fragments corrects Parkin-induced mitochondrial dysfunction through interaction with SLP-2
Authors: Zanon Alessandra , Guida Marianna , Lavdas Alexandros A. , Corti Corrado , Castelo Rueda Maria Paulina , Negro Alessandro , Pramstaller Peter P. , Domingues Francisco S. , Hicks Andrew A. , Pichler Irene
Published: January 2024

Background

Loss-of-function mutations in the PRKN gene, encoding Parkin, are the most common cause of autosomal recessive Parkinson’s disease (PD). We have previously identified mitoch

ondrial Stomatin-like protein 2 (SLP-2), which functions in the assembly of respiratory chain proteins, as a Parkin-binding protein. Selective knockdown of either Parkin or SLP-2 led to reduced mitochondrial and neuronal function in neuronal cells and Drosophila, where a double knockdown led to a further worsening of Parkin-deficiency phenotypes. Here, we investigated the minimal Parkin region involved in the Parkin-SLP-2 interaction and explored the ability of Parkin-fragments and peptides from this minimal region to restore mitochondrial function.

Methods

In fibroblasts, human induced pluripotent stem cell (hiPSC)-derived neurons, and neuroblastoma cells the interaction between Parkin and SLP-2 was investigated, and the Parkin domain responsible for the binding to SLP-2 was mapped. High resolution respirometry, immunofluorescence analysis and live imaging were used to analyze mitochondrial function.

Results

Using a proximity ligation assay, we quantitatively assessed the Parkin-SLP-2 interaction in skin fibroblasts and hiPSC-derived neurons. When PD-associated PRKN mutations were present, we detected a significantly reduced interaction between the two proteins. We found a preferential binding of SLP-2 to the N-terminal part of Parkin, with a highest affinity for the RING0 domain. Computational modeling based on the crystal structure of Parkin protein predicted several potential binding sites for SLP-2 within the Parkin RING0 domain. Amongst these, three binding sites were observed to overlap with natural PD-causing missense mutations, which we demonstrated interfere substantially with the binding of Parkin to SLP-2. Finally, delivery of the isolated Parkin RING0 domain and a Parkin mini-peptide, conjugated to cell-permeant and mitochondrial transporters, rescued compromised mitochondrial function in Parkin-deficient neuroblastoma cells and hiPSC-derived neurons with endogenous, disease causing PRKN mutations.

Conclusions

These findings place further emphasis on the importance of the protein–protein interaction between Parkin and SLP-2 for the maintenance of optimal mitochondrial function. The possibility of restoring an abolished binding to SLP-2 by delivering the Parkin RING0 domain or the Parkin mini-peptide involved in this specific protein–protein interaction into cells might represent a novel organelle-specific therapeutic approach for correcting mitochondrial dysfunction in Parkin-linked PD.
A benchmarking framework for the accurate and cost-effective detection of clinically-relevant structural variants for cancer target identification and diagnosis
Authors: Zhuang Guiwu , Zhang Xiaotao , Du Wenjing , Xu Libin , Ma Jiyong , Luo Haitao , Tang Hongzhen , Wang Wei , Wang Peng , Li Miao , Yang Xu , Wu Dongfang , Fang Shencun
Published: January 2024

Background

Accurate clinical structural variant (SV) calling is essential for cancer target identification and diagnosis but has been historically challenging due to the lack of ground truth for clinical specimens. Meanwhile, reduced clinical-testing cost is the key to the widespread clinical utility.

Methods

We analyzed massive data from tumor samples of 476 patients and developed a computational framework for accurate and cost-effective detection of clinically-relevant SVs. In addition, standard materials and classical experiments including immunohistochemistry and/or fluorescence in situ hybridization were used to validate the developed computational framework.

Results

We systematically evaluated the common algorithms for SV detection and established an expert-reviewed SV call set of 1,303 tumor-specific SVs with high-evidence levels. Moreover, we developed a random-forest-based decision model to improve the true positive of SVs. To independently validate the tailored ‘two-step’ strategy, we utilized standard materials and classical experiments. The accuracy of the model was over 90% (92–99.78%) for all types of data.

Conclusion

Our study provides a valuable resource and an actionable guide to improve cancer-specific SV detection accuracy and clinical applicability.
Tissue engineering RPE sheet derived from hiPSC-RPE cell spheroids supplemented with Y-27632 and RepSox
Authors: Wang Wenxuan , Yang Tingting , Chen Sihui , Liang Liying , Wang Yingxin , Ding Yin , Xiong Wei , Ye Xiuhong , Guo Yonglong , Shen Shuhao , Chen Hang , Chen Jiansu
Published: January 2024

Background

Retinal pigment epithelium (RPE) cell therapy is a promising way to treat many retinal diseases. However, obtaining transplantable RPE cells is time-consuming and less effective. This study aimed to develop novel strategies for generating engineered RPE patches with physiological characteristics.

Results

Our findings revealed that RPE cells derived from human induced pluripotent stem cells (hiPSCs) successfully self-assembled into spheroids. The RPE spheroids treated with Y27632 and Repsox had increased expression of epithelial markers and RPE-specific genes, along with improved cell viability and barrier function. Transcriptome analysis indicated enhanced cell adhesion and extracellular matrix (ECM) organization in RPE spheroids. These RPE spheroids could be seeded and bioprinted on collagen vitrigel (CV) membranes to construct engineered RPE sheets. Circular RPE patches, obtained by trephining a specific section of the RPE sheet, exhibited abundant microvilli and pigment particles, as well as reduced proliferative capacity and enhanced maturation.

Conclusions

Our study suggests that the supplementation of small molecules and 3D spheroid culture, as well as the bioprinting technique, can be effective methods to promote RPE cultivation and construct engineered RPE sheets, which may support future clinical RPE cell therapy and the development of RPE models for research applications.
LncRNA AL139294.1 can be transported by extracellular vesicles to promote the oncogenic behaviour of recipient cells through activation of the Wnt and NF-κB2 pathways in non-small-cell lung cancer
Authors: Ma Xinyi , Chen Zhenhua , Chen Wei , Chen Ziyuan , Shang Yue , Zhao Yikai , Li Leyi , Zhou Chengwei , He Jinxian , Meng Xiaodan
Published: January 2024

Background

Extracellular vesicles (EVs) participate in cancer development via cell-to-cell communication. Long non-coding RNAs (lncRNAs), one component of EVs, can play an essential role in non-small-cell lung cancer (NSCLC) through EV-mediated delivery.

Methods

The NSCLC-associated lncRNA AL139294.1 in EVs was identified via lncRNA microarray analysis. The role of AL139294.1 in NSCLC was examined in vitro and in vivo. Confocal microscopy was used to observe the encapsulation of AL139294.1 into EVs and its transport to recipient cells. A co-culture device was used to examine the effects of transported AL139294.1 on the oncogenic behaviour of recipient cells. Dual-luciferase reporter assay was performed to verify the direct interaction of miR-204-5p with AL139294.1 and bromodomain-containing protein 4 (BRD4). AL139294.1 and miR-204-5p in EVs were quantified using quantitative polymerase chain reaction. Receiver operating characteristic analyses were conducted to evaluate the diagnostic efficiency.

Results

The lncRNA AL139294.1 in EVs promoted NSCLC progression in vitro and in vivo. After AL139294.1 was encapsulated into EVs and transported to recipient cells, it promoted the cells’ proliferation, migration, and invasion abilities by competitively binding with miR-204-5p to regulate BRD4, leading to the activation of the Wnt and NF-κB2 pathways. Additionally, the expression of serum lncRNA AL139294.1 in EVs was increased, whereas miR-204-5p in EVs was decreased in NSCLC. High levels of lncRNA AL139294.1 and low levels of miR-204-5p in EVs were associated with advanced pathological staging, lymph node metastasis, and distant metastasis, underscoring their promising utility for distinguishing between more and less severe manifestations of the disease.

Conclusions

This study reveals a novel lncRNA in EVs associated with NSCLC, namely, AL139294.1, providing valuable insights into the development of NSCLC and introducing potential diagnostic biomarkers for NSCLC.
Bisphenol A triggers apoptosis in mouse pre-antral follicle granulosa cells via oxidative stress
Authors: Wang Chen , He Chaofan , Xu Shumin , Gao Yuanyuan , Wang Kaixian , Liang Meng , Hu Ke
Published: January 2024

Background

Bisphenol A (BPA), an endocrine disrupting chemical with weak estrogenic and anti-androgenic activity, is widely present in various environmental media and organisms. It has certain reproductive toxicity and can cause a variety of female reproductive system diseases. Although BPA-stimulated apoptosis of granulosa cells has been widely elaborated, the effect of BPA on mouse pre-antral follicle granulosa cells (mpGCs) has not been well elucidated.

Results

In this study, the results of live-dead cell staining showed that high concentrations of BPA severely impaired mpGCs growth viability and affected the cell cycle transition of mpGCs. We confirmed that BPA promotes the production of reactive oxygen species (ROS) and facilitates oxidative stress in mpGCs. In addition, immunofluorescence, transmission electron microscopy, and flow cytometry experiments demonstrated that BPA treatment for mpGCs resulted in apoptotic features, such as rounding, cytoplasmic crinkling, and mitochondrial damage. This was accompanied by a large production of ROS and apoptosis-inducing factor (AIF) translocation from the mitochondria to the nucleus. RNA-seq data showed that several apoptosis-related pathways were enriched in the high concentration BPA-treated group compared with the normal group, such as the p53 pathway, MAPK pathway, etc.

Conclusions

These results suggest that cells undergo oxidative stress effects and apoptosis after BPA treatment for mpGCs, which affects normal follicle development. The potential mechanism of BPA-induced female reproductive toxicity was elucidated, while providing a research basis for the prevention and treatment of female reproductive diseases.
Virus-like particle vaccine displaying an external, membrane adjacent MUC16 epitope elicits ovarian cancer-reactive antibodies
Authors: Tu Hsin-Fang , Wong Margaret , Tseng Ssu-Hsueh , Ingavat Nattha , Olczak Pola , Notarte Kin Israel , Hung Chien-fu , Roden Richard B.S.
Published: January 2024

Background

MUC16 is a heavily glycosylated cell surface mucin cleaved in the tumor microenvironment to shed CA125. CA125 is a serum biomarker expressed by > 95% of non-mucinous advanced stage epithelial ovarian cancers. MUC16/CA125 contributes to the evasion of anti-tumor immunity, peritoneal spread and promotes carcinogenesis; consequently, it has been targeted with antibody-based passive and active immunotherapy. However, vaccination against this self-antigen likely requires breaking B cell tolerance and may trigger autoimmune disease. Display of self-antigens on virus-like particles (VLPs), including those produced with human papillomavirus (HPV) L1, can efficiently break B cell tolerance.

Results

A 20 aa juxta-membrane peptide of the murine MUC16 (mMUC16) or human MUC16 (hMUC16) ectodomain was displayed either via genetic insertion into an immunodominant loop of HPV16 L1-VLPs between residues 136/137, or by chemical coupling using malemide to cysteine sulfhydryl groups on their surface. Female mice were vaccinated intramuscularly three times with either DNA expressing L1-MUC16 fusions via electroporation, or with alum-formulated VLP chemically-coupled to MUC16 peptides. Both regimens were well tolerated, and elicited MUC16-specific serum IgG, although titers were higher in mice vaccinated with MUC16-coupled VLP on alum as compared to L1-MUC16 DNA vaccination. Antibody responses to mMUC16-targeted vaccination cross-reacted with hMUC16 peptide, and vice versa; both were reactive with the surface of CA125+ OVCAR3 cells, but not SKOV3 that lack detectable CA125 expression. Interestingly, vaccination of mice with mMUC16 peptide mixed with VLP and alum elicited mMUC16-specific IgG, implying VLPs provide robust T help and that coupling may not be required to break tolerance to this epitope.

Conclusion

Vaccination with VLP displaying the 20 aa juxta-membrane MUC16 ectodomain, which includes the membrane proximal cleavage site, is likely to be well tolerated and induce IgG targeting ovarian cancer cells, even after CA125 is shed.
Evidence of steady-state fibroblast subtypes in the normal human breast as cells-of-origin for perturbed-state fibroblasts in breast cancer
Authors: Bagger Mikkel Morsing , Sjölund Jonas , Kim Jiyoung , Kohler Katharina Theresa , Villadsen René , Jafari Abbas , Kassem Moustapha , Pietras Kristian , Rønnov-Jessen Lone , Petersen Ole William
Published: January 2024

Background

Human breast cancer most frequently originates within a well-defined anatomical structure referred to as the terminal duct lobular unit (TDLU). This structure is endowed with its very own lobular fibroblasts representing one out of two steady-state fibroblast subtypes—the other being interlobular fibroblasts. While cancer-associated fibroblasts (CAFs) are increasingly appreciated as covering a spectrum of perturbed states, we lack a coherent understanding of their relationship—if any—with the steady-state fibroblast subtypes. To address this, we here established two autologous CAF lines representing inflammatory CAFs (iCAFs) and myofibroblast CAFs (myCAFs) and compared them with already established interlobular- and lobular fibroblasts with respect to their origin and impact on tumor formation.

Methods

Primary breast tumor-derived CAFs were transduced to express human telomerase reverse transcriptase (hTERT) and sorted into CD105low and CD105high populations using fluorescence-activated cell sorting (FACS). The two populations were tested for differentiation similarities to iCAF and myCAF states through transcriptome-wide RNA-Sequencing (RNA-Seq) including comparison to an available iCAF-myCAF cell state atlas. Inference of origin in interlobular and lobular fibroblasts relied on RNA-Seq profiles, immunocytochemistry and growth characteristics. Osteogenic differentiation and bone formation assays in culture and in vivo were employed to gauge for origin in bone marrow-derived mesenchymal stem cells (bMSCs). Functional characteristics were assessed with respect to contractility in culture and interaction with tumor cells in mouse xenografts. The cells’ gene expression signatures were tested for association with clinical outcome of breast cancer patients using survival data from The Cancer Genome Atlas database.

Results

We demonstrate that iCAFs have properties in common with interlobular fibroblasts while myCAFs and lobular fibroblasts are related. None of the CAFs qualify as bMSCs as revealed by lack of critical performance in bone formation assays. Functionally, myCAFs and lobular fibroblasts are almost equally tumor promoting as opposed to iCAFs and interlobular fibroblasts. A myCAF gene signature is found to associate with poor breast cancer-specific survival.

Conclusions

We propose that iCAFs and myCAFs originate in interlobular and lobular fibroblasts, respectively, and more importantly, that the tumor-promoting properties of lobular fibroblasts render the TDLU an epicenter for breast cancer evolution.
Molecular imaging for evaluation of synovitis associated with osteoarthritis: a narrative review
Authors: Lee Kwanghoon , Niku Soheil , Koo Sonya J. , Belezzuoli Ernest , Guma Monica
Published: January 2024

Recent evidence highlights the role of low-grade synovial inflammation in the progression of osteoarthritis (OA). Inflamed synovium of OA joints detected by imaging modalities are associated with subsequent progression of OA. In this sense, detecting and quantifying synovitis of OA by imaging modalities may be valuable in predicting OA progressors as well as in improving our understanding of OA progression. Of the several imaging modalities, molecular imaging such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) has an advantage of visualizing the cellular or subcellular events of the tissues. Depending on the radiotracers used, molecular imaging method can potentially detect and visualize various aspects of synovial inflammation. This narrative review summarizes the recent progresses of imaging modalities in assessing inflammation and OA synovitis and focuses on novel radiotracers. Recent studies about imaging modalities including ultrasonography (US), magnetic resonance imaging (MRI), and molecular imaging that were used to detect and quantify inflammation and OA synovitis are summarized. Novel radiotracers specifically targeting the components of inflammation have been developed. These tracers may show promise in detecting inflamed synovium of OA and help in expanding our understanding of OA progression.
Comparison of aloe vera gel dressing with conventional dressing on pressure ulcer pain reduction: a clinical trial
Authors: Malek Hosseini Azam , Rostam Khani Mohammad , Abdi Sina , Abdi Siavash , Sharifi Nader
Published: January 2024

Background

Aloe Vera has a strong analgesic and anti-inflammatory effect, and its use effectively controls pain. This study aimed to determine the effect of Aloe Vera gel versus saline on pain relief of pressure ulcers.

Methods

This study is a double-blind, randomized clinical trial conducted in Valiasr Hospital in Arak, Markazi Province, in the center of Iran from May 2020 to April 2022. Using the available sampling method, 95 patients with pressure ulcers were assessed for eligibility, 64 patients were selected, 33 patients were placed in the experimental and 34 patients in control. For the experimental group, the ulcers were first cleaned with normal saline to remove the slough and then the already prepared Aloe Vera gel was evenly applied. For control groups, the ulcers were first washed with normal saline to remove off the slough and then covered with a sterile cotton gage, and the wound was tightly bandaged with a cotton roll to keep the “daily dressing” in place. A visual pain scale was used to assess the patient’s pain level. Data analysis was done using SPSS 17. Descriptive statistics, ANOVA, and greenhouse tests were used. The significance level was 0.05.

Results

The results showed that the average pain score in both groups had a downward trend; that is, both dressings effectively reduced pressure ulcer pain (P < 0.001). The greenhouse test results showed that the difference between the two groups was significant (P < 0.001).

Conclusion

The results showed the effect of Aloe Vera gel in reducing pressure ulcer pain. Dressing with Aloe Vera gel is preferable to reducing pain during dressing changes in patients with pressure ulcers.

Trial registration

Iranian Registry of Clinical Trials IRCT20180715040478N2, 2021-08-17.