bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison of RNA-Seq data preprocessing pipelines for transcriptomic predictions across independent studies
Authors: Van Richard , Alvarez Daniel , Mize Travis , Gannavarapu Sravani , Chintham Reddy Lohitha , Nasoz Fatma , Han Mira V.
Published: May 2024

Background

RNA sequencing combined with machine learning techniques has provided a modern approach to the molecular classification of cancer. Class predictors, reflecting the disease class, can be constructed for known tissue types using the gene expression measurements extracted from cancer patients. One challenge of current cancer predictors is that they often have suboptimal performance estimates when integrating molecular datasets generated from different labs. Often, the quality of the data is variable, procured differently, and contains unwanted noise hampering the ability of a predictive model to extract useful information. Data preprocessing methods can be applied in attempts to reduce these systematic variations and harmonize the datasets before they are used to build a machine learning model for resolving tissue of origins.

Results

We aimed to investigate the impact of data preprocessing steps—focusing on normalization, batch effect correction, and data scaling—through trial and comparison. Our goal was to improve the cross-study predictions of tissue of origin for common cancers on large-scale RNA-Seq datasets derived from thousands of patients and over a dozen tumor types. The results showed that the choice of data preprocessing operations affected the performance of the associated classifier models constructed for tissue of origin predictions in cancer.

Conclusion

By using TCGA as a training set and applying data preprocessing methods, we demonstrated that batch effect correction improved performance measured by weighted F1-score in resolving tissue of origin against an independent GTEx test dataset. On the other hand, the use of data preprocessing operations worsened classification performance when the independent test dataset was aggregated from separate studies in ICGC and GEO. Therefore, based on our findings with these publicly available large-scale RNA-Seq datasets, the application of data preprocessing techniques to a machine learning pipeline is not always appropriate.
Environmental specificity of karst cave habitats evidenced by diverse symbiotic bacteria in Opiliones
Authors: Zhao Likun , Xiao Ruoyi , Zhang Shanfeng , Zhang Chao , Zhang Feng
Published: May 2024

Background

Karst caves serve as natural laboratories, providing organisms with extreme and constant conditions that promote isolation, resulting in a genetic relationship and living environment that is significantly different from those outside the cave. However, research on cave creatures, especially Opiliones, remains scarce, with most studies focused on water, soil, and cave sediments.

Results

The structure of symbiotic bacteria in different caves were compared, revealing significant differences. Based on the alpha and beta diversity, symbiotic bacteria abundance and diversity in the cave were similar, but the structure of symbiotic bacteria differed inside and outside the cave. Microorganisms in the cave play an important role in material cycling and energy flow, particularly in the nitrogen cycle. Although microbial diversity varies inside and outside the cave, Opiliones in Beijing caves and Hainan Island exhibited a strong similarity, indicating that the two environments share commonalities.

Conclusions

The karst cave environment possesses high microbial diversity and there are noticeable differences among different caves. Different habitats lead to significant differences in the symbiotic bacteria in Opiliones inside and outside the cave, and cave microorganisms have made efforts to adapt to extreme environments. The similarity in symbiotic bacteria community structure suggests a potential similarity in host environments, providing an explanation for the appearance of Sinonychia martensi in caves in the north.
Genome-wide identification, molecular evolution and gene expression of P450 gene family in Cyrtotrachelus buqueti
Authors: Fu Chun , Yang Ding , Long Wen Cong , Xiao XiMeng , Wang HanYu , Jiang Na , Yang YaoJun
Published: May 2024

Background

Insect Cytochrome P450 monooxygenase (CYPs or P450s) plays an important role in detoxifying insecticides, causing insect populations to develop resistance. However, the molecular functions of P450 gene family in Cyrtotrachelus buqueti genome are still lacking.

Results

In this study, 71 CbuP450 genes have been identified. The amino acids length of CbuP450 proteins was between 183 aa ~ 1041 aa. They are proteins with transmembrane domains. The main component of their secondary structure is α-helix and random coils. Phylogenetic analysis showed that C. buqueti and Rhynchophorus ferrugineus were the most closely related. This gene family has 29 high-frequency codons, which tend to use A/T bases and A/T ending codons. Gene expression analysis showed that CbuP450_23 in the female adult may play an important role on high temperature resistance, and CbuP450_17 in the larval may play an important role on low temperature tolerance. CbuP450_10, CbuP450_17, CbuP450_23, CbuP450_10, CbuP450_16, CbuP450_20, CbuP450_23 and CbuP450_ 29 may be related to the regulation of bamboo fiber degradation genes in C. buqueti. Protein interaction analysis indicates that most CbuP450 proteins are mainly divided into three aspects: encoding the biosynthesis of ecdysteroids, participating in the decomposition of synthetic insecticides, metabolizing insect hormones, and participating in the detoxification of compounds.

Conclusions

We systematically analyzed the gene and protein characteristics, gene expression, and protein interactions of CbuP450 gene family, revealing the key genes involved in the stress response of CbuP450 gene family in the resistance of C. buqueti to high or low temperature stress, and identified the key CbuP450 proteins involved in important life activity metabolism. These results provided a reference for further research on the function of P450 gene family in C. buqueti.
Genome-wide identification of WRKY transcription factors in Casuarina equisetifolia and the function analysis of CeqWRKY11 in response to NaCl/NaHCO3 stresses
Authors: Zhao Xiaohong , Qi Guoning , Liu Jinhong , Chen Kui , Miao Xinxin , Hussain Jamshaid , Liu Shenkui , Ren Huimin
Published: May 2024

Background

Casuarina equisetifolia (C. equisetifolia) is a woody species with many excellent features. It has natural resistance against drought, salt and saline-alkali stresses. WRKY transcription factors (TFs) play significant roles in plant response to abiotic stresses, therefore, molecular characterization of WRKY gene family under abiotic stresses holds great significance for improvement of forest trees through molecular biological tools. At present, WRKY TFs from C. equisetifolia have not been thoroughly studied with respect to their role in salt and saline-alkali stresses response. The current study was conducted to bridge the same knowledge gap.

Results

A total of 64 WRKYs were identified in C. equisetifolia and divided into three major groups i.e. group I, II and III, consisting of 10, 42 and 12 WRKY members, respectively. The WRKY members in group II were further divided into 5 subgroups according to their homology with Arabidopsis counterparts. WRKYs belonging to the same group exhibited higher similarities in gene structure and the presence of conserved motifs. Promoter analysis data showed the presence of various response elements, especially those related to hormone signaling and abiotic stresses, such as ABRE (ABA), TGACG (MeJA), W-box ((C/T) TGAC (T/C)) and TC-rich motif. Tissue specific expression data showed that CeqWRKYs were mainly expressed in root under normal growth conditions. Furthermore, most of the CeqWRKYs were up-regulated by NaCl and NaHCO3 stresses with few of WRKYs showing early responsiveness to both stresses while few others exhibiting late response. Although the expressions of CeqWRKYs were also induced by cold stress, the response was delayed compared with other stresses. Transgenic C. equisetifolia plants overexpressing CeqWRKY11 displayed lower electrolyte leakage, higher chlorophyll content, and enhanced tolerance to both stresses. The higher expression of abiotic stress related genes, especially CeqHKT1 and CeqPOD7, in overexpression lines points to the maintenance of optimum Na+/K+ ratio, and ROS scavenging as possible key molecular mechanisms underlying salt stress tolerance.

Conclusions

Our results show that CeqWRKYs might be key regulators of NaCl and NaHCO3 stresses response in C. equisetifolia. In addition, positive correlation of CeqWRKY11 expression with increased stress tolerance in C. equisetifolia encourages further research on other WRKY family members through functional genomic tools. The best candidates could be incorporated in other woody plant species for improving stress tolerance.
Examining the immunological responses to COVID-19 vaccination in multiple myeloma patients: a systematic review and meta-analysis
Authors: Harandi Hamid , Fallahtafti Parisa , Karimi Amirali , Hashemi Seyedeh Melika , Mahalleh Mehrdad , Ashouri Moein , Salehi Mohammad Amin , Hoveidaei Armin
Published: May 2024

Background

Impaired immune response in multiple myeloma renders the patients vulnerable to infections, such as COVID-19, and may cause worse response to vaccines. Researchers should analyze this issue to enable the planning for special preventive measures, such as increased booster doses. Therefore, this meta-analysis aimed to evaluate the response and efficacy of COVID-19 vaccines in patients with multiple myeloma.

Methods

This meta-analysis followed PRISMA 2020 guidelines, conducting a comprehensive database search using specified keywords. Study selection involved a two-phase title/abstract and full-text screening process. Data extraction was performed by two researchers, and statistical analysis involved meta-analysis, subgroup analysis based on vaccine dosage and study time, random effects meta-regression, and heterogeneity testing using the Q test.

Results

The meta-analysis revealed that patients with multiple myeloma (MM) had a lower likelihood of developing detectable antibodies after COVID-19 vaccination compared to healthy controls (Log odds ratio with 95% CI: -3.34 [-4.08, -2.60]). The analysis of antibody response after different doses showed consistent lower seropositivity in MM patients (after first dose: -2.09, [-3.49, -0.69], second: -3.80, 95%CI [-4.71, -3.01], a booster dose: -3.03, [-5.91, -0.15]). However, there was no significant difference in the mean level of anti-S antibodies between MM patients and controls (Cohen’s d -0.72, [-1.86, 0.43]). Evaluation of T-cell responses indicated diminished T-cell-mediated immunity in MM patients compared to controls. Seven studies reported clinical response, with breakthrough infections observed in vaccinated MM patients.

Conclusions

These findings highlight the impaired humoral and cellular immune responses in MM patients after COVID-19 vaccination, suggesting the need for further investigation and potential interventions.
Validating interRAI Chinese self-reported carer needs (SCaN) assessment and predicting caregiving distress among informal Chinese caregivers of older adults
Authors: Xu Shicheng , Lou Vivian W. Q. , Chi Iris , Ng Wai Chong , Zhou Jing , Huang Lung-Kuan , Hok Ka Ma Carol , Jagasia Moana
Published: May 2024

Background

This study aims to (1) determine the reliability and validity of the interRAI Chinese Self-reported Carer Needs (SCaN) assessment among informal Chinese caregivers of older adults, (2) identify predictors of caregiving distress in Asian regions with long-standing Confucian values of filial piety and family responsibility.

Methods

This cross-sectional study recruited 531 informal Chinese caregivers of older adults in Hong Kong, Shanghai, Taiwan, and Singapore. The scale reliability was examined using Cronbach’s alphas (α) and McDonald’s omega coefficient (ω). The concurrent validity and discriminant validity were assessed using Spearman rank correlations (rho). To examine the predictors of caregiving distress among informal caregivers of older adults, we employed hierarchical linear regression analyses informed by the Model of Carer Stress and Burden and categorized the predictors into six domains.

Results

Results revealed good internal consistency reliability (α = 0.83–0.96) and concurrent validity (rho = 0.45–0.74) of the interRAI Chinese SCaN assessment. Hierarchical linear regression analysis revealed that entering the background factors, primary stressors, secondary stressors, appraisal, and exacerbating factors all significantly enhanced the model’s predictability, indicating that the source of caregiving distress is multidimensional. In the full model, caregivers with longer informal care time, lack of support from family and friends, have unmet needs, experience role overload, have sleep problems, and low IADL functioning are at a higher risk of caregiving distress.

Conclusions

The interRAI Chinese SCaN Assessment was found to be a reliable and valid tool among the Chinese informal caregivers of older adults. It would be useful for determining family caregivers’ strengths, needs, and challenges, and tailoring interventions that address the potentially modifiable factors associated with caregiving distress and maximize support. Healthcare providers working in home and community settings should be aware of the early identification of caregiving distress and routine assessment of their needs and empower them to continue taking care of their needs and providing adequate care to the care recipient.
Need for informed providers: exploring LA-PrEP access in focus groups with PrEP-indicated communities in Baltimore, Maryland
Authors: Kaptchuk Rose Pollard , Thomas Amber M. , Dhir Amit “Mickey” , Solomon Sunil S. , Clipman Steven J.
Published: May 2024

Background

The approval of long-acting pre-exposure prophylaxis PrEP (LA-PrEP) in the United States brings opportunities to overcome barriers of oral PrEP, particularly among sexual and gender minority communities who bear a higher HIV burden. Little is known about real-time decision-making among potential PrEP users of LA-PrEP post-licensure.

Methods

We held focus group discussions with people assigned male at birth who have sex with men in Baltimore, Maryland to explore decision-making, values, and priorities surrounding PrEP usage. A sexual and gender minority-affirming health center that provides PrEP services supported recruitment. Discussions included a pile-sorting activity and were audio-recorded. Recordings were transcribed and analyzed iteratively, combining an inductive and deductive approach.

Results

We held five focus groups from Jan-June 2023 with 23 participants (21 cisgender men who have sex with men, two transgender women who have sex with men; mean age 37). Among participants, 21 were on oral PrEP, one was on injectable PrEP, and one had never taken PrEP. Most had never heard about LA-PrEP. When making decisions about PrEP, participants particularly valued efficacy in preventing HIV, side effects, feeling a sense of security, and ease of use. Perceptions varied between whether oral or injectable PrEP was more convenient, but participants valued the new opportunity for a choice in modality. Factors influencing PrEP access included cost, individual awareness, provider awareness, and level of comfort in a healthcare environment. Participants emphasized how few providers are informed about PrEP, placing the burden of being informed about PrEP on them. Comfort and trust in a provider superseded proximity as considerations for if and where to access PrEP.

Conclusions

There is still low awareness about LA-PrEP among sexual and gender minority communities; thus, healthcare providers have a critical role in influencing access to LA-PrEP. Despite this, providers are still vastly underinformed about PrEP and underprepared to support clients in contextualized ways. Clients are more likely to engage in care with affirming providers who offer non-judgmental conversations about sex and life experiences. Provider education in the United States is urgently needed to better support clients in choosing a PrEP modality that is right for them and supporting adherence for effective HIV prevention.
Impact of COVID-19 pandemic on food availability and affordability: an interrupted time series analysis in Ghana
Authors: Kawakatsu Yoshito , Damptey Ohene , Sitor John , Situma Ruth , Aballo Jevaise , Shetye Mrunal , Aiga Hirotsugu
Published: May 2024

Background

In Africa, approx. 675 million people were at risk of food insecurity. COVID-19 pandemic is likely to have exacerbated this situation, by damaging populations’ access to and affordability of foods. This study is aimed at estimating the impacts of the COVID-19 pandemic on availability and prices of essential food commodities at 20 large markets in Ghana.

Methods

Data on food availability and food retail prices collected through weekly market-level data during the period from July 2017 to September 2020 were used in this study. We performed interrupted time-series analyses and estimated the percentage increases between the observed and predicted food prices by food group and by region to assess the impact of COVID-19 pandemic on food prices.

Results

As a result, the impact of COVID-19 on food availability was limited. However, the results of interrupted time-series analyses indicate a significant increase in overall mean food prices in Greater Accra, Eastern and Upper East regions. It was also found that mean price of starchy roots, tubers and plantains significantly increased across regions.

Discussion

The impact of COVID-19 pandemic on food availability and prices was significant but varied by food type and regions in Ghana. Continuous monitoring and responses are critical to maintain food availability and affordability.
Exploring dental professionals’ outlook on the future of dental care amidst the integration of artificial intelligence in dentistry: a pilot study in Pakistan
Authors: Qamar Wajiha , Khaleeq Nadia , Nisar Anita , Tariq Sahibzadi Fatima , Lajber Mehreen
Published: May 2024

Objective

The purpose of this study is to explore the perspectives, familiarity, and readiness of dental faculty members regarding the integration and application of artificial intelligence (AI) in dentistry, with a focus on the possible effects on dental education and clinical practice.

Methodology

In a mix-method cross-sectional quantitative and quantitative study conducted between June 1st and August 30th, 2023, the perspectives of faculty members from a public sector dental college in Pakistan regarding the function of AI were explored. This study used qualitative as well as quantitative techniques to analyse faculty’s viewpoints on the subject. The sample size was comprised of twenty-three faculty members. The quantitative data was analysed using descriptive statistics, while the qualitative data was analysed using theme analysis.

Results

Position-specific differences in faculty familiarity underscore the value of individualized instruction. Surprisingly few had ever come across AI concepts in their professional lives. Nevertheless, many acknowledged that AI had the potential to improve patient outcomes. The majority thought AI would improve dentistry education. Participants suggested a few dental specialties where AI could be useful.

Conclusion

The study emphasizes the significance of addressing in dental professionals’ knowledge gaps about AI. The promise of AI in dentistry calls for specialized training and teamwork between academic institutions and AI developers. Graduates of dentistry programs who use AI are better prepared to navigate shifting environments. The study highlights the positive effects of AI and the value of faculty involvement in maximizing its potential for better dental education and practice.
Children with palliative care needs – the landscape of the nordic countries
Authors: Winger Anette , Holmen Heidi , Birgisdóttir Dröfn , Lykke Camilla , Lövgren Malin , Neergaard Mette Asbjoern , Grönroos Marika , Kero Johanna , Kristinsdóttir Oddný , Pétursdóttir Ásta Bjarney , Castor Charlotte
Published: May 2024

Background

To strengthen palliative care for children in the Nordic countries, an updated status of current needs, resources, clinical services, education, and research is necessary to align and consolidate future research. A Nordic research collaboration initiative for children with palliative care needs was assembled in 2023. Building on this initiative, this paper presents an overview of pediatric palliative care (PPC) in the Nordic countries’ (a) population characteristics, (b) care models and setting of care, (c) education and training, and (d) research.

Methods

The Nordic initiative researchers collaboratively gathered and assessed available data on the characteristics of PPC within Denmark, Finland, Greenland, Iceland, Norway, the Faroe Islands, Sweden, and Åland. Data were compiled in a matrix with population characteristics, models- and setting of care, education and training, and areas of research in a Nordic context. The findings are narratively and descriptively presented, providing an overview of Nordic PPC.

Results

In total, the Nordic child population comprises around six million children (0–19 years), of which about 41.200 are estimated to be living with a life-limiting and/or life-threatening condition. Healthcare services are provided through various care models, ranging from specialized care to homecare settings. Overall, there remain few opportunities for education and training with some exceptions. Also, Nordic research within PPC has been shown to be a growing field although much remains to be done.

Conclusion

This overview is the first outline of the current PPC in Nordic countries. Although some differences remain important to acknowledge, overall, the strengths and challenges faced within PPC in the Nordic countries are comparable and call for joint action to increase evidence, services, and education to better serve the children, families, and healthcare personnel within PPC. Despite the varying structural premises for PPC, research endeavors aiming to provide evidence in this field seem increasing, timely and relevant for the Nordic countries, as well as the international context.
Experience of undergraduate nursing students participating in artificial intelligence + project task driven learning at different stages: a qualitative study
Authors: Kong Weijuan , Ning Yanhua , Ma Ting , Song Fei , Mao Yuxin , Yang Cailing , Li Xinjin , Guo Yahong , Liu Haiyan , Shi Jing , Liu Lingna
Published: May 2024

Background

Artificial intelligence is a growing phenomenon that will soon facilitate wide-scale changes in many professions, and is expected to play an important role in the field of medical education. This study explored the realistic feelings and experiences of nursing undergraduates participating in different stages of artificial intelligence + project task driven learning, and provide a basis for artificial intelligence participation in nursing teaching.

Methods

We conducted face-to-face semi-structured interviews with nursing undergraduates participating in Nursing Research Course which adopts artificial intelligence + project task driven learning from a medical university in Ningxia from September to November 2023, to understand their experience of using artificial intelligence for learning and the emotional changes at different stages. The interview guide included items about their personal experience and feelings of completing project tasks through dialogue with artificial intelligence, and suggestions for course content. Thematic analysis was used to analyze interview data. This study followed the COREQ checklist.

Results

According to the interview data, three themes were summarized. Undergraduate nursing students have different experiences in participating in artificial intelligence + project task driven learning at different stages, mainly manifested as diverse emotional experiences under initial knowledge deficiency, the individual growth supported by external forces during the adaptation period, and the expectations and suggestions after the birth of the results in the end period.

Conclusions

Nursing undergraduates can actively adapt to the integration of artificial intelligence into nursing teaching, dynamically observe students’ learning experience, strengthen positive guidance, and provide support for personalized teaching models, better leveraging the advantages of artificial intelligence participation in teaching.
Lower comorbidity scores and severity levels in Veterans Health Administration hospitals: a cross-sectional study
Authors: Dizon Matthew P. , Chow Adam , Ong Michael K. , Phibbs Ciaran S. , Vanneman Megan E. , Zhang Yue , Yoon Jean
Published: May 2024

Background

Previous studies found that documentation of comorbidities differed when Veterans received care within versus outside Veterans Health Administration (VHA). Changes to medical center funding, increased attention to performance reporting, and expansion of Clinical Documentation Improvement programs, however, may have caused coding in VHA to change.

Methods

Using repeated cross-sectional data, we compared Elixhauser-van Walraven scores and Medicare Severity Diagnosis Related Group (DRG) severity levels for Veterans’ admissions across settings and payers over time, utilizing a linkage of VHA and all-payer discharge data for 2012–2017 in seven US states. To minimize selection bias, we analyzed records for Veterans admitted to both VHA and non-VHA hospitals in the same year. Using generalized linear models, we adjusted for patient and hospital characteristics.

Results

Following adjustment, VHA admissions consistently had the lowest predicted mean comorbidity scores (4.44 (95% CI 4.34–4.55)) and lowest probability of using the most severe DRG (22.1% (95% CI 21.4%-22.8%)). In contrast, Medicare-covered admissions had the highest predicted mean comorbidity score (5.71 (95% CI 5.56–5.85)) and highest probability of using the top DRG (35.3% (95% CI 34.2%-36.4%)).

Conclusions

More effective strategies may be needed to improve VHA documentation, and current risk-adjusted comparisons should account for differences in coding intensity.
Opportunity and accessibility: an environmental scan of publicly available data repositories to address disparities in healthcare decision-making
Authors: Vinals Lydia , Radhakrishnan Amruta , Sarri Grammati
Published: May 2024

Background

Health disparities, starkly exposed and exacerbated by coronavirus disease 2019, pose a significant challenge to healthcare system access and health outcomes. Integrating health inequalities into health technology assessment calls for robust analytical methodologies utilizing disaggregated data to investigate and quantify the scope of these disparities. However, a comprehensive summary of population datasets that can be used for this purpose is lacking. The objective of this review was to identify publicly accessible health inequalities data repositories that are potential resources for healthcare decision-making and future health technology assessment submissions.

Methods

An environmental scan was conducted in June of 2023 of six international organizations (World Health Organization, Organisation for Economic Co-operation and Development, Eurostat, United Nations Inter-agency Group for Child Mortality Estimation, the United Nations Sustainable Development Goals, and World Bank) and 38 Organisation for Economic Co-operation and Development countries. The official websites of 42 jurisdictions, excluding non-English websites and those lacking English translations, were reviewed. Screening and data extraction were performed by two reviewers for each data repository, including health indicators, determinants of health, and health inequality metrics. The results were narratively synthesized.

Results

The search identified only a limited number of country-level health inequalities data repositories. The World Health Organization Health Inequality Data Repository emerged as the most comprehensive source of health inequality data. Some country-level data repositories, such as Canada’s Health Inequality Data Tool and England’s Health Inequality Dashboard, offered rich local insights into determinants of health and numerous health status indicators, including mortality. Data repositories predominantly focused on determinants of health such as age, sex, social deprivation, and geography.

Conclusion

Interactive interfaces featuring data exploration and visualization options across diverse patient populations can serve as valuable tools to address health disparities. The data they provide may help inform complex analytical methodologies that integrate health inequality considerations into healthcare decision-making. This may include assessing the feasibility of transporting health inequality data across borders.
MiR-146a reduces fibrosis after glaucoma filtration surgery in rats
Authors: Han Ruiqi , Zhong Huimin , Zhang Yang , Yu Huan , Zhang Yumeng , Huang Shouyue , Yang Zijian , Zhong Yisheng
Published: May 2024

Purpose

To explore the impact of microRNA 146a (miR-146a) and the underlying mechanisms in profibrotic changes following glaucoma filtering surgery (GFS) in rats and stimulation by transforming growth factor (TGF)-β1 in rat Tenon’s capsule fibroblasts.

Methods

Cultured rat Tenon’s capsule fibroblasts were treated with TGF-β1 and analyzed with microarrays for mRNA profiling to validate miR-146a as the target. The Tenon’s capsule fibroblasts were then respectively treated with lentivirus-mediated transfection of miR-146a mimic or inhibitor following TGF-β1 stimulation in vitro, while GFS was performed in rat eyes with respective intraoperative administration of miR-146a, mitomycin C (MMC), or 5-fluorouracil (5-FU) in vivo. Profibrotic genes expression levels (fibronectin, collagen Iα, NF-KB, IL-1β, TNF-α, SMAD4, and α-smooth muscle actin) were determined through qPCR, Western blotting, immunofluorescence staining and/or histochemical analysis in vitro and in vivo. SMAD4 targeting siRNA was further used to treat the fibroblasts in combination with miR-146a intervention to confirm its role in underlying mechanisms.

Results

Upregulation of miR-146a reduced the proliferation rate and profibrotic changes of rat Tenon’s capsule fibroblasts induced by TGF-β1 in vitro, and mitigated subconjunctival fibrosis to extend filtering blebs survival after GFS in vivo, where miR-146a decreased expression levels of NF-KB-SMAD4-related genes, such as fibronectin, collagen Iα, NF-KB, IL-1β, TNF-α, SMAD4, and α-smooth muscle actin(α-SMA). Additionally, SMAD4 is a key target gene in the process of miR-146a inhibiting fibrosis.

Conclusions

MiR-146a effectively reduced TGF-β1-induced fibrosis in rat Tenon’s capsule fibroblasts in vitro and in vivo, potentially through the NF-KB-SMAD4 signaling pathway. MiR-146a shows promise as a novel therapeutic target for preventing fibrosis and improving the success rate of GFS.
Deep learning based digital pathology for predicting treatment response to first-line PD-1 blockade in advanced gastric cancer
Authors: Liu Yifan , Chen Wei , Ruan Ruiwen , Zhang Zhimei , Wang Zhixiong , Guan Tianpei , Lin Qi , Tang Wei , Deng Jun , Wang Zhao , Li Guanghua
Published: May 2024

Background

Advanced unresectable gastric cancer (GC) patients were previously treated with chemotherapy alone as the first-line therapy. However, with the Food and Drug Administration’s (FDA) 2022 approval of programmed cell death protein 1 (PD-1) inhibitor combined with chemotherapy as the first-li ne treatment for advanced unresectable GC, patients have significantly benefited. However, the significant costs and potential adverse effects necessitate precise patient selection. In recent years, the advent of deep learning (DL) has revolutionized the medical field, particularly in predicting tumor treatment responses. Our study utilizes DL to analyze pathological images, aiming to predict first-line PD-1 combined chemotherapy response for advanced-stage GC.

Methods

In this multicenter retrospective analysis, Hematoxylin and Eosin (H&E)-stained slides were collected from advanced GC patients across four medical centers. Treatment response was evaluated according to iRECIST 1.1 criteria after a comprehensive first-line PD-1 immunotherapy combined with chemotherapy. Three DL models were employed in an ensemble approach to create the immune checkpoint inhibitors Response Score (ICIsRS) as a novel histopathological biomarker derived from Whole Slide Images (WSIs).

Results

Analyzing 148,181 patches from 313 WSIs of 264 advanced GC patients, the ensemble model exhibited superior predictive accuracy, leading to the creation of ICIsNet. The model demonstrated robust performance across four testing datasets, achieving AUC values of 0.92, 0.95, 0.96, and 1 respectively. The boxplot, constructed from the ICIsRS, reveals statistically significant disparities between the well response and poor response (all p-values < = 0.001).

Conclusion

ICIsRS, a DL-derived biomarker from WSIs, effectively predicts advanced GC patients’ responses to PD-1 combined chemotherapy, offering a novel approach for personalized treatment planning and allowing for more individualized and potentially effective treatment strategies based on a patient’s unique response situations.
Global existence and attractivity for Riemann-Liouville fractional semilinear evolution equations involving weakly singular integral inequalities
Authors: Jiang Caijing , Xu Keji
Published: May 2024

In this paper, we obtain several results on the global existence, uniqueness and attractivity for fractional evolution equations involving the Riemann-Liouville type by exploiting some results on weakly singular integral inequalities in Banach spaces. Some boundedness conditions of the nonlinear term are considered to obtain the main results that generalize and improve some well-known works.
Australian public perspectives on genomic newborn screening: which conditions should be included?
Authors: Lynch Fiona , Best Stephanie , Gaff Clara , Downie Lilian , Archibald Alison D. , Gyngell Christopher , Goranitis Ilias , Peters Riccarda , Savulescu Julian , Lunke Sebastian , Stark Zornitza , Vears Danya F.
Published: May 2024

Background

Implementing genomic sequencing into newborn screening programs allows for significant expansion in the number and scope of conditions detected. We sought to explore public preferences and perspectives on which conditions to include in genomic newborn screening (gNBS).

Methods

We recruited English-speaking members of the Australian public over 18 years of age, using social media, and invited them to participate in online focus groups.

Results

Seventy-five members of the public aged 23–72 participated in one of fifteen focus groups. Participants agreed that if prioritisation of conditions was necessary, childhood-onset conditions were more important to include than later-onset conditions. Despite the purpose of the focus groups being to elicit public preferences, participants wanted to defer to others, such as health professionals or those with a lived experience of each condition, to make decisions about which conditions to include. Many participants saw benefit in including conditions with no available treatment. Participants agreed that gNBS should be fully publicly funded.

Conclusion

How many and which conditions are included in a gNBS program will be a complex decision requiring detailed assessment of benefits and costs alongside public and professional engagement. Our study provides support for implementing gNBS for treatable childhood-onset conditions.
Clinical implications of DNA methylation-based integrated classification of histologically defined grade 2 meningiomas
Authors: Ehret Felix , Perez Eilís , Teichmann Daniel , Meier Sandra , Geiler Carola , Zeus Cosmas , Franke Helene , Roohani Siyer , Wasilewski David , Onken Julia , Vajkoczy Peter , Schweizer Leonille , Kaul David , Capper David
Published: May 2024

The combination of DNA methylation analysis with histopathological and genetic features allows for a more accurate risk stratification and classification of meningiomas. Nevertheless, the implications of this classification for patients with grade 2 meningiomas, a particularly heterogeneous tumor entity, are only partially understood. We correlate the outcomes of histopathologically confirmed grade 2 meningioma with an integrated molecular-morphologic risk stratification and determine its clinical implications. Grade 2 meningioma patients treated at our institution were re-classified using an integrated risk stratification involving DNA methylation array-based data, copy number assessment and TERT promoter mutation analyses. Grade 2 meningioma cases according to the WHO 2021 criteria treated between 2007 and 2021 (n = 100) were retrospectively analyzed. The median clinical and radiographic follow-up periods were 59.8 and 54.4 months. A total of 38 recurrences and 17 deaths were observed. The local control rates of the entire cohort after 2-, 4-, and 6-years were 84.3%, 68.5%, and 50.8%, with a median local control time of 77.2 months. The distribution of the integrated risk groups were as follows: 31 low, 54 intermediate, and 15 high risk cases. In the multivariable Cox regression analysis, integrated risk groups were significantly associated with the risk of local recurrence (hazard ratio (HR) intermediate: 9.91, HR high-risk: 7.29, p < 0.01). Gross total resections decreased the risk of local tumor progression (HR gross total resection: 0.19, p < 0.01). The comparison of 1p status and integrated risk groups (low vs. intermediate/high) revealed nearly identical local control rates within their respective subgroups. In summary, only around 50% of WHO 2021 grade 2 meningiomas have an intermediate risk profile. Integrated molecular risk stratification is crucial to guide the management of patients with grade 2 tumors and should be routinely applied to avoid over- and undertreatment, especially concerning the use of adjuvant radiotherapy.
Successful treatment for pseudoaneurysm following distal pancreatectomy with celiac axis resection without postoperative pancreatic fistula: a case report
Authors: Fukuda Kaito , Koyama Ken , Kyoden Yusuke
Published: May 2024

Background

Distal pancreatectomy with celiac axis resection (DP–CAR) represents an innovative surgical approach for locally advanced pancreatic body cancer in cases involving celiac axis invasion. However, this procedure carries significant perioperative risks, including arterial aneurysms and organ ischemia. Understanding these risks is crucial for optimizing patient outcomes and guiding treatment decisions.

Case presentation

This case report describes a unique case of a 74-year-old male patient who was diagnosed with locally advanced pancreatic body cancer with invasion of the celiac and splenic arteries. He underwent DP–CAR after six cycles of chemotherapy. His postoperative course was uneventful without any evidence of postoperative pancreatic fistula. However, at the 10-month postoperative follow-up, pseudoaneurysm was incidentally detected in the anterior superior pancreaticoduodenal artery by follow-up computed tomography. It was successfully treated with coil embolization. He had no signs of tumor recurrence or relapse of pseudoaneurysm formation 2 years postoperatively. This case report discusses the potential risks of pseudoaneurysm formation in patients undergoing DP–CAR due to hemodynamic changes. We emphasize the significance of close monitoring in such cases.

Conclusions

The case highlights the importance of recognizing and managing potential complications associated with DP–CAR in patients with pancreatic cancer. Despite its effectiveness in achieving complete resection, DP–CAR carries inherent risks, including the development of pseudoaneurysms. Vigilant surveillance and prompt intervention are crucial for optimizing patient outcomes and minimizing postoperative complications.
Promotion of practical technology of the thermal management system for cylindrical power battery
Authors: Li Ge
Published: May 2024

Amidst the industrial transformation and upgrade, the new energy vehicle industry is at a crucial juncture. Power batteries, a vital component of new energy vehicles, are currently at the forefront of industry competition with a focus on technological innovation and performance enhancement. The operational temperature of a battery significantly impacts its efficiency, making the design of a reliable Thermal Management System (TMS) essential to ensure battery safety and stability. Cylindrical power batteries are widely utilized in the industry. This article outlines the four main structures and their drawbacks of TMS for cylindrical power batteries. Among these structures, air cooling falls short in meeting high heat dissipation requirements. Liquid cooling is expensive, intricate, and adds considerable weight. Phase Change Materials (PCM) are not yet prevalent in practical applications. Similarly, heat pipes are relatively uncommon in large high-power battery packs. To better align with the new energy vehicle industry’s demands for top-notch performance, cost-effectiveness, eco-friendliness, and reliability, this paper strongly recommends delving deeper into composite cooling solutions. The construction of an economically viable and fully optimized composite cooling method is poised to become a significant scientific challenge for future research endeavors.
CYP19A1 Expression Is Controlled by mRNA Stability of the Upstream Transcription Factor AP-2γ in Placental JEG3 Cells
Authors: Kotomura Naoe , Shimono Yohei , Ishihara Satoru
Published: May 2024

CYP19A1 encodes aromatase, which converts testosterone to estrogen, and is induced during placental maturation. To elucidate the molecular mechanism underlying this function, histone methylation was analyzed using the placental cytotrophoblast cell line, JEG3. Treatment of JEG3 cells with 3-deazaneplanocin A, an inhibitor of several methyltransferases, resulted in increased CYP19A1 expression, accompanied by removal of the repressive mark H3K27me3 from the CYP19A1 promoter. However, this increase was not observed in cells treated with GSK126, another specific inhibitor for H3K27me3 methylation. Expression of TFAP2C, which encodes AP-2γ, a transcription factor that regulates CYP19A1, was also elevated on 3-deazaneplanocin A treatment. Interestingly, TFAP2C messenger RNA (mRNA) was readily degraded in JEG3 cells but protected from degradation in the presence of 3-deazaneplanocin A. TFAP2C mRNA contained N6-methyladenosines, which were reduced on drug treatment. These observations indicate that the TFAP2C mRNA undergoes adenosine methylation and rapid degradation, whereas 3-deazaneplanocin A suppresses methylation, resulting in an increase in AP-2γ levels. We conclude that the increase in AP-2γ expression via stabilization of the TFAP2C mRNA is likely to underlie the increased CYP19A1 expression.
Operative Nuances of Capsular Dissection Techniques and Capsule Morphology in Pituitary Adenomas: Past 1-Year Case Experiences of a Tertiary Center
Authors: Yilmaz Eren , Uzuner Ayse , Ceylan Ecem Cemre , Yildirim Pinar , Duman Ozturk Seda , Emengen Atakan , Gokbel Aykut , Caklili Melih , Cabuk Burak , Anik Ihsan , Ceylan Savas
Published: May 2024

BACKGROUND AND OBJECTIVES:

The widespread use of endoscope and increased surgical experiences in pituitary adenomas (PAs) has raised the expectations for higher resection and cure rates. The subject that will meet this expectation in all types of adenomas is the capsule and its dissection. The purpose of this study was to go beyond the commonly mentioned pseudocapsule definition for small-sized adenomas in previous studies and to describe the capsule structure in different morphologies present in pituitary adenomas of all sizes. This includes detailing the nuances of capsular dissection (CD) and presenting postoperative surgical outcomes through the experiences of a high-volume tertiary center.

METHODS:

In our center, 534 patients underwent endoscopic trans-sphenoidal surgery because of pituitary adenoma in 2022 by the same surgeon. The data of the patients were examined retrospectively. The surgical techniques applied were grouped as adenoma resection only, capsular resection after internal debulking, and direct extracapsular resection.

RESULTS:

CD was performed in 275 (51.5%) patients. The gross total resection (GTR) rate in nonsecretory adenomas with and without CD was 90.7% (97/107) and 90.7% (97/107), respectively. The remission rate in secretory adenomas with and without CD was 81.0% (136/168) and 44.0% (67/152), respectively. When the patients were examined in 2 groups as those who underwent CD and those who did not, the application of CD had a positive predictive value in terms of GTR/remission (P: .036). Capsule thickness was not found to be statistically significant depending on tumor subtype, size, and aggressiveness, but capsule thickness was statistically significant in terms of total capsular resection (P: .045).

CONCLUSION:

The morphology of the capsule, tumor size/subtype/consistency, and patient-specific factors are crucial for the selection of the surgical technique to be applied. It is possible to increase the GTR/remission rates in adenomas of all sizes by capsule dissection. Moreover, performing CD does not contribute significantly to the development of potential complications in such cases.
Learning Curve of Robotic End-to-Side Microanastomoses
Authors: Rabbin-Birnbaum Corinne , Wiggan Daniel D. , Sangwon Karl L. , Negash Bruck , Gutstadt Eleanor , Rutledge Caleb , Baranoski Jacob , Raz Eytan , Shapiro Maksim , Sharashidze Vera , Riina Howard A. , Nelson Peter Kim , Liu Albert , Choudhry Osamah , Nossek Erez
Published: May 2024

BACKGROUND AND OBJECTIVES:

Robotics are becoming increasingly widespread within various neurosurgical subspecialties, but data pertaining to their feasibility in vascular neurosurgery are limited. We present our novel attempt to evaluate the learning curve of a robotic platform for microvascular anastomoses.

METHODS:

One hundred and sixty one sutures were performed and assessed. Fourteen anastomoses (10 robotic [MUSA-2 Microsurgical system; Microsure] and 4 hand-sewn) were performed by the senior author on 1.5-mm caliber tubes and recorded with the Kinevo 900 (Zeiss) operative microscope. We separately compared interrupted sutures (from needle insertion until third knot) and running sutures (from needle insertion until loop pull-down). Average suture timing across all groups was compared using an unpaired Student's t test. Exponential smoothing (α = 0.2) was then applied to the robotic data sets for validation and a second set of t tests were performed.

RESULTS:

We compared 107 robotic sutures with 54 hand-sewn sutures. There was a significant difference between the average time/stitch for the robotic running sutures (n = 55) and the hand-sewn running sutures (n = 31) (31.2 seconds vs 48.3 seconds, respectively; P-value = .00052). Exponential smoothing (α = 0.2) reinforced these results (37.6 seconds vs 48.3 seconds; P-value = .014625). Average robotic running times surpassed hand-sewn by the second anastomosis (38.8 seconds vs 48.3 seconds) and continued to steadily decrease with subsequent stitches. The average of the robotic interrupted sutures (n = 52) was significantly longer than the hand-sewn (n = 23) (171.3 seconds vs 70 seconds; P = .000024). Exponential smoothing (α = 0.2) yielded similar results (196.7 seconds vs 70 seconds; P = .00001). However, average robotic interrupted times significantly decreased from the first to the final anastomosis (286 seconds vs 105.2 seconds; P = .003674).

CONCLUSION:

Our results indicate the learning curve for robotic microanastomoses is short and encouraging. The use of robotics warrants further study for potential use in cerebrovascular bypass procedures.