bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciphering breast cancer dynamics: insights from single-cell and spatial profiling in the multi-omics era
Authors: Xiong Xin , Wang Xin , Liu Cui-Cui , Shao Zhi-Ming , Yu Ke-Da 
Published: September 2024

AbstractAs one of the most common tumors in women, the pathogenesis and tumor heterogeneity of breast cancer have long been the focal point of research, with the emergence of tumor metastasis and drug resistance posing persistent clinical challenges. The emergence of single-cell sequencing (SCS) technology has introduced novel approaches for gaining comprehensive insights into the biological behavior of malignant tumors. SCS is a high-throughput technology that has rapidly developed in the past decade, providing high-throughput molecular insights at the individual cell level. Furthermore, the advent of multitemporal point sampling and spatial omics also greatly enhances our understanding of cellular dynamics at both temporal and spatial levels. The paper provides a comprehensive overview of the historical development of SCS, and highlights the most recent advancements in utilizing SCS and spatial omics for breast cancer research. The findings from these studies will serve as valuable references for future advancements in basic research, clinical diagnosis, and treatment of breast cancer.
Profiling the lncRNA–miRNA–mRNA interaction network in the cold-resistant exercise period of grape (Vitis amurensis Rupr.)
Authors: Ma Weifeng , Ma Lijuan , Ma Zonghuan , Li Wenfang , Lu Shixiong , Gou Huimin , Mao Juan , Chen Baihong 
Published: September 2024

Abstract
Background
Grape is a plant that is sensitive to low temperature and vulnerable to low-temperature damage. However, little is known about the roles of lncRNAs, miRNAs and mRNAs in regulating the hypothermia response mechanism in Vitis amurensis Rupr.

Methods
In this study, the expression and regulatory network of low-temperature response genes were studied in the phloem of grape under different low-temperature stress.

Results
Here, we performed analyses related to RNA-seq and miRNA-seq on grape phloem tissues from five periods of cold resistance campaigns. Three RNAs (lncRNAs, miRNAs and mRNAs) obtained by KEGG and GO analyses were used to identify starch and sucrose metabolism associated with cold resistance, and specific changes in BP, CC, and MF were identified in four comparisons. Venn diagrams, thermograms and pathway maps were used to analyze the differentially expressed genes (DEGs), and their specific gene expression during the cold exercise were obtained. The six DEGs finally selected were used for qRT-PCR to verify the RNA-seq data. In addition, we found that the regulatory networks of miRNAs and lncRNAs correspond to the six DEGs. This study will contribute to further experimental studies to elucidate the cold resistance mechanism of Vitis amurensis Rupr.

Conclusions
The low-temperature response genes of grape are mainly enriched in the starch and sucrose metabolism, and they are regulated by miRNAs and lncRNAs. The conclusions will provide basic information for further understanding of the cold resistance mechanism of grape in the future.

Graphical Abstract
Remifentanil vs. dexmedetomidine for cardiac surgery patients with noninvasive ventilation intolerance: a multicenter randomized controlled trial
Authors: Hao Guang-wei , Wu Jia-qing , Yu Shen-ji , Liu Kai , Xue Yan , Gong Qian , Xie Rong-cheng , Ma Guo-guang , Su Ying , Hou Jun-yi , zhang Yi-jie , Liu Wen-jun , Li Wei , Tu Guo-wei , Luo Zhe 
Published: September 2024

AbstractBackgroundThe optimal sedative regime for noninvasive ventilation (NIV) intolerance remains uncertain. The present study aimed to assess the efficacy and safety of remifentanil (REM) compared to dexmedetomidine (DEX) in cardiac surgery patients with moderate-to-severe intolerance to NIV.MethodsIn this multicenter, prospective, single-blind, randomized controlled study, adult cardiac surgery patients with moderate-to-severe intolerance to NIV were enrolled and randomly assigned to be treated with either REM or DEX for sedation. The status of NIV intolerance was evaluated using a four-point NIV intolerance score at different timepoints within a 72-h period. The primary outcome was the mitigation rate of NIV intolerance following sedation.ResultsA total of 179 patients were enrolled, with 89 assigned to the REM group and 90 to the DEX group. Baseline characteristics were comparable between the two groups, including NIV intolerance score [3, interquartile range (IQR) 3–3 vs. 3, IQR 3–4,p = 0.180]. The chi-squared test showed that mitigation rate, defined as the proportion of patients who were relieved from their initial intolerance status, was not significant at most timepoints, except for the 15-min timepoint (42% vs. 20%,p = 0.002). However, after considering the time factor, generalized estimating equations showed that the difference was statistically significant, and REM outperformed DEX (odds ratio = 3.31, 95% confidence interval: 1.35–8.12,p = 0.009). Adverse effects, which were not reported in the REM group, were encountered by nine patients in the DEX group, with three instances of bradycardia and six cases of severe hypotension. Secondary outcomes, including NIV failure (5.6% vs. 7.8%,p = 0.564), tracheostomy (1.12% vs. 0%,p = 0.313), ICU LOS (7.7 days, IQR 5.8–12 days vs. 7.0 days, IQR 5–10.6 days,p = 0.219), and in-hospital mortality (1.12% vs. 2.22%,p = 0.567), demonstrated comparability between the two groups.ConclusionsIn summary, our study demonstrated no significant difference between REM and DEX in the percentage of patients who achieved mitigation among cardiac surgery patients with moderate-to-severe NIV intolerance. However, after considering the time factor, REM was significantly superior to DEX.Trial registrationClinicalTrials.gov (NCT04734418), registered on January 22, 2021. URL of the trial registry record:https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000AM4S&selectaction=Edit&uid=U00038YX&ts=3&cx=eqn1z0.
Comparative study of the growth, stress status and reproductive capabilities of four wild-type zebrafish (Danio rerio) lines
Authors: Chevalier Céline , Denis Clémence , Nedjar Sid-Ahmed , Ledoré Yannick , Silvestre Frédéric , Schaerlinger Bérénice , Milla Sylvain 
Published: September 2024

Abstract
Background
Zebrafish are widely used in various research fields and to fulfil the diverse research needs, numerous zebrafish lines are available, each with a unique domestication background, potentially resulting in intraspecies differences in specific biological functions. Few studies have compared multiple zebrafish lines under identical conditions to investigate both inter- and intra-line variability related to different functions. However, such variability could pose a challenge for the reproducibility of results in studies utilising zebrafish, particularly when the line used is not clearly specified. This study assessed growth, stress status (cortisol, serotonin) and reproductive capabilities (maturity, fecundity, fertilisation rate, sperm quality) of four commonly used wild-type zebrafish lines (AB, SJD, TU, WIK) using standardized protocols.

Results
The stress markers levels were found to be similar across the lines, indicating that the endocrine stress status is robust to diverse domestication histories. Variations were observed in the growth and reproductive parameters. The lines exhibited differences in the timing of puberty (86 dpf for AB and SJD lines vs. 107 dpf for the WIK line) despite achieving similar sizes, suggesting that there are line-specific variations in the induction of maturation. Additionally, the AB line demonstrated higher sperm quality than did the other lines and higher fecundity and fertilization rates than did the SJD line. The AB line also exhibiting a smaller adult size but a heavier brain relative to its body weight.

Conclusion
These findings emphasize the importance of line selection for zebrafish research, indicating that researchers should consider line-specific traits to ensure the biological relevance and reproducibility of the results.
Virtual reality in telepsychiatry is a new horizon for immersive mental health therapy
Authors: Hasan Md. Kamrul 
Published: September 2024

AbstractThe use of virtual reality (VR) in telepsychiatry signifies a paradigm shift in mental health care. VR provides realistic, interactive environments for therapies like exposure therapy and cognitive behavioral therapy, resulting in reliable and reproducible scenarios that improve treatment effectiveness. This technology enhances accessibility for those with geographical or physical limitations, lowers stigma, and boosts patient engagement and adherence by making treatment activities more pleasurable and interesting. Furthermore, VR may emulate social interactions and circumstances that are difficult to replicate in typical treatment settings, providing useful practice for people with social anxiety or autism spectrum disorders (ASD). Despite its great potential, integrating VR into telepsychiatry offers problems such as high VR equipment costs, assuring clinical effectiveness and safety, and securing patient data. Future research should prioritize large-scale, randomized controlled trials to determine the efficacy of VR-based therapy, investigate long-term consequences, and offer cost-effective solutions. By tackling these issues and investing in novel research, VR has the potential to greatly improve telepsychiatry, making mental health care more effective, engaging, and easily available to people all over the world.
The pathway to delivering injectable CAB for HIV prevention: strategies from global PrEP leaders leveraging an adapted version of the Intervention Scalability Assessment Tool (ISAT)
Authors: Violette Lauren R. , Zewdie Kidist , Gitahi Nyawira , Beima-Sofie Kristin , Heffron Renee 
Published: September 2024

Abstract
Background
Longer-acting cabotegravir (CAB) is a novel, safe, and efficacious pre-exposure prophylaxis (PrEP) for HIV prevention. As we near a time for CAB scale-up, the experience of global leaders in PrEP research and implementation can be leveraged to identify optimal strategies for scaling and integrating CAB into existing PrEP infrastructure worldwide.

Methods
We recruited leaders of HIV prevention clinical trials and large PrEP programs through a combination of purposive and snowball sampling for participation in individual interviews. We conducted interviews using a semi-structured guide that compared CAB to oral PrEP and sought perspectives on barriers and strategies for CAB scale-up. Interviews were conducted virtually, audio recorded, and transcribed. We used thematic analysis, grounded in an adapted version of the Intervention Scalability Assessment Tool (ISAT), to identify critical elements for optimizing delivery of CAB.

Results
From October 2021 to April 2022, we interviewed 30 participants with extensive experience in PrEP research, care, and programming. Participants worked in all seven WHO regions and reported a median of 20 years working in HIV and 10 years in PrEP. Participants agreed that CAB was efficacious and discrete, therefore having the potential to address current concerns about oral PrEP adherence and stigma. Participants indicated direct and indirect costs for provider training, expansion of existing medical infrastructure, and the current medication cost of CAB as major concerns for roll out. The true cost to the end-user and health system were unknown. There were some conflicting strategies on how to best address product targeting, presentation of efficacy, and timing of product availability with scale-up. Some thought that targeting CAB for the general population could normalize PrEP and decrease stigma, while others thought that prioritizing key populations could optimize impact by targeting those with highest risk. Overall, participants emphasized that to ensure successful CAB scale-up, communities and stakeholders must be involved at every stage of planning and implementation.

Conclusions
Our evaluation found that although there is a clear and urgent need for additional HIV PrEP options beyond daily oral PrEP, CAB scale-up must be thoughtful, flexible, and based in lessons learned from oral PrEP rollout.
Area deprivation index, a marker of socioeconomic disadvantage, may predict severity of COVID-19 in patients and which families may experience worse symptoms of PTSD, anxiety, and depression post-ICU
Authors: Mayer Megan , Althoff Meghan , Csikesz Nicholas , Yu Stephanie , Cruse Hope , Stapleton Renee , Amass Timothy 
Published: September 2024

Abstract
Background
COVID-19 disproportionately impacted marginalized populations early in the pandemic. Families of patients admitted to the intensive care unit (ICU) experienced significant psychological effects. Little is known about whether individual and patient psychological outcomes after a loved ones stay in the ICU differs by socioeconomic status, as measured by the area deprivation index (ADI).

Methods
Family members of patients with COVID-19 respiratory failure admitted to the ICU at twelve hospitals in five US states were enrolled in a larger study looking at rates of symptoms of post-traumatic stress disorder (PTSD), anxiety, and depression in the months following their loved one's ICU stay. This secondary data analysis includes eight of the twelve hospitals in four of the five states. Each participant was assigned a number indicating a level of neighborhood disadvantage based on the patient’s zip code. Patient and family level characteristics as well as symptoms of anxiety, depression, and PTSD were assessed among each neighborhood.

Results
Patients from the most disadvantaged neighborhoods had the highest proportion of patients that needed to be intubated (p = 0.005). All the patients in the most disadvantaged neighborhoods were a race other than white (p = 0.17). At 12 months post-hospitalization, there was a statistically significant difference in the proportion of family members who experienced symptoms of PTSD, anxiety, and depression between the ADI groups.

Conclusions
ADI may be a predictor of COVID-19 disease severity for patients on presentation to the ICU. Patients and family members experience psychological effects after a loved one’s admission to the ICU, and these outcomes vary among individuals of different socioeconomic status’, as measured by the ADI. A larger study of family members’ incidence of anxiety, depression, and post-traumatic stress disorder is needed to understand the extent to which these symptoms are impacted by neighborhood level factors as measured by the ADI.
Age and Sex Affects the Frequency and Mutation Type of FGFR2 Alterations in Cholangiocarcinoma
Authors: Hu Z. Ian , Ross Jeffrey S. , Pavlick Dean , Hsiehchen David 
Published: September 2024

PURPOSE FGFR2 alterations are infrequent but currently represent the most common targetable mutation in cholangiocarcinoma. We performed a large-scale genomic analysis to assess associations between FGFR2 and other driver gene alterations in cholangiocarcinoma with patient demographics. METHODS Clinical and molecular data for patients with intrahepatic cholangiocarcinoma were abstracted from the Foundation Medicine (FMI) and Genomics, Evidence, Neoplasia, Information, Exchange (GENIE) genomic databases. The Chi-squared test was used to assess the association between sex and alterations in driver genes. FGFR2 fusion partners were analyzed using descriptive statistics. RESULTS Across both FMI (N = 7,859) and GENIE (N = 1,395) cohorts, FGFR2 rearrangements were more frequent in female than male patients with cholangiocarcinoma (odds ratio, 1.69 and 2.45). By contrast, FGFR2 missense mutations, TP53 mutations, and KRAS mutations were not associated with sex. Stratifying patients by age groups showed that FGFR2 rearrangements were specifically enriched in younger ages (<45 years). Although the most common FGFR2 fusion partners were shared across both sexes, a subset of fusion partners was recurrent and uniquely associated with female or male patients. CONCLUSION FGFR2 rearrangements but not other driver alterations in cholangiocarcinoma are concentrated in young female patients, where the prevalence reached nearly 20% across two large patient cohorts. These results suggest that the molecular basis of FGFR2 rearrangements may be distinct between sexes. These results indicate the importance of genetic testing in cholangiocarcinoma, particularly for younger patients, and suggest that patient recruitment strategies in trials for FGFR2-targeting therapies should seek to reduce barriers to enhance the enrollment of young female patients.
Investigating the Salience of Clinical Meaningfulness and Clinically Meaningful Outcomes in Metastatic Breast Cancer Care Delivery
Authors: Graff Stephanie L. , Freeman Emily C. , Roach Meaghan , Wilson Rozanne , Cagle Claire , Lunsford Sarah , Maravic Melissa Culhane , Fairley Ricki , Gullatte Mary , Stemland Jeanne , Wochal Paulina , Katz Julie , Hoffner Brianna , Scott Julie M. , May Suepattra G. 
Published: September 2024

PURPOSE As metastatic breast cancer (mBC) treatment evolves, there is a need to understand how clinical meaningfulness, or a meaningful change in a patient's daily life, and clinically meaningful outcomes inform patient-centered care. Partnering with key stakeholders ensures patient-centered research incorporates the knowledge and expertise of advisors with lived experience. We describe a multistakeholder engagement approach to examine how people living with mBC (PLWmBC), caregivers, and health care providers interpret clinical meaningfulness and clinically meaningful outcomes and their influence on mBC treatment decision making and care. METHODS Qualitative focus groups with PLWmBC, caregivers, and health care providers were conducted and analyzed along three overarching themes: interpretations of clinical meaningfulness and clinically meaningful outcomes; treatment recommendations, preferences, and decisions; and implications for clinical practice. Patient-led and professional organizations served as research partners in study design, implementation, and interpretation of findings. RESULTS Partnerships were established with four patient-led and three professional organizations representing diverse constituencies throughout the United States. Twenty-two focus groups were conducted with 50 PLWmBC, 24 caregivers, and 41 health care providers (oncologists, n = 11; advanced practice providers, n = 13; oncology nurses, n = 17) between March and June 2023. PLWmBC and caregivers were unfamiliar with the concepts of clinical meaningfulness and clinically meaningful outcomes. Although health care providers were familiar, they did not use the terms when discussing treatment with PLWmBC. Across groups, participants emphasized the importance of meaningful outcomes beyond overall survival, including quality of life and improvement in symptoms and functioning. Participants noted that outcomes considered meaningful are individualized and dynamic. CONCLUSION This study offers insight into how partnering with patient advocacy and professional organizations can enhance research quality and aid translation of findings to clinical practice, thereby supporting patient-centered care.
Phase II Study of Samotolisib in Children and Young Adults With Tumors Harboring Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Pathway Alterations: Pediatric MATCH APEC1621D
Authors: Laetsch Theodore W. , Ludwig Kathleen , Williams P. Mickey , Roy-Chowdhuri Sinchita , Patton David R. , Coffey Brent , Reid Joel M. , Piao Jin , Saguilig Lauren , Alonzo Todd A. , Berg Stacey L. , Mhlanga Joyce , Fox Elizabeth , Weigel Brenda J. , Hawkins Douglas S. , Mooney Margaret M. , Takebe Naoko , Tricoli James V. , Janeway Katherine A. , Seibel Nita L. , Parsons Donald Williams 
Published: September 2024

PURPOSE Patients age 1-21 years with relapsed or refractory solid and CNS tumors were assigned to phase II studies of molecularly targeted therapies on the National Cancer Institute-Children's Oncology Group (NCI-COG) Pediatric Molecular Analysis for Therapy Choice (MATCH) trial. Patients whose tumors harbored predefined genetic alterations in the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway and lacked mitogen-activated protein kinase pathway activating alterations were treated with the PI3K/mTOR inhibitor samotolisib. METHODS Patients received samotolisib twice daily in 28-day cycles until disease progression or unacceptable toxicity. A rolling 6 limited dose escalation was performed as, to our knowledge, this was the first pediatric study of samotolisib. The primary end point was the objective response rate; secondary end points included progression-free survival (PFS) and the recommended phase II dose and toxicity of samotolisib in children. RESULTS A total of 3.4% (41/1,206) of centrally tested patients were matched to this arm. Seventeen patients were treated. Among treated patients, the most common diagnoses included osteosarcoma (n = 6) and high-grade glioma (n = 5) harboring alterations in phosphatase and tensin homolog (n = 6), PIK3CA (n = 5), and tuberous sclerosis complex 2 (n = 3). No objective responses or prolonged stable disease were observed. Three-month PFS was 12% (95% CI, 2 to 31). Two patients experienced dose-limiting toxicities (mucositis and pneumonitis). Dose level 2 (115 mg/m2/dose twice daily) was determined to be the recommended phase II dose of samotolisib in children. CONCLUSION This nationwide study was successful at identifying patients and evaluating the efficacy of molecularly targeted therapy for rare molecular subgroups of patients in a histology-agnostic fashion. Unfortunately, there was no activity of samotolisib against tumors with PI3K/mTOR pathway alterations. Prospective trials such as the NCI-COG Pediatric MATCH are necessary to evaluate the efficacy of molecularly targeted therapies given their increasing use in clinical practice.
Organizational Selection of Innovation
Authors: Böttcher Lucas , Klingebiel Ronald 
Published: September 2024

Budgetary constraints force organizations to pursue only a subset of possible innovation projects. Identifying which subset is most promising is an error-prone exercise, and involving multiple decision makers may be prudent. This raises the question of how to most effectively aggregate their collective nous. Our model of organizational portfolio selection provides some first answers. We show that portfolio performance can vary widely. Delegating evaluation makes sense when organizations employ the relevant experts and can assign projects to them. In most other settings, aggregating the impressions of multiple agents leads to better performance than delegation. In particular, letting agents rank projects often outperforms alternative aggregation rules—including averaging agents’ project scores and counting their approval votes—especially when organizations have tight budgets and can select only a few project alternatives out of many. Funding: L. Böttcher acknowledges financial support from hessian.AI and the Army Research Office [Grant W911NF-23-1-0129]. Supplemental Material: The data files are available at https://doi.org/10.1287/orsc.2023.17357 .