bluuebunny/crossref_metadata_2025_split huggingface dataset:
Between equilibrium and chaos, with little restitution: a narrative analysis of qualitative interviews with clinicians and parent carers of children with medical complexity
Authors: Hodgson Stephanie , Noack Kirsten , Griffiths Ashleigh , Hodgins Michael 
Published: April 2024

Abstract
Background
Children with medical complexity (CMC) comprise 1% of the paediatric population, but account for over 30% of health service costs. Lack of healthcare integration and coordination for CMC is well-documented. To address this, a deep understanding of local contextual factors, experiences, and family-identified needs is crucial. The aim of this research was to investigate the lived experiences of CMC, their families, and healthcare staff, focusing on understanding the dynamics of care coordination and the challenges faced in providing integrated care, in order to inform the development of effective, family-centred models of care.

Methods
In April to July 2022, 31 semi-structured interviews were conducted with parents/guardians of CMC and healthcare professionals who care for CMC. Interviews explored complex paediatric care and care coordination barriers. An inductive thematic analysis was undertaken. Themes were then further explored using Frank’s narrative approach.

Results
Through analysis, we identified that the restitution typology was absent from both staff and parent/guardian narratives. However, we uncovered narratives reflective of the chaos and quest typologies, depicting overwhelming challenges in managing complex medical needs, and proactive efforts to overcome barriers. Importantly, a novel typology termed ‘equilibrium’ was uncovered. Narratives aligning with this typology described medical complexity as a balance of power and a negotiation of roles. Within the equilibrium typology, illness trajectory was described as a series of negotiations or balancing acts between healthcare stakeholders, before finally reaching equilibrium. Participants described seeking a balance, where their expertise is respected, whilst maintaining the ability to rely on professional guidance and support. These insights provide a nuanced understanding of the multifaceted narratives shaping care experiences for CMC and their families.

Conclusions
Our research delineates multifaceted challenges within the care landscape for CMC, their families, and healthcare staff. Embracing the equilibrium narrative typology highlights the criticality of tailored, integrated care models. This necessitates prioritising clear role delineation and communication among caregivers, implementing support systems addressing the challenges of continuous caregiving, and integrating parents/guardians as essential members of the care team. These insights advocate for pragmatic and sustainable strategies to address the unique needs of CMC and their families within healthcare systems.
Listeria-vectored cervical cancer vaccine candidate strains reduce MDSCs via the JAK-STAT signaling pathway
Authors: Zhang Yunwen , Lei Yao , Ou Qian , Chen Mengdie , Tian Sicheng , Tang Jing , Li Ruidan , Liang Qian , Chen Zhaobin , Wang Chuan 
Published: April 2024

Abstract
Background
Immunosuppressive status is prevalent in cancer patients and increases the complexity of tumor immunotherapy. It has been found that Listeria-vectored tumor vaccines had the potential ability of two-side regulatory effect on the immune response during immunotherapy.

Results
The results show that the combined immunotherapy with the LM∆E6E7 and LI∆E6E7, the two cervical cancer vaccine candidate strains constructed by our lab, improves the antitumor immune response and inhibits the suppressive immune response in tumor-bearing mice in vivo, confirming the two-sided regulatory ability of the immune response caused by Listeria-vectored tumor vaccines. The immunotherapy reduces the expression level of myeloid-derived suppressor cells (MDSCs)-inducing factors and then inhibits the phosphorylation level of STAT3 protein, the regulatory factor of MDSCs differentiation, to reduce the MDSCs formation ability. Moreover, vaccines reduce the expression of functional molecules associated with MDSCs may by inhibiting the phosphorylation level of the JAK1-STAT1 and JAK2-STAT3 pathways in tumor tissues to attenuate the immunosuppressive function of MDSCs.

Conclusions
Immunotherapy with Listeria-vectored cervical cancer vaccines significantly reduces the level and function of MDSCs in vivo, which is the key point to the destruction of immunosuppression. The study for the first to elucidate the mechanism of breaking the immunosuppression.
Genomic insights into the seawater adaptation in Cyprinidae
Authors: Wang Ying , Zhang Xuejing , Wang Jing , Wang Cheng , Xiong Fei , Qian Yuting , Meng Minghui , Zhou Min , Chen Wenjun , Ding Zufa , Yu Dan , Liu Yang , Chang Yumei , He Shunping , Yang Liandong 
Published: April 2024

Abstract
Background
Cyprinidae, the largest fish family, encompasses approximately 367 genera and 3006 species. While they exhibit remarkable adaptability to diverse aquatic environments, it is exceptionally rare to find them in seawater, with the Far Eastern daces being of few exceptions. Therefore, the Far Eastern daces serve as a valuable model for studying the genetic mechanisms underlying seawater adaptation in Cyprinidae.

Results
Here, we sequenced the chromosome-level genomes of two Far Eastern daces (Pseudaspius brandtii and P. hakonensis), the two known cyprinid fishes found in seawater, and performed comparative genomic analyses to investigate their genetic mechanism of seawater adaptation. Demographic history reconstruction of the two species reveals that their population dynamics are correlated with the glacial-interglacial cycles and sea level changes. Genomic analyses identified Pseudaspius-specific genetic innovations related to seawater adaptation, including positively selected genes, rapidly evolving genes, and conserved non-coding elements (CNEs). Functional assays of Pseudaspius-specific variants of the prolactin (prl) gene showed enhanced cell adaptation to greater osmolarity. Functional assays of Pseudaspius specific CNEs near atg7 and usp45 genes suggest that they exhibit higher promoter activity and significantly induced at high osmolarity.

Conclusions
Our results reveal the genome-wide evidence for the evolutionary adaptation of cyprinid fishes to seawater, offering valuable insights into the molecular mechanisms supporting the survival of migratory fish in marine environments. These findings are significant as they contribute to our understanding of how cyprinid fishes navigate and thrive in diverse aquatic habitats, providing useful implications for the conservation and management of marine ecosystems.
Hypoxia exposure blunts angiogenic signaling and upregulates the antioxidant system in endothelial cells derived from elephant seals
Authors: Allen Kaitlin N. , Torres-Velarde Julia María , Vazquez Juan Manuel , Moreno-Santillán Diana D. , Sudmant Peter H. , Vázquez-Medina José Pablo 
Published: April 2024

Abstract
Background
Elephant seals exhibit extreme hypoxemic tolerance derived from repetitive hypoxia/reoxygenation episodes they experience during diving bouts. Real-time assessment of the molecular changes underlying protection against hypoxic injury in seals remains restricted by their at-sea inaccessibility. Hence, we developed a proliferative arterial endothelial cell culture model from elephant seals and used RNA-seq, functional assays, and confocal microscopy to assess the molecular response to prolonged hypoxia.

Results
Seal and human endothelial cells exposed to 1% O2 for up to 6 h respond differently to acute and prolonged hypoxia. Seal cells decouple stabilization of the hypoxia-sensitive transcriptional regulator HIF-1α from angiogenic signaling. Rapid upregulation of genes involved in glutathione (GSH) metabolism supports the maintenance of GSH pools, and intracellular succinate increases in seal but not human cells. High maximal and spare respiratory capacity in seal cells after hypoxia exposure occurs in concert with increasing mitochondrial branch length and independent from major changes in extracellular acidification rate, suggesting that seal cells recover oxidative metabolism without significant glycolytic dependency after hypoxia exposure.

Conclusions
We found that the glutathione antioxidant system is upregulated in seal endothelial cells during hypoxia, while this system remains static in comparable human cells. Furthermore, we found that in contrast to human cells, hypoxia exposure rapidly activates HIF-1 in seal cells, but this response is decoupled from the canonical angiogenesis pathway. These results highlight the unique mechanisms that confer extraordinary tolerance to limited oxygen availability in a champion diving mammal.
Very short sleep duration reveals a proteomic fingerprint that is selectively associated with incident diabetes mellitus but not with incident coronary heart disease: a cohort study
Authors: Svensson Thomas , Svensson Akiko Kishi , Kitlinski Mariusz , Engström Gunnar , Nilsson Jan , Orho-Melander Marju , Nilsson Peter M. , Melander Olle 
Published: April 2024

Abstract
Background
The molecular pathways linking short and long sleep duration with incident diabetes mellitus (iDM) and incident coronary heart disease (iCHD) are not known. We aimed to identify circulating protein patterns associated with sleep duration and test their impact on incident cardiometabolic disease.

Methods
We assessed sleep duration and measured 78 plasma proteins among 3336 participants aged 46–68 years, free from DM and CHD at baseline, and identified cases of iDM and iCHD using national registers. Incident events occurring in the first 3 years of follow-up were excluded from analyses. Tenfold cross-fit partialing-out lasso logistic regression adjusted for age and sex was used to identify proteins that significantly predicted sleep duration quintiles when compared with the referent quintile 3 (Q3). Predictive proteins were weighted and combined into proteomic scores (PS) for sleep duration Q1, Q2, Q4, and Q5. Combinations of PS were included in a linear regression model to identify the best predictors of habitual sleep duration. Cox proportional hazards regression models with sleep duration quintiles and sleep-predictive PS as the main exposures were related to iDM and iCHD after adjustment for known covariates.

Results
Sixteen unique proteomic markers, predominantly reflecting inflammation and apoptosis, predicted sleep duration quintiles. The combination of PSQ1 and PSQ5 best predicted sleep duration. Mean follow-up times for iDM (n = 522) and iCHD (n = 411) were 21.8 and 22.4 years, respectively. Compared with sleep duration Q3, all sleep duration quintiles were positively and significantly associated with iDM. Only sleep duration Q1 was positively and significantly associated with iCHD. Inclusion of PSQ1 and PSQ5 abrogated the association between sleep duration Q1 and iDM. Moreover, PSQ1 was significantly associated with iDM (HR = 1.27, 95% CI: 1.06–1.53). PSQ1 and PSQ5 were not associated with iCHD and did not markedly attenuate the association between sleep duration Q1 with iCHD.

Conclusions
We here identify plasma proteomic fingerprints of sleep duration and suggest that PSQ1 could explain the association between very short sleep duration and incident DM.
Integrated multi-omics analysis and machine learning developed a prognostic model based on mitochondrial function in a large multicenter cohort for Gastric Cancer
Authors: Ma Yimeng , Jin Jingjing , Xue Zixuan , Zhao Jungang , Cai Weiyang , Zhang Wanli 
Published: April 2024

Abstract
Background
Gastric cancer (GC) is a common and aggressive type of cancer worldwide. Despite recent advancements in its treatment, the prognosis for patients with GC remains poor. Understanding the mechanisms of cell death in GC, particularly those related to mitochondrial function, is crucial for its development and progression. However, more research is needed to investigate the significance of the interaction between mitochondrial function and GC cell death.

Methods
We employed a robust computational framework to investigate the role of mitochondria-associated proteins in the progression of GC in a cohort of 1,199 GC patients. Ten machine learning algorithms were utilized and combined into 101 unique combinations. Ultimately, we developed a Mitochondrial-related-Score (MitoScore) using the machine learning model that exhibited the best performance. We observed the upregulation of LEMT2 and further explored its function in tumor progression. Mitochondrial functions were assessed by measuring mitochondrial ATP, mitochondrial membrane potential, and levels of lactate, pyruvate, and glucose.

Results
MitoScore showed significant correlations with GC immune and metabolic functions. The higher MitoScore subgroup exhibited enriched metabolic pathways and higher immune activity. Overexpression of LETM2 (leucine zipper and EF-hand containing transmembrane protein 2) significantly enhanced tumor proliferation and metastasis. LETM2 plays a role in promoting GC cell proliferation by activating the mTOR pathway, maintaining mitochondrial homeostasis, and promoting glycolysis.

Conclusion
The powerful machine learning framework highlights the significant potential of MitoScore in providing valuable insights and accurate assessments for individuals with GC. This study also enhances our understanding of LETM2 as an oncogene signature in GC. LETM2 may promote tumor progression by maintaining mitochondrial health and activating glycolysis, offering potential targets for diagnosis, treatment, and prognosis of GC.
Investigating midwives and nurses reporting of ‘infant feeding at hospital discharge’: an online survey across NSW Australia
Authors: Henry Lynne , Burns Elaine , Jones Rachel , White Lisa , Simmons Michelle , Kirby Adrienne , Melov Sarah J. 
Published: April 2024

Abstract
Background
The collection of data on ‘infant feeding at hospital discharge’ is used to monitor breastfeeding outcomes, health service benchmarking, and research. While some Australian states have clear definitions of this data collection point, there is no operational definition of ‘infant feeding at hospital discharge’ in the Australian state of New South Wales. Little is known about how midwives interpret the term ‘infant feeding at hospital discharge’, in particular, the timeframe used to calculate these important indicators. The purpose of this study was to explore midwives’ and nurses’ practices of reporting ‘infant feeding at hospital discharge’ in the Australian state of New South Wales.

Methods
An online survey was distributed across public and private maternity hospitals in New South Wales, Australia. The survey asked midwives and nurses their practice of reporting ‘infant feeding at discharge’ from categories offered by the state Mothers and Babies report of either “full breastfeeding”, “any breastfeeding”, and “infant formula only”. The Qualtrics survey was available from December 2021 to May 2022.

Results
There were 319 completed surveys for analysis and all 15 NSW Health Districts were represented. Some participants reported using the timeframe ‘since birth’ as a reference (39%), however, the majority (54%, n = 173) referenced one of the feeding timeframes within the previous 24 h. Most midwives and nurses (83%, n = 265) recommended 24 h before discharge as the most relevant reference timeframe, and 65% (n = 207) were in favour of recording data on ‘exclusive breastfeeding’ since birth.

Conclusion
This study identified multiple practice inconsistencies within New South Wales reporting of ‘infant feeding at hospital discharge’. This has ramifications for key health statistics, state reporting, and national benchmarking. While the Baby Friendly Hospital Initiative accreditation requires hospitals to demonstrate and continuously monitor at least a 75% exclusive breastfeeding rate on discharge, only 11 New South Wales facilities have achieved this accreditation. We recommend introducing an option to collect ‘exclusive breastfeeding’ on discharge’ which is in line with participant recommendations and the Baby Friendly Hospital accreditation. Other important considerations are the updated World Health Organization indicators such as, “Ever breastfed”; “Early initiation of breastfeeding” (first hour); “Exclusively breastfed for the first two days after birth”.
Diagnostic and prognostic value of plasma miR-106a-5p levels in patients with acute heart failure
Authors: Fei Aike , Li Li , Li Yunfang , Zhou Tie , Liu Yanfei 
Published: April 2024

Abstract
Background
It is essential to find reliable biomarkers for early diagnosis and prognosis of acute heart failure (AHF) for its mitigation. Currently, increasing attention is paid to the role of microRNAs (miRNAs/miRs) as diagnostic or prognostic markers for cardiovascular diseases. Since plasma miR-106a-5p has been observed to be downregulated in AHF, its value in the diagnosis and prognostic assessment of AHF deserves further exploration. Accordingly, this study analyzed the diagnostic and prognostic value of plasma miR-106a-5p in AHF patients.

Methods
Prospectively, this study included 127 AHF patients who met the 2021 European Society of Cardiology Guidelines and 127 control individuals. Plasma miR-106a-5p levels were determined with RT-qPCR. Spearman correlation analysis was performed to evaluate the correlation of plasma miR-106a-5p levels with NT-proBNP and hs-CRP levels in AHF patients. All AHF patients were followed up for 1 year and allocated into poor and good prognosis groups, and plasma miR-106a-5p levels were compared. The diagnostic and prognostic value of plasma miR-106a-5p for AHF was assessed with a receiver-operating characteristic curve.

Results
Plasma miR-106a-5p was lowly expressed in AHF patients versus controls (0.53 ± 0.26 vs. 1.09 ± 0.46) and showed significant negative correlations with NT-proBNP and hs-CRP levels. Plasma miR-106a-5p level < 0.655 could assist in AHF diagnosis. Plasma miR-106a-5p levels were markedly lower in poor-prognosis AHF patients than in good-prognosis patients. Plasma miR-106a-5p level < 0.544 could assist in predicting poor prognosis in AHF patients.

Conclusion
Plasma miR-106a-5p is downregulated in AHF patients and could assist in diagnosis and poor prognosis prediction of AHF.
Conventional and novel [18F]FDG PET/CT features as predictors of CAR-T cell therapy outcome in large B-cell lymphoma
Authors: Leithner Doris , Flynn Jessica R. , Devlin Sean M. , Mauguen Audrey , Fei Teng , Zeng Shang , Zheng Junting , Imber Brandon S. , Hubbeling Harper , Mayerhoefer Marius E. , Bedmutha Akshay , Luttwak Efrat , Corona Magdalena , Dahi Parastoo B. , Luna de Abia Alejandro , Landego Ivan , Lin Richard J. , Palomba M. Lia , Scordo Michael , Park Jae H. , Tomas Ana Alarcon , Salles Gilles , Lafontaine Daniel , Michaud Laure , Shah Gunjan L. , Perales Miguel-Angel , Shouval Roni , Schöder Heiko 
Published: April 2024

AbstractRelapse and toxicity limit the effectiveness of chimeric antigen receptor T-cell (CAR-T) therapy for large B-cell lymphoma (LBCL), yet biomarkers that predict outcomes and toxicity are lacking. We examined radiomic features extracted from pre-CAR-T 18F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) scans (n = 341) of 180 patients (121 male; median age, 66 years). Three conventional (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], total lesion glycolysis [TLG]) and 116 novel radiomic features were assessed, along with inflammatory markers, toxicities, and outcomes. At both pre-apheresis and pre-infusion time points, conventional PET features of disease correlated with elevated inflammatory markers. At pre-infusion, MTV was associated with grade ≥ 2 cytokine release syndrome (odds ratio [OR] for 100 mL increase: 1.08 [95% confidence interval (CI), 1.01–1.20], P = 0.031), and SUVmax was associated with failure to achieve complete response (CR) (OR 1.72 [95% CI, 1.24–2.43], P < 0.001). Higher pre-apheresis and pre-infusion MTV values were associated with shorter progression-free survival (PFS) (HR for 10-unit increase: 1.11 [95% CI, 1.05–1.17], P < 0.001; 1.04 [95% CI, 1.02–1.07], P < 0.001) and shorter overall survival (HR for 100-unit increase: 1.14 [95% CI, 1.07–1.21], P < 0.001; 1.04 [95% CI, 1.02–1.06], P < 0.001). A combined MTV and LDH measure stratified patients into high and low PFS risk groups. Multiple pre-infusion novel radiomic features were associated with CR. These quantitative conventional [18F]FDG PET/CT features obtained before CAR-T cell infusion, which were correlated with inflammation markers, may provide prognostic biomarkers for CAR-T therapy efficacy and toxicity. The use of conventional and novel radiomic features may thus help identify high-risk patients for earlier interventions.
Chemotherapy-elicited extracellular vesicle CXCL1 from dying cells promotes triple-negative breast cancer metastasis by activating TAM/PD-L1 signaling
Authors: Wang Shengqi , Li Jing , Hong Shicui , Wang Neng , Xu Shang , Yang Bowen , Zheng Yifeng , Zhang Juping , Pan Bo , Hu Yudie , Wang Zhiyu 
Published: April 2024

Abstract
Background
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and chemotherapy still serves as the cornerstone treatment functioning by inducing cytotoxic cell death. Notably, emerging evidence suggests that dying cell-released signals may induce cancer progression and metastasis by modulating the surrounding microenvironment. However, the underlying molecular mechanisms and targeting strategies are yet to be explored.

Methods
Apoptotic TNBC cells induced by paclitaxel or adriamycin treatment were sorted and their released extracellular vesicles (EV-dead) were isolated from the cell supernatants. Chemokine array analysis was conducted to identify the crucial molecules in EV-dead. Zebrafish and mouse xenograft models were used to investigate the effect of EV-dead on TNBC progression in vivo.

Results
It was demonstrated that EV-dead were phagocytized by macrophages and induced TNBC metastasis by promoting the infiltration of immunosuppressive PD-L1+ TAMs. Chemokine array identified CXCL1 as a crucial component in EV-dead to activate TAM/PD-L1 signaling. CXCL1 knockdown in EV-dead or macrophage depletion significantly inhibited EV-dead-induced TNBC growth and metastasis. Mechanistic investigations revealed that CXCL1EV-dead enhanced TAM/PD-L1 signaling by transcriptionally activating EED-mediated PD-L1 promoter activity. More importantly, TPCA-1 (2-[(aminocarbonyl) amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide) was screened as a promising inhibitor targeting CXCL1 signals in EVs to enhance paclitaxel chemosensitivity and limit TNBC metastasis without noticeable toxicities.

Conclusions
Our results highlight CXCL1EV-dead as a novel dying cell-released signal and provide TPCA-1 as a targeting candidate to improve TNBC prognosis.

Graphical abstract