bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex differences and dietary patterns in the association of air pollutants and hypertension
Authors: Zhang Chen , Wang Yuanyuan , Xie Wei , Zhang Jingxian , Tian Ting , Zhu Qianrang , Fang Xinyu , Sui Jing , Pan Da , Xia Hui , Wang Shaokang , Sun Guiju , Dai Yue
Published: April 2024

Background

Hypertension is one of the major public health problems in China. Limited evidence exists regarding sex differences in the association between hypertension and air pollutants, as well as the impact of dietary factors on the relationship between air pollutants and hypertension. The aim of this study was to investigate the sex-specific effects of dietary patterns on the association between fine particulate matter (PM2.5), ozone(O3) and hypertension in adults residing in Jiangsu Province of China.

Methods

A total of 3189 adults from the 2015 China Adult Chronic Disease and Nutrition Surveillance in Jiangsu Province were included in this study. PM2.5 and O3 concentrations were estimated using satellite space-time models and assigned to each participant. Dietary patterns were determined by reduced rank regression (RRR), and multivariate logistic regression was used to assess the associations of the obtained dietary patterns with air pollutants and hypertension risk.

Results

After adjusting for confounding variables, we found that males were more sensitive to long-term exposure to PM2.5 (Odds ratio (OR) = 1.42 95%CI:1.08,1.87), and females were more sensitive to long-term exposure to O3 (OR = 1.61 95%CI:1.15,2.23). Traditional southern pattern identified through RRR exhibited a protective effect against hypertension in males (OR = 0.73 95%CI: 0.56,1.00). The results of the interaction between dietary pattern score and PM2.5 revealed that adherence to traditional southern pattern was significantly associated with a decreased risk of hypertension in males (P < 0.05), while no significant association was observed among females.

Conclusions

Our findings suggested that sex differences existed in the association between dietary patterns, air pollutants and hypertension. Furthermore, we found that adherence to traditional southern pattern may mitigate the risk of long-term PM2.5 exposure-induced hypertension in males.
Retraction Note: Children’s physical activity level and sedentary behaviour in Norwegian early childhood education and care: effects of a staff-led cluster-randomised controlled trial
Authors: Andersen Eivind , Øvreås Steinar , Jørgensen Kari Anne , Borch-Jenssen Janne , Moser Thomas
Published: April 2024

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12889-024-18629-0.
Socioeconomic and cultural factors associated with pap smear screening among French women living in Réunion Island
Authors: Houpert Rémi , Bendiane Marc-Karim , Huiart Laetitia , Bouhnik Anne-Deborah , Alleaume Caroline , Touzani Rajae , Veronique-Baudin Jacqueline , Mancini Julien , Joachim Clarisse , Chirpaz Emmanuel
Published: April 2024

Background

Réunion Island is a French overseas territory located in the southern Indian Ocean, with a challenging socioeconomic and multicultural context. Compared to mainland France, Réunion has an overincidence and overmortality of cervical cancer. In order to investigate these two issues, it is important to evaluate the barriers and potential levers to Pap smear screening among female inhabitants of the island. We aimed to identify the specific socio-demographic factors, cultural factors, and living conditions associated with Pap smear screening in Réunion, with a view to increasing uptake.

Methods

We conducted a Knowledge Attitude Behavior and Practices (KABP) survey on cervical cancer screening practices among women aged between 25 and 65 years old living in Réunion Island, selected using random digit dialing sampling. Data were collected using Computer Assistant Telephone Interviews. Weighted chi-squared tests and Student’s t-tests were used to compare women who had up-to-date Pap smear screening with women who did not. Weighted logistic models were used to identify the factors associated with not having up-to-date screening.

Results

A total of 1000 women were included in the study. Of these, 88.1% had a Pap smear test during the previous three years. Factors independently associated with not being up to date were as follows: aged over 55 (AOR 2.3 [1.2–4.3]), no children (AOR 2.5 [1.4–4.3]), having free universal health coverage (AOR 1.7 [1.1–2.7]), an income per unit consumption lower than 1500€ per month (AOR 2.0 [1.1–3.7]), low health literacy (AOR 2.7 [1.7–4.1]), not consulting a general practitioner in the prior 12 months (AOR 3.6 [2.0-6.5]), and a BMI > 30 (AOR 2.6 [1.5–4.4]).

Conclusions

This is the first large-scale survey focusing on recommended Pap smear screening uptake in Réunion Island. Although self-reported screening incidence was higher than in mainland France, national screening policies must take into account the island’s diverse social and cultural characteristics (e.g., an ageing population, low health literacy), while implementing actions to fight against poverty and increase general access to healthcare.
Chinese and Belgian pediatricians’ perspectives toward pediatric palliative care: an online survey
Authors: Zhong Yajing , Cavolo Alice , Labarque Veerle , de Casterlé Bernadette Dierckx , Gastmans Chris
Published: April 2024

Background

As pediatricians play a vital role in pediatric palliative care (PPC), understanding their perspectives toward PPC is important. PPC is established for a long time in Belgium, but has a shorter tradition in China, although it is growing in the last decade. Sampling and comparing the perspectives of these pediatricians could be insightful for both countries. Therefore, we sampled and compared perspectives of pediatricians in China and Belgium toward PPC, and explored factors influencing their perspectives.

Methods

We conducted a cross-sectional online survey using the validated Pediatric Palliative Care Attitude Scale (PPCAS). Over a five-month period, we recruited pediatricians practicing in China (C) and Flanders (F), Belgium. Convenience sampling and snowballing were used. We analyzed data with descriptive statistics, and evaluated group differences with univariate, multivariate and correlation tests.

Results

440 complete surveys were analyzed (F: 115; C: 325). Pediatricians in both regions had limited PPC experience (F: 2.92 ± 0.94; C: 2.76 ± 0.92). Compared to Flemish pediatricians, Chinese pediatricians perceived receiving less unit support (F: 3.42 ± 0.86; C: 2.80 ± 0.89); perceived PPC less important (F: 4.70 ± 0.79; C: 4.18 ± 0.94); and faced more personal obstacles while practicing PPC (F: 3.50 ± 0.76; C: 2.25 ± 0.58). Also, select socio-demographic characteristics (e.g., experiences caring for children with life-threatening condition and providing PPC) influenced pediatricians’ perspectives. Correlational analyses revealed that pediatricians’ PPC experiences significantly correlated with perceived unit support (ρF = 0.454; ρC=0.661).

Conclusions

Chinese pediatricians faced more barriers in practicing PPC. Expanding PPC experiences can influence pediatricians’ perspectives positively, which may be beneficial for the child and their family.
Endometriosis in infertile women: an observational and comparative study of quality of life, anxiety, and depression
Authors: Mori Lilian Pagano , Zaia Victor , Montagna Erik , Vilarino Fabia Lima , Barbosa Caio Parente
Published: April 2024

Background

A women’s chances of getting pregnant decreases in cases of infertility, which may have several clinical etiologies. The prevalence of infertility is estimated as 10–15% worldwide. One of the causes of infertility is endometriosis, defined as the presence of an endometrial gland and/or stroma outside the uterus, inducing a chronic inflammatory reaction. Thus, infertility and endometriosis are diagnoses that significantly affect women’s mental health. This study accessed and compared the levels of depression, anxiety, and quality of life in infertile women with and without endometriosis.

Methods

was an observational and cross-sectional study which included 201 infertile women, 81 of whom were also diagnosed with endometriosis. The STROBE Guidelines was used. The data were collected using validated scales: Hamilton D Questionnaire, Beck Depression Inventory, and Fertility Quality of Life Questionnaire; The data were collected at the Ideia Fertil Institute (Santo Andre, Brazil), between February 28 and June 8, 2019.

Results

the infertile women with endometriosis reported higher presence of depressive symptoms and a lower quality of life compared to women with infertility only. Similar presence of anxiety symptoms was observed regardless of being diagnosed with endometriosis. Women with infertility and endometriosis presented lower levels in quality-of-life domains when compared to women with infertility only - Mind and Body (58.33 × 79.17, p < 0.001), Relational (75 × 81.25, p = 0.009), Social (66.67 × 77.08, p = 0.001), Emotional (50.62 × 67.43, p < 0.001).

Conclusion

the findings indicate the need for increased psychosocial support care for women suffering from infertility and endometriosis to assist them in maintaining and managing their own mental health and achieving their reproductive goals.
Anti-inflammatory effect of curcuminoids and their analogs in hyperosmotic human corneal limbus epithelial cells
Authors: Kasetsuwan Ngamjit , Reinprayoon Usanee , Uthaithammarat Lita , Sereemaspun Amornpun , Sae-liang Nutchanart , Chaichompoo Waraluck , Suksamrarn Apichart
Published: April 2024

Background

To assess the efficacy of curcuminoids (curcumin, demethoxycurcumin, bisdemethoxycurcumin [BDC]) and their analogs (tetrahydrocurcumin [THC], tetrahydrodemethoxycurcumin [THDC], tetrahydrobisdemethoxycurcumin) in reducing inflammatory cytokines and their toxicity to primary human corneal limbal epithelial cells, these cells were cultured and exposed to these compounds.

Methods

The PrestoBlue assay assessed cell viability after treatment. Anti-inflammatory effects on hyperosmotic cells were determined using real-time polymerase chain reaction and significance was gauged using one-way analysis of variance and Tukey’s tests, considering p-values < 0.05 as significant.

Results

Curcuminoids and their analogs, at 1, 10, and 100 µM, exhibited no effect on cell viability compared to controls. However, cyclosporin A 1:500 significantly reduced cell viability more than most curcuminoid treatments, except 100 µM curcumin and BDC. All tested curcuminoids and analogs at these concentrations significantly decreased mRNA expression levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-17 A, matrix metallopeptidase-9, and intercellular adhesion molecule-1 after 90 mM NaCl stimulation compared to untreated cells. Furthermore, proinflammatory cytokine levels from hyperosmotic cells treated with 1, 10, and 100 µM curcumin, 100 µM BDC, 100 µM THC, 1 and 100 µM THDC mirrored those treated with cyclosporin A 1:500.

Conclusion

The anti-inflammatory efficiency of 1 and 10 µM curcumin, 100 µM THC, 1 and 100 µM THDC was comparable to that of cyclosporin A 1:500 while maintaining cell viability.
Enhancing clinical reasoning for management of non-communicable diseases: virtual patient cases as a learning strategy for nurses in primary healthcare centers: a pre-post study design
Authors: Nyiringango Gerard , Fors Uno , Forsberg Elenita , Tumusiime David K.
Published: April 2024

Background

In Rwanda, nurses manage all primary care at health centres, and therefore are their clinical reasoning skills important. In this study, a web-based software that allows the creation of virtual patient cases (VP cases) has been used for studying the possibility of using VP cases for the continuous professional development of nurses in primary health care in Rwanda. Previous studies in pre-service education have linked VP cases with the enhancement of clinical reasoning, a critical competence for nurses. This study investigated the feasibility of continuous professional development through VP cases to further train in-service nurses in clinical reasoning.

Method

The study used a pre-post test design. Initially, seventy-six participants completed a questionnaire as part of the pre-test phase, subsequently invited to engage with all four VP cases, and finally responded to the post-test questionnaire evaluating clinical reasoning skills. Fifty-six participants successfully completed the entire study process and were considered in the analysis. The primary outcomes of this study were evaluated using a paired t-test for the statistical analysis.

Results

The results show that the mean score of clinical reasoning increased significantly from the pre-test to the post-test for all four illness areas (p < 0.001). The study findings showed no statistically significant difference in participants’ scores based on demographic factors, including whether they worked in urban or rural areas. 

Conclusion and recommendation

Utilizing VP cases appears to significantly enhance the continuous professional development of nurses, fostering a deliberate learning process that enables them to reflect on how they manage cases and, in turn, refine their clinical reasoning skills. This study strongly recommends incorporating VP cases in the continuous professional development of nurses at the primary health level (health centers). This is especially pertinent in a context where nurses are required to perform diagnostic processes similar to those employed by physicians.
Mapping of Alzheimer’s disease related data elements and the NIH Common Data Elements
Authors: Hao Xubing , Abeysinghe Rashmie , Zheng Fengbo , Schulz Paul E. ,   The Alzheimer’s Disease Neuroimaging Initiative, Cui Licong
Published: April 2024

Background

Alzheimer’s Disease (AD) is a devastating disease that destroys memory and other cognitive functions. There has been an increasing research effort to prevent and treat AD. In the US, two major data sharing resources for AD research are the National Alzheimer’s Coordinating Center (NACC) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI); Additionally, the National Institutes of Health (NIH) Common Data Elements (CDE) Repository has been developed to facilitate data sharing and improve the interoperability among data sets in various disease research areas.

Method

To better understand how AD-related data elements in these resources are interoperable with each other, we leverage different representation models to map data elements from different resources: NACC to ADNI, NACC to NIH CDE, and ADNI to NIH CDE. We explore bag-of-words based and word embeddings based models (Word2Vec and BioWordVec) to perform the data element mappings in these resources.

Results

The data dictionaries downloaded on November 23, 2021 contain 1,195 data elements in NACC, 13,918 in ADNI, and 27,213 in NIH CDE Repository. Data element preprocessing reduced the numbers of NACC and ADNI data elements for mapping to 1,099 and 7,584 respectively. Manual evaluation of the mapping results showed that the bag-of-words based approach achieved the best precision, while the BioWordVec based approach attained the best recall. In total, the three approaches mapped 175 out of 1,099 (15.92%) NACC data elements to ADNI; 107 out of 1,099 (9.74%) NACC data elements to NIH CDE; and 171 out of 7,584 (2.25%) ADNI data elements to NIH CDE.

Conclusions

The bag-of-words based and word embeddings based approaches showed promise in mapping AD-related data elements between different resources. Although the mapping approaches need further improvement, our result indicates that there is a critical need to standardize CDEs across these valuable AD research resources in order to maximize the discoveries regarding AD pathophysiology, diagnosis, and treatment that can be gleaned from them.
Non-dispensing pharmacists integrated into general practices as a new interprofessional model: a qualitative evaluation of general practitioners’ experiences and views
Authors: Hazen A.C.M. , Sloeserwij V.M. , de Groot E. , de Gier J.J. , de Wit N.J. , de Bont A.A. , Zwart D.L.M.
Published: April 2024

Background

A new interprofessional model incorporating non-dispensing pharmacists in general practice teams can improve the quality of pharmaceutical care. However, results of the model are dependent on the context. Understanding when, why and how the model works may increase chances of successful broader implementation in other general practices. Earlier theories suggested that the results of the model are achieved by bringing pharmacotherapeutic knowledge into general practices. This mechanism may not be enough for successful implementation of the model. We wanted to understand better how establishing new interprofessional models in existing healthcare organisations takes place.

Methods

An interview study, with a realist informed evaluation was conducted. This qualitative study was part of the Pharmacotherapy Optimisation through Integration of a Non-dispensing pharmacist in primary care Teams (POINT) project. We invited the general practitioners of the 9 general practices who (had) worked closely with a non-dispensing pharmacist for an interview. Interview data were analysed through discussions about the coding with the research team where themes were developed over time.

Results

We interviewed 2 general practitioners in each general practice (18 interviews in total). In a context where general practitioners acknowledge the need for improvement and are willing to work with a non-dispensing pharmacist as a new team member, the following mechanisms are triggered. Non-dispensing pharmacists add new knowledge to current general practice. Through everyday talk (discursive actions) both general practitioners and non-dispensing pharmacists evolve in what they consider appropriate, legitimate and imaginable in their work situations. They align their professional identities.

Conclusions

Not only the addition of new knowledge of non-dispensing pharmacist to the general practice team is crucial for the success of this interprofessional healthcare model, but also alignment of the general practitioners’ and non-dispensing pharmacists’ professional identities. This is essentially different from traditional pharmaceutical care models, in which pharmacists and GPs work in separate organisations. To induce the process of identity alignment, general practitioners need to acknowledge the need to improve the quality of pharmaceutical care interprofessionally. By acknowledging the aspect of interprofessionality, both general practitioners and non-dispensing pharmacists will explore and reflect on what they consider appropriate, legitimate and imaginable in carrying out their professional roles.

Trial registration

The POINT project was pre-registered in The Netherlands National Trial Register, with Trial registration number NTR-4389.
Diabetic kidney disease screening status and related factors: a cross-sectional study of patients with type 2 diabetes in six provinces in China
Authors: Xia Zhang , Luo Xuechun , Wang Yanzhi , Xu Tingling , Dong Jianqun , Jiang Wei , Jiang Yingying
Published: April 2024

Objective

To understand the awareness and practice of diabetic kidney disease (DKD) or nephropathy screening among community-based patients with type 2 diabetes in six provinces and cities in China, and to analyse the related factors affecting screening practices.

Methods

From December 2021 to March 2022, a cross-sectional survey was conducted using a structured questionnaire in 6230 patients with type 2 diabetes aged 18 years and older. The content of the questionnaire includes three parts: the general situation of diabetic patients (gender, age, ethnicity, marriage, education, occupation, etc.), DKD screening practices, and the evaluation of DKD screening services.

Results

89.70% of the patients had their fasting blood glucose measured every six months, 21.12% of the patients had their glycosylated hemoglobin measured every six months, and only 13.11% and 9.34% of the patients had a urine protein-creatinine ratio test and estimated glomerular filtration rate test every 12 months. The proportions of glycosylated hemoglobin, urine protein-creatinine ratio, and estimated glomerular filtration rate were relatively high in young, northern, highly educated, and long-duration type 2 diabetic patients.

Conclusion

The results of this survey found that the proportion of urine protein-creatinine ratio testing, estimated glomerular filtration rate testing, and glycosylated hemoglobin testing in Chinese patients with type 2 diabetes was very low. Patients with type 2 diabetes in rural areas, southern areas, with low education level, and short course of disease have lower detection rates for DKD, and hence lower rates of prevention and treatment.
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

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

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

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

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

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

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

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

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

Relapse 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

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
Growth impairment in children with atrophic autoimmune thyroiditis and pituitary hyperplasia
Authors: Corica Domenico , Abbate Tiziana , Kucharska Anna Malgorzata , Wojcik Malgorzata , Vierucci Francesco , Valenzise Mariella , Li Pomi Alessandra , Pepe Giorgia , Tuli Gerdi , Pyrzak Beata , Aversa Tommaso , Wasniewska Malgorzata
Published: April 2024

Background

Atrophic autoimmune thyroiditis (AAT) is a rare phenotype of autoimmune thyroiditis (AT) in pediatric age. AAT occurs without thyroid enlargement leading to a delay in its diagnosis. Growth impairment is infrequent in autoimmune thyroiditis, if timely diagnosed. Prolonged severe hypothyroidism is a rare cause of pituitary hyperplasia (PH) in childhood. Loss of thyroxine negative feedback causes a TRH-dependent hyperplasia of pituitary thyrotroph cells resulting in adenohypophysis enlargement. A transdifferentiation of pituitary somatotroph cells into thyrotroph cells could explain growth failure in those patients.

Methods

Twelve patients were retrospectively evaluated at five Italian and Polish Centres of Pediatric Endocrinology for height growth impairment. In all Centres, patients underwent routine clinical, biochemical and radiological evaluations.

Results

At the time of first assessment, the 75% of patients presented height growth arrest, while the remaining ones showed growth impairment. The study of thyroid function documented a condition of hypothyroidism, due to AT, in the entire cohort, although all patients had no thyroid enlargement. Thyroid ultrasound showed frankly atrophic or normal gland without goiter. Cerebral MRI documented symmetrical enlargement of the adenohypophysis in all patients and a homogeneous enhancement of the gland after the administration of Gadolinium-DPTA. Replacement therapy with levothyroxine was started and patients underwent close follow-up every 3 months. During the 12 months of follow-up, an improvement in terms of height growth has been observed in 88% of patients who continued the follow-up. Laboratory findings showed normalization of thyroid function and the control brain MRI documented complete regression of PH to a volume within the normal range for age and sex.

Conclusions

This is the largest pediatric cohort with severe autoimmune primary hypothyroidism without goiter, but with pituitary hyperplasia in which significant growth impairment was the most evident presenting sign. AAT phenotype might be correlated with this specific clinical presentation. In youths with growth impairment, hypothyroidism should always be excluded even in the absence of clear clinical signs of dysthyroidism.
Comparison of different genetic testing modalities applied in paediatric patients with steroid-resistant nephrotic syndrome
Authors: Cheng Xueting , Chen Jiahuan , Yang Xueying , Chan Han , Yang Xia , Jiao Jia , Wang Anshuo , Zhang Gaofu , Chen Xuelan , Li Xiaoqin , Wang Mo , Yang Baohui , Yang Haiping , Li Qiu
Published: April 2024

Background

Steroid-resistant nephrotic syndrome (SRNS) are monogenic in some cases, however, there are still no clear guidelines on genetic testing in the clinical practice of SRNS in children.

Methods

Three hundred thirty-two children were diagnosed with SRNS, and all children underwent genetic testing, including gene panels and/or whole-exome/genome sequencing (WES/WGS), during treatment. We analysed the relationship between clinical manifestation and genotype, and compared different genetic testing methods’ detection rates and prices.

Results

In this study, 30.12% (100/332) of children diagnosed with SRNS had monogenic causes of the disease. With 33.7% (122/332) of children achieving complete remission, 88.5% (108/122) received steroids combined with tacrolimus (TAC). In detectability, WES increased by 8.69% (4/46) on gene panel testing, while WGS increased by 4.27% (5/117) on WES, and WES was approximately 1/7 of the price of WGS for every further 1% increase in pathogenicity.

Conclusions

We verified that steroids combined with TAC were the most effective option in paediatric SRNS. In detection efficiency, we found that WGS was the highest, followed by WES. The panel was the lowest, but the most cost-effective method when considering the economic-benefit ratio, and thus it should be recommended first in SRNS.