bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caring for high-need patients
Authors: Hempel Susanne , Bolshakova Maria , Hochman Michael , Jimenez Elvira , Thompson Gina , Motala Aneesa , Ganz David A. , Gabrielian Sonya , Edwards Samuel , Zenner James , Dennis Ben , Chang Evelyn 
Published: November 2023

Abstract
Objective
We aimed to explore the construct of “high need” and identify common need domains among high-need patients, their care professionals, and healthcare organizations; and to describe the interventions that health care systems use to address these needs, including exploring the potential unintended consequences of interventions.

Methods
We conducted a modified Delphi panel informed by an environmental scan. Expert stakeholders included patients, interdisciplinary healthcare practitioners (physicians, social workers, peer navigators), implementation scientists, and policy makers. The environmental scan used a rapid literature review and semi-structured interviews with key informants who provide healthcare for high-need patients. We convened a day-long virtual panel meeting, preceded and followed by online surveys to establish consensus.

Results
The environmental scan identified 46 systematic reviews on high-need patients, 19 empirical studies documenting needs, 14 intervention taxonomies, and 9 studies providing construct validity for the concept “high need.” Panelists explored the construct and terminology and established that individual patients’ needs are unique, but areas of commonality exist across all high-need patients. Panelists agreed on 11 domains describing patient (e.g., social circumstances), 5 care professional (e.g., communication), and 8 organizational (e.g., staffing arrangements) needs. Panelists developed a taxonomy of interventions with 15 categories (e.g., care navigation, care coordination, identification and monitoring) directed at patients, care professionals, or the organization. The project identified potentially unintended consequences of interventions for high-need patients, including high costs incurred for patients, increased time and effort for care professionals, and identification of needs without resources to respond appropriately.

Conclusions
Care for high-need patients requires a thoughtful approach; differentiating need domains provides multiple entry points for interventions directed at patients, care professionals, and organizations. Implementation efforts should consider outlined intended and unintended downstream effects on patients, care professionals, and organizations.
An economic evaluation of pharmacopuncture versus usual care for chronic neck pain: a pragmatic randomized controlled trial
Authors: Kim Doori , Kim Eun-San , Song Hyun Jin , Park Sun-Young , Park Kyoung Sun , Lee Yoon Jae , Ha In-Hyuk 
Published: November 2023

Abstract
Background
This study aimed to evaluate the cost utility of pharmacopuncture in comparison with usual care for patients with chronic neck pain.

Methods
A 12-week, multicenter, pragmatic randomized controlled trial was conducted, and 101 patients suffering from chronic neck pain for more than six months were randomly placed into the pharmacopuncture and usual care groups to receive four weeks of treatment and 12 weeks of follow-up observations. The quality-adjusted life year (QALY) was calculated using EQ-5D and SF-6D. Concerning costs in 2019, a primary analysis was performed on societal perspective cost, and an additional analysis was performed on healthcare perspective cost.

Results
Compared to usual care, pharmacopuncture was superior as it showed a slightly higher QALY and a lower incremental cost of $1,157 from a societal perspective. The probability that pharmacopuncture would be more cost-effective at a willingness-to-pay (WTP) of $26,374 was 100%. Pharmacopuncture was also superior from a healthcare perspective, with a lower incremental cost of $26. The probability that pharmacopuncture would be more cost-effective at a WTP of $26,374 was 83.7%.

Conclusions
Overall, pharmacopuncture for chronic neck pain was found to be more cost-effective compared to usual care, implying that clinicians and policy makers should consider new treatment options for neck pain.

Trial registration
Number NCT04035018 (29/07/2019) Clinicaltrials.gov; Number KCT0004243 (26/08/2019) Clinical Research Information Service.
Trajectories of primary health care utilization: a 10-year follow-up after the Swedish Patient Choice Reform of primary health care
Authors: Kohnke Hannes , Zielinski Andrzej , Beckman Anders , Ohlsson Henrik 
Published: November 2023

Abstract
Background
In January 2010, the choice reform was instituted in Swedish primary health care establishing free entry for private primary health care providers and enabling patients to choose freely among primary health care centers. The motivation behind the reform was to improve access to primary care and responsiveness to patient expectations. Reform effects on health care utilization have previously been investigated by using subgroup analyses assuming a pattern of homogeneous subgroups of the population. By using a different methodological approach, the aim of this study was to, from an equity perspective, investigate long term trends of primary health care utilization following the choice reform.

Method
A closed cohort was created based on register data from Region Skåne, the third most populated region in Sweden, describing individuals’ health care utilization between 2007–2017. Using a novel approach, utilization data, measured as primary health care visits, was matched with socioeconomic and geographic determinants, and analyzed using logistic regression models.

Results
A total of 659,298 individuals were included in the cohort. Sex differences in utilization were recorded to decrease in the older age group and to increase in the younger age group. Multivariable logistic regression showed increasing utilization in older men to be associated with higher socioeconomic position, while in women it was associated with lower socioeconomic position. Furthermore, groups of becoming high utilizers were all associated with lower socioeconomic position and with residence in urban areas.

Conclusion
The impact of demographic, socioeconomic and geographic determinants on primary health care utilization varies in magnitude and direction between groups of the population. As a result, the increase in utilization as observed in the general population following the choice reform is unevenly distributed between different population groups.
Gene expression profiles separate endometriosis lesion subtypes and indicate a sensitivity of endometrioma to estrogen suppressive treatments through elevated ESR2 expression
Authors: Marla Sushma , Mortlock Sally , Heinosalo Taija , Poutanen Matti , Montgomery Grant W. , McKinnon Brett David 
Published: November 2023

Abstract
Background
Endometriosis is a common, gynaecological disease characterised by the presence of endometrial-like cells growing outside the uterus. Lesions appear at multiple locations, present with variation in appearance, size and depth of invasion. Despite hormones being the recommended first-line treatment, their efficacy, success and side effects vary widely amongst study populations. Current, hormonal medication for endometriosis is designed to suppress systemic oestrogen. Whether these hormones can influence the lesions themselves is not yet clear. Evidence of hormone receptor expression in endometriotic lesions and their ability to respond is conflicting. A variation in their expression, activation of transcriptional co-regulators and the potential to respond may contribute to their variation in patient outcomes. Identifying patients who would benefit from hormonal treatments remain an important goal in endometriosis research.

Methods
Using gene expression data from endometriosis lesions including endometrioma (OMA, n = 28), superficial peritoneal lesions (SUP, n = 72) and deeply infiltrating lesions (DIE, n = 78), we performed principal component analysis, differential gene expression and gene correlation analyses to assess the impact of menstrual stage, lesion subtype and hormonal treatment on the gene expression.

Results
The gene expression profiles did not vary based on menstrual stage, but could distinguish lesion subtypes with OMA significantly differentiating from both SUP and DIE. Additionally, the effect of oestrogen suppression medication altered the gene expression profile in OMA, while such effect was not observed in SUP or DIE. Analysis of the target receptors for hormonal medication indicated ESR2 was differentially expressed in OMA and that genes that correlated with ESR2 varied significantly between medicated and non-medicated OMA samples.

Conclusions
Our results demonstrate of the different lesion types OMA present with strongest response to hormonal treatment directly through ESR2. The data suggests that there may be the potential to target treatment options to individual patients based on pre-surgical diagnoses.
Platelet and mitochondrial RNA is decreased in plasma-derived extracellular vesicles in women with preeclampsia—an exploratory study
Authors: Lekva Tove , Sundaram Arvind Y.FM. , Roland Marie Cecilie Paasche , Åsheim June , Michelsen Annika E. , Norwitz Errol R. , Aukrust Pål , Gilfillan Gregor D. , Ueland Thor 
Published: November 2023

Abstract
Background
Circulating extracellular vesicles (EVs) are increased in preeclampsia (PE) and are associated with severity and progression. We examined in this exploratory cohort study if the mRNAs and long noncoding RNAs (lncRNAs) in plasma-derived EVs were dysregulated in PE compared to normal pregnancy and display different temporal patterns during gestation.

Methods
We isolated EVs from plasma at weeks 22–24 and 36–38 in women with and without PE (n=7 in each group) and performed RNA-seq, focusing on mRNAs and lncRNAs. We validated highly expressed mitochondrial and platelet-derived RNAs discovered from central pathways in 60 women with/without PE. We examined further one of the regulated RNAs, noncoding mitochondrially encoded tRNA alanine (MT-TA), in leukocytes and plasma to investigate its biomarker potential and association with clinical markers of PE.

Results
We found abundant levels of platelet-derived and mitochondrial RNAs in EVs. Expression of these RNAs were decreased and lncRNAs increased in EVs from PE compared to without PE. These findings were further validated by qPCR for mitochondrial RNAs MT-TA, MT-ND2, MT-CYB and platelet-derived RNAs PPBP, PF4, CLU in EVs. Decreased expression of mitochondrial tRNA MT-TA in leukocytes at 22–24 weeks was strongly associated with the subsequent development of PE.

Conclusions
Platelet-derived and mitochondrial RNA were highly expressed in plasma EVs and were decreased in EVs isolated from women with PE compared to without PE. LncRNAs were mostly increased in PE. The MT-TA in leukocytes may be a useful biomarker for prediction and/or early detection of PE.

Graphical Abstract
Impact of high-power short-duration atrial fibrillation ablation technique on the incidence of silent cerebral embolism: a prospective randomized controlled study
Authors: Chen Wei-Jie , Gan Chun-Xia , Cai Yang-Wei , Liu Yang-Yang , Xiao Pei-Lin , Zou Li-Li , Xiong Qing-Song , Qin Fang , Tao Xie-Xin , Li Ran , Du Hua-An , Liu Zeng-Zhang , Yin Yue-Hui , Ling Zhi-Yu 
Published: November 2023

Abstract
Background
High-power short-duration (HPSD) ablation strategy has emerged as a popular approach for treating atrial fibrillation (AF), with shorter ablation time. The utilized Smart Touch Surround Flow (STSF) catheter, with 56 holes around the electrode, lowers electrode-tissue temperature and thrombus risk. Thus, we conducted this prospective, randomized study to investigate if the HPSD strategy with STSF catheter in AF ablation procedures reduces the silent cerebral embolism (SCE) risk compared to the conventional approach with the Smart Touch (ST) catheter.

Methods
From June 2020 to September 2021, 100 AF patients were randomized 1:1 to the HPSD group using the STSF catheter (power set at 50 W) or the conventional group using the ST catheter (power set at 30 to 35 W). Pulmonary vein isolation was performed in all patients, with additional lesions at operator’s discretion. High-resolution cerebral diffusion-weighted magnetic resonance imaging (hDWI) with slice thickness of 1 mm was performed before and 24–72 h after ablation. The incidence of new periprocedural SCE was defined as the primary outcome. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA) test.

Results
All enrolled AF patients (median age 63, 60% male, 59% paroxysmal AF) underwent successful ablation. Post-procedural hDWI identified 106 lesions in 42 enrolled patients (42%), with 55 lesions in 22 patients (44%) in the HPSD group and 51 lesions in 20 patients (40%) in the conventional group (p = 0.685). No significant differences were observed between two groups regarding the average number of lesions (p = 0.751), maximum lesion diameter (p = 0.405), and total lesion volume per patient (p = 0.669). Persistent AF and CHA2DS2-VASc score were identified as SCE determinants during AF ablation procedure by multivariable regression analysis. No significant differences in MoCA scores were observed between patients with SCE and those without, both immediately post-procedure (p = 0.572) and at the 3-month follow-up (p = 0.743).

Conclusions
Involving a small sample size of 100 AF patients, this study reveals a similar incidence of SCE in AF ablation procedures, comparing the HPSD strategy using the STSF catheter to the conventional approach with the ST catheter.

Trial registration
Clinicaltrials.gov: NCT04408716.

Graphical Abstract
AF = Atrial fibrillation, DWI = Diffusion-weighted magnetic resonance imaging, HPSD = High-power short-duration, ST = Smart Touch, STSF = Smart Touch Surround Flow.
Retinal nerve fibre layer thinning and corneal nerve loss in patients with Bardet-Biedl syndrome
Authors: Belkadi Aziz , Thareja Gaurav , Khan Adnan , Stephan Nisha , Zaghlool Shaza , Halama Anna , Ahmed Ayeda Abdulsalam , Mohamoud Yasmin A. , Malek Joel , Suhre Karsten , Malik Rayaz A. 
Published: November 2023

Abstract
Background
Bardet-Biedl syndrome (BBS) is an autosomal recessive, genetically heterogeneous, pleiotropic disorder caused by variants in genes involved in the function of the primary cilium. We have harnessed genomics to identify BBS and ophthalmic technologies to describe novel features of BBS.

Case presentation
A patient with an unclear diagnosis of syndromic type 2 diabetes mellitus, another affected sibling and unaffected siblings and parents were sequenced using DNA extracted from saliva samples. Corneal confocal microscopy (CCM) and retinal spectral domain optical coherence tomography (SD-OCT) were used to identify novel ophthalmic features in these patients. The two affected individuals had a homozygous variant in C8orf37 (p.Trp185*). SD-OCT and CCM demonstrated a marked and patchy reduction in the retinal nerve fiber layer thickness and loss of corneal nerve fibers, respectively.

Conclusion
This report highlights the use of ophthalmic imaging to identify novel retinal and corneal abnormalities that extend the phenotype of BBS in a patient with syndromic type 2 diabetes.
Preeclampsia impedes foetal kidney development by delivering placenta-derived exosomes to glomerular endothelial cells
Authors: Gu Mengqi , Chen Pengzheng , Zeng Dongmei , Jiang Xiaotong , Lv Qingfeng , Li Yuchen , Zhang Fengyuan , Wan Shuting , Zhou Qian , Lu Yuan , Wang Xietong , Li Lei 
Published: November 2023

Abstract
Background
Foetal renal dysplasia is still the main cause of adult renal disease. Placenta-derived exosomes are an important communication tool, and they may play an important role in placental (both foetal and maternal) function. We hypothesize that in women with preeclampsia, foetal renal dysplasia is impeded by delivering placenta-derived exosomes to glomerular endothelial cells.

Methods
In the present study, we established a PE trophoblast oxidative stress model to isolate exosomes from supernatants by ultracentrifugation (NO-exo and H/R-exo) and collected normal and PE umbilical cord blood plasma to isolate exosomes by ultracentrifugation combined with sucrose density gradient centrifugation (N-exo and PE-exo), then we investigated their effects on foetal kidney development by in vitro, ex vivo and in vivo models.

Results
The PE trophoblast oxidative stress model was established successfully. After that, in in vitro studies, we found that H/R-exo and PE-exo could adversely affect glomerular endothelial cell proliferation, tubular formation, migration, and barrier functions. In ex vivo studies, H/R-exo and PE-exo both inhibited the growth and branch formation of kidney explants, along with the decrease of VE-cadherin and Occludin. In in vivo studies, we also found that H/R-exo and PE-exo could result in renal dysplasia, reduced glomerular number, and reduced barrier function in foetal mice.

Conclusions
In conclusion, we demonstrated that PE placenta-derived exosomes could lead to foetal renal dysplasia by delivering placenta-derived exosomes to foetal glomerular endothelial cells, which provides a novel understanding of the pathogenesis of foetal renal dysplasia.
Altered m6A RNA methylation governs denervation-induced muscle atrophy by regulating ubiquitin proteasome pathway
Authors: Sun Junjie , Zhou Hai , Chen Zehao , Zhang Han , Cao Yanzhe , Yao Xinlei , Chen Xin , Liu Boya , Gao Zihui , Shen Yuntian , Qi Lei , Sun Hualin 
Published: November 2023

Abstract
Background
Denervation-induced muscle atrophy is complex disease involving multiple biological processes with unknown mechanisms. N6-methyladenosine (m6A) participates in skeletal muscle physiology by regulating multiple levels of RNA metabolism, but its impact on denervation-induced muscle atrophy is still unclear. Here, we aimed to explore the changes, functions, and molecular mechanisms of m6A RNA methylation during denervation-induced muscle atrophy.

Methods
During denervation-induced muscle atrophy, the m6A immunoprecipitation sequencing (MeRIP-seq) as well as enzyme-linked immunosorbent assay analysis were used to detect the changes of m6A modified RNAs and the involved biological processes. 3-deazidenosine (Daa) and R-2-hydroxyglutarate (R-2HG) were used to verify the roles of m6A RNA methylation. Through bioinformatics analysis combined with experimental verification, the regulatory roles and mechanisms of m6A RNA methylation had been explored.

Results
There were many m6A modified RNAs with differences during denervation-induced muscle atrophy, and overall, they were mainly downregulated. After 72 h of denervation, the biological processes involved in the altered mRNA with m6A modification were mainly related to zinc ion binding, ubiquitin protein ligase activity, ATP binding and sequence-specific DNA binding and transcription coactivator activity. Daa reduced overall m6A levels in healthy skeletal muscles, which reduced skeletal muscle mass. On the contrary, the increase in m6A levels mediated by R-2HG alleviated denervation induced muscle atrophy. The m6A RNA methylation regulated skeletal muscle mass through ubiquitin–proteasome pathway.

Conclusion
This study indicated that decrease in m6A RNA methylation was a new symptom of denervation-induced muscle atrophy, and confirmed that targeting m6A alleviated denervation-induced muscle atrophy.
Perinatal foodborne titanium dioxide exposure-mediated dysbiosis predisposes mice to develop colitis through life
Authors: Carlé Caroline , Boucher Delphine , Morelli Luisa , Larue Camille , Ovtchinnikova Ekaterina , Battut Louise , Boumessid Kawthar , Airaud Melvin , Quaranta-Nicaise Muriel , Ravanat Jean-Luc , Dietrich Gilles , Menard Sandrine , Eberl Gérard , Barnich Nicolas , Mas Emmanuel , Carriere Marie , Al Nabhani Ziad , Barreau Frédérick 
Published: November 2023

Abstract
Background
Perinatal exposure to titanium dioxide (TiO2), as a foodborne particle, may influence the intestinal barrier function and the susceptibility to develop inflammatory bowel diseases (IBD) later in life. Here, we investigate the impact of perinatal foodborne TiO2 exposure on the intestinal mucosal function and the susceptibility to develop IBD-associated colitis. Pregnant and lactating mother mice were exposed to TiO2 until pups weaning and the gut microbiota and intestinal barrier function of their offspring was assessed at day 30 post-birth (weaning) and at adult age (50 days). Epigenetic marks was studied by DNA methylation profile measuring the level of 5-methyl-2′-deoxycytosine (5-Me-dC) in DNA from colic epithelial cells. The susceptibility to develop IBD has been monitored using dextran-sulfate sodium (DSS)-induced colitis model. Germ-free mice were used to define whether microbial transfer influence the mucosal homeostasis and subsequent exacerbation of DSS-induced colitis.

Results
In pregnant and lactating mice, foodborne TiO2 was able to translocate across the host barriers including gut, placenta and mammary gland to reach embryos and pups, respectively. This passage modified the chemical element composition of foetus, and spleen and liver of mothers and their offspring. We showed that perinatal exposure to TiO2 early in life alters the gut microbiota composition, increases the intestinal epithelial permeability and enhances the colonic cytokines and myosin light chain kinase expression. Moreover, perinatal exposure to TiO2 also modifies the abilities of intestinal stem cells to survive, grow and generate a functional epithelium. Maternal TiO2 exposure increases the susceptibility of offspring mice to develop severe DSS-induced colitis later in life. Finally, transfer of TiO2-induced microbiota dysbiosis to pregnant germ-free mice affects the homeostasis of the intestinal mucosal barrier early in life and confers an increased susceptibility to develop colitis in adult offspring.

Conclusions
Our findings indicate that foodborne TiO2 consumption during the perinatal period has negative long-lasting consequences on the development of the intestinal mucosal barrier toward higher colitis susceptibility. This demonstrates to which extent environmental factors influence the microbial-host interplay and impact the long-term mucosal homeostasis.