bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural small molecules synergize mesenchymal stem cells for injury repair in vital organs: a comprehensive review
Authors: Qu Yanling , Wang Zhe , Dong Lingjuan , Zhang Dan , Shang Fengqing , Li Afeng , Gao Yanni , Bai Qinhua , Liu Dan , Xie Xiaodong , Ming Leiguo 
Published: August 2024

AbstractMesenchymal stem cells (MSCs) therapy is a highly researched treatment that has the potential to promote immunomodulation and anti-inflammatory, anti-apoptotic, and antimicrobial activities. It is thought that it can enhance internal organ function, reverse tissue remodeling, and achieve significant organ repair and regeneration. However, the limited infusion, survival, and engraftment of transplanted MSCs diminish the effectiveness of MSCs-based therapy. Consequently, various preconditioning methods have emerged as strategies for enhancing the therapeutic effects of MSCs and achieving better clinical outcomes. In particular, the use of natural small molecule compounds (NSMs) as a pretreatment strategy is discussed in this narrative review, with a focus on their roles in regulating MSCs for injury repair in vital internal organs. Additionally, the discussion focuses on the future directions and challenges of transforming mesenchymal stem cell research into clinical applications.
Association between diabetes mellitus and giant cell arteritis: a bidirectional 2-sample mendelian randomization study
Authors: Chen Si , Zeng Xiaoli , Ma Xu , Luan Haixia , Nie Rui , Wang Yan , Liao Hua , Pan Lili , Yuan Hui 
Published: August 2024

Abstract
Objective
Recent studies have indicated a potential association between giant cell arteritis (GCA) and diabetes mellitus, encompassing both type 1 diabetes (T1D) and type 2 diabetes (T2D). However, the exact nature of this relationship requires further investigation to be fully elucidated.

Methods
Genetic links between T1D/T2D and GCA were explored using data from genome-wide association studies available to the public, focusing on populations of European ancestry. We applied a bidirectional mendelian randomization (MR) approach to assess the potential association between these diseases. Confirmatory analyses, including additional datasets and a comprehensive meta-analysis, were utilized. The inverse-variance-weighted (IVW) method was applied to pinpoint heterogeneity and pleiotropy, while subsequent sensitivity analyses aimed to trace the origins of any heterogeneity.

Results
Initial analysis demonstrated a correlation between T1D and an elevated likelihood of developing GCA (IVW odds ratio = 1.33, with a 95% confidence interval of 1.22–1.46, and a P-value of 9.42E−10). The causal association was verified through four validation datasets and meta-analysis (all P-value < 0.001). However, the reverse MR analysis was unable to detect any genetic basis for the increased risk of T1D due to GCA. Furthermore, we could not establish any causal links between T2D and GCA.

Conclusion
T1D patients may have a higher risk of developing GCA, whereas an inverse causal relationship was not evident. Furthermore, no causal relationship was detected between T2D and GCA. These insights shed light on the possible pathological mechanisms underlying GCA and may influence the future clinical handling of both T1D and GCA.
Happy times, careers and happenstance in UK psychiatry: time, timeliness, timelessness, eternity and contemporality
Authors: Ikkos George , Bouras Nick 
Published: August 2024

SummaryTo address some challenges facing psychiatrists today we discuss issues of happenstance and fulfilment in psychiatric careers through some of the record and reflections of four psychiatrists since the 1950s. We trace the changes in psychiatry attendant to the transition from the welfare to the neoliberal state and=its contemporary postmodern culture. We highlight the crucial importance of political-cultural as well as technological developments in determining psychiatric service management and provision, and clinical practice and career outcomes. In the light of this impact, in a global era that some highly respected authorities consider in apocalyptic terms, we advocate for the incorporation of training in political awareness and activism in the psychiatric curriculum and practice. We suggest that this is necessary for social justice and patient welfare and that it will help safeguard psychiatric professionalism, conscience and self-esteem.
Association between a selective 5-HT4 receptor agonist and incidence of major depressive disorder: emulated target trial
Authors: de Cates Angharad N. , Harmer Catherine J. , Harrison Paul J. , Cowen Philip J. , Emmanuel Anton , Travis Simon , Murphy Susannah E. , Taquet Maxime 
Published: August 2024

BackgroundThe serotonin 4 receptor (5-HT4R) is a promising target for the treatment of depression. Highly selective 5-HT4R agonists, such as prucalopride, have antidepressant-like and procognitive effects in preclinical models, but their clinical effects are not yet established.AimsTo determine whether prucalopride (a 5-HT4R agonist and licensed treatment for constipation) is associated with reduced incidence of depression in individuals with no past history of mental illness, compared with anti-constipation agents with no effect on the central nervous system.MethodUsing anonymised routinely collected data from a large-scale USA electronic health records network, we conducted an emulated target trial comparing depression incidence over 1 year in individuals without prior diagnoses of major mental illness, who initiated treatment with prucalopride versus two alternative anti-constipation agents that act by different mechanisms (linaclotide and lubiprostone). Cohorts were matched for 121 covariates capturing sociodemographic factors, and historical and/or concurrent comorbidities and medications. The primary outcome was a first diagnosis of major depressive disorder (ICD-10 code F32) within 1 year of the index date. Robustness of the results to changes in model and population specification was tested. Secondary outcomes included a first diagnosis of six other neuropsychiatric disorders.ResultsTreatment with prucalopride was associated with significantly lower incidence of depression in the following year compared with linaclotide (hazard ratio 0.87, 95% CI 0.76–0.99; P = 0.038; n = 8572 in each matched cohort) and lubiprostone (hazard ratio 0.79, 95% CI 0.69–0.91; P < 0.001; n = 8281). Significantly lower risks of all mood disorders and psychosis were also observed. Results were similar across robustness analyses.ConclusionsThese findings support preclinical data and suggest a role for 5-HT4R agonists as novel agents in the prevention of major depression. These findings should stimulate randomised controlled trials to confirm if these agents can serve as a novel class of antidepressant within a clinical setting.
Pre-Prediabetes: Insulin Resistance Is Associated With Cardiometabolic Risk in Nonobese Patients (STOP DIABETES)
Authors: Armato John , DeFronzo Ralph A , Abdul-Ghani Muhammad , Ruby Ron 
Published: August 2024

Abstract

Context
Prior studies have demonstrated glycemic and cardiometabolic risk in the prediabetic state.

Objective
This work aims to examine if insulin resistance (IR) is associated with markers of glycemic, cardiometabolic, and atherosclerotic risk in nonobese, nonprediabetic individuals compared to insulin-sensitive (IS) individuals matched for body mass index (BMI), sex, and age.

Methods
Of 1860 patients from the STOP DIABETES study, 624 had normal fasting plasma glucose, BMI less than 30, and glycated hemoglobin A1c (HbA1c) less than 5.7%. All received an oral glucose tolerance test. Insulin sensitivity was quantitated using the Matsuda index: less than the 25th percentile equals IR (n = 151) and 25th percentile or greater equals IS (n = 473). Measures of dysglycemia and cardiometabolic risk were compared between IR individuals (n = 151) and a subset of IS individuals who were matched for BMI, sex, and age (n = 151). Carotid intima media thickness and carotid plaque were measured in 65 IR and 76 IS individuals.

Results
Compared to matched IS patients, IR nonobese individuals demonstrated increased indicators of glycemic and cardiometabolic risk, including increased 60-minute plasma glucose and percentage of patients with 60-minute plasma glucose greater than 155 mg/dL; increased 120-minute plasma glucose; unrecognized impaired glucose tolerance and type 2 diabetes, decreased disposition index; increased systolic and diastolic blood pressure; elevated plasma triglycerides (TGs); reduced high-density lipoprotein (HDL) cholesterol; increased TGs/HDL ratio, and high-sensitivity C-reactive protein. The presence, size, and number of carotid plaques was greater in the IR group.

Conclusion
Approximately 1 in 4 nonobese patients in this population with normal fasting glucose and HbA1c were IR. In these nonobese participants, IR was associated with multiple indicators of dysglycemia and cardiometabolic risk.
Associations of Glycemic Measures in the Normal Range With All-Cause Mortality in the Absence of Traditional Risk Factors
Authors: Wu Deshan , Shi Shuxiao , Li Kexin , Zhong Victor W 
Published: August 2024

Abstract

Context
The investigation of the association between blood glucose within normal range and all-cause mortality among individuals without traditional risk factors is limited.

Objective
To determine the associations of 3 glycemic measures (fasting plasma glucose [FPG], hemoglobin A1c [HbA1c], and 2-hour glucose) in the normal range with all-cause mortality among individuals without traditional risk factors.

Methods
Retrospective cohort study of US National Health and Nutrition Examination Survey in 1988-1994 and 1999-2018. Nonpregnant adults who had a measurement of 2-hour glucose, FPG, and HbA1c, and absence of traditional risk factors were included. Cox proportional hazard models were performed to examine the associations of normal FPG (n = 5793), normal HbA1c (n = 8179), and normal 2-hour glucose (n = 3404) with all-cause mortality.

Results
A significant association was found between 2-hour glucose within the normal range and all-cause mortality among those without traditional risk factors. Compared with participants with 2-hour glucose &lt;80 mg/dL, participants with a higher normal 2-hour glucose level had a higher risk of all-cause mortality (110-139 mg/dL; HR 1.80, 95% CI 1.03-3.15). In the subgroup analysis, significant associations were also found among people aged ≥60 years and men. No significant associations were found between normal FPG and HbA1c levels and all-cause mortality.

Conclusion
Among US adults without traditional risk factors, high normal 2-hour glucose level was positively associated with all-cause mortality. This result highlights the potential importance of maintaining a lower normal level of 2-hour glucose for preventing mortality in individuals who are conventionally considered to be cardiovascular healthy.
Association of Adiposity Phenotypes With 27-Hydroxycholesterol and Sex Hormones: The Multiethnic Cohort Study
Authors: Li Yuqing , Streicher Samantha A , Franke Adrian A , Tome Anne N , White Kami K , Shvetsov Yurii , Lim Unhee , Setiawan Veronica W , DeRouen Mindy C , Hernandez Brenda Y , Wu Anna H , Wilkens Lynne R , Le Marchand Loïc , Loo Lenora W M , Cheng Iona 
Published: August 2024

Abstract

Context
The distribution of body fat has been linked to circulating levels of lipids and sex steroid hormones. The cholesterol metabolite and endogenous selective estrogen receptor modulator, 27-hydroxychlolesterol (27HC), may be influenced by adiposity phenotypes, particularly among females. No study has examined the relationships of 27HC with adiposity phenotypes.

Objective
To investigate the associations of 27HC and steroid hormones with detailed adiposity phenotypes among a multiethnic population of postmenopausal women.

Methods
A cross-sectional study was conducted among 912 postmenopausal women from the Multiethnic Cohort Adiposity Phenotype study. Multivariable linear regression examined the associations of circulating levels of 27HC, steroid hormones, and sex hormone–binding globulin (SHBG) with detailed adiposity phenotypes, adjusting for demographics, lifestyle factors, diabetes status, and use of lipid-lowering drugs. Subgroup analyses were conducted across race and ethnicity.

Results
Total fat mass (P trend = .003), subcutaneous adipose tissue (SAT) (P trend = .006), and superficial subcutaneous adipose tissue (P trend = 4.41 × 10−4) were inversely associated with circulating 27HC levels. In contrast, visceral adipose tissue (VAT) (P trend = .003) and liver fat (P trend = .005) were positively associated with 27HC levels. All adiposity phenotypes were associated with higher levels of free estradiol and testosterone and lower levels of SHBG. Generally, similar patterns of associations were observed across race and ethnicity.

Conclusion
Adiposity phenotypes, such as SAT, VAT, and liver fat, were differentially associated with circulating 27HC, while consistent directions of associations were seen for circulating hormones among postmenopausal women. Future studies are warranted to further understand the biology and relationships of 27HC and adiposity-related diseases.
A pre-vertebrate endodermal origin of calcitonin-producing neuroendocrine cells
Authors: Rees Jenaid M. , Kirk Katie , Gattoni Giacomo , Hockman Dorit , Sleight Victoria A. , Ritter Dylan J. , Benito-Gutierrez Èlia , Knapik Ela W. , Crump J. Gage , Fabian Peter , Gillis J. Andrew 
Published: August 2024

ABSTRACT
Vertebrate calcitonin-producing cells (C-cells) are neuroendocrine cells that secrete the small peptide hormone calcitonin in response to elevated blood calcium levels. Whereas mouse C-cells reside within the thyroid gland and derive from pharyngeal endoderm, avian C-cells are located within ultimobranchial glands and have been reported to derive from the neural crest. We use a comparative cell lineage tracing approach in a range of vertebrate model systems to resolve the ancestral embryonic origin of vertebrate C-cells. We find, contrary to previous studies, that chick C-cells derive from pharyngeal endoderm, with neural crest-derived cells instead contributing to connective tissue intimately associated with C-cells in the ultimobranchial gland. This endodermal origin of C-cells is conserved in a ray-finned bony fish (zebrafish) and a cartilaginous fish (the little skate, Leucoraja erinacea). Furthermore, we discover putative C-cell homologs within the endodermally-derived pharyngeal epithelium of the ascidian Ciona intestinalis and the amphioxus Branchiostoma lanceolatum, two invertebrate chordates that lack neural crest cells. Our findings point to a conserved endodermal origin of C-cells across vertebrates and to a pre-vertebrate origin of this cell type along the chordate stem.
PAPEL DA MOEDA E A FUNÇÃO DOS TRIBUTOS NA TEORIA MONETÁRIA MODERNA
Authors: Ribeiro Ricardo Lodi 
Published: August 2024

A Teoria Moderna da Moeda preconiza que o Estado que emite a sua própria moeda não precisa de tributos para o financiamento dos gastos públicos. Com isso, toda a fundamentação tradicional dos tributos cai por terra, uma vez que estes não mais parecem ser necessários para o custeio das despesas públicas. No entanto, os tributos ainda guardam quatro funções fundamentais: (i) a valorização da moeda nacional necessária ao pagamento dos tributos; (ii) a abertura de espaço para o gasto público a partir do enxugamento do excesso de liquidez do mercado; (iii) a promoção da redistribuição de rendas com a adoção de um sistema tributário progressivo; e (iv) indução a determinados comportamentos e abstenções, por meio da extrafiscalidade. A superação dos dogmas da austeridade seletiva são um caminho pavimentado para a adoção da ideia de responsabilidade fiscal que seja harmonizada com os direitos fundamentais, com a utilização dos tributos e dos gastos públicos na implementação de políticas públicas.
A COMPARATIVE ANALYSIS OF LUMBAR INTERVERTEBRAL MOTION BETWEEN LOW BACK PAIN SUBGROUPS AND HEALTHY CONTROLS USING QUANTITATIVE FLUOROSCOPY
Authors: Rix J. , du Rose A. , Mellor F. , De Carvalho D. , Breen A. 
Published: August 2024

Study purpose and backgroundKinematic variables have been identified as potential biomarkers for low back pain patients; however, an in-depth comparison between chronic (n=22), acute (n=15), and healthy controls (n=136) has not been done. This retrospective data analysis compared intervertebral lumbar motion parameters, angular range of motion, translation, maximum disc height, motion share inequality (MSI) and variability (MSV), and laxity, between these groups.Methods and resultsKinematic parameters were determined using video tracking techniques utilising quantitative fluoroscopy (QF), during both weight-bearing and recumbent controlled sagittal bending tasks. Data was analysed for normality, and appropriate statistical tests were applied to determine differences between groups. There were no significant differences between the groups for age, height, weight and sex. Whilst few differences were found between acute and healthy groups, differences were shown between both chronic and healthy, and acute and chronic groups for all six parameters. Of particular note were examples of differences in the motion share parameters between the acute and chronic populations, with an increased MSI in the chronic group during recumbent flexion, and MSV during recumbent extension, and inversely an increase in MSV in the acute group during weight-bearing flexion.ConclusionAnalysis of intervertebral lumbar motion provides valuable insights into kinematic differences between chronic, acute, and healthy control populations. These findings suggest that there is variation between the groups which is knowledge that may benefit management strategies. Further exploration of the time varying data is warranted to explore how such differences may relate to the motion share inequalities and variability shown.Conflicts of InterestNo conflicts of interestSources of FundingNo funding obtained
“THERE'S MY BACK, DO WHAT YOU WANT!”: PATIENTS’ EXPECTATIONS OF TREATMENT FOR LOW BACK PAIN
Authors: Penney H. , Roberts L. C. 
Published: August 2024

Purpose and backgroundUnderstanding patients’ expectations of back pain treatment can help improve their experiences, adherence and outcomes. Patients typically expect a diagnosis and exercise-based physiotherapy, but often undervalue the role of psychological factors. This study explored patients’ expectations of outpatient physiotherapy treatment for back pain in primary care.Methods and ResultsThe design, a secondary analysis of a qualitative cross-sectional study, involved 25 patients (13M:12F), aged 20–81, referred with low back pain (duration 7 weeks to 9 years). This sample did not include patients with serious spinal pathologies, known psychological disorders, or those unable to communicate without assistance. Face-to-face interviews were undertaken in patients’ homes, which were audio-recorded, transcribed verbatim and analysed using the six stages of thematic analysis outlined by Braun and Clarke.Patients expected a caring clinician and a strong therapeutic relationship, where they felt believed, openly communicated with and valued as an individual. Most patients expected a diagnosis and credible explanation for their pain. There was an almost equal split between those keen to take responsibility for their care and those who felt this was the clinicians’ role. Expectations of passive therapies were slightly higher in this study than existing research. Most patients were realistic about outcomes and expected treatment to reduce their pain, but not cure it.ConclusionA positive experience mattered most to patients, valuing the relational aspects of their care more than the clinical content provided. Patients saw back pain through a biomedical lens, and most failed to recognise the role of psychosocial factors in their condition or treatment.Conflicts of interestNoneSources of fundingFunding for primary data: Arthritis Research UK (now Versus Arthritis)
THE ASSOCIATION BETWEEN INDIVIDUAL LUMBAR INTERVERTEBRAL DISC DEGENERATION FEATURES AND LOW BACK PAIN IS MODIFIED BY GENETIC PROPENSITY TO PAIN
Authors: Suri P. , Kazemi-Naini M. , Freidin M.B. , Tsepilov Y. , Elgaeva E. , Granville-Smith I. , Compte R. , Williams F.M.K. 
Published: August 2024

BackgroundThe association between lumbar intervertebral disc degeneration (LDD) and low back pain (LBP) is modest. We have recently shown that genetic propensity to pain is an effect modifier of the LDD-LBP relationship when LDD is defined as a summary score of LDD (LSUM), suggesting the association may be driven by individuals with the greatest genetic predisposition to pain. This study examined the association between individual spine magnetic resonance imaging (MRI)-determined LDD features and LBP in subgroups defined by genetic predisposition to pain.MethodWe developed a polygenic risk score (PRS) for “genetic propensity to pain” defined as the number of non-back pain locations (head, face, neck/shoulder, stomach/abdomen, hip, and knee) with duration ≥3 months in 377,538 UK Biobank participants of European ancestry. This PRS was used to stratify TwinsUK MRI samples (n=645) into four strata of genetic propensity to pain. We examined the association between LBP and MRI features of lumbar disc height, disc signal intensity, disc bulge, and osteophytes with adjustments for age, sex, PRS strata, interaction terms for each MRI feature x PRS strata, and twin status.ResultsWe found significant effect modification of the LDD-LBP relationship by genetic propensity to pain for the lumbar MRI features of disc height (p=0.03 for the interaction term with highest quartile of genetically-predicted propensity to pain) and disc signal intensity (p=0.001), but not for disc bulge and osteophytes.ConclusionGenetic propensity to pain modifies the association between individual LDD features and LBP and should be considered in LBP clinical studies.Conflicts of interestNo conflicts of interestSources of fundingNo funding obtainedAcknowledgementUKBB data were obtained under the project #18219This paper is submitted to the Spine journal and is under review.