bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disease patterns of coronary heart disease and type 2 diabetes harbored distinct and shared genetic architecture
Authors: Xiao Han , Ma Yujia , Zhou Zechen , Li Xiaoyi , Ding Kexin , Wu Yiqun , Wu Tao , Chen Dafang 
Published: December 2022

Abstract
Background
Coronary heart disease (CHD) and type 2 diabetes (T2D) are two complex diseases with complex interrelationships. However, the genetic architecture of the two diseases is often studied independently by the individual single-nucleotide polymorphism (SNP) approach. Here, we presented a genotypic-phenotypic framework for deciphering the genetic architecture underlying the disease patterns of CHD and T2D.

Method
A data-driven SNP-set approach was performed in a genome-wide association study consisting of subpopulations with different disease patterns of CHD and T2D (comorbidity, CHD without T2D, T2D without CHD and all none). We applied nonsmooth nonnegative matrix factorization (nsNMF) clustering to generate SNP sets interacting the information of SNP and subject. Relationships between SNP sets and phenotype sets harboring different disease patterns were then assessed, and we further co-clustered the SNP sets into a genetic network to topologically elucidate the genetic architecture composed of SNP sets.

Results
We identified 23 non-identical SNP sets with significant association with CHD or T2D (SNP-set based association test, P < 3.70 × $${10}^{-4}$$

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). Among them, disease patterns involving CHD and T2D were related to distinct SNP sets (Hypergeometric test, P < 2.17 × $${10}^{-3}$$

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3

). Accordingly, numerous genes (e.g., KLKs, GRM8, SHANK2) and pathways (e.g., fatty acid metabolism) were diversely implicated in different subtypes and related pathophysiological processes. Finally, we showed that the genetic architecture for disease patterns of CHD and T2D was composed of disjoint genetic networks (heterogeneity), with common genes contributing to it (pleiotropy).

Conclusion
The SNP-set approach deciphered the complexity of both genotype and phenotype as well as their complex relationships. Different disease patterns of CHD and T2D share distinct genetic architectures, for which lipid metabolism related to fibrosis may be an atherogenic pathway that is specifically activated by diabetes. Our findings provide new insights for exploring new biological pathways.
Involvement of abnormal dystroglycan expression and matriglycan levels in cancer pathogenesis
Authors: Quereda Cristina , Pastor Àngels , Martín-Nieto José 
Published: December 2022

AbstractDystroglycan (DG) is a glycoprotein composed of two subunits that remain non-covalently bound at the plasma membrane: α-DG, which is extracellular and heavily O-mannosyl glycosylated, and β-DG, an integral transmembrane polypeptide. α-DG is involved in the maintenance of tissue integrity and function in the adult, providing an O-glycosylation-dependent link for cells to their extracellular matrix. β-DG in turn contacts the cytoskeleton via dystrophin and participates in a variety of pathways transmitting extracellular signals to the nucleus. Increasing evidence exists of a pivotal role of DG in the modulation of normal cellular proliferation. In this context, deficiencies in DG glycosylation levels, in particular those affecting the so-called matriglycan structure, have been found in an ample variety of human tumors and cancer-derived cell lines. This occurs together with an underexpression of the DAG1 mRNA and/or its α-DG (core) polypeptide product or, more frequently, with a downregulation of β-DG protein levels. These changes are in general accompanied in tumor cells by a low expression of genes involved in the last steps of the α-DG O-mannosyl glycosylation pathway, namely POMT1/2, POMGNT2, CRPPA, B4GAT1 and LARGE1/2. On the other hand, a series of other genes acting earlier in this pathway are overexpressed in tumor cells, namely DOLK, DPM1/2/3, POMGNT1, B3GALNT2, POMK and FKTN, hence exerting instead a pro-oncogenic role. Finally, downregulation of β-DG, altered β-DG processing and/or impaired β-DG nuclear levels are increasingly found in human tumors and cell lines. It follows that DG itself, particular genes/proteins involved in its glycosylation and/or their interactors in the cell could be useful as biomarkers of certain types of human cancer, and/or as molecular targets of new therapies addressing these neoplasms.
Association of physical activity, sedentary behaviour, and daylight exposure with sleep in an ageing population: findings from the Whitehall accelerometer sub-study
Authors: Le Cornu Quentin , Chen Mathilde , van Hees Vincent , Léger Damien , Fayosse Aurore , Yerramalla Manasa S. , Sabia Séverine 
Published: December 2022

Abstract
Background
Ageing is accompanied by changes in sleep, while poor sleep is suggested as a risk factor for several health outcomes. Non-pharmacological approaches have been proposed to improve sleep in elderly; their impact remains to be investigated. The aim of this study was to examine the independent day-to-day associations of physical behaviours and daylight exposure with sleep characteristics among older adults.

Methods
Data were drawn from 3942 participants (age range: 60–83 years; 27% women) from the Whitehall II accelerometer sub-study. Day-to-day associations of objectively-assessed daytime physical behaviours (sedentary behaviour, light-intensity physical activity (LIPA), moderate-to-vigorous physical activity (MVPA), mean acceleration, physical activity chronotype) and daylight exposure (proportion of waking window with light exposure > 1000 lx and light chronotype) with sleep characteristics were examined using mixed models.

Results
A 10%-increase in proportion of the waking period spent sedentary was associated with 5.12-minute (4.31, 5.92) later sleep onset and 1.76-minute shorter sleep duration (95%confidence interval: 0.86, 2.66). Similar increases in LIPA and MVPA were associated with 6.69 (5.67, 7.71) and 4.15 (2.49, 5.81) earlier sleep onset respectively and around 2-minute longer sleep duration (2.02 (0.87, 3.17) and 2.23 (0.36, 4.11), respectively), although the association was attenuated for MVPA after adjustment for daylight exposure (1.11 (− 0.84, 3.06)). A 3-hour later physical activity chronotype was associated with a 4.79-minute later sleep onset (4.15, 5.43) and 2.73-minute shorter sleep duration (1.99, 3.47). A 10%-increase in proportion of waking period exposed to light> 1000 lx was associated with 1.36-minute longer sleep (0.69, 2.03), independently from mean acceleration. Associations found for sleep duration were also evident for duration of the sleep windows with slightly larger effect size (for example, 3.60 (2.37, 4.82) minutes for 10%-increase in LIPA), resulting in associations with sleep efficiency in the opposite direction (for example, − 0.29% (− 0.42, − 0.16) for 10%-increase in LIPA). Overall, associations were stronger for women than for men.

Conclusions
In this study, higher levels of physical activity and daylight exposure were associated with slightly longer sleep in older adults. Given the small effect sizes of the associations, increased physical activity and daylight exposure might not be enough to improve sleep.
Muscle sodium content in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Authors: Petter Elisabeth , Scheibenbogen Carmen , Linz Peter , Stehning Christian , Wirth Klaus , Kuehne Titus , Kelm Marcus 
Published: December 2022

Abstract
Background
Muscle fatigue and pain are key symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Although the pathophysiology is not yet fully understood, there is ample evidence for hypoperfusion which may result in electrolyte imbalance and sodium overload in muscles. Therefore, the aim of this study was to assess levels of sodium content in muscles of patients with ME/CFS and to compare these to healthy controls.

Methods
Six female patients with ME/CFS and six age, BMI and sex matched controls underwent 23Na-MRI of the left lower leg using a clinical 3T MR scanner before and after 3 min of plantar flexion exercise. Sodium reference phantoms with solutions of 10, 20, 30 and 40 mmol/L NaCl were used for quantification. Muscle sodium content over 40 min was measured using a dedicated plugin in the open-source DICOM viewer Horos. Handgrip strength was measured and correlated with sodium content.

Results
Baseline tissue sodium content was higher in all 5 lower leg muscle compartments in ME/CFS compared to controls. Within the anterior extensor muscle compartment, the highest difference in baseline muscle sodium content between ME/CFS and controls was found (mean ± SD; 12.20 ± 1.66 mM in ME/CFS versus 9.38 ± 0.71 mM in controls, p = 0.0034). Directly after exercise, tissue sodium content increased in gastrocnemius and triceps surae muscles with + 30% in ME/CFS (p = 0.0005) and + 24% in controls (p = 0.0007) in the medial gastrocnemius muscle but not in the extensor muscles which were not exercised. Compared to baseline, the increase of sodium content in medial gastrocnemius muscle was stronger in ME/CFS than in controls with + 30% versus + 17% to baseline at 12 min (p = 0.0326) and + 29% versus + 16% to baseline at 15 min (p = 0.0265). Patients had reduced average handgrip strength which was associated with increased average muscle tissue sodium content (p = 0.0319, R2 = 0.3832).

Conclusion
Muscle sodium content before and after exercise was higher in ME/CFS than in healthy controls. Furthermore, our findings indicate an inverse correlation between muscle sodium content and handgrip strength. These findings provide evidence that sodium overload may play a role in the pathophysiology of ME/CFS and may allow for potential therapeutic targeting.
A comparison of health-related factors between patients diagnosed with ME/CFS and patients with a related symptom picture but no ME/CFS diagnosis: a cross-sectional exploratory study
Authors: Bernhoff Gabriella , Rasmussen-Barr Eva , Bunketorp Käll Lina 
Published: December 2022

Abstract
Background
In chronic fatigue syndrome/myalgic encephalomyelitis (ME/CFS), the capacity for activity and participation is strongly limited. The disease definition is very broad, and considering the lack of evidence for best treatment, it is important to understand what is ME/CFS-specific in the biopsychosocial perspective in comparison with similar syndromes. The objective was to study the difference between those diagnosed with ME/CFS and those with similar symptoms but no ME/CFS diagnosis for self-perceived level of physical activity, work ability, anxiety/depression, and health-related quality of life.

Methods
This was a clinical cross-sectional study with data collected from mailed questionnaires. The following variables were compared between patients diagnosed with ME/CFS (n = 205) and those with similar symptoms but no diagnosis (n = 57); level of physical activity, Work ability index (WAI), Hospital anxiety and depression scale (HAD-A/HAD-D), and RAND-36 Physical functioning, Role limitations due to physical health problems, Role limitations due to personal or emotional problems, Social functioning, Energy/fatigue, Bodily pain, Emotional well-being, and General health perceptions. The Chi-squared test (nominal data), the Mann-Whitney U test, the Student’s t test and regression analysis were used to analyze the data.

Results
The group diagnosed with ME/CFS had a more impaired physical and mental exertion ability as compared to the group that had similar symptoms but was not diagnosed with ME/CFS, shown by a RAND-36 lower index of physical role functioning, social functioning, energy, worse pain and poorer overall health (p ≤ 0.05). In contrast, no significant group differences emerged for weekly level of physical activity, work ability, anxiety/depression, and RAND-36 Emotional role limitation and well-being.

Conclusion
Our results indicate that those with a diagnosis of ME/CFS are characterized by an impaired ability for physical or mental exertion, worse pain, and poorer overall health as compared to individuals with similar symptoms but for whom ME/CFS-diagnosis was not established. The results may be cautiously interpreted as support when focusing on patients’ self-care in terms of management of energy levels. The results must however be verified in future studies.
Association of leukocyte mitochondrial DNA copy number with longitudinal C-reactive protein levels and survival in older adults: a cohort study
Authors: Wu I-Chien , Liu Chin-San , Cheng Wen-Ling , Lin Ta-Tsung , Chen Hui-Ling , Chen Pei-Fen , Wu Ray-Chin , Huang Chen-Wei , Hsiung Chao A. , Hsu Chih-Cheng 
Published: December 2022

Abstract
Background
Systemic chronic inflammation occurs with age. The association of the leukocyte mitochondrial DNA copy number, a measure of mitochondrial function in aging, with the temporal profile of serum high-sensitivity C-reactive protein and mortality risk remains uncertain. The objectives of this study were to examine the association of the leukocyte mitochondrial DNA copy number with longitudinal high-sensitivity C-reactive protein levels and the association of the longitudinal high-sensitivity C-reactive protein levels with mortality risk.

Methods
This prospective cohort study included 3928 adults aged ≥ 55 years without systemic inflammation in the baseline examination of the Healthy Aging Longitudinal Study in Taiwan, which started in 2009. Each participant received leukocyte mitochondrial DNA copy number measurement using a fluorescence-based quantitative polymerase chain reaction at baseline, serum high-sensitivity C-reactive protein measurements at baseline and the follow-up examination five years later, and the ascertainment of all-cause death (until November 30, 2021). The relationships among the leukocyte mitochondrial DNA copy number, longitudinal serum high-sensitivity C-reactive protein levels, and time to all-cause mortality were examined using the joint longitudinal and survival modeling analysis.

Results
Of the 3928 participants (mean age: 69 years; 2060 [52%] were women), 837 (21%) died during follow-up. In the adjusted analysis, one standard deviation lower natural log-transformed baseline leukocyte mitochondrial DNA copy number was associated with an increase of 0.05 (95% confidence interval [CI], 0.02 to 0.08) standard deviation in serum high-sensitivity C-reactive protein in subsequent years. An increase of 1 standard deviation in instantaneous high-sensitivity C-reactive protein levels was associated with a hazard ratio (HR) for all-cause mortality of 1.22 (95% CI, 1.14 to 1.30). Similar results were obtained after further adjusting for baseline high-sensitivity C-reactive protein levels (HR [95% CI], 1.27 [1.16 to 1.38]) and after excluding those with serum high-sensitivity C-reactive protein above 10 mg/L (HR [95% CI], 1.21[1.11 to 1.31]) or 3 mg/L (HR [95% CI], 1.19 [1.06 to 1.31]) during follow-up.

Conclusions
A lower leukocyte mitochondrial DNA copy number was associated with persistently higher high-sensitivity C-reactive protein levels. Moreover, these higher time-varying high-sensitivity C-reactive protein levels were instantaneously associated with a higher risk of death.
Why is the prevailing model of joint manipulation (still) incorrect?
Authors: Evans David W. 
Published: December 2022

AbstractFor manipulation, this paper addresses arguably the most fundamental question that can be asked about any therapeutic intervention: what is it? In answering this question, this paper presents the prevailing model of joint manipulation (of Sandoz) and explains why this influential model is fundamentally flawed. The early research on ‘joint cracking’ that led to the development of this model is described in chronological order, alongside how this research was misinterpreted, which gave rise to the model’s flaw. Of concern, the flaw in this model makes worrying predictions that could lead to dangerous clinical decisions. Understandably, these predictions have attracted criticism over the use of manipulation as a therapeutic intervention. A corrected model, first published by Evans and Breen more than 15 years ago, is then presented and explained. Unlike the flawed model, this corrected model makes predictions in line with all available empirical data and additionally provides reassuring answers to critics. Many current definitions of manipulation have inherited the flaw from Sandoz’s model. Hence, a better, empirically derived definition, consistent with the corrected model, is now required.
Diversity of the chiropractic profession in Canada: a cross-sectional survey of Canadian Chiropractic Association members
Authors: Southerst Danielle , Bakaa Nora , Côté Pierre , Macedo Luciana , Carlesso Lisa , MacDermid Joy , Mior Silvano 
Published: December 2022

AbstractBackgroundLittle is known about the diversity of the chiropractic profession with respect to gender, sexual orientation, race, ethnicity and community of practice. This knowledge is important as profession representation of key equity seeking groups may impact quality of care and access for vulnerable communities. The aim of this cross-sectional survey was to explore the diversity of the chiropractic profession in Canada.MethodsAll registered members of the Canadian Chiropractic Association (N = 7721) were invited to participate in a web-based survey between May and June 2021. Survey questions explored diversity with respect to personal demographics (age, sex, gender, sexual orientation, race, ethnicity, language) and practice characteristics (community setting, practice type). Where possible, survey data was compared to data from the 2016 Census of the Canadian population.ResultsWe received a total of 3143 survey responses (response rate—41%). The average age of our sample was 44.7 years (standard deviation 12.7). Forty-five percent were female with the same proportion (45.2%) self-identifying as women. Ninety-one percent of the sample self-identified as heterosexual. With respect to race, 80% of respondents were Caucasian. Seventy percent of chiropractors in our sample identified with Canadian ancestry and 29% with European ancestry. In comparison to the Canadian population, some visible minorities were underrepresented. The greatest discrepancy between the Canadian population and our sample was in the proportion of Black and Indigenous chiropractors. With respect to ethnicity, chiropractors identifying themselves with Canadian ancestry were overrepresented in our sample compared to others, specifically those with North American Indigenous and South, Central and Latin American ancestry. Sixty-one percent of chiropractors practiced in major cities and most work in interdisciplinary clinics (42% Complementary and Alternative Medicine and 33% rehabilitation).ConclusionsThis study provides an initial description of diversity within the chiropractic profession in Canada. Women represent less than 50% of the profession nationally. Overall, there is little racial and ethnic diversity in the chiropractic profession compared to the Canadian population, with Black and Indigenous peoples being underrepresented. Future work should focus strategies to foster the development of a more diverse chiropractic workforce.
Endoscopic-assisted descending aortic replacement through a small intercostal incision: a case report
Authors: Wada Takeshi , Sako Hidenori , Kizu Kenya , Tashima Takahiro , Takayama Tetsushi , Miyamoto Shinji 
Published: December 2022

Abstract
Background
Descending aortic replacement often involves making large incisions; thus, it results in massive invasions. We report the case of a patient with dilated descending aorta treated using endoscopic-assisted descending aortic replacement with essentially minimal invasions.

Case presentation
We performed endoscopic-assisted descending aortic replacement with a single incision involving six wounds by trocar puncturing on a 59-year-old man who was diagnosed with dilated descending aorta by stent graft-induced new entry. Subsequently, the patient was discharged on postoperative day 11 without any complications.

Conclusions
Despite minor incisions, our approach can be indicated to almost the same group of patients in whom the conventional approach can be performed. Our procedure involved a single incision of only 8 cm and six wounds by trocar puncturing. Thus, endoscopic-assisted surgery can be a useful option in descending aortic surgery.
EIF4A inhibition targets bioenergetic homeostasis in AML MOLM-14 cells in vitro and in vivo and synergizes with cytarabine and venetoclax
Authors: Fooks Katie , Galicia-Vazquez Gabriela , Gife Victor , Schcolnik-Cabrera Alejandro , Nouhi Zaynab , Poon William W. L. , Luo Vincent , Rys Ryan N. , Aloyz Raquel , Orthwein Alexandre , Johnson Nathalie A. , Hulea Laura , Mercier Francois E. 
Published: December 2022

Abstract
Background
Acute myeloid leukemia (AML) is an aggressive hematological cancer resulting from uncontrolled proliferation of differentiation-blocked myeloid cells. Seventy percent of AML patients are currently not cured with available treatments, highlighting the need of novel therapeutic strategies. A promising target in AML is the mammalian target of rapamycin complex 1 (mTORC1). Clinical inhibition of mTORC1 is limited by its reactivation through compensatory and regulatory feedback loops. Here, we explored a strategy to curtail these drawbacks through inhibition of an important effector of the mTORC1signaling pathway, the eukaryotic initiation factor 4A (eIF4A).

Methods
We tested the anti-leukemic effect of a potent and specific eIF4A inhibitor (eIF4Ai), CR-1-31-B, in combination with cytosine arabinoside (araC) or the BCL2 inhibitor venetoclax. We utilized the MOLM-14 human AML cell line to model chemoresistant disease both in vitro and in vivo. In eIF4Ai-treated cells, we assessed for changes in survival, apoptotic priming, de novo protein synthesis, targeted intracellular metabolite content, bioenergetic profile, mitochondrial reactive oxygen species (mtROS) and mitochondrial membrane potential (MMP).

Results
eIF4Ai exhibits anti-leukemia activity in vivo while sparing non-malignant myeloid cells. In vitro, eIF4Ai synergizes with two therapeutic agents in AML, araC and venetoclax. EIF4Ai reduces mitochondrial membrane potential (MMP) and the rate of ATP synthesis from mitochondrial respiration and glycolysis. Furthermore, eIF4i enhanced apoptotic priming while reducing the expression levels of the antiapoptotic factors BCL2, BCL-XL and MCL1. Concomitantly, eIF4Ai decreases intracellular levels of specific metabolic intermediates of the tricarboxylic acid cycle (TCA cycle) and glucose metabolism, while enhancing mtROS. In vitro redox stress contributes to eIF4Ai cytotoxicity, as treatment with a ROS scavenger partially rescued the viability of eIF4A inhibition.

Conclusions
We discovered that chemoresistant MOLM-14 cells rely on eIF4A-dependent cap translation for survival in vitro and in vivo. EIF4A drives an intrinsic metabolic program sustaining bioenergetic and redox homeostasis and regulates the expression of anti-apoptotic proteins. Overall, our work suggests that eIF4A-dependent cap translation contributes to adaptive processes involved in resistance to relevant therapeutic agents in AML.