bluuebunny/crossref_metadata_2025_split huggingface dataset:
TET2-mutant clonal hematopoiesis and risk of gout
Authors: Agrawal Mridul , Niroula Abhishek , Cunin Pierre , McConkey Marie , Shkolnik Veronica , Kim Peter G. , Wong Waihay J. , Weeks Lachelle D. , Lin Amy E. , Miller Peter G. , Gibson Christopher J. , Sekar Aswin , Schaefer Inga-Marie , Neuberg Donna , Stone Richard M. , Bick Alexander G. , Uddin Md Mesbah , Griffin Gabriel K. , Jaiswal Siddhartha , Natarajan Pradeep , Nigrovic Peter A. , Rao Deepak A. , Ebert Benjamin L. 
Published: June 2022

Abstract
Gout is a common inflammatory arthritis caused by precipitation of monosodium urate (MSU) crystals in individuals with hyperuricemia. Acute flares are accompanied by secretion of proinflammatory cytokines, including interleukin-1β (IL-1β). Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition predisposing to hematologic cancers and cardiovascular disease. CHIP is associated with elevated IL-1β, thus we investigated CHIP as a risk factor for gout. To test the clinical association between CHIP and gout, we analyzed whole exome sequencing data from 177 824 individuals in the MGB Biobank (MGBB) and UK Biobank (UKB). In both cohorts, the frequency of gout was higher among individuals with CHIP than without CHIP (MGBB, CHIP with variant allele fraction [VAF] ≥2%: odds ratio [OR], 1.69; 95% CI, 1.09-2.61; P = .0189; UKB, CHIP with VAF ≥10%: OR, 1.25; 95% CI, 1.05-1.50; P = .0133). Moreover, individuals with CHIP and a VAF ≥10% had an increased risk of incident gout (UKB: hazard ratio [HR], 1.28; 95% CI, 1.06-1.55; P = .0107). In murine models of gout pathogenesis, animals with Tet2 knockout hematopoietic cells had exaggerated IL-1β secretion and paw edema upon administration of MSU crystals. Tet2 knockout macrophages elaborated higher levels of IL-1β in response to MSU crystals in vitro, which was ameliorated through genetic and pharmacologic Nlrp3 inflammasome inhibition. These studies show that TET2-mutant CHIP is associated with an increased risk of gout in humans and that MSU crystals lead to elevated IL-1β levels in Tet2 knockout murine models. We identify CHIP as an amplifier of NLRP3-dependent inflammatory responses to MSU crystals in patients with gout.
Insulin-inducible THRSP maintains mitochondrial function and regulates sphingolipid metabolism in human adipocytes
Authors: Ahonen Maria A. , Höring Marcus , Nguyen Van Dien , Qadri Sami , Taskinen Juuso H. , Nagaraj Meghana , Wabitsch Martin , Fischer-Posovszky Pamela , Zhou You , Liebisch Gerhard , Haridas P. A. Nidhina , Yki-Järvinen Hannele , Olkkonen Vesa M. 
Published: June 2022

Abstract
Background
Thyroid hormone responsive protein (THRSP) is a lipogenic nuclear protein that is highly expressed in murine adipose tissue, but its role in humans remains unknown.

Methods
We characterized the insulin regulation of THRSP in vivo in human adipose tissue biopsies and in vitro in Simpson-Golabi-Behmel syndrome (SGBS) adipocytes. To this end, we measured whole-body insulin sensitivity using the euglycemic insulin clamp technique in 36 subjects [age 40 ± 9 years, body mass index (BMI) 27.3 ± 5.0 kg/m2]. Adipose tissue biopsies were obtained at baseline and after 180 and 360 min of euglycemic hyperinsulinemia for measurement of THRSP mRNA concentrations. To identify functions affected by THRSP, we performed a transcriptomic analysis of THRSP-silenced SGBS adipocytes. Mitochondrial function was assessed by measuring mitochondrial respiration as well as oxidation and uptake of radiolabeled oleate and glucose. Lipid composition in THRSP silencing was studied by lipidomic analysis.

Results
We found insulin to increase THRSP mRNA expression 5- and 8-fold after 180 and 360 min of in vivo euglycemic hyperinsulinemia. This induction was impaired in insulin-resistant subjects, and THRSP expression was closely correlated with whole-body insulin sensitivity. In vitro, insulin increased both THRSP mRNA and protein concentrations in SGBS adipocytes in a phosphoinositide 3-kinase (PI3K)-dependent manner. A transcriptomic analysis of THRSP-silenced adipocytes showed alterations in mitochondrial functions and pathways of lipid metabolism, which were corroborated by significantly impaired mitochondrial respiration and fatty acid oxidation. A lipidomic analysis revealed decreased hexosylceramide concentrations, supported by the transcript concentrations of enzymes regulating sphingolipid metabolism.

Conclusions
THRSP is regulated by insulin both in vivo in human adipose tissue and in vitro in adipocytes, and its expression is downregulated by insulin resistance. As THRSP silencing decreases mitochondrial respiration and fatty acid oxidation, its downregulation in human adipose tissue could contribute to mitochondrial dysfunction. Furthermore, disturbed sphingolipid metabolism could add to metabolic dysfunction in obese adipose tissue.
A Robotic System with Robust Remote Center of Motion Constraint for Endometrial Regeneration Surgery
Authors: Li Jianhua , Wang Chongyang , Wang Zhenxing , Zheng Xiong , Wang Zhidong , Tan Jichun , Liu Hao 
Published: June 2022

AbstractSurgical robots have been widely used in different procedures to improve and facilitate the surgery. However, there is no robot designed for endometrial regeneration surgery, which is a new therapy for restoring fertility in women using stem cells. Endometrial regeneration surgery requires processing of the endometrium and transplantation of stem cells with minimal trauma to the uterus. In this paper, we introduce a surgical robotic system that consists of a dexterous hysteroscope, supporting arm, and additional novel instruments to facilitate the operation and decrease trauma to the uterus. Remote center of motion (RCM) constraint is required to protect the cervix of the uterus. First, the supporting arm and hysteroscope are controlled separately in kinematics to ensure that the RCM constraint and hysteroscope’s shape and posture are predictable. Then, a task-decoupled method is used to improve the robustness of the RCM constraint. Experiments confirm that the proposed method is more robust and achieves higher RCM accuracy. In addition, the master-slave control of a robot with RCM constraint is also verified. This study proposes the realization of a robot with robust RCM control for endometrial regeneration surgery.
Modified Multifidelity Surrogate Model Based on Radial Basis Function with Adaptive Scale Factor
Authors: Liu Yin , Wang Shuo , Zhou Qi , Lv Liye , Sun Wei , Song Xueguan 
Published: June 2022

AbstractMultifidelity surrogates (MFSs) replace computationally intensive models by synergistically combining information from different fidelity data with a significant improvement in modeling efficiency. In this paper, a modified MFS (MMFS) model based on a radial basis function (RBF) is proposed, in which two fidelities of information can be analyzed by adaptively obtaining the scale factor. In the MMFS, an RBF was employed to establish the low-fidelity model. The correlation matrix of the high-fidelity samples and corresponding low-fidelity responses were integrated into an expansion matrix to determine the scaling function parameters. The shape parameters of the basis function were optimized by minimizing the leave-one-out cross-validation error of the high-fidelity sample points. The performance of the MMFS was compared with those of other MFS models (MFS-RBF and cooperative RBF) and single-fidelity RBF using four benchmark test functions, by which the impacts of different high-fidelity sample sizes on the prediction accuracy were also analyzed. The sensitivity of the MMFS model to the randomness of the design of experiments (DoE) was investigated by repeating sampling plans with 20 different DoEs. Stress analysis of the steel plate is presented to highlight the prediction ability of the proposed MMFS model. This research proposes a new multifidelity modeling method that can fully use two fidelity sample sets, rapidly calculate model parameters, and exhibit good prediction accuracy and robustness.
Temporal stability of parent-reported behavior problems in late talkers over 2 years: a prospective case-control study from toddlerhood to preschool age
Authors: Lu Hsin-Hui , Tsai Jeng-Dau , Tsao Feng-Ming 
Published: June 2022

Abstract
Background
Late talking (LT) in toddlers is a risk factor for language weakness that may interfere with the development of using language to regulate behavior and emotion and contribute to the development of behavior problems from early childhood. This study examined the temporal stability of parent-reported behavior problems among Mandarin-speaking LT toddlers from ages 2 to 4 in Taiwan.

Methods
Thirty-one LT and 31 typical language development (TLD) toddlers were assessed for their vocabulary production at age 2 with the Words and Sentences Forms of the MacArthur-Bates Communicative Developmental Inventories Toddler Form (Taiwan version). Additionally, participants’ receptive and expressive language abilities were assessed using the receptive and expressive language subscales of the Bayley Scales of Infant and Toddler Development, Third Edition. At age 4, the Child Language Disorder Scale-Revised was applied and included the two core subtests for auditory comprehension and expressive communication. At ages 2 and 4 years, behavior problems were assessed with the Child Behavior Checklist.

Results
There was a higher percentage of participants with persistent behavior problems among LT toddlers than among TLD toddlers. Moreover, toddlers with larger vocabularies were less likely to develop withdrawal behaviors by preschool age.

Conclusions
This study supported the temporal stability of parent-reported behavior problems among LT toddlers across early childhood. Early identification of and intervention for behavior problems associated with LT in toddlerhood is essential to alleviate their behavior problems later in preschool years.
Identification of the key flavonoid and lipid synthesis proteins in the pulp of two sea buckthorn cultivars at different developmental stages
Authors: Du Wei , Ding Jian , Lu Shunguang , Wen Xiufeng , Hu Jianzhong , Ruan Chengjiang 
Published: June 2022

Abstract
Background
Sea buckthorn is an economically important woody plant for desertification control and water soil conservation. Its berry pulp is rich in flavonoids and unsaturated fatty acids. Cultivars containing high oil and flavonoid contents have higher economic value and will increase in the planting area. However, the cause of the differences in oil and flavonoid contents among cultivars is still unclear. The influence of key enzymes in the lipid and flavonoid synthesis pathways on their content needs to be explored and clarified.

Results
The flavonoid content in XE (Xin’e 3) was 54% higher than that in SJ (Suiji 1). Rutin was the main flavonoid in sea buckthorn pulp, and the differences in the rutin content could cause flavonoid differences between the two cultivars. The oil content of XE was 31.58% higher than that of SJ, and the difference in oil content was highest at 50–70 DAF. High-throughput proteomics was used to quantify key enzymes of flavonoid and lipid synthesis pathways in two cultivars at three developmental stages. By functional annotation and KEGG analysis, 41 key enzymes related to phenylpropanoid biosynthesis, flavonoid biosynthesis, flavone and flavonol biosynthesis, fatty acid biosynthesis and TAG biosynthesis were quantified. CHS, F3H, ANS, fabD, FATA, FAB2, LPIN and plcC showed significant differences between the two cultivars. In addition, we quantified 6 oleosins. With the exception of a 16 kDa oleosin, the other oleosins in the two cultivars were positively correlated with oil content.

Conclusions
In the flavonoid synthesis pathway, CHS and F3H were the main enzymes responsible for the difference in flavonoid content between the two cultivars. In the lipid synthesis pathway, LPIN, plcC and MGD were the main enzymes with different contents in the middle to late stages. Higher contents of LPIN and plcC in XE than in SJ could cause DAG to generate TAG from PC, since the difference in DGAT between the two cultivars was not significant. Investigating the causes of flavonoid and oil content differences among different cultivars from the perspective of proteomics, could provide a basis for understanding the regulatory mechanism of flavonoids and lipid synthesis in sea buckthorn pulp.
Characteristics of intracardiac electrogram of the interventricular septum in the left bundle branch pacing
Authors: Cai Xiaojie , Jiang Longfu , Zhuo Shanshan , Wu Hao 
Published: June 2022

Abstract
Background
Left bundle branch pacing (LBBP) has become a hot topic in the field of physiological pacing. However, only a few studies have described the characteristics of the intrinsic intracardiac electrogram (EGM) while placing the left bundle branch (LBB) lead.

Case presentation
Herein, we reported a case with atrial premature contractions to the ventricle during the LBBP procedure. Paced and intrinsic (supraventricular) EGMs were recorded and analyzed.

Conclusions
The myocardium of the interventricular septum could be divided into four regions based on electrophysiology: the right septal area, the left septal area, the endocardium of the left ventricular septum, and the LBB area. This might guide the electrophysiological localization of the LBB lead in the septum.
Adherence to self-care recommendations and associated factors among adult heart failure patients in public hospitals, Addis Ababa, Ethiopia, 2021: cross-sectional study
Authors: Baymot Aemiro , Gela Debela , Bedada Tadesse 
Published: June 2022

Abstract
Background
Adherence to self-care recommendations in heart failure (HF) patients is essential to improve the patients’ quality of life, prevent hospital admission, and reduce mortality and morbidity. Nevertheless, poor adherence to self-care recommendations remains to be an extensive problem for HF patients. Thus, the aim was to assess adherence to self-care recommendations and associated factors among HF patients in public hospitals, Addis Ababa, Ethiopia, 2021.

Methods
An institutional-based cross-sectional study was conducted among adult HF patients from February 15 to April 15, 2021, in five public hospitals, in Addis Ababa, Ethiopia. A total of 294 adult HF patients completed an interviewer-administered questionnaire in the Amharic language. The Revised HF Compliance Questionnaire was used to measure the adherence to self-care recommendations of HF patients. Data was collected using the Revised HF Compliance Questionnaire, the Japanese heart failure knowledge scale, the multidimensional scale of perceived social support, and the chronic diseases self-efficacy scale. Study participants were selected through a systematic random sampling technique. Data were entered into Epi-info version 7.1 and then exported to SPSS Version 25 for analysis. Descriptive and logistic regression analyses were performed and the statistical significance of associations between the variables was determined using ORs with 95% CI and p-values < 0.05.

Results
Adherence to self-care recommendations among adult HF patients in public hospitals, in Addis Ababa, Ethiopia was 32.70%. Being female (AOR 4.66, 95% CI 1.58–13.67), patients who had high family monthly income (AOR 10.32, 95% CI 2.00–5.13), NYHA class III (AOR: 7.01, 95% CI 2.18–22.57) and class IV (AOR: 6.30, 95% CI 1.01–39.22), who had good self-efficacy (AOR 7.63, 95% CI 2.64–21.97), and who had good knowledge about HF (AOR 3.95, 95% CI 1.56–9.95) were more likely to have good adherence to self-care recommendations, p-value < 0.05.

Conclusion
This study revealed that 32.70% of adult HF patients had good adherence to self-care recommendations. Factors associated with adherence to self-care recommendations of adult HF patients are sex, family monthly income, NYHA classification, self-efficacy, and knowledge about HF. Therefore, interventions focused on sex, family monthly income, NYHA classification, self-efficacy, and knowledge about HF are required to improve adherence to self-care recommendations of adult HF patients.
Views of breast cancer survivors on work participation guidance by general practitioners: a qualitative study
Authors: Sarfo Marie-Christine , van Asselt Kristel M. , Frings-Dresen Monique H. , de Jong Femke , van Dijk Nynke , de Boer Angela G. E. M. 
Published: June 2022

AbstractBackgroundBreast cancer survivors can be at high risk of having work-related problems. Previous studies suggest that GPs could discuss work participation with cancer patients and provide guidance.The aim this study is to explore the experiences and expectations of breast cancer survivors with their GPs’ role regarding guidance on work participation and return to work.MethodsA qualitative study with Dutch female breast cancer survivors was held in the Netherlands. Four focus groups with 25 participants were conducted and audio-taped. Transcripts were analysed using thematic analysis.ResultsBreast cancer survivors reported a wide range of experiences with guidance from their GPs regarding work participation. Patients who contacted their GPs with work-related issues felt listened to during the consultation. Some patients experienced very limited or no guidance, while others were intensively guided by their GPs. The guidance was provided in the form of counseling, psychosocial support, and referral to other health care professionals. When cancer patients experienced problems with reintegration in work, they expected GPs to have a supportive and referring role in work participation guidance.ConclusionIn returning to work, breast cancer survivors expect their GPs to play a supportive role, especially when they encounter difficulties in reintegrating. However, their actual experience of guidance received from their GPs varied, from none received at all, to intensive support provided.
The effect of structured medication review followed by face-to-face feedback to prescribers on adverse drug events recognition and prevention in older inpatients – a multicenter interrupted time series study
Authors: Klopotowska Joanna E. , Kuks Paul F. M. , Wierenga Peter C. , Stuijt Clementine C. M. , Arisz Lambertus , Dijkgraaf Marcel G. W. , de Keizer Nicolette , Smorenburg Susanne M. , de Rooij Sophia E. ,   on behalf of the WINGS Study Group, Hoekstra Joost L. B. , Jansen Minke E. P. , Meijer Wim G. , van der Kleij Bea M. , Lagaay Anne M. , van der Hoeven Ruud T. M. 
Published: June 2022

Abstract
Background
The effectiveness of interventions to improve medication safety in older inpatients is unclear, given a paucity of properly designed intervention studies applying clinically relevant endpoints such as hospital-acquired preventable Adverse Drug Events (pADEs) and unrecognized Adverse Drug Events (uADEs). Therefore, we conducted a quality improvement study and used hospital-acquired pADEs and uADEs as main outcomes to assess the effect of an intervention aimed to improve medication safety in older inpatients.

Method
The study followed an interrupted time series design and consisted of three equally spaced sampling points during baseline and during intervention measurements. Each sampling point included between 80 to 90 patients. A total of 500 inpatients ≥65 years and admitted to internal medicine wards of three Dutch hospitals were included. An expert team retrospectively identified and assessed ADEs via a structured patient chart review. The findings from baseline measurement and meetings with the internal medicine and hospital pharmacy staff were used to design the intervention. The intervention consisted of a structured medication review by hospital pharmacists, followed by face-to-face feedback to prescribers, on average 3 days per week.

Results
The rate of hospital-acquired pADEs per 100 hospitalizations was reduced by 50.6% (difference 16.8, 95% confidence interval (CI): 9.0 to 24.6, P <  0.001), serious hospital-acquired pADEs by 62.7% (difference 12.8, 95% CI: 6.4 to 19.2, P <  0.001), and uADEs by 51.8% (difference 11.2, 95% CI: 4.4 to 18.0, P <  0.001). Additional analyses confirmed the robustness of the intervention effect, but residual bias cannot be excluded.

Conclusions
The intervention significantly decreased the overall and serious hospital-acquired pADE occurrence in older inpatients, and significantly improved overall ADE recognition by prescribers.

Trial registration
International Standard Randomized Controlled Trial Number Register, trial registration number: ISRCTN64974377, registration date (date assigned): 07/02/2011.
Impact of age on the postural stability measured by a virtual reality tracker-based posturography and a pressure platform system
Authors: Liang Huey-Wen , Chi Shao-Yu , Tai Tzu-Ling , Li Yue-Hua , Hwang Yaw-Huei 
Published: June 2022

Abstract
Background
Center of pressure (CoP) parameters are commonly used to evaluate age-related changes in postural control during standing. However, they mainly reflect ankle strategies and provide limited information about hip strategies, which are essential for postural control among the aged population. Body displacement at the lumbar level (LD) can be used as a proxy for hip strategies.

Objectives
We set up a virtual reality tracker-based posturography to measure LD and compared the CoP and LD parameters in two age groups to explore the roles of ankle and hip strategies during bipedal stance.

Methods
Twenty-seven older healthy participants (63.8 ± 7.1 years old) and 27 younger controls (31.7 ± 9.9 years old) performed four standing tasks with their postural steadiness measured simultaneously with both systems under four stance conditions (combination of eyes-open/eyes-closed and wide-based/narrow-based). Five parameters were calculated from the trajectories of the CoP and LD. The difference in the parameters between two groups was analyzed with the Mann–Whitney U test. The discriminative ability of the parameters from the two systems was computed by the receiver operating characteristic curve analysis and area under the curve (AUC). We also used the intraclass correlation coefficient (ICC) to assess the correlation between two measures.

Results
Most of the parameters obtained from both systems were significantly different between the younger and older groups. Mean velocity in the medial–lateral and anterior–posterior directions could effectively discriminate age-related changes, especially with the LD parameters. The receiver’s operation curve analysis gained the largest AUC (0.85 with both systems) with mean velocity in the medial–lateral direction during narrow-based standing with eyes closed. Meanwhile, we observed a low correlation between parameters obtained from the two methods in velocity measures, with the lowest ICC in the mean velocity in the medial–lateral direction in the older group (ICC = 0.34 ~ 0.41).

Conclusion
Both systems could differentiate age-related changes in postural steadiness, but with dissociated information about mean velocity, especially the mean velocity in the medial–lateral direction in the older group. The results support the complimentary role of using tracker-based posturography to understand the effect of age on the mechanisms of postural control.