bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving Emotional Well‐Being and Cardio‐Metabolic Health with Continuous Glucose Monitoring
Authors: Walson Francis , Thomas Natalya , Poff Angela M. , Alnajar Reeman , Johnson Ayesha , Ari Csilla , Visovski Constance , Matthew Kelly , Hull Allison , D'Agostino Dominic P. 
Published: May 2022

Continuous glucose monitoring (CGM) is extensively used in diabetic populations but understudied in non‐diabetic patients. Glycemic variability is a risk factor for cardiovascular disease, and emerging evidence suggests close monitoring of glycemic control may have a positive impact on chronic disease. CGM increases awareness of glycemic dysregulation and empowers patients to create sustainable changes in eating behaviors. The purpose of this study (ClinicalTrials.gov Identifier: NCT04920058) was to determine if access to continuous blood glucose data using a CGM‐Levels software system improves cardiometabolic health, sleep quality, and emotional well‐being in nondiabetic patients undergoing a comprehensive wellness program.In this 12‐week randomized clinical trial, patients enrolled in a low carbohydrate‐based wellness program were randomly assigned to monitor glucose using a CGM with Levels software (CGM, N=14) or classic glucometer (Ctrl, N=11). Weight, BMI, waist circumference, liver fat (via abdominal ultrasound), and a cardiometabolic blood panel were measured pre‐and post‐program. Ketones were tested weekly, and glucose tested daily using a glucometer in both groups (CGM and Ctrl). Psychological measures of emotional well‐being, depression, anxiety and sleep quality were performed with a subjective well‐being survey, Patient Health Questionnaire‐9 (PHQ9), generalized anxiety disorder‐7 (GAD‐7) and Pittsburgh Sleep Quality Index (PSQI), respectively, pre‐program, week 6, and post‐program.Differences were observed between the groups for liver fat which decreased over time in the CGM but not Ctrl group (p<0.05). Other cardio‐metabolic biomarkers improved in both groups over the course of the study, including weight loss, BMI, waist circumference, triglycerides, VLDL, and fasting insulin, but no differences between groups were observed. Total cholesterol, Non‐HDL, LDL, and HDL ratio increased in both groups over time, but did not differ between groups. Assessments of emotional well‐being, depression, anxiety, and sleep quality also improved in both groups over time, again with no intergroup differences.In a non‐diabetic population, a 12‐week comprehensive wellness program inclusive of glycemic monitoring using CGM was effective at improving liver fat while several biomarkers of cardio‐metabolic health, sleep quality, and emotional well‐being improved regardless of the type of glycemic monitor used. CGM was endorsed by patients to be more comfortable and easier to use than finger stick glucometers, and its use did not impair trial results compared to Ctrl. Thus, CGM with Levels software appears to be a viable and effective method for monitoring glycemic variability in a non‐diabetic population seeking to improve cardio‐metabolic health.
Yap and Taz promote osteogenesis in neural crest cells by preventing chondrogenesis
Authors: Zhao Xiaolei , Tang Li , Nguyen Bao H. , Le Tram P. , Chen Wen , Zheng Mingjie , Yamaguchi Hiroyuki , Martinez‐Traverso Idaliz M. , Wang Jianxin , Li Min , Martin James F. , Lee Brendan H. , Komatsu Yoshihiro , Wang Jun 
Published: May 2022

The neural crest (NC) is a unique migratory stem cell population only existed during vertebrate embryogenesis. It has remarkable multipotency to give rise to various cell types including osteoblasts and chondrocytes, which contribute to majority of the cranial skeleton development. Defects in NC development led to many congenital diseases, including cleft palate and craniofacial abnormities. Recently, the Hippo‐Yap pathway, a conserved fundamental pathway has been indicated to play a key role in NCCs. Yet, the roles of Yap and Taz, function as Hippo signaling effectors, in NCC cells are still poorly understood.To understand the roles of Yap and Taz, we performed both in vitro, ex vivo and in vivo studies using O9‐1 NC cells and Yap/Taz conditionally knockout (CKO) mice driven by Wnt1creSOR. We found that Yap/Taz are required for the osteogenic versus chondrogenic cell fate decision of NC cells. Yap/Taz prevent O9‐1 NC cells from differentiating into chondrocytes to favor osteogenesis, and Yap/Taz deficiency in NC cells resulted in chondrogenesis instead of osteogenesis. Notably, in vivo, we observed NC‐derived cranial bone defects accompanied by ectopic cartilage formation. From RNA‐seq and CUT/RUN datasets we found that Yap/Taz directly regulate key genes that govern osteogenesis (Dlx5, Runx2,…) and chondrogenesis (Sox9/5/6,…). Interestingly, many of those genes are known Wnt target genes. Moreover, our data from ATAC‐seq, PLA and Co‐IP demonstrated that Yap/Taz directly interact with β‐catenin to coordinately regulate related genes expression in NCCs to orchestrate the osteogenic or chondrogenic cell fate, such as the key chondrogenesis gene Sox9.In summary, our data indicated that Yap/Taz play pivotal roles in determining osteogenesis or chondrogenesis of NC, partly through interactions with the Wnt‐β‐catenin pathway, which reveal potential novel diagnostic and therapeutic targets for the NC‐derived diseases.
Vascular and Skeletal Muscle Remodeling: Beyond Physical Inactivity
Authors: Pedrinolla Anna , Cavedon Valentina , Milanese Chiara , Barbi Chiara , La Ginestra Fabio , Giuriato Gaia , Martignon Camilla , Venturelli Massimo 
Published: May 2022

Vascular remodeling refers to the changes in the structure and function of vessels. This adaptability of the arteries is essential to successfully handle vascular distress and arterial disease. Both, skeletal muscle mass and the level of physical activity are independent mechanisms that plays a role in this physiological phenomenon. However, the direct impact of the skeletal muscle mass remodeling on the structure and function of the vessels is not clear.PURPOSETo determine the impact of skeletal muscle mass remodeling on lower limbs arterial diameter, blood flow and arterial stiffness.METHODSNine young (33±13 yrs) physical active individuals with a single‐leg amputation (transtibial amputation) were recruited for the study. Vascular size (femoral artery diameter), hemodynamics (femoral artery blood flow) and arterial stiffness (carotid‐femoral pulse wave velocity) were measure with an ultrasound doppler device at the level of the common femoral artery in both amputee (AL) and whole limbs (WL). Skeletal muscle mass of both limbs was measured with a DEXA system. Both AL and WL were equally utilized by the individuals for ambulation and recreational sports.RESULTSThe skeletal muscle mass of the AL was significantly reduced in comparison to the WL (3.2±1.2 Kg Vs 9.4±2.1 Kg; P=0.0011). Also, the diameter of the femoral artery was significantly reduced in the AL 0.5±0.1 cm in comparison to the WL 0.9±0.2 (p=0.0012). However, femoral artery blood flow normalized for the muscle mass (mean difference 49.07 ml۰min‐1۰kg‐1; p = 0.11) and carotid‐femoral Pulse Wave Velocity (mean difference 0.91 cm۰s‐1; p =0.21) were similar between the two legs. Interestingly, linear regression analysis shows a significant correlation between skeletal muscle mass and femoral artery diameter (p=0.0031).CONCLUSIONThe results of this study revealed that the massive skeletal muscle reduction caused by a transtibial amputation, but independent form the level of physical activity, is coupled by a dramatic arterial diameter decrease. Interestingly, local circulation and arterial stiffness seems not impacted by these structural changes.
Hypoxia Regulates Endothelin‐1 Production and Microglial Cell Activation
Authors: Bailey Blake E. , Ojeda Carlos T. , De Dios Luz , Vazquez Ricardo , Inostroza‐Nieves Yaritza 
Published: May 2022

Oxidative stress and inflammatory responses play critical roles in hypoxic‐ischemic brain injury.Microglial cells are rapidly activated in response to injury and stressful stimuli, including hypoxia.Endothelin‐1 (ET‐1) is a potent vasoconstrictor that has been associated with cerebrovascular diseases. Hypoxia stimulates endothelial ET‐1 production. However, the role of ET‐1 in microglia under hypoxia is not clear. The aim of this project was to characterize the effect of hypoxia in a human microglial cell line, HMC3. We induced hypoxia using a chamber (1% O2, 5% CO2, and 92 % N2) at 37 °C for 4h. MUSE Oxidative Stress Assay was performed to measure reactive oxygen species (ROS) formation, ELISA to determine TNF, IL‐6, and ET‐1 levels, qPCR to measure gene expression of ET‐1, and immunofluorescence staining to visualize and compare the presence of ET‐1 in hypoxic and controlgroup cells. It was observed that, when compared to normoxic HMC3 cells, hypoxic HMC3 exposure significantly increased the ROS by a factor of 2.5 (p&lt;0.001, n=3), the pro‐inflammatory cytokine TNF‐α increased 3.8 times (p&lt;0.01, n=4), and IL‐6 increased by a factor of 1.6 (p&lt;0.01, n=4). In addition, hypoxia stimulates ET‐1 gene expression 5.0‐fold (p&lt;0.001, n=4) and increased protein production 1.3 times (p&lt;0.01, n=4). Consequently, treatment with ET‐1 increased the amount of ROS, TNF‐α, and IL‐6 in HMC3 cells by a factor of 1.4 (p&lt;0.05, n=4), 1.6 (p&lt;0.001, n=4), and 1.9 (p&lt;0.05, n=4), respectively. All these events were blocked by ET‐1 receptor A (ETRA) antagonist, BQ123. Our results suggest that hypoxic conditions create a cycle of microglial cell activation leading to increased ROS and ET‐1 production that further stimulate microglial cells. Thus, we posit that the ET‐1 receptor blockade represents a promising therapeutic approach to regulate microglial cell responses in hypoxic‐ischemic brain injury.
Elevated Urinary Arginine Vasopressin Concentrations during Preeclamptic Pregnancies do not Persist Postpartum
Authors: Santillan Mark K. , Funk Meghan L. , Brandt Debra , Nuckols Virgina , Stroud Amy , Pierce Gary , Santillan Donna A. 
Published: May 2022

BackgroundPreeclampsia (PreE) is a common hypertensive disorder during the second and third trimesters of pregnancy. It is estimated to affect 5‐7% of all U.S. pregnancies; about 400,000 pregnancies per year. PreE leads to increased risks of fetal abnormalities, pregnancy complications, chronic hypertension, and cardiovascular disease. Arginine vasopressin (AVP) plays an important role in controlling osmotic balance, regulating blood pressure, maintaining sodium homeostasis, and functioning of the kidney. AVP is secreted by the hypothalamus as a proprotein with copeptin. Because copeptin and vasopressin are secreted in a 1:1 molar ratio, copeptin measurements can be used a surrogate measure of vasopressin. Our lab has previously demonstrated that vasopressin, as measured by copeptin, is elevated in plasma and urine throughout preeclamptic pregnancies; even before PreE can be clinically diagnosed. However, it is unknown whether urine vasopressin is elevated chronically postpartum. Our objective was to determine whether there is a difference in copeptin concentration between women with and without a history of preeclampsia at 1‐4 years postpartum. We hypothesized that AVP concentrations of subjects who had received a PreE diagnosis would continue to be elevated postpartum.MethodsInclusion criteria for this study (IRB# 201808705) included being 1‐4 years postpartum, not currently pregnant, non‐prisoner, and able to provide informed consent. Women without (N=26; Age 34 +/‐ 3.4 yrs, BMI 25.99 +/‐ 6.34 kg/m2) and with a history (N=25; age 33 +/‐ 4.5 yrs, BMI 30.32 +/‐ 9.12 kg/m2) of preeclampsia in their most recent pregnancy were enrolled. Women fasted, did not smoke, and did not have caffeine for 4 hours prior to their study visit, nor did they have alcohol or exercise for the prior 24 hours. Urine samples were assayed for copeptin concentrations via an automated immunoassay (Brahms KRYPTOR), creatinine concentrations via a QuantiChrom assay, total protein concentrations via a bicinchoninic acid (BCA) protein assay, osmolality by freezing point depression, and specific gravity using a hydrometer.ResultsThere were no differences between the cohorts in race or ethnicity. There was no statistically significant difference in urinary copeptin, as a marker of AVP, in the postpartum period between women with vs. without a history of preeclampsia (4.5 vs. 3.2 mg/dL, P=0.4). No significant differences in copeptin were detected in women without a current hypertension diagnosis (5.49 mg/dL, N=43) and those being treated for hypertension (4.79 mg/dL, N=7, P=0.35).ConclusionsThis study suggests that copeptin, a surrogate measure for AVP, is not chronically elevated in urine after a preeclamptic pregnancy.
Gas Phase Diffusion Does Not Limit Lung Volatile Anesthetic Uptake Rate
Authors: Peyton Philip J. 
Published: May 2022

Background
Inefficiency of lung gas exchange during general anesthesia is reflected in alveolar (end-tidal) to arterial (end-tidal–arterial) partial pressure gradients for inhaled gases, resulting in an increase in alveolar deadspace. Ventilation–perfusion mismatch is the main contributor to this, but it is unclear what contribution arises from diffusion limitation in the gas phase down the respiratory tree (longitudinal stratification) or at the alveolar–capillary barrier, especially for gases of high molecular weight such as volatile anesthetics.

Methods
The contribution of longitudinal stratification was examined by comparison of end-tidal–arterial partial pressure gradients for two inhaled gases with similar blood solubility but different molecular weights: desflurane and nitrous oxide, administered together at 2 to 3% and 10 to 15% inspired concentration (FiG), respectively, in 17 anesthetized ventilated patients undergoing cardiac surgery before cardiopulmonary bypass. Simultaneous measurements were done of tidal gas concentrations, of arterial and mixed venous blood partial pressures by headspace equilibration, and of gas uptake rate calculated using the direct Fick method using thermodilution cardiac output measurement. Adjustment for differences between the two gases in FiG and in lung uptake rate (VG) was made on mass balance principles. A 20% larger end-tidal–arterial partial pressure gradient relative to inspired concentration (PetG – PaG)/FiG for desflurane than for N2O was hypothesized as physiologically significant.

Results
Mean (SD) measured (PetG – PaG)/FiG for desflurane was significantly smaller than that for N2O (0.86 [0.37] vs. 1.65 [0.58] mmHg; P < 0.0001), as was alveolar deadspace for desflurane. After adjustment for the different VG of the two gases, the adjusted (PetG – PaG)/FiG for desflurane remained less than the 20% threshold above that for N2O (1.62 [0.61] vs. 1.98 [0.69] mmHg; P = 0.028).

Conclusions
No evidence was found in measured end-tidal to arterial partial pressure gradients and alveolar deadspace to support a clinically significant additional diffusion limitation to lung uptake of desflurane relative to nitrous oxide.

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Sacral-Alar-Iliac (SAI) Fixation in Patients With Previous Pelvic Osteotomy
Authors: Mun Frederick , Vankara Ashish , Suresh Krishna V. , Margalit Adam , Sponseller Paul D. 
Published: May 2022

Study Design:
This was a retrospective study.

Objective:
The purpose of this study was to investigate the technical challenges and outcomes of sacral-alar-iliac (SAI) fixation for scoliosis in patients who had previously undergone a pelvic osteotomy for hip dysplasia.

Summary of Background Data:
Patients with neuromuscular disease are at high risk for developing hip dislocation and scoliosis. Surgical correction of one may affect the other.

Methods:
We reviewed the records of patients aged 18 years and below who underwent spinal fusion using SAI screws after having undergone a pelvic osteotomy, with ≥2-year follow-up. We recorded the SAI screw dimensions, time from osteotomy to SAI fixation, type of osteotomy, and any complications performing SAI fixation due to the pelvic osteotomy. Bivariate statistics were used to analyze the data with statistical significance defined as P-value <0.05.

Results:
Thirty-two patients were included. The average age was 10.3±3.2 years at pelvic osteotomy and 13.5±3.4 years at SAI fixation. Most patients had cerebral palsy (87.5%) and a unilateral Dega osteotomy (78.1%). Average screw dimensions were significantly shorter on the side of the osteotomy (66 vs. 72 mm, P<0.05). SAI screw placement was technically challenging in 8 patients (25%), due to pelvic distortion from the pelvic osteotomy. The use of a curved awl helped to find the intracortical channel. No patients had complications due to the SAI screw, and there were no significant differences in pelvic obliquity and major coronal curve correction. Two patients (6.3%) had screw lucency >2 mm around the SAI screw on the side of the pelvic osteotomy but no clinical symptoms.

Conclusions:
SAI fixation in patients with previous pelvic osteotomy is technically challenging due to pelvic morphology and prior implants. Often, a shorter SAI screw is required on the side of the osteotomy. However, outcomes in this patient population are satisfactory, with no significant complications at a 2-year follow-up.

Level of Evidence:
Level IV.
Clinicopathologic Features of Facial Dermatofibromas, a Cohort Study, and a Systematic Review of Literature
Authors: Alsawas Mouaz , Dundar Bilge , Prokop Larry , Murad M. Hassan , Swick Brian 
Published: May 2022

Background:
Dermatofibromas are common skin tumors that typically occur on the extremities and trunk and demonstrate benign behavior, frequent recurrences, and very rare metastasis. Facial dermatofibromas are rare and not well studied. We analyzed clinicopathologic features of facial dermatofibromas.

Design:
Considering the rarity of the condition, we conducted a cohort study and a systematic review. We queried medical records of a single tertiary care center for dermatofibromas from January 1, 2000, to July 1, 2021. A systematic review of multiple databases was conducted through October 27, 2021, to include studies reporting facial dermatofibromas. Random-effects meta-analysis was used to estimate pooled odds ratio and proportions with associated 95% confidence interval (CI).

Results:
The cohort study identified 2858 cases of dermatofibromas, of which, 23 cases from 18 patients were on the face (1%). The mean age was 52.7 ± 17.8 years. Fifty-six percent of the cases were women. The most common location was the forehead (6 cases). The mean follow-up was 54 months. Forty-four percent of the cases had subcutaneous involvement, and 39% were the cellular type. Margins were positive in 89% of the cases, recurrence rate was 22%, and no metastases were observed. The systematic review included 10 studies (119 patients). Meta-analyses showed that facial dermatofibromas were 2% of all dermatofibromas (95% CI: 1%–3%). The local recurrence rate was 14% (95% CI: 6%–26%). Facial dermatofibromas with subcutaneous involvement were more likely to recur [odds ratio 4.53 (95% CI: 1.12–18.24)]. Before histopathologic examination, clinical differential diagnosis included dermatofibromas in only 9% of the cases (95% CI: 2%–19%).

Conclusion:
Facial dermatofibromas are rare and are difficult to fully excise. Cellular type and subcutaneous or muscular involvement are common in these cases and tend to have higher local recurrence rate than other nonfacial dermatofibromas. Wider excisions might be necessary for complete excision.
Connexin 43 Expression in Cutaneous Biopsies of Lupus Erythematosus
Authors: Fernandez-Flores Angel , Varela-Vazquez Adrian , Mayan Maria D. , Cassarino David , Fonseca Eduardo 
Published: May 2022

Introduction:
Gap junctions are channels between adjacent cells formed by connexins (Cxs). Cxs also form hemichannels that connect the cell with its extracellular milieu. These channels allow the transport of ions, metabolites, and small molecules; therefore, Cxs, and more specifically, connexin (Cx) 43 has been demonstrated to be in control of several crucial events such as inflammation and cell death.

Material and methods:
We examined the immunostaining of Cx43 in the endothelia of the cutaneous blood vessels of biopsies from 28 patients with several variants of lupus erythematosus.

Results:
In 19 cases (67.86%), staining of more than half of the dermal vessels including both vessels of the papillary and of the reticular dermis was identified. Only in 4 cases (14.28%), less than 25% of the vessels in the biopsy showed expression of the marker.

Conclusions:
Our results suggest a role of Cx43 in regulating the endothelial activity in lupus erythematosus, which also opens a door for targeted therapeutic options.
DELAYED FOLLOW-UP IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION TREATED UNDER UNIVERSAL HEALTH COVERAGE
Authors: Rozon Jean-Philippe , Hébert Mélanie , Laverdière Carolane , Lachance Alexandre , Bourgault Serge , Caissie Mathieu , Letartre Laurence , Tourville Eric , Dirani Ali 
Published: May 2022

Background/Purpose:
To report the rate of delayed follow-up visits (DFU), to identify risk factors of DFU, and to assess the impact of DFU on outcomes in neovascular age-related macular degeneration.

Methods:
This retrospective study included all patients with neovascular age-related macular degeneration (n = 1,291) treated with antivascular endothelial growth factor injections between January 2013 and December 2020 in 2 centers in Quebec, Canada. A DFU was defined as a delay of ≥4 weeks than scheduled. Visual outcomes, especially ≥15 letters loss, were reported.

Results:
A total of 351 patients (27.2%) experienced ≥1 DFU. Odds were greater among older patients (P = 0.005), patients treated at the hospital rather than the clinic (P < 0.001), and patients with worse initial visual acuity (P = 0.024). A DFU was associated with a mean visual acuity loss of 4.2 ± 13.4 letters (P < 0.001) and an increased incidence of intraretinal fluid and subretinal fluid (P = 0.001, P = 0.005) at 6 months despite resumption of injections. Central foveal thickness increased after DFU but returned to pre-DFU visit at 6 months.

Conclusion:
The DFU rate in patients with neovascular age-related macular degeneration treated under a universal health care system was around 27%. Delayed follow-up visits caused significant decreases in visual acuity and increases in intraretinal fluid and subretinal fluid on optical coherence tomography that did not recover after injections resumption despite normalization of central foveal thickness.