bluuebunny/crossref_metadata_2025_split huggingface dataset:
Force-Bioreactor for Assessing Pharmacological Therapies for Mechanobiological Targets
Authors: Scholp Austin J. , Jensen Jordan , Chinnathambi Sathivel , Atluri Keerthi , Mendenhall Alyssa , Fowler Timothy , Salem Aliasger K. , Martin James A. , Sander Edward A. 
Published: July 2022

Tissue fibrosis is a major health issue that impacts millions of people and is costly to treat. However, few effective anti-fibrotic treatments are available. Due to their central role in fibrotic tissue deposition, fibroblasts and myofibroblasts are the target of many therapeutic strategies centered primarily on either inducing apoptosis or blocking mechanical or biochemical stimulation that leads to excessive collagen production. Part of the development of these drugs for clinical use involves in vitro prescreening. 2D screens, however, are not ideal for discovering mechanobiologically significant compounds that impact functions like force generation and other cell activities related to tissue remodeling that are highly dependent on the conditions of the microenvironment. Thus, higher fidelity models are needed to better simulate in vivo conditions and relate drug activity to quantifiable functional outcomes. To provide guidance on effective drug dosing strategies for mechanoresponsive drugs, we describe a custom force-bioreactor that uses a fibroblast-seeded fibrin gels as a relatively simple mimic of the provisional matrix of a healing wound. As cells generate traction forces, the volume of the gel reduces, and a calibrated and embedded Nitinol wire deflects in proportion to the generated forces over the course of 6 days while overhead images of the gel are acquired hourly. This system is a useful in vitro tool for quantifying myofibroblast dose-dependent responses to candidate biomolecules, such as blebbistatin. Administration of 50 μM blebbistatin reliably reduced fibroblast force generation approximately 40% and lasted at least 40 h, which in turn resulted in qualitatively less collagen production as determined via fluorescent labeling of collagen.
Design of an Integrated Microvascularized Human Skin-on-a-Chip Tissue Equivalent Model
Authors: Jones Christian F. E. , Di Cio Stefania , Connelly John T. , Gautrot Julien E. 
Published: July 2022

Tissue-engineered skin constructs have been under development since the 1980s as a replacement for human skin tissues and animal models for therapeutics and cosmetic testing. These have evolved from simple single-cell assays to increasingly complex models with integrated dermal equivalents and multiple cell types including a dermis, epidermis, and vasculature. The development of micro-engineered platforms and biomaterials has enabled scientists to better recreate and capture the tissue microenvironment in vitro, including the vascularization of tissue models and their integration into microfluidic chips. However, to date, microvascularized human skin equivalents in a microfluidic context have not been reported. Here, we present the design of a novel skin-on-a-chip model integrating human-derived primary and immortalized cells in a full-thickness skin equivalent. The model is housed in a microfluidic device, in which a microvasculature was previously established. We characterize the impact of our chip design on the quality of the microvascular networks formed and evidence that this enables the formation of more homogenous networks. We developed a methodology to harvest tissues from embedded chips, after 14 days of culture, and characterize the impact of culture conditions and vascularization (including with pericyte co-cultures) on the stratification of the epidermis in the resulting skin equivalents. Our results indicate that vascularization enhances stratification and differentiation (thickness, architecture, and expression of terminal differentiation markers such as involucrin and transglutaminase 1), allowing the formation of more mature skin equivalents in microfluidic chips. The skin-on-a-chip tissue equivalents developed, because of their realistic microvasculature, may find applications for testing efficacy and safety of therapeutics delivered systemically, in a human context.
Survival and risk factors associated with surgical repair of ventricular septal rupture after acute myocardial infarction: A single-center experience
Authors: Zhao Keyan , Li Baoyin , Sun Biao , Tao Dengshun , Jiang Hui , Wang Huishan 
Published: July 2022

ObjectiveTo analyze the survival and risk factors associated with the surgical treatment of ventricular septal rupture (VSR) after acute myocardial infarction (AMI).MethodsWe retrospectively analyzed 45 consecutive patients with VSR after AMI whose procedures were performed in the Department of Cardiovascular Surgery at the General Hospital of Northern Theater Command between January 2012 and December 2021. Relevant clinical data, surgery-related conditions, and follow-up data of all patients were summarized. Patients were divided into the survival group and the death group. The Kaplan–Meier method and log-rank test were used to determine the cumulative incidence of all-cause mortality. Multivariate logistic regression was used to evaluate the independent risk factors for all-cause mortality.ResultsThe average postoperative follow-up time was 42.1 ± 34.1 months. The overall mortality rate was 20% (9/45 patients) and the operative mortality rate was 8.9% (4/45 patients). Logistic analysis showed that the death group had higher serum creatinine (127.32 ± 47.82 vs. 82.61 ± 27.80 μmol/L, respectively; P = 0.0238) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) [8,654.00 pg/mL (6,197.00–11,949.00 pg/mL) vs. 4,268.96 pg/mL (1,800.00–7,894.00 pg/mL), respectively; P = 0.0134] levels than the survival group. The cardiopulmonary bypass time (CPB) was longer in the death group than in the survival group [131.00 min (121.00–184.00 min) vs. 119.00 min (103.00–151.50 min), respectively; P = 0.0454]. Significantly more red blood cells were transfused in the death group than in the survival group [11.60 units (6.10–16.50) vs. 3.75 units (0.00–7.00 units), respectively; P = 0.0025]. Intra-aortic balloon pump (IABP) implantation (P = 0.016) and ventilation time (P = 0.0022) were risk factors for mortality. A 1-month landmark analysis showed that compared with patients with VSR to surgical time &gt;14 days, patients who underwent surgery within 14 days had a higher rate of all-cause mortality (25.00 vs. 3.33%; log-rank P = 0.023). Patients with VSR within 14 days also had a higher rate of residual shunts that were higher than moderate. Multivariate analysis showed that transfusion of red blood cells and NT-proBNP level were risk factors for all-cause mortality, as well as major adverse cardiovascular and cerebrovascular events.ConclusionsSurgical repair resulted in good outcomes for patients with VSR after AMI. Patients with VSR to surgical time &gt;14 days had a lower rate of all-cause mortality. Treatment strategies for VSR should be based on the patient's condition and comprehensively determined through real-time evaluation and monitoring.
Ablation and antiarrhythmic drug effects on PITX2+/− deficient atrial fibrillation: A computational modeling study
Authors: Jin Ze , Hwang Inseok , Lim Byounghyun , Kwon Oh-Seok , Park Je-Wook , Yu Hee-Tae , Kim Tae-Hoon , Joung Boyoung , Lee Moon-Hyoung , Pak Hui-Nam 
Published: July 2022

IntroductionAtrial fibrillation (AF) is a heritable disease, and the paired-like homeodomain transcription factor 2 (PITX2) gene is highly associated with AF. We explored the differences in the circumferential pulmonary vein isolation (CPVI), which is the cornerstone procedure for AF catheter ablation, additional high dominant frequency (DF) site ablation, and antiarrhythmic drug (AAD) effects according to the patient genotype (wild-type and PITX2+/− deficient) using computational modeling.MethodsWe included 25 patients with AF (68% men, 59.8 ± 9.8 years of age, 32% paroxysmal AF) who underwent AF catheter ablation to develop a realistic computational AF model. The ion currents for baseline AF and the amiodarone, dronedarone, and flecainide AADs according to the patient genotype (wild type and PITX2+/− deficient) were defined by relevant publications. We tested the virtual CPVI (V-CPVI) with and without DF ablation (±DFA) and three virtual AADs (V-AADs, amiodarone, dronedarone, and flecainide) and evaluated the AF defragmentation rates (AF termination or changes to regular atrial tachycardia (AT), DF, and maximal slope of the action potential duration restitution curves (Smax), which indicates the vulnerability of wave-breaks.ResultsAt the baseline AF, mean DF (p = 0.003), and Smax (p &lt; 0.001) were significantly lower in PITX2+/− deficient patients than wild-type patients. In the overall AF episodes, V-CPVI (±DFA) resulted in a higher AF defragmentation relative to V-AADs (65 vs. 42%, p &lt; 0.001) without changing the DF or Smax. Although a PITX2+/− deficiency did not affect the AF defragmentation rate after the V-CPVI (±DFA), V-AADs had a higher AF defragmentation rate (p = 0.014), lower DF (p &lt; 0.001), and lower Smax (p = 0.001) in PITX2+/− deficient AF than in wild-type patients. In the clinical setting, the PITX2+/− genetic risk score did not affect the AF ablation rhythm outcome (Log-rank p = 0.273).ConclusionConsistent with previous clinical studies, the V-CPVI had effective anti-AF effects regardless of the PITX2 genotype, whereas V-AADs exhibited more significant defragmentation or wave-dynamic change in the PITX2+/− deficient patients.
Prescribing Time in Nature for Human Health and Well-Being: Study Protocol for Tailored Park Prescriptions
Authors: Schultz Courtney L. , Bocarro Jason N. , Hipp J. Aaron , Bennett Gary J. , Floyd Myron F. 
Published: July 2022

BackgroundeHealth technologies offer an efficient method to integrate park prescriptions into clinical practice by primary health care (PHC) providers to help patients improve their health via tailored, nature-based health behavior interventions. This paper describes the protocol of the GoalRx Prescription Intervention (GPI) which was designed to leverage community resources to provide tailored park prescriptions for PHC patients.MethodsThe GPI study was designed as a 3-arm, multi-site observational study. We enrolled low-income, rural adults either at-risk of or living with hypertension or diabetes (n = 75) from Federally Qualified Health Centers (FQHC) in two counties in North Carolina, USA into the 3-month intervention. Eligible participants self-selected to receive (1) a tailored park prescription intervention; (2) a tailored home/indoor PA prescription intervention; or (3) a healthy eating prescription (with no PA prescription beyond standard PA counseling advice that is already routinely provided in PHC) as the comparison group. The GPI app paired patient health data from the electronic health record with stated patient preferences and triggered app-integrated SMS motivation and compliance messaging directly to the patient. Patients were assessed at baseline and at a 3-month follow-up upon the completion of the intervention. The primary outcome (mean difference in weekly physical activity from baseline (T0) to post-intervention (T1) as measured by the Fitbit Flex 2) was assessed at 3 months. Secondary outcomes included assessment of the relationship between the intervention and biological markers of health, including body mass index (BMI), systolic and diastolic blood pressure, HbA1c or available glucose test (if applicable), and a depression screen score using the Patient Health Questionnaire 9. Secondary outcomes also included the total number of SMS messages sent, number of SMS messages responded to, number of SMS messages ignored, and opt-out rate.DiscussionThe goal was to create a protocol utilizing eHealth technologies that addressed the specific needs of rural low-income communities and fit into the natural rhythms and processes of the selected FQHC clinics in North Carolina. This protocol offered a higher standard of health care by connecting patients to their PHC teams and increasing patient motivation to make longer-lasting health behavior changes.
Non-Occlusive Mesenteric Ischemia in Children With Diabetic Ketoacidosis: Case Report and Review of Literature
Authors: Frontino Giulio , Di Tonno Raffaella , Castorani Valeria , Rigamonti Andrea , Morotti Elisa , Sandullo Federica , Scialabba Francesco , Arrigoni Francesca , Foglino Riccardo , Dionisi Benedetta , Ferri Chiara Irene Carla , Zirpoli Salvatore , Barera Graziano , Meschi Franco , Bonfanti Riccardo 
Published: July 2022

IntroductionDespite the use of technology, recurrent diabetic ketoacidosis (DKA) prevention remains an unmet need in children and adolescents with T1D and may be accompanied by life-threatening acute complications. We present a rare case of non-occlusive mesenteric ischemia (NOMI) with overt manifestation after DKA resolution and a discussion of recent literature addressing DKA-associated NOMI epidemiology and pathogenesis in children and adolescents.Case PresentationA 13-year-old female with previously diagnosed T1D, was admitted at our emergency department with hypovolemic shock, DKA, hyperosmolar state and acute kidney injury (AKI). Mildly progressive abdominal pain persisted after DKA correction and after repeated ultrasound evaluations ultimately suspect for intestinal perforation, an intraoperative diagnosis of NOMI was made.ConclusionThe diagnosis of DKA-associated NOMI must be suspected in pediatric patients with DKA, persistent abdominal pain, and severe dehydration even after DKA resolution.
Correlation Between Bioelectrical Impedance Analysis and Chest CT-Measured Erector Spinae Muscle Area: A Cross-Sectional Study
Authors: Cao Jie , Zuo Didi , Han Tingting , Liu Hongxia , Liu Wenwen , Zhang Jia , Weng Yurong , Jin Xian , Chen Zengai , Hu Yaomin 
Published: July 2022

BackgroundSkeletal muscle mass (SMM) plays an important part in diverse health and disease states. Bioelectrical impedance analysis (BIA) and computed tomography (CT) are available for its assessment. However, muscle mass assessed by BIA may be influenced by multiple factors. The erector spinae muscle area (ESA) on chest CT is recently presumed to be representative of SMM. This study aimed to derive BIA from the ESA and evaluate the magnitude of association (between ESA measured from chest CT) and BIA.MethodsSubjects hospitalized for health checkups between December 2020 and December 2021, having undergone both BIA (50 kHz, 0.8 mA) and chest CT, were included. ESA was quantified at the level of the 12th thoracic vertebra (T12-ESA) by a standardized semi-automated segmentation algorithm. Low SMM was defined using the Asian Working Group for Sarcopenia criteria. The association between T12-ESA and BIA was then evaluated. Stratified analyses by sex and BMI were also performed.ResultsAmong 606 included subjects (59.7 ± 16.6 years, 63.5% male), 110 (18.2%) had low SMM. BMI in low and normal SMM groups was 20.1 and 24.7 kg/m2, respectively. Current smoking, drinking, chronic obstructive pulmonary disease, and chronic renal dysfunction were more frequently seen in the low SMM group than in the normal SMM group. The final regression model included T12-ESA, weight, BMI, and age, and had an adjusted R2 of 0.806 with BIA. In the validation group, the correlation between T12-ESA-derived BIA and BIA remained high (Pearson correlation = 0.899). Stratified analysis disclosed a stronger correlation between T12-ESA and BIA in male subjects than in female subjects (adjusted R2 = 0.790 vs. adjusted R2 = 0.711, p &lt; 0.05), and a better correlation was observed in obese (BMI ≥ 30 kg/m2) compared with underweight (BMI &lt; 18.5 kg/m2) subjects (adjusted R2 = 0.852 vs. adjusted R2 = 0.723, p &lt; 0.05). Additional analysis revealed a significant correlation between T12-ESA and skeletal muscle cross-sectional area at the 3rd lumbar vertebra (L3-CSA) (adjusted R2 = 0.935, p &lt; 0.001).ConclusionsCT-based assessment of ESA at the T12 level is feasible and correlated well with BIA, especially in male subjects and obese subjects.
Using Glycated Albumin and Stimulated C-Peptide to Define Partial Remission in Type 1 Diabetes
Authors: Shi Mei , Ji Xiaolin , Xie Yuting , Zhong Ting , Tang Rong , Fan Li , Li Xia 
Published: July 2022

ObjectiveTo propose a new definition of partial remission (PR) for patients with type 1 diabetes (T1D) of all-ages using insulin dose and glycated albumin (GA), and find the optimal cut-off values for stimulated C-peptide to diagnose PR in different age-groups.Research Design and MethodsPatients with newly diagnosed T1D (n=301) were included. GA/insulin dose was used to diagnose PR, and insulin dose-adjusted glycated albumin (IDAGA) was proposed to facilitate clinical application. The optimal diagnostic levels of IDAGA and stimulated C-peptide were determined in different age-groups (≤ 12y, 12-18y and ≥ 18y). Furthermore, the diagnostic consistency between different PR definitions was studied.ResultsGA≤ 23%/insulin dose ≤ 0.5u/kg/day was used to define PR, and IDAGA (GA (%) + 40 * insulin dose(u/kg/day)) ≤ 40 was feasible in all age-groups. Whereas, the optimal diagnostic level showed difference for stimulated C-peptide (265.5, 449.3 and 241.1 pmol/L for the ≤ 12y, 12-18y and ≥ 18y age-group, respectively). About 40% of patients met the PR definition by stimulated C-peptide but not GA/insulin dose or IDAGA, who showed dyslipidemia and higher insulin resistance.ConclusionsA new definition of the PR phase is proposed using GA/insulin dose, and the calculated IDAGA≤ 40 applies to all age-groups. The stimulated C-peptide to diagnose PR is the highest in the 12-18y age-group, which reflects the effect of puberty on metabolism. For patients with insulin resistance, it is not recommended to use stimulated C-peptide alone to diagnose PR.
Linagliptin in Combination With Metformin Ameliorates Diabetic Osteoporosis Through Modulating BMP-2 and Sclerostin in the High-Fat Diet Fed C57BL/6 Mice
Authors: Nirwan Nikita , Vohora Divya 
Published: July 2022

BackgroundDiabetic osteoporosis is a poorly managed serious skeletal complication, characterized by high fracture risk, increased bone resorption, reduced bone formation, and disrupted bone architecture. There is a need to investigate drugs that can improve bone health along with managing glycemic control. DPP-4 inhibitors and metformin have proven benefits in improving bone health. Here, we investigated the effects of linagliptin, a DPP inhibitor, and metformin alone and in combination to treat diabetic osteoporosis in high-fat-fed mice.MethodsC57BL/6 mice were kept on the high-fat diet (HFD) for 22 weeks to induce diabetic osteoporosis. Linagliptin (10mg/Kg), metformin (150mg/Kg), and their combination were orally administered to the diabetic mice from the 18th-22nd week. Femur and tibial bone microarchitecture together with bone mineral density (BMD) were evaluated using µCT and histopathological changes were assessed. Further, bone turnover biomarkers namely bone morphogenetic protein-2 (BMP-2), sclerostin, tartrate-resistant acid phosphatase (TRAP), osteocalcin, alkaline phosphatase (ALP), calcium, and pro-inflammatory cytokines were assessed. Additionally, metabolic parameters including body weight, fasting blood glucose (FBG), glucose &amp; insulin tolerance, lipids profile, and leptin were measured.ResultsHFD feeding resulted in impaired bone microarchitecture, reduced BMD, distorted bone histology, and altered bone turnover biomarkers as indicated by the significant reduction in bone ALP, BMP-2, osteocalcin, and an increase in sclerostin, TRAP, and serum calcium. Interestingly, treatment with linagliptin and its combination with metformin significantly reverted the impaired bone architecture, BMD, and positively modulated bone turnover biomarkers, while metformin alone did not exhibit any significant improvement. Further, HFD induced diabetes and metabolic abnormalities (including an increase in body weight, FBG, impaired glucose and insulin tolerance, leptin, triglycerides, cholesterol), and pro-inflammatory cytokines (TNF-alpha and IL-1β) were successfully reversed by treatment with linagliptin, metformin, and their combination.ConclusionLinagliptin and its combination with metformin successfully ameliorated diabetic osteoporosis in HFD-fed mice possibly through modulation of BMP-2 and sclerostin. The study provides the first evidence for the possible use of linagliptin and metformin combination for managing diabetic osteoporosis.
New Insight Into the Reproductive Biology and Catch of Juveniles of the Lutjanus purpureus in a Portion of the Great Amazon Reef System Off the Northern Brazilian Coast
Authors: Freire Julliany L. , Sarmento Gabriela C. , Lutz Ítalo , Bentes Bianca , Isaac Victoria J. 
Published: July 2022

The Southern red snapper, Lutjanus purpureus, is a valuable economic resource, especially in international market. However, no recent data are available on the reproductive biology of this species in Brazilian waters, in particular, the stock found on the Amazon reef. The present study evaluated the population structure and reproductive biology of L. purpureus, and the volume of the catch of juveniles taken by the local commercial fisheries. A total of 923 specimens were analyzed, of which, 577 were female and 346 male (sex ratio: 0.6:1; p &lt; 0.05). The analysis of the gonadosomatic index (GSI) and the distribution of maturation stages indicated that the males and females are able to reproduce throughout the year, however the reproductive peak occurs simultaneously with the increase in the water discharge of the Amazon River. The spawning females were registered in the study area, indicating that L. purpureus does not perform long distance reproductive migrations, different from the previously proposed. The Fork length at first sexual maturation (FL50) was estimated to be 35.2 cm in the males and 32.1 cm in the females. The high frequency of juveniles (&lt; FL50) captured by the commercial snapper fleet using longlines (33.67% of the total catch) and traps (42.1%) indicates the poor selectivity of the fishing gear used by the snapper fleet, which may contribute to the accelerated depletion of the L. purpureus stock. Although the results of this study show a catch percentage of juveniles &gt;50%, it is still a significant percentage of juveniles that are being caught due to little or no guidance and enforcement of fishing gear to ensure compliance with current legislation. Considering the data presented in this study and the current situation of declining fish stocks of L. purpureus, an assessment is recommended for the inclusion of the species in the IUCN Red List of Threatened Species, which is currently a species categorized as “vulnerable” in the Brazilian Red List.