bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pleiotropic Effects of Simvastatin and Losartan in Preclinical Models of Post-Traumatic Elbow Contracture
Authors: David Michael A. , Reiter Alex J. , Dunham Chelsey L. , Castile Ryan M. , Abraham James A. , Iannucci Leanne E. , Shah Ishani D. , Havlioglu Necat , Chamberlain Aaron M. , Lake Spencer P. 
Published: February 2022

Elbow trauma can lead to post-traumatic joint contracture (PTJC), which is characterized by loss of motion associated with capsule/ligament fibrosis and cartilage damage. Unfortunately, current therapies are often unsuccessful or cause complications. This study aimed to determine the effects of prophylactically administered simvastatin (SV) and losartan (LS) in two preclinical models of elbow PTJC: an in vivo elbow-specific rat injury model and an in vitro collagen gel contraction assay. The in vivo elbow rat (n = 3–10/group) injury model evaluated the effects of orally administered SV and LS at two dosing strategies [i.e., low dose/high frequency/short duration (D1) vs. high dose/low frequency/long duration (D2)] on post-mortem elbow range of motion (via biomechanical testing) as well as capsule fibrosis and cartilage damage (via histopathology). The in vitro gel contraction assay coupled with live/dead staining (n = 3–19/group) evaluated the effects of SV and LS at various concentrations (i.e., 1, 10, 100 µM) and durations (i.e., continuous, short, or delayed) on the contractibility and viability of fibroblasts/myofibroblasts [i.e., NIH3T3 fibroblasts with endogenous transforming growth factor-beta 1 (TGFβ1)]. In vivo, no drug strategy prevented elbow contracture biomechanically. Histologically, only SV-D2 modestly reduced capsule fibrosis but maintained elevated cellularity and tissue hypertrophy, and both SV strategies lessened cartilage damage. SV modest benefits were localized to the anterior region, not the posterior, of the joint. Neither LS strategy had meaningful benefits in capsule nor cartilage. In vitro, irrespective of the presence of TGFβ1, SV (≥10 μM) prevented gel contraction partly by decreasing cell viability (100 μM). In contrast, LS did not prevent gel contraction or affect cell viability. This study demonstrates that SV, but not LS, might be suitable prophylactic drug therapy in two preclinical models of elbow PTJC. Results provide initial insight to guide future preclinical studies aimed at preventing or mitigating elbow PTJC.
Protein Splicing of Inteins: A Powerful Tool in Synthetic Biology
Authors: Wang Hao , Wang Lin , Zhong Baihua , Dai Zhuojun 
Published: February 2022

Inteins are protein segments that are capable of enabling the ligation of flanking extein into a new protein, a process known as protein splicing. Since its discovery, inteins have become powerful biotechnological tools for applications such as protein engineering. In the last 10 years, the development in synthetic biology has further endowed inteins with enhanced functions and diverse utilizations. Here we review these efforts and discuss the future directions.
Enhancing the Catalytic Performance of Candida antarctica Lipase B by Chemical Modification With Alkylated Betaine Ionic Liquids
Authors: Xue Yu , Zhang Xiao-Guang , Lu Ze-Ping , Xu Chao , Xu Hua-Jin , Hu Yi 
Published: February 2022

Various betaine ionic liquids composed of different chain lengths and different anions were designed and synthesized to modify Candida antarctica lipase B (CALB). The results showed that the catalytic activity of all modified lipases improved under different temperature and pH conditions, while also exhibiting enhanced thermostability and tolerance to organic solvents. With an increase in ionic liquid chain length, the modification effect was greater. Overall, CALB modified by [BetaineC16][H2PO4] performed best, with the modified CALB enzyme activity increased 3-fold, thermal stability increased 1.5-fold when stored at 70°C for 30 min, with tolerance increased 2.9-fold in 50% DMSO and 2.3-fold in 30% mercaptoethanol. Fluorescence and circular dichroism (CD) spectroscopic analysis showed that the introduction of an ionic liquid caused changes in the microenvironment surrounding some fluorescent groups and the secondary structure of the CALB enzyme protein. In order to establish the enzyme activity and stability change mechanisms of the modified CALB, the structures of CALB modified with [BetaineC4][Cl] and [BetaineC16][Cl] were constructed, while the reaction mechanisms were studied by molecular dynamics simulations. Results showed that the root mean square deviation (RMSD) and total energy of modified CALB were less than those of native CALB, indicating that modified CALB has a more stable structure. Root mean square fluctuation (RMSF) calculations showed that the rigidity of modified CALB was enhanced. Solvent accessibility area (SASA) calculations exhibited that both the hydrophilicity and hydrophobicity of the modified enzyme-proteins were improved. The increase in radial distribution function (RDF) of water molecules confirmed that the number of water molecules around the active sites also increased. Therefore, modified CALB has enhanced structural stability and higher hydrolytic activity.
“It Just Kind of Feels Like a Different World Now:” Stress and Resilience for Adolescents With Type 1 Diabetes in the Era of COVID-19
Authors: O’Donnell Maeve B. , Hilliard Marisa E. , Cao Viena T. , Bradford Miranda C. , Barton Krysta S. , Hurtado Samantha , Duran Brenda , Perez Samantha Garcia , Rahman Kiswa S. , Scott Samantha , Malik Faisal S. , DeSalvo Daniel J. , Pihoker Catherine , Zhou Chuan , Rosenberg Abby R. , Yi-Frazier Joyce P. 
Published: February 2022

PurposeThe COVID-19 pandemic has been a major stressor for adolescents. Given the unique implications of the pandemic for youth with type 1 diabetes (T1D), who already navigate multiple stressors as a function of their chronic condition, we aimed to describe the impact of the pandemic on adolescents with T1D and describe their coping strategies and resilience resources.Research MethodIn a 2-site (Seattle WA, Houston TX) clinical trial of a psychosocial intervention targeting stress/resilience, adolescents 13-18 years old with T1D ≥ 1 year and elevated diabetes distress were enrolled August 2020 – June 2021. Participants completed a baseline survey about the pandemic, including open-ended questions about the effects of the pandemic, what was helping them navigate, and how it impacted T1D management. Hemoglobin A1c (A1c) was extracted from clinical records. Free text responses were analyzed using an inductive content approach. Survey responses and A1c were summarized using descriptive statistics and associations were assessed by Chi-squared tests.ResultsAdolescents (n=122) were 56% female. 11% of adolescents reported diagnosis of COVID-19 and 12% had a family member/other important person die from COVID-19 complications. Adolescents described Social Relationships, Personal Health/Safety Practices, Mental Health, Family Relationships, and School to be primary areas affected by COVID-19. Helpful resources included: Learned Skills/Behaviors, Social Support/Community, and Meaning-Making/Faith. Among participants indicating that the pandemic had an impact on their T1D management (n=35), the most commonly described areas were: Food, Self-Care, Health/Safety, Diabetes Appointments, and Exercise. Compared to adolescents who reported minimal difficulty managing T1D during the pandemic (71%), those reporting moderate to extreme difficulty (29%) were more likely to have A1C ≥ 8% (80% vs. 43%, p&lt;.01).ConclusionsResults underscore the pervasive impact of COVID-19 on teens with T1D across multiple major life domains. Their coping strategies aligned with stress, coping, and resilience theories and suggest resilient responses in the face of stress. Despite experiencing pandemic-related stressors in many areas, diabetes-related functioning was relatively protected for most teens, highlighting their diabetes-specific resilience. Discussing the pandemic impact on T1D management may be an important focus for clinicians, especially for adolescents with diabetes distress and above-target A1C.
Embryonic Hypotaurine Levels Contribute to Strain-Dependent Susceptibility in Mouse Models of Valproate-Induced Neural Tube Defects
Authors: Steele John W. , Lin Ying Linda , Chen Nellie , Wlodarczyk Bogdan J. , Chen Qiuying , Attarwala Nabeel , Venkatesalu Madhu , Cabrera Robert M. , Gross Steven S. , Finnell Richard H. 
Published: February 2022

Valproic acid (VPA, valproate, Depakote) is a commonly used anti-seizure medication (ASM) in the treatment of epilepsy and a variety of other neurological disorders. While VPA and other ASMs are efficacious for management of seizures, they also increase the risk for adverse pregnancy outcomes, including neural tube defects (NTDs). Thus, the utility of these drugs during pregnancy and in women of childbearing potential presents a continuing public health challenge. Elucidating the underlying genetic or metabolic risk factors for VPA-affected pregnancies may lead to development of non-teratogenic ASMs, novel prevention strategies, or more targeted methods for managing epileptic pregnancies. To address this challenge, we performed unbiased, whole embryo metabolomic screening of E8.5 mouse embryos from two inbred strains with differential susceptibility to VPA-induced NTDs. We identified metabolites of differential abundance between the two strains, both in response to VPA exposure and in the vehicle controls. Notable enriched pathways included lipid metabolism, carnitine metabolism, and several amino acid pathways, especially cysteine and methionine metabolism. There also was increased abundance of ω-oxidation products of VPA in the more NTD-sensitive strain, suggesting differential metabolism of the drug. Finally, we found significantly reduced levels of hypotaurine in the susceptible strain regardless of VPA status. Based on this information, we hypothesized that maternal supplementation with L-carnitine (400 mg/kg), coenzyme A (200 mg/kg), or hypotaurine (350 mg/kg) would reduce VPA-induced NTDs in the sensitive strain and found that administration of hypotaurine prior to VPA exposure significantly reduced the occurrence of NTDs by close to one-third compared to controls. L-carnitine and coenzyme A reduced resorption rates but did not significantly reduce NTD risk in the sensitive strain. These results suggest that genetic variants or environmental exposures influencing embryonic hypotaurine status may be factors in determining risk for adverse pregnancy outcomes when managing the health care needs of pregnant women exposed to VPA or other ASMs.
Prevalence of Clostridium difficile Infection in the Hematopoietic Transplantation Setting: Update of Systematic Review and Meta-Analysis
Authors: Luo Ying , Zhang Sumei , Shang Hua , Cui Weitong , Wang Qinglu , Zhu Bin 
Published: February 2022

Hematopoietic stem cell transplant (HSCT) recipients are vulnerable to Clostridium difficile infection (CDI) due to risk factors such as immunosuppression, antimicrobial use, and frequent hospitalization. We systematically searched PubMed and Embase to screen relevant studies from April 2014 to November 2021. A meta-analysis was performed to identify the association between CDI and hematopoietic transplantation based on the standard mean difference and 95% confidence intervals (CIs). Among the 431 retrieved citations, we obtained 43 eligible articles, which included 15,911 HSCT patients at risk. The overall estimated prevalence of CDI was 13.2%. The prevalence of CDI among the 10,685 allogeneic transplantation patients (15.3%) was significantly higher than that among the 3,840 autologous HSCT recipients (9.2%). Different incidence rates of CDI diagnosis over the last 7 years were found worldwide, of which North America (14.1%) was significantly higher than Europe (10.7%) but not significantly different from the prevalence among Asia (11.6%). Notably, we found that the estimated prevalence of CDI diagnosed by polymerase chain reaction (PCR) (17.7%) was significantly higher than that diagnosed by enzyme immunoassay (11.5%), indicating a significant discrepancy in the incidence rate of CDI owing to differences in the sensibility and specificity of the detection methods. Recurrence of CDI was found in approximately 15% of the initial patients with CDI. Furthermore, 20.3% of CDI cases were severe. CDI was found to be a common complication among HSCT recipients, displaying an evident increase in the morbidity of infection.
Value of Fast MVO Identification From Contrast-Enhanced Cine (CE-SSFP) Combined With Myocardial Strain in Predicting Adverse Events in Patients After ST-Elevation Myocardial Infarction
Authors: Zhang Min , Lu Yuan , Li Zhi , Shao Yameng , Chen Lei , Yang Yu , Xi Jianning , Chen Minglong , Jiang Tingbo 
Published: February 2022

ObjectivesCardiac magnetic resonance imaging (CMR) can be used for a one-step evaluation of myocardial function and pathological features after acute ST-elevation myocardial infarction (STEMI). We aimed to evaluate the value of fast microvascular occlusion (MVO) identification from contrast-enhanced steady-state free precession (CE-SSFP) combined with myocardial strain in predicting major cardiovascular adverse events (MACEs) in primary percutaneous coronary intervention (pPCI) patients with STEMI.MethodsIn total, 237 patients with STEMI who received pPCI and completed CMR scans within the following week were enrolled, MVO identification and the myocardial strain analysis were performed in CE-SSFP images without an additional method. The primary endpoint was the presence of MACE, which is defined as a composite of death, reinfarction, and congestive heart failure (HF).ResultsAfter 13 months of follow-up [interquartile range (IQR): 11–24], 30 patients (14%) developed MACE; the MVO (hazard ratio (HR) was 3.10; 95% CI: 1.14–8.99, p = 0.028), and the infarct size (IS) (HR: 1.03; 95% CI: 1.0–1.06, p = 0.042) and global longitudinal strain (GLS) (HR: 1.08; 95% CI: 1.01–1.17, p = 0.029) were finally associated with MACE. Receiver operating characteristic (ROC) analyses show that the area under the curve (AUC) of GLS was large (0.73 [95% CI, 0.63–0.82], p = 0.001), and the best cut-off was −11.8%, with 76.7% sensitivity and 58.9% specificity, which are greater than those of IS (0.70, 95% CI, 0.60–0.81, p &lt; 0.001) and MVO (0.68, 95% CI, 0.58–0.78, p &lt; 0.001). However, combining MVO and GLS resulted in a much greater finding (AUC = 0.775, 95% CI: 0.727–0.824, p &lt; 0.001) and better sensitivity and specificity (83.3%, 66.5%).ConclusionMicrovascular occlusion identification from contrast-enhanced cine combined with myocardial strain could be a quick and reliable option for patients with STEMI who underwent pPCI; it correlates well with the prognosis of patients with STEMI in terms of MACE.
Intravascular Lithotripsy in Calcified Coronary Lesions: A Single-Center Experience in “Real-World” Patients
Authors: Mastrangelo Angelo , Monizzi Giovanni , Galli Stefano , Grancini Luca , Ferrari Cristina , Olivares Paolo , Chiesa Mattia , Calligaris Giuseppe , Fabbiocchi Franco , Montorsi Piero , Bartorelli Antonio L. 
Published: February 2022

ObjectivesThis study aims to describe the outcome of intravascular lithotripsy (IVL) when used with different indications and to assess the short- and long-term outcomes of IVL-facilitated percutaneous coronary intervention (PCI).BackgroundIntravascular lithotripsy can improve the results of PCI of calcified coronary lesions with a low rate of periprocedural complications.MethodsA total of 105 consecutive patients with 110 calcified lesions underwent IVL. A total of 87de novolesions were treated by IVL with the following indications: 25 before attempting other balloon-based devices (primary IVL), 51 after the failure of non-compliant balloon dilatation (secondary IVL), and 11 after stent implantation because of stent under expansion (bailout IVL). In 23 lesions, IVL was used for the treatment of in-stent restenosis (ISR). Effectiveness (angiographic success) and safety [major adverse cardiovascular events (MACEs) and IVL-related procedural complications] endpoints were assessed.ResultsAngiographic success was achieved in 84.6% of lesions. Early MACEs were periprocedural MI only, ranging from 6.7 to 20% depending on MI definition. The flow-limiting dissections rate was 2.7%. A total of five (4.5%) IVL balloons ruptured during treatment with subsequent vessel perforation in 1 case. MACEs at 12 months were 13.3%, with TLR occurring in 8 lesions (12% primary IVL, 0% secondary IVL, 0% bailout IVL, and 21.7% IVL for ISR,p= 0.002).ConclusionTreatment of calcified coronary lesions with IVL in a “real-world” setting can be performed with high success, low rate of procedural complications, and an acceptable MACEs rate. Target lesion failure may be more frequent when IVL is performed for the treatment of ISR due to calcium-mediated stent under expansion.
Physical Inactivity Is Associated With Post-discharge Mortality and Re-hospitalization Risk Among Swedish Heart Failure Patients—The HARVEST-Malmö Study
Authors: Zaghi Amir , Holm Hannes , Korduner Johan , Dieden Anna , Molvin John , Bachus Erasmus , Jujic Amra , Magnusson Martin 
Published: February 2022

BackgroundSeveral studies have examined the role of physical activity as a predictor of heart failure (HF) mortality and morbidity. Here, we aimed to evaluate the role of self-reported physical activity as an independent risk factor of post-discharge mortality and re-hospitalization in patients hospitalized for HF, as well as study the association between physical activity and 92 plasma proteins associated with cardiovascular disease (CVD).MethodsFour-hundred-and-thirty-four patients hospitalized for HF (mean age 75 years; 32% women) were screened for physical activity derived from questionnaires in the Swedish national public health survey. The median follow-up time to death and re-hospitalization was 835 (interquartile range, 390–1,432) and 157 (43–583) days, respectively. Associations between baseline reported physical activity, mortality and re-hospitalization risk were analyzed using multivariable Cox regression analysis. Plasma samples from 295 study participants were analyzed with a proximity extension assay consisting of 92 proteins. Associations between proteins and physical activity were explored using a false discovery rate of &lt;5%, and significant associations were taken forward to multivariate analyses.ResultsIn the multivariate Cox regression model, physical inactivity, defined as physical activity time &lt;1 h throughout the week was associated with increased risk of all-cause mortality (HR 1.71; CI95% 1.26–2.31; p = 5.9 × 10−4) as well as all-cause re-hospitalization (HR 1.27; CI95% 1.01–1.60; p = 0.038). Further, physical inactivity was associated with elevated plasma levels of Metalloproteinase inhibitor 4, Soluble interleukin 1 receptor-like 1, Elafin and Transferrin receptor protein 1, which are implicated in myocardial fibrosis, migration and apoptosis.ConclusionsSelf-reported low weekly physical activity is associated with increased risk of mortality and re-hospitalization in patients hospitalized for HF independent of traditional risk factors. Furthermore, physical inactivity was associated with elevated levels of 4 proteins linked to cardiovascular disease.
Experimental Simulation of Burial Diagenesis and Subsequent 2D-3D Characterization of Sandstone Reservoir Quality
Authors: Charlaftis Dimitrios , Dobson Katherine J. , Jones Stuart J. , Lakshtanov Dmitry , Crouch Jonathan , Cook Jennie 
Published: February 2022

Characterization of deeply buried sandstones and their reservoir quality is of paramount importance for exploring, developing, and subsurface storage of energy resources. High reservoir quality in deeply buried sandstones is commonly correlated with the occurrence of grain coatings that inhibit quartz cementation. The development of reliable models that can predict reservoir quality relies on incorporating quantitative understanding of these diagenetic processes. Hydrothermal experiments simulating burial diagenesis were integrated with multi-scale X-ray tomography to quantify the 3-dimensional evolution of grain coating volume and porosity with increasing temperature; while microscopic and automated quantitative mineralogy analysis were used to track the associated mineralogical alterations. To simulate reservoir evolution, sandstone samples from the Lower Jurassic Cook Formation (Oseberg Field, 30/6-17R, Norway) were exposed to a silica supersaturated Na2CO3 (0.1 M) solution for up to 360 h at temperatures of 100–250°C. The experimental results show the main porosity and permeability reduction window is associated with pore-filling kaolinite, and lies between 150 and 200°C, above which little change occurs. Volumetric increases in grain coating start to occur at ∼150°C through precipitation of authigenic chlorite, and continue to 250°C, irrespective of the experimental duration. Together with preexisting siderite coatings, the newly precipitated chlorite prevents the loss of reservoir quality by inhibiting quartz overgrowth development. Pore flow simulations based on the observed temperature-dependent 3-dimensional pore networks allow us to characterize pore-throat and permeability evolution and gain quantitative understanding of the impact of diagenetic overprinting on deeply buried sandstone reservoirs.
The Effect of Antioxidants on Sperm Quality Parameters and Pregnancy Rates for Idiopathic Male Infertility: A Network Meta-Analysis of Randomized Controlled Trials
Authors: Li Kun-peng , Yang Xue-song , Wu Tao 
Published: February 2022

PurposeMale infertility is a global public health issue recognized by the WHO. Recently, antioxidants are increasingly used to treat idiopathic male infertility. However, the lack of available evidence has led to the inability to rank the effects of antioxidants on the sperm quality parameters and pregnancy rate of infertile men. This network meta-analysis studied the effects of different antioxidants on the sperm quality and pregnancy rate of idiopathic male infertility.MethodsWe searched PubMed, Embase, Web of Science, and Cochrane Library databases for randomized controlled trials (RCTs). The weighted mean difference (WMD) and odds ratio (OR) were applied for the comparison of continuous and dichotomous variables, respectively, with 95% CIs. The outcomes were sperm motility, sperm concentration, sperm morphology, and pregnancy rate.ResultsA total of 23 RCTs with 1,917 patients and 10 kids of antioxidants were included. l-Carnitine, l-carnitine+l-acetylcarnitine, coenzyme-Q10, ω-3 fatty acid, and selenium were more efficacious than placebo in sperm quality parameters. l-Carnitine was ranked first in sperm motility and sperm morphology (WMD 6.52% [95% CI: 2.55% to 10.05%], WMD 4.96% [0.20% to 9.73%]). ω-3 fatty acid was ranked first in sperm concentration (WMD 9.89 × 106/ml, [95% CI: 7.01 to 12.77 × 106/ml]). In terms of pregnancy rate, there was no significant effect as compared with placebo.Conclusionsl-Carnitine was ranked first in sperm motility and sperm morphology. ω-3 fatty acid was ranked first in sperm concentration. Coenzyme-Q10 had better effective treatment on sperm motility and concentration. Furthermore, high-quality RCTs with adequate sample sizes should be conducted to compare the outcomes of different antioxidants.