bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of oxidative stress-mediated cytotoxicity and genotoxicity of copper and flubendiamide: amelioration by antioxidants in vivo and in vitro
Authors: Mandil Rajesh , Prakash Atul , Rahal Anu , Koli Swati , Kumar Rahul , Garg Satish K 
Published: March 2023

Abstract
Present study was designed to evaluate toxic effects of copper (Cu) (@ 33 mg/kg b.wt.) and flubendimide (Flb) (@ 200 mg/kg b.wt.) alone and/or in combination on blood-biochemical indices, oxidative stress, and drug metabolizing enzymes (DMEs) in vivo in male Wistar rats following oral exposure continuously for 90 days and their immunotoxic (cyto-genotoxic and apoptotic) potential in vitro on thymocytes. In in vivo study, ameliorative potential of α-tocopherol was assessed, whereas α-tocopherol, curcumin, resveratrol, and catechin were evaluated for protective effect in vitro. Significantly (P &lt; 0.05) increased AST activity and increment in total bilirubin, uric acid, creatinine, and BUN levels; however, reduction in total protein, GSH content, reduced activities of SOD and GST, and increased lipid peroxidation and GPx activity with severe degenerative changes in histopathological examination of liver and kidney in group of Cu and Flb were observed. Treatment with α-tocopherol improved biochemical variables, redox status, and histoarchitecture of liver and kidney tissues. Reduced hepatic CYP450, CYPb5, APH, UGT, and GST activities observed in both Cu and α-tocopherol alone and their combination groups, whereas significant increment in Flb alone, while α-tocopherol in combination with xenobiotics improved the activities of hepatic DMEs. Primary cell culture of thymocytes (106 cells/ml) exposed to Cu and Flb each @ 40 μM increased TUNEL+ve cells, micronuclei induction, DNA shearing, and comet formation establishes their apoptotic and genotoxic potential, whereas treatment with antioxidants showed concentration-dependent significant reduction and their order of potency on equimolar concentration (10 μM) basis is: curcumin &gt; resveratrol &gt; catechin = α-tocopherol.
Adenosine A2A receptor activation reduces chondrocyte senescence
Authors: Friedman Benjamin , Larranaga‐Vera Ane , Castro Cristina M. , Corciulo Carmen , Rabbani Piul , Cronstein Bruce N. 
Published: March 2023

AbstractOsteoarthritis (OA) pathogenesis is associated with reduced chondrocyte homeostasis and increased levels of cartilage cellular senescence. Chondrosenescence is the development of cartilage senescence that increases with aging joints and disrupts chondrocyte homeostasis and is associated with OA. Adenosine A2A receptor (A2AR) activation in cartilage via intra‐articular injection of liposomal A2AR agonist, liposomal‐CGS21680, leads to cartilage regeneration in vivo and chondrocyte homeostasis. A2AR knockout mice develop early OA isolated chondrocytes demonstrate upregulated expression of cellular senescence and aging‐associated genes. Based on these observations, we hypothesized that A2AR activation would ameliorate cartilage senescence. We found that A2AR stimulation of chondrocytes reduced beta‐galactosidase staining and regulated levels and cell localization of common senescence mediators p21 and p16 in vitro in the human TC28a2 chondrocyte cell line. In vivo analysis similarly showed A2AR activation reduced nuclear p21 and p16 in obesity‐induced OA mice injected with liposomal‐CGS21680 and increased nuclear p21 and p16 in A2AR knockout mouse chondrocytes compared to wild‐type mice. A2AR agonism also increased activity of the chondrocyte Sirt1/AMPK energy‐sensing pathway by enhancing nuclear Sirt1 localization and upregulating T172‐phosphorylated (active) AMPK protein levels. Lastly, A2AR activation in TC28a2 and primary human chondrocytes reduced wild‐type p53 and concomitantly increased p53 alternative splicing leading to increase in an anti‐senescent p53 variant, Δ133p53α. The results reported here indicate that A2AR signaling promotes chondrocyte homeostasis in vitro and reduces OA cartilage development in vivo by reducing chondrocyte senescence.
Artificial Intelligence Screening of Medical School Applications: Development and Validation of a Machine-Learning Algorithm
Authors: Triola Marc M. , Reinstein Ilan , Marin Marina , Gillespie Colleen , Abramson Steven , Grossman Robert I. , Rivera Rafael 
Published: March 2023

Purpose
To explore whether a machine-learning algorithm could accurately perform the initial screening of medical school applications.

Method
Using application data and faculty screening outcomes from the 2013 to 2017 application cycles (n = 14,555 applications), the authors created a virtual faculty screener algorithm. A retrospective validation using 2,910 applications from the 2013 to 2017 cycles and a prospective validation using 2,715 applications during the 2018 application cycle were performed. To test the validated algorithm, a randomized trial was performed in the 2019 cycle, with 1,827 eligible applications being reviewed by faculty and 1,873 by algorithm.

Results
The retrospective validation yielded area under the receiver operating characteristic (AUROC) values of 0.83, 0.64, and 0.83 and area under the precision–recall curve (AUPRC) values of 0.61, 0.54, and 0.65 for the invite for interview, hold for review, and reject groups, respectively. The prospective validation yielded AUROC values of 0.83, 0.62, and 0.82 and AUPRC values of 0.66, 0.47, and 0.65 for the invite for interview, hold for review, and reject groups, respectively. The randomized trial found no significant differences in overall interview recommendation rates according to faculty or algorithm and among female or underrepresented in medicine applicants. In underrepresented in medicine applicants, there were no significant differences in the rates at which the admissions committee offered an interview (70 of 71 in the faculty reviewer arm and 61 of 65 in the algorithm arm; P = .14). No difference in the rate of the committee agreeing with the recommended interview was found among female applicants (224 of 229 in the faculty reviewer arm and 220 of 227 in the algorithm arm; P = .55).

Conclusions
The virtual faculty screener algorithm successfully replicated faculty screening of medical school applications and may aid in the consistent and reliable review of medical school applicants.
Early Complications After Posterior Spinal Fusion in Patients With Rett Syndrome
Authors: Taylor Tristen N. , Bridges Callie S. , Nordstrom Luke A. , Hanson Darrell S. , Gerow Frank T. , Smith Brian G. 
Published: March 2023

Background:
Neuromuscular scoliosis in Rett syndrome (RS) is common, progressive, and often requires posterior spinal fusion (PSF). While PSF is associated with improved overall outcomes, there is a paucity of information describing complications. We aimed to report the postoperative complications, readmissions, and reoperations for patients with RS undergoing PSF.

Methods:
Female pediatric patients with RS treated by PSF with segmental instrumentation, with or without concurrent pelvis fixation, during January 2012 to August 2022 were included. Preoperative patient characteristics, intraoperative data (estimated blood loss, cell saver, packed red blood cells transfused), postoperative complications according to the Modified Clavien-Dindo-Sink classification within 90 days, unplanned readmissions within 30 days, and unplanned reoperations within 90 days were recorded.

Results:
A total of 25 females were included. The mean (SD) age at surgery was 12.9 (1.8) years and the mean follow-up of 38.6 (24.9) months. The mean preoperative major coronal curve was 79 degrees (23 degrees) which decreased to 32 degrees (15 degrees) by the last follow-up (P<0.001). The median estimated blood loss was 600 mL and length of stay was 7 days. There were 81 total postoperative complications (3.2 complications/patient). Eight (32%) had grade IVa complications (disseminated intravascular coagulopathy, hypotensive shock, respiratory failure, chronic urosepsis). Five (20%) patients experienced seizures, 48% had pulmonary complications, and 56% had gastrointestinal complications. There were 3 readmissions (12%) within 30 days for pneumonia and 2 (8%) reoperations (an incision and drainage and C2-T2 fusion for significant kyphosis) within 90 days. One patient also had their fusion extended to the pelvis 1 year later. There were more nonambulatory patients in the group fused to the pelvis, but otherwise no differences between those fused and unfused to the pelvis.

Conclusions:
This is the largest review of early postoperative complications for patients with RS who underwent PSF. PSF effectively reduced the major coronal curve, but surgeons and families should be aware of a high postoperative seizure and respiratory complication rate, as well as 8% having reoperations within 90 days and 12% being readmitted within 30 days.

Level of Evidence:
Level IV—therapeutic study.
Does Fitzpatrick Score Predict Flap Loss? Microsurgical Breast Reconstruction Outcomes of Varying Skin Color
Authors: Perez Kevin , Steppe Cyrus , Teotia Sumeet S. , Haddock Nicholas T. 
Published: March 2023

Background:
The aim of this study was to seek evidence that patients with darker Fitzpatrick score skin tones are more susceptible to flap loss due to unsalvaged vascular compromise in autologous flap breast reconstruction.

Methods:
This is a retrospective study conducted on patients who underwent any type of autologous flap breast reconstruction performed by the two senior authors at an academic center between January 2010 and December 2021. The sole primary outcome variable was flap loss. Patient skin tone was assessed using the Fitzpatrick scale on clinical photographs of patients.

Results:
A total of 1115 pateints underwent autologous flap breast reconstruction, of which only 56 met both exclusion and inclusion criteria with 58 individual breasts being included in the final study population. The most common race of subjects was White (n = 33; 56.9%) while the most common Fitzpatrick score skin tone was type II (n = 22; 37.9%). The Cochran-Armitage test of trend showed a statistically significant linear trend, P = 0.006, with darker Fitzpatrick score skin tones associated with a higher proportion of flap loss in patients who had vascular compromise. A logistic regression showed that none of the predictor variables were significant.

Conclusions:
Patients with darker Fitzpatrick skin tones were associated with flap loss after vascular compromise. To prevent flap loss in patients who have darker Fitzpatrick score skin tones, more aggressive flap monitoring should be taken into consideration in the immediate postoperative setting.
Comparison of Long-term Surgical Outcomes and Microsurgical Skills between Independent and Integrated Plastic Surgery Trainees
Authors: Hassan Abbas M. , Egro Francesco M. , Talanker Michael M. , Shah Nikhil R. , Liu Jun , Maricevich Renata S. , Chang Edward I. , Hanasono Matthew M. , Selber Jesse C. , Butler Charles E. 
Published: March 2023

Background:
We compared the surgical skills and outcomes of microsurgical fellows who completed an independent versus integrated plastic surgery residency.

Methods:
We reviewed outcomes of abdominal wall reconstructions performed autonomously by microsurgical fellows at our institution from March 2005 to June 2019; outcome measures included hernia recurrence, surgical site occurrence, surgical site infection, length of hospital stay, unplanned return to the operating room, and 30-day readmission. The microsurgical skills were prospectively evaluated using the validated Structured Assessment of Microsurgical Skills at the start and end of the fellowship, in an animal laboratory model and clinical microsurgical cases. Multivariable hierarchical models were constructed to evaluate study outcomes.

Results:
We identified 44 fellows and 118 consecutive patients (52% women) who met our inclusion criteria. Independent fellows performed 55% (n = 65) of cases, and 45% were performed by integrated fellows. We found no significant difference in hernia recurrence, surgical site occurrences, surgical site infections, 30-day readmission, unplanned return to the operating room, or length of stay between the two groups in adjusted models. Although laboratory scores were similar between the groups, integrated fellows demonstrated higher initial clinical scores (42.0 ± 4.9 versus 37.7 ± 5.0, P = 0.04); however, the final clinical scores were similar (50.8 ± 6.0 versus 48.9 ± 5.2, P = 0.45).

Conclusions:
Independent and integrated fellows demonstrated similar long-term patient outcomes. Although integrated fellows had better initial microsurgical skills, evaluation at the conclusion of fellowship revealed similar performance, indicating that fellowship training allows for further development of competent surgeons.
How Big Is Too Big? Exploring the Relationship between Breast Implant Volume and Postoperative Complication Rates in Primary Breast Augmentations
Authors: Medor Maria C. , Bouhadana Gabriel , Churchill Isabella F. , Hemmerling Thomas , Bonapace-Potvin Michelle , Papanastasiou Constantine , Mussie Abiye , Borsuk Daniel E. , Papanastasiou Vasilios W. 
Published: March 2023

Background:
There is no consensus regarding implant size as an independent risk factor for complications in primary breast augmentation. Choosing appropriate implant volume is an integral part of the preoperative planning process. The current study aims to assess the relationship between implant size and the development of complications following augmentation mammaplasty.

Methods:
A retrospective chart review of patients undergoing primary breast augmentation at the Westmount Institute of Plastic Surgery between January 2000 and December 2021 was conducted. Demographics, implant characteristics, surgical technique, postoperative complications, and follow-up times were recorded. Univariate logistic regression was used to identify independent predictors, which were then included in multivariate logistic regressions of implant volume and implant volume/body mass index (BMI) ratio regarding complications.

Results:
A total of 1017 patients (2034 breasts) were included in this study. The average implant volume used was 321.4 ± 57.5 cm3 (range: 110–605). Increased volume and volume/BMI ratio were associated with a significant increase in risk of implant rupture (odds ratio = 1.012, P < 0.001 and 1.282, P < 0.001 respectively). Rates of asymmetry were significantly associated with increases in implant volume and volume/BMI ratio (odds ratio = 1.005, P = 0.004 and 1.151, P < 0.001, respectively). No single implant volume or volume/BMI ratio above which risks of complications significantly increase was identified.

Conclusions:
Implant rupture and postoperative asymmetries are positively correlated with bigger implant volumes. Implant size could likely be a useful independent predictor of certain complications, especially in patients with high implant to BMI ratios.
Reconstruction of the Flexor Pollicis Longus Tendon with Vascularized Tendon with Ulnar Artery Preservation
Authors: Cavadas Pedro C. , Padial Beatriz 
Published: March 2023

Background:
Reconstruction of the flexor pollicis longus tendon using staged grafting yields modest results. A modification of the pedicled vascularized flexor digitorum superficialis transfer, without division of the ulnar artery, was used in five patients.

Methods:
The flexor digitorum superficialis and its gliding tissue were transferred in five patients, based on a branch of the ulnar artery without division of the ulnar vessels. Functional results were evaluated using a total active range of motion and Buck-Gramko score at 10 months by an independent hand therapist.

Results:
The mean total active motion of the interphalangeal joint was 49 degrees, with a Buck-Gramko score of excellent in three cases and good in two. No complications were recorded.

Conclusion:
Reconstruction of the flexor pollicis longus tendon with single-staged vascularized FDS transfer without ulnar artery division yielded good results in a small cohort of five cases.
Bilateral Knee Soft-tissue Reconstruction after High-voltage Electrical Burn Injuries
Authors: Déniz Martínez Alejandro , Santamaría Córdoba Natalia , Ayala Parra David G. 
Published: March 2023

Summary:
This is the case of a 21-year-old man who had extensive and bilateral knee soft-tissue damage after a high-voltage electrical discharge. In its reconstruction, we simultaneously performed the pedicled medial sural artery perforator flap. Even though mild complications took place, this alternative proved helpful and reliable, providing an easily adjustable skin island and allowing for the patient’s rapid rehabilitation and a satisfactory aesthetic outcome. Although this flap’s reconstructive potential is known in other etiologies, the present report outlines its substantial potential in the case of electrical burn injuries, as it has barely been recognized before.
Analysis of Breast Aesthetic Revision Procedures after Unilateral Abdominal-based Free-flap Breast Reconstruction: A Single-center Experience with 1251 Patients
Authors: Smith J. Michael , Boukovalas Stefanos , Chang Edward I. , Liu Jun , Selber Jesse C. , Hanson Summer E. , Reece Gregory P. 
Published: March 2023

Background:
Although autologous free-flap breast reconstruction is the most durable means of reconstruction, it is unclear how many additional operations are needed to optimize the aesthetic outcome of the reconstructed breast. The present study aimed to determine the average number of elective breast revision procedures performed for aesthetic reasons in patients undergoing unilateral autologous breast reconstruction and to analyze variables associated with undergoing additional procedures.

Methods:
A retrospective review of all unilateral abdominal-based free-flap breast reconstructions performed from 2000 to 2014 was undertaken at a tertiary academic center.

Results:
Overall, 1251 patients were included in the analysis. The average number of breast revision procedures was 1.1 ± 0.9, and 903 patients (72.2%) underwent at least one revision procedure. Multiple logistic regression analysis demonstrated that younger age, higher body mass index, and prior oncologic surgery on the reconstructed breast were factors associated with increased likelihood of undergoing a revision procedure. The probability of undergoing at least one revision increased by 4% with every 1-unit (kg/m2) increase in a patient’s body mass index. Multiple Poisson regression modeling demonstrated that younger age, prior oncologic surgery on the reconstructed breast, and bipedicle flap reconstruction were significant factors associated with undergoing a greater number of revision procedures.

Conclusions:
Most patients who undergo unilateral autologous breast reconstruction require at least one additional operation to optimize their breast aesthetic results. Young age and obesity increase the likelihood of undergoing additional operations. These findings can aid reconstructive microsurgeons in counseling patients and establishing patient expectations prior to their undergoing microvascular breast reconstruction.
Effects of continuous positive airway pressure on very short-term blood pressure variability associated with sleep-disordered breathing by pulse transit time-based blood pressure measurements
Authors: Misaka Tomofumi , Yoshihisa Akiomi , Yokokawa Tetsuro , Takeishi Yasuchika 
Published: March 2023

Background:
Blood pressure (BP) variability (BPV) is a predictor of cardiovascular outcomes independently of BP absolute values. We previously reported that pulse transit time (PTT) enables monitoring beat-to-beat BP, identifying a strong relationship between the extent of very short-term BPV and the severity of sleep-disordered breathing (SDB). Here, we investigated the effects of continuous positive airway pressure (CPAP) on very short-term BPV.

Methods:
We studied 66 patients (mean age 62 years old, 73% male) with newly diagnosed SDB who underwent full polysomnography on two consecutive days for diagnosis (baseline) and CPAP, together with PTT-driven BP continuous recording. PTT index was defined as the average number of acute transient rises in BP (≥12 mmHg) within 30 s/h.

Results:
CPAP treatment effectively improved SDB parameters, and attenuated PTT-based BP absolute values during the night-time. Very short-term BPV that includes PTT index and standard deviation (SD) of systolic PTT-BP was significantly reduced by CPAP therapy. The changes in PTT index from baseline to CPAP were positively correlated with the changes in apnea-hypopnea index, obstructive apnea index (OAI), oxygen desaturation index, minimal SpO2, and mean SpO2. Multivariate regression analysis revealed that changes in OAI and minimal SpO2, as well as heart failure, were the independent factors in determining the reduction of PTT index following CPAP.

Conclusion:
PTT-driven BP monitoring discovered the favorable effects of CPAP on very short-term BPV associated with SDB events. Targeting very short-term BPV may be a novel approach to identifying individuals who experience greater benefits from CPAP.
Interferon regulatory factor 4 deletion protects against kidney inflammation and fibrosis in deoxycorticosterone acetate/salt hypertension
Authors: Gao Ying , Liu Benquan , Guo Xiaoqing , Nie Jiayi , Zou Hao , Wen Shihong , Yu Wenqiang , Liang Hua 
Published: March 2023

Background:
Inflammation and renal interstitial fibrosis are the main pathological features of hypertensive nephropathy. Interferon regulatory factor 4 (IRF-4) has an important role in the pathogenesis of inflammatory and fibrotic diseases. However, its role in hypertension-induced renal inflammation and fibrosis remains unexplored.

Method and results:
We showed that deoxycorticosterone acetate (DOCA)-salt resulted in an elevation of blood pressure and that there was no difference between wild-type and IRF-4 knockout mice. IRF-4−/− mice presented less severe renal dysfunction, albuminuria, and fibrotic response after DOCA-salt stress compared with wild-type mice. Loss of IRF-4 inhibited extracellular matrix protein deposition and suppressed fibroblasts activation in the kidneys of mice subjected to DOCA-salt treatment. IRF-4 disruption impaired bone marrow-derived fibroblasts activation and macrophages to myofibroblasts transition in the kidneys in response to DOCA-salt treatment. IRF-4 deletion impeded the infiltration of inflammatory cells and decreased the production of proinflammatory molecules in injured kidneys. IRF-4 deficiency activated phosphatase and tensin homolog and weakened phosphoinositide-3 kinase/AKT signaling pathway in vivo or in vitro. In cultured monocytes, TGFβ1 also induced expression of fibronectin and α-smooth muscle actin and stimulated the transition of macrophages to myofibroblasts, which was blocked in the absence of IRF-4. Finally, macrophages depletion blunted macrophages to myofibroblasts transition, inhibited myofibroblasts accumulation, and ameliorated kidney injury and fibrosis.

Conclusion:
Collectively, IRF-4 plays a critical role in the pathogenesis of kidney inflammation and fibrosis in DOCA-salt hypertension.