bluuebunny/crossref_metadata_2025_split huggingface dataset:
Manipulation of Menthol and Nicotine Content in Cigarettes: Effects on Smoking Behavior and Toxicant Exposure in Women Menthol Smokers
Authors: Oncken Cheryl , Litt Mark D , Thurlow Sheila , Mead-Morse Erin L , Wang Lanqing , Hatsukami Dorothy K 
Published: September 2022

AbstractBackgroundThe purpose of this study was to determine the effects of smoking and other outcomes of assigning cigarettes with reduced nicotine and/or no menthol to female menthol smokers.Aims and MethodsNontreatment-seeking female menthol smokers (N = 263) participated in a randomized controlled trial in which levels of menthol and nicotine in cigarettes were manipulated using experimental cigarettes. After a baseline period, participants were assigned to the following conditions for 6 weeks: (1) their own brand of cigarette (conventional nicotine with menthol), (2) a conventional nicotine cigarette with no menthol, (3) a cigarette with reduced nicotine (RNC) with menthol, or (4) a RNC cigarette and no menthol. Participants then returned to using their own brand and were followed for another 6 weeks. Outcomes included cigarettes smoked, biomarkers of exposure, and dependence measures.ResultsResults indicated that, after an initial increase, rates of smoking of all three experimental cigarettes were at or below baseline rates of smoking of one’s own brand. Levels of biomarkers also decreased during the experimental phase but rebounded somewhat after participants resumed smoking their own brand. There was evidence that the overall amount of smoking decreased similarly among women who switched to non-menthol and/or RNC cigarettes.ConclusionsThese results suggest that no detrimental effect will occur in nicotine or toxicant exposure levels with a ban on characterizing menthol and/or a product standard on nicotine content in cigarettes.ImplicationsThe implication of this work is that there would be no risk to women menthol smokers associated with regulations restricting nicotine and eliminating menthol in cigarettes.
Screening and validation of nickel ion cytotoxicity biomarkers based on transcriptomic and proteomic technology
Authors: Zhang Fudan , Huang Yan , Zhang Yajing , Lü Xiaoying 
Published: September 2022

Abstract
The aim of this study was to screen cytotoxicity biomarkers of nickel ions (Ni2+) using transcriptomic and proteomic approaches combined with molecular biology validation. First, the MTT method was used to evaluate cytotoxicity in L929 cells treated with Ni2+ at different concentrations. Ni2+ at both 100 μM and 200 μM affected cell proliferation. Then, transcriptomic and proteomic technology was used to study the effects of Ni2+ on the expression of genes/proteins in cells. It was found that 1490, 789, 652 and 729 genes (12, 24, 48 and 72 h, respectively) and 177, 2191 and 2095 proteins (12, 24 and 48 h, respectively) were differentially expressed after treatment with 100 μM Ni2+. In total, 1403, 963, 916 and 1230 genes (12, 24, 48 and 72 h, respectively) and 83, 1681 and 2398 proteins (12, 24 and 48 h, respectively) were differentially expressed after treatment with 200 μM Ni2+. Then, four target gene/protein biomarkers were filtered by combined screening using gene/proteomic experimental data and biological pathway analyses. Further expression level validation of all these target biomarkers and functional validation of selected gene/protein biomarkers were carried out, and a final gene/protein biomarker (UQCRB) was identified.
DEVELOPMENT AND ESTIMATION OF HUMAN DOSIMETRY OF A NEW 47SC-RISEDRONATE FOR RADIOPHARMACEUTICAL APPLICATION
Authors: Moghaddam-Banaem Leila , Deilami-nezhad Leila , Sadeghi Mahdi , Jalilifar Mostafa 
Published: September 2022

Abstract
Bisphosphonate risedronate (2-(3-pyridinyl)-1-hydroxyethane diphosphonic acid) was radiolabeled with scandium-47 (47Sc) as potential therapeutic radiopharmaceutical for skeletal metastases. Its time-dependent biodistribution in mice was measured and its human dosimetry was derived. The labelling process was performed at 95 °C for 30 min. The stability of the radio-conjugate was tested in human serum at 37 °C and its biodistribution was studied in balb/c mice. The radiochemical yield of ≥90% was obtained corresponding to a specific activity of 277 MBq/mg. The radio-conjugate showed good stability in human serum up to 48 h. A high bone uptake by 48 h post-injection was achieved, which suggests that 47Sc-risedronate may be therapeutically beneficial for the palliation of painful bone metastasis. The estimated absorbed dose coefficient and the time-integrated activity coefficient (ã (rs, TD)) in the bone were 1.35 mGy/MBq and 31.04 (Bq-h/Bq), respectively. The absorbed doses to non-osseous normal organs were much lower than that to the bone.
Evaluation of fermented corn protein and its effects in either high or low branch chain amino acid to leucine ratio diets on nursery pig performance and feed intake preference
Authors: Stas Ethan B , Chance Jenna A , Goodband Robert D , Tokach Mike D , Woodworth Jason C , DeRouchey Joel M , Gebhardt Jordan T 
Published: September 2022

Abstract
Three experiments were conducted to evaluate fermented corn protein (FCP) in nursery pig diets. The removal of non-fermentable components before fermentation of DDGS results in high protein dried distillers grains (HPDDGs). Fermented corn protein is produced when protein and yeast fraction syrup from ethanol production is added back to HPDDGs resulting in a product with up to 50% CP and 2% Lys. In Exp. 1, 350 barrows, initially 6.0 kg, were used to evaluate FCP as a replacement to enzymatically treated soybean meal. Treatments were arranged in a 2 × 2 + 1 factorial with main effects of specialty protein source (FCP or enzymatically treated soybean meal) and level (5 or 10%) or a control diet without any specialty protein source. There were 5 pigs per pen and 14 replications per treatment. From d 0 to 31, pigs fed enzymatically treated soybean meal had improved (P &lt; 0.05) ADG and feed efficiency (G:F) compared to pigs fed FCP. In Exp. 2, 350 pigs, initially 12.1 kg, were used to determine the effects of FCP with high or low Ile and Val (Ile + Val):Leu ratio on growth performance. Treatments were arranged in a 2 × 2 + 1 factorial with main effects of FCP level (10 or 20%) and Ile + Val:Leu ratio (low or high) in addition to a corn-soybean meal control diet with 5 pigs per pen and 14 replications per treatment. From d 0 to 21, ADG, ADFI, and G:F worsened (linear, P &lt; 0.001) as FCP increased. High Ile + Val:Leu improved (P &lt; 0.05) G:F compared to low Ile + Val:Leu. In Exp. 3, 180 pigs, initially 7.7 kg, were used in a feed intake preference trial evaluating various FCP fractions. A total of 6 diet comparisons with 5 pigs per pen and 6 replications per comparison were used. Corn protein sources and fractions used included: FCP, HPDDGs, whole stillage solids (approximately 2/3 of FCP), and thin stillage solids (approximately 1/3 of FCP), and a control diet. Pigs preferred (P &lt; 0.001) the control diet by consuming 82.5% of their intake compared with a diet containing FCP. There was no difference (P &gt; 0.05) in feed consumption of diets containing whole stillage solids compared to FCP. Pigs preferred (P = 0.001) the diet containing thin stillage solids by consuming 75.8% of their intake with this diet compared to the diet containing FCP. In conclusion, feeding FCP decreased growth performance in nursery pigs, but increasing Ile + Val:Leu improved G:F. Diet preference comparisons suggest that whole stillage solids are the component of FCP that leads to reduced feed intake.
A New Approach Methodology (NAM) Based Assessment of Butylated hydroxytoluene (BHT) for Endocrine Disruption Potential
Authors: De Abrew K Nadira , Natoli Ted , Lester Cathy C , Wang Xiaohong , Shobair Mahmoud , Subramanian Arvind , Daston George P 
Published: September 2022

Abstract
Butylated hydroxytoluene (BHT) is a synthetic antioxidant widely used in many industrial sectors. BHT is a well-studied compound for which there are many favorable regulatory decisions. However, a recent opinion by the French Agency for Food, Environmental and Occupational Health and Safety (ANSES) hypothesizes a role for BHT in endocrine disruption (ANSES (2021). This opinion is based on observations in mostly rat studies where changes to thyroid physiology are observed. Enzymatic induction of Cytochrome P450-mediated thyroid hormone catabolism has been proposed as a mechanism for these observations, however, a causal relationship has not been proven. Other evidence proposed in the document includes a read across argument to butylated hydroxyanisole (BHA), another Community Rolling Action Plan (CoRAP)-listed substance with endocrine disruption concerns. We tested the hypothesis that BHT is an endocrine disruptor by using a Next Generation Risk Assessment (NGRA) method. Four different cell lines: A549, HCC1428, HepG2, and MCF7 were treated with BHT and a series of BHT analogs at 5 different concentrations, RNA was isolated from cell extracts and run on the L1000 gene array platform. A toxicogenomics-based assessment was performed by comparing BHT’s unique genomic signature to a large external database containing signatures of other compounds (including many known endocrine disruptors) to identify if any endocrine disruption-related modes of action (MoAs) are prevalent among BHT and other compounds with similar genomic signatures. In addition, we performed a toxicogenomics-based structure activity relationship (SAR) assessment of BHT and a series of structurally similar analogs to understand if endocrine disruption is a relevant MoA for chemicals that are considered suitable analogs to BHT using the P&G read across framework (Wu et al., 2010). Neither BHT nor any of its analogs connected to compounds that had endocrine activity for estrogens, androgens, thyroid, or steroidogenesis.
Machine learning and artificial intelligence in physiologically based pharmacokinetic modeling
Authors: Chou Wei-Chun , Lin Zhoumeng 
Published: September 2022

Abstract
Physiologically based pharmacokinetic (PBPK) models are useful tools in drug development and risk assessment of environmental chemicals. PBPK model development requires the collection of species-specific physiological, and chemical-specific absorption, distribution, metabolism, and excretion (ADME) parameters, which can be a time-consuming and expensive process. This raises a need to create computational models capable of predicting input parameter values for PBPK models, especially for new compounds. In this review, we summarize an emerging paradigm for integrating PBPK modeling with machine learning (ML) or artificial intelligence (AI)-based computational methods. This paradigm includes 3 steps (1) obtain time-concentration PK data and/or ADME parameters from publicly available databases, (2) develop ML/AI-based approaches to predict ADME parameters, and (3) incorporate the ML/AI models into PBPK models to predict PK summary statistics (eg, area under the curve and maximum plasma concentration). We also discuss a neural network architecture “neural ordinary differential equation (Neural-ODE)” that is capable of providing better predictive capabilities than other ML methods when used to directly predict time-series PK profiles. In order to support applications of ML/AI methods for PBPK model development, several challenges should be addressed (1) as more data become available, it is important to expand the training set by including the structural diversity of compounds to improve the prediction accuracy of ML/AI models; (2) due to the black box nature of many ML models, lack of sufficient interpretability is a limitation; (3) Neural-ODE has great potential to be used to generate time-series PK profiles for new compounds with limited ADME information, but its application remains to be explored. Despite existing challenges, ML/AI approaches will continue to facilitate the efficient development of robust PBPK models for a large number of chemicals.
Novel biomarkers identifying hypertrophic cardiomyopathy and its obstructive variant based on targeted amino acid metabolomics
Authors: Guo Lanyan , Wang Bo , Zhang Fuyang , Gao Chao , Hu Guangyu , Zhou Mengyao , Wang Rutao , Zhao Hang , Yan Wenjun , Zhang Ling , Ma Zhiling , Yang Weiping , Guo Xiong , Huang Chong , Cui Zhe , Sun Fangfang , Song Dandan , Liu Liwen , Tao Ling 
Published: September 2022

Abstract

Background:
Hypertrophic cardiomyopathy (HCM) is an underdiagnosed genetic heart disease worldwide. The management and prognosis of obstructive HCM (HOCM) and non-obstructive HCM (HNCM) are quite different, but it also remains challenging to discriminate these two subtypes. HCM is characterized by dysmetabolism, and myocardial amino acid (AA) metabolism is robustly changed. The present study aimed to delineate plasma AA and derivatives profiles, and identify potential biomarkers for HCM.

Methods:
Plasma samples from 166 participants, including 57 cases of HOCM, 52 cases of HNCM, and 57 normal controls (NCs), who first visited the International Cooperation Center for HCM, Xijing Hospital between December 2019 and September 2020, were collected and analyzed by high-performance liquid chromatography–mass spectrometry based on targeted AA metabolomics. Three separate classification algorithms, including random forest, support vector machine, and logistic regression, were applied for the identification of specific AA and derivatives compositions for HCM and the development of screening models to discriminate HCM from NC as well as HOCM from HNCM.

Results:
The univariate analysis showed that the serine, glycine, proline, citrulline, glutamine, cystine, creatinine, cysteine, choline, and aminoadipic acid levels in the HCM group were significantly different from those in the NC group. Four AAs and derivatives (Panel A; proline, glycine, cysteine, and choline) were screened out by multiple feature selection algorithms for discriminating HCM patients from NCs. The receiver operating characteristic (ROC) analysis in Panel A yielded an area under the ROC curve (AUC) of 0.83 (0.75–0.91) in the training set and 0.79 (0.65–0.94) in the validation set. Moreover, among 10 AAs and derivatives (arginine, phenylalanine, tyrosine, proline, alanine, asparagine, creatine, tryptophan, ornithine, and choline) with statistical significance between HOCM and HNCM, 3 AAs (Panel B; arginine, proline, and ornithine) were selected to differentiate the two subgroups. The AUC values in the training and validation sets for Panel B were 0.83 (0.74–0.93) and 0.82 (0.66–0.98), respectively.

Conclusions:
The plasma AA and derivatives profiles were distinct between the HCM and NC groups. Based on the differential profiles, the two established screening models have potential value in assisting HCM screening and identifying whether it is obstructive.
COVID-19 and the Integrated Plastic Surgery Match: An Update on Match Trends by Applicant Location
Authors: Kebede Sara , Marxen Troy , Om Anjali , Bakayoko Ngafla , Losken Albert 
Published: September 2022

Background:
COVID-19 significantly impacted the residency match process. Away rotations and in-person interviews were canceled in 2021, resulting in a geographic shift in integrated plastic surgery match results. Although several of these limitations were lifted during the 2022 cycle, the resulting geographic outcomes have yet to be described. This study aims to determine whether the changes seen during the previous cycle persisted despite loosened restrictions.

Methods:
Integrated plastic surgery match results and applicants’ home institutions from the 2022 match cycle were determined using publicly available data. Geographic data from this cycle were then compared with pre-COVID-19 match cycles (2016–2020) and the COVID-19-affected 2021 match cycle.

Results:
Eighty percent (n = 68) of US integrated plastic surgery programs were included in this study. In 2022, 18.42% of applicants matched at their home institution compared with 25.12% in 2021. There was no significant difference in home, state, or regional match rates between 2022 and the five cycles preceding the pandemic (2016–2020). Combining these data to reflect the non-COVID-19-affected cycles (2016–2020 and 2022) and comparing to the COVID-19-affected cycle (2021), a significant difference in rates of home matches (P = 0.0395) was identified.

Conclusions:
A significant increase in home institution match rates was not noted during the 2022 cycle. This return to pre-COVID-19 rates is likely attributed to the loosening of restrictions and more opportunities for interaction between applicants and programs outside of their home institution.
Meniscus-Shaped Stromal Lenticule Addition Keratoplasty for Corneal Regularization and Thickening in Advanced Keratoconus
Authors: Pedrotti Emilio , Bonacci Erika , Fasolo Adriano , Fraccaroli Sebastiano , Anastasi Marco , Vinciguerra Riccardo , Vinciguerra Paolo , Giorgio Marchini 
Published: September 2022

Purpose:
The aim of this study was to investigate the outcome of the meniscus-shaped stromal lenticule addition keratoplasty (MS-SLAK) in corneal regularization and thickness.

Methods:
Patients waiting for deep anterior lamellar keratoplasty for advanced keratoconus with an intolerance to contact lenses (CLs) underwent the MS-SLAK procedure by FSL 80 kHz ablation (VICTUS, Technolas Perfect Vision, DE). Customized positive meniscus-shaped stromal lenticules were obtained and implanted. Examination was performed at baseline and at 3-, 6-, and 12-month follow-up and included corrected distance visual acuity both with spectacles and CLs (spectacle CDVA and CL-CDVA), manifest refraction spherical equivalent, slit-lamp examination, anterior segment optical coherence tomography, corneal topography, and in vivo confocal microscopy.

Results:
Fifteen patients completed the study. Statistical increases in corneal thickness values were found from the first follow-up (P < 0.001). Improvement in the Surface Asymmetry Index (P = 0.04), Symmetry Index (P = 0.02), spherical aberration (P < 0.001), coma (P= 0.18), high-order aberration (P = 0.37), and anterior asphericity index (Q) (P = 0.31) were found at 12 months. At the 12-month follow-up, no improvement were found in spectacle CDVA (P = 0.23); however, all patients reported CL wearing tolerance recovery, and significant improvement in CL-CDVA (P = 0.002) was found. The confocal microscopy at 12 months showed a significant increase in keratocyte density within the lenticule and absence of fibrotic reactions in both anterior and posterior interfaces.

Conclusions:
MS-SLAK seems to be effective in regularizing the corneal surface as showed by the significant improvement in topographic symmetry indices, coma, and high-order aberration. The corneal regularization is also confirmed by the results in anterior Q and the recovery of the CL wearing tolerance.
Association between prescribed opioid dose and risk of motor vehicle crashes
Authors: Quinn Patrick D. , Chang Zheng , Pujol Toyya A. , Bair Matthew J. , Gibbons Robert D. , Kroenke Kurt , D'Onofrio Brian M. 
Published: September 2022

Abstract
Opioid-involved motor vehicle traffic fatalities have increased over the past 2 decades. However, the extent to which prescribed opioids increase the risk of motor vehicle crashes remains uncertain. This study used real-world healthcare claims data to examine the association between prescription opioid dose and motor vehicle crash risk. Using nationwide US commercial insurance claims data for 2010 to 2018, we identified 772,404 adults who received incident, noncancer opioid therapy. We examined associations between daily prescription opioid dose, calculated in morphine milligram equivalents (MME) from filled prescription claims, and risk of motor vehicle crashes, assessed as diagnoses of motor vehicle injuries in claims for emergency visits, inpatient hospitalizations, and ambulance transportation. We estimated associations using a within-individual design, which ruled out all time-stable confounding. We complemented the design with time-varying statistical adjustment for other pharmacotherapies and a negative control pain pharmacotherapy analysis (with incident cyclic antidepressant prescriptions). During 2,150,009 person-years of follow-up, there were 12,123 motor vehicle crashes (5.64 crashes per 1000 person-years). In within-individual comparisons, crash risk was greater during opioid prescription periods involving doses ≤60 MME/day (odds ratio [OR], 3.86; 95% confidence interval [CI], 3.54, 4.21), >60 to 120 MME/day (OR, 5.46; 95% CI, 4.44, 6.73), and >120 MME/day (OR, 3.45; 95% CI, 2.31, 5.15) than during off-treatment periods. The negative control analysis supported the specificity of the results to opioids rather than to other processes associated with pharmacologic pain management. These findings suggest that the receipt of prescription opioids, even at doses ≤60 MME/day, is associated with an increased risk of motor vehicle crashes.
Targeting Epidermal Growth Factor Receptor in Head and Neck Cancer
Authors: Bhatia Aarti 
Published: September 2022

Abstract
Head and neck squamous cell carcinomas are rising in incidence worldwide, and despite the advent of improved surgical and radiation techniques, a substantial proportion of patients have disease recurrence, where systemic therapies are the mainstay of management. Recent advances in systemic therapy include the development of epidermal growth factor receptor– and programmed death 1–targeting drugs, which have produced incremental improvements in disease outcomes. However, for most patients, responses to treatment remain elusive because of primary or acquired resistance. Novel drugs and rational drug combinations need to be tested based on biomarker identification and preclinical science that will ultimately advance outcomes for our patients. This review focuses on efforts untaken for epidermal growth factor receptor targeting in head and neck squamous cell carcinoma to date.