bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro and In Vivo Biocompatibility of Bacterial Cellulose
Authors: Girard Vincent‐Daniel , Chaussé Jérémie , Borduas Martin , Dubuc Émile , Iorio‐Morin Christian , Brisebois Simon , Vermette Patrick 
Published: October 2024

ABSTRACTBacterial cellulose is a unique biomaterial produced by various species of bacteria that offers a range of potential applications in the biomedical field. To provide a cost‐effective alternative to soft‐tissue implants used in cavity infills, remodeling, and subdermal wound healing, in vitro cytotoxicity and in vivo biocompatibility of native bacterial cellulose were investigated. Cytotoxicity was assessed using a metabolic assay on Swiss 3T3 fibroblasts and INS‐1832/13 rat insulinoma. Results showed no cytotoxicity, whether the cells were seeded over or under the bacterial cellulose scaffolds. Biocompatibility was performed on Sprague–Dawley rats (males and females, 8 weeks old) by implanting bacterial cellulose membranes subcutaneously for 1 or 12 weeks. The explanted scaffolds were then sliced and stained with hematoxylin and eosin for histological characterization. The first series of results revealed acute and chronic inflammation persisting over 12 weeks. Examination of the explants indicated a high number of granulocytes within the periphery of the bacterial cellulose, suggesting the presence of endotoxins within the membrane, confirmed by a Limulus amebocyte lysate test. This discovery motivated the development of non‐pyrogenic bacterial cellulose scaffolds. Following this, a second series of animal experiments was done, in which materials were implanted for 1 or 2 weeks. The results revealed mild inflammation 1 week after implantation, which then diminished to minimal inflammation after 2 weeks. Altogether, this study highlights that unmodified, purified native bacterial cellulose membranes may be used as a cost‐effective biomedical device provided that proper endotoxin clearance is achieved.
Addressing Drug–Drug Interaction Knowledge Gaps at the Time of Approval: An Analysis of FDA Postmarketing Requirements and Commitments from 2009 to 2023
Authors: Ridge Sarah , Yang Xinning , Madabushi Rajanikanth , Ramamoorthy Anuradha 
Published: October 2024

AbstractIt has become increasingly common for patients to rely on the use of multiple prescription medications. The management of polypharmacy requires careful consideration for how drugs are metabolized and their potential for interaction with other drugs. Drug–drug interaction (DDI) assessments are typically performed in a stepwise manner during drug development, though knowledge gaps can exist at the time of approval. The US Food and Drug Administration can establish postmarketing requirements (PMRs) or postmarketing commitments (PMCs) to address these knowledge gaps. In this study, we systematically evaluated PMRs and PMCs established to new molecular entities (NMEs) at the time of initial approval between 2009 and 2023, for the assessment of pharmacokinetics‐based DDIs (i.e., drug metabolizing enzyme‐ and transporter‐related DDIs). We found that 22% of NMEs had at least one DDI‐related PMR or PMC, with a total of 263 that were pharmacokinetic based. Of these, 67% were for the assessment of drug metabolizing enzymes, which were established most frequently for their evaluation as a substrate, and 28% for transporters, which were established most frequently for their evaluation as an inhibitor. The 89% of PMRs and PMCs that were considered fulfilled had a revision to the United States prescribing information, the majority of which resulted in updated new instructions for use. This study highlights the value in conducting DDI‐related studies early in the drug development process allowing broad patient inclusion at the time of initial drug approval.[Correction added on October 28, 2024, after first online publication: The last sentence of the abstract has been updated in this version.]
Reasons and root causes: Conventional characterizations of doctoral engineering attrition obscure underlying structural issues
Authors: Sallai Gabriella M. , Berdanier Catherine G. P. 
Published: October 2024

AbstractBackgroundAlthough most engineering graduate students are funded and usually complete their degrees faster than other disciplines, attrition remains a problem in engineering. Existing research has explored the psychological and sociological factors contributing to attrition but not the structural factors impacting attrition.Purpose/HypothesisUsing systems theory, this study seeks to understand nuance in how underlying structural causes affect engineering graduate students' attrition experiences in ways that may differ from their official reasons for departure.Design/MethodsData were collected through semi‐structured interviews with seven departing or already departed engineering doctoral students from R1 graduate programs across the United States. Using thematic analysis, root cause analyses were conducted to understand participants' attrition experiences to explore how structures influence causes of departure.ResultsThe ways participants discuss root causes of their departure indicate differences in formal reasons for departure and underlying causes of departure. We highlight the role of informal and formal policy as root causes of a different attrition rationale often passed off as interpersonal issues. When interpreted as evidence of structural issues, the causes of departure show ways in which action–inaction, policy–“null” policy serve as structural features governing student attrition decision processes. We also highlight a form of benign neglect toward struggling graduate students.ConclusionThis study reveals important nuances underlying face‐value reasons of attrition indicating foundational structural issues contributing to engineering graduate student attrition. Coaching faculty in team management and encouraging close revision of departmental policies could help mitigate students' negative graduate experiences and decrease unnecessary attrition.
Initial treatment efficacy and safety of durvalumab plus tremelimumab combination therapy in unresectable hepatocellular carcinoma in clinical practice
Authors: Tomonari Tetsu , Tani Joji , Sato Yasushi , Tanaka Hironori , Morishita Akihiro , Okamoto Koichi , Kawano Yutaka , Sogabe Masahiro , Miyamoto Hiroshi , Takayama Tetsuji 
Published: October 2024

AbstractBackground and AimsWe aimed to evaluate the efficacy and safety of durvalumab plus tremelimumab (Dur + Tre) combination therapy in patients with unresectable hepatocellular carcinoma (uHCC) in clinical practice.MethodsWe retrospectively evaluated 37 patients with uHCC from our institutions between April 2023 and January 2024. Patients were divided into first‐ and later‐line groups for analysis of antitumor efficacy, adverse events (AEs), and transition rate to second‐line treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST).ResultsThe disease control rate (DCR) for the first‐line group was 80.9%, which was significantly higher than that for the later‐line group (50%). The incidence of immune‐related AEs (irAEs) was 24.3%, with grade 3 or higher irAEs including increased transaminase (8.1%), diarrhea (8.1%), and adrenal insufficiency (2.7%). The rates of drug withdrawal and discontinuation owing to AEs were 23.8% and 19%, respectively, in the first‐line treatment and 31.2% and 12.5%, respectively, in the later‐line treatment, with no significant difference. Analysis of changes in liver reserve using the albumin–bilirubin (ALBI) score showed no obvious loss of liver reserve for up to 12 weeks. The transition rate from first‐ to second‐line therapy after progressive disease (PD) was as high as 94.7%.ConclusionThe efficacy and safety of Dur + Tre in clinical practice were comparable to those reported in a recent phase III trial. The first‐line Dur + Tre therapy had a higher DCR than that of the later lines, and the transition rate to second‐line therapy was considerably high, suggesting that Dur + Tre therapy would be more beneficial in first‐line treatment.
Comparison of Nocifensive Behavior in NaV1.7–, NaV1.8–, and NaV1.9–Channelrhodopsin‐2 Mice by Selective Optogenetic Activation of Targeted Sodium Channel Subtype‐Expressing Afferents
Authors: Maruta Toyoaki , Kouroki Satoshi , Kurogi Mio , Hidaka Kotaro , Koshida Tomohiro , Miura Ayako , Nakagawa Hikaru , Yanagita Toshihiko , Takeya Ryu , Tsuneyoshi Isao 
Published: October 2024

ABSTRACTVoltage‐gated sodium channels, including NaV1.7, NaV1.8, and NaV1.9, play important roles in pain transmission and chronic pain development. However, the specific mechanisms of their action remain unclear, highlighting the need for in vivo stimulation studies of these channels. Optogenetics, a novel technique for targeting the activation or inhibition of specific neural circuits using light, offers a promising solution. In our previous study, we used optogenetics to selectively excite NaV1.7‐expressing neurons in the dorsal root ganglion of mice to induce nocifensive behavior. Here, we further characterize the impact of nocifensive behavior by activation of NaV1.7, NaV1.8, or NaV1.9‐expressing neurons. Using CRISPR/Cas9‐mediated homologous recombination, NaV1.7–iCre, NaV1.8–iCre, or NaV1.9–iCre mice expressing iCre recombinase under the control of the endogenous NaV1.7, NaV1.8, or NaV1.9 gene promoter were produced. These mice were then bred with channelrhodopsin‐2 (ChR2) Cre–reporter Ai32 mice to obtain NaV1.7–ChR2, NaV1.8–ChR2, or NaV1.9–ChR2 mice. Blue light exposure triggered paw withdrawal in all mice, with the strongest response in NaV1.8–ChR2 mice. These light sensitivity differences observed across NaV1.x–ChR2 mice may be dependent on ChR2 expression or reflect the inherent disparities in their pain transmission roles. In conclusion, we have generated noninvasive pain models, with optically activated peripheral nociceptors. We believe that studies using optogenetics will further elucidate the role of sodium channel subtypes in pain transmission.
Mapping between measurement scales in meta‐analysis, with application to measures of body mass index in children
Authors: Davies Annabel L. , Ades A. E. , Higgins Julian P. T. 
Published: October 2024

AbstractQuantitative evidence synthesis methods aim to combine data from multiple medical trials to infer relative effects of different interventions. A challenge arises when trials report continuous outcomes on different measurement scales. To include all evidence in one coherent analysis, we require methods to “map” the outcomes onto a single scale. This is particularly challenging when trials report aggregate rather than individual data. We are motivated by a meta‐analysis of interventions to prevent obesity in children. Trials report aggregate measurements of body mass index (BMI) either expressed as raw values or standardized for age and sex. We develop three methods for mapping between aggregate BMI data using known or estimated relationships between measurements on different scales at the individual level. The first is an analytical method based on the mathematical definitions of z‐scores and percentiles. The other two approaches involve sampling individual participant data on which to perform the conversions. One method is a straightforward sampling routine, while the other involves optimization with respect to the reported outcomes. In contrast to the analytical approach, these methods also have wider applicability for mapping between any pair of measurement scales with known or estimable individual‐level relationships. We verify and contrast our methods using simulation studies and trials from our data set which report outcomes on multiple scales. We find that all methods recreate mean values with reasonable accuracy, but for standard deviations, optimization outperforms the other methods. However, the optimization method is more likely to underestimate standard deviations and is vulnerable to non‐convergence.
Yeast cell biocarrier for the encapsulation of ascorbic acid: effect of plasmolysis process, suspension media and ascorbic acid levels on the physicochemical, morphological and bioactive properties of microcapsules
Authors: Hatip Gamze , Karaman Kevser 
Published: October 2024

AbstractBACKGROUNDAscorbic acid is a water‐soluble vitamin and shows weak stability against external factors such as heat, oxygen, light etc. Due to its lower stability, encapsulation is an effective process for the preservation of its activity. Although there are a wide variety of encapsulation methods, the technique of encapsulation with yeast cells has been followed with increasing interest in recent years. In this study, encapsulation possibilities of ascorbic acid by yeast cells were investigated. In this context, Saccharomycess cerevisiae yeast cells in plasmolyzed and non‐plasmolyzed forms were used in two different suspension media (water and ethanol) and effect of ascorbic acid concentrations (10, 20 and 50 g per 10 g yeast) were studied. A total of 12 different yeast microcapsule samples were produced and some physicochemical, bioactive and structural characterizations were performed.RESULTSThe ascorbic acid level of yeast microcapsule samples was determined as 206.4–713.9 and 202.8–726.1 mg g−1 for plasmolyzed and non‐plasmolyzed yeast cell types, respectively. ABTS radical scavenging activity increased from 27.23 to 233.04 μg TE g−1 by increased ascorbic acid levels. Ascorbic acid capsules were used in soft candy processing against free ascorbic acid and it was found that 47.9% ascorbic acid loss was detected for control sample at the 24‐day storage while the ascorbic acid loss was approximately 25% for yeast microcapsules.CONCLUSIONIt was concluded that yeast cells are capable of preserving ascorbic acid stability during storage and yeast cells can be used effectively and safely for the manufacturing of the ascorbic acid microcapsules. © 2024 Society of Chemical Industry.
Overall survival and prognostic factors associated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy combined with intraoperative radiation therapy in patients with advanced abdominopelvic malignancies: A single center retrospective analysis of 159 patients
Authors: Alaswad Marwan , Arabi Tarek Z. , Alhosainy Ziad , Alammar Juman , Azzam Ayman Z. , Amin Tarek M. 
Published: October 2024

AbstractBackground and ObjectivesThe aim of this study was to look at the overall survival (OS), progression‐free survival (PFS), and prognostic factors associated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) combined with intraoperative radiation therapy (IORT).MethodsThis study is a single center retrospective study performed on 159 patients who underwent treatment with CRS and HIPEC combined with IORT for abdominopelvic malignancies. OS and PFS were used to evaluate the efficacy of this treatment strategy amongst patients with abdominopelvic malignancies.ResultsThe cohort's median age was 53 years, with a male predominance (58.5%). The median OS was not reached, but the mean OS was 76.87 months. In univariate analysis, several factors, including synchronous organ metastasis, Pathologic Peritoneal Carcinomatosis Index (pPCI) ≥10, increased estimated blood loss, and severe postoperative complications, were associated with worse OS. However, multivariate analysis identified pPCI ≥ 10 as the sole independent predictor of worse OS. The 1‐ and 3‐year survival rates were 83% and 70.4%, respectively. pPCI ≥ 10 and severe postoperative complications were significant predictors of worse survival outcomes.ConclusionsRadical surgery alone is not enough, and CRS combined with HIPEC and IORT, when indicated, was proven to be safe and effective with no added morbidity or mortality.
Care Patterns and Outcomes for Intrahepatic Cholangiocarcinoma by Rurality of Patient Residence in a Midwestern State
Authors: Suraju Mohammed O. , Gordon Darren M. , Kahl Amanda R. , McCracken Ana , Maduokolam Erica , Grimmett Jordan , Guedeze Komlan , Nash Sarah , Hassan Aziz 
Published: October 2024

ABSTRACTBackgroundIntrahepatic cholangiocarcinoma (ICC) is the second most common malignancy of the liver and has the worst prognosis of any tumor arising from the liver, with a 5‐year survival as low as 10%. However, whether the rurality of a patient's residence impacts care received and survival has not been well studied. We aimed to assess differences in care patterns associated with the rurality of patient's residences and their impact on survival outcomes, hypothesizing that patients in rural areas would experience lower survival.MethodsAdult patients diagnosed with ICC between 2010 and 2020 were identified in the Iowa Cancer Registry. Chi‐square tests were used to compare values categorical variables by rural/urban status. Cox proportional hazards regression was used to determine associations with cancer‐specific mortality.ResultsOf 672 patients diagnosed with ICC during the study period, 53%, 27%, and 21% resided in metropolitan, micropolitan, and rural areas, respectively. There were no significant differences in age, sex, stage at diagnosis, the proportion receiving chemotherapy within 12 weeks of diagnosis, and undergoing surgery across all groups. Additionally, the proportion receiving definitive care at a National Cancer Institute (NCI) designated center was comparable across the three groups (37% metro vs. 43% micro vs. 35% rural). However, rural residents had the highest proportion of traveling ≥ 50 miles for definitive care (22% metro vs. 41% micro vs. 56% rural). In multivariable analysis of patients with Stage 1–3 disease, younger age, receipt of chemotherapy, surgery, and definitive care at an NCI center were independently associated with decreased mortality risk. However, rural residence was not significantly associated with survival (HR: 0.64 [95% CI: 0.38–1.06]).ConclusionSimilar to other complex cancer diagnoses, we found that definitive care at an NCI center was associated with decreased mortality risk for patients with ICC. Although rural residence was not independently associated with survival in this cohort, rural residents traveled significantly longer distances to access definitive care. This highlights a crucial need to improve access to specialized centers for complex cancer care.
Development of an Untargeted Method for the Analysis of the Volatile Profile of Onions via Solid‐Phase Microextraction Arrow‐Headspace‐Gas Chromatography‐Mass Spectrometry Using Design of Experiments
Authors: Böckstiegel Lea , Schaumann Theresa , Egert Björn , Kulling Sabine E. , Weinert Christoph H. 
Published: October 2024

ABSTRACTThe distinctive aroma of onions, consisting primarily of sulfur‐containing compounds, is one of the reasons for the popularity of the vegetable. The rapid enzymatic and chemical reactions that occur after the destruction of onion bulb tissue render the analysis of the volatile profile challenging. Therefore, sample preparation is a crucial step in the analysis of the onion volatilome, but it often does not receive the necessary attention in the literature. In this work, we focused on two aspects: Firstly, we compared different sample preparation approaches to maximize the volatile yield and to enable the description of the onion volatile profile as it would emerge after a solid‐phase microextraction (SPME) Arrow sampling procedure. For headspace (HS)‐gas chromatography‐mass spectrometry analysis, onion juice with the addition of an ammonium sulfate solution proved to be the best option. Secondly, we optimized the HS sampling and desorption parameters (enrichment time, enrichment temperature, agitator speed, desorption time) for onion volatiles using the efficient design of experiments (DoE) approach. The optimal conditions for the analysis with HS‐SPME Arrow were an enrichment time of 75 min at 60°C with an agitator speed of 713 rpm and a desorption time of 120 s.
Effect of Ultrasound‐Guided External Oblique Intercostal Block on Postoperative Recovery After Subxiphoid Video‐Assisted Thoracoscopic Thymectomy
Authors: Li Zhiang , Hu Lihong , Xi Yong , Wang Lingzhi , Zhang Xuwei , Mugaanyi Joseph 
Published: October 2024

ObjectiveSevere postoperative pain can occur after subxiphoid video‐assisted thoracoscopic thymectomy (SVATT), affecting the quality of postoperative recovery. This study aimed to evaluate the effect of ultrasound‐guided external oblique intercostal (EOI) block on recovery after SVATT.MethodsA total of 60 patients undergoing SVATT were randomly divided into the EOI group (group E, n = 30) and the control group (group C, n = 30). Group E underwent ultrasound‐guided bilateral EOI block at the 6th rib level and was injected 20 mL of 0.375% ropivacaine on each side. Group C was injected with 20 mL of 0.9% saline at the same site. After the operation, both groups received a patient‐controlled intravenous analgesic (PCIA) pump. The 15‐item Quality of Recovery (QoR‐15) scores were recorded at 24 hours before surgery (T0), 24 hours after surgery (T3), and 48 hours after surgery (T4). The sufentanil usage in the first 24 hours postoperatively, the remifentanil dosage during surgery, the time of first pressing PCIA, and the cases of rescue analgesia were recorded. The visual analog scale (VAS) scores of patients at 6 (T1), 12 (T2), 24 (T3), and 48 hours (T4) after an operation during rest and coughing were recorded. The dermatomes of the sensory plane, block complications in group E, and the incidence of other postoperative adverse reactions in both groups were also recorded.ResultsCompared with group C, the QoR‐15 scores of patients were significantly higher at T3 and T4 in the group E. The VAS scores were significantly lower at T1, T2, and T3 during rest and coughing in the group E. The sufentanil usage in the first 24 hours postoperatively, the remifentanil dosage during surgery, and the cases of rescue analgesia were significantly lower in group E, and the time of first pressing PCIA was significantly increased in group E (all P < .05).ConclusionUltrasound‐guided EOI block can be safely used in patients undergoing SVATT, which can improve the quality of postoperative recovery and reduce postoperative pain.
Texture‐Based Classification of Fetal Growth Restriction From Intrauterine Neurosonographic Image
Authors: Chen Zehao , Chen Mengjie , Huang Shiying , Wang Zhongming , Zhang Yiheng , Huang Yuhan , Li Weiling , Huang Xiaowei 
Published: October 2024

ObjectiveFetal growth restriction (FGR) is a condition where fetuses fail to reach their genetic potential for growth, posing a significant health challenge for newborns. The aim of this research was to explore the efficacy of texture‐based analysis of neurosonographic images in identifying FGR in fetuses, which may provide a promising tool for early assessment of FGR.MethodsA retrospective analysis collected 100 intrauterine neurosonographic images from 50 FGR and 50 gestational age‐appropriate fetuses. Using MaZda software, approximately 300 texture features were extracted from occipital white matter (OWM) and cerebellum of intrauterine neurosonographic images, respectively. Then 10 optimal features were separately selected by 3 algorithms, including the Fisher coefficient method, the method of minimizing classification error probability and average correlation coefficients, and the mutual information coefficient method. Further, the 10 statistically most significant features were selected from these sets to form the mixed feature set. After nonlinear discriminant analysis was performed to reduce feature dimensionality, the artificial neural network (ANN) classifier was conducted, respectively.ResultsFor OWM and cerebellum, a total of 11 and 14 statistically significant features were selected. When the mixed feature sets of OWM and cerebellum were applied to ANN classifier, classification accuracy were 90.00% (κ = 0.800; P < .001) and 93.00% (κ = 0.860; P < .001), and the receiver operating characteristic curve for identifying FGR showed an area under the curve of 0.82 and 0.87.ConclusionsTexture analysis of fetal intrauterine neurosonographic images is a feasible and noninvasive strategy for evaluating FGR fetuses.