bluuebunny/crossref_metadata_2025 huggingface dataset:
The Icelandic Heart Failure Registry—A nationwide assessment tool for HF care and intervention in HF treatment
Authors: Ingimarsdóttir Inga Jóna , Hansen Johan Sindri , Bergmann Hekla María , Einarsson Hafsteinn
Published: August 2024

Introduction

The incidence of heart failure (HF) is increasing, largely because populations are both ageing and growing. Most clinical HF treatment trials are conducted on selected cohorts, only a few of which include elderly patients, among whom HF is common. HF registries can include all HF patients, independent of age or comorbidity profile, and thus reflect reality in healthcare management.

Methods

The Icelandic Heart Failure Registry (IHFR) was created in the autumn of 2019 and has operated since 1 January 2020. Based on the Swedish Heart Failure Registry (SwedeHF), it quickly acquired several extensions. All patients admitted for HF to the Department of Cardiology (DC) at Landspítali – The National University Hospital of Iceland are included. Several variables are collected, including the aetiology of HF, comorbidities, clinical assessment at admission, blood tests, imaging results, treatment given and medical therapy at discharge.

Results

During the 3 years from 2020 to 2022, the DC admitted 1890 patients. As some were readmitted during the study period, the true total was 2384 admissions. Because the IHFR 2023 edition includes 327 variables, automation of many of them is imperative for data collection.

Conclusion

HF is a heterogenous disease with numerous underlying factors. HF management differs among HF phenotypes. A registry can serve as an unbiased indicator of care quality and has the potential to be studied in the future to assess the long‐term effects of HF treatment. A registry like the IHFR, therefore, can impact the treatment of all patients recorded in it, reduce the rate of readmissions and even optimize HF management costs.
Association between muscle‐localized bioelectrical impedance analysis parameters and performance in a multi‐set exercise on the isokinetic dynamometer in young women
Authors: Fukuoka Aryanne H. , Oliveira Núbia M. , Matias Catarina N. , Guariglia Débora A. , Guerra‐Júnior Gil , Gonçalves Ezequiel M.
Published: August 2024

This study aimed to verify the relationship between changes in thigh muscle‐localized bioelectrical impedance analysis (ML‐BIA) parameters and performance in a multiple‐set exercise. The sample consisted of 30 female university students (22.1 ± 3.2 years). The ML‐BIA parameters, including localized muscle resistance (ML‐R), reactance (ML‐Xc), and phase angle (ML‐AngF), were evaluated using a tetrapolar bioelectric impedance device operating at a frequency of 50 KHz. The multiple sets protocol was performed with an isokinetic dynamometer. For body composition, total and leg lean soft tissue (LST) were evaluated using dual X‐ray absortiometry. Student's t‐test for paired samples was used to compare the ML‐BIA parameters and thigh circumference pre and postexercise. Linear regression analysis was performed to verify the ∆ML‐PhA as a predictor of peak torque for the three sets alone while controlling for total and leg LST. There were differences in the ML‐R (∆ = 0.02 ± 1.45 Ω; p = 0.001; and E.S = 0.19), ML‐Xc (∆ = 2.90 ± 4.12 Ω; p = 0.043; and E.S = 0.36), and thigh circumference (∆ = 0.82 ± 0.60 cm; p < 0.001; and E.S = 0.16) pre‐ and post‐multiple sets. ΔML‐PhA was a predictor of performance in the first set (p = 0.002), regardless of total and leg LST. However, the ΔML‐PhA lost its explanatory power in the other sets (second and third), and the variables that best explained performance were total and leg LST. The ML‐BIA (ML‐R and ML‐Xc) parameters were sensitive and changed after the multiple sets protocol, and the ΔML‐PhA was a predictor of performance in the first set regardless of the total and leg LST.
A Resonance‐Based Study of the Output Characteristics of Spring‐Assisted Triboelectric Nanogenerator
Authors: Zhang Cheng , Wu Zhongjiang , Li Miaoli , Huang Xili , Ling Ziyun
Published: August 2024

The triboelectric nanogenerator (TENG) is a new type of energy conversion technology capable of transforming various forms of environmental energy into electricity. However, most of the existing spring‐assisted TENGs (S‐TENGs) are based on the vertical contact‐separation mode, which has low energy‐harvesting efficiency and insufficient research on the performance output of TENG under near‐resonant frequency conditions. In this article, a low‐cost S‐TENG with independent layer mode is designed for vibration energy harvesting. The effects of different vibration parameters and structural parameters on the output performance are comprehensively investigated. In the experimental results, it is shown that the output voltage of the S‐TENG reaches its peak at a frequency of 50 Hz, achieving ≈40 V. To validate the capability of S‐TENG in powering low‐power devices, 20 LED lights are successfully lit. It is found that the maximum output power across the external resistor of 8 MΩ is 0.4 mw. It is also investigated that the output characteristics of S‐TENG under resonance and the results showed that higher output electric power can be achieved when the vibration frequency is close to the intrinsic frequency of the S‐TENG. In this finding, the potential of S‐TENG in optimized energy‐harvesting applications, particularly in resonance‐enhanced scenarios.
Fluid flow zones along fracture corridors inferred from collapse dolines in carbonates of the Irecê Basin, Brazil
Authors: Maia Rubson P. , Auler Augusto S. , Bezerra Francisco H. R. , Borges Sérgio V. F. , La Bruna Vincenzo , Pujoni Diego , dos Santos Eliana E. , Vidal Alexandre C.
Published: August 2024

Dolines are a widespread karst landform, and understanding their genesis can provide critical information about the evolution of subsurface karstification and groundwater flow zones. Swarms of collapse dolines characterise the karst in the southern portion of the Irecê Basin, northeastern Brazil. The basin comprises Neoproterozoic carbonate rocks approximately 100 m thick, bounded by less soluble older quartzites. The distribution of dolines is not uniform, as they cluster along NW‐SE axes and are aligned with cave systems and permeability (fracture) corridors mostly associated with the Almas and Água de Rega ephemeral rivers. Detailed analysis of sectors with a higher density of dolines was performed using LiDAR and unmanned aerial vehicle (UAV) imagery at two different scales to obtain morphometric and orientation patterns. As expected, scale dependency is observed, with an increase in density and circularity index at a higher resolution scale, but a decrease in mean area and perimeter. However, Voronoi polygon indices are similar at both scales (6.86 ± 1); the departure from the more stable number of six due to the clustering of dolines associated with NW‐SE oriented structural trends. Doline density trends closely follow the orientation of caves, but they are not always spatially connected, since doline evolution may either occlude the caves or be related to a non‐identified void. The Irecê Basin karst system displays a continuum of landforms evolving initially from high‐density fracture zones (fracture corridors), which work as favourable dissolution zones, grading into more integrated flow routes, cave systems and eventually clusters of collapse dolines. Collapse dolines are widespread karst landforms worldwide, and their genesis requires the presence of dissolution voids at depth, which may pass undetected from the surface. In some sectors of Irecê Basin, the existence of doline alignments but the absence of known caves indicates the potential of collapse dolines to be used as proxies for subsurface karstification. Such an approach may allow the prediction of the location and orientation of subsurface zones of enhanced dissolution that can potentially represent productive aquifers or favourable zones for geofluids.
Carbon‐Based Cathode Design for Next‐Generation Potassium‐Sulfur Batteries: Status and Perspective
Authors: Bharti Vikram Kishore , Dawsey Tim , Gupta Ram K.
Published: August 2024

The increasing concern for environmental pollution has fastened the development of energy storage devices. Among various devices, lithium‐ion battery (LIB) technology has been leapfrogged owing to its stable performance for various applications ranging from electronic gadgets to electric vehicles (EVs). For ever‐increasing number of EVs has increased the demand for batteries increasing the overall cost. An alternative energy storage device that can replace the dependence on lithium reserves can be another game changer in this area. Potassium‐sulfur batteries (KSBs) have attracted enormous attention owing to the higher abundance of sulfur and potassium. In addition, sulfur bears the highest capacity as a cathodic material (nearly five times higher than the commercial LIBs) and when clubbed with potassium anode can deliver a theoretical energy density of 914 Wh/kg (significantly higher for EVs). However, KSB development is still in the nascent stage owing to the intrinsic challenges including insulating sulfur, volume variation, and shuttle effect of polysulfides. In addition, unstable potassium anode and its dendrite formation is another thorny problem for KSB. The use of carbon matrices for cathode fabrication has been proven to be an excellent choice by initial research on KSB and experience with other metal‐sulfur batteries. This can be related to the higher electronic conductivity of carbon, easy tunability, high specific surface area, and porous morphology. This review is an attempt to show the usage of carbon as a sulfur host for KSBs and its performance. Further, we shed light on flexible and binder‐free carbon electrodes for the development of KSBs, which can be adopted to develop flexible batteries to be used in wearable devices. Finally, we present our perspective for developing a high‐performance carbon‐based cathode material for developing a reliable and long‐cycle life KSB.
Deep‐frying impact on food and oil chemical composition: Strategies to reduce oil absorption in the final product
Authors: Valle Consuelo , Echeverría Francisca , Chávez Vilma , Valenzuela Rodrigo , Bustamante Andrés
Published: August 2024

During frying, oils can deteriorate due to autoxidation and hydrolytic alterations, processes influenced by the oil's fatty acid composition (FAC) and antioxidant content. However, there are different techniques to improve fried food quality and reduce oil absorption. This review aims to assess existing literature on the interactions between frying methods, oil selection, and the chemical composition of foods. To achieve this goal, the article examines the impact of oil FAC, antioxidants, pretreatments, and alternative frying technologies. A literature search was conducted from 2016 to 2023. The keywords used were (AND/OR) frying, fried foods, oil, oil absorption, and fatty acids. Oils rich in monounsaturated fatty acids and antioxidants, such as olive oil, are recommended for their nutritional benefits and improved oil stability. The water content and structure of the food also play a significant role in oil absorption. Pretreatments to diminish food moisture content contribute to a lower oil absorption in the fried food while mitigating excessive accumulation of lipid oxidation products. Proper selection of frying oils, incorporation of antioxidants, and the use of pretreatments could help prevent chemical changes and minimize oil absorption during frying. These measures contribute to maintaining the nutritional quality and safety of fried foods while also enhancing their overall sensory appeal.
TLE3 Is a Novel Fusion Partner of JAK2 in Myeloid/Lymphoid Neoplasm With Eosinophilia Responding to JAK2 Inhibition
Authors: Lazarevic Vladimir , Lilljebjörn Henrik , Olsson‐Arvidsson Linda , Orsmark‐Pietras Christina , Ågerstam Helena
Published: August 2024

Chromosomal rearrangements involving Janus kinase 2 (JAK2) are rare but recurrent findings in lymphoid or myeloid neoplasia. Detection of JAK2 fusion genes is important as patients with aberrantly activated JAK2 may benefit from treatment with tyrosine kinase inhibitors such as ruxolitinib. Here, we report a novel fusion gene between the transcriptional co‐repressor‐encoding gene transducin‐like enhancer of split 3 (TLE3) and JAK2 in a patient initially diagnosed with chronic eosinophilic leukemia with additional mutations in PTPN11 and NRAS. The patient was successfully treated with the JAK2 inhibitor ruxolitinib for 8 months before additional somatic mutations were acquired and the disease progressed into an acute lymphoblastic T‐cell leukemia/lymphoma. The present case shows similarities to previously reported cases with PCM1::JAK2 and BCR::JAK2 with regard to disease phenotype and response to ruxolitinib, and importantly, provides an example that also patients harboring other JAK2 fusion genes may benefit from treatment with JAK2 inhibitors.
Medicaid expansion and opioid prescriptions: Evidence from the Medical Expenditure Panel Survey
Authors: McClellan Chandler , Moriya Asako
Published: August 2024

Evidence is mixed on whether increased access to insurance, specifically through the ACA's Medicaid expansion, exacerbated the opioid public health crisis through increased opioid prescribing. Using survey data on retail prescription drug fills from 2008 to 2019, we did not find a significant relationship between Medicaid expansion and opioid prescribing in the newly eligible Medicaid population. It may be that the dangers of opioids were known well enough by the time of the Medicaid expansion that lack of access to care was no longer a binding constraint on opioid prescription receipt.
The PI3Kδ inhibitor zandelisib on intermittent dosing in relapsed/refractory follicular lymphoma: Results from a global phase 2 study
Authors: Zelenetz Andrew D. , Jurczak Wojciech , Ribrag Vincent , Linton Kim , Collins Graham P. , Jiménez Javier L. , Bishton Mark , Dholaria Bhagirathbhai , Mengarelli Andrea , Phillips Tycel J. , Sungala Nagendraprasad , Musuraca Gerardo , Sheehy Oonagh , Van Den Neste Eric , Odera Mitsuhiko , Miao Lu , Gold Daniel P. , Ghalie Richard G. , Zinzani Pier L.
Published: August 2024

In this global phase 2 study in patients with relapsed/refractory follicular lymphoma (FL), zandelisib was administered on intermittent dosing to mitigate immune‐related adverse events and infections that have been reported with oral PI3Kδ inhibitors administered daily continuously. Eligible patients with measurable disease and progression after at least two prior therapies were administered zandelisib until disease progression or intolerability. The primary efficacy endpoint was objective response rate (ORR) and the key secondary efficacy endpoint was duration of response (DOR). We report on 121 patients with FL administered zandelisib on intermittent dosing after 8 weeks of daily dosing for tumor debulking. The median number of prior therapies was 3 (range, 2–8) and 45% of patients had refractory disease. The ORR was 73% (95% confidence interval [CI], 63.9–80.4), the complete response (CR) rate was 38% (95% CI, 29.3–47.3), and the median DOR was 16.4 months (95% CI, 9.5–not reached). With a median follow‐up of 14.3 months (range, 1–30.5), the median progression‐free survival was 11.6 months (95% CI, 8.3–not reached). Twenty‐one patients (17%) discontinued therapy due to an adverse event. Grade 3–4 class‐related toxicities included 6% diarrhea, 5% lung infections, 3% colitis (confirmed by biopsy or imaging), 3% rash, 2% AST elevation, and 1% non‐infectious pneumonitis. Zandelisib achieved a high rate of durable responses in heavily pretreated patients with relapsed/refractory FL. The intermittent dosing resulted in a relatively low incidence of severe class‐related toxicities, which supports the evaluation of zandelisib as a single agent and in combination with indolent B‐cell malignancies.
Role of gut microbiome in the outcome of lymphoma patients treated with checkpoint inhibitors—The MicroLinf Study
Authors: Casadei Beatrice , Conti Gabriele , Barone Monica , Turroni Silvia , Guadagnuolo Serafina , Broccoli Alessandro , Brigidi Patrizia , Argnani Lisa , Zinzani Pier Luigi
Published: August 2024

Biomarkers for immune checkpoint inhibitors (ICIs) response and resistance include PD‐L1 expression and other environmental factors, among which the gut microbiome (GM) is gaining increasing interest especially in lymphomas. To explore the potential role of GM in this clinical issue, feces of 30 relapsed/refractory lymphoma (Hodgkin and primary mediastinal B‐cell lymphoma) patients undergoing ICIs were collected from start to end of treatment (EoT). GM was profiled through Illumina, that is, 16S rRNA sequencing, and subsequently processed through a bioinformatics pipeline. The overall response rate to ICIs was 30.5%, with no association between patients clinical characteristics and response/survival outcomes. Regarding GM, responder patients showed a peculiar significant enrichment of Lachnospira, while non‐responder ones showed higher presence of Enterobacteriaceae (at baseline and maintained till EoT). Recognizing patient‐related factors that may influence response to ICIs is becoming critical to optimize the treatment pathway of heavily pretreated, young patients with a potentially long‐life expectancy. These preliminary results indicate potential early GM signatures of ICIs response in lymphoma, which could pave the way for future research to improve patients prognosis with new adjuvant strategies.
tigeR: Tumor immunotherapy gene expression data analysis R package
Authors: Chen Yihao , He Li‐Na , Zhang Yuanzhe , Gong Jingru , Xu Shuangbin , Shu Yuelong , Zhang Di , Yu Guangchuang , Zuo Zhixiang
Published: August 2024

Immunotherapy shows great promise for treating advanced cancers, but its effectiveness varies widely among different patients and cancer types. Identifying biomarkers and developing robust predictive models to discern which patients are most likely to benefit from immunotherapy is of great importance. In this context, we have developed the tumor immunotherapy gene expression R package (tigeR 1.0) to address the increasing need for effective tools to explore biomarkers and construct predictive models. tigeR encompasses four distinct yet closely interconnected modules. The Biomarker Evaluation module enables researchers to evaluate whether the biomarkers of interest are associated with immunotherapy response via built‐in or custom immunotherapy gene expression data. The Tumor Microenvironment Deconvolution module integrates 10 open‐source algorithms to obtain the proportions of different cell types within the tumor microenvironment, facilitating the investigation of the association between immune cell populations and immunotherapy response. The Prediction Model Construction module equips users with the ability to construct sophisticated prediction models using a range of built‐in machine‐learning algorithms. The Response Prediction module predicts the immunotherapy response for the patients from gene expression data using our pretrained machine learning models or public gene expression signatures. By providing these diverse functionalities, tigeR aims to simplify the process of analyzing immunotherapy gene expression data, thus making it accessible to researchers without advanced programming skills. The source code and example for the tigeR project can be accessed at http://github.com/YuLab-SMU/tigeR.
Synthesis, molecular docking, drug‐likeness analysis, and ADMET prediction of nickel and zinc tetraphenyl‐porphyrin complexes as possible antioxidant agents
Authors: Lanez Elhafnaoui , Zerrouk Lalmi , Bechki Lazhar , Lanez Touhami , Adaika Aicha , Zegheb Nadjiba , Nesba Kaouther
Published: August 2024

Nickel tetraphenyl‐porphyrin (NiTPPH₂) and zinc tetra(4‐methophenyl)‐porphyrin (ZnTPPH₂(p‐methyl)) were successfully synthesized and characterized using 1H NMR spectroscopy. Their antioxidant activities and interactions with the superoxide anion radical () were evaluated using cyclic voltammetry. Remarkably, NiTPPH₂ displayed superior antioxidant activity with an IC50 value of 54.57 μg mL−1, significantly outperforming α‐tocopherol (IC50 = 353.27 μg mL−1), indicating its potential as a potent antioxidant. Binding free energy calculations demonstrated that electrostatic interactions predominantly govern the binding, with values of −23.47 kJ mol−1 for NiTPPH₂ and −22.50 kJ mol−1 for ZnTPPH₂(p‐methyl). These values suggest robust binding affinities with . Quantum chemical parameters, obtained through density functional theory (DFT), showed a strong correlation with experimental results, validating the computational approach. Additionally, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) and drug‐likeness assessments, alongside molecular docking studies, highlighted favorable pharmacokinetic profiles and binding affinities. These findings underscore the potential of NiTPPH₂ and ZnTPPH₂(p‐methyl) as promising candidates for antioxidant therapy, exhibiting drug‐like properties and favorable pharmacokinetics. This research advances the understanding of these porphyrin derivatives and their application in the development of novel antioxidant therapeutics.
Safety, Tolerability, and Pharmacokinetics of Single Doses of Exidavnemab (BAN0805), an Anti‐α‐Synuclein Antibody, in Healthy Western, Caucasian, Japanese, and Han Chinese Adults
Authors: Boström Emma , Bachhav Sagar S. , Xiong Hao , Zadikoff Cindy , Li Qingbo , Cohen Eric , Dreher Ingeborg , Torrång Anna , Osswald Gunilla , Moge Mikael , Appelkvist Paulina , Fälting Johanna , Odergren Tomas
Published: August 2024

Exidavnemab is a monoclonal antibody (mAb) with a high affinity and selectivity for pathological aggregated forms of α‐synuclein and a low affinity for physiological monomers, which is in clinical development as a disease‐modifying treatment for patients with synucleinopathies such as Parkinson's disease. Safety, tolerability, pharmacokinetics, immunogenicity, and exploratory biomarkers were assessed in two separate Phase 1 single ascending dose studies, including single intravenous (IV) (100 to 6000 mg) or subcutaneous (SC) (300 mg) administration of exidavnemab in healthy volunteers (HVs). Across the two studies, a total of 98 Western, Caucasian, Japanese, and Han Chinese HVs were enrolled, of which 95 completed the study. Exidavnemab was generally well tolerated. There were no serious adverse events or safety issues identified in laboratory analyses. Headache, asymptomatic COVID‐19, back pain, and post lumbar puncture syndrome were the most frequently reported treatment‐emergent adverse events. Following IV infusion, the pharmacokinetics of exidavnemab was approximately dose linear in the range 100‐6000 mg. The terminal half‐life was approximately 30 days, and the exposure was comparable across Western, Caucasian, Japanese, and Han Chinese volunteers. The absolute SC bioavailability was ∼71%. Cerebrospinal fluid exposure relative to serum after single dose was within the range expected for mAbs (approximately 0.2%). The anti‐drug antibody rates were low and there was no effect of immunogenicity on the pharmacokinetics or safety. Dose‐dependent reduction of free α‐synuclein in plasma was observed. In summary, exidavnemab was found to have an excellent pharmacokinetic profile and was well tolerated in HVs, supporting the continued clinical development.
Predict the Drug–Drug Interaction of a Novel PI3Kα/δ Inhibitor, TQ‐B3525, and Its Two Metabolites Using Physiologically Based Pharmacokinetic Modeling
Authors: Zhu Shixing , Yu Ding , Wang Xunqiang , Wang Xin
Published: August 2024

A novel dual PI3K α/δ inhibitor, TQ‐B3525, has been developed for the targeted treatment of lymphoma and solid tumors. TQ‐B3525 is primarily metabolized by CYP3A4 and FOM3, while also serving as a substrate for the P‐glycoprotein transporter. The aim of this study was to anticipate the drug–drug interaction (DDI) of TQ‐B3525 and its two metabolites with CYP3A4 enzyme potent inducer (rifampicin) and CYP3A4/P‐gp inhibitor (itraconazole) utilizing a physiologically based pharmacokinetic (PBPK) modeling approach. Clinical data from healthy and cancer patient adults were employed to construct and evaluate the PBPK model for TQ‐B3525, M3, and M8‐3. Models involving rifampicin combined with midazolam, itraconazole combined with midazolam or digoxin were utilized to showcase the robustness of evaluating DDI effects. The simulated drug exposure of TQ‐B3525, M3, and M8‐3 in healthy and patient adults were consistent with clinical data, and the mean fold error values were within the acceptable ranges. The simulated results of positive substrates correspond to those reported in the literature. Co‐administration with rifampicin reduces Cmax and AUC of TQ‐B3525 to 76.1% and 46.0%, while increasing the levels of M3 and M8‐3. With itraconazole, Cmax and AUC of TQ‐B3525 rise to 131% and 204%, but decrease substantially for M3 and M8‐3. PBPK model simulation results showed that the systemic exposure of TQ‐B3525 was significantly affected when co‐administered with CYP3A4/P‐gp inducers and inhibitors. This indicates that the combination with strong inducers and inhibitors should be carefully avoided or adjust the dosage of TQ‐B3525 in clinic.
Leveraging the dynamics of microalgal CO2 capture to estimate the maximum inherent photosynthetic potential
Authors: Battula Satyanarayana Reddy , Sen Ramkrishna
Published: August 2024

BACKGROUND

Natural photosynthesis, utilizing intelligent molecular machinery to harness sunlight, stands as the benchmark for efficient energy generation. Despite its high quantum efficiency compared to synthetic methods, challenges persist due to dynamic nutritional and light requirements in plant, microalgae, and cyanobacteria‐driven processes. Reported microalgae CO2 uptake rates rely on biomass dry cell weight measurement after certain incubation period and systematic study of required CO2 concentrations for optimal photobioreactor operation remaining unexplored. This research is thus aimed at evaluating the critical dissolved CO2 (Ccrit ∙ CO2) concentration and specific CO2 uptake rates (SCUR) of Chlorella minutissima (CM) culture in the presence of surplus light and other nutrients by online monitoring and measuring the dynamic CO2 uptake rates which will help in maintaining the optimal rate of CO2 delivery for continuous cultivation of microalgae while minimizing the escape of CO2.

RESULTS

Dissolved Ccrit ∙ CO2 was determined to be in the range of 16–20 mg/L, and the maximum SCUR in BBM (Bold Basal Medium) was found to be 0.73 mg CO2 (mg dcw ∙ h)−1. Interestingly, this SCUR value is nearly three times greater than that of the most efficient in vitro artificial photosynthetic novel pathway reported so far.

CONCLUSION

From the calculated SCUR values, it may be noted that 9.6 g of biomass can be obtained from 1 g of microalgal inoculum in a day, thereby setting a benchmark for the scientists working in the areas of bioprocess engineering, synthetic biology, and metabolic engineering to comply. © 2024 Society of Chemical Industry (SCI).
Development and evaluation of a surgical 3D simulation model on submental flap surgery training
Authors: Tahami Hadis , Rahpeyma Amin , Shooshtari Zahra , Shahri Arsalan , Pourianezhad Bita , Khajehahmadi Saeedeh
Published: August 2024

Objectives

The purpose of the present study was to design and assess a 3D simulation model for submental flap surgery in training oral and maxillofacial surgery (OMFS) residents.

Methods

This quasi‐experimental study involved a total of 20 OMFS residents attending and was conducted from September 2023 to December 2023. A 3D submental flap surgical phantom was designed using Mimics V.21 software and printed using fused deposition modeling technology. Participants were first tested on their knowledge of submental flap surgery before being randomly assigned to experimental or control groups. The experimental group received a lecture and demonstration using the developed phantom, while the control group had traditional lecture education only. Afterward, the same test was administered to all participants post‐training. Pre‐ and post‐test scores were calculated and compared between the two groups. p‐Value < 0.05 was considered statistically significant.

Results

The average pre‐intervention test scores in the control and experimental group, were 2.5 ± 1.43 and 3 ± 0.816, respectively (p = 0.35). Post‐intervention, the experimental group exhibited significantly higher exam scores compared to the group who had only received academic lecture training (6.9 ± 0.87 vs. 4.9 ± 0.99) (p < 0.001). Irrespective of the applied teaching method, both groups showed a significant increase in exam scores after receiving submental flap training (p < 0.001 for both groups, paired‐sample t‐test).

Conclusion

The use of the developed submental flap phantom model significantly improved OMFS residents' test scores and knowledge of the surgical technique, suggesting its potential integration into the conventional resident training curriculum.
A Predictive Model for Initial Platinum‐Based Chemotherapy Efficacy in Patients with Postoperative Epithelial Ovarian Cancer Using Tissue‐Derived Small Extracellular Vesicles
Authors: Shen Shizhen , Wang Conghui , Gu Jiaxin , Song Feifei , Wu Xiaodong , Qian Fangfang , Chen Xiaojing , Wang Lingfang , Peng Qiaohua , Xing Ziyu , Gu Lingkai , Wang Fenfen , Cheng Xiaodong
Published: August 2024

Epithelial ovarian cancer (EOC) is an often‐fatal malignancy marked by the development of resistance to platinum‐based chemotherapy. Thus, accurate prediction of platinum drug efficacy is crucial for strategically selecting postoperative interventions to mitigate the risks associated with suboptimal therapeutic outcomes and adverse effects. Tissue‐derived extracellular vesicles (tsEVs), in contrast to their plasma counterparts, have emerged as a powerful tool for examining distinctive attributes of EOC tissues. In this study, 4D data‐independent acquisition (DIA) proteomic sequencing was performed on tsEVs obtained from 58 platinum‐sensitive and 30 platinum‐resistant patients with EOC. The analysis revealed a notable enrichment of differentially expressed proteins that were predominantly associated with immune‐related pathways. Moreover, pivotal immune‐related proteins (IRPs) were identified by LASSO regression. These factors, combined with clinical parameters selected through univariate logistic regression, were used for the construction of a model employing multivariate logistic regression. This model integrated three tsEV IRPs, CCR1, IGHV_35 and CD72, with one clinical parameter, the presence of postoperative residual lesions. Thus, this model could predict the efficacy of initial platinum‐based chemotherapy in patients with EOC post‐surgery, providing prognostic insights even before the initiation of chemotherapy.
Proximity ligation‐based sequencing for the identification of human papillomavirus genomic integration sites in formalin‐fixed paraffin embedded oropharyngeal squamous cell carcinomas
Authors: Demers Imke , Balaji Harini , Feitsma Harma , Stelloo Ellen , Swennenhuis Joost , Sergeeva Irina , Wuerdemann Nora , van den Hout Mari F. C. M. , Wagner Steffen , Kremer Bernd , Klussmann Jens P. , Huebbers Christian U. , Speel Ernst‐Jan M.
Published: August 2024

Human papillomavirus (HPV) infections are an increasing cause of oropharyngeal squamous cell carcinomas (OPSCC). Integration of the viral genome into the host genome is suggested to affect carcinogenesis, however, the correlation with OPSCC patient prognosis is still unclear. Research on HPV integration is hampered by current integration detection technologies and their unsuitability for formalin‐fixed paraffin‐embedded (FFPE) tissues. This study aims to develop and validate a novel targeted proximity‐ligation based sequencing method (targeted locus amplification/capture [TLA/TLC]) for HPV integration detection in cell lines and FFPE OPSCCs. For the identification of HPV integrations, TLA/TLC was applied to 7 cell lines and 27 FFPE OPSCCs. Following preprocessing steps, a polymerase chain reaction (PCR)‐based HPV enrichment was performed on the cell lines and a capture‐based HPV enrichment was performed on the FFPE tissues before paired‐end sequencing. TLA was able to sequence up to hundreds of kb around the target, detecting exact HPV integration loci, structural variants, and chromosomal rearrangements. In all cell lines, one or more integration sites were identified, in accordance with detection of integrated papillomavirus sequences PCR data and the literature. TLC detected integrated HPV in 15/27 FFPE OPSCCs and identified simple and complex integration patterns. In general, TLA/TLC confirmed PCR data and detected additional integration sites. In conclusion TLA/TLC reliably and robustly detects HPV integration in cell lines and FFPE OPSCCs, enabling large, population‐based studies on the clinical relevance of HPV integration. Furthermore, this approach might be valuable for clonality assessment of HPV‐related tumors in clinical diagnostics.
Early postnatal development of the primary visual areas 17 and 18 of the cat cerebral cortex: An SMI‐32 study
Authors: Mikhalkin A. A. , Nikitina N. I. , Merkulyeva N. S.
Published: August 2024

Using anti‐neurofilament H non‐phosphorylated antibodies (SMI‐32) as markers for the neuronal maturation level and Y channel responsible for motion processing, we investigated early postnatal development of the primary visual areas 17 and 18 in cats aged 0, 10, 14, and 34 days and in adults. Two analyzed parameters of SMI‐32‐immunolabeling were used: the total proportion of SMI‐32‐labeling and the density of labeled neurons. (i) The developmental time course of the total proportion of SMI‐32‐labeling shows the general increase in the accumulation of heavy‐chain neurofilaments. This parameter showed a different time course for cortical layer development; the maximal increment in the total labeling in layer V occurred between the second and fifth postnatal weeks and in layers II–III and VI after the fifth postnatal week. In addition, the delay in accumulation of SMI‐32‐labeling was shown in layer V of the area 17 periphery representation during the first two postnatal weeks. (ii) The density of SMI‐32‐labeled neurons decreased in all layers of area 18, but was increased, decreased, or had a transient peak in layers II–III, V, and VI of area 17, respectively. The transient peak is in good correspondence with some transient neurochemical features previously revealed for different classes of cortical and thalamic neurons and reflects the time course of the early development of the thalamocortical circuitry. Some similarities between the time courses for the development of SMI‐32‐labeling in areas 17/18 and in A‐ and C‐laminae of the LGNd allow us to propose heterochronous postnatal development of two Y sub‐channels.
Exercise improves load bearing bone structural properties in female secreted protein acidic and rich in cysteine (SPARC) null mice but not in males
Authors: Kaneda Giselle , Huang Dave , Pham Nathalie , Gonzalez Alfonso R. , Tawackoli Wafa , Lee Seunghwan , Suzuki Miyako , Nelson Trevor J. , Glaeser Juliane D. , Millecamps Magali , Stone Laura S. , Sheyn Dmitriy , Metzger Melodie F.
Published: August 2024

Secreted protein acidic and rich in cysteine (SPARC) is the most abundant glycoprotein in bone and is thought to play a critical role in bone remodeling and homeostasis. However, the effect of SPARC in relation to gender and exercise on bone quality is not well understood. The purpose of this study was to quantify differences in the structural and biomechanical properties between calvarial and femoral bone from male and female wild‐type (WT) and SPARC null (SPARC(−/−)) mice as well as the ability of exercise to rescue bone health. Male and female WT and transgenic SPARC(−/−) mice were given either a fixed or rotating running wheel for exercise. Bone structural, biomechanical, and morphological parameters were quantified using micro computed tomography, push out testing for the calvaria, three‐point flexural testing for the femurs, histological and immunofluorescent staining. Similar reductions in structural and biomechanical strength were observed in both male and female SPARC(−/−) calvaria, most of which were not significantly affected by exercise. In femurs, SPARC(−/−) had a significant effect on structural parameters in both sexes, but was more pronounced in females with some properties being rescued with running. Interestingly, the effect of SPARC(−/−) on bone mineral density was only detected in female SPARC(−/−) mice, not males, and was subsequently rescued with exercise. This study emphasizes the differences between sexes in WT and SPARC(−/−) mice in regard to structural parameters and biomechanical properties. Research into gender differences can help inform and personalize treatment options to more accurately meet patient needs.
Influence of biliary and vascular resection types on morbidity in hepatectomies with vascular involvement
Authors: Silva Jonatha C. F. da , Diniz Alessandro L. , Torres Silvio M. , Silva Dante A. , Ribeiro Héber S. d. C. , de Godoy André Luiz , de Farias Igor Correia , Felismino Tiago Cordeiro , da Costa Junior Wilson L. , Coimbra Felipe José F.
Published: August 2024

Introduction

Hepatectomies associated with vascular resections pose a technical challenge for surgeons, involving multiple reconstruction techniques. Moreover, adding clinical and surgical risks in the postoperative setting of these complex procedures are mainly due to prolonged surgical periods and potential complications inherent to vascular manipulation. Leveraging the expertise of a Cancer Center, we propose an institutional assessment utilizing the case series from A. C. Camargo Cancer Center in hepatectomies associated with vascular resection, evaluating postoperative complications and outcomes while highlighting clinical, laboratory, pathological, and surgical factors that may influence results.

Objective

To assess mortality and morbidity associated with hepatectomies involving vascular resection.

Materials and Methods

From a prospective database, a study was performed evaluating postoperative survival and morbidity using scoring systems such as Clavien−Dindo through a cohort analysis.

Results

From a total of 1021 liver resections for a period of 10 years, 31 cases were evaluated from a unique cancer center in Brazil! Factors such as the performance of major hepatectomies, the need for blood transfusion, and the administration of neoadjuvant or adjuvant systemic therapy did not appear to influence the outcome of morbidity or mortality. However, the resection of the associated bile duct and the type of vascular resection seemed to influence morbidity outcomes with statistical significance (p = 0.006+ …).

Conclusion

Hepatectomies associated with vascular resections are safe in selected cases and when performed in referral centers. Factors such as associated bile duct resection and type of vascular resection should be considered for procedure indication.
Comparing cadaveric and 3D‐printed laryngeal models in transcutaneous injection laryngoplasty
Authors: Chandna Megha , Siddiqui Sana , Bertoni Dylan , Sakkal Marah , Belko Sara , Boon Maurits , Spiegel Joseph
Published: August 2024

Background

There is increasing focus on the development of high‐quality simulation models for medical education. Cadaveric models, although considered more realistic, may be difficult to obtain and costly. The advent of three‐dimensional (3D) printing has offered a low‐cost, reliable, and reproducible alternative. This study sought to compare the utility of 3D‐printed to cadaveric models for training in transcutaneous injection laryngoplasty (TIL).

Methods

A simulation course with a cross‐over design was employed. Video laryngoscopes were utilized for both the 3D and cadaveric models to assess the accuracy of injection into the vocal fold. Pre‐procedure and post‐procedure surveys were administered to evaluate understanding and comfort level on a Likert scale of 1–10. Each model was also rated on a 1–5 Likert scale for self‐efficacy, fidelity, and educational value.

Results

Pre‐ and post‐survey data were completed by 15 otolaryngology residents and medical students. Mean pre‐seminar understanding and comfort level were 3.7 and 2.2, respectively, compared to 6.9 and 5.9 (p < .05) following use of the 3D model and 6.4 and 4.7 (p < .05) following use of the cadaver model. When comparing 3D and cadaveric models, no significant differences were observed regarding self‐efficacy, fidelity, and educational value.

Conclusion

There was a similar mean increase in understanding and comfort following use of the 3D and cadaveric models. 3D‐printing can provide an excellent adjunct to, and eventually a potential replacement for hands‐on cadaveric training in medical education, particularly for TIL.

Level of Evidence

Level III.
Oropharyngeal reconstruction with buccinator myomucosal island flaps: Functional outcomes and quality of life. A retrospective observational study
Authors: Carnevale C. , Sarría‐Echegaray P. , Morales Olavarría C. , Til‐Pérez G.
Published: August 2024

Background

The buccinator myomucosal island flaps are an excellent option for “like with like” oropharyngeal reconstruction in selected cases. We report a series of 15 patients and discuss the functional outcomes.

Methods

From January 1, 2020 to February 31, 2023, 15 patients underwent oropharyngeal tumor resection and reconstruction with myomucosal island flaps. Buccal artery myomucosal island flap and tunnelized facial artery myomucosal island flap were used in 10 and 5 patients, respectively. In four cases, a total soft palate reconstruction was performed. Before removing the nasogastric tube, a videoendoscopy was performed in all cases to assess postoperative swallowing. Functional assessment was evaluated after a follow‐up of at least 12 months. Speech intelligibility and patient speech perception were assessed using the Hirose's 10‐point scoring system and the Voice Handicap Index. Dysphagia was assessed using the Dysphagia Outcome and Severity Scale and the Dysphagia Handicap Index. Finally, donor site morbidity was analyzed, and quality of life was assessed using the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ‐C30).

Results

The median length of hospital stay was 10.5 days. Nasal feeding tube was removed on average in 8.6 days after surgery, and all patients were able to tolerate an oral soft diet. Intelligibility was very good in all cases. No major complications were detected, and donor site morbidity was low. Global quality of life was acceptable in all cases.

Conclusions

Buccinator myomucosal island flaps represent a very interesting and versatile option for the functional reconstruction of oropharyngeal defects up to 7–8 cm.

Level of Evidence

IV
3D‐printed neck phantoms with detailed anatomy for ultrasound‐guided procedure and device testing
Authors: Hasson Aida M. , Patel Rahul D. , Sissoko Cheick A. , Brattain Laura , Dion Gregory R.
Published: August 2024

Objectives

With rapid advances in ultrasound‐guided procedures, there is an unmet need for echogenic phantoms with sufficient anatomical details for artificial intelligence and ultrasound‐guided device testing. We developed a method for creating neck phantoms for novel otolaryngology‐related device testing. To achieve accurate representation of the anatomy, we utilized CT scans and 3D printing technology to create customized agar molds, thus providing high‐fidelity yet cost‐effective tools.

Methods

Based on previous studies, the key components in our neck phantom include the cervical vertebrae, trachea, common carotid arteries, internal jugular veins, thyroid gland, and surrounding soft tissue. Open‐source image analysis software were employed to process CT data to generate high fidelity 3D models of the target structures. Resin molds were 3D printed and filled with various agar mixtures to mimic anatomical echogenicity.

Results

Following the method proposed, we successfully assembled the neck phantom which provided a detailed representation of the target structures. To evaluate the results, ultrasound data was collected on the phantom and living tissue and analyzed with ImageJ. We were able to demonstrate echogenicity comparable to that of living tissue.

Conclusion

The proposed method for building neck phantoms with detailed anatomical features offers a valuable, detailed, low‐cost tool for medical training and device testing in otolaryngology, particularly for novel devices that involve artificial intelligence (AI) guidance and robotic‐based needle insertion. Additional anatomical refinements and validation studies could further enhance the consistency and accuracy, thus paving the way for future advancements in ultrasound training and research, and ultimately benefiting patient care and safety.
Factors associated with total laryngectomy following organ‐preserving treatment of laryngeal SCC
Authors: Victor Mitchell T. , Faraji Farhoud , Voora Rohith , Kalavacherla Sandhya , Mell Loren K. , Rose Brent S. , Guo Theresa W.
Published: August 2024

Objective(s)

A subset of laryngeal squamous cell carcinoma (LSCC) patients undergoing larynx preserving treatment ultimately require total laryngectomy (TL) for oncologic or functional reasons. This study aims to identify TL risk factors in these patients.

Methods

Retrospective cohort study using Veterans Affairs (VA) database. T1–T4 LSCC cases treated with primary radiotherapy (XRT) or chemoradiotherapy (CRT) were assessed for TL and recurrence. Binary logistic and Cox regression and Kaplan–Meier analyses were implemented.

Results

Of 5390 cases, 863 (16.0%) underwent TL. On multivariable analysis, age (adjusted odds ratio: 0.97 [0.96–0.98]; p < .001) and N3 disease (0.42 [0.18–1.00]; p = .050) were associated with reduced risk of TL, whereas current alcohol use (1.22 [1.04–1.43]; p = .015) and >T1 disease (T2, 1.76 [1.44–2.17]; p < .001; T3, 2.06 [1.58–2.68]; p < .001; T4, 1.79 [1.26–2.53]; p = .001) were associated with increased risk of TL. However, N2 (adjusted hazard ratio: 1.30 [1.10–1.55]; p = .003) and N3 (2.02 [1.25–3.26]; p = .004) disease were associated with an increased risk for local recurrence. Compared to XRT, treatment with CRT was associated with reduced risk for local recurrence after adjusting for other factors (0.84 [0.70–0.99]; p = .044). Those who do not receive TL following local recurrence have poorer disease‐specific survival (log‐rank, p < .001). In patients without local recurrence, N2 disease was associated with a fourfold increase in risk of TL (4.24 [1.83–9.82]; p < .001).

Conclusion

Advanced nodal stage was associated with reduced rates of salvage TL in the setting of local recurrence, and subsequent worse prognosis after recurrence. Conversely, advanced nodal stage may increase the risk for functional salvage TL in patients without recurrence.

Level of Evidence

Level 3.