bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of Mycotoxin Response of DNA-Wrapped Nanotube Sensor with Machine Learning
Authors: Rabbani Yahya , Behjati Sara , Lambert Benjamin , Sajjadi Sayyed Hashem , Shariaty-Niassar Mojtaba , Boghossian Ardemis Anoush
Published: February 2024

DNA-wrapped single-walled carbon nanotubes (SWCNTs) have demonstrated great versatility in their use as optical sensors. SWCNTs emit a near-infrared fluorescence that is responsive to even the slightest changes in the nanotube environment, enabling sensors that can respond to single-molecule fluctuations within the vicinity of their surfaces. The fluorescence response and surface interactions of these sensors are determined by the DNA wrapping sequence. However, the lack of information on the relationship between the DNA sequence and its effect on the SWCNT fluorescence remains a bottleneck for designing sequences that are specific to analytes of interest. We have recently demonstrated the use of directed volution to control the fluorescence response of SWCNTs through DNA design. Iterative cycles of DNA mutation, screening, and selection allowed us to evolve sequences that yield DNA-wrapped SWCNT sensors with a desired fluorescence response to mycotoxins.

In this work, we apply the screening results of the DNA libraries used in this approach to train machine learning (ML) algorithms. Artificial neural network (ANN) and support vector machine (SVM) methods were used to predict the response of ssDNA-SWCNT sensors to a specific mycotoxin. The reliability of these models was further assessed through cross-validation. The ANN and SVM models with cross-validation were able to accurately classify the various DNA sequences as yielding either a high or low fluorescence response with an accuracy of 73 and 81%, respectively. The models were further used to predict the performance of alternative DNA sequences outside the initial training dataset, using the Hierarchy and k-means++ clustering methods to evaluate the similarity and dissimilarity of each DNA sequence. Compared to the SVM model, the ANN model showed an improved ability to predict high responses for dissimilar DNA sequences. We further applied a combinatorial approach based on SVM and ANN models to design new DNA sequences for improving sensor performance. The success of this approach was validated experimentally, demonstrating the rational design of improved sensors with 95% prediction accuracy.

The application of ML algorithms to directed evolution libraries of DNA thus allows one to accurately map the performances of these sensors within a particular sequence space. The computational success of this mapping provides a framework for replacing current empirical approaches with the rational design of DNA sequences for SWCNT sensing.

Keywords: Nano Biosensor, DNA-SWCNT, Mycotoxin, Machine learning, Directed evolution method.
Developing Hybrid Aqueous Li/Na-Ion Capacitors by Electrodes Synthesized by Facile Recycling and Reuse Process: Waste to Wealth
Authors: Das Himadri Tanaya
Published: February 2024

The explosive evolution of industrialization and technologies has grabbed eyeball attention in

the current scenario for improving the living standard of the human beings irrespective of the threat and risk possessed by the environment. So to overcome this catastrophe, there has been a significant focus on progressive development of electrochemical energy storage and conversion systems to resolve the intermittency nature of renewable energy sources. The electrochemical energy storage devices such as batteries and supercapacitors have been relied upon the ability to store the charge in the wide potential region with high Coulombic efficiency and long-term stability. However, transition metal oxides are well known, for their high theoretical specific capacity but suffer from low electronic conduction and capacity fading during cycling. To address these shortfalls metal oxides are usually, embedded within a conductive carbon-based matrix (for instance graphene). The use of graphene would afford easy pathway for electron movement and increases the surface area for higher interaction of active electrode materials with electrolyte. Subsequently, graphene based transition metal oxides composites have attracted active research pursuits in synthesizing the low cost effective electrode materials for energy storage devices. And if graphene is recycled and reused then it’s very much cheap and efficient electrodes for hybrid energy storage devices. In this work, electrode materials are developed by facile and economic approach with an aim to achieve improved electrochemical activity. The conversion of utilized electrode materials (e-waste) to efficient graphene electrodes (wealth) is validated in this research. The challenges in this work are (i) recycling pure samples, (ii) resynthesizing the graphene and tuning its layers, (iii) stability and efficiency of electrode materials, (iv) optimization of electrode materials and (v) practical demonstration of hybrid-ion capacitors. The fascinating part of the research finding is both the electrode materials are derived via. recycling, for which device can be promise to be sustainable and clean energy. The details will be presented in ECS conference. Such scheme could serve as precedent to the development of potential electrode materials for energy storage devices.
An-All-Solid State Supercapacitor Device from E-Waste Derived Activated Carbon
Authors: Dubey Prashant , Sundriyal Shashank , Maheshwari Priyanka
Published: February 2024

Recycling solid waste has substantial economic and environmental advantages. Electronic waste (e-waste) has the complex intrinsic trait of combining metals and non-metals contained in the same waste stream, which limits the recycling technologies that are now available for it. Much interest has been created by the outstanding surface and conductive qualities of carbon-based materials made from waste. In this article, we transformed e-waste (end of life keyboard) into highly porous activated carbon for its application as high-performance electrode material for supercapacitor. The as-synthesized activated carbon is characterized via material characterization techniques such as XRD, Raman, FTIR and BET. E-waste derived porous carbon (EWPC) rendered decent electrochemical performance in 1M H2SO4 electrolyte. Furthermore, an-all-solid-state symmetric supercapacitor device (EWPC//EWPC) has been fabricated and recorded convincing results in terms of energy density, power density, and cyclic stability. Hence, this study open up new avenues for recovering and creating high-performance, environmentally friendly materials from discarded e-wastes.
Advanced Characterization of Pillared Graphene-Based Materials for Supercapacitors
Authors: Ben Cherifi Yassine , Pouget Stephanie , Chenavier Yves , Dubois Lionel , Mendil-Jakani Hakima , Duclairoir Florence
Published: February 2024

Materials for supercapacitors have to display large surface area to maximize the number of adsorbed ions [1], and they must also possess a hierarchical porosity (Fig. 1) to favour ions diffusion. Graphene-derived materials are studied as they –theoretically- combine all these porosity-related parameters. However experimentally the achieved capacitance (CSP) remains limited because graphene sheets tend to re-aggregate. Our group has selected a method to avoid this issue by creating an expanded graphene structure by bridging and separating the sheets using aliphatic diamine pillars. These assemblies are called Pillared Graphene materials (PGM). Electrochemical results showed that these PGM display higher capacitance than reference non pillared materials [2,3]. However, it was not possible to correlate these storage performances improvements to adsorption active surface area determined with N2 gas sorption (BET), which questions the suitability of this technique for measuring the full porosity of the samples, which is likely to be more accessible in an electrolytic environment. Therefore, to further correlate storage performances of PGM to their structure, structural advanced characterization techniques such as small angle X-ray and neutron scattering (SAXS/SANS) were employed.

These methods enable to assess samples porosity at the local scale (~30 to 140nm) as well as the solid phase density. In the frame of this presentation, SAXS/SANS not only have been applied to pristine materials, but also to specifically formulated samples (pellet, electrodes) in order to highlight structural differences arising from synthesis protocol or from molecular pillaring. The ionic charge diffusion and adsorption in specific porosity ranges, analyzed using preliminary Operando scattering techniques, will be evoked. So far the interplay between increased adsorption sites and improved electrochemical performances has only been intuited on the basis of indirect electrochemical studies; the strategy devised herein proposes the use of direct structural techniques to confirm these interpretations.
Activated Carbon Nanofiber Sheets Derived from Electrospun Lignin: PVA Blend for Flexible Supercapacitors
Authors: Singh Mandeep , Gupta Ashish , Sundriyal Shashank , Dhakate Sanjay
Published: February 2024

The present investigation reports the performance of ultra-flexible activated carbon nanofiber sheets (ACNF) as a flexible electrode for supercapacitors application. ACNF was fabricated by pre-carbonization at 600 °C and then by activation using potassium hydroxide (KOH) at 800 °C.

These ACNF sheets prepared via the facile electrospinning technique possess the morphology of the nanofiber network with the diameter range (600-1400 nm) of the carbon. The findings demonstrate that the activation method not only enhances the sheet's surface area (806.9 m2/g) and total pore volume (0.519 cc/g) but also eliminates the lignin polymer's inherent sodium (Na) impurity through washing. This interconnected nanofiber sheet possesses high electrical conductivity of 8.40 S/cm. These sheets exhibit cloth-like flexibility with high electrical conductivity and porosity, making them suitable candidates for flexible electrodes. Raman spectroscopy was also carried out to get information about sp2 carbon. Cyclic Voltammetry (CV), Galvanostatic Charge-Discharge (GCD), and Electrochemical Impedance Spectroscopy (EIS) were performed to understand the electrochemical performance of the sheets as electrodes. This ACNF sheet demonstrate a higher specific capacitance of 203.29 F/g at a current density of 1 A/g in a three-electrode configuration. Furthermore, a flexible supercapacitor device was fabricated using an ACNF sheet due to its high flexibility, stand-alone character, and excellent performance as an electrode. The device exhibits a high energy density of 65.52 Wh/kg and a power density of 1036.27 W/kg with high coulombic efficiency (99.6%) after 10,000 cycles. Also, the prepared device illuminated the seven-segment display in various bending conditions showing its flexibility.
Study and Characterization of Solid State, Flexible, Wire-Shaped Supercapacitor for Textile Energy Storage Purpose
Authors: Seller Francesco , Serrapede Mara , Zaccagnini Pietro , Pedico Alessandro , Lamberti Andrea
Published: February 2024

Flexible and lightweight energy storage devices have become increasingly important for the development of wearable and portable electronics. In this work, we present a novel wire-shape supercapacitor based on carbon nanotube (CNT) yarns and an ionic liquid based polymer electrolyte. The combination of these materials offers high surface area, high conductivity and excellent flexibility, making them a promising candidate for flexible energy storage.

The CNT yarns were characterized in a three-electrode configuration by means of electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) either in water-based electrolytes and polymer electrolytes. The polymer electrolytes were prepared by mixing polymers with ionic liquid, which was characterized by thermal analysis and electrochemical measurements.

The wire-shape supercapacitor was assembled by coating two CNT yarns with the polymer electrolyte and twisting them together. The devices exhibited high specific capacitance for a waterless system, additionally, they maintained their performance even under extreme deformation: the flexibility of the devices were tested by bending at different angles .

Overall, this work highlights the advantages of using CNT yarns and ionic liquid polymer electrolytes for the development of flexible and high-performance supercapacitors. The wire-shape design of the device offers additional advantages for integration into wearable or flexible electronics, providing a promising path towards the development of highly efficient and adaptable energy storage systems.
NASA SPRINT exercise program efficacy for vastus lateralis and soleus skeletal muscle health during 70 days of simulated microgravity
Authors: Trappe Todd A. , Minchev Kiril , Perkins Ryan K. , Lavin Kaleen M. , Jemiolo Bozena , Ratchford Stephen M. , Claiborne Alex , Lee Gary A. , Finch W. Holmes , Ryder Jeffrey W. , Ploutz-Snyder Lori , Trappe Scott W.
Published: February 2024

This study provides unique exercise countermeasures development information for astronauts on long-duration spaceflights. The NASA SPRINT program was protective for quadriceps myocellular and whole muscle health, whereas the triceps surae (soleus) was only partially protected as has been shown with other programs. The bedrest control group data may provide beneficial information for overall exercise dose and targeting fast-twitch muscle fibers. Other unique approaches for the triceps surae are needed to supplement existing exercise programs.
Influence of the chest wall on respiratory function at birth in near-term lambs
Authors: Diedericks Cailin , Crossley Kelly J. , Davies Indya M. , Riddington Paige J. , Cannata Ebony R. , Martinez Olivia L. , Thiel Alison M. , te Pas Arjan B. , Hooper Stuart B.
Published: February 2024

This study investigated how changes in chest wall mechanics influence respiratory function after birth. Our data indicate that the application of continuous external subatmospheric pressure greatly improves respiratory function in near-term lambs with respiratory distress, whereas external positive pressures impair respiratory function. Our findings indicate that, during neonatal resuscitation at birth, the forces applied to the chest wall should not be ignored as they can have a major impact on neonatal respiratory function.
Comparison of skeletal muscle oxidative function in young, middle-aged, and older males and females with similar physical activity levels
Authors: Landers-Ramos Rian Q. , Merriman Kai , Chartier Gregory L. , Parks Jordyn , Park Hyunjeong , Knuth Nicolas D.
Published: February 2024

Compared with younger adults, mitochondrial capacity and microvascular reperfusion of the tibialis anterior (TA) muscle are well maintained in similarly physically active middle-aged and older adults, with no sex differences observed in either outcome. However, greater tissue oxygen utilization in older adults during walking highlights how whole body functional movement may place an additional demand on the TA that reveals a potential compensatory response to lower functional reserve not evident in distinct measures of mitochondrial capacity and microvascular reperfusion.
Ablation of skeletal muscle estrogen receptor alpha impairs contractility in male mice
Authors: Sullivan Brian P. , Collins Brittany C. , McMillin Shawna L. , Toussaint Elise , Stein Clara Z. , Spangenburg Espen E. , Lowe Dawn A.
Published: February 2024

We comprehensively measured in vitro and in vivo contractility of leg muscles with reduced estrogen receptor α (ERα) in male mice and reported that force generation and contraction kinetics are impaired. In contrast to findings in females, phosphorylation of myosin regulatory light chain cannot account for low force production in male skeletal muscle ERα knockout mice. These results indicate that ERα is required for optimal contractility in males and females but via sexually dimorphic means.
An interventional sheep model of severe aortic valve stenosis hemodynamics for the evaluation of alterations in coronary physiology and microvascular function
Authors: Minten Lennert , Langenaeken Tom , McCutcheon Keir , Bennett Johan , Van Hecke Manon , Algoet Michiel , Bézy Stéphanie , Duchenne Jürgen , Puvrez Alexis , Wouters Laurine , Voigt Jens-Uwe , Adriaenssens Tom , Desmet Walter , Sinnaeve Peter , Verbrugghe Peter , Oosterlinck Wouter , Claus Piet , Meuris Bart , Dubois Christophe
Published: February 2024

In an animal model of aortic valve stenosis (AS), coronary physiological changes are characterized by increased resting coronary flow and hyperemic coronary resistance. These changes can impact coronary indices frequently used to assess concomitant coronary artery disease (CAD). At this point, the best way to assess and treat CAD in AS remains unclear. Our data suggest that fractional flow reserve may underestimate CAD, and nonhyperemic pressure ratios may overestimate CAD severity before aortic valve replacement.
Lacrimal Drainage System and Nasal Cavity Melanoma after Complete Treatment of Conjunctival Melanoma
Authors: Veisi Amirreza , Dastborhan Zahra , Dastmardi Mohsen , Rezaie Kanavi Mozhgan , Rezaei Saeid
Published: February 2024

Malignant melanoma of the conjunctiva is a rare tumor of the ocular surface with potential fatal consequences and a high likelihood of recurrence. Although routes for extending the tumor, including local, hematogenous, and lymphatogenous, are pretty straightforward, the indirect extension through free-floating tumoral cells to the nasolacrimal duct is not described thoroughly. We report a case of malignant melanoma of the conjunctiva which presented with local recurrence in the intranasal cavity and lacrimal sac two years after the primary surgery (without involvement of the ocular surface and punctum on the second occasion). However, there was no evidence of distant metastasis on either occasion. This case demonstrates the possible noncontiguous spreading route of melanoma tumoral cells and highlights the need for attention to the surgical technique, and careful follow-up to detect further disease activity.
YOLO‐UNet Architecture for Detecting and Segmenting the Localized MRI Brain Tumor Image
Authors: Iriawan Nur , Pravitasari Anindya A. , Nuraini Ulfa S. , Nirmalasari Nur I. , Azmi Taufik , Nasrudin Muhammad , Fandisyah Adam F. , Fithriasari Kartika , Purnami Santi W. , Irhamah  , Ferriastuti Widiana
Published: February 2024

Brain tumor detection and segmentation are the main issues in biomedical engineering research fields, and it is always challenging due to its heterogeneous shape and location in MRI. The quality of the MR images also plays an important role in providing a clear sight of the shape and boundary of the tumor. The clear shape and boundary of the tumor will increase the probability of safe medical surgery. Analysis of this different scope of image types requires refined computerized quantification and visualization tools. This paper employed deep learning to detect and segment brain tumor MRI images by combining the convolutional neural network (CNN) and fully convolutional network (FCN) methodology in serial. The fundamental finding is to detect and localize the tumor area with YOLO‐CNN and segment it with the FCN‐UNet architecture. This analysis provided automatic detection and segmentation as well as the location of the tumor. The segmentation using the UNet is run under four scenarios, and the best one is chosen by the minimum loss and maximum accuracy value. In this research, we used 277 images for training, 69 images for validation, and 14 images for testing. The validation is carried out by comparing the segmentation results with the medical ground truth to provide the correct classification ratio (CCR). This study succeeded in the detection of brain tumors and provided a clear area of the brain tumor with a high CCR of about 97%.
Effect of Sustainable Pretreatments on the Nutritional and Functionality of Chickpea Protein: Implication for Innovative Food Product Development
Authors: Patil Nikhil Dnyaneshwar , Bains Aarti , Sridhar Kandi , Rashid Summya , Kaur Sawinder , Ali Nemat , Chawla Prince , Sharma Minaxi
Published: February 2024

Chickpea is a globally cultivated legume, rich in vitamins, protein, carbohydrates, polyphenols, fatty acids, fibers, and flavonoids. Despite its nutritional benefits, chickpeas contain antinutritional factors that can hinder nutrient absorption. Therefore, we reviewed the various pretreatment methods to enhance chickpea protein’s nutritional value and functional properties. Thermal and biochemical treatments and food applications of chickpea protein are thoroughly reviewed. The review revealed that the physical, thermal, and biochemical treatments were reported to be effective in reducing antinutritional factors and improving protein solubility, emulsifying capacity, and foaming properties. Chickpea proteins were used in cereals and bakery products to meet consumer demand. Encapsulation of chickpea protein enhances nutrient stability, and its inclusion in gluten-free products has different effects on the glycemic index, antioxidant activity, and overall acceptability. These findings highlight chickpea’s potential to improve the nutritional and functional aspects of food products while offering health benefits to consumers.
An Accelerated Fixed-Point Algorithm Applied to Quadratic Convex Separable Knapsack Problems
Authors: Alves Atécio , Silva Jônatas O. L. , Matioli Luiz C. , Santos Paulo S. M. , Souza Sissy S.
Published: February 2024

In this article, we propose a root-finding algorithm for solving a quadratic convex separable knapsack problem, which is more straightforward than existing methods and competitive in practice. Besides, we also present an extension of the proposal, which improves its computational time, and then we incorporate the accelerated Anderson’s and Aitken’s fixed-point algorithms to obtain better results. The algorithm only performs function evaluations. We present partial convergence results of the algorithm. Moreover, we illustrate superior computational results in medium and large problems as well as the applicability of the algorithm with real-life applications to show their efficiency.
Fuzzy Fractional Differential Equation Involving the Fuzzy Conformable Derivative and the α−Semigroups
Authors: Ibrahim Abdou Amir Fouad , El Ghazouani Aziz , El Omari M’hamed , Melliani Said
Published: February 2024

In this work, we discuss solutions to the abstract Cauchy problem of fuzzy conformal fractional. In addition, the method of fuzzy fractional semigroups is used to obtain analytical solutions to the fractional differential equation. We use the concept of Krasnoselskii’s fixed point theorem to determine the existence and uniqueness of the solution. An application is also given to illustrate our main abstract results.
Figure 2 from ESR1 F404 Mutations and Acquired Resistance to Fulvestrant in ESR1-Mutant Breast Cancer
Authors: Kingston Belinda , Pearson Alex , Herrera-Abreu Maria Teresa , Sim Li-Xuan , Cutts Rosalind J. , Shah Heena , Moretti Laura , Kilburn Lucy S. , Johnson Hannah , Macpherson Iain R. , Ring Alistair , Bliss Judith M. , Hou Yingwei , Toy Weiyi , Katzenellenbogen John A. , Chandarlapaty Sarat , Turner Nicholas C.
Published: February 2024

Acquired mutations on fulvestrant. A, Incidence of acquired alterations (n = 69 assessable patients), colored by targetability of the alterations (Methods). Level 2B denotes the highest level of supporting evidence (“Standard care biomarker recommended by the National Comprehensive Cancer Network or other professional advice guidelines predictive of response to an FDA-approved drug”), whereas level 4 is the lowest (“Compelling biochemical evidence supports the biomarker as being predictive of response to a drug”). B, Incidence of acquired ESR1 mutations (n = 14 patients) and resultant amino acid changes. C,ESR1 F404 locus in the DNA-binding domain of the estrogen receptor. The number of base changes identified within the data set that result in the three different missense mutations are illustrated using https://proteinpaint.stjude.org/ (36). D,cis/trans analysis of F404 and E380Q in the three patients with assessable targeted sequencing data. Both alleles of chromosome 6 are represented, with annotated locations of the F404 and E380Q on each respective allele representing the cis/trans relationship of the variants. E, Mutations at phenylalanine 404 result in the substitution of amino acid residues without an aromatic ring. F,In silico modeling predicts the aromatic ring of F404 contributes to a pi-stacking bond between the receptor and both estrogen and fulvestrant.
Figure 1 from ESR1 F404 Mutations and Acquired Resistance to Fulvestrant in ESR1-Mutant Breast Cancer
Authors: Kingston Belinda , Pearson Alex , Herrera-Abreu Maria Teresa , Sim Li-Xuan , Cutts Rosalind J. , Shah Heena , Moretti Laura , Kilburn Lucy S. , Johnson Hannah , Macpherson Iain R. , Ring Alistair , Bliss Judith M. , Hou Yingwei , Toy Weiyi , Katzenellenbogen John A. , Chandarlapaty Sarat , Turner Nicholas C.
Published: February 2024

Baseline ESR1 mutations and fulvestrant efficacy. A, % Incidence of mutations in indicated genes at baseline in Cohort A (n = 79 assessable patients). B, Incidence of baseline ESR1 alterations within Cohort A (n = 79 assessable patients). C, PFS of patients in Cohort A, divided by baseline ESR1 Y537C mutation status (left) and ESR1 Y537S mutation status (right). P values from the log-rank test. HR >1 denotes worse PFS for that group. WT, wild-type; mt, mutant. D, MCF7 cells were cotransfected with the indicated ESR1 expression constructs and treated with the indicated concentration of fulvestrant in the presence of 1 nmol/L estradiol for 24 hours and estrogen response element-luciferase reporter activity determined. Two independent experiments.
Supplementary Figure 5 from NKG2A Is a Therapeutic Vulnerability in Immunotherapy Resistant MHC-I Heterogeneous Triple-Negative Breast Cancer
Authors: Taylor Brandie C. , Sun Xiaopeng , Gonzalez-Ericsson Paula I. , Sanchez Violeta , Sanders Melinda E. , Wescott Elizabeth C. , Opalenik Susan R. , Hanna Ann , Chou Shu-Ting , Van Kaer Luc , Gomez Henry , Isaacs Claudine , Ballinger Tarah J. , Santa-Maria Cesar A. , Shah Payal D. , Dees Elizabeth C. , Lehmann Brian D. , Abramson Vandana G. , Pietenpol Jennifer A. , Balko Justin M.
Published: February 2024

Combination anti-PDL1 and anti-NKG2A treatment in genetically modified tumors
Supplementary Figure 4 from NKG2A Is a Therapeutic Vulnerability in Immunotherapy Resistant MHC-I Heterogeneous Triple-Negative Breast Cancer
Authors: Taylor Brandie C. , Sun Xiaopeng , Gonzalez-Ericsson Paula I. , Sanchez Violeta , Sanders Melinda E. , Wescott Elizabeth C. , Opalenik Susan R. , Hanna Ann , Chou Shu-Ting , Van Kaer Luc , Gomez Henry , Isaacs Claudine , Ballinger Tarah J. , Santa-Maria Cesar A. , Shah Payal D. , Dees Elizabeth C. , Lehmann Brian D. , Abramson Vandana G. , Pietenpol Jennifer A. , Balko Justin M.
Published: February 2024

Immune and collagen profiling of murine MHC-IHET tumors.
Supplementary Data Table S9 from Loss-of-Function but Not Gain-of-Function Properties of Mutant TP53 Are Critical for the Proliferation, Survival, and Metastasis of a Broad Range of Cancer Cells
Authors: Wang Zilu , Burigotto Matteo , Ghetti Sabrina , Vaillant François , Tan Tao , Capaldo Bianca D. , Palmieri Michelle , Hirokawa Yumiko , Tai Lin , Simpson Daniel S. , Chang Catherine , Huang Allan Shuai , Lieschke Elizabeth , Diepstraten Sarah T. , Kaloni Deeksha , Riffkin Chris , Huang David C.S. , Li Wai Suen Connie S.N. , Garnham Alexandra L. , Gibbs Peter , Visvader Jane E. , Sieber Oliver M. , Herold Marco J. , Fava Luca L. , Kelly Gemma L. , Strasser Andreas
Published: February 2024

Supplementary Table S9 showing the impact of removal of mutant KRAS in human cancer cell lines in vitro by RNAi by mining the DepMap database
Supplementary Data Figure S19 from Loss-of-Function but Not Gain-of-Function Properties of Mutant TP53 Are Critical for the Proliferation, Survival, and Metastasis of a Broad Range of Cancer Cells
Authors: Wang Zilu , Burigotto Matteo , Ghetti Sabrina , Vaillant François , Tan Tao , Capaldo Bianca D. , Palmieri Michelle , Hirokawa Yumiko , Tai Lin , Simpson Daniel S. , Chang Catherine , Huang Allan Shuai , Lieschke Elizabeth , Diepstraten Sarah T. , Kaloni Deeksha , Riffkin Chris , Huang David C.S. , Li Wai Suen Connie S.N. , Garnham Alexandra L. , Gibbs Peter , Visvader Jane E. , Sieber Oliver M. , Herold Marco J. , Fava Luca L. , Kelly Gemma L. , Strasser Andreas
Published: February 2024

Supplementary Figure S19 showing that removal of mutant TP53 does not impair the migration of human cancer cell lines in vitro
Supplementary Data Figure S17 from Loss-of-Function but Not Gain-of-Function Properties of Mutant TP53 Are Critical for the Proliferation, Survival, and Metastasis of a Broad Range of Cancer Cells
Authors: Wang Zilu , Burigotto Matteo , Ghetti Sabrina , Vaillant François , Tan Tao , Capaldo Bianca D. , Palmieri Michelle , Hirokawa Yumiko , Tai Lin , Simpson Daniel S. , Chang Catherine , Huang Allan Shuai , Lieschke Elizabeth , Diepstraten Sarah T. , Kaloni Deeksha , Riffkin Chris , Huang David C.S. , Li Wai Suen Connie S.N. , Garnham Alexandra L. , Gibbs Peter , Visvader Jane E. , Sieber Oliver M. , Herold Marco J. , Fava Luca L. , Kelly Gemma L. , Strasser Andreas
Published: February 2024

Supplementary Figure S17 showing that removal of mutant TP53 does not impact colony formation of human cancer cell lines in vitro
Supplementary Data Figure S10 from Loss-of-Function but Not Gain-of-Function Properties of Mutant TP53 Are Critical for the Proliferation, Survival, and Metastasis of a Broad Range of Cancer Cells
Authors: Wang Zilu , Burigotto Matteo , Ghetti Sabrina , Vaillant François , Tan Tao , Capaldo Bianca D. , Palmieri Michelle , Hirokawa Yumiko , Tai Lin , Simpson Daniel S. , Chang Catherine , Huang Allan Shuai , Lieschke Elizabeth , Diepstraten Sarah T. , Kaloni Deeksha , Riffkin Chris , Huang David C.S. , Li Wai Suen Connie S.N. , Garnham Alexandra L. , Gibbs Peter , Visvader Jane E. , Sieber Oliver M. , Herold Marco J. , Fava Luca L. , Kelly Gemma L. , Strasser Andreas
Published: February 2024

Supplementary Figure S10 showing that complete removal of mutant TP53 in MDA-MB-468 cells does not impair survival and proliferation in culture
Supplementary Table 4 from Alveolar Differentiation Drives Resistance to KRAS Inhibition in Lung Adenocarcinoma
Authors: Li Zhuxuan , Zhuang Xueqian , Pan Chun-Hao , Yan Yan , Thummalapalli Rohit , Hallin Jill , Torborg Stefan , Singhal Anupriya , Chang Jason C. , Manchado Eusebio , Dow Lukas E. , Yaeger Rona , Christensen James G. , Lowe Scott W. , Rudin Charles M. , Joost Simon , Tammela Tuomas
Published: February 2024

Supplementary Table 4 shows the differential gene expression analysis of autochthonous KP LUAD cells following treatment with vehicle or MRTX1133.
Supplementary Table 2 from Alveolar Differentiation Drives Resistance to KRAS Inhibition in Lung Adenocarcinoma
Authors: Li Zhuxuan , Zhuang Xueqian , Pan Chun-Hao , Yan Yan , Thummalapalli Rohit , Hallin Jill , Torborg Stefan , Singhal Anupriya , Chang Jason C. , Manchado Eusebio , Dow Lukas E. , Yaeger Rona , Christensen James G. , Lowe Scott W. , Rudin Charles M. , Joost Simon , Tammela Tuomas
Published: February 2024

Supplementary Table 2 shows the differential gene expression analysis of lineage-traced AT2 cell progeny expressing shRenilla or shKras following hyperoxia injury.
Supplementary Data Figure S21 from Loss-of-Function but Not Gain-of-Function Properties of Mutant TP53 Are Critical for the Proliferation, Survival, and Metastasis of a Broad Range of Cancer Cells
Authors: Wang Zilu , Burigotto Matteo , Ghetti Sabrina , Vaillant François , Tan Tao , Capaldo Bianca D. , Palmieri Michelle , Hirokawa Yumiko , Tai Lin , Simpson Daniel S. , Chang Catherine , Huang Allan Shuai , Lieschke Elizabeth , Diepstraten Sarah T. , Kaloni Deeksha , Riffkin Chris , Huang David C.S. , Li Wai Suen Connie S.N. , Garnham Alexandra L. , Gibbs Peter , Visvader Jane E. , Sieber Oliver M. , Herold Marco J. , Fava Luca L. , Kelly Gemma L. , Strasser Andreas
Published: February 2024

Supplementary Figure S21 showing that removal of mutant TRP53 does not impact the growth and survival of Eu-Myc mouse lymphoma cells in vitro and in vivo
Precision Targeting of Mutant PI3Kα
Authors: Gong Grace Q. , Vanhaesebroeck Bart
Published: February 2024

PIK3CA, which encodes the p110α catalytic subunit of PI 3-kinase alpha (PI3Kα), is one of the most frequently genetically activated kinases in solid tumors. In two back-to-back papers, Varkaris and colleagues report on the development of a novel allosteric PI3Kα-mutant–selective inhibitor and early clinical experience with this compound.

See related article by Varkaris et al., p. 227 (6) .

See related article by Varkaris et al., p. 240 (5) .
INHBA is Enriched in HPV-negative Oropharyngeal Squamous Cell Carcinoma and Promotes Cancer Progression
Authors: Abou Kors Tsima , Hofmann Linda , Betzler Annika , Payer Kathrina , Bens Martin , Truong Jens , von Witzleben Adrian , Thomas Jaya , Kraus Johann M. , Kalaajieh Randa , Huber Diana , Ezić Jasmin , Benckendorff Julian , Greve Jens , Schuler Patrick J. , Ottensmeier Christian H. , Kestler Hans A. , Hoffmann Thomas K. , Theodoraki Marie-Nicole , Brunner Cornelia , Laban Simon
Published: February 2024

Patients with oropharyngeal squamous cell carcinoma (OPSCC) caused by human papilloma virus (HPV) exhibit a better prognosis than those with HPV-negative OPSCC. This study investigated the distinct molecular pathways that delineate HPV-negative from HPV-positive OPSCC to identify biologically relevant therapeutic targets. Bulk mRNA from 23 HPV-negative and 39 HPV-positive OPSCC tumors (n = 62) was sequenced to uncover the transcriptomic profiles. Differential expression followed by gene set enrichment analysis was performed to outline the top enriched biological process in the HPV-negative compared with HPV-positive entity. INHBA, the highest overexpressed gene in the HPV-negative tumor, was knocked down. Functional assays (migration, proliferation, cell death, stemness) were conducted to confirm the target's oncogenic role. Correlation analyses to reveal its impact on the tumor microenvironment were performed. We revealed that epithelial-to-mesenchymal transition (EMT) is the most enriched process in HPV-negative compared with HPV-positive OPSCC, with INHBA (inhibin beta A subunit) being the top upregulated gene. INHBA knockdown downregulated the expression of EMT transcription factors and attenuated migration, proliferation, stemness, and cell death resistance of OPSCC cells. We uncovered that INHBA associates with a pro-tumor microenvironment by negatively correlating with antitumor CD8+ T and B cells while positively correlating with pro-tumor M1 macrophages. We identified three miRNAs that are putatively involved in repressing INHBA expression. Our results indicate that the upregulation of INHBA is tumor-promoting. We propose INHBA as an attractive therapeutic target for the treatment of INHBA-enriched tumors in patients with HPV-negative OPSCC to ameliorate prognosis.

Significance:

Patients with HPV-negative OPSCC have a poorer prognosis due to distinct molecular pathways. This study reveals significant transcriptomic differences between HPV-negative and HPV-positive OPSCC, identifying INHBA as a key upregulated gene in HPV-negative OPSCC's oncogenic pathways. INHBA is crucial in promoting EMT, cell proliferation, and an immunosuppressive tumor environment, suggesting its potential as a therapeutic target for HPV-negative OPSCC.
Genomic Characterization and Clinical Outcomes of Patients with Peritoneal Metastases from the AACR GENIE Biopharma Collaborative Colorectal Cancer Registry
Authors: Sanz-Garcia Enrique , Brown Samantha , Lavery Jessica A. , Weiss Jessica , Fuchs Hannah E. , Newcomb Ashley , Postle Asha , Warner Jeremy L. , LeNoue-Newton Michele L. , Sweeney Shawn M. , Pillai Shirin , Yu Celeste , Nichols Chelsea , Mastrogiacomo Brooke , Kundra Ritika , Schultz Nikolaus , Kehl Kenneth L. , Riely Gregory J. , Schrag Deborah , Govindarajan Anand , Panageas Katherine S. , Bedard Philippe L.
Published: February 2024

Peritoneal metastases (PM) are common in metastatic colorectal cancer (mCRC). We aimed to characterize patients with mCRC and PM from a clinical and molecular perspective using the American Association of Cancer Research Genomics Evidence Neoplasia Information Exchange (GENIE) Biopharma Collaborative (BPC) registry. Patients’ tumor samples underwent targeted next-generation sequencing. Clinical characteristics and treatment outcomes were collected retrospectively. Overall survival (OS) from advanced disease and progression-free survival (PFS) from start of cancer-directed drug regimen were estimated and adjusted for the left truncation bias. A total of 1,281 patients were analyzed, 244 (19%) had PM at time of advanced disease. PM were associated with female sex [OR: 1.67; 95% confidence interval (CI): 1.11–2.54; P = 0.014] and higher histologic grade (OR: 1.72; 95% CI: 1.08–2.71; P = 0.022), while rectal primary tumors were less frequent in patients with PM (OR: 0.51; 95% CI: 0.29–0.88; P < 0.001). APC occurred less frequently in patients with PM (N = 151, 64% vs. N = 788, 79%) while MED12 alterations occurred more frequently in patients with PM (N = 20, 10% vs. N = 32, 4%); differences in MED12 were not significant when restricting to oncogenic and likely oncogenic variants according to OncoKB. Patients with PM had worse OS (HR: 1.45; 95% CI: 1.16–1.81) after adjustment for independently significant clinical and genomic predictors. PFS from initiation of first-line treatment did not differ by presence of PM. In conclusion, PM were more frequent in females and right-sided primary tumors. Differences in frequencies of MED12 and APC alterations were identified between patients with and without PM. PM were associated with shorter OS but not with PFS from first-line treatment.

Significance:

Utilizing the GENIE BPC registry, this study found that PM in patients with colorectal cancer occur more frequently in females and right-sided primary tumors and are associated with worse OS. In addition, we found a lower frequency of APC alterations and a higher frequency in MED12 alterations in patients with PM.
Exploring Traditional Medicine Diagnostic Classification for Parkinson’s Disease Using Hierarchical Clustering
Authors: Zhao HuiYan , Kwon Ojin , Cha Jiyun , Jung In Chul , Jun Purumea , Jang Jae Young , Jang Jung-Hee
Published: February 2024

Introduction: Personalized diagnosis and therapy for Parkinson’s disease (PD) are needed due to the clinical heterogeneity of PD. Syndrome differentiation (SD) in traditional medicine (TM) is a diagnostic method for customized therapy that comprehensively analyzes various symptoms and systemic syndromes. However, research identifying PD classification based on SD is limited. Methods: Ten electronic databases were systematically searched from inception to August 10, 2021. Clinical indicators, including 380 symptoms, 98 TM signs, and herbal medicine for PD diagnosed with SD, were extracted from 197 articles; frequency statistics on clinical indicators were conducted to classify several subtypes using hierarchical clustering. Results: Four distinct cluster groups were identified, each characterized by significant cluster-specific clinical indicators with 95% confidence intervals of distribution. Subtype 2 had the most severe progression, longest progressive duration, and highest association with greater late-stage PD-associated motor symptoms, including postural instability and gait disturbance. The action properties of the herbal formula and original SD presented in the data sources for subtype 2 were associated with Yin deficiency syndrome. Discussion/Conclusion: Hierarchical clustering analysis distinguished various symptoms and TM signs among patients with PD. These newly identified PD subtypes may optimize the diagnosis and treatment with TM and facilitate prognosis prediction. Our findings serve as a cornerstone for evidence-based guidelines for TM diagnosis and treatment.
Multi-Stakeholder Opinion Statement on the Care of Individuals Born with Differences of Sex Development: Common Ground and Opportunities for Improvement
Authors: Cools Martine , Cheng Earl Y. , Hall Joanne , Alderson Julie , Amies Oelschlager Anne-Marie , Balen Adam H. , Chan Yee-Ming , Geffner Mitchell E. , Gravholt Claus H. , Güran Tülay , Hoebeke Piet , Lee Peter , Magritte Ellie , Matos Dina , McElreavey Ken , Meyer-Bahlburg Heino F.L. , Rink Richard C. , Springer Alexander , Szymanski Konrad M. , Vilain Eric , Williams Jo , Wolffenbuttel Katja P. , Sandberg David E. , Subramaniam Ramnath
Published: February 2024

Background: In the last 15 years, the care provided for individuals born with differences of sex development (DSD) has evolved, with a strong emphasis on interdisciplinary approaches. However, these developments have not convinced some stakeholders to embrace the current model of care. This care model has also paid insufficient attention to socio-cultural differences and global inequalities. Summary: This article is an opinion statement, resulting from in-depth discussions and reflection among clinicians, patients, and family support organizations based in the USA and Europe, where we seek areas of common ground and try to identify opportunities to further develop resources. The product of these conversations is summarized in 10 panels. The corresponding sections provide additional discussion on some of the panel items. Key Messages: Participants identified areas of agreement, gained a deeper understanding of the reasons behind disagreements on certain matters, and identified the necessary steps to foster future consensus. We offer preliminary recommendations for guiding clinical management and resource allocation. By promoting a broader consensus, we aim to enhance the quality of care and well-being for individuals of all ages who have a DSD.
Effect of Hemodialysis with Medium Cut-Off versus High-Flux Membranes on Endothelial Function of Patients with Chronic Kidney Disease
Authors: Armani Rachel Gatti , Carvalho Aluizio Barbosa , Vercia Rocha e Silva Monique , Verardino Renata , Bortolotto Luiz , Canziani Maria Eugenia F.
Published: February 2024

Introduction: Endothelial dysfunction (ED) is considered a marker of vascular complications, especially in patients with end-stage kidney disease (ESKD). Inflammation and the uremic state contribute to ED in patients undergoing hemodialysis (HD). Recently, the medium cut-off (MCO) dialysis membrane has been proposed to efficiently remove inflammatory cytokines and large, middle-sized uremic toxins, with the potential effect to improve endothelial function. This study aimed to compare the effect of dialysis with MCO or high-flux membranes on the endothelial function of patients on chronic HD. Methods: A prospective, randomized, crossover study in which 32 patients with ESKD were dialyzed for 12 weeks with each membrane, including a 4-week washout period between treatments. Endothelial function was assessed by flow-mediated dilation (FMD) using brachial artery ultrasound at weeks 1, 12, 16, and 28. Results: The population consisted of 59% men, 52.7 ± 13.4 years, 16% non-black, on HD for 8.8 (4.1–15.1) years, and 72% with arteriovenous fistula. Hypertension was the most common etiology of chronic kidney disease, and 34% of patients had previous cardiovascular disease. Patients were grouped, regardless of treatment sequence, into MCO or high-flux groups, since no carryover (p = 0.634) or sequence (p = 0.998) effects were observed in the FMD assessment. The ANOVA model with repeated measures showed no effects of treatment (p = 0.426), time (p = 0.972), or interaction (p = 0.413) in the comparison of FMD between the MCO and high-flux groups. Conclusion: Dialysis performed with MCO, or high-flux membranes, had no influence on endothelial function in patients undergoing HD. However, a trend towards increased FMD was observed with the use of the MCO membrane.
Secular Trends in Outcomes and Impact of Novel Oral Anticoagulants in Atrial Fibrillation–Related Acute Ischemic Stroke
Authors: Lee Minwoo , Lee Byung-Chul , Yu Kyung-Ho , Oh Mi-Sun , Kim Beom Joon , Kim Jun Yup , Kang Jihoon , Lee Keon-Joo , Kim Do Yeon , Park Jong-Moo , Kang Kyusik , Park Tai Hwan , Lee Kyung Bok , Hong Keun-Sik , Park Hong-Kyun , Cho Yong-Jin , Kim Dong-Eog , Lee Soo Joo , Kim Jae Guk , Lee Jun , Cha Jae-Kwan , Kim Dae-Hyun , Kim Joon-Tae , Choi Kang-Ho , Choi Jay Chol , Sohn Sung-il , Hong Jeong-Ho , Lee Sang-hwa , Kim Chulho , Shin Dong-Ick , Yum Kyu Sun , Lee Juneyoung , Lee Ji Sung , Gorelick Philip B. , Bae Hee-Joon ,   on behalf of the CRCS-K Investigators
Published: February 2024

BACKGROUND:

Novel oral anticoagulants (NOACs) are currently recommended for the secondary prevention of stroke in patients with acute ischemic stroke (AIS) accompanied by atrial fibrillation (AF). However, the impact of NOACs on clinical outcomes in real-world practice remains ambiguous. This study analyzes the trend of clinical events in patients with AF-related AIS and determines how much the introduction of NOACs has mediated this trend.

METHODS:

We identified patients with AIS and AF between January 2011 and December 2019 using a multicenter stroke registry. Annual rates of NOAC prescriptions and clinical events within 1 year were evaluated. The primary outcome was a composite of recurrent stroke, myocardial infarction, and all-cause mortality. To assess the mediation effect of NOACs on the relationship between the calendar year and these outcomes, we used natural effect models and conducted exposure-mediator, exposure-outcome, and mediator-outcome analyses using multivariable regression models or accelerated failure time models, adjusting for potential confounders.

RESULTS:

Among the 12 977 patients with AF-related AIS, 12 500 (average age: 74.4 years; 51.3% male) were analyzed after excluding cases of valvular AF. Between 2011 and 2019, there was a significant decrease in the 1-year incidence of the primary composite outcome from 28.3% to 21.7%, while the NOAC prescription rate increased from 0% to 75.6%. A 1-year increase in the calendar year was independently associated with delayed occurrence of the primary outcome (adjusted time ratio, 1.10 [95% CI, 1.07–1.14]) and increased NOAC prescription (adjusted odds ratio, 2.20 [95% CI, 2.14–2.27]). Increased NOAC prescription was associated with delayed occurrence of the primary outcome (adjusted time ratio, 3.82 [95% CI, 3.17 to 4.61]). Upon controlling for NOAC prescription (mediator), the calendar year no longer influenced the primary outcome (adjusted time ratio, 0.97 [95% CI, 0.94–1.00]). This suggests that NOAC prescription mediates the association between the calendar year and the primary outcome.

CONCLUSIONS:

Our study highlights a temporal reduction in major clinical events or death in Korean patients with AF-related AIS, mediated by increased NOAC prescription, emphasizing NOAC use in this population.
Russian Aggression against Ukraine and the Making of Refugees
Authors: Burtsev Dmytro
Published: February 2024

This article examines the Russian invasion of Ukraine from the perspectives of Russian ideology, the tools used by the Russian Federation in the war against Ukraine, and refugee-making. The article uses offensive realism as an approach to understanding the actions of Russia against Ukraine. Russian full-scale aggression against Ukraine in February 2022 provoked international crises in numerous dimensions: political, security, humanitarian, and ecological. It became not only a war between countries, but a war between ways of thinking and ideologies. The reasoning and international policies behind this war might have very different and controversial interpretations; however, some explanation can be found by analyzing Russian inner-political discourse during the last two decades and the development of Russian ideology. The key research question of the article concerns the issue of Russian ideology and its role in Russia’s full-scale invasion of Ukraine.