bluuebunny/crossref_metadata_2025 huggingface dataset:
A highly sensitive and stable MXene/bacterial cellulose double network hydrogel flexible strain sensor for human activities monitoring
Authors: Zhang Xuefeng , Sun Henghao , Zhang Jiayin , Wang Zhengdong
Published: November 2024

The limited strength and stability of conductive hydrogels greatly impede their practical applications in wearable devices. Therefore, a conductive double‐network hydrogel with high strength, high toughness, and high stability was prepared by one‐pot method in this paper. The rigid and flexible skeletons as well as the three‐dimensional dense honeycomb lattice network structure endow the hydrogel with good strength. The reversible cross‐linking synergistic effect between the rigid bacterial cellulose chains scaffolding uniformly dispersed Ti3C2 MXene nanosheets and the flexible acrylic acid chains doped with propylene glycol presents the hydrogel with excellent stability and elongation at break (862%). Consequently, a strain sensor based on the prepared hydrogel exhibits high sensitivity (GF = 1.28), rapid response (150 ms), and superior stability (over 2000 cycles) within a very wide strain range (5%–620%). Various strain signals generated by human activities are successfully detected by the presented strain sensor, which promises its broad applications in health monitoring.
Review of respiratory anatomy adaptations in whales
Authors: Reidenberg Joy S. , Laitman Jeffrey T.
Published: November 2024

Whales (cetaceans, including dolphins and porpoises) are superbly adapted to life in water, but retain vestiges of their terrestrial ancestry, particularly the need to breathe air. Their respiratory tract exhibits many differences from their closest relatives, the terrestrial artiodactyls (even toed ungulates). In this review, we describe the anatomy of cetacean respiratory adaptions. These include protective features (e.g., preventing water incursions during breathing or swallowing, mitigating effects of pressure changes during diving/ascent) and unique functions (e.g., underwater sound production, regulating gas exchange during the dive cycle).
Polymer Electrolytes with High Ionic Conductivities at Freezing Temperature for Aqueous Hybrid Batteries
Authors: Tian Zhongdong , Gao Yuan , Tian Peishu , Tian Silong , Shi Fengwei , Mei Jun
Published: November 2024

Rechargeable and flexible aqueous batteries (ABs) have emerged as one of promising energy devices which is primarily due to the safety, environmental friendliness and economic efficiency. However, because of the freezing behavior of aqueous electrolytes, most ABs possess poor performance when the working temperature drops below zero. To solve this problem, a gel polymer electrolyte (GPE) with high ionic conductivity (IC) and frost‐resistance is designed for aqueous Zn−Li hybrid batteries by a biomass‐based polymers complex consisting of carboxyl modified sodium alginate (SA) and zwitterionic betaine (BA). Introducing iminodiacetic acid to enrich −COOH groups along the SA main chains could improve IC of the prepared GPEs to 41.27 and 20.96 mS cm−1 at 20 and −20 °C, respectively. At −20 °C, the discharge capacity of the resultant cell is two times higher than that of the liquid electrolyte‐based cell, and the cell presents a capacity retention of 91.6 % after 300 charge/discharge cycles at 1 C. This proposed strategy greatly improve the IC of GPEs at freezing temperature, which is expected to broaden the practical application of GPEs in wide range of temperature.
Predictors of Immediate Deterioration of the Child‐Pugh Classification From A to B After Transcatheter Arterial Chemo‐Embolization for Treatment‐Naive Hepatocellular Carcinoma
Authors: Asano Kazuo , Kageyama Ken , Yamamoto Akira , Jogo Atsushi , Nakano Mariko , Murai Kazuki , Yukawa‐Muto Yoshimi , Odagiri Naoshi , Kotani Kohei , Kozuka Ritsuzo , Kawamura Etsushi , Fujii Hideki , Uchida‐Kobayashi Sawako , Enomoto Masaru , Kawada Norifumi , Miki Yukio
Published: November 2024

Aim

The purpose of this study was to evaluate the predictors of deterioration of the Child‐Pugh classification 1 month after transcatheter arterial chemo‐embolization (TACE) in patients with treatment‐naive hepatocellular carcinoma (HCC).

Methods

Between 2010 and 2020, consecutive patients who underwent conventional TACE using epirubicin as the initial treatment were enrolled. Patients with Barcelona Clinic Liver Cancer stage‐0, A or B and Child‐Pugh class A were included. The Child‐Pugh score was evaluated before treatment and 1 month after TACE. The following variables were analyzed by univariate and multivariate analyses as predictors of deterioration of the Child‐Pugh class from A to B: age, sex, etiology, serum albumin, bilirubin, prothrombin time (PT), encephalopathy, ascites, largest tumor diameter, tumor number, tumor location, α‐fetoprotein, protein induced by vitamin K absence or antagonist‐II, epirubicin dosage, ethiodized oil dosage, and number of treated liver segments.

Results

A total of 152 patients were retrospectively enrolled. The deterioration rate of the Child‐Pugh class from A to B was 8.6%. Multivariable analysis showed that serum albumin ≤ 3.8 g/dL, PT ≤ 80%, and largest tumor diameter ≥ 3.8 cm were predictors of deterioration of the Child‐Pugh class. The deterioration rate to Child‐Pugh class B was 0% in patients with up to one of these factors, 14.3% in those with two factors, and 70% in those with three factors.

Conclusions

A combination of serum albumin ≤ 3.8 g/dL, PT ≤ 80%, and largest tumor diameter ≥ 3.8 cm can predict the immediate deterioration of the Child‐Pugh classification from A to B following TACE.
xCT as a Predictor for Survival in a Population‐Based Cohort of Head and Neck Squamous Cell Carcinoma
Authors: Nissi Linda , Tuominen Sanni , Routila Johannes , Huusko Teemu , Ketonen Petra , Sundvall Maria , Leivo Ilmo , Irjala Heikki , Minn Heikki , Grönroos Tove J. , Ventelä Sami
Published: November 2024

Background

xCT, also known as SLC7A11 (solute carrier Family 7 Member 11), is a cystine/glutamate antiporter protein that mediates regulated cell death and antioxidant defense. The aim of this study was to investigate the effect of xCT on the outcome of patients diagnosed with new head and neck squamous cell carcinoma (HNSCC).

Methods

This retrospective cohort study utilized a population‐based dataset, comprising all patients (n = 1033) diagnosed with new HNSCC during 2005–2015 in a population of 697,000 people. All patients (n = 585) with a tumor tissue sample available for immunohistochemical (IHC) staining were included. The follow‐up rates were 97% and 81% at 3 and 5 years, respectively. Also, the specificity of the anti‐xCT antibody was validated.

Results

The expression level and prognostic significance of xCT were strongly dependent on tumor location. In oropharyngeal squamous cell carcinoma (OPSCC) patients, xCT expression was a significant prognostic factor for 5‐year overall survival (OAS) (HR: 2.71; 95% CI 1.67–4.39; p < 0.001), disease‐specific survival (DSS) (HR: 2.58; 95% CI 1.47–4.54; p = 0.001), and disease‐free survival (DFS) (HR: 2.69; 95% CI 1.55–4.64; p < 0.001). Five‐year survival rates for OPSCC patients with high and low levels of xCT were OAS 34% versus 62%; DSS 51% versus 73%; DFS 43% versus 73%, respectively. According to a multivariate model adjusted for age, T‐class, nodal positivity, and tobacco consumption, xCT was an independent prognostic factor for 3‐year survival, in which it outperformed p16 IHC. Similar associations were not observed in squamous cell carcinomas of oral cavity or larynx. Regarding treatment modalities, xCT was most predictive in HNSCC patients who received radiotherapy.

Conclusions

High xCT expression was associated with poor prognosis in OPSCC. Our findings suggest that joint analysis of xCT and p16 may add significant value in OPSCC treatment stratification.
Mature mediastinal teratoma with adhesions to the pericardium: A rare case report
Authors: Mansour Somar , Badr Ali , Mansour Majd , Badr Mouhamad , Afif Ali , Rajab Samer , Alshehabi Zuheir
Published: November 2024

Key Clinical Message

Mature mediastinal teratoma (MMT) is a benign tumor that is composed of well‐differentiated tissues from all three germ cell layers. Malignant tumors have a distinct feature of adhering to the surrounding organs. Therefore, adhesion of MMT to the adjacent tissues, as a benign tumor, is rare and considered a surgical challenge. It leads to incomplete tumor resection to avoid damage to the surrounding tissues.

MMT is a germ cell tumor that contains well‐differentiated tissues from ectodermal, mesodermal, and endodermal germ cell layers. MMT comprises approximately 3%–12% of mediastinal tumors in adults and 60%–70% of mediastinal germ cell tumors. Complete surgical resection is the standard treatment. When adhesion to the surrounding tissues is present, residual tissues could be retained to reduce the injury of the peripheral blood vessels and nerves. We are reporting a rare case of MMT with adhesions to the pericardium and discussing the diagnostic and surgical challenges.
N‐P Type Charge Compensatory Synergistic Effect for Schottky and Efficient Photoelectrocatalysis Applications: Doping Mechanism in (Nb/Re)@WS2/Graphene Heterojunctions
Authors: Zhou Zhonghao , Qi Wei , Li Zhi , Yang Li , Lin Zhichao , Guan Renguo
Published: November 2024

Band gap engineering based on doped two‐dimensional (2D) transition metal dichalcogenides (TMDs) has shown great potential in the design and development of new nano photoelectronic devices and their application in photoelectrocatalysis. However, there are two key issues that are difficult to take into account, namely the impurity levels induced by dopant atoms appear in the forbidden band of the doping system, which can become the recombination center of photogenerated carriers, thereby reducing the photocatalytic efficiency. Compared with the carrier mobility of the corresponding doped systems, that of intrinsic 2D TMDs is too low. Understanding the doping mechanism of heteroatoms in these systems and designing corresponding crystal structures rationally is important for solving these problems. In this study, the crystal structures of co‐doped monolayer WS2 with Nb and Re atoms were designed using density functional theory, and doping systems with graphene (high carrier mobility) were assembled into a heterostructure using the concept of heterorecombination. The N‐P type co‐doping of Nb and Re atoms retained the continuous band characteristics of the original monolayer WS2 while also providing the high carrier mobility of graphene, yielding an excellent multipurpose material for manufacturing high‐speed Schottky devices and efficient water‐splitting H evolution catalysts.
Origins of Catalysis in Non‐Heme Fe(II)/2‐Oxoglutarate‐Dependent Histone Lysine Demethylase KDM4A with Differently Methylated Histone H3 Peptides
Authors: Devadas Sudheesh , Thomas Midhun George , Rifayee Simahudeen Bathir Jaber Sathik , Varada Bhargav , White Walter , Sommer Ethan , Campbell Kylin , Schofield Christopher J. , Christov Christo Z.
Published: November 2024

Histone lysine demethylase 4 A (KDM4A), a non‐heme Fe(II)/2‐oxoglutarate (2OG) dependent oxygenase that catalyzes the demethylation of tri‐methylated lysine residues at the 9, 27, and 36 positions of histone H3 (H3 K9me3, H3 K27me3, and H3 K36me3). These methylated residues show contrasting transcriptional roles; therefore, understanding KDM4A's catalytic mechanisms with these substrates is essential to explain the factors that control the different sequence‐dependent demethylations. In this study, we use molecular dynamics (MD)‐based combined quantum mechanics/molecular mechanics (QM/MM) methods to investigate determinants of KDM4A catalysis with H3 K9me3, H3 K27me3 and H3 K36me3 substrates. In KDM4A‐H3(5–14)K9me3 and KDM4A‐H3(23–32)K27me3 ferryl complexes, the O−H distance positively correlates with the activation barrier of the rate‐limiting step, however in the KDM4A‐H3(32–41)K36me3, no direct one‐to‐one relationship was found implying that the synergistic effects between the geometric parameters, second sphere interactions and the intrinsic electric field contribute for the effective catalysis for this substrate. The intrinsic electric field along the Fe−O bond changes between the three complexes and shows a positive correlation with the HAT activation barrier, suggesting that modulating electric field can be used for fine engineering KDM catalysis with a specific substrate. The results reveal how KDM4A uses a combination of strategies to enable near equally efficient demethylation of different H3Kme3 residues.
Synthesis of 1,10‐Phenanthroline‐2,9‐bistriazoles: Evaluation as G‐Quadruplex Binders and Anti‐Tumor Activity
Authors: Figueiredo Joana , Carreira‐Barral Israel , Lourenço Pedro , Miranda André , Lopes‐Nunes Jéssica , Quesada Roberto , Laranjo Mafalda , Mergny Jean‐Louis , Cruz Carla
Published: November 2024

Novel 1,10‐phenanthroline‐2,9‐bistriazoles derivatives have been synthesized by copper‐catalyzed azide/alkyne cycloaddition reactions and assessed for their ability to bind and stabilize G‐quadruplex (G4) structures. Ten novel compounds were evaluated using Förster resonance energy transfer (FRET) melting, circular dichroism (CD), and fluorescence spectroscopy on several G4 sequences. Biophysical characterization led to the identification of compounds 4 a, 4 b, and 5 b as good G4 ligands of KRAS G4 sequences. The impact on cell viability of all derivatives was also assessed, revealing weak effects. However, compound 2 a exhibited cytotoxicity activity on A549 and H1299 cancer cells and low cytotoxicity towards MRC‐5 non‐malignant cells MRC‐5 not connected with its G4‐binding ability. Flow cytometry showed that 2 a induced a cell viability decrease in S and G2/M phases for A549 and H1299; thus, more studies should be performed to explore the proteins involved in cell cycle regulation.
Ac34deoGlcNAz: A Selective Probe for Identifying O‐GlcNAc‐Modified Proteins in Prostate Cancer
Authors: Xu Guoliang , Zhu Jiangtao , Wang Xihao , Liu Pengyue , Yan Yongjun , Li Xiaodong , Wang Lianqu , Wang Jiajia
Published: November 2024

GlcNAcylation is a prevalent protein modification in eukaryotic cells and increasing evidences indicated that over‐expressed O‐GlcNAcylation are intimately linked to the development and prognosis of prostate cancer. Thus, exploring this modification in the context of prostate cancer is vital for understanding the underlying mechanisms and hopefully used for future targeted therapies. In this paper, we use our previously established metabolic probes to comprehensively compare the labeling efficiency of O‐GlcNAc modified proteins in PC3 cells. Our results demonstrated that all the tested probes were non‐toxic to PC3 cells and only Ac4GlcNAz, Ac4GalNAz and Ac34deoGlcNAz exhibited robust labeling signals amongst the probes. Further investigations by western blot and flow cytometry analysis revealed that Ac34deoGlcNAz was a specific and efficient probe for intracelluar protein labeling with negligible S‐glyco‐modification signal. In addition, proteomic analysis further confirmed that 94 % of the proteins identified by Ac34deoGlcNAz were in the form of O‐linked GlcNAc rather than S‐glyco‐modification, these enriched O‐GlcNAcylated proteins were mainly involved in the regulated processes of prostate cancer. Our results here together prove Ac34deoGlcNAz is a safe and reliable probe for metabolic labeling O‐GlcNAc modified proteins in prostate cancer, providing a mean to fully exploit the regulatory mechanism of O‐GlcNAcylation in the process of prostate cancer.
Two‐Factor Rule for Distinguishing the Covalent and Tetrel Bonds
Authors: Bartashevich Ekaterina , Tsirelson Vladimir
Published: November 2024

Understanding and exploring the existence of a recognizable boundary between the noncovalent tetrel bond (TtB) and the coordination or weakened covalent bond are important for the bonding characterization. We have developed a simple methodology for analysing the type of bonds based on comparison of the electrostatic and total static potentials along the bond line. For the typical σ‐hole noncovalent bond formed by a Tt atom in a tetrahedral molecule, we have found that the space gap between positions of the maxima of the total static potential and the negative quantity of electrostatic potential is much wider than that for the coordination bonds in a trigonal bipyramid molecular system for the Cl−Tt/Cl⋅⋅⋅Tt and N−Tt/N⋅⋅⋅Tt (Tt=C, Si, Ge) bonds in molecules and molecular complexes. The distinction between the weakened covalent and strengthened noncovalent bonds is well reflected in behaviour of the Fermi hole along the bond line. Two‐factor empirical rule based on the superposition of the electrostatic and total static potentials is suggested.
High‐Performance Intermetallic Pt3Co/C Electrocatalyst for the Oxygen Reduction Reaction Synthesized by Pre‐Lithiation Method
Authors: Zhang Zhengying , Fang Dong , Li Liyang , Yang Hua , Liu Jian , Liu Feng , Gao Yong , Ruzimuradov Olim
Published: November 2024

Fuel cells are recognized as promising alternatives to existing conventional energy systems for a sustainable future. However, the synthesis of efficient and robust platinum (Pt) based catalysts remains a challenge for practical fuel cell applications. Herein, the Pt3Co/C nanoparticles with about 4.45 nm are firstly prepared by a “pre‐lithiation‐deposition” strategy on C carrier and used as efficient electrocatalysts for cathodic oxygen reduction reaction. Notably, after heat treatment at 600 °C, the obtained Pt3Co/C‐600 catalyst shows excellent mass and specific activities (MA and SA) of 0.69 A mg 
and 1.01 mA cm 
, respectively, which are more than one order of magnitude higher than that of Pt/C‐600. In particular, after accelerated durability testing with 20k cycles, the durability of the Pt3Co/C‐600 catalyst (98.3 % retention of MA) is much higher than that of Pt3Co/C‐600 without pre‐lithiation (42.5 % retention of MA). The alloying of Pt and Co and the use of “pre‐lithiation” to enable strong interactions between the carbon carriers and the Pt‐Co nanoparticles contributed to the increased activity and excellent stability. This work provides a new perspective for the development of high‐performance and low‐cost Pt alloy electrocatalysts.
A Simple Regeneration Process Using a CO2‐Switchable‐Polarity Solvent for Cellulose Hydrogels
Authors: Matsui Arata , Ayu Putri Deandra , Thomas Morgan L. , Takeoka Yuko , Rikukawa Masahiro , Yoshizawa‐Fujita Masahiro
Published: November 2024

Cellulose is one of the main components of plant cell walls, abundant on earth, and can be acquired at a low cost. Furthermore, there has been increasing interest in its use in environmentally friendly, carbon‐neutral, sustainable materials. It is expected that the applications of cellulose will expand with the development of a simple processing method. In this study, we dissolved cellulose in aqueous N‐butyl‐N‐methylpyrrolidinium hydroxide solution ([C4mpyr][OH]/H2O) and investigated the cellulose regeneration process based on changes in solubility upon application of CO2 gas. We investigated the effect of transformation of the anion chemical structure on cellulose solubility by flowing CO2 gas into [C4mpyr][OH]/H2O and conducted pH, FT‐IR, and 13C NMR measurements. We observed that the changes in anion structure allowed for the modulation of cellulose solubility in [C4mpyr][OH]/H2O, thus establishing a simple and safe cellulose regeneration process. This regeneration process was also applied to enable the production of cellulose hydrogels. The hydrogel formed using this method was revealed to have higher mechanical strength than an analogous hydrogel produced using the same dissolution solvent with the addition of a cross‐linker. The ability to produce cellulose‐based hydrogels of different mechanical properties is expected to expand the possible applications.
A beginner's guide to supervised analysis for mass cytometry data in cancer biology
Authors: Wlosik Julia , Granjeaud Samuel , Gorvel Laurent , Olive Daniel , Chretien Anne‐Sophie
Published: November 2024

Mass cytometry enables deep profiling of biological samples at single‐cell resolution. This technology is more than relevant in cancer research due to high cellular heterogeneity and complexity. Downstream analysis of high‐dimensional datasets increasingly relies on machine learning (ML) to extract clinically relevant information, including supervised algorithms for classification and regression purposes. In cancer research, they are used to develop predictive models that will guide clinical decision making. However, the development of supervised algorithms faces major challenges, such as sufficient validation, before being translated into the clinics. In this work, we provide a framework for the analysis of mass cytometry data with a specific focus on supervised algorithms and practical examples of their applications. We also raise awareness on key issues regarding good practices for researchers curious to implement supervised ML on their mass cytometry data. Finally, we discuss the challenges of supervised ML application to cancer research.
Generation and Characterization of a TRIM21 Overexpressing Mouse Line
Authors: Mehlmann Lisa M. , Uliasz Tracy F. , Yee Siu‐Pok , Kaback Deborah , Lowther Katie M.
Published: November 2024

Specific removal of a protein is a key to understanding its function. “Trim‐Away” utilizes TRIM21, an antibody receptor and ubiquitin ligase, for acute and specific reduction of proteins. When TRIM21 is expressed in cells, introduction of a specific antibody causes rapid degradation of the targeted protein; however, TRIM21 is endogenously expressed in few cell types. We have generated a mouse line using CRISPR to insert a conditional overexpression cassette of TRIM21 into the safe harbor site, Rosa26. These conditionally‐expressing mice can be bred to a wide variety of Cre mice to target cell‐specific TRIM21 overexpression in different tissues. Zp3Cre mice expressed TRIM21 protein specifically in oocytes, whereas HprtCre mice expressed the protein globally. When TRIM21‐overexpressing oocytes were microinjected with specific antibodies targeting either the IP3 receptor or SNAP23, these proteins were effectively degraded. In addition, cortical neural cells from globally‐overexpressing TRIM21 mice showed a dramatic reduction in IP3 receptor protein within hours after electroporation of a specific antibody. These experiments confirm the effectiveness of the Trim‐Away method for protein reduction. These mice should make a valuable addition to the broader research community, as a wide range of proteins and cell types can be studied using this method.
Template‐Free ZSM‐5 Synthesis Using Bio‐Sourced Waste Materials
Authors: Schneider Helena , Schmitz Thaís , Gomes Flores Camila , Louis Benoît , Cristina Tessaro Isabel , Romeu Marcilio Nilson
Published: November 2024

Hydrochars synthesized from lignocellulosic waste (rice husk and exhausted black wattle bark) through hydrothermal carbonization were used as pore‐forming agents in template‐free ZSM‐5 zeolites. The influence of the amount of hydrochar added to the zeolite synthesis and the nature of the hydrochar on the zeolite features and catalytic performance were evaluated. It was observed that the hydrochar had little influence on the textural properties and Si/Al ratio of the zeolites. However, the hydrochar was able to enhance the number of Brønsted acid sites in the zeolite and led to different ZSM‐5 crystal morphologies (french‐fries and twinned crystals). The latter zeolites exhibited a higher cracking activity of n‐hexane, favoring the formation of light olefins, due to the presence of Brønsted sites and suitable shape selectivity. In contrast, they exhibited a lower conversion of methanol into hydrocarbons (MTH), favoring the formation of dimethylether due to rapid deactivation. The hydrochars acted therefore, in the synthesis of template‐free ZSM‐5 zeolite, as a mean to both raise the acidity and control the aggregation of zeolite crystals.
Atomically Precise Rhodium‐Gold Carbonyl Nanoclusters: In‐Depth Synthesis and Multivalence Investigation of [Rh16Au6(CO)36]6−, and its Correlation with [Rh10Au(CO)26]3−
Authors: Ruggieri Silvia , Bussoli Guido , Bortoluzzi Marco , Cesari Cristiana , Funaioli Tiziana , Zacchini Stefano , Iapalucci Maria Carmela , Femoni Cristina
Published: November 2024

The synthesis of the previously‐reported atomically‐precise [Rh16Au6(CO)36]6− (1) nanocluster has been optimized by screening different reaction variables like solvent, stoichiometric ratio, counterion and atmosphere. Its multivalence properties have also been studied by means of electrochemical and spectroelectrochemical techniques; the results pointed out a remarkable electron‐sponge behaviour, as under such experimental conditions 1 is capable to release one electron and accept up to four more, while retaining its molecular structure. This scarce structural variation has been confirmed through DFT calculations on those species whose redox processes showed the maximum reversibility, namely [Rh16Au6(CO)36]7− and [Rh16Au6(CO)36]5−. Moreover, we report herein the isolation and characterization of the new [Rh10Au(CO)26]3− (2) nanocluster, which represents one of the major fallouts of the synthetic pathway investigation of 1. Finally, we disclosed the existence of further species that, from preliminary results, appear to be new large atomically‐precise Rh−Au nanoclusters, which will be the subject of future investigations. Cluster 2 has been identified via single‐crystal X‐ray diffraction analysis, and the characterization of both clusters 1 and 2 completed by infrared (IR) spectroscopy and Electrospray Ionization Mass Spectrometry (ESI‐MS).
Direct visualization of microwires in hybrid depth electrodes using high‐resolution photon‐counting CT
Authors: Smeijers Steven , Coudyzer Walter , Keirse Elina , Bougou Vasiliki , Decramer Thomas , Theys Tom
Published: November 2024

Hybrid depth electrodes are increasingly being used for epilepsy monitoring and human neurophysiology research. Microwires extending from the tip of the Behnke‐Fried (BF) electrode into (sub)cortical areas allow to isolate single neurons and perform microstimulation. Conventional CT or MRI visualize the entire microwire bundle as an artifact extending from the BF electrode tip with low resolution, without proper identification of individual microwires. We illustrate the first direct visualization method of individual microwires using high‐resolution photon‐counting CT (PCCT). Coregistration of the PCCT scan with a preoperative MRI can visualize individual wires directly in cortex, which is an advantage as it provides feedback on the accuracy of the implantation method and can guide future implantations. This PCCT technique allows for accurately depicting individual microwires which could be relevant for neuroscientific research through improved visualization and implantation of specific cortical and subcortical brain areas.

Plain Language Summary

Researchers are using hybrid depth electrodes to study epilepsy and brain activity. These electrodes, called Behnke‐Fried (BF) electrodes, have microwires at the tip that can record single neurons and stimulate brain areas. Regular CT or MRI scans do not show the individual microwires clearly. The authors use a new high‐resolution photon‐counting CT (PCCT) technique, which can show each individual microwire in the brain. By combining PCCT with MRI, the authors can precisely see where the microwires are located. This could improve future implantation surgeries and brain research.
Depression Treatment Trajectories and Associated Social Determinants: A Three‐Year Follow‐Up Study in 66,540 Older Adults Undergoing First‐Time Depression Treatment in Denmark
Authors: Ishtiak‐Ahmed Kazi , Rohde Christopher , Köhler‐Forsberg Ole , Christensen Kaj Sparle , Gasse Christiane
Published: November 2024

Objective

This study aimed to describe depression treatment patterns, identify unique trajectory groups using a group‐based trajectory approach, and explore associated social determinants in older adults undergoing first‐time depression treatment during a 3‐year follow‐up.

Methods

This Danish register‐based cohort study included all adults aged ≥ 65 who initiated depression treatment by redeeming first‐time antidepressant prescriptions (no prescriptions in the last 10 years) between 2006 and 2015. The outcome of interest during the 2‐year follow‐up was depression treatment, assessed as antidepressant prescriptions redemptions and psychiatric hospital contacts for depression. Latent class growth analyses were applied to model treatment trajectories during 3 years. Multinomial logistic regression analyses were used to analyze adjusted associations between social determinates and trajectory group membership.

Results

Among the 66,540 older adults (55.2% females, mean age: 77.3 years), we identified three distinct groups with unique patterns of depression treatment trajectories: ‘brief‐treatment’ where individuals stopped depression treatment within 6 months (33.7%); ‘gradual‐withdrawal’ (26.5%) where treatment was gradually stopped over 2 years; and ‘persistent‐treatment’ where individuals continued depression treatment for the entire 3 years (39.8%). Females, single‐person households, and residents of less‐urbanized regions were associated with higher odds of membership in the ‘persistent‐treatment’ group, while older age, widowhood or separation, and non‐Danish ethnicities were associated with lower odds.

Conclusions

Three distinct patterns of depression treatment trajectories were identified in older adults, indicating differential clinical courses of depression—potentially influenced by social determinants, including sex, marital status, urban residence, and ethnicity. Early patient stratification and targeted interventions are crucial in depression care for older adults.
Language Matters: The Semantics and Politics of “Assisted Dying”
Authors: Elsner Anna M. , Frank Charlotte E. , Keller Marc , McCullough Jordan O. , Rampton Vanessa
Published: November 2024

This essay examines the impact of linguistic choices on the perception and regulation of assisted dying, particularly in Canada. It argues that euphemistic terms like “medical assistance in dying” and its acronym, “MAID,” serve to normalize the practice, potentially obscuring its moral gravity. This contrasts with what is seen in Belgium and the Netherlands, where terms like “euthanasia” are used, as well as in France and the United Kingdom, where terminology remains divisive and contested. By tracing the evolution of these terms and what they reveal about different cultural and legal approaches, this essay sheds light on the politics of language in end‐of‐life discourses. It suggests that the shift toward euphemistic language reflects a broader discomfort with death that can shape public attitudes and legal frameworks. It calls for a more transparent, philosophically grounded approach to terminology and suggests that continued debate about semantics is necessary to capture the complexities and ethical significance of assisted dying.
Synthetic Health Data: Real Ethical Promise and Peril
Authors: Susser Daniel , Schiff Daniel S. , Gerke Sara , Cabrera Laura Y. , Cohen I. Glenn , Doerr Megan , Harrod Jordan , Kostick‐Quenet Kristin , McNealy Jasmine , Meyer Michelle N. , Price W. Nicholson , Wagner Jennifer K.
Published: November 2024

Researchers and practitioners are increasingly using machine‐generated synthetic data as a tool for advancing health science and practice, by expanding access to health data while—potentially—mitigating privacy and related ethical concerns around data sharing. While using synthetic data in this way holds promise, we argue that it also raises significant ethical, legal, and policy concerns, including persistent privacy and security problems, accuracy and reliability issues, worries about fairness and bias, and new regulatory challenges. The virtue of synthetic data is often understood to be its detachment from the data subjects whose measurement data is used to generate it. However, we argue that addressing the ethical issues synthetic data raises might require bringing data subjects back into the picture, finding ways that researchers and data subjects can be more meaningfully engaged in the construction and evaluation of datasets and in the creation of institutional safeguards that promote responsible use.
Parity, Poverty, and Physician Aid in Dying: Policy Recommendations for PAD in Light of Social Injustices
Authors: Walsh Em
Published: November 2024

In light of the proposed expansion of eligibility for physician aid in dying (PAD) in Canada to people with psychiatric disorders, there is a new subset of individuals seeking PAD—those with poverty‐induced depression. The dominant account defending the expansion is known as the “parity argument.” Defenders of the parity argument maintain that the expansion of PAD to those with psychiatric conditions is needed to reflect that the seriousness of a patient's suffering does not depend on the cause of that suffering. Parity accounts, as they stand, would allow cases of poverty‐induced depression to qualify. I raise a moral dilemma that the parity theorist must face considering this new subset of cases—expanding access to PAD, without adequate social protections, could produce more social inequality by aiming to reduce it. I propose six recommendations that policy‐makers should consider before expanding PAD given these cases, social injustice, and the social determinants of mental health.
Gender, Pediatric Care, and Evidence
Authors: Gorin Moti
Published: November 2024

This letter responds to the Other Voices commentaries “Troubling Trends in Health Misinformation Related to Gender‐Affirming Care,” by Stef M. Shuster and Meredithe McNamara; “Values and Evidence in Gender‐Affirming Care,” by Os Keyes and Elizabeth Dietz; “Breaking Binaries: The Critical Need for Feminist Bioethics in Pediatric Gender‐Affirming Care,” by Lisa Campo‐Engelstein, Grayson Jackson, and Jacob Moses; and “Minors Lack the Autonomy to Consent to Gender‐Affirming Care: Best Interests Must Be Primary,” by John C. Bester, in the May‐June 2024 issue of the Hastings Center Report.
On Normothermic Regional Perfusion
Authors: Lee Harrison
Published: November 2024

This letter responds to the article “Neither Ethical nor Prudent: Why Not to Choose Normothermic Regional Perfusion,” by Adam Omelianchuk et al., in the July‐August 2024 issue of the Hastings Center Report.
Adam Omelianchuk, Alexander Morgan Capron, Lainie Friedman Ross, Arthur R. Derse, James L. Bernat, and David Magnus reply:
Authors: Omelianchuk Adam , Capron Alexander Morgan , Ross Lainie Friedman , Derse Arthur R. , Bernat James L. , Magnus David
Published: November 2024

This letter responds to letters by Garson Leder and by Harrison Lee in the same issue, September‐October 2024, of the Hastings Center Report.
Moral Nuances in Broad Policies
Authors: Haupt Laura
Published: November 2024

In the September‐October 2024 issue of the Hastings Center Report, two pieces examine attitudes toward and policy on medical aid in dying (MAID). An essay by Anna Elsner and colleagues analyzes terminology, including euphemistic language, used in Canada and other countries to refer to this practice. The authors recommend explicit public discussion of the values at stake in the use of this terminology. An article by Em Walsh concerns a subset of people who could become eligible for MAID under Canada's proposed expansion of eligibility for this assistance: people suffering from poverty‐induced depression. Cautioning that the expansion of PAD could exacerbate inequality, Walsh offers six recommendations for policy‐makers’ consideration. The issue's lead article, by Eric Juengst and colleagues, focuses on governance issues that could be raised by human genome editing research that aims to strengthen individuals’ resistance to disease beyond what is regarded as the human functional range. Juengst et al. identify and analyze three potential principles that could help policy‐makers navigate what can be a blurry line between goals of prevention and enhancement in human genome editing research.
Frontoparietal Structural Network Disconnections Correlate With Outcome After a Severe Stroke
Authors: Frontzkowski Lukas , Fehring Felix , Frey Benedikt M. , Wróbel Paweł P. , Reibelt Antonia , Higgen Focko , Wolf Silke , Backhaus Winifried , Braaß Hanna , Koch Philipp J. , Choe Chi‐un , Bönstrup Marlene , Cheng Bastian , Thomalla Götz , Gerloff Christian , Quandt Fanny , Schulz Robert
Published: November 2024

Structural disconnectome analyses have provided valuable insights into how a stroke lesion results in widespread network disturbances and how these relate to deficits, recovery patterns, and outcomes. Previous analyses have primarily focused on patients with relatively mild to moderate deficits. However, outcomes vary among survivors of severe strokes, and the mechanisms of recovery remain poorly understood. This study assesses the association between lesion‐induced network disconnection and outcome after severe stroke. Thirty‐eight ischaemic stroke patients underwent MRI brain imaging early after stroke and longitudinal clinical follow‐up. Lesion information was integrated with normative connectome data to infer individual disconnectome profiles on a localized regional and region‐to‐region pathway level. Ordinal logistic regressions were computed to link disconnectome information to the modified Rankin Scale after 3–6 months. Disconnections of ipsilesional frontal, parietal, and temporal cortical brain areas were significantly associated with a worse motor outcome after a severe stroke, adjusted for the initial deficit, lesion volume, and age. The analysis of the underlying pathways mediating this association revealed location‐specific results: For frontal, prefrontal, and temporal brain areas, the association was primarily driven by relatively sparse intrahemispheric disconnections. In contrast, the ipsilesional primary motor cortex, the dorsal premotor cortex, and various parietal brain regions showed a remarkable involvement of either frontoparietal intrahemispheric or additionally interhemispheric disconnections. These results indicate that localized disconnection of multiple regions embedded in the structural frontoparietal network correlates with worse outcomes after severe stroke. Specifically, primary motor and parietal cortices might gain particular importance as they structurally link frontoparietal networks of both hemispheres. These data shed novel light on the significance of distinct brain networks for recovery after a severe stroke.
The Role of Radiotherapy in Indolent Ocular Adnexal and Orbital Lymphomas
Authors: Yazici Gozde , Akin Serkan , Kahvecioglu Alper , Yigit Ecem , Turker Fatma Alev , Yildiz Ferah
Published: November 2024

Background

This study evaluates the oncological outcomes and toxicities of indolent ocular adnexal and orbital lymphomas (OOLs) treated with radiotherapy (RT) ± systemic therapy.

Methods

A retrospective analysis of 44 patients with indolent OOLs treated with RT was conducted.

Results

Most patients (87%) had early‐stage disease. Treatment involved RT alone (34%) or RT + systemic therapy (66%). The median RT dose was 30 Gy, with a median follow‐up of 45 months. Local and systemic recurrence rates were 4% and 9%, respectively. Five‐year overall and disease‐free survival (DFS) rates were 96.2% and 83.6%. Early‐stage patients showed similar DFS rates regardless of whether they received RT alone or RT plus systemic therapy. No grade 3 RT‐related toxicity occurred, but systemic therapy led to grade 3 toxicity in 17% of patients.

Conclusions

RT is essential for treating indolent OOLs, and combination with systemic therapies does not enhance outcomes for early‐stage patients.
A silent pandemic of violence against providers in obstetrics and gynecology: A mixed‐methods study based on a global survey
Authors: Endler Margit , Ramirez‐Negrin Atziri , Sohail Rubina ,   the FIGO Committee on Women Facing Crises
Published: November 2024

Objectives

To quantify and qualify the experience of workplace violence (WPV) in a global sample of providers in obstetrics and gynecology (OBGYN).

Methods

We performed a mixed‐methods analysis on data from a global survey. Survey content was designed around categorical and open‐ended questions in relation to WPV; the occurrence and character, the physical and psychological consequences, training and support structures, and perceived triggers of the experience of WPV. Quantitative data were analyzed using descriptive statistics and text data using mixed deductive‐inductive content analysis. These data were integrated using convergent joint display.

Results

Between October 2023 and January 2024, survey responses were collected from 77 individual countries. Among the final sample, 764/1016 (75.2%) had experienced WPV, 699/1016 (68.8%) verbal, and 123/1016 (12.1%) physical violence. The violence affected physical health, psychological health, or job satisfaction for 106/764 (13.9%), 36/7642 (47.4%), and 222/764 (29.1%) of individuals respectively; 216/764 (28.3%) received support. Main WPV triggers were staff shortages, lack of security personnel, and long waiting times, identified by 38.8%, 37.5%, and 37.3% of respondents respectively. Qualitative data indicated that violence caused severe and long‐lasting suffering. Catalysts for WPV were often reported as complex interplays between unmet or unrealistic expectations and insufficient resources. Lack of support for WPV was explained as violence being “part of the job” and a culture of assumed resilience among providers.

Conclusion

WPV against OBGYN providers seems to be ubiquitous, arises from a complex interplay of factors, and causes significant injury while receiving insufficient mitigation and support.
Telemedicine ultrasound assessment for placenta accreta spectrum: Utility and interobserver reliability of asynchronous remote imaging review
Authors: Nieto‐Calvache Albaro José , Benavides‐Calvache Juan Pablo , Aryananda Rozi , Palacios‐Jaraquemada Jose M. , Jauniaux Eric , Fox Karin A. , Coutinho Conrado Milani , Adu‐Bredu Theophilus , Shih Jin‐Chung , Hussein Ahmed M. , Timor‐Tritsch Ilan E. , Bartels Helena C. , Hamer Jorge , Cali Giuseppe , D'Antonio Francesco , Nieto‐Calvache Alejandro Solo , López Jaime Octavio , Rivera‐Torres Luisa Fernanda , Pajkrt Eva , Rijken Marcus J.
Published: November 2024

Objective

Management of patients with placenta accreta spectrum (PAS) by trained multidisciplinary teams is associated with improved outcomes. Ultrasound can predict intraoperative risks, but expert ultrasound imaging of PAS is often limited. Telemedicine is used increasingly in obstetrics, permitting expert consultation when essential resources are not available locally. Our objective was to evaluate the feasibility of teleconsultation using standardized ultrasound image acquisition and reporting, and to correlate prognosis with intraoperative findings in patients at risk for PAS.

Methods

A total of 12 PAS imaging experts (teleconsultants) were selected to asynchronously review deidentified standardized grayscale and color Doppler ultrasound images for five patients who had completed treatment for PAS, resulting in 60 individual teleconsultations. All patients were managed at a center using standardized imaging acquisition and intraoperative topographic classification to individualize surgical management. Teleconsultants reported the predicted topographic classification and recommended a surgical approach based on the topographic classification algorithm. Prognoses were compared with that reported by the local sonologist and with intraoperative findings.

Results

In all five patients, local sonologist prognosis and antenatal topographic classification was confirmed during surgery and the final surgical approach matched that which was recommended preoperatively. Teleconsultant antenatal evaluation and management plans matched those of the local team in 71.7% of the cases. When reports differed, PAS severity was overestimated in nine reviews (16.9%) and was underestimated in six reviews (11.3%).

Conclusion

Remote imaging teleconsultation provides accurate prenatal staging in most patients at risk for PAS. Teleconsultation is a feasible strategy to improve prenatal imaging, management planning, and guidance for local teams in settings with limited healthcare resources.
Aminoacyl‐tRNA synthetase defects in neurological diseases
Authors: Zhang Hong , Ling Jiqiang
Published: November 2024

Aminoacyl‐tRNA synthetases (aaRSs) are essential enzymes to support protein synthesis in all organisms. Recent studies, empowered by advancements in genome sequencing, have uncovered an increasing number of disease‐causing mutations in aaRSs. Monoallelic aaRS mutations typically lead to dominant peripheral neuropathies such as Charcot–Marie–Tooth (CMT) disease, whereas biallelic aaRS mutations often impair the central nervous system (CNS) and cause neurodevelopmental disorders. Here, we review recent progress in the disease onsets, molecular basis, and potential therapies for diseases caused by aaRS mutations, with a focus on biallelic mutations in cytoplasmic aaRSs.
3D Bioprinting a Novel Skin Co‐Culture Model Using Human Keratinocytes and Fibroblasts
Authors: Andrade Thiago A. M. , da Silva Victor Allisson , Scheck Kali , Garay Tania , Sharma Ruchi , Willerth Stephanie M.
Published: November 2024

3D bioprinting can generate the organized structures found in human skin for a variety of biological, medical, and pharmaceutical applications. Challenges in bioprinting skin include printing different types of cells in the same construct while maintaining their viability, which depends on the type of bioprinter and bioinks used. This study evaluated a novel 3D bioprinted skin model containing human keratinocytes (HEKa) and human dermal fibroblasts (HDF) in co‐culture (CC) using a high‐viscosity fibrin‐based bioink produced using the BioX extrusion‐based bioprinter. The constructs containing HEKa or HDF cells alone (control groups) and in CC were evaluated at 1, 10, and 20 days after bioprinting for viability, immunocytochemistry for specific markers (K5 and K10 for keratinocytes; vimentin and fibroblast specific protein [FSP] for fibroblasts). The storage, loss modulus, and viscosity properties of the constructs were also assessed to compare the effects of keratinocytes and fibroblasts individually and combined, providing important insights when bioprinting skin. Our findings revealed significantly higher cell viability in the CC group compared to individual keratinocyte and fibroblast groups, suggesting the combined cell presence enhanced survival rates. Additionally, proliferation rates of both cell types remained consistent over time, indicating non‐competitive growth within the construct. Interestingly, keratinocytes exhibited a greater impact on the viscoelastic properties of the construct compared to fibroblasts, likely due to their larger size and arrangement. These insights contribute to optimizing bioprinting strategies for skin tissue engineering and emphasize the important role of different cell types in 3D skin models.