bluuebunny/crossref_metadata_2025 huggingface dataset:
Double CHEK2 Pathogenic and Low-Risk Variants and Associated Cancer Phenotypes
Authors: Bychkovsky Brittany L. , Agaoglu Nihat B. , Horton Carolyn , Polfus Linda , Richardson Marcy E. , Young Colin , Scheib Rochelle , Garber Judy E. , Rana Huma Q.
Published: January 2025

Importance

CHEK2 pathogenic and likely pathogenic variants (PVs) are common, and low-risk (LR) variants, p.I157T, p.S428F, and p.T476M, are even more common. Biallelic CHEK2 PVs are associated with specific cancer phenotypes, including early age at onset of breast cancers. Whether biallelic LR variants are associated with cancer predisposition is unknown.

Objective

To characterize the cancer phenotype among individuals with biallelic CHEK2 variants, specifically those that have been associated with lower cancer risk in the heterozygous state.

Design, Setting, and Participants

This retrospective observational cohort study examining cancer phenotype by CHEK2 genotype was conducted at a single diagnostic genetic testing laboratory. Of 36 821 individuals who underwent genetic testing, 3783 (10.3%) with CHEK2 PVs or LR variants were ascertained from July 1, 2012, to September 30, 2019. Analyses were conducted from September 2022 to January 2024.

Exposures

Cancer phenotype among individuals with 2 LR variants and those with 1 PV and 1 LR variant was compared with cancer phenotype among individuals with wild type (WT) (n = 33 034), single LR variant (n = 1566), single PV controls (n = 2167), and 2 PVs (n = 21). Cancer phenotypes were investigated for any cancer, multiple primary cancers, female breast cancer, and bilateral female breast cancers.

Main Outcomes and Measures

Cancer phenotype of CHEK2 2 LRs and 1 PV and 1 LR.

Results

Of 36 821 individuals, 92.1% were female, and the median age at testing was 53 years (IQR, 44-63 years); 3787 (10.3%) were identified as having a CHEK2 PV or LR variant. There were 13 individuals with 2 LR variants and 20 with 1 PV and 1 LR variant. Among those with 2 LR variants, prevalence of any cancer (76.9%) and breast cancer (60.0%) were similar to those with WT (any cancer, 69.8%; breast cancer, 52.7%) and those with a single LR variant (any cancer, 70.9%; breast cancer, 57.5%). Among participants with 1 PV and 1 LR variant, 95.0% had a prior cancer diagnosis, a higher rate than among those with a single PV (76.8%), but the difference was not statistically significant. Among female individuals with 1 PV and 1 LR variant, 86.7% had a breast cancer diagnosis, compared with 67.1% with a single PV, although these differences were not statistically significant.

Conclusions and Relevance

In this cohort study, individuals with 2 LR variants in CHEK2 had a cancer phenotype similar to those with a single LR variant and similar to WT controls. Individuals with 1 PV and 1 LR variant may have a more penetrant cancer phenotype than individuals with a single PV. Future studies focused on CHEK2 LR variants will aid in better understanding whether these variants are genetic modifiers associated with cancer risk.
Geographic Distribution of US Ophthalmic Surgical Subspecialists
Authors: Ahmed Aishah , Ali Muhammad , Dun Chen , Cai Cindy X. , Makary Martin A. , Woreta Fasika A.
Published: January 2025

Importance

While urban counties maintain higher densities of ophthalmologists than rural counties, the geographic distribution of ophthalmic surgical subspecialists has not yet been elucidated. A potential workforce discrepancy may impact the burden of care faced by rural surgeons.

Objective

To assess the geographic distribution of the ophthalmic subspecialist surgeon workforce and evaluate factors associated with practicing in rural areas.

Design, Setting, and Participants

This cross-sectional population-based study of Medicare patients and surgeons performing subspecialized procedures took place from 2012 through 2022. Medicare Fee-for-Service claims were analyzed in 2023 for patients 65 years or older who underwent subspecialized ophthalmic procedures between 2012 and 2022 using Current Procedural Terminology codes (n = 1 619 043). Surgeons were defined as a subspecialist based on Current Procedural Terminology codes, indicating performance of at least 1 subspecialty procedure from the following subspecialties: cornea, glaucoma, oculoplastic, retina, or strabismus (n = 13 526).

Main outcomes and measures

The primary outcome was the population density of practice for subspecialist surgeons and residence for patients (rural or urban). The secondary outcomes were the characteristics associated with rural practice.

Results

Among 13 526 ophthalmic surgical subspecialists, 9823 were male (72.6%), 3235 were female (26.8%), and 4484 (33.2%) practiced in the South. There were 2540 cornea subspecialists (18.5%), 3676 glaucoma subspecialists (26.8%), 1951 oculoplastic subspecialists (14.2%), 4123 retina subspecialists (30.0%), and 1236 strabismus subspecialists (9.0%). Across subspecialties, a higher proportion of patients (17.4%; 95% CI, 16.9%-17.9%) resided in rural areas relative to surgeons (5.6%; 95% CI, 5.3%-5.9%) with differences ranging from 6.2% to 14.8% across subspecialities. Female surgeons (adjusted odds ratio [aOR], 0.63; 95% CI, 0.51-0.79; P < .001), surgeons in the Northeast (aOR, 0.62; 95% CI, 0.48-0.78; P < .001), surgeons in the West (aOR, 0.63; 95% CI, 0.50-0.79; P < .001), and recent graduates relative to those who graduated 11 to 20 years ago (aOR, 1.66; 95% CI, 1.25-2.21; P < .001), 21 to 30 years ago (aOR, 1.83; 95% CI, 1.38-2.42; P < .001), or 31 years ago or longer (aOR, 1.43; 95% CI, 1.08-1.90; P = .013), were less likely to practice rurally.

Conclusions and Relevance

This cross-sectional study between 2012 and 2022 identified higher proportions of rural patients compared with rural surgeons. Percentages of rural surgeons declined over time, with female surgeons and recent medical school graduates less likely to practice rurally. This suggests a disparity in the number of rural subspecialist surgeons available to serve rural patients.
Review of Ferroelectric Materials and Devices toward Ultralow Voltage Operation
Authors: Wang Aiji , Chen Rui , Yun Yu , Xu Jeffrey , Zhang Jinxing
Published: January 2025

Ferroelectrics are considered to be promising candidates for highly energy‐efficient electronic devices in future information technologies owing to their nonvolatile and low‐energy operation of spontaneous electric polarization. Driven by the pervasive and growing demands for miniaturization and energy efficiency in nanoelectronics, further reductions in the operating voltage of ferroelectric‐based devices are dispensable and thus have received immense attentions. Recent remarkable advances in atomic‐scale synthesis, cutting‐edge characterizations, and multiscale theoretical calculations of ferroelectrics have gained unprecedented insights into the manipulation of emergent functionalities in multiple length scales, which helps the discovery of nontrivial polar structures and designs of device architectures toward the promise of ultralow‐power consumption. Here, state‐of‐the‐art strategies for reducing operating voltage in ferroelectric materials and devices are reviewed. This article starts with a brief introduction and major achievements in ferroelectrics, and expounds on the techniques to probe the polarization‐switching process. Moreover, this article focuses predominantly on recent advancements in achieving low operating voltages through various prevalent strategies such as thickness scaling, defect engineering, chemical doping, surface and interfacial design, strain engineering. Finally, perspectives with scientific and technical challenges are discussed, aiming to facilitate the energy‐efficient applications of ferroelectric materials and devices in future information technologies.
All‐Electric Functional PdSe2 Planar‐Hall Logic Field‐Effect Transistors
Authors: Chen Ciao‐Fen , Huang Tzu‐Chuan , Wu Pei‐Tzu , Chou Yu‐An , Wang Chin‐Te , Cheng Shu‐Min , Lin Shu‐Fu , Chen Wan‐Hsin , Amrit Pratyay , Kuo Chia‐Nung , Watanabe Kenji , Taniguchi Takashi , Lin Chun‐Liang , Lue Chin‐Shan , Lin Yen‐Fu , Lo Shun‐Tsung
Published: January 2025

2D semiconductor logic has advantages of reconfigurable multi‐state operation through extrinsic charge‐transfer doping mechanisms such as molecular adsorption and light illumination. However, their precise control remains challenging and they bring defects and blur the specified logic protocol for computation. Semiconducting 2D layered palladium diselenide (PdSe2), a noble transition‐metal dichalcogenide with a puckered pentagonal atomic structure, has shown great potential for multi‐functional devices owing to its low crystal symmetry. Here, anisotropic charge transport in band‐like, variable‐range hopping, and quantum‐dot tunneling regimes are demonstrated in a multi‐terminal PdSe2 transistor. The gate‐tunable oscillatory Hall charge movement due to zero‐magnetic‐field pseudo‐planar Hall effect provides a physical reference to encode the dynamical PdSe2 anisotropic energy dispersions up to room temperature. Complementary XOR and XNOR logic relations between Hall voltage output and gate/drain voltage inputs are identified and they are reconfigurable with each other by changing the current injection direction. Controlling the layer number further reconfigures the planar‐Hall effect polarity and Hall logic. This work paves an all‐electric reconfigurable way to a planar‐Hall logic transistor, enabling the initialization, manipulation, and detection of anisotropic electronic states, and offers opportunities for next‐generation computing utilizing multiple energy bands of engineered anisotropies in puckered pentagonal 2D materials.
Realizing C–C Coupling via Accumulation of C1 Intermediates within Dual‐Vacancy‐Induced Dipole‐Limited Domain Field to Propel Photoreduction of CO2‐to‐C2 Fuel
Authors: Li Yang , Chen Yujie , Wang Qiu , Ye Yinyue , Zeng Jianshan , Liu Zhi
Published: January 2025

Photocatalytic conversion of CO2 and H2O into high‐value‐added C2 fuels remains a tough challenge, mainly due to the insufficient concentration of photogenerated electrons for the instability of C1 intermediates, which often tend to desorb easily and disable to form C─C bonds. In this work, photoreduction of CO2‐to‐C2H6 is successfully achieved by introducing adjacent C, N dual‐vacancy sites within the heptazine rings of ultrathin g‐C3N4, which results in the opening of two neighboring heptazine rings and forms a distinctive dipole‐limited domain field (DLDF) structure. In situ X‐ray photoelectron spectra and in situ fourier transform infrared spectra provide direct evidence of the rapid accumulation and transformation of C1 intermediates, especially CO* and CHO*, within the DLDF. Ab initio molecular dynamics further substantiates the role of DLDF in promoting C–C coupling between CO* and CHO*, through the analysis of interaction trajectories and energy changes of their central atoms, ultimately achieving a high yield of C2H6 up to 57.86 µmol g−1 h−1. It is for the first time to propose the concept of DLDF for significant advancement in photoreduction of CO2‐to‐C2 fuel with the evident breakthrough to address the challenge of coupling carbon‐containing intermediates between active sites, offering new insights for the design of C–C coupling sites in single‐component photocatalysts.
Alzheimer's disease plasma biomarkers and physical functioning in a diverse sample of adults
Authors: Knell Gregory , Hall James R. , Large Stephanie , Abdullah Lubnaa , Petersen Melissa , Johnson Leigh A. , O'Bryant Sid E.
Published: January 2025

INTRODUCTION

The relationship between Alzheimer's disease (AD) plasma biomarkers, and physical functioning (PF) across diverse races and ethnicities remains unclear. This study aims to explore this association in an ethno‐racially diverse sample of cognitively unimpaired community‐dwelling adults.

METHODS

Data clinical examinations, neuropsychological tests, blood draws, and PF exams (Timed Up and Go [TUG] and Short Physical Performance Battery [SPPB]) were analyzed. Multivariable linear regressions assessed the association between PF and AD plasma biomarkers (amyloid beta [Aβ]40, Aβ42, total tau [t‐tau], neurofiliament light chain [NfL]).

RESULTS

The sample (n = 2358; mean age 64.7 years; 65.9% female), was 20% African American, 41.9% non‐Hispanic White, and 38.1% Hispanic. Findings indicate that worse PF is linked to higher biomarker levels (p < 0.05). Associations differed by race and ethnicity group. TUG time was associated (p < 0.05) with Aβ40, Aβ42, and tau among non‐Hispanic Whites, whereas SPPB scores were associated (p < 0.05) with t‐tau and NfL among African Americans.

DISCUSSION

PF, ethnic/racial, and plasma AD biomarker data should be used to aid in developing risk profiles for neurodegenerative diseases.

Highlights

Alzheimer's disease (AD) biomarkers are associated with physical functioning (PF)

Ethno‐racial variation exists in AD biomarker and PF associations

Race and ethnicity should considered when assessing neurodegenerative disease risk
π‐Conjugated Polymers for High‐Performance Organic Electrochemical Transistors: Molecular Design Strategies, Applications and Perspectives
Authors: Chen Zhicai , Ding Xinliang , Wang Junwei , Guo Xugang , Shao Shiyang , Feng Kui
Published: January 2025

The last decade has witnessed significant progress in organic electrochemical transistors (OECTs) due to their enormous potential applications in various bioelectronic devices, such as artificial synapses, biological interfaces, and biosensors. The remarkable advance in this field is highly powered by the development of novel organic mixed ionic/electronic conductors (OMIECs). π‐Conjugated polymers (CPs), which are widely used in various optoelectronics, are emerging as key channel materials for OECTs. In this review, after briefly introducing OECT, we then mainly focus on the latest progress in CPs for high‐performance OECTs. The correlations of their structure, basic physicochemical properties, and device performance are elucidated by evaluating their electronic characters, optoelectronic properties, and OECT performance. Then, the applications of CP‐based OECTs are briefly presented. Finally, we discuss several remaining issues or challenges in this field and give our insights into advancing CPs for enhanced OECT performance.
External Base‐Free Approach for Copper‐Catalyzed N‐Arylation of Indoles and Pyrroles in Green Reaction Medium
Authors: Tahu Mohendra , Konwar Dipika , Dolakasharia Dibyashree , Bora Utpal
Published: January 2025

N‐Arylated heterocyclic molecules are extensively found as key components in numerous pharmaceutical and agrochemical compounds. Herein, inexpensive 1,10‐phenanthroline‐assisted copper‐catalyzed sustainable greener methodology has been developed for N‐arylation of indoles and pyrrole under commercial base and additive‐free conditions. Waste biomass–derived water extract of banana peel ash (WEB) has been used as safe reaction medium and base instead of hazardous solvents, and hence, the current green protocol has achieved an environmentally benign profile. Reaction of pyrrole with aryl iodides and electronically diverse indoles with aryl iodides/aryl bromides in the presence of CuI as catalyst, 1,10‐phenanthroline as ligand, and WEB as a base and solvent at 100°C has furnished N‐arylated product within 12 h. Reaction of indoles with aryl iodides furnished up to 93% yields while aryl bromides resulted in up to 54% yield of the desired product. The utilization of waste biomass derivative for organic transformation reaction is the key step of this protocol, which is in consistence with the goals of green chemistry.
Synthesis and Antibacterial Properties of New Quinazoline Analogs Catalyzed by Chloroacetic Acid–Immobilized Nanocobaltferrite
Authors: Navazi Fatemeh , Gholami Ahmad , Mokhtary Masoud , Nikpassand Mohammad , Asadpour Leila
Published: January 2025

In this research, an effective procedure for the one‐pot construction of new quinazoline analogs using chloroacetic acid–immobolized nanocobaltferrite (nano‐CoFe2O4@SiO2@CPTES‐[(Ph₂PCH₂)₂‐CH2CO2H]2+2Cl−) as an efficient novel magnetic nanocatalyst under ultrasound irradiation at 80°C was presented. Chloroacetic acid–immobilized nanocobferrite was characterized by FT‐IR, XRD, FE‐SEM, TEM, EDX, TGA, VSM, and ICP‐mass analyses. Furthermore, the nanocatalyst could be comfortably isolated via magnetic attraction and recycled at least five times without remarkable loss of its catalytic activity. Additionally, in this protocol, quinazoline analogs were screened for their antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus. The results showed that quinazolines 4a, 4b, 4c, 4d, and 4g had good antibacterial activity toward Pseudomonas aeruginosa and Staphylococcus aureus.
Improving Tribological Performance of Flame‐Sprayed Polyamide Coatings via Incorporation of Oil‐Containing Microcapsules
Authors: Chen Zhaoxiang , Hu Linglong , Ren Limei , Wang Jingbo , Qian Lihe
Published: January 2025

In order to improve the tribological performance of polyamide 11 (PA11) coatings, oil‐containing microcapsules, consisting of the heat‐resistant polysulfone (PSF) as the wall material and the polyalphaolefin 40 (PAO40) oil as the core material, were fabricated by the solvent evaporation method and then incorporated into PA11 coatings via the flame spray process. The microstructure and tribological performance of PA11 coatings were investigated before and after the incorporation of PAO40@PSF microcapsules. Results show that the synthesized PAO40@PSF microcapsules had an average diameter of 70 μm and exhibited good heat stability up to 380°C. Surface and cross‐sectional observations of coatings reveal that PAO40@PSF microcapsules were uniformly embedded in the PA11 coating. The incorporation of PAO40@PSF microcapsules had remarkable influence on the tribological performance of PA11 coatings. Specifically, comparing the PA11/PAO40@PSF composite coating containing 10 wt.% microcapsules to the pure PA11 coating, the friction coefficient and the wear rate were reduced by 67% and 45%, respectively, under the normal load of 370 N and at the rotational speed of 100 r/min. However, further increase in the content of PAO40@PSF microcapsules up to 15 wt.% resulted in a spike in the wear rate due to the decreased coating hardness and bonding strength.
Investigation of the Molecular Level Interaction in [CH3OH−CH2X2] Complexes (X=I, Br, and Cl) using Matrix‐Isolation IR Spectroscopy
Authors: Kumar Agrawal Sumit , Chakraborty Amrita , Chakraborty Shamik
Published: January 2025

The
(X=Cl, Br, and I) complexes have been studied to understand the tendency towards the formation of hydrogen bonds and halogen bonds. Three different types of interactions viz., C–X
O, C‐H
O, and O‐H
X, are possible between the
and
. Experiments have been carried out in low temperature
matrix using Fourier Transform Infrared spectroscopy. Electronic structure calculations have been performed to identify the possible binding motifs between
and
. Formation of more than one complex has been confirmed in
(X=Br and I) mixture, using the experimental and simulated IR spectra, whereas only one type of complex is found in
mixture. Energy decomposition analysis, quantum theory of atoms in molecules, and non‐covalent interaction analysis have been performed to understand the nature of interaction and the driving force for complexation under experimental conditions.
Surgical Treatment of Transgender and Gender‐Diverse Individuals and Health Outcomes
Authors: Boskey Elizabeth R. , Kant Jessica D.
Published: January 2025

Gender affirming surgeries are procedures that are used by transgender and gender diverse individuals to align their bodies to their gender identities. These have been shown to improve the mental health and wellbeing of those individuals who choose to access them. Rates of regret associated with gender affirming surgeries are low, and in addition to improving mental health and quality of life, these procedures have the potential to make it safer for transgender and gender diverse people to move through the world. This article provides a narrative review that places gender affirming surgeries in the current sociopolitical context of the United States. It describes common types of gender affirming surgery, protocols for surgical assessment, and the risks and benefits of surgery.
Is It the (Sexist) Company You're Keeping? Examining the Connection Between Psychological Health and Perceptions of Sexism Endorsement in One's Personal Network
Authors: Smith C. Veronica , Shaw Caitlin M. , Øverup Camilla S.
Published: January 2025

Ambivalent sexism theory proposes that people endorse both positive/benevolent and negative/hostile views towards both women and men. Although some work has examined the effects of endorsing these views, no work to date has examined whether the perceived sexist beliefs of one's personal network are connected to one's own psychological health. Using a sample of American adults (N = 273), the current study used a novel methodology designed to assess the perceptions of the sexism in one's personal network (e.g., friends, co‐workers, romantic partners, family members), along with multiple measures of psychological health. Results suggest that perceived network hostile sexism towards women was associated with lower well‐being and greater distress, but perceived network benevolence towards women was associated with higher life satisfaction. Unexpectedly, perceiving one's network to endorse more hostile sexism towards men than oneself was associated with lower levels of distress and higher well‐being. Results were mostly consistent for both men and women.
Ultrasound‐Assisted Ionic Liquid Extraction of Polysaccharides From Crataegus songarica K. Koch Fruits: Structural Characterization and Antioxidant Activity
Authors: Jiang Sheng‐qi , Chai Yu‐yang , Ma Shu‐fang , Wang Jun‐long , Shi Wen‐pan , He Peng‐peng , Pang Juan‐xia , Lin Yong‐gang
Published: January 2025

In this study, we optimal the ultrasound‐assisted ionic liquid extraction (UAILE) process of polysaccharides from Crataegus songarica K. Koch fruits. The optimal conditions determined were ultrasonic power of 400 W, temperature of 79°C, extraction time of 78 min, ethylammonium dodecyl sulfate (EADS) concentration of 1.52 mg/mL, and liquid–solid ratio of 51:1 mL/g. Under these conditions, the polysaccharides yield was 34.37%, which was significantly higher than that obtained by the conventional ultrasound‐assisted extraction (UAE) and hot water extraction (HWE) methods. After purification, we studied the chemical composition, physicochemical properties, and structural characteristics of polysaccharides (CSP). The results showed that CSP is a heteropolysaccharide containing α‐linkage glucopyranose, which is mainly composed of mannose, arabinose, galactose, and glucose, with a molecular weight (Mw) of 27.82 × 104 Da. In addition, CSP demonstrated significant free radical scavenging ability and was able to efficiently reduce the H2O2‐induced HepG2 cellular malondialdehyde (MDA) content, while enhancing superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px) activities, showing its superior antioxidant activity. On the basis of these properties, CSP is expected to be used as a novel efficacy factor in the food and pharmaceutical industries.
Synergistic Anti‐Inflammatory Effects of Dibenzoylmethane and Silibinin: Insights From LPS‐Induced RAW 264.7 Cells and TPA‐Induced Mouse Model
Authors: Huang Zebin , Zhang Wanying , Shu Qi , Guo Xiao‐Chun , Zheng Xi , Lu Yu‐Jing
Published: January 2025

Inflammation is an important predisposing factor for many chronic diseases. The dietary flavonoid silibinin (SB) has excellent anti‐inflammatory properties in cells, but its low bioavailability in the blood compromises its therapeutic potential. This study aims to investigate the potential of dibenzoylmethane (DBM) to synergistically enhance the anti‐inflammatory benefits of SB. The synergistic effects of DBM and SB in combination were evaluated in lipopolysaccharide (LPS)‐induced RAW264.7 cells and 12‐O‐tetradecanoylphorbol 13‐acetate (TPA)‐induced mice. In addition, a network pharmacology approach and molecular docking were used to explore the key targets and signaling pathways of DBM and SB in combination. The results showed that DBM and SB synergistically inhibited the production of nitric oxide (NO), reactive oxygen species (ROS), interleukin‐1β (IL‐1β), and tumor necrosis factor‐α (TNF‐α) in a 1:1 concentration ratio. These two compounds may exert their synergistic effects by modulating the nuclear factor kappa‐B (NF‐κB) and HIF‐1 signaling pathways, among others. Molecular docking revealed that both compounds exhibited high binding affinities to inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2). Compared with single‐compound use, the two compounds in combination significantly reduced ear edema and inflammatory cell infiltration and inhibited the protein expression of iNOS and COX‐2 in TPA‐induced mice. This research provides a rationale for the combination of DBM and SB as an effective anti‐inflammatory agent.
Cytotoxic Ruthenium(II)‐Diphosphine Complexes Affect the Mitochondrial Respiration of Lung Cancer Cells
Authors: Palmeira‐Mello Marcos V. , Mesdom Pierre , Burckel Pierre , Hidalgo Samia , Blacque Olivier , Gasser Gilles , Batista Alzir A.
Published: January 2025

In this work, we studied six Ruthenium(II)‐diphosphine compounds containing different mercapto ligands (N−S), with general formula [Ru(N−S)(dppm)2]Cl (dppm=1,1‐bis(diphenylphosphino)methane). These compounds were characterized by several techniques (NMR [1H, 31P(1H), and 13C], HRMS, IR, UV‐Vis and XRD) and their purity confirmed by elemental analysis. DLS experiments revealed low diameters and polydispersity indexes, and positive log P values in n‐octanol/PBS indicated their preference for the organic phase. In general, these compounds are stable in different media over 48 h. Cytotoxicity experiments revealed promising IC50 values on A549 breast cancer cells, 0.48 μM and 0.80 μM for [Ru(mtz)(dppm)2]Cl (1) and [Ru(mmi)(dppm)2]Cl (2), respectively (mtz and mmi are 2‐mercapto‐2‐thiazoline and mercapto‐1‐methylimidazole in their deprotonated form, respectively). Clonogenic and migration experiments indicated their antiproliferative and anti‐migratory capacity. ICP‐MS results indicated their cellular accumulation in the nucleus, with little amounts in mitochondria. No covalent DNA binding was observed by ICP‐MS. JC‐1 and cell Mito Stress test confirmed mitochondrial dysfunction, which was verified by mitochondrial membrane potential uncoupling and drastic alterations in the oxygen consumption rate. Taken together, our results provide crucial insights regarding the anticancer potential of ruthenium(II)‐phosphine compounds.
Unmasking the Hidden Threat: The Role of Left Ventricular Subendocardial Involvement in Autoimmune Rheumatic Disease
Authors: Wu Danni , Li Xiao , Guo Tianchen , Feng Xiaojin , Li Xinhao , Wang Yining , Chen Wei
Published: January 2025

Background

Late gadolinium enhancement (LGE) has been found in patients with autoimmune rheumatic disease (ARD). However, the prognostic implications of some specific LGE patterns in ARD patients remain unclear.

Purpose

To investigate the prevalence and prognostic significance of left ventricular (LV) subendocardium‐involved LGE (LGEse) in a cohort of ARD patients.

Materials and Methods

This retrospective study evaluated 176 patients diagnosed with ARD with clinically suspected cardiac involvement between 2018 and 2023. LV LGEse was defined as LGE involving the LV subendocardium that did not correspond to a coronary vascular distribution. The endpoints included a composite of cardiac death, heart failure‐related admission, cardiogenic shock, and appropriate pacemaker or implantable cardioverter‐defibrillator therapy.

Results

Of the 176 consecutive patients, LV LGEse was observed in 22 patients (13%). During a median follow‐up of 776 days (interquartile range, 395–1405 days), 20 patients (11%) experienced a composite endpoint. Compared with those without LV LGEse, the LV LGEse group had a greater proportion of men (64% vs. 14%; p < 0.001), lower LV ejection fraction (50% vs. 60%; p = 0.001), greater LV end‐diastolic volume index (78 vs. 75; p = 0.043), and more adverse outcomes (32% vs. 8%; p = 0.005). In the univariable and multivariable Cox regression analyses, the LV LGEse showed independent prognostic value. In the sensitivity analyses, the prognostic difference in terms of LV subendocardial involvement remained.

Conclusion

In our cohort, LV subendocardial involvement, an underrecognized LGE pattern, was observed in 13% of all patients with autoimmune disease and indicated a worse prognosis.
Beyond the Screen: Socialization, Community Building, and Interpersonal Connectivity in Bangladesh Through Video Games
Authors: Hossain Syed Arman , Fahad Abdullah Al
Published: January 2025

This article explores the intricate dynamics of video gaming among the youth of Dhaka, Bangladesh, exploring its profound influence on socialization and community building within the framework of theories such as the Theory of Attainment, Imagined Community, User and Gratification Theory, and Bourdieu's concept of “social capital.” Through a comprehensive blend of digital and autoethnographic methods, the research unveils how gaming transcends its solitary image to emerge as a potent cultural force in Bangladeshi society. The findings underscore the pivotal role of gaming in forging social bonds and nurturing communities, both in virtual realms and physical spaces. Gamers actively engage in collaboration, strategic planning, and the exchange of experiences, mirroring the dynamics of real‐world social networks. Despite concerns regarding addiction, the article illuminates the impact of video games on social cohesion among the youth demographic. Furthermore, it inquires into gaming culture's remarkable resilience in the face of societal norms and regulatory challenges, shedding light on the adaptive strategies employed by gamers to navigate and thrive in diverse contexts. By exploring the intricate interplay between virtual and real‐life experiences, this research contributes to a deeper understanding of how video games shape socialization among urban youth in the ever‐evolving landscape of Bangladesh.
The Rise of Type 2 Diabetes in Children and Adolescents: An Emerging Pandemic
Authors: Goyal Shiwali , Vanita Vanita
Published: January 2025

Aim

This review explores the increasing prevalence of Type 2 Diabetes Mellitus (T2DM) in children and adolescents, focusing on its etiology, risk factors, complications, and the importance of early detection and management. It also highlights the need for a multidisciplinary, family‐centered approach in managing T2DM in pediatric populations, with an emphasis on nutrition, exercise, and lifestyle interventions.

Materials and Methods

A literature review was conducted using PubMed, Google Scholar, and Scopus to incorporate studies from 2015 to 2024 on T2DM in youths/adolescents/children, focusing on epidemiology, risk factors, and prevention strategies. Studies on Type 1 Diabetes Mellitus (T1DM) or adult populations were excluded.

Results

T2DM is a complex metabolic disorder with various societal, behavioral, environmental, and genetic risk factors. It accounts for one in three new childhood diabetes cases, with rising incidence among American Indian/Alaska Native, Black, and Hispanic/Latino children. The increase in T2DM incidence correlates with growing childhood obesity rates. Early onset significantly raises the risk of complications like retinopathy, nephropathy, neuropathy, cardiovascular diseases, nonalcoholic fatty liver disease, and obstructive sleep apnea. Early detection, screening, and treatment can prevent or delay these complications. A family‐centered, multidisciplinary approach is essential for effective management, including lifestyle and behavioral support.

Conclusions

T2DM in children is a growing health concern with severe implications. Early detection and management, including nutrition and exercise counseling, are critical in reducing long‐term complications. A multidisciplinary approach is vital for improving outcomes and minimizing morbidity and mortality.
Pleiotropic Function of Cellular Prion Protein: Encompassing Endoplasmic‐Reticulum Stress, Cell Proliferation in Vascular Smooth Muscle Cells
Authors: Bose Rumela , Ghosh Madhubanti , Ain Rupasri
Published: January 2025

Cellular prion protein (PRNP) has been implicated in various physiological processes in different cell types, for decades. Little has been known how PRNP functions in multiple, yet related processes within a particular system. In our current study, with the aid of high‐throughput RNA‐sequencing technique, we have presented an overall transcriptome profile of rat vascular smooth muscle cells (VSMCs) with Prnp knockdown. Fifty‐one genes were found to be differentially regulated, of which, genes involved in cell proliferation and endoplasmic reticulum (ER) stress pathway, show significant upregulation. That PRNP negatively regulates VSMC proliferation, has been demonstrated using immunoblot assays, BrdU incorporation assay and Ki‐67 immunofluorescence staining. As revealed from our RNA‐Seq data, ATF4, a downstream effector of the PERK arm of ER stress pathway is upregulated upon RNA interference of Prnp in VSMCs. As a result, the expression of the functional phosphorylated isoform of translation initiation factor eIF2α (p‐eIF2α) is elevated. Additionally, we also showed that downregulation of Prnp leads to excess intracellular ROS accumulation, subsequently leading to splicing of Xbp1 mRNA and triggering unfolded protein response (UPR) within the cell. Therefore, our findings highlight that PRNP directly or indirectly modulates an array of biological processes and plays a pivotal role in preserving the equilibrium between excess proliferation and optimal endoplasmic reticulum function, in VSMCs.
Vacuolar H+‐ATPase and Megalin‐Mediated Prorenin Uptake: Focus on Elements Beyond the (Pro)Renin Receptor
Authors: Wang Na , Lu Xifeng , Jan Danser A. H.
Published: January 2025

Megalin is a multiple‐ligand receptor that contributes to protein reabsorption in the kidney. Recently, megalin was found to act as a novel endocytic receptor for prorenin. Internalization depended on the (pro)renin receptor. This receptor is an accessory protein of vacuolar H+‐ATPase (V‐ATPase), a complex consisting of 14 subunits and two accessory proteins. Here we explored whether V‐ATPase elements other than the (P)RR affect megalin‐mediated prorenin uptake. Using RNAi technology, we inhibited each individual V‐ATPase subunit in megalin‐expressing BN16 cells. Subsequently, we quantified megalin expression and the uptake of prorenin. To unravel the underlying molecular mechanisms, we investigated the adaptor proteins autosomal recessive hypercholesterolemia (ARH) and Disabled‐2 (Dab2), which are important for the endocytosis of megalin, glycogen synthase kinase 3β (GSK3β), a regulatory factor of megalin recycling, and endoplasmic reticulum stress factors (ERSF). Silencing subunit Atp6voa1 reduced prorenin uptake by 19%, while silencing accessory protein Atp6ap1 increased it by 15%. Silencing other subunits exerted a more modest or no effect. Silencing Atp6voa1 reduced surface megalin density, without altering its mRNA and protein levels, and this was associated with increased GSK3β phosphorylation and no change in ARH, Dab2, and ERSF. Silencing Atp6ap1 increased megalin mRNA and protein expression and this was accompanied by upregulation of ARH and ERSF, while Dab2 expression was unaltered. In conclusion, V‐ATPase units differently affect megalin‐mediated reabsorption of prorenin, thereby offering novel pharmacological targets to not only affect renal renin‐angiotensin system activity, but also to treat renal diseases that are associated with disturbed protein reabsorption, like Dent's disease.
The Killing of Cousins and Siblings‐In‐Law in Korea: A Descriptive Study
Authors: Shon Leah C. J. , Shon Phillip
Published: January 2025

The killing of cousins and siblings‐in‐law has been examined as part of ‘relative killings’ in prior research. However, they have not been disaggregated and examined in their own right. A content analysis of a major Korean newspaper (Chosun Ilbo) and sentencing verdicts from regional trial courts of original jurisdiction in Korea was conducted. This paper examines the offence characteristics in cousin and siblings‐in‐law killings. Cousin and siblings‐in‐law killings made up 4% of 682 family homicides. The victims and offenders were primarily men who used edged weapons to kill one another during the course of arguments. Women appeared as offenders and victims in the early period (1948–1962) while they appeared primarily as victims in the latter period (2013–2023). The data suggest a shift in the age structure of victims and putative motivations across time. The average age of victims and offenders increased by 20 years; the character of violence also shifted from confrontational homicides to killings in the context of domestic disputes between relatives' spouses.
Genetic Conservation and Diversity of SARS‐CoV‐2 Envelope Gene Across Variants of Concern
Authors: Liu Benjamin M. , Yao Qiaobin , Cruz‐Cosme Ruth , Yarbrough Casey , Draper Kyah , Suslovic William , Muhammad Imaan , Contes Kaia M. , Hillyard David R. , Teng Shaolei , Tang Qiyi
Published: January 2025

SARS‐CoV‐2 Envelope (E) protein is critical in viral assembly, release, and virulence. E gene was considered highly conserved and evolving slowly. Pan‐sarbecoviruses–conserved regions in the E gene have been used as targets for various RT‐PCR assays to detect SARS‐CoV‐2. It remains elusive whether SARS‐CoV‐2 variants of concern (VOCs) have accumulated significant E mutations that may affect protein stability and diagnostic RT‐PCR assays. Herein we aimed to perform a comprehensive genetic analysis on the conservation and diversity of the E gene of SARS‐CoV‐2 and its VOCs in comparison with other human coronaviruses (HCoVs). In silico analysis of 20 326 HCoV E gene sequences retrieved from GenBank and GISAID suggests that SARS‐CoV‐2 E gene has multiple pan‐HCoVs– and pan‐SARS‐CoV‐2–conserved positions but accumulates significant mutations in VOC B.1.351 and Omicron strains. Mutations were often found in the 5′ and 3′ variable regions, whereas the central region is conserved. Nucleotide changes C109U and A114G may lead to potential failure of first‐line SARS‐CoV‐2 diagnostic/screening assays. Nucleotide change C212U and its concomitant amino acid substitution Pro71Leu (i.e., C212U/Pro71Leu) is a hallmark mutation of B.1.351 variants, while C26U/Thr9Ile is characteristic of all Omicron variants. Later Omicron subvariants, such as XBB.1.5 and EG.5, additionally acquired the A31G/Thr11Ala mutation, as was confirmed by whole genome sequencing of SARS‐CoV‐2 in 118 pediatric cases. Wild‐type E protein exhibits cytotoxicity to cells, but the mutations Thr9Ile, Thr11Ala, Thr9Ile + Thr11Ala, or Pro71Leu reduces its cytotoxicity. The Thr9Ile + Thr11Ala mutation stabilizes the E proteins of Omicron variants, while Pro71Leu alters the cellular distribution of the E protein, reducing its colocalization with the Golgi body. Altogether, this study not only sheds light on the conservation and diversity of the E gene in SARS‐CoV‐2 and its VOCs but also informs the improvement and development of SARS‐CoV‐2 or pan‐HCoVs screening and diagnostic assays.
Automatic Segmentation of Vestibular Schwannoma From MRI Using Two Cascaded Deep Learning Networks
Authors: Häußler Sophia Marie , Betz Christian S. , Della Seta Marta , Eggert Dennis , Schlaefer Alexander , Bhattacharya Debayan
Published: January 2025

Objective

Automatic segmentation and detection of vestibular schwannoma (VS) in MRI by deep learning is an upcoming topic. However, deep learning faces generalization challenges due to tumor variability even though measurements and segmentation of VS are essential for growth monitoring and treatment planning. Therefore, we introduce a novel model combining two Convolutional Neural Network (CNN) models for the detection of VS by deep learning aiming to improve performance of automatic segmentation.

Methods

Deep learning techniques have been employed for automatic VS tumor segmentation, including 2D, 2.5D, and 3D UNet‐like architectures, which is a specific CNN designed to improve automatic segmentation for medical imaging. Specifically, we introduce a sequential connection where the first UNet's predicted segmentation map is passed to a second complementary network for refinement. Additionally, spatial attention mechanisms are utilized to further guide refinement in the second network.

Results

We conducted experiments on both public and private datasets containing contrast‐enhanced T1 and high‐resolution T2‐weighted magnetic resonance imaging (MRI). Across the public dataset, we observed consistent improvements in Dice scores for all variants of 2D, 2.5D, and 3D CNN methods, with a notable enhancement of 8.86% for the 2D UNet variant on T1. In our private dataset, a 3.75% improvement was reported for 2D T1. Moreover, we found that T1 images generally outperformed T2 in VS segmentation.

Conclusion

We demonstrate that sequential connection of UNets combined with spatial attention mechanisms enhances VS segmentation performance across state‐of‐the‐art 2D, 2.5D, and 3D deep learning methods.

Level of Evidence

3 Laryngoscope, 2025
Ein Wassertropfen als „Blatt‐Lupe“
Authors: Schlichting Hans Joachim
Published: January 2025

Die mit winzigen Härchen ausgestattete Unterseite eines Blatts verhindert die Benetzung, verringert die Lichtstreuung und ermöglicht dadurch einen klaren Blick auf feine Details.
Konfrontationen und Kollisionen
Authors: Loos Andreas
Published: January 2025

Physikalische wie ethisch‐politische Kollisionen durchziehen das Leben des Gesuchten.
Self‐Healing Biobased Thermoreversible Polymer Networks by Photo‐Diels‐Alder Chemistry
Authors: Alrefai Masa , Maric Milan
Published: January 2025

Poly(furfuryl methacrylate) (poly(FMA)) homopolymers with controlled molecular weights made via ICAR ATRP undergo photo‐crosslinking (λ = 254 nm) with 1,1′‐(methylenedi‐4,1‐phenylene)bismaleimide (BM) by Diels‐Alder (DA) chemistry, and are compared to the same DA reaction under non‐UV initiated, ambient conditions (RT‐DA). FTIR and DSC analysis confirm DA adduct formation and the retro‐DA reaction. Co‐ and terpolymers of FMA with C13MA (alkyl methacrylate with average side length = 13) and isobornyl methacrylate (IBOMA) are prepared to enhance mechanical properties. Poly(C13MA‐co‐FMA) samples are used to study curing condition effects and BM loading on crosslinking density and thermal behavior. Varying BM loading (0.05–0.2 BM: FMA) in samples cured by photo‐DA and RT‐DA, UV cured samples showing higher gel content (50% versus 25% for 0.2 BM loading) and two endothermic peaks in the first heating run, unlike RT cured samples which display a single peak. Subsequently, poly(C13MA‐co‐IBOMA‐co‐FMA) are crosslinked with BM via photo‐DA with resulting networks indicating self‐healing/recyclability. FTIR and DSC results confirm DA and retro‐DA reactions, while scratched samples of crosslinked terpolymers exhibit self‐healing upon heating. Microscopic images show complete scratch healing in just 20 min due to furan‐maleimide adduct formation, facilitated by the presence of flexible low Tg poly (C13MA) segments and rigid poly (IBOMA) repeating units.
5G Remote Robot‐Assisted Hepatobiliary and Pancreatic Surgery: A Report of Five Cases and a Literature Review
Authors: Fan Yuxin , Ma Chao , Wu Xinyu , Cai Tianyong , Liang Xiao , Li Zheyong , Cai Xiujun
Published: January 2025

Background

This study aimed to explore the feasibility and safety of using 5G communication technology for domestic surgical robots to perform ultra‐remote hepatobiliary and pancreatic surgery.

Methods

A retrospective analysis was conducted on the clinical data of five cases of ultra‐remote domestic robot‐assisted laparoscopic hepatobiliary and pancreatic surgery completed at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine (referred to as Hangzhou, Zhejiang) and Sir Run Run Shaw Hospital, Alaer Hospital, Zhejiang University School of Medicine (referred to as Alaer city, Xinjiang) from February to September 2023. The main system of the operating desk at Hangzhou, Zhejiang, uses 5G network signal transmission to remotely control the bedside operating system at Alaer City, Xinjiang. The physical distance between the two locations is 4670.2 km, and the network communication distance is 5031.2 km. The operators and assistants are immobilised.

Results

The operations were successful. The number of network image frames was 50, the median delay was 73 (70.25–126.1) ms, and the median operation time was 39 (31–128) min. The median intraoperative blood loss was 2 (2–30) mL. No occurrence of network disruption or data packet loss was observed. One case of instrument adverse event occurred, and the patient returned to normal after replacement. The median times taken to get out of bed, ventilation, and hospitalisation were 19 (15–46) h, 2 (2–4) d, and 3 (3–13) d, respectively. According to the Clavien–Dindo classification, the postoperative complications in one patient were Grade I; no other surgical complications were observed. No abnormalities were observed in the patients after a 30‐day re‐examination. All patients successfully recovered after a 2‐month follow‐up.

Conclusions

It is safe and feasible for domestic robots to perform 5G remote robot‐assisted hepatobiliary and pancreatic surgery.
Integrated Design and Prototyping of a Robotic Head for Ocular and Craniofacial Trauma Simulators
Authors: Gallerani Marcello , Pitzalis Roberto F. , Novi Gianluca De , Ottensmeyer Mark P. , Berselli Giovanni
Published: January 2025

Background

Medical simulation is relevant for training medical personnel in the delivery of medical and trauma care, with benefits including quantitative evaluation and increased patient safety through reduced need to train on patients.

Methods

This paper presents a prototype medical simulator focusing on ocular and craniofacial trauma (OCF), for training in management of facial and upper airway injuries. It consists of a physical, electromechanical representation of head and neck structures, including the mandible, maxillary region, neck, orbit and peri‐orbital regions to replicate different craniofacial traumas. Actuation and hydraulic systems are designed to control animatronic features and flow of simulated blood, tears, and cerebrospinal fluid.

Results

Experimentally validated, the OCF simulator achieves structural and functional characteristics as close as possible to those of a human body.

Conclusions

The OCF Simulator can be used as a stand‐alone active simulator, it can be transported and used to train surgeons in simulated real‐life scenarios.

Clinical Trial Registration

The authors declare that this statement is not applicable since no clinical tests have been performed.