bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a combined transcutaneous carbon dioxide pressure and pulse oximetry sensor in adult sheep and dogs
Authors: Vogt Rainer , Rohling Roman , Kästner Sabine
Published: March 2007

Objective—To evaluate a combined transcutaneous carbon dioxide pressure (tcPCO2) and pulse oximetry sensor in sheep and dogs.

Animals—13 adult sheep and 11 adult dogs.

Procedures—During inhalation anesthesia, for the first 10 minutes following sensor placement, arterial blood gas was analyzed and tcPCO2 was recorded every 2 minutes. Subsequently, the animals were hyper-, normo-, and hypoventilated. The simultaneously obtained tcPCO2 and PaCO2 values were analyzed by use of Bland-Altman statistical analysis.

Results—Mean ± SD overall difference between tcPCO2 and PaCO2 10 minutes after sensor application was 13.3 ± 8.4 mm Hg in sheep and 8.9 ± 12 mm Hg in dogs. During hyper-, normo-, and hypoventilation, mean difference (bias) and precision (limits of agreement [bias ± 2 SD]) between tcPCO2 and PaCO2 values were 13.2 ± 10.4 mm Hg (limits of agreement, −7.1 and 33.5 mm Hg) in sheep and 10.6 ± 10.5 mm Hg (limits of agreement, −9.9 and 31.2 mm Hg) in dogs, respectively. Changes in PaCO2 induced by different ventilation settings were detected by the tcPCO2 sensor with a lag (response) time of 4.9 ± 3.5 minutes for sheep and 6.2 ± 3.6 minutes for dogs.

Conclusions and Clinical Relevance—The tcPCO2 sensor overestimated PaCO2 in sheep and dogs and followed changes in PaCO2 with a considerable lag time. The tcPCO2 sensor might be useful for noninvasive monitoring of changes but cannot be used as a surrogate measure for PaCO2.
Validation of two-dimensional kinematic analysis of walk and sit-to-stand motions in dogs
Authors: Feeney Lauren C. , Lin Cheng-Feng , Marcellin-Little Denis J. , Tate Amanda R. , Queen Robin M. , Yu Bing
Published: March 2007

Objective—To assess the intra- and interobserver repeatability of 2-dimensional (2-D) kinematic analysis of walk and sit-to-stand motions in dogs.

Animals—10 healthy adult Labrador Retrievers.

Procedures—10 dogs were filmed during walk and sit-to-stand motions. Five trials were recorded for each dog, 3 of which were digitized. Two observers manually marked 15 landmarks on each frame during the motions of interest for these 3 trials. Each observer repeated the procedure approximately 1 week later. The 2-D joint angles were calculated. Intra- and interobserver coefficients of multiple correlations (CMCs) were calculated for each joint angle–time history.

Results—Intraobserver repeatability, assessed as the mean CMCs of 12 joint angle measurements made for 10 dogs by 2 observers, was good or excellent in 23 of 24 (96%) mean CMCs of the joints measured. Interobserver variation, assessed by comparing CMCs of measurements made by 2 observers on 10 dogs on 2 days, was good or excellent in 161 of 240 (67%) CMCs of joints measured.

Conclusions and Clinical Relevance—Intraobserver repeatability of 2-D kinematic measurements made on digitized videotapes was excellent. Interobserver repeatability of these measurements was acceptable.
Immunohistochemical evaluation of substance P and calcitonin gene-related peptide in skin and periosteum after extracorporeal shock wave therapy and radial pressure wave therapy in sheep
Authors: Abed Janan M. , McClure Scott R. , Yaeger Michael J. , Evans Richard B.
Published: March 2007

Objective—To evaluate the effect of focused extracorporeal shock wave therapy (ESWT) and radial pressure wave therapy (RPWT) on immunohistochemical staining for substance P and calcitonin gene-related peptide (CGRP) in the skin and periosteum of sheep.

Animals—36 sheep.

Procedures—All 4 limbs of 36 sheep were treated with ESWT, RPWT, or a sham treatment. For 14 days after treatment, at least 2 sheep were euthanized daily and tissue was harvested for histologic evaluation of nerves via staining for substance P and CGRP in the skin and periosteum.

Results—No effects of ESWT or RPWT were observed on the number of nerves with stain uptake for substance P or CGRP in the skin or periosteum.

Conclusions and Clinical Relevance—Substance P- and CGRP-containing nerve fibers are not disrupted by EWST or RPWT. Further studies are needed to identify the mechanism of analgesia observed in association with these treatment modalities.
Assessment of ultrasonography and computed tomography for the evaluation of unilateral orbital disease in dogs
Authors: Boroffka Susanne A. E. B. , Verbruggen Anne-Marie , Grinwis Guy C. M. , Voorhout George , Barthez Paul Y.
Published: March 2007

Objective—To describe clinical, ultrasonographic, and computed tomographic (CT) features of confirmed neoplastic and nonneoplastic disease in dogs with unilateral orbital diseases, determine criteria to differentiate between the 2 conditions, and assess the relative value of ultrasonography and CT for the differential diagnosis of these 2 conditions.

Design—Prospective study.

Animals—29 dogs with unilateral neoplastic orbital disease and 16 dogs with unilateral nonneoplastic orbital disease.

Procedures—Clinical history and results of physical and ophthalmologic examinations were recorded. Ultrasonographic and CT images were evaluated, and discriminating factors were identified to differentiate neoplastic from nonneoplastic diseases. Diagnostic value of ultrasonography and CT was assessed.

Results—Dogs with neoplastic disease were significantly older; had clinical signs for a longer time before initial examination; had more progressive onset of clinical signs; and more frequently had protrusion of the nictitating membrane, fever, and anorexia. The most discriminating factor for both imaging modalities was delineation of the margins (odds ratio was 41.7 for ultrasonography and 45 for CT), with neoplastic lesions clearly delineated more often. Ultrasonographically, neoplastic lesions were more frequently hypoechoic and homogeneous, with indentation of the globe and bone involvement evident more frequently than for nonneoplastic lesions. Mineralization was detected only with neoplasia. Fluctuant fluid was seen more frequently in dogs with nonneoplastic disease. Computed tomography more frequently revealed extraorbital involvement. Diagnostic value was similar for both imaging modalities.

Conclusions and Clinical Relevance—Ultrasonography and CT are valuable imaging modalities to assist in differentiating neoplastic from nonneoplastic unilateral orbital disease in dogs.
Hemophagocytic syndrome in dogs: 24 cases (1996–2005)
Authors: Weiss Douglas J.
Published: March 2007

Objective—To determine the frequency, potential causes, and clinical and clinicopathologic features of hemophagocytic syndrome in dogs.

Design—Retrospective study.

Animals—24 client-owned dogs.

Procedures—Records for dogs in which diagnostic bone marrow specimens (including an aspiration smear and core biopsy material) were obtained from 1996 to 2005 were reviewed. Inclusion criteria were presence of bicytopenia or pancytopenia in the blood and > 2% hemophagocytic macrophages in the bone marrow aspirate.

Results—Of 617 bone marrow specimens evaluated, evidence of hemophagocytic syndrome was detected in 24 (3.9%). The Tibetan Terrier breed was overrepresented among dogs with hemophagocytic syndrome. Clinical signs associated with hemophagocytic syndrome included fever, icterus, splenomegaly, hepatomegaly, and diarrhea. Hemophagocytic syndrome was associated with immune-mediated, infectious, and neoplastic-myelodysplastic conditions and also occurred as an idiopathic condition. Overall, dogs with infection-associated hemophagocytic syndrome had better 1-month survival rates than dogs with immune-associated and idiopathic hemophagocytic syndrome.

Conclusions and Clinical Relevance—Results indicated that hemophagocytic syndrome may occur more frequently in dogs than has previously been suspected on the basis of the paucity of reported cases. Although most dogs had definable underlying disease conditions, idiopathic hemophagocytic syndrome was also identified. Hemophagocytic syndrome of any cause is potentially life-threatening; however, the prognosis should be adjusted on the basis of the associated disease process and potential for successful treatment.
Validation of DermSat-7 for Assessing Treatment Satisfaction in Patients With Psoriasis
Authors: Armstrong April W. , Lee Kathryn , Yee Danielle , Woodbury Michael , Zundell Melissa , Zagona-Prizio Caterina , Yousif Jenna , Grant Carly , Shields Ali , Chou Peichi , Callis Duffin Kristina , Gottlieb Alice B. , Merola Joseph F. , Perez-Chada Lourdes
Published: February 2025

Importance

A critical need exists for developing a validated dermatologic-specific treatment satisfaction instrument.

Objective

To evaluate the structural validity, internal consistency, construct validity, and test-retest reliability of the 7-item dermatology-specific treatment satisfaction (DermSat-7) instrument in patients with psoriasis.

Design, Setting, and Participants

This survey study was conducted from July 2020 to April 2023 in dermatology outpatient clinics at the University of Southern California, Brigham and Women’s Hospital, and Mount Sinai Union Square and included adults (aged ≥18 years) with psoriasis who were fluent in English. On day 1, the clinician at the study sites assessed psoriasis disease severity in person using the Psoriasis Area and Severity Index (PASI), body surface area (BSA), and Physician Global Assessment (PGA). On day 1, study participants completed the DermSat-7, the generic 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9), and the Dermatology Life Quality Index (DLQI). They also answered demographic questions and reported their own disease severity using the Patient Global Assessment (PtGA). On day 14 (±2 days), the patient then completed the DermSat-7 and PtGA a second time.

Main Outcomes and Measures

The DermSat-7 is a 7-item self-administered instrument with a recall period of 14 days that assesses patient satisfaction with their treatments across various inflammatory dermatology diseases, including psoriasis. Construct validity, structural validity, internal consistency, and test-retest reliability of DermSat-7 were assessed as defined by the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) taxonomy and reported following the COSMIN reporting guideline for studies on measurement properties.

Results

The analysis included 142 patients with psoriasis (mean [SD] age, 51.1 [15.5] years; 77 males [54.2%]). Exploratory factor analysis and confirmatory factor analysis supported the unidimensionality of the DermSat-7 domains. The internal consistency of the effectiveness and convenience domains was high with a Cronbach α of 0.88 and 0.81, respectively. Regarding construct validity, differences between groups based on PASI/PGA scores were aligned with preexisting hypotheses, and the correlations between DermSat-7 and TSQM-9 subscores were strong to very strong (ρ = 0.75 for effectiveness; ρ = 0.66 for convenience; and ρ = 0.70 for overall satisfaction; all P < .001). Intraclass correlation was 0.85, indicating high test-retest reliability.

Conclusions and Relevance

This survey study found that the DermSat-7 may be a valid and reliable instrument for measuring treatment satisfaction in patients with psoriasis.
Trends in Guideline-Concordant Care for Inflammatory Breast Cancer
Authors: Tadros Audree , Diskin Brian , Sevilimedu Varadan , Xu Amy , Vingan Perri , Nelson Jonas , Iwai Yoshiko , Morrow Monica , Fayanju Oluwadamilola M.
Published: February 2025

Importance

Inflammatory breast cancer (IBC) is an aggressive variant for which trimodality treatment (ie, neoadjuvant systemic therapy [NST] followed by modified radical mastectomy without immediate reconstruction and postmastectomy radiotherapy [PMRT]) represents guideline-concordant care (GCC) and is associated with improved overall survival (OS). However, it is unclear whether there are disparities in trimodality treatment receipt among patients with IBC and how such disparities might affect OS.

Objective

To assess trends in IBC trimodality treatment receipt in a contemporary cohort.

Design, Setting, and Participants

A retrospective cohort study was conducted using data from the National Cancer Database. Women with nonmetastatic IBC treated from calendar years 2010 to 2018 were included. Data analysis was performed from April 1, 2023, to March 1, 2024.

Exposures

Guideline-concordant care (ie, trimodality treatment administered in the correct sequence with time to NST initiation <60 days post diagnosis).

Main Outcomes and Measures

The main outcomes were associations between patient-, disease-, treatment-, and facility-level factors and receipt of overall and modality-specific GCC and associations between these factors and adjusted OS.

Results

Of 6945 patients identified (median age, 57 [IQR, 47-66] years; 2.4% Asian or Pacific Islander, 7.8% Hispanic, 17.1% non-Hispanic Black, and 71.5% non-Hispanic White), only 1740 (25.1%) received all forms of GCC: 91.3% (n = 5662) received NST initiation less than 60 days post diagnosis, 63.3% (n = 4395) received PMRT, and 51.3% (n = 3564) underwent guideline-concordant surgery (ie, modified radical mastectomy without immediate reconstruction with >6 lymph nodes removed). Receipt of GCC did not differ significantly by race and ethnicity, insurance status, or location. Asian (odds ratio [OR], 0.48; 95% CI, 0.27-0.84), Black (OR, 0.53; 95% CI, 0.41-0.68), and Hispanic (OR, 0.40; 95% CI, 0.29-0.55) patients were less likely to have NST initiation less than 60 days post diagnosis vs White patients (all P ≤ .001). Recipients of GCC had improved adjusted OS vs nonrecipients (hazard ratio [HR], 0.75; 95% CI, 0.68-0.84; P < .001). Black patients had significantly lower adjusted OS ,compared with White recipients (HR, 1.41; 95% CI, 1.26-1.58; P < .001). When GCC was received for triple-negative IBC, there was no racial and ethnic disparity in OS.

Conclusions and Relevance

In this cohort study of women with nonmetastatic IBC, there were no disparities observed in GCC receipt, but only 25.1% of patients with IBC received all forms of GCC for which they were eligible. Among those who received GCC, there was no racial disparity in survival for triple-negative IBC, suggesting opportunities to improve equity through standardization of care.
Genetic Correlates of Treatment-Resistant Depression
Authors: Xu Bohan , Forthman Katherine L. , Kuplicki Rayus , Ahern Jonathan , Loughnan Robert , Naber Firas , Thompson Wesley K. , Nemeroff Charles B. , Paulus Martin P. , Fan Chun Chieh
Published: February 2025

Importance

Treatment-resistant depression (TRD) is a major challenge in mental health, affecting a significant number of patients and leading to considerable burdens. The etiological factors contributing to TRD are complex and not fully understood.

Objective

To investigate the genetic factors associated with TRD using polygenic scores (PGS) across various traits and explore their potential role in the etiology of TRD using large-scale genomic data from the All of Us (AoU) Research Program.

Design, Setting, and Participants

This study was a cohort design with observational data from participants in the AoU Research Program who have both electronic health records and genomic data. Data analysis was performed from March 27 to October 24, 2024.

Exposures

PGS for 61 unique traits from 7 domains.

Main Outcomes and Measures

Logistic regressions to test if PGS was associated with treatment-resistant depression (TRD) compared with treatment-responsive major depressive disorder (trMDD). Cox proportional hazard model was used to determine if the progressions from MDD to TRD were associated with PGS.

Results

A total of 292 663 participants (median [IQR] age, 57 (41-69) years; 175 981 female [60.1%]) from the AoU Research Program were included in this analysis. In the discovery set (124 945 participants), 11 of the selected PGS were found to have stronger associations with TRD than with trMDD, encompassing PGS from domains in education, cognition, personality, sleep, and temperament. Genetic predisposition for insomnia (odds ratio [OR], 1.11; 95% CI, 1.07-1.15) and specific neuroticism (OR, 1.11; 95% CI, 1.07-1.16) traits were associated with increased TRD risk, whereas higher education (OR, 0.88; 95% CI, 0.85-0.91) and intelligence (OR, 0.91; 95% CI, 0.88-0.94) scores were protective. The associations held across different TRD definitions (meta-analytic R2 >83%) and were consistent across 2 other independent sets within AoU (the whole-genome sequencing Diversity dataset, 104 388, and Microarray dataset, 63 330). Among 28 964 individuals followed up over time, 3854 developed TRD within a mean of 944 days (95% CI, 883-992 days). All 11 previously identified and replicated PGS were found to be modulating the conversion rate from MDD to TRD.

Conclusions and Relevance

Results of this cohort study suggest that genetic predisposition related to neuroticism, cognitive function, and sleep patterns had a significant association with the development of TRD. These findings underscore the importance of considering psychosocial factors in managing and treating TRD. Future research should focus on integrating genetic data with clinical outcomes to enhance understanding of pathways leading to treatment resistance.
Thermal proteome profiling and proteome analysis using high‐definition mass spectrometry demonstrate modulation of cholesterol biosynthesis by next‐generation galeterone analog VNPP433‐3β in castration‐resistant prostate cancer
Authors: Thankan Retheesh S. , Thomas Elizabeth , Weldemariam Mehari M. , Purushottamachar Puranik , Huang Weiliang , Kane Maureen A. , Zhang Yuji , Ambulos Nicholas , Wang Bi‐Dar , Weber David , Njar Vincent C. O.
Published: February 2025

Cholesterol (CHOL) homeostasis is significantly modulated in prostate cancer (PCa) suggesting an active role in PCa development and progression. Several studies indicate a strong correlation between elevated CHOL levels and increased PCa risk and severity. Inhibition of CHOL biosynthesis at different steps, including lanosterol synthase (LSS), has shown significant efficacy against both hormone‐dependent and castration‐resistant PCa. Earlier, we reported proteasomal degradation of androgen receptor (AR)/AR‐Vs and Mnk1/2 as the primary mechanisms of action of VNPP433‐3β in inhibiting PCa cell proliferation and tumor growth. Through thermal proteome profiling, comparative proteomics and cellular thermal shift assay, we identified VNPP433‐3β's ancillary effect of lowering CHOL by binding to LSS and lanosterol 14‐alpha demethylase, potentially inhibiting CHOL biosynthesis in PCa cells and tumors. Additionally, in conjunction with our previously reported transcriptome analysis, proteomics reveals that VNPP433‐3β modulated upstream regulators and pathways critical for PCa stem cell maintenance and recurrence. The inhibition of CHOL biosynthesis by VNPP433‐3β reinforces its multifaceted effects in PCa across all stages, highlighting its potential as a single‐agent therapy. Achieving reduced CHOL levels aligns with better treatment outcomes, further substantiating VNPP433‐3β's therapeutic potential.
Capturing what matters: Patient‐reported LGI1‐ANTibody encephalitis outcome RatiNg scale (LANTERN)
Authors: Kelly Mark J , Wagner Barbara , Ceronie Bryan , Strippel Christine , Lin Ann Yee , Handel Adam , Soltys John , Binks Sophie , Powell Philip A , Irani Sarosh R
Published: February 2025

Background

LGI1‐antibody encephalitis (LGI1‐Ab‐E) is a common form of autoimmune encephalitis where most patients demonstrate ‘good’ clinician‐rated outcomes. However, more targeted questionnaires reveal numerous debilitating symptoms for many years. To better quantify these persistent features, we designed the LGI1‐Antibody Encephalitis Rating (LANTERN) scale, a quantified, disease‐specific patient‐reported outcome measure (PROM), adhering to FDA guidelines.

Methods

A participant‐driven mixed‐methods approach to develop a clinically valid questionnaire over three stages: (1) Item generation through semi‐structured interviews; (2) Repeated cognitive debriefing rounds to advance comprehensibility, relevance and comprehensiveness; (3) Psychometric survey to condense the most sensitive and valid questions. Analyses incorporated sensitivity testing with multiple internal and external validations.

Results

From 73 items across six domains (Stage 1; n = 18), a questionnaire assessing the frequency and severity of 43 symptoms (80 questions), plus nine activities of daily living (ADL), was developed through cognitive debriefing (Stage 2; n = 15). This 89‐question survey was completed (Stage 3; n = 66 patients and 32 relatives) and distilled, using exploratory factor analyses, to a three‐factor symptom‐burden questionnaire comprising 41 questions (19 symptoms and 6 ADL), separated into physical, cognitive/behavioural and ADL domains. These factors demonstrated strong internal reliability (Cronbach alpha: 0.85–0.91), correlations with relative‐completed questionnaires (R = 0.73–0.85; p < 0.001), good‐to‐excellent intraclass re‐testing correlations (0.81–0.98; n = 19) and strong associations with numerous predefined external measures.

Discussion

LANTERN represents a PROM for LGI1‐Ab‐E, with initial content, structural and construct validity and test–retest reliability. It can be used as a reliable, tailored, efficient and sensitive method to establish symptom burden in people with LGI1‐Ab‐E, both in clinical practice and trials.
High‐Fat and Low‐Carbohydrate Dietary Environments Are Linked to Reduced Idiopathic Epilepsy Incidence and Prevalence
Authors: Ni Duan , Senior Alistair , Raubenheimer David , Simpson Stephen J. , Nanan Ralph
Published: February 2025

Dietary manipulations like ketogenic diets are established interventions for recalcitrant epilepsy. However, it remains unknown whether specific macronutrient exposure through dietary environments could possibly extend to primary preventive qualities, associated with changes in epilepsy disease burden (prevalence and incidence). Here, macronutrient supply, GDP, and idiopathic epilepsy disease burden data were collated from more than 150 countries from 1990 to 2018. Nutritional geometry generalized additive mixed models (GAMMs) modeling unraveled that dietary environments with high‐fat and low‐carbohydrate supplies were linked to lower epilepsy incidence and prevalence. Our analyses suggested a plausible primary preventive role of dietary manipulations for epilepsy.
Production of Parallel Aligned Nanofiber Rovings From Continuous Bundles
Authors: Yıldırım Behzat , Kılıç Ali , İçoğlu Halil İbrahim , Topalbekiroğlu Mehmet
Published: February 2025

This study presents a novel approach to converting electrospun polyacrylonitrile (PAN) nanofiber bundles into rovings, essential for nanofiber yarn spinning, through the implementation of false twisting and drawing processes. The false twisting process is optimized by varying the input bundle angle (40° to 60°), twister type (A, B, C), and rotation speed (20, 50, and 80 rpm). A bundle input angle of 55°, twister type B, and a twister rotation speed of 80 rpm show the best results in terms of longer twisted length, lower average thickness, and thickness variation values. The morphological, physical, and mechanical properties of the resulting nanofiber rovings for drawing process implementation are also evaluated. Scanning electron microscope (SEM) analysis further reveals significant improvements in nanofiber alignment and uniformity. The drawing process reduces the average nanofiber diameter from 297 to 200 nm and decreases the standard deviation of alignment angles from 14.2° to 8.1°, indicating a substantial enhancement in parallel nanofiber alignment. These morphological changes contribute to a marked increase in tensile strength from 2.2 to 3.3 cN tex−1. Integrating false twisting and drawing processes in electrospun nanofiber production can significantly enhance the mechanical properties and alignment of nanofibers, making them more suitable for advanced textile applications.
Geniposidic Acid Targeting FXR “S332 and H447” Mediated Conformational Change to Upregulate CYPs and miR‐19a‐3p to Ameliorate Drug‐Induced Liver Injury
Authors: Fan Minqi , Xu Yuanhang , Wu Bingxin , Long Jiachan , Liu Caihong , Liang Zuhui , Zhang Rong , Liu Zhongqiu , Wang Caiyan
Published: February 2025

Drug‐induced liver injury (DILI), caused by chemical drugs and traditional Chinese medicine, often leads to severe outcomes like liver failure due to a lack of early detection markers. Farnesoid X receptor (FXR), a key regulator of bile acid (BA) and cholesterol metabolism, is a potential therapeutic target. This study investigates the pathogenesis, markers, and treatment strategies for DILI, focusing on the hepatoprotective effects of geniposidic acid (GPA) from Gardenia jasminoides J. Ellis. Using cellular and animal models of acute and chronic DILI induced by acetaminophen and triptolide, we explored GPA's mechanisms in BA and cholesterol metabolism. Lipidomic and BA analyses revealed that GPA alleviates DILI by enhancing bile acid synthesis and transport via FXR activation. Experiments using AAV‐shFXR, Fxr−/− mice and molecular assays demonstrated that GPA targets Ser332 and His447 on FXR ligand‐binding domain, promoting FXR nuclear translocation and initiating cytochrome P450 proteins (CYPs) transcriptional activation for BA metabolism. Additionally, miRNA sequencing and RNA‐pulldown assays showed that GPA‐activated FXR upregulates miR‐19a‐3p, binding to LXR 3'UTR to inhibit cholesterol production. These findings reveal the GPA‐FXR “structure‐target” relationship, highlighting a dual mechanism in which GPA promotes CYPs‐mediated bile acid metabolism and miR‐19a‐3p‐mediated cholesterol synthesis inhibition, providing a basis for FXR‐targeted DILI therapies.
Mesoporous Silica‐Enhanced Sulfonated Poly(Ether Ether Ketone)/Polyvinyl Alcohol Self‐Healable Membrane for High Concentration Direct Methanol Fuel Cells
Authors: Tai Mae Hwa , Thiam Hui San , Tee Shiau Foon , Lim Yun Seng , Saw Lip Huat , Lai Soon Onn
Published: February 2025

Proton exchange membranes (PEMs) in direct methanol fuel cells (DMFCs) transport protons while minimizing fuel crossover. However, commercial Nafion membranes face durability and methanol permeability issues. This study introduces a novel self‐healable mesoporous silica (MSN) modified sulfonated poly(ether ketone) (SPEEK)/polyvinyl alcohol (PVA) membrane to improve DMFC efficiency and longevity. The composite membrane comprising 3 wt% MSN (S/PVA/MSN3) shows proton conductivity comparable to the pristine SPEEK, despite the inclusion of non‐conductive PVA. MSN's large specific surface area and high porosity enhance water retention and facilitate proton transport. The methanol permeability of S/PVA/MSN3 is reduced by 29% compared to the pristine SPEEK, attributed to the combined effect of PVA's superior selectivity for water over methanol and the tortuous pathways created by MSN. Thanks to its improved selectivity, a DMFC with S/PVA/MSN3 achieves a remarkable open‐circuit voltage (OCV) of 0.63 V, even with a high methanol concentration of 8 M, and a peak power density of 8.79 mW cm−2, which is 2.13 times greater than the commercial Nafion 117. Moreover, S/PVA/MSN3 demonstrates significant recoveries of 91% in OCV and 87% in maximum power output following damage and self‐healing. These findings suggest that the self‐healable S/PVA/MSN has the potential for future use in DMFCs.
Spectroscopic and Theoretical Tools Unravel the Thermally‐Stabilized Behavior of Eu3+‐Based Complex Incorporated in Sustainable Urethanesil Film
Authors: Caixeta Fábio José , Saraiva Leonardo Figueiredo , de Freitas Beatriz Damasio , Domingos Onishi Bruno Seiki , Santagneli Silvia Helena , Bortoletto-Santos Ricardo , Pires Ana Maria , Ribeiro Sidney J.L.
Published: February 2025

Despite significant ongoing efforts to develop luminescent rare‐earth β‐diketonate complexes, achieving thermal stability remains a persistent challenge. In this study, we present a thermally stable organic‐inorganic hybrid (OIH) compound, SiCO‐[Eu(tta)3(H2O)2], where tta = thenoyltrifluoroacetonate, Si = 3‐(triethoxysilyl)propyl isocyanate, and CO = castor oil. Spectroscopic analysis reveals that while [Eu(tta)3(H2O)2] in its powder form undergoes irreversible photoluminescence quenching at 60 °C and embedding it in the SiCO polymer preserves its luminescence even after being annealed up to 180 °C. Notably, the hybrid film maintains stable emission properties after multiple heating‐cooling cycles (29–70 °C) and exhibits reversible emission behavior. This finding is attributed to polymer‐complex interactions and/or the replacement of water molecules with polymer coordination, resulting in a more rigid environment in the Eu3+ coordination sphere. The thermal dependence of intramolecular energy transfer (IET) indicates that the decrease in Eu3+ luminescence is linked to faster depopulation of the emitting level, driven by non‐radiative relaxation and back‐energy transfer. This outcome enabled us to strategize approaches to mitigate luminescence quenching in OIH while providing valuable insights into the photophysical properties of these compounds, thus offering a guide towards how we can boost the capabilities of these materials.
Untangling the Molecular Mechanisms Contributing to Autism Spectrum Disorder Using Stem Cells
Authors: Mattingly Zoe , Chetty Sundari
Published: February 2025

Autism spectrum disorder (ASD) is a complex neuro developmental condition characterized by significant genetic and phenotypic variability, making diagnosis and treatment challenging. The heterogeneity of ASD‐associated genetic variants and the absence of clear causal factors in many cases complicate personalized care. Traditional models, such as postmortem brain tissue and animal studies, have provided valuable insights but are limited in capturing the dynamic processes and human‐specific aspects of ASD pathology. Recent advances in human induced pluripotent stem cell (iPSC) technology have transformed ASD research by enabling the generation of patient‐derived neural cells in both two‐dimensional cultures and three‐dimensional brain organoid models. These models retain the donor's genetic background, allowing researchers to investigate disease‐specific cellular and molecular mechanisms while identifying potential therapeutic targets tailored to individual patients. This commentary highlights how stem cell‐based approaches are advancing our understanding of ASD and paving the way for more personalized diagnostic and therapeutic strategies.
Waiting Times and Influencing Factors in Children and Adults Undergoing Assessment for Autism, ADHD, and Other Neurodevelopmental Differences
Authors: Maciver Donald , Roy Anusua Singh , Johnston Lorna , Boilson Marie , Curnow Eleanor , Johnstone‐Cooke Victoria , Rutherford Marion
Published: February 2025

This study explored waiting times and the factors influencing them in child and adult populations undergoing assessment for autism, ADHD, and other neurodevelopmental differences. The analysis focused on a retrospective review of 408 cases with assessments completed between October 2021 and May 2022, conducted by 30 diagnosing teams in Scotland. Data included age, final diagnosis, demographics, medical and developmental history, contact frequency, and assessment service adherence to best‐practice standards. Waiting times were calculated, and relationships were analyzed using linear regression. Median waiting times were 525 days (IQR 329–857) for children/adolescents and 252 days (IQR 106–611) for adults. Only 20% of children's and 47% of adult assessments met the proposed 252‐day diagnostic time target. Autism and ADHD were the most common diagnoses. Receiving > 1 neurodevelopmental diagnosis on completion was uncommon. Demographic factors did not significantly affect waiting times. Children/adolescents with more complex developmental and medical histories experienced longer waits (100.3 weeks vs. 67.7 weeks; p < 0.001), while adults with similar histories had shorter waits (32.7 weeks vs. 57.4 weeks; p = 0.016). Adults with ADHD experienced longer waits than autistic adults (63.4 weeks vs. 38.6 weeks, p = 0.002). Adherence to best‐practice quality standards was associated with shorter waits for children (β = 0.27, p = 0.002), but the relationship between standard adherence at different stages and for adults was less clear. More frequent appointments correlated with shorter adult waits (33.7 weeks vs. 59.2 weeks, p = 0.015). Gender distribution was balanced among adults, but children's services included more boys. The study highlights long waits and the need for improvement in processes.
Herpes Zoster Oticus With Facial Palsy and Hearing Loss: A Case Report of Ramsay Hunt Syndrome in an Older Patient
Authors: Kakeeto James , Atukunda Ronaldine Anne , Asio Priscilah , Pitua Ivaan
Published: February 2025

Ramsay Hunt syndrome (RHS) is a rare complication of varicella‐zoster virus (VZV) reactivation, typically presenting with a combination of painful vesicular lesions in the ear, facial nerve palsy, and hearing loss. Early diagnosis and antiviral therapy are critical in minimizing long‐term sequelae, such as persistent facial weakness and hearing impairment. This case highlights the importance of prompt recognition and treatment in older patients, particularly those with pre‐existing hearing difficulties. An 87‐year‐old female presented with a 2‐week history of painful, blister‐like lesions on the right ear and lips, associated with a burning sensation. Over several days, the lesions progressed to visible wounds. The patient also reported increasing weakness, difficulty eating, and worsening hearing impairment. Physical examination revealed vesicular lesions on the right pinna and lips, along with right‐sided facial weakness (House‐Brackmann Grade IV) and slight ipsilateral lagophthalmos with mild conjunctival erythema. No new vesicles or generalized rash were observed. The patient's medical history included hypertension and long‐standing bilateral hearing difficulty. Ramsay Hunt syndrome was diagnosed based on the characteristic symptoms of painful vesicular lesions, facial nerve palsy, and hearing loss. The patient was treated with oral acyclovir, dexamethasone, and supportive care. Significant improvement was noted by Day 7, with reduced pain, partial recovery of facial function, and improvement in hearing. By Day 14, all lesions had healed, and facial symmetry was restored. This case emphasizes the importance of early recognition and intervention in improving clinical outcomes in older patients with RHS.
Ectopic Pregnancy After In Vitro Fertilization With Donor Eggs in a 54‐Year‐Old Woman; Bad News After Wishful Thinking for the Last Chance of Pregnancy
Authors: Stavros Sofoklis , Potiris Anastasios , Kozonis Alexios , Zikopoulos Athanasios , Gerede Angeliki , Lazari Paraskevi , Karampitsakos Theodoros , Skentou Charikleia , Domali Ekaterini , Drakakis Peter
Published: February 2025

This case presents a rare form of an ectopic pregnancy after retrograde migration of the transferred blastocyst to the fallopian tube. The presence of hydrosalpinx and extremely advanced maternal age further increases the risk. This case highlights the possibility of blastocyst migration even after ultrasound guidance during embryo transfer.
4‐Exo‐Trig Radical Cyclization: A Promising Approach to Four‐Membered Rings
Authors: Xu Sangxuan , Zhou Yulu , Zheng Hanliang , Zhu Gangguo
Published: February 2025

The 4‐exo‐trig radical cyclization represents a formidable challenge owing to the unfavorable thermodynamics associated with the formation of highly strained four‐membered rings. Stimulated by the explosive advancements of radical chemistry over the past decades, significant progresses have been made in this area, including the SmI2‐mediated 4‐exo‐trig carbonyl‐alkene cyclization, n‐Bu3SnH‐mediated 4‐exo cyclization of functionalized alkenes or alkynes, transition metal‐catalyzed 4‐exo‐trig ring closures, and visible light‐induced 4‐exo‐trig cyclization cascade, providing efficient protocols to overcome the inherent limitations and expand the synthetic utility of this methodology. Representative examples, reaction mechanism, scope and limitations, and synthetic applications are presented and discussed in detail. We believe that the systematic review of recent advances on 4‐exo‐trig radical cyclization will provide more insights in this field, and may enable further development of this cyclization process for the concise synthesis of four‐membered carbo‐ and heterocycles that are difficult to access via traditional methods.
Direct Decarboxylative Phosphorylation of α‐Amino Acids via Continous‐Flow Electrochemistry
Authors: Li Zhao‐Yu , Chen Na , Xu Hai‐Chao
Published: February 2025

Comprehensive Summary

Herein we present a novel electrochemical method for the direct decarboxylative phosphorylation of α‐amino acids to α‐amino phosphonates, a key structural element in various biologically active compounds. This method bypasses the need for strong chemical oxidants and 2‐step processes involving preliminary conversions, making it a more straightforward synthetic tool. Key to the success of the method is to establish a microenvironment on the anode surface in an acidic solution to facilitate selective anodic decarboxylation and subsequent C–P formation. The electrosynthetic process in continuous flow ensures benign conditions and excellent scalability through continuous production with parallel reactors.
CCL2/C–C chemokine receptor type 2‐mediated interactions among mast cells, basophils, and endothelial cells
Authors: Rihar Maruša , Bahri Rajia , Forstnerič Vida , Bulfone‐Paus Silvia , Korošec Peter
Published: February 2025

Background

IL‐33 is involved in allergic processes by promoting the release of various mast cell (MC) chemokines, including CCL2. However, it is yet unclear which specific cell type is primarily responsible for producing CCL2 during acute allergic reactions. This study aims to investigate the role of IL‐33 in promoting CCL2 production in mast cells and assess the effect of MC‐derived CCL2 on basophil migration and endothelial permeability.

Methods

Human blood‐derived MCs (hMCs) were generated from peripheral blood precursors, passively sensitized with IgE, treated with IL‐33, and stimulated with anti‐IgE. The concentrations of nine cytokines known to influence immune cell chemotaxis (CCL2, CCL5, CCL11, MIP‐1α, IL‐8, IL‐10, IL‐13, granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), and vascular endothelial growth factor (VEGF) were assessed in the supernatants of hMCs. Subsequently, we investigated the impact of MC‐derived CCL2 on basophil migration in vitro, as well as its effect on endothelial monolayer permeability using human umbilical vein endothelial cells (HUVECs).

Results

Stimulation with anti‐IgE induced a significant release of CCL2, GM‐CSF, IL‐8 and VEGF from hMCs. Additionally, incubation with IL‐33 overnight increased the production of several cytokines. Mast cell‐derived CCL2 not only enhanced basophil migration in vitro but also increased endothelial monolayer permeability in HUVECs. The effect was reversed by a C–C chemokine receptor type 2 (CCR2) antagonist, indicating the involvement of CCL2 signaling through the CCR2 receptor.

Conclusions

IL‐33 induces the production of chemotactic cytokines in hMCs. Mast cell‐derived CCL2 plays an important role in basophil chemotaxis in vitro and affects endothelial monolayer permeability in the HUVEC model.
Single Atom Sites in Ga‐Ni Supported Catalytically Active Liquid Metal Solutions (SCALMS) for Selective Ethylene Oligomerization
Authors: Søgaard Alexander , Hsieh Tzung-En , Steffen Julien , Carl Simon , Wu Mingjian , Ramzi Yousuf Raed , Maisel Sven , Will Johannes , Efimenko Anna , Gorgoi Mihaela , Wilks Regan G. , Frisch Johannes , Taccardi Nicola , Haumann Marco , Spiecker Erdmann , Görling Andreas , Bär Marcus , Wasserscheid Peter
Published: February 2025

Supported catalytically active liquid metal solutions (SCALMS) are materials composed of a liquid metal alloy deposited on a porous support. Due to the dynamic properties of the liquid metal alloy, these systems are suggested to form single atom sites, resulting in unique catalytic properties. Ga–Ni SCALMS were successfully applied to ethylene oligomerization, yielding catalysts that were stable up to 120 h time on stream. A workflow based on synchrotron‐based X‐ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM) as well as density function theory (DFT) and ab initio molecular dynamics (AIMD) simulations was applied to investigate the nature of the active species in these materials. The combination of XPS with DFT calculations indeed indicates the presence of isolated single Ni atoms on the liquid metal surface, while TEM measurements show high dynamics in the liquid metal with intermetallic phase dissolution and transformation. Furthermore, DFT/AIMD methods allowed for rationalizing the role of hydrogen pretreatment in enriching the Ni atom at the surface of the liquid metal alloy.
Ginsenoside CK Promotes Cell Apoptosis via Regulating P53 Signal Pathway in Non‐Small Cell Lung Cancer
Authors: Liu Xinze , Feng Lin , Jin Xin , Sun Kaijing , Sun Ying , Wu Xinmin , Xia Mingjie , Tan Renbo , Yang Hongmei , Li Guangzhe , Wu Wei , Zu Shuang , Li Anning , Chen Changbao , Wan Xilin
Published: February 2025

Non‐small cell lung cancer (NSCLC) is a malignant tumor with high morbidity and mortality. Ginsenosides have been shown to have strong antitumor activity, inhibiting tumor cell growth and promoting apoptosis. In this paper, the effects of ginsenoside CK on the proliferation and apoptosis of NSCLC 95D and NCI‐H460 cells were investigated by CCK8, colony formation assay, flow cytometry, fluorescence staining assay, and Western Blot, and it was found that ginsenoside CK could significantly inhibit the growth and proliferation of non‐small cell lung cancer, and it was also clarified that the mechanism of its action was realized by the mitochondrial apoptosis pathway. It provides new therapeutic ideas for lung cancer and other major tumor diseases.
Toward a Specific and Descriptive Definition of Avoidant/Restrictive Food Intake Disorder: A Proposal for Updated Diagnostic Criteria
Authors: Zickgraf Hana F. , Cares Samuel R. , Schwartz Rachel A. , Breiner Courtney E. , Stettler Nicole M.
Published: February 2025

The diagnostic criteria for avoidant/restrictive food intake disorder (ARFID) have been the source of confusion since its introduction to the DSM in 2013. In the current state, ARFID is diagnosed based on impairment, with no requirement that a specific pattern of behavioral or cognitive/affective symptoms be present. In this paper, we make the case for more positive etiologically based criteria for ARFID wherein Criterion A defines the psychopathology of ARFID. We propose a framework for DSM criteria involving food avoidance that is maintained by beliefs/hedonic reactions that are temporally close to and realistically/functionally associated with a specific food or eating occasion, characterized by one or more of the following expected aversive responses: disgust/distaste, anhedonia/uncomfortable fullness, and acute fear/panic. Our proposed Criterion B retains the four manifestations of impairment in the current definition as necessary, but not sufficient, for the ARFID diagnosis. When both Criteria A and B are met, our revised Criteria D (ARFID vs. other restrictive eating disorders) and E (ARFID vs. other medical/psychiatric conditions) state that ARFID should be diagnosed regardless of co‐occurring/comorbid conditions. We discuss how this positive definition of ARFID would impact clinical diagnosis and subsequent treatment, with specific considerations for differential diagnosis between ARFID and other eating disorders, other forms of psychopathology, and relevant medical conditions. Additionally, we discuss how it might enhance research opportunities by providing increasingly homogeneous samples through which researchers could better understand the etiological mechanisms of ARFID.
Anamorelin Efficacy in Non–Small‐Cell Lung Cancer Patients With Cachexia: Insights From ROMANA 1 and ROMANA 2
Authors: Laird Barry J. A. , Skipworth Richard , Bonomi Philip D. , Fallon Marie , Kaasa Stein , Giorgino Ruben , McMillan Donald C. , Currow David C.
Published: February 2025

Background

Cancer cachexia presents a significant challenge, but the ghrelin agonist anamorelin shows promise as a potential treatment. This study examined whether the baseline systemic inflammatory response (SIR) (measured by the modified Glasgow Prognostic Score [mGPS]), low BMI or greater weight loss, was associated with a differential treatment effect of anamorelin in people with cachexia and non–small‐cell lung cancer (NSCLC).

Methods

ROMANA 1 and ROMANA 2 were double‐blind, placebo‐controlled, randomised Phase 3 trials that enrolled people with inoperable stage III/IV NSCLC with cachexia (≥ 5% weight loss within 6 months or body mass index [BMI] < 20 kg/m2). Patients were randomised 2:1 to anamorelin 100 mg once daily or placebo, for 12 weeks. This is a post hoc analysis of efficacy endpoints (body weight and body composition: lean body mass [LBM] and fat mass [FM]), stratified by baseline mGPS, BMI and weight loss and measured in the modified intent‐to‐treat pooled population.

Results

Seven hundred ninety‐five patients had available data. Anamorelin improved body weight (p < 0.001) and body composition parameters (LBM and FM, p < 0.01) in all mGPS groups. In patients with mGPS = 2, anamorelin increased weight > 5% and improved hand grip strength (HGS) and the Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Subscale (FAACT A/CS). In patients with BMI < 20 kg/m2 at baseline or weight loss ≥ 10% in the prior 6 months, anamorelin led to significant increases in body weight from baseline (p < 0.001) versus placebo. Patients with weight loss ≥ 10% in the prior 6 months showed the highest improvements in LBM (p < 0.001). Patients with BMI < 20 kg/m2 at baseline showed the highest improvements in FM (p < 0.001).

Conclusion

Anamorelin improved body composition parameters in all patients, as well as physical function and symptom burden, particularly in patients with systemic inflammation, BMI < 20 kg/m2 and weight loss ≥ 10%. These results highlight that the anabolic mechanisms of anamorelin are more effective in high‐risk groups.

Trial Registration

NCT identifiers: ROMANA 1: NCT01387269; ROMANA 2: NCT01387282.