bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of neoadjuvant chemoimmunotherapy and chemotherapy in patients with potentially resectable stage IIIA/IIIB NSCLC: a retrospective study
Authors: Wang Yuchen , Ma Xiaobo , Ma Kewei , Chen Xi , He Hua , Zhao Xiangye , Fan Mengge , Xu Yinghui
Published: January 2025

Background

Treatment of locally advanced unresectable non-small cell lung cancer (NSCLC) is a significant challenge, especially for patients with IIIA/IIIB NSCLC. Patients receiving neoadjuvant chemoimmunotherapy (NCI) show improved pathological responses and disease-free survival (DFS) compared to those receiving Neoadjuvant chemotherapy (NC). However, there is still no consensus on the treatment for potentially resectable stage IIIA/IIIB NSCLC.

Methods

This retrospective study included 71 patients newly diagnosed with stage III NSCLC at our institution between 2017 and 2023: 46 patients received NCI and 25 patients received NC followed by surgical resection. Their clinicopathological characteristics were reviewed and analyzed.

Results

Patients who received NCI had a significantly longer DFS. The median DFS was 15 months in the NC group (hazard ratio: 0.186, 95% confidence interval[CI]: 0.073–0.479; P<0.001) but had not been reached in the NCI group. The percentage of patients achieving a major pathologic response was 65.9% (29/44, 95% CI: 50.0%–79.1%) with NCI and 16.7% (4/24, 95% CI: 5.5%–38.2%) with NC alone(P<0.001). The percentage of patients with pathologic complete response was 36.4% (16/44, 95% CI: 22.8%–52.3%) after NCI compared with 8.3% (2/24, 95% CI: 1.5%–28.5%) after NC (P = 0.012). The survival curve shows that the overall survival for the NCI group has a better trend than that of the NC group, but there is no significant difference (P=0.193). The incidence of all-grade adverse events was greater in the NCI group than in the NC group (80.4% vs. 64.0%). The incidence of grade ≥3 adverse events was 10.9% (n=5) and 8.0% (n=2), respectively; however, these differences were insignificant.

Conclusions

NCI is more effective and safer for patients with potentially resectable stage IIIA/IIIB NSCLC. Compared with NC alone, NCI significantly improves the pathological response and DFS without increasing adverse events.
Macrophage-derived extracellular vesicles as new players in chronic non-communicable diseases
Authors: Lin Fengjuan , Luo Huiyu , Wang Jiexian , Li Qing , Zha Longying
Published: January 2025

Macrophages are innate immune cells present in all tissues and play an important role in almost all aspects of the biology of living organisms. Extracellular vesicles (EVs) are released by cells and transport their contents (micro RNAs, mRNA, proteins, and long noncoding RNAs) to nearby or distant cells for cell-to-cell communication. Numerous studies have shown that macrophage-derived extracellular vesicles (M-EVs) and their contents play an important role in a variety of diseases and show great potential as biomarkers, therapeutics, and drug delivery vehicles for diseases. This article reviews the biological functions and mechanisms of M-EVs and their contents in chronic non-communicable diseases such as cardiovascular diseases, metabolic diseases, cancer, inflammatory diseases and bone-related diseases. In addition, the potential application of M-EVs as drug delivery systems for various diseases have been summarized.
IgG4-mediated M2 macrophage polarization in tertiary lymphoid structures of esophageal cancer: implications for immunosuppression
Authors: Wang Hui , Li Jirui , Wang Yinghai , Chen Yang , Zhang Weifeng , Pan Xinyan , Su Chanjuan , Li Ziteng , Wang Li , Gu Jiang
Published: January 2025

Background

Our previous research highlighted the potential role of immunoglobulin G4 (IgG4) in mediating immunosuppression within the tumor microenvironment (TME). Tertiary lymphoid structures (TLS) in the TME have important immune-related functions. This study aims to analyze the distribution characteristics of IgG4-expressing cells, regulatory T cells (Tregs), and M2-type macrophages as well as to elucidate the relationship between IgG4 and the polarization of M2 macrophages within TLS in esophageal cancer.

Object

To elucidate the distribution of IgG4, Treg cells, and M2 macrophages in TLS and to assess the impact of IgG4 on macrophage polarization.

Methods

Esophageal cancer tissue were analyzed with multiplex immunofluorescence to determine the spatial distribution and density of B cells, T cells, and their subtypes. The relationship between IgG4 and CD8+ T cells in TLS, along with interleukin-10 (IL-10) expression and Treg presence, was studied. Serum IgG4 and IL-10 levels were compared between patients and healthy controls. In vitro, the impact of IgG4 on monocyte differentiation into M2 macrophages was observed.

Results

IgG4 density was inversely related with CD8+ T cells in mature TLS indicating a potential immunosuppressive role (P<0.05,*). Serum analysis revealed that both IgG4 (P<0.01, **) and IL-10 (P<0.0001, ****) were significantly elevated and positively correlated in tumor patients compared to controls (P<0.01, **). In vitro experiments confirmed that IgG4 monocyte differentiation into M2 macrophages, potentially enhancing the immunosuppressive phenotype in TLS.

Conclusion

IgG4 and IL-10 may contribute to immunosuppression in esophageal cancer by promoting the polarization of M2 macrophages within TLS, which could be a therapeutic target.
Liver sinusoidal endothelial cells regulate the balance between hepatic immunosuppression and immunosurveillance
Authors: Kremer Kimberly N. , Khammash Hadeel A. , Miranda Anjelica M. , Rutt Lauren N. , Twardy Shannon M. , Anton Paige E. , Campbell Margaret L. , Garza-Ortiz Christian , Orlicky David J. , Pelanda Roberta , McCullough Rebecca L. , Torres Raul M.
Published: January 2025

As a metabolic center, the liver prevents inappropriate immune responses to abundant dietary antigens within the liver that could result in liver injury. This self-preservation mechanism can however decrease the efficiency of immunosurveillance of malignant cells by CD8 T cells. Hepatocellular carcinoma (HCC) is initiated by chronic viral infections, chronic alcohol consumption, and/or a fatty diet that leads to liver injury, fibrosis, and cirrhosis. HCC patients have high levels of dysfunctional and exhausted T cells, however, it is unclear which stage of HCC development contributes to T cell dysfunction. Repair of liver injury is initiated by interactions between injured hepatocytes and liver sinusoidal endothelial cells (LSEC), however, chronic injury can lead to fibrosis. Here, using a diethylnitrosamine/carbon tetrachloride (DEN/CCl4) mouse model of early HCC development, we demonstrate that chronic liver injury and fibrosis are sufficient to induce a CD8 T cell exhaustion signature with a corresponding increase in expression of immunosuppressive molecules on LSEC. We show that LSEC alter T cell function at various stages of T cell differentiation/activation. LSEC compete with dendritic cells presenting the same antigen to naïve CD8 T cells resulting in a unique T cell phenotype. Furthermore, LSEC abrogate killing of target cells, in an antigen-dependent manner, by previously activated effector CD8 T cells, and LSEC change the effector cell cytokine profile. Moreover, LSEC induce functional T cell exhaustion under low dose chronic stimulation conditions. Thus, LSEC critically regulate the balance between preventing/limiting liver injury and permitting sufficient tumor immunosurveillance with normal hepatic functions likely contributing to HCC development under conditions of chronic liver insult.
Neurological history both twinned and queried by generative artificial intelligence
Authors: Lee Jung-Hyun , Choi Eunhee , Angulo Sergio L. , McDougal Robert A. , Lytton William W.
Published: January 2025

Background and objectives

We propose the use of GPT-4 to facilitate initial history-taking in neurology and other medical specialties. A large language model (LLM) could be utilized as a digital twin which could enhance queryable electronic medical record (EMR) systems and provide healthcare conversational agents (HCAs) to replace waiting-room questionnaires.

Methods

In this observational pilot study, we presented verbatim history of present illness (HPI) narratives from published case reports of headache, stroke, and neurodegenerative diseases. Three standard GPT-4 models were designated Models P: patient digital twin; N: neurologist to query Model P; and S: supervisor to synthesize the N-P dialogue into a derived HPI and formulate the differential diagnosis. Given the random variability of GPT-4 output, each case was presented five separate times to check consistency and reliability.

Results

The study achieved an overall HPI content retrieval accuracy of 81%, with accuracies of 84% for headache, 82% for stroke, and 77% for neurodegenerative diseases. Retrieval accuracies for individual HPI components were as follows: 93% for chief complaints, 47% for associated symptoms and review of systems, 76% for relevant symptom details, and 94% for histories of past medical, surgical, allergies, social, and family factors. The ranking of case diagnoses in the differential diagnosis list averaged in the 89th percentile.

Discussion

Our tripartite LLM model demonstrated accuracy in extracting essential information from published case reports. Further validation with EMR HPIs, and then with direct patient care will be needed to move toward adaptation of enhanced diagnostic digital twins that incorporate real-time data from health-monitoring devices and self-monitoring assessments.
Impact of liver graft steatosis on long-term post-transplant hepatic steatosis and fibrosis via magnetic resonance quantification
Authors: Mak Lung-Yi , Fung James , Lo Gladys , Lo Christine Shing-Yen , Wu Trevor Kwan-Hung , Chung Matthew Shing-Hin , Wong Tiffany Cho-Lam , Seto Wai-Kay , Chan Albert Chi-Yan , Yuen Man-Fung
Published: January 2025

Background

The rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has led to an increased occurrence of steatotic liver grafts (SLG) in liver transplantation (LT). However, the implications of SLG on post-transplant de novo hepatic steatosis (PTHS) and advanced fibrosis (≥F3) remain uncertain. This study aimed to characterize PTHS and ≥ F3 using magnetic resonance imaging (MRI) in patients who underwent LT for non-MASLD indications and to examine their relationship with SLG.

Methods

Post-LT patients with implant biopsy fat content data were recruited for MRI assessments. MRI-proton density fat fraction (MRI-PDFF) and MR elastography (MRE) were performed using a 1.5 Tesla Optima 450 W MR scanner with a 3D volumetric sequence. PTHS and ≥ F3 were defined as MRI-PDFF ≥5% and MRE ≥3.64 kPa, respectively. SLG was defined as implant biopsy fat content ≥5%.

Results

A total of 292 patients (70.5% men, median age at LT: 51.9 years, 22.6% with SLG) were recruited. The majority (73.6%) were transplanted for hepatitis B virus (HBV)-related complications. MRI performed at a median of 12.2 years post-LT identified PTHS in 27.4 and 10.6% of patients. PTHS was independently associated with SLG (OR 2.067, 95% CI 1.082–3.951), central obesity (OR 3.952, 95% CI 1.768–8.832), and hypertension (OR 2.510, 95% CI 1.268–4.966). In contrast, ≥F3 was associated with sex, change in BMI, and abnormal liver biochemistry but not with PTHS or SLG.

Conclusion

MRI identified a high prevalence of PTHS, which was associated with SLG and metabolic risk factors among Chinese patients transplanted for non-MASLD indications. Advanced graft fibrosis was not associated with PTHS or SLG.
Factors influencing image quality in Tibetan children by optical coherence tomography
Authors: Yao Yao , Liu Jiawen , Li Lei , Chen Weiwei , Meng Zhaojun , Fu Jing
Published: January 2025

Purpose

This study aim to investigate the clinical findings of subjects characteristics and image quality related factors in Tibetan children by optical coherence tomography (OCT) in epidemiological cohort study.

Methods

Participants were 1,856 first-grade students (mean age = 6.82 ± 0.46 years) from seven selected elementary schools in Lhasa. Following comprehensive systemic and ophthalmic examinations, OCT scans were assessed by specialists with manual segmentation as needed.

Results

A total of 1,698 students completed the examination protocol in this study (91.5%). After manual screening, 1,447 (78%) and 1,289 (70%) images could be analyzed in the macular and optic disc regions, respectively. Common image flaws were blinking or fixation error (70%+), poor focusing, and positioning errors. Among students who have completed OCT, a higher percentage of boys (X2 = 8.48, P = 0.004) and suburban students (X2 = 34.97, P < 0.001) with younger age (t = -2.20, P = 0.03), worse near vision (t = -3.95, P < 0.001), higher IOP (t = 2.38, P = 0.017) and higher heart rate (t = 3.15, P = 0.002) have unsatisfactory image quality in the macular region, almost same as the optic disc region. Students in suburban schools (OR = 1.74, P < 0.001) with lower near VA (OR = 6.64, P < 0.001) or boys (OR = 0.78, P = 0.03) were more likely to have worse image quality on OCT scans when corrected for ethnicity. Manual segmentation was more prevalent in the optic disc region, resulting in increased retinal thickness across most subregions.

Conclusion

This study underscores the imperative for stringent image quality control in pediatric OCT assessments to ensure precise clinical outcomes.
Ligilactobacillus agilis W70: a probiotic with capacity to enhance ammonia assimilation in the rumen
Authors: Duan Xiaowei , Vigors Stafford , Ma Rui , Ma Lu , Gu Jingang , Bu Dengpan
Published: January 2025

Ruminants excrete both undigested and excess consumed nitrogen (N) through feces and urine, which results in the waste of feed protein and environmental pollution. This study aims to screen bacteria to identify strains with potential to improve nitrogen utilization in the rumen. In a tube screening test, when 30 mmol/L ammonium sulfate was added as the only nitrogen source in liquid medium, among 115 bacterial strains belonging to Bacillus and lactic-acid bacteria, 10 strains with the highest growth (OD600nm level) in comparison to the other evaluated strains were identified, and of these, Ligilactobacillus agilis W70 and Limosilactobacillus fermentum M50, had the highest ammonia nitrogen utilizing capabilities of ammonium sulfate (32.09 and 40.64%, respectively). A subsequent in vitro fermentation experiment was conducted with the diet consisting of 0.5 g TMR, 50 mL buffer solution, and 25 mL fresh rumen fluid per serum bottle which was incubated at 39°C for 24 h. The experiment consisted of 3 treatments, CTL, L. agilis W70 (1 × 109 cfu/mL), and L. fermentum M50 (1 × 109 cfu/mL), each treatment had 6 replicates, repeated across 3 batches. The addition of L. agilis W70 decreased NH3N (p < 0.01), the ratio of acetate to propionate (A:P) (p < 0.01), and increased the yields of microbial protein (MCP) (p < 0.01) and enzymatic activities of glutamate dehydrogenase (GDH) (p < 0.05) and glutamine synthetase (GS) (p < 0.05). Further genome analysis revealed that the L. agilis W70 harbors the glutamate dehydrogenase and glutamine synthetase-encoding genes gdhA and glnA that play key roles in ammonia utilization. This study identified L. agilis W70 as a strain which exhibits high NH3N utilization capability and enhances ammonia assimilation in vitro. The strain was further characterized to elucidate this ammonia assimilation potential. Further studies will be conducted to develop strain L. agilis W70 as a new feed additive to improve the nitrogen utilization efficiency in ruminant animals.
Global trends and emerging insights in BRAF and MEK inhibitor resistance in melanoma: a bibliometric analysis
Authors: Bai Jianhao , Wan Zhongqi , Zhou Wanru , Wang Lijun , Lou Wei , Zhang Yao , Jin Haiying
Published: January 2025

Objective

This study aims to perform a comprehensive bibliometric analysis of global research on BRAF and MEK inhibitor resistance in melanoma, identifying key research trends, influential contributors, and emerging themes from 2003 to 2024.

Methods

A systematic search was conducted in the Web of Science Core Collection (WoSCC) database to retrieve publications related to BRAF and MEK inhibitor resistance from 1 January 2003, to 1 September 2024. Bibliometric analyses, including publication trends, citation networks, and keyword co-occurrence patterns, were performed using VOSviewer and CiteSpace. Collaborative networks, co-cited references, and keyword burst analyses were mapped to uncover shifts in research focus and global cooperation.

Results

A total of 3,503 documents, including 2,781 research articles and 722 review papers, were analyzed, highlighting significant growth in this field. The United States, China, and Italy led in publication volume and citation impact, with Harvard University and the University of California System among the top contributing institutions. Research output showed three phases of growth, peaking in 2020. Keyword and co-citation analyses revealed a transition from early focus on BRAF mutations and MAPK pathway activation to recent emphasis on immunotherapy, combination therapies, and non-apoptotic cell death mechanisms like ferroptosis and pyroptosis. These trends reflect the evolving priorities and innovative approaches shaping the field of resistance to BRAF and MEK inhibitors in melanoma.

Conclusion

Research on BRAF and MEK inhibitor resistance has evolved significantly. This analysis provides a strategic framework for future investigations, guiding the development of innovative, multi-modal approaches to improve treatment outcomes for melanoma patients.
Application of the Uniform Data Set version 3 tele-adapted test battery (T-cog) for remote cognitive assessment preoperatively in older adults
Authors: Rockholt Mika M. , Wu Rachel R. , Zhu Elaine , Perez Raven , Martinez Hamleini , Hui Jessica J. , Commeh Ekow B. , Denoon Romario B. , Bruno Gabrielle , Saba Braden V. , Waren Daniel , O'Brien Courtney , Aggarwal Vinay K. , Rozell Joshua C. , Furgiuele David , Macaulay William , Schwarzkopf Ran , Schulze Evan T. , Osorio Ricardo S. , Doan Lisa V. , Wang Jing
Published: January 2025

Introduction

Older adults undergoing surgery are at risk of postoperative neurocognitive disorders, prompting the need for preoperative cognitive screening in this population. Traditionally, cognitive screening has been conducted in-person using brief assessment tools such as the Montreal Cognitive Assessment (MoCA) or the Mini-Mental State Examination (MMSE). More comprehensive test batteries, such as the Uniform Data Set (UDS) Neuropsychological Battery, and its remote testing version, the Uniform Data Set version 3 tele-adapted test battery (UDS v3.0 T-cog), have been developed to assess cognitive decline in normal aging and disease conditions, but have not been applied in the perioperative setting.

Methods

We assessed the feasibility of using this remote UDS v3.0 T-cog battery for preoperative cognitive assessment in 81 older adults 65+ scheduled for lower extremity joint replacement surgery.

Results

Our results indicate that the UDS v3.0 T-cog achieves 99% completion rates and demonstrates high patient satisfaction. Further, we found 28% of subjects were cognitively impaired in this patient cohort.

Discussion

These findings suggest that the UDS v3.0 T-cog is a feasible tool for assessing cognitive function in the older adult perioperative population. To our knowledge, this is the first study to apply this comprehensive remote test battery in the preoperative setting.
Cross-modality fusion with EEG and text for enhanced emotion detection in English writing
Authors: Wang Jing , Zhang Ci
Published: January 2025

Introduction

Emotion detection in written text is critical for applications in human-computer interaction, affective computing, and personalized content recommendation. Traditional approaches to emotion detection primarily leverage textual features, using natural language processing techniques such as sentiment analysis, which, while effective, may miss subtle nuances of emotions. These methods often fall short in recognizing the complex, multimodal nature of human emotions, as they ignore physiological cues that could provide richer emotional insights.

Methods

To address these limitations, this paper proposes Emotion Fusion-Transformer, a cross-modality fusion model that integrates EEG signals and textual data to enhance emotion detection in English writing. By utilizing the Transformer architecture, our model effectively captures contextual relationships within the text while concurrently processing EEG signals to extract underlying emotional states. Specifically, the Emotion Fusion-Transformer first preprocesses EEG data through signal transformation and filtering, followed by feature extraction that complements the textual embeddings. These modalities are fused within a unified Transformer framework, allowing for a holistic view of both the cognitive and physiological dimensions of emotion.

Results and discussion

Experimental results demonstrate that the proposed model significantly outperforms text-only and EEG-only approaches, with improvements in both accuracy and F1-score across diverse emotional categories. This model shows promise for enhancing affective computing applications by bridging the gap between physiological and textual emotion detection, enabling more nuanced and accurate emotion analysis in English writing.
Automatic etiological classification of stroke thrombus digital photographs using a deep learning model
Authors: Lucero-Garófano Álvaro , Aliena-Valero Alicia , Vielba-Gómez Isabel , Escudero-Martínez Irene , Morales-Caba Lluís , Aparici-Robles Fernando , Tarruella Hernández Diana L. , Fortea Gerardo , Tembl José I. , Salom Juan B. , Manjón José V.
Published: January 2025

Background

Etiological classification of ischemic stroke is fundamental for secondary prevention, but frequently results in undetermined cause. We aimed to develop a Deep Learning (DL)-based model for automatic etiological classification of ischemic stroke using digital images of thrombi retrieved by mechanical thrombectomy.

Methods

Patients with large vessel occlusion stroke subjected to mechanical thrombectomy between April 2016 and January 2023 at La Fe University and Polytechnic Hospital in Valencia were included. Thrombus digital images were obtained and clinical characteristics, including TOAST etiological classification as reference standard, were retrieved. Statistical analysis was performed to compare clinical characteristics between atherothrombotic and cardioembolic strokes. A DL method was designed based on two deep neural networks for: (1) image segmentation and (2) image classification including clinical characteristics. The metrics used were DICE coefficient for the segmentation network, and accuracy, precision, sensitivity, specificity and area under the curve (AUC) for the predictions of the classification network.

Results

A total of 166 patients (mean age 69 [SD, 13], 67 female) were included. TOAST classification was: 31 atherothrombotic, 87 cardioembolic, and 48 cryptogenic. The segmentation network achieved an average DICE coefficient of 0.96 [SD, 0.13]. The optimal fused imaging and clinical classification network had a 0.968 accuracy [95% CI, 0.935–0.994], and AUC of 0.947 [95% CI, 0.870–1]. Cryptogenic thrombi were classified as cardioembolic (96%) or atherothrombotic (4%).

Conclusion

Two convolutional neural networks perform the automatic segmentation of thrombus images and, combined with selected clinical characteristics, their accurate and precise classification into atherothrombotic or cardioembolic etiology in patients with acute ischemic stroke.
Method for assessing visual saliency in children with cerebral/cortical visual impairment using generative artificial intelligence
Authors: Matsunaga Kate , Avramidis Kleanthis , Borchert Mark S. , Narayanan Shrikanth , Chang Melinda Y.
Published: January 2025

Cerebral/cortical visual impairment (CVI) is a leading cause of pediatric visual impairment in the United States and other developed countries, and is increasingly diagnosed in developing nations due to improved care and survival of children who are born premature or have other risk factors for CVI. Despite this, there is currently no objective, standardized method to quantify the diverse visual impairments seen in children with CVI who are young and developmentally delayed. We propose a method that combines eye tracking and an image-based generative artificial intelligence (AI) model (SegCLIP) to assess higher- and lower-level visual characteristics in children with CVI. We will recruit 40 CVI participants (aged 12 months to 12 years) and 40 age-matched controls, who will watch a series of images on a monitor while eye gaze position is recorded using eye tracking. SegCLIP will be prompted to generate saliency maps for each of the images in the experimental protocol. The saliency maps (12 total) will highlight areas of interest that pertain to specific visual features, allowing for analysis of a range of individual visual characteristics. Eye tracking fixation maps will then be compared to the saliency maps to calculate fixation saliency values, which will be assigned based on the intensity of the pixel corresponding to the location of the fixation in the saliency map. Fixation saliency values will be compared between CVI and control participants. Fixation saliency values will also be correlated to corresponding scores on a functional vision assessment, the CVI Range-CR. We expect that fixation saliency values on visual characteristics that require higher-level processing will be significantly lower in CVI participants compared to controls, whereas fixation saliency values on lower-level visual characteristics will be similar or higher in CVI participants. Furthermore, we anticipate that fixation saliency values will be significantly correlated to scores on corresponding items on the CVI Range-CR. Together, these findings would suggest that AI-enabled saliency analysis using eye tracking can objectively quantify abnormalities of lower- and higher-order visual processing in children with CVI. This novel technique has the potential to guide individualized interventions and serve as an outcome measure in future clinical trials.
Muscle-specific Bet1L knockdown induces neuromuscular denervation, motor neuron degeneration, and motor dysfunction in a rat model of familial ALS
Authors: Eckardt Adam , Marble Charles , Fern Bradley , Moritz Henry , Kotula Charles , Ke Jiayi , Rebancos Clarisse , Robertson Samantha , Nishimune Hiroshi , Suzuki Masatoshi
Published: January 2025

Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease characterized by specific loss of motor neurons in the spinal cord and brain stem. Although ALS has historically been characterized as a motor neuron disease, there is evidence that motor neurons degenerate in a retrograde manner, beginning in the periphery at the neuromuscular junctions (NMJs) and skeletal muscle. We recently reported a vesicle trafficking protein Bet1L (Bet1 Golgi Vesicular Membrane Trafficking Protein Like) as a new molecule possibly linked to NMJ degeneration in ALS. In this study, we tested the hypothesis that Bet1L gene silencing in skeletal muscle could influence NMJ integrity, motor neuron function, and survival in a rat model of familial ALS (SOD1G93A transgenic). Small interfering RNA (siRNA) targeting the Bet1L gene was injected on a weekly basis into the hindlimb muscle of pre-symptomatic ALS and wild-type (WT) rats. After 3 weeks, intramuscular Bet1L siRNA injection significantly increased the number of denervated NMJs in the injected muscle. Bet1L knockdown decreased motor neuron size in the lumbar spinal cord, which innervated the siRNA-injected hindlimb. Impaired motor function was identified in the hindlimbs of Bet1L siRNA-injected rats. Notably, the effects of Bet1L knockdown on NMJ and motor neuron degeneration were more significant in ALS rats when compared to WT rats. Together, Bet1L knockdown induces denervation of NMJs, but also this knockdown accelerates the disease progression in ALS. Our results provide new evidence to support the potential roles of Bet1L as a key molecule in NMJ maintenance and ALS pathogenesis.
Maintenance of patient-reported health-related quality of life post neoadjuvant relugolix prior to the initiation of prostate radiation therapy
Authors: Koh Min Jung , Koh Min Ji , Hsueh Jessica Y. , Gallagher Lindsey , Danner Malika , Zwart Alan , Ayoob Marilyn , Kumar Deepak , Carrasquilla Michael , Leger Paul , Dawson Nancy A. , Suy Simeng , Collins Sean P.
Published: January 2025

Introduction

Studies have demonstrated that injectable GnRH receptor agonists further suppress cancer progression when paired with radiotherapy (RT) in patients with intermediate- to high-risk prostate adenocarcinoma. Relugolix is a newly available oral GnRH receptor antagonist that achieves swift and profound castration (total testosterone <20 ng/dl) at high rates, which may shape patients’ health-related quality of life. The main objective of this prospective study was to explore the effects of neoadjuvant relugolix on health-related quality of life in prostate cancer patients immediately prior to stereotactic body radiation therapy (SBRT).

Methods

Patients treated at Georgetown between January 2021 and September 2023 with neoadjuvant relugolix per an institutional protocol were included in the study (IRB 12-1775). The five-item EQ-5D-3L, a well-established tool for quantifying patient-reported health status, was administered to each patient at baseline (prior to relugolix treatment) and again 1 h before the start of SBRT. Higher EQ Visual Analog Scale (VAS) overall scores reflected better quality of life (range 0 to 100). In line with the questionnaire framework, individual elements (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) were rated on a three-point scale from 1 (no problems) to 3 (severe problems). McNemar’s test and paired-sample t-test were performed to analyze changes pre- and post-relugolix treatment. Our investigation determined clinical significance based on minimally important difference (MID) calculated as 0.5 times the baseline standard deviation.

Results

Among the 87 patients, average age was 71 years, 42% were non-white, and 24% were considered obese (BMI ≥30 kg/m²). Relugolix was initiated a median of 4 months before SBRT initiation (IQR: 3.9–5.4), with 87% of patients reaching profound castration (<20 ng/dl). The VAS overall score was notably higher at baseline (mean ± SD: 82 ± 10) compared to the paired score before RT (79 ± 14, p = 0.02), although this difference was not clinically significant. No statistically or clinically significant changes were observed in any of the five individual items.

Conclusion

The use of neoadjuvant relugolix prior to prostate radiation therapy had no clinically significant impact on patient-reported health-related quality of life. Moreover, no statistically significant reductions were observed in any of the five individual health-related quality of life measures. As a key direction for future research, relugolix-associated changes to healthy-related quality of life should be contrasted to those brought about by injectable GnRH agonists.
Retrospective analysis of 1539 nasopharyngeal carcinoma cases: chemotherapy should not be excluded for non-Asian patients with T1-2N1M0 stage
Authors: Li Xin-Yu , Zhong Chang-Ying , Xu Hui-Xian
Published: January 2025

Background

Many results suggested that chemotherapy cannot provide survival benefit for stage II nasopharyngeal carcinoma. It remained unclear whether the efficacy of chemotherapy differed in non-Asian populations.

Objective

It was designed to analyze the effect of chemotherapy for Asian and non-Asian patients with stage II nasopharyngeal carcinoma.

Method

Patients were collected using the SEER program. The variables included age, sex, race, marital status, survival time, survival status, TNM stage, radiation and chemotherapy. Utilizing the Rstudio (version: 2024.4.1.748) and R (version: 4.4.1), backward elimination method was employed to screen the variables and multivariate Cox regression analyses was conducted on the screened variables. Kaplan-Meier method was utilized to analyze the survival of sub-stages and different races with T1-2N1M0 stage. The log-rank test was used for statistical analysis.

Result

1539 patients were collected. Chemotherapy was statistically significant, with a hazard ratio (HR) of 0.64, P=0.003 in stage II patients. The HR for radiation was 0.33, P<0.001. Chemotherapy didn’t improve cancer-specific survival for patients with T2N0M0 stage. Asian and non-Asian races showed no difference in cancer-specific survival in T2N0M0 stage with HR of 1.85, P=0.13. For patients with T1-2N1M0 stage, chemotherapy improved cancer-specific survival with a HR of 0.53, P<0.001. No significant difference was in the Kaplan-Meier analysis between the two sub-stages (P=0.065). In T1-2N1M0 stage, multivariate Cox regression analysis for Asian race indicated that chemotherapy didn’t improve cancer-specific survival with a HR of 0.64, P=0.190. For non-Asian race, chemotherapy was found to improve cancer-specific survival, with a HR of 0.51, P<0.001. The Kaplan-Meier analysis of Asian and non-Asian patients with T1-2N1M0 stage exhibited significant differences (P<0.0001).

Conclusion

Chemotherapy is correlated with the cancer-specific survival in non-Asian patients with T1-2N1M0-stage nasopharyngeal carcinoma, but not in Asian patients at the same stage. For patients with the T2N0M0 stage, chemotherapy is not correlated with the cancer-specific survival rate, regardless of ethnicity.
Case Report: Successful treatment of metastatic retinoblastoma with CNS involvement with anti-GD2 immunotherapy, intrathecal topotecan and reduced systemic chemotherapy
Authors: Larrosa Cristina , Simao-Rafael Margarida , Salvador Noelia , Muñoz Juan Pablo , Lavarino Cinzia , Chantada Guillermo , Mora Jaume
Published: January 2025

High-dose chemotherapy with autologous stem cell rescue has improved outcomes in patients with metastatic retinoblastoma (RB). Despite significant advances, acute and long-term side-effects, particularly in visually impaired and cancer-predisposed patients, underscore the need for additional treatment options. Monoclonal antibodies (mAbs) directed against the tumor-associated antigen GD2 are of considerable interest. Additional lines of RB research include tracking minimal disseminated disease (MDD) to permit timely intervention in patients with CNS metastasis. We present two cases of bilateral, metastatic RB, managed with the anti-GD2 mAb naxitamab following reduced intensity myeloablative chemotherapy and autologous stem cell transplant (ASCT) with intrathecal topotecan for MDD detected in the CSF. The patients remain disease-free 10 and 9 years after initial diagnosis. While additional studies are needed, the results suggest anti-GD2 mAbs and CNS-directed chemotherapy may improve long-term outcomes and reduce cytotoxicity for high-risk patients with RB.
Plant protein-derived anti-breast cancer peptides: sources, therapeutic approaches, mechanisms, and nanoparticle design
Authors: Zhang Deju , Yuan Ying , Zeng Qingdong , Xiong Juan , Gan Yiming , Jiang Kai , Xie Ni
Published: January 2025

Breast cancer causes the deaths of approximately 685,000 women annually, posing a severe threat to women’s health. Consequently, there is an urgent need for low-cost, low-toxicity and effective therapeutic methods to prevent or mitigate breast cancer progression. PDBP are natural, non-toxic, and affordable substances and have demonstrated excellent anti-breast cancer activities in inhibiting proliferation, migration, and invasion, and promoting apoptosis both in vitro and in vivo, thus effectively preventing or inhibiting breast cancer. However, there are no comprehensive reviews summarizing the effects and mechanisms of PDBP on the treatment of breast cancer. Therefore, this review described the inhibitory effects and mechanisms of active peptides from different plant protein sources on breast cancer. Additionally, we summarized the advantages and preparation methods of plant protein-derived anticancer peptide-encapsulated nanoparticles and their effects in inhibiting breast cancer. This review provides a scientific basis for understanding the anti-breast cancer mechanisms of PDBP and offers guidance for the development of therapeutic adjuvants enriched with these peptides.
Post-extrasystolic variation of ST segment and T wave as a mortality risk predictor after myocardial infarction
Authors: Dirschinger Ralf J. , Müller Alexander , Barthel Petra , Steger Alexander , Dommasch Michael , Bauer Axel , Laugwitz Karl-Ludwig , Schmidt Georg , Sinnecker Daniel
Published: January 2025

Aims

Efficient use of preventive cardiac therapies is often limited by inefficient risk prediction, calling for new prediction tools. Ventricular premature complexes (VPCs) elicit electrocardiographic changes in the repolarization of the first post-extrasystolic normal beat. The aim of this study was to assess whether this post-extrasystolic ST segment and T wave variation (PEST) conveys prognostic information regarding the mortality risk of cardiac patients.

Methods

PEST was calculated from 30-min ECGs obtained from 941 survivors of acute myocardial infarction (AMI) as mean difference between the sum of squared voltages from three orthogonal leads (XYZ) of the first (post-extrasystolic) and second (reference) beat after each VPC, in a time window between the limits ϕ1 and ϕ2. Optimal limits yielding a maximum area under the receiver-operating characteristics (ROC) curve were determined by systematic testing, covering the time window from the J point to the end of the T wave. A strong association was found with ϕ1/ϕ2 encompassing 40–230 ms after the J point, which was used to calculate PEST in the analysis. Kaplan-Meier curves and univariable/multivariable Cox proportional hazards models were used to study mortality prediction by PEST. The findings were validated in an independent cohort of 1.788 general population subjects aged 60 years or older.

Results

The area under the ROC curve for PEST was 0.72, with an optimum cutoff at ≤ −6.69 mV2. The 88 patients with PEST values below this cutoff had a considerably higher mortality than the remainder of the patients (25% vs. 5.8%, p < 0.0001; univariable hazard ratio 4.7, 95% CI 2.4–12.0, p < 0.001). In a multivariable Cox regression analysis considering left-ventricular ejection fraction, presence of diabetes mellitus, and Global Registry of Acute Coronary Events (GRACE) score, PEST remained significantly associated with mortality (hazard ratio 3.6, 95% CI 1.9–6.9, p < 0.0001). In the validation cohort, abnormal PEST was also associated with significantly increased 4-year mortality (11.9% vs. 4.3%, p = 0.00095).

Conclusion

PEST is a strong independent predictor of all-cause mortality in AMI survivors and elderly subjects from the general population. While the pathophysiology of this association remains to be investigated, PEST may complement current risk prediction tools in various clinical settings.
Atrioventricular nodal reentrant tachycardia onset, sustainability, and spontaneous termination in rabbit atrioventricular node model with autonomic nervous system control
Authors: Ryzhii Maxim , Ryzhii Elena
Published: January 2025

Atrioventricular nodal reentrant tachycardia (AVNRT) is one of the most common types of paroxysmal supraventricular tachycardia. The activity of the autonomic nervous system (ANS) is known to influence episodes of AVNRT, yet the precise mechanisms underlying this effect remain incompletely understood. In this study, we update our compact multifunctional model of the rabbit atrioventricular (AV) node with ANS control to simulate AVNRT. The refractoriness of the model cells is adjusted by a specific ANS coefficient, which impacts the effective refractory periods, conduction delays, and intrinsic frequency of pacemaker cells. Using this model, we investigate the onset, sustainability, and spontaneous termination of typical slow-fast and atypical fast-slow forms of AVNRT under ANS modulation. The conditions for the onset and sustainability of AVNRT can exist independently in various combinations. Differences in the effective refractory periods of the slow and fast pathways of the AV node during anterograde and retrograde conduction determine the specific form of AVNRT. For the first time, a computer model reveals the potential to identify hidden processes within the AV node, thereby bringing us closer to understanding the role of ANS control in AVNRT. The results obtained are consistent with clinical and experimental data and represent a novel tool for studying the electrophysiological mechanisms behind this type of arrhythmia.
Parental effects of physiological integration on growth of a clonal herb
Authors: Zhang Li-Min , Zheng Li-Li , Yu Fei-Hai
Published: January 2025

Although numerous studies have independently tested the roles of physiological integration and parental effects on the performance of clonal plant species, few have assessed them simultaneously. Moreover, the capacity for physiological integration differs greatly within species of clonal plants. We conducted a greenhouse experiment with eight genotypes of the clonal herb Hydrocotyle verticillata. In the first phase, we either severed or maintained the connections between the original proximal nodes (the basal portion) and the new distal nodes (the apical portion) of each genotype. In the second phase, the ramets in the apical portion produced in the first phase were selected and cultivated, and their connections were subjected to the same severance treatments. In the first phase, the negative effects of severance on the apical portion balanced the positive effects of severance on the basal portion, resulting in no net effect of severance on total mass, leaf mass, stem mass, and ramet number for the whole clone. In the second phase, the effects of parental severance on stem mass of the apical portion of H. verticillata varied among the eight genotypes. Additionally, the positive effect of physiological integration on offspring generations was greater in the apical portion and the whole clone of one genotype when the parental connections were intact than when they were severed, whereas it was greater in the apical portion of another genotype when the parental connections were severed than when they were intact. Our results suggest that clonal parental effects can influence the capacity for physiological integration of offspring generations and that these effects may differ among genotypes within a species.
The formaldehyde stress on photosynthetic efficiency and oxidative stress response of moss Racomitrium japonicum L.
Authors: Li Wanting , Zhang Jiawen , Ma Siqi , Zhou Min , Li Ruixin , Tang Hao , Qiu Haiyan , Ren Peng , Tang Yunlai , Lu Yunmei , Huang Renhua , Chen Ke
Published: January 2025

Introduction

Formaldehyde is a common gaseous pollutant emitted by buildings and decorative materials. In recent years, growing concerns have been raised regarding its harmful effects on health in indoor air. Therefore, this study aims to investigate the physiological and photosynthetic response mechanisms of Racomitrium japonicum under formaldehyde stress.

Methods

R. japonicum was exposed to dynamic fumigation with formaldehyde for 7 days, with each day comprising an 8-h exposure period within a sealed container. The effects on plant structure, pigment content, photosynthetic efficiency, and reactive oxygen species (ROS) generation were assessed.

Results and discussion

Our findings revealed that formaldehyde stress caused structural damage, reduced pigment content, decreased photosynthetic efficiency, and increased ROS production in R. japonicum. Significantly, distinct stress-response pathways were observed at different formaldehyde concentrations. In response to low and moderate formaldehyde concentrations, R. japonicum activated its antioxidant enzyme system to mitigate ROS accumulation. In contrast, the high-concentration treatment group demonstrated suppressed antioxidant enzyme activity. In response, R. japonicum used nonphotochemical quenching and activated cyclic electron flow to mitigate severe cellular damage. This study provides an in-depth understanding of the physiological changes in R. japonicum under formaldehyde stress, elucidating its response mechanisms. The findings offer valuable insights for developing effective indoor formaldehyde monitoring and purification methods.
Disentangling “polarization in religion”
Authors: Rodenhausen Lina
Published: January 2025

This paper examines phenomena at the intersection of polarization, religion, and social media. In particular, it disentangles and highlights the concept of “polarization in religion.” Polarization is a well-studied concept in political science and it has been considered in relation to religion before. However, these attempts are usually either interested in political polarization and the role religion plays in it, or conflate socio-political attitudes and religious issues. To fully understand polarization as a phenomenon of religion, it is important to disentangle it from politics and examine the beliefs and identities that are unique to religious traditions. The focus is on the progressive and conservative characteristics that are specific to religious groups. It is proposed to conceptualize and study polarization in religion as the construction of new religious identities. A collective identity approach can be used to examined how “progressive religious” and “conservative religious” emerge as distinct and coherent identities. Identity formation is facilitated in digital space, which is one of the reasons why polarization in religion is conceptualized as inherently involving social media. Social media in general can contribute to polarization, and contemporary religion in general cannot be understood without considering digital religion. Religion encounters a particularly conducive environment for transformation processes on social media platforms such as the transformation process of polarization with the creation of progressive and conservative religious identities. The theoretical framework presented in this paper provides a foundation for future empirical research on polarization in religion, as its broader examination is necessary to develop a more comprehensive understanding of this phenomenon and thus of contemporary religion in general.
How (and why) languages became more complex as we evolved more prosocial: the human self-domestication view
Authors: Benítez-Burraco Antonio
Published: January 2025

This paper aims to re-examine the problem of the emergence of present-day languages from the specific perspective of the self-domestication account of human evolution. According to this view, our species went through an evolutionary process that parallels the changes experienced by domesticated mammals. Relying on evidence of diverse kind (from paleogenetic to clinical), the paper argues that our self-domestication might have potentiated the cognitive and behavioral features of the human phenotype with an impact on language acquisition and use. Specifically, it might have facilitated the creation of the cultural niche that favors the complexification of languages via a cultural mechanism. The paper further proposes a model of language complexification in the past under the effects of human self-domestication, including the complexification of the structural aspects of language (grammar, prosody, and semantics) and the potentiation of its functional properties (pragmatics). The paper concludes with some suggestions for any future research aimed to test and improve this view.