bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a novel SPTB gene splicing mutation in hereditary spherocytosis: a case report and diagnostic insights
Authors: Li Xiaobing , Zhang Tingqiang , Li Xuemei , Wang Li , Li Qian , Liu Qianqian , He Chengyin , Zhang Li , Liu Yongsheng , Tang Junling
Published: January 2025

Background

Hereditary spherocytosis (HS) is a group of genetically heterogeneous hereditary hemolytic disorders characterized by anemia, splenomegaly, jaundice, reticulocytosis, and spherical red blood cells on peripheral blood smears. Mutations in key genes, including SPTB, ANK1, SLC4A1, SPTA1, and EPB42, are commonly implicated in HS.

Case Presentation

We report the case of a 22-year-old female presenting with anemia, jaundice, and a family history of splenectomy. Laboratory investigations revealed hemolytic anemia, elevated bilirubin levels, and peripheral blood smear findings consistent with HS. Genetic testing identified a novel SPTB gene splicing mutation (NM_001355436.2: c.1645-1G>A), inherited maternally, which is predicted to disrupt normal RNA splicing and protein synthesis.

Discussion

The identified SPTB mutation expands the known mutation spectrum of the SPTB gene and highlights its role in the pathogenesis of HS. Clinical findings, combined with genetic analysis, confirmed the diagnosis of HS and underscored the importance of comprehensive molecular testing for accurate diagnosis, especially in patients with a strong family history.

Conclusion

This case emphasizes the utility of genetic testing in diagnosing hereditary spherocytosis, particularly for novel gene mutations. Early and accurate molecular diagnosis facilitates better clinical management, family counseling, and treatment decisions for patients with HS.
Quest Narratives and Heroine Journeys: the road to freebirth and the joy of undisturbed physiological birth
Authors: McKenzie Gemma
Published: January 2025

Freebirth (intentionally giving birth without doctors or midwives present) is a taboo and stigmatised birthing decision. In this study, 16 women who had freebirthed their babies in the UK were interviewed, and the data was analysed using the voice-centred relational method (VCRM). This methodology produces a range of outputs, including I-Poetry. Previous scholars have noted the difficulty in presenting results from VCRM research and have devised varied and creative ways of subverting these obstacles. Uniquely, this article relies on the theories of Joseph Campbell, Arthur Frank, and Kim Hudson to present women's freebirth accounts as both Quest Narratives and Heroine Journeys. The article outlines the theoretical underpinnings of the Heroine’s Journey and demonstrates its use with women's freebirth accounts as they pertain to the joy of undisturbed physiological birth.
Development and validation of a nomogram for predicting immune-mediated colitis in lung cancer patients treated with immune checkpoint inhibitors: a retrospective cohort study in China
Authors: Xu Qianjie , Li Xiaosheng , Yuan Yuliang , Liang Guangzhong , Hu Zuhai , Zhang Wei , Wang Ying , Lei Haike
Published: January 2025

Background

The increasing utilization of immune checkpoint inhibitors (ICIs) has led to a concomitant rise in the incidence of immune-related adverse events (irAEs), notably immune-mediated colitis (IMC). This study aimed to identify the clinical risk factors associated with IMC development in patients with lung cancer and to develop a risk prediction model to facilitate personalized treatment and care strategies.

Methods

The data collected included 21 variables, including sociodemographic characteristics, cancer-related factors, and routine blood markers. The dataset was randomly partitioned into a training set (70%) and a validation set (30%). Univariate and multivariate logistic regression analyses were conducted to identify independent predictors of IMC development. On the basis of the results of the multivariate analysis, a nomogram prediction model was developed. Model performance was assessed via the area under the receiver operating characteristic curve (AUC), calibration curve analysis, decision curve analysis (DCA), and clinical impact curve (CIC).

Results

Among the 2103 patients, 66 (3.14%) developed IMCs. Multivariate logistic regression analysis revealed female sex, small cell lung cancer (SCLC), elevated β2 microglobulin (β2-MG) and globulin (GLB) levels, and an increased neutrophil−lymphocyte ratio (NLR) as independent predictors of IMC development (all P < 0.05). Conversely, a higher white blood cell (WBC) count, CD4/CD8 ratio, and platelet−lymphocyte ratio (PLR) were identified as factors associated with a reduced risk of IMC development (all P < 0.05). The nomogram prediction model demonstrated good discrimination, achieving an AUC of 0.830 (95% CI: 0.774–0.887) in the training set and 0.827 (95% CI: 0.709–0.944) in the validation set. Analysis of the calibration curve, DCA, and CIC indicated good predictive accuracy and clinical utility of the developed model.

Conclusion

This study identified eight independent predictors of IMC development in patients with lung cancer and subsequently developed a nomogram-based prediction model to assess IMC risk. Utilization of this model has the potential to assist clinicians in implementing appropriate preventive and therapeutic strategies, ultimately contributing to a reduction in the incidence of IMC among this patient population.
Chromatin accessibility and differentially expressed genes profiling in large yellow croaker (Larimichthys crocea) head kidney cells following iridovirus infection
Authors: Song Chaowei , Huang Ying , Han Fang , Wang Zhiyong
Published: January 2025

Introduction

The large yellow croaker iridovirus (LYCIV) poses a significant threat to the aquaculture industry of Larimichthys crocea. Understanding the host defense response to LYCIV infection is crucial for developing effective strategies to mitigate its impact.

Methods

In this study, an epigenetic approach was employed to investigate dynamic changes in chromatin accessibility using the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq). Additionally, RNA sequencing (RNA-seq) was used to analyze the expression pattern of immune response genes upon LYCIV infection.

Results

Substantial alterations in chromatin accessibility were observed, particularly in the regulatory regions of key immune-related genes. Significant changes in the expression of AP-1 transcription factors, including the Batf gene, were noted. CUT&Tag results revealed that AP-1 was significantly enriched in the open chromatin regions of cytokine genes, with Batf potentially regulating the cytokine genes LIF and CLCF1.

Discussion

These findings suggest that AP-1 may play a crucial role in the defense response against viral infection by modulating inflammatory cytokines and contributing to cellular inflammatory responses. This study provides a comprehensive analysis of the epigenomic landscape and gene expression regulation during iridovirus infection in L. crocea, offering valuable insights for breeding programs aimed at combating iridovirus infections.
Preoperative assessment of liver regeneration using T1 mapping and the functional liver imaging score derived from Gd-EOB-DTPA-enhanced magnetic resonance for patient with hepatocellular carcinoma after hepatectomy
Authors: Li Qian , Zhang Tong , Yao Shan , Gao Feifei , Nie Lisha , Tang Hehan , Song Bin , Wei Yi
Published: January 2025

Objectives

To explore whether T1 mapping parameters and the functional liver imaging score (FLIS) based on Gd-EOB-DTPA MRI could evaluate liver regeneration after hepatectomy for HCC patient.

Methods

This retrospective study finally included 60 HCC patients (48 men and 12 women, with a median age of 53 years). T1 relaxation time of liver before gadoxetic acid injection (T1pre) and during the hepatobiliary phase (T1HBP), reduction rate (Δ%) and FLIS were calculated, their correlations with liver fibrosis stage, hepatic steatosis, and liver regeneration, quantified as regeneration index (RI), were assessed by Kendall’s tau-b correlation test or Spearman’s correlation test. Multivariate linear regression analyses were used to explore the indicator of RI.

Results

T1pre, T1HBP, Δ%, and FLIS manifested significant correlation with fibrosis stage (r = 0.434, P =0.001; r = 0.546, P < 0.001; r = -0.356, P =0.005; r = -0.653, P <0.001, respectively). T1pre showed significant correction with steatosis grade (r = 0.415, P =0.001). Fibrosis stage and steatosis grade were associated with RI (r = -0.436, P<0.001; r = -0.338, P =0.008). Accordingly, T1pre, T1HBP and FLIS were the significant predictors (P<0.05) of RI in multivariate analysis. Similarly, in the patients undergoing minor hepatectomy (n=35), T1HBP, Δ% and FLIS were related to RI (P<0.05) in multivariate analysis. Nevertheless, in the patients undergoing major hepatectomy (n=25), no T1 mapping parameter and FLIS was the independent predictor of RI.

Conclusions

T1 mapping parameters and FLIS were the potential noninvasive indicators of liver regeneration, except for HCC patients undergoing major hepatectomy.

Clinical relevance statement

The value of T1 mapping and FLIS with Gd-EOB-DTPA MRI for accurate preoperative evaluation of liver regeneration is critical to prevent liver failure and improve prognosis of HCC patients.
NF-κB signaling and the tumor microenvironment in osteosarcoma: implications for immune evasion and therapeutic resistance
Authors: Shi Shaoyan , Ou Xuehai , Liu Chao , Li Rui , Zheng Qianjin , Hu Leiming
Published: January 2025

Osteosarcoma, a highly aggressive malignancy with a generally poor prognosis, is characterized by tumor cells’ ability to evade immune responses and resist treatment. The nuclear transcription factor NF-κB signaling pathway is crucial in regulating inflammatory and immune reactions. It occupies a central position in the development of the osteosarcoma tumor microenvironment. This research aimed to explore how NF-κB influences the recruitment and polarization of tumor-associated macrophages and myeloid-derived suppressor cells, both of which contribute to immunosuppression. Furthermore, NF-κB facilitates immune surveillance evasion in osteosarcoma cells by altering the expression of immune checkpoint molecules, such as PD-L1. It also enhances tumor cell resistance to chemotherapy and radiotherapy by activating anti-apoptotic signaling pathways and exacerbating treatment-induced inflammation. Potential therapeutic approaches include using NF-κB inhibitors, possibly in combination with immune checkpoint inhibitors, to overcome tumor cell resistance mechanisms and reshape antitumor immune responses. A thorough examination of NF-κB’s role in osteosarcoma development is expected to yield novel clinical treatment strategies, and significantly improve patient prognosis by targeting this key signaling pathway.
Peripheral blood cell counts as predictors of immune-related adverse events in cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis
Authors: Zhang Xinyu , Zhang Bei , Li Danfei , Yang Yunchao , Lin Sen , Zhao Ruiqi , Li Yijia , Peng Lisheng
Published: January 2025

Background

In recent years, immune checkpoint inhibitors (ICIs) have shown significant efficacy in treating various malignancies and have become a key therapeutic approach in cancer treatment. However, while ICIs activate the immune system, they can also induce immune-related adverse events (irAEs). Due to the variability in the frequency and severity of irAEs, clinical management faces a significant challenge in balancing antitumor efficacy with the risk of irAEs. Predicting and preventing irAEs during the early stages of treatment has become a critical research focus in cancer immunotherapy. This study aims to evaluate the predictive value of peripheral blood cell counts for irAEs.

Methods

Studies meeting the inclusion criteria were identified through database searches. The standardized mean difference (SMD) was used to compare continuous blood cell counts. For studies that did not provide adjusted odds ratios (ORs) and 95% confidence intervals (CIs), crude ORs for categorized blood cell counts were calculated. The study protocol was registered on PROSPERO (CRD42024592126).

Results

The meta-analysis included 60 studies involving 16,736 cancer patients treated with ICIs. Compared to patients without irAEs, those experiencing irAEs had significantly higher baseline continuous ALC (SMD = 0.12, 95% CI = 0.01-0.24), while ANC (SMD = -0.18, 95% CI = -0.28 to -0.07) and PLR (SMD = -0.32, 95% CI = -0.60 to -0.04) were significantly lower. Similarly, categorized blood cell counts indicated that higher baseline ALC (OR = 2.46, 95% CI = 1.69-3.57) and AEC (OR = 2.05, 95% CI = 1.09-3.85), along with lower baseline NLR (OR = 0.64, 95% CI = 0.50-0.81) and PLR (OR = 0.63, 95% CI = 0.48-0.82), were associated with an increased risk of irAEs. Subgroup analysis further identified cutoff values for ALC (2×10^9/L), NLR (5 or 3), and PLR (180) as better predictors of irAEs.

Conclusion

Higher baseline ALC and AEC, along with lower baseline ANC, NLR, and PLR, are associated with an increased risk of irAEs. However, further research is needed to determine the optimal cutoff values and to explore the efficacy of blood cell counts in predicting specific types of irAEs.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024592126.
Supplementation with active vitamin D3 ameliorates experimental autoimmune thyroiditis in mice by modulating the differentiation and functionality of intrathyroidal T-cell subsets
Authors: Wang Chun-Mei , Chen Ying-Jie , Yang Bo-Cheng , Yang Jia-Wen , Wang Wei , Zeng Yang , Jiang Jun
Published: January 2025

Objective

People with Hashimoto’s thyroiditis (HT) often have low vitamin D3 concentrations. Some research has suggested that vitamin D3 supplementation reduces thyroid inflammation, but this remains controversial.

Methods

EAT was induced in female NOD/ShiLtJ mice by giving them water containing 0.05% sodium iodide, and 1μg/kg of 1α,25-(OH)2D3 was injected intraperitoneally every other day. After 8 weeks, the morphological architecture of the mouse thyroid follicles was examined by histological sections, thyroid autoantibodies and thyroid hormone concentrations were determined by enzyme-linked immunosorbent assays (ELISAs), and the major functions and subsets of B- and T-lymphocytes in the mouse thyroid were determined by tissue multiple immunofluorescence technology and ELISA.

Results

EAT caused thyroiditis follicle destruction and interfollicular lymphocyte infiltration in mice, increased concentrations of circulating thyroid autoimmune antibodies TG-Ab and TPO-Ab, and abnormal thyroid hormone levels. EAT also increased the number and functionality of CD4+ Tfh, Th17,Th1 and Th2 cells in the thyroid, while decreasing the number and functionality of CD4+ Treg cells and CD19+B10 cells. Treatment with VD3 reversed these changes.

Conclusion

Vitamin D3 supplementation can effectively treat autoimmune thyroiditis in mice. VD3 reduces autoimmune thyroid damage and decreases serum thyroid antibody levels in mice by inhibiting the differentiation and functionality of pro-inflammatory Tfh, Th17, Th1 and Th2 cells and by facilitating the differentiation and functionality of anti-inflammatory B10 cells and Treg.
Restoration of Type 17 immune signaling is not sufficient for protection during influenza-associated pulmonary aspergillosis
Authors: Ahmad Aijaz , Singh Ravineel B. , Nickolich Kara L. , Pilewski Matthew J. , Ngeow Caden , Frempong-Manso Kwame , Robinson Keven M.
Published: January 2025

Introduction

Influenza-associated pulmonary aspergillosis (IAPA) is a severe complication of influenza infection that occurs in critically ill patients and results in higher mortality compared to influenza infection alone. Interleukin-17 (IL-17) and the Type 17 immune signaling pathway cytokine family are recognized for their pivotal role in fostering protective immunity against various pathogens. In this study, we investigate the role of IL-17 and Type 17 immune signaling components during IAPA.

Methods

Wild-type mice were challenged with influenza A H1N1 (flu) and then exposed to Aspergillus fumigatus ATCC42202 resting conidia on day 6 post-influenza infection, followed by the quantification of cytokines and chemokines at 48 h post-fungal infection.

Results and discussion

The gene and protein expression levels revealed that IL-17 and Type 17 immune cytokines and antimicrobial peptides are downregulated during IAPA compared to mice singularly infected solely with A. fumigatus. Restoration of Type 17 immunity was not sufficient to provide protection against the increased fungal burden observed during IAPA. These findings contrast those observed during post-influenza bacterial super-infection, in which restoration of Type 17 immune signaling protects against exacerbation seen during super-infection. Our study highlights the need for future studies to understand the immune mechanisms that increase susceptibility to fungal infection.
Progress in the application of novel inflammatory indicators in chronic kidney disease
Authors: Gao Wenrui , Wang Xiangyu , Zou Yulin , Wang Sheng , Dou Jun , Qian Senlin
Published: January 2025

Chronic kidney disease has become a public health problem endangering the health of all humans because of its high prevalence, high mortality and high medical burden. The chronic micro-inflammatory state is recognized as a significant component of CKD, playing a key role in disease progression. Intervening in chronic inflammation during the disease course can enhance prognosis. Recent studies have demonstrated that novel inflammatory indices, such as the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune-inflammatory index are closely associated with CKD, meanwhile may serve as prognostic monitors of all-cause death and poor renal prognosis for the disease. This article comprehensively reports on the mechanisms of micro-inflammation in CKD, the relationship between inflammatory indicators and CKD, and their impact on prognosis.
Should miliary tuberculosis be considered as a possible cause of infertility in the new era: a case report and literature review
Authors: Cvetkovic Aleksandra , Blanka Protic Ana , Jovanovic Jelena , Adzic Vukicevic Tatjana
Published: January 2025

Introduction

Miliary tuberculosis (MTB) is a potentially lethal form of tuberculosis that can occur in pregnant women, especially those who have conceived by in vitro fertilization (IVF).

Case description

A 28-year-old, female patient, after IVF’s fourth attempt, at the end of the first trimester, developed a dry cough, high fever, abdominal pain, and vaginal bleeding, which led to the pregnancy termination without resolution of systemic symptoms despite various antibiotics. Because of the appearance of headaches, brain nuclear magnetic resonance (NMR) was done, and diffuse nodular brain lesions were found, which were initially interpreted as metastatic cancer disease. Afterward, the miliary changes were discovered in various organ systems, and the presence of Mycobacterium tuberculosis was confirmed. The antituberculosis treatment was initiated with the standard antituberculosis regimen with excellent clinical response and resolution of miliary changes.

Conclusion

Miliary tuberculosis is more common in cases of pregnancies related to IVF. It should be taken into consideration as a possible risk for infertility in the presence of nonspecific symptoms. Screening methods for latent tuberculosis in IVF patients are needed even in a low-burden TB country.
Correlation between gallstones and fasting blood glucose to serum high-density lipoprotein cholesterol ratio among American adults
Authors: Wu Bo , Zheng Huachao , Zhuang Caixiang , Mao Jiesheng , Yuncheng Luo , Huang Lidong , Li Min , Feiyang Zhao , Lin Sisi , Wang Pengwei , Hu Yiren
Published: January 2025

Background

Research indicates that the ratio of fasting blood glucose (FBG) to serum high-density lipoprotein cholesterol (HDL-C) (GHR) can accurately predict many diseases. Nevertheless, the relationship between GHR and the risk of gallbladder stones remains unclear. This study investigates the possible relationship between GHR and the incidence of gallbladder stones.

Methods

This research used information gathered from the National Health and Nutrition Examination Survey (NHANES) between March 2017 and March 2020. A calculation was made to determine the GHR by dividing the fasting blood glucose level by the HDL-C level. Several statistical methods, including analysis of threshold effects, smoothed curve fitting, multiple logistic regression modeling, and subgroup analysis, were utilized to investigate the connection between GHR and gallstones.

Results

In 3898 U.S. adults, GHR was significantly positively associated with the prevalence of gallbladder stones. In a fully adjusted model, the incidence of gallbladder stones increased by 7% with each 1-unit increase in GHR (OR [95% Cl] = 1.07 [1.02, 1.14]). Compared with members in the low group, those in the high group had a 100% higher likelihood of getting gallbladder stones (OR [95% CI] = 2.00 [1.31, 3.04]), and this stabilizing connection was always present in the different subgroups. With the help of smooth curve fitting, the research also showed that there was a connection that was formed like an upside-down L shape between GHR and gallbladder stones. The analysis of the threshold effect revealed that the inflection point was 4.28.

Conclusion

The results revealed an inverted L-shaped connection between GHR and gallbladder stones. Keeping GHR levels within a certain range is associated with a lower incidence of gallstones in the general population.
Polygonatum kingianum polysaccharide alleviated intestinal injuries by mediating antioxidant ability and microbiota
Authors: Qiu Reng , Pan Chuangye , Qin Yuxi , Wei Qianfei , Yu Yue , Zhang Ying , Xie Xuehan , Li Jianqin , Chen Shouhai , Li Kun , Fouad Dalia , Wu Yi , Zhong Qiu
Published: January 2025

Introduction

Polygonatum kingianum is a well-known medicinal herb with proven bioactivities; however, little is known about the effects of its polysaccharide on intestinal injuries in animals induced by lipopolysaccharide (LPS).

Methods

A total of 30 Institute of Cancer Research (ICR) mice were divided into control (CH), induced (MH), and treated (H) groups. Mice in group H were supplemented with 100 mg/kg Polygonatum kingianum polysaccharides, while groups C and M were treated with the same amount of normal saline by gavage for 18 days. On the 18th day animals in groups M and H were induced by LPS (10 mg/kg).

Results

The results showed the weight of mice in group MH significantly dropped (P < 0.0001), while mice in the PK group had a higher weight (P < 0.01). Pathological analysis found that the majority of the villi in mice induced by LPS were broken and short, while PK-treated animals had longer and considerably integrated villi. The villi length in groups CH (P < 0.0001) and H (P < 0.0001) was longer than that in group M, and the value of villi length/crypt depth in group MH was smaller than that in groups CH (P < 0.0001) and H (P < 0.0001), while the crypt depth in group MH was higher than in groups CH (P < 0.0001) and H (P < 0.0001). Serum inspection showed that MAD (P < 0.05), IL-1β (P < 0.05), IL-6 (P < 0.05), and TNF-α (P < 0.01) were significantly higher in group MH, while SOD (P < 0.001), T-AOC (P < 0.01), and GSH-Px (P < 0.01) were notably higher in groups CH and H. Microbiome sequencing of mice obtained 844,477 raw and 725,469 filtered reads. There were 2,407 ASVs detected in animals, and there were 312 and 328 shared ASVs between CH and MH, and CH and H, respectively. There were 5 phyla and 20genera of remarkable bacteria found among mice groups including genera of Escherichia, Pseudomonas_E, Mailhella, Paramuribaculum, NM07-P-09, Odoribacter, Nanosyncoccus, SFM01, Onthenecus, Clostridium_Q, UBA6985, Ructibacterium, UBA946, Lachnoclostridium_B, Evtepia, CAG-269, Limivicinus, Formimonas, Dehalobacterium, Dwaynesavagella, and UBA6985. We revealed that Polygonatum kingianum polysaccharide could alleviate intestinal injuries by promoting oxidation resistance, decreasing inflammatory responses, and accommodating the intestinal microbiota of mice.

Discussion

Our results suggest the possibility of developing novel therapies for intestinal diseases.
Climate change-driven shifts in the global distribution of tomato and potato crops and their associated bacterial pathogens
Authors: Hubab Muhammad , Lorestani Niloufar , Al-Awabdeh Rogayah Akram Mheisin , Shabani Farzin
Published: January 2025

Introduction

Climate change is increasingly affecting the global distribution and productivity of critical food crops, including Solanum lycopersicum (tomato) and Solanum tuberosum (potato). In particular, bacterial pathogens such as Clavibacter michiganensis and Ralstonia solanacearum are expected to shift their geographic ranges, posing new risks to these crops. This study hypothesizes that under future climate scenarios, the geographic overlap between these crops and their pathogens will increase in certain regions, leading to heightened agricultural risks, especially in areas currently considered safe from these pathogens.

Methods

To test our hypotheses, the objective was to evaluate the potential impact of climate change on the geographic distribution of two key food crops (tomato and potato) and their bacterial pathogens for the current time and by 2050. This study used four species distribution models (SDMs) to predict current and future habitat suitability for both tomato and potato crops, as well as their associated pathogens, under two shared socioeconomic pathways (SSP4.5 and SSP8.5) and four global circulation models (GCMs).

Results

The models projected significant poleward shifts in suitable habitats for tomatoes and potatoes, with notable expansions in higher-latitude regions such as Canada, northern Europe, and Russia, and contractions in current major production zones such as the United States (US), Brazil, parts of Africa, and China. For Clavibacter michiganensis, the overlap with tomatoes was substantial, whereas the overlap between potatoes and Ralstonia solanacearum was comparatively smaller.

Discussion

Our hypothesis was partially supported by the results. While the overall overlap between crop and pathogen habitats remains limited, the risk areas for both pathogens are expected to expand under future climate conditions in regions such as eastern Australia, Japan, Spain, and France. These findings underscore the importance of region-specific agricultural planning and pathogen management strategies to mitigate the risks posed by climate change. Future efforts should focus on vulnerable areas to prevent significant economic losses and ensure food security.
Oxytocin as a physiological correlate of dyadic music therapy relationships — a randomized crossover pilot study
Authors: Busse Paula Kristin , Neugebauer Lutz , Kaschubowski Götz , Anheyer Dennis , Ostermann Thomas
Published: January 2025

Rationale

Music therapy has been in practice for years. However, the mechanism of action of music or music therapy is not well understood. It is only recently that the neuroendocrinological basis of therapeutic relationships has become the subject of growing research interest. The aim of this pilot study (Clinical Trial No: DRKS00035174) is to investigate whether oxytocin is usable and feasible as a biomarker of attachment to demonstrate the development of therapeutic alliance between therapist and patient in a dyadic music therapy setting.

Methods

In a single-measure crossover design, children aged 6–12 years from a special school for social and emotional disorders, were randomly with either music therapy followed by a waiting list control group that performed silent work, or vice versa. The respective interventions were conducted on the school premises on different days over a period of 1 month. The primary outcome was salivary oxytocin, with tests performed immediately before and after each 30-min intervention.

Results

Thirty-two children were included in the study, resulting in n = 16 children per allocation sequence. During the implementation of the study, difficulties were encountered with protocol adherence both in terms of the duration of the music therapy and the implementation of the silent work in the control group. There were no dropouts, however, only 28 children were included in the final data analysis as two participants in each group were excluded due to large fluctuations in oxytocin levels. Between-group comparison and within-group comparisons showed no significant changes in oxytocin levels. However, the music therapist showed a significant increase in oxytocin levels in the before after measurement. No side effects or adverse events were reported during the trial.

Conclusion

The findings indicated a responsiveness of oxytocin to musical stimulation. Although feasibility of oxytocin measurement was clearly demonstrated, evaluation of the results is difficult against the background of many remaining questions regarding individual and contextual factors influencing the oxytocinergic system. Moreover, the clinical significance of changes in oxytocin levels remains a topic for further research to better understand the role of oxytocin in the attachment formation between therapist and patient in music therapy.
Enhancing balance and auditory function in bilateral vestibulopathy through otolithic vestibular stimulation: insights from a pilot study on cochlea-vestibular implant efficacy
Authors: Ramos-de-Miguel Ángel , Sluydts Morgana , Falcón Juan Carlos , Manrique-Huarte Raquel , Rodriguez Isaura , Zarowski Andrzej , Barbara Maurizio , Manrique Manuel , Borkoski Silvia , Lorente Joan , Leblanc Marc , Rambault Antonin , Van Baelen Erika , Van Himbeeck Carl , Huarte Alicia , Macías Ángel Ramos
Published: January 2025

Introduction

This study evaluates cochleovestibular implants (CVI) for improving auditory and vestibular function in patients with bilateral vestibulopathy and severe-to-profound hearing loss. CVI uniquely combines auditory and vestibular stimulation, offering a potential solution for dual impairments in hearing and balance.

Methods

Ten patients underwent CVI implantation. Auditory function was assessed with pure-tone audiometry (PTA) and speech recognition at baseline, 3, and 9 months post-implantation. Vestibular function was measured using the Dynamic Gait Index (DGI), Sensory Organization Test (SOT), posturography, and the Dizziness Handicap Inventory (DHI). Placebo-controlled tests verified cochleovestibular stimulation specificity.

Results

Auditory outcomes showed PTA improvements from 78 dB HL preoperatively to 34 dB HL at 3 months and 36 dB HL at 9 months, alongside speech recognition gains. Vestibular improvements included significant DGI (p < 0.05) and SOT score increases (33% to 68%, p < 0.05). DHI scores reflected reduced dizziness-related disability. Residual balance gains after device deactivation suggest neural adaptation, and placebo tests confirmed cochleovestibular stimulation specificity.

Discussion

CVI effectively restores auditory and vestibular function, with improvements in hearing, balance, and quality of life. Neural plasticity likely supports long-term benefits. Future research should refine device design and stimulation protocols to enhance outcomes further.
Seasonal fluctuation of total water intake and hydration status among young men and women: a prospective cohort study
Authors: Zhang Jianfen , Zhang Na , Lu Junbo , Liu Shufang , Lin Yongwei , Ma Guansheng
Published: January 2025

Background

Water intake and hydration status have been reported to fluctuate throughout the year. This study investigated seasonal fluctuations of total water intake and hydration status among young adults in Baoding, China.

Methods

This prospective cohort study enrolled 82 young adults aged 18–23 years in Baoding, China. Total drinking fluids consumed and water from food were assessed, and the osmolality and electrolyte concentrations of 24-h urine and fasting blood samples were determined. Differences among the four seasons were compared by mixed linear models, followed by determinations of least-significant differences (LSD), with spring used as the reference.

Results

Seventy-nine participants (43 men and 36 women) completed the study. Total water intake (TWI) was 359 ~ 429 mL higher in spring and summer than in autumn and winter and was 116 mL higher in summer than in winter (all p < 0.05). Chinese recommendations for TWI were met by 13.9% to 22.8% of participants, and recommendations for total fluid intake were met by 10.1% to 16.5%, but these differences were not statistically significant (p > 0.05). Urinary and plasma biomarkers differed significantly among the four seasons (p < 0.05), with osmolality and urine specific gravity (USG) being significantly higher in summer than in other seasons (p < 0.05). The percentage of participants with optimal hydration status increased from 38.0% in summer to 62.0% in spring (p < 0.05). Men had more concentrated urine as well as higher plasma osmolality and solute concentrations than women during each season of the year (p < 0.05).

Conclusion

TWI and urinary and plasma biomarkers of hydration were found to vary seasonally among Chinese young adults, with hydration status being poorer in summer. Men need to pay more attention than women to maintain optimal hydration status.

Clinical trial registration

https://www.chictr.org.cn/showproj.html?proj=124857, ChiCTR2100045268.
Characteristic of volatile flavor compounds in ‘Fengtangli’ plum (Prunus salicina Lindl.) were explored based on GC×GC-TOF MS
Authors: Hu Xianfeng , Li Deyan , Ding Yi , Zhang Yubo , Ren Chunguang
Published: January 2025

Introduction

The ‘Fengtangli’ plum (Prunus salicina Lindl.) is favoured by consumers for its characteristic flavor. The purpose of this study was to explore the characteristics of volatile flavor compounds in ‘Fengtangli’ plum.

Methods

The flavor compounds of both ‘Fengtangli’ and ‘Siyueli’ plums were analyzed using comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOF MS).

Results

The results revealed the presence of 495 volatile flavor compounds in ‘Fengtangli’ plum and 466 in ‘Siyueli’ plum. The relative concentrations of hydrocarbons, alcohols, ketones, and esters in ‘Fengtangli’ plum were significantly elevated compared to those detected in ‘Siyueli’ plum. Moreover, the sensorial attributes of sweetness, citrus, herbal, floral, and fruity notes were more prominent in ‘Fengtangli’ plum relative to those of ‘Siyueli’ plum. Through the integration of differential metabolite analysis and relative odor activity assessment, it is hypothesized that furan-2-pentyl; (E)-2-octenal; and 1-octen-3-one may represent the characteristic of volatile flavor compounds in ‘Fengtangli’ plum.

Discussion

The research results may provide a theoretical reference for the development and application of ‘Fengtangli’ plum and the study of the synthesis mechanism of characteristic flavor compounds.
Inhibition effect of AGEs formation in vitro by the two novel peptides EDYGA and DLLCIC derived from Pelodiscus sinensis
Authors: Chen Nuo , Wang Nan , Fang Qiaoyun , Yu Zuolong , Hu Yiyuan , Jin Jiancang , Yang Shengli
Published: January 2025

The antioxidant activity of natural products is closely related to their antiglycation effects. This study aimed to examine the antiglycation activity and elucidate the underlying mechanisms of two specific peptides, EDYGA (Glu-Asp-Tyr-Gly-Ala) and DLLCIC (Asp-Leu-Leu-Cys-Ile-Val), derived from protein hydrolysates of the Pelodiscus sinensis. Both EDYGA and DLLCIC were efficient in bovine serum albumin (BSA)/glucose model to inhibit BSA glycation, while DLLCIC showed higher antiglycation activity than EDYGA. Firstly, it was found that EDYGA and DLLCIC could inhibit the formation of NEG and AGEs. Moreover, EDYGA and DLLCIC were able to maintain the protein secondary structure and stabilize the band positions (amide I & II). Additionally, molecular simulations indicated that DLLCIC can spontaneously interact with the central site of BSA, specifically at Lys114 and Glu424 residues, through hydrogen bonds with an energy strength of −0.7 kcal/mol. Furthermore, CCK-8 and morphological experiments confirmed that EDYGA and DLLCIC improved cell survival against AGEs-induced cytotoxicity, with EC50 values of 17.64 μM for EDYGA and 15.08 μM for DLLCIC. These findings serve as a significant reference for the development of EDYGA and DLLCIC as effective antiglycation agents in the prevention of glycation-mediated diseases.
Prognostic determinants and functional role of PIK3C2G in stage IIb-IIIa lung adenocarcinoma: insights from clinical and molecular analyses
Authors: Gao Chao , Zhang Jiaqi , Du Xin , Gao Xuehan , Diao Xiayao , Zhao Ke , Chen Yeye , Li Shanqing
Published: January 2025

Background

To investigate the prognostic factors for stage IIb and IIIa lung adenocarcinoma following radical surgery and to explore the molecular mechanisms underlying these prognostic markers, focusing on the role of PIK3C2G.

Methods

A retrospective analysis of patients with stage IIb or IIIa lung adenocarcinoma who underwent radical surgery between January 2017 and June 2023 was conducted. Baseline clinical and pathological data, surgical methods, and postoperative treatments were analyzed to assess overall survival (OS). Univariate and multivariate Cox regression analyses were conducted to identify prognostic factors. Whole-exome sequencing (WES) was performed on a subset of the patients with preserved tumor tissues and no matched targeted therapies to identify high-frequency mutated genes. Functional experiments in A549 lung adenocarcinoma cells were performed to evaluate the role of the significant genes in tumor progression through cell proliferation, migration, invasion, apoptosis, and cell cycle assays.

Results

The survival analysis of 877 stage IIb and IIIa lung adenocarcinoma cases revealed significant differences in clinical characteristics and outcomes. Stage IIb patients had a median OS of 58 months compared to 37 months for stage IIIa, with 5-year OS rates of 46.9% and 30.5%, respectively. Univariate and multivariate Cox regression identified pathological stage, number of positive lymph nodes, age, and targeted therapy as independent prognostic factors. WES of 184 patients with no matched targeted therapies revealed high-frequency mutations in genes such as TP53 and PIK3C2G, with the latter emerging as the most significant prognostic marker. Functional assays demonstrated that the knockdown of PIK3C2G in A549 cells significantly reduced proliferation, migration and invasion while promoting apoptosis and disrupting cell cycle progression.

Conclusion

PIK3C2G was identified as a significant prognostic marker in stage IIb and IIIa lung adenocarcinoma, with functional data supporting its therapeutic potential. Taken together, this study integrates clinical and molecular findings, which could be used as a reference to guide personalized treatment strategies.
Neoadjuvant programmed death ligand-1 with chemotherapy versus chemotherapy alone for limited-stage small-cell lung cancer: a retrospective study
Authors: Yang Zhi , Wang Yan-qing , Chang Xiujun
Published: January 2025

Summary background

Our objective was to investigated the safety and feasibility of neoadjuvant treatment with PD(L)1 inhibitors and chemotherapy followed by surgery for resectable SCLC.

Methods

In this retrospective cohort study, we included patients with limited-stage SCLC treated with neoadjuvant chemotherapy (with/without)ICI at Beijing Chest Hospital (Beijing, China) between July 2020 and December 2021. Seventeen patients with LD-SCLC were enrolled in the study. Two groups were assigned for further statistical analysis: neoadjuvant chemotherapy (group C), in which only preoperative chemotherapy was administered; and neoadjuvant ICI (group I), in which surgery was combined with both preoperative ICI and chemotherapy. Patient demographics, radiological and pathological evaluations of tumor response, surgical information, toxicity profiles, tumor marker and follow-up results of both groups were evaluated.

Results

17 patients were included in this retrospective study, of which, 11 patients received ICI and chemotherapy-containing regimens and 6 patients received neoadjuvant chemotherapy only. Herein, we firstly reported that neoadjuvant PD-(L)1 blockade plus chemotherapy led to a pCR rate of 45.5% in patients with limited-stage small cell lung cancer. The MPR rate of 72.7% due to treatment with neoadjuvant PD-(L)1 blockade plus chemotherapy group (group I) was significantly higher than those in the traditional neoadjuvant chemotherapy group (16.7%)(group C). We first found that ProGRP is a good the evaluation indicator for neoadjuvant immunotherapy in small cell lung cancer and found that the ProGRP levels decreased significantly in both group after neoadjuvant therapy, and it was more obvious in group I(P=0.003).All Of the 17 patients (100.0%) had R0 resection. There were no perioperative deaths.

Conclusions

Neoadjuvant immunotherapy shows lower toxicity and fewer perioperative complications. ICI combined chemotherapy can achieve more pathological relief and clinical benefits in the neoadjuvant treatment of LS-SCLC without increased irAE and perioperative complications. However, the small sample size limits the reliability of the research.
Case report of the first use of a hydrogel rectal spacer for prostate cancer reirradiation via LDR brachytherapy: applications and technical notes
Authors: Lazrek Amina , Finocchi Ghersi Sebastiano , Petre Adeline , Houabes Sarah , Serre Anne-Agathe , Gassa Frederic , Sandt Magali , Laude Cecile , Roukoz Camille , Cozzi Salvatore
Published: January 2025

Introduction

Prostate cancer remains a prevalent malignancy among men, often necessitating innovative therapeutic strategies for effective management of recurrent cases. This article examines the critical role of a biodegradable hydrogel spacer, which creates a temporary interspace between the prostate and the rectum, thus reducing radiation exposure to healthy tissues.

Case description

We present a case of a man with a history of intermediate-risk prostate adenocarcinoma initially treated with external beam radiotherapy in 2015. Despite initial remission, the patient experienced a rise in prostate-specific antigen (PSA) levels indicative of local recurrence in 2022. Salvage treatment with iodine-125 brachytherapy, preceded by the placement of a rectal spacer in January 2024, resulted in a significant reduction of PSA levels. The patient remains asymptomatic with no urinary or gastrointestinal complications 6 months after the salvage treatment.

Discussion

This case illustrates the complexities in managing recurrent prostate cancer and the evolving role of reirradiation strategies. Salvage iodine-125 brachytherapy with the placement of a rectal spacer provided precise radiation delivery while minimizing rectal toxicities. The significant biochemical response observed underscores the efficacy of this approach in controlling disease progression. The rectal spacer enhances treatment safety by reducing radiation exposure to adjacent tissues, highlighting its importance in reirradiation protocols. This case contributes to the growing evidence supporting the rectal spacer’s role in enhancing the safety and efficacy of salvage brachytherapy for recurrent prostate cancer.

Conclusions

Our experience advocates for the integration of a hydrogel rectal spacer as a valuable tool in prostate cancer reirradiation protocols, offering a strategic approach to optimize treatment safety by minimizing rectal toxicity.
Intravascular large B-cell lymphoma of the central nervous system with renal involvement: a case report and literature review
Authors: Li Jun , Li Zhaojiao , Shi Yifeng , Chen Jiajie , Zhao Heng , Mao Xueye , Li Shan , Wang Huiying , Meng Qiang , Liu Lingchun
Published: January 2025

Intravascular large B-cell lymphoma (IVLBCL) is a highly aggressive type of non-Hodgkin’s lymphoma. The clinical manifestations and imaging of this disease are nonspecific, making diagnosis challenging. We report a case of a patient with recurrent stroke-like symptoms, primarily characterized by hemiplegia, vertigo, ataxia, and proteinuria. Brain MRI revealed multiple cerebral infarctions, microbleeds, and meningeal enhancement. Ultimately, the patient was diagnosed with IVLBCL through a brain tissue biopsy, and involvement of the kidneys was suspected. We suggest considering IVLBCL in patients who present with recurrent stroke-like symptoms, fluctuating neurological deficits, the aforementioned MRI findings, and involvement of other organs. Additionally, central nervous system vasculitis(CNSV) may represent a transitional manifestation of the disease. Pathological biopsy is the gold standard for diagnosis. We hope that through this case, doctors can gain a deeper understanding of IVLBCL, enabling early diagnosis and timely treatment to improve prognosis.
Utilization of patient-reported outcomes to assess adherence to relugolix when combined with stereotactic body radiation therapy for intermediate to high-risk prostate cancer
Authors: Gaudian Kelly , Koh Min Jung , Koh Min Ji , Collins Ryan R. , Eden Shaine , Zwart Zoya , Danner Malika , Zwart Alan , Fallick Mark , Kumar Deepak , Leger Paul , Dawson Nancy A. , Suy Simeng , Collins Sean P.
Published: January 2025

Introduction

Injectable GnRH receptor agonists have been shown to improve cancer control when combined with radiotherapy (RT). Relugolix is an oral GnRH receptor antagonist that achieves rapid testosterone suppression. Non-adherence to oral medications due to poor social support or bothersome side effects may increase the risk of cancer recurrence. This prospective study sought to evaluate early testosterone suppression and relugolix drug adherence when combined with prostate stereotactic body radiation therapy (SBRT). Utilization of patient-reported outcomes (PROs) to assess oral medication adherence and guide intervention may improve the appropriate utilization of oral medications. This study focuses on the use of the Simplified Medication Adherence Questionnaire (SMAQ) as a tool to assess relugolix adherence.

Methods

Relugolix was initiated at least 2 months prior to questionnaire administration. Adherence was assessed using the SMAQ. Total testosterone levels were obtained at the time of SMAQ administration. Castration was defined as serum testosterone ≤ 50 ng/dL. Poor drug adherence was delineated as failure to reach castration or non-adherence per the SMAQ (any non-adherence answer, missed > 2 doses in last week or since last visit). To compare the demographic and clinical characteristics of patients who adhered to treatment versus who did not, t-test, Wilcoxon rank sum test, Chi-square test, and Fisher’s exact test were used. A p-value < 0.05 determined statistical significance.

Results

Between August 2021 and December 2023, 78 men were treated at Georgetown with relugolix and prostate SBRT per an institutional protocol. The median age was 72, and 41% of patients were non-white. Patients initiated relugolix at a median of 4 months prior to the SMAQ (2-19 months). 96% of patients achieved castration (≤ 50 ng/dL) at the time of the SMAQ. 96% of men reported always taking relugolix at the appropriate time. 1% discontinued medication due to bothersome side effects, 17% reported forgetting to take the medication, and 4% reported missing a dose during the weekend. 98% and 93% did not miss a dose more than 2 times in the last week and since the last visit, respectively. Overall patient-reported drug adherence was 75%. No patient demographic or clinical characteristic predicted non-adherence.

Discussion

Relugolix allows for high rates of castration and drug adherence when combined with prostate SBRT. Monitoring drug adherence during treatment allows for prompt detection of non-adherence and timely intervention. Future studies should focus on how to optimally incorporate this questionnaire into patient management.