bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial transcriptomics: a new frontier in accurate localization of breast cancer diagnosis and treatment
Authors: Zhang Yang , Gong Shuhua , Liu Xiaofei
Published: October 2024

Breast cancer is one of the most prevalent cancers in women globally. Its treatment and prognosis are significantly influenced by the tumor microenvironment and tumor heterogeneity. Precision therapy enhances treatment efficacy, reduces unwanted side effects, and maximizes patients’ survival duration while improving their quality of life. Spatial transcriptomics is of significant importance for the precise treatment of breast cancer, playing a critical role in revealing the internal structural differences of tumors and the composition of the tumor microenvironment. It offers a novel perspective in studying the spatial structure and cell interactions within tumors, facilitating more effective personalized treatments for breast cancer. This article will summarize the latest findings in the diagnosis and treatment of breast cancer from the perspective of spatial transcriptomics, focusing on the revelation of the tumor microenvironment, identification of new therapeutic targets, enhancement of disease diagnostic accuracy, comprehension of tumor progression and metastasis, assessment of drug responses, creation of high-resolution maps of tumor cells, representation of tumor heterogeneity, and support for clinical decision-making, particularly in elucidating the tumor microenvironment, tumor heterogeneity, immunotherapy and their correlation with clinical outcomes.
Clinical advances and challenges associated with TCR-T cell therapy for cancer treatment
Authors: Li Jianing , Zhang Yongsheng , Fu Tong , Xing Guoli , Cai Hongbo , Li Kaiqing , Xu Yutong , Tong Ying
Published: October 2024

Background

T cell receptor (TCR)-T cell therapy is an innovative form of cancer immunotherapy that genetically modifies patients’ T cells to target and destroy cancer cells. However, the current status of clinical trials of TCR-T cell therapy for the treatment of cancer remains unclear. This study aimed to comprehensively analyze the registration trials related to TCR-T cell therapy for the treatment of cancer.

Methods

A comprehensive search was conducted in the Trialtrove database for all clinical trials related to TCR-T cell therapy registered by August 1, 2024. Inclusion criteria focused on trials targeting TCR-T cell therapy for oncology, and excluded observational studies and incomplete data. Statistical analysis was performed on key trial characteristics, with between-group comparisons utilizing chi-square or Fisher’s exact tests.

Results

Analysis of 174 eligible clinical trials revealed that TCR-T cell therapy exhibits significant efficacy across various tumor types, particularly in refractory hematologic malignancies and certain solid tumors. Additionally, combining TCR-T cell therapy with other immunotherapies enhanced these anti-tumor effects.

Conclusion

TCR-T cell therapy holds substantial promise for cancer treatment. Future research should focus on optimizing treatment protocols, enhancing efficacy, and minimizing prices to fully realize the potential of this therapy.
Numerical simulation of non-uniform suspended sediment flowing into the Yangtze River Estuary, China based on a river network model
Authors: Ge Hua , Zhu Lingling , Mao Bing
Published: October 2024

The non-uniform suspended sediment flowing into the Yangtze River Estuary (YRE) has a substantial impact on riverbed evolution and the ecological environment. Conducting a numerical simulation can provide missing measurement data and act as an important support for river management. In this study, we developed a formula for determining the non-uniform suspended sediment-carrying capacity (SCC) based on the statistical theory of sediment transport. The formula was applied to a river network model domaining the tidal section of the lower reaches of the Yangtze River (LYR) to simulate the non-uniform suspended sediment flowing into the YRE. The verification results showed that the model accurately simulated fine-grained sediments with a high measurement accuracy. The simulation results for coarse-grained sediments were consistent with riverbed evolution that manifests as erosion. Owing to the sediment transport complexity in natural rivers, we propose a method for optimizing calculations of the SCC that provides more accurate modeling results and can be adapted when the observational measurement accuracy is improved in the future. These findings provide support for simulations and measurements of non-uniform suspended sediment transported in the LYR.
The first child with mixed invasive pulmonary Mucor and Aspergillus infection: a case report and literature review
Authors: Wang Shifu , Yang Shangmin , Ma Jing , Zhang Chunyan , Li Zheng , Wang Mengyuan , Yu Wenwen , Liu Guohua
Published: October 2024

Purpose

Coinfections or consecutive infections of Mucor and Aspergillus are exceedingly uncommon in children, we report the case to offer the valuable experience for colleagues facing similar situations.

Case report

This report documents the first recorded case of successful treatment for pulmonary mixed infection in a diabetic girl. Initially, the patient underwent treatment based on voriconazole, but the infection continued to deteriorate. Subsequently, bronchoalveolar lavage fluid culture and metagenomic next-generation sequencing (mNGS) were conducted, leading to a clear diagnosis of simultaneous infection by Aspergillus fumigatus and Rhizopus microsporus. Susceptibility testing revealed fungal resistance to voriconazole. Therefore, a combined treatment regimen of AmB liposomes and isavuconazole effectively eradicated the fungal infection.

Conclusion

This case underscores the importance of early and precise identification of fungal pathogens, determination of effective antifungal medications, and timely implementation of well-planned therapeutic strategies. Furthermore, we comprehensively reviewed 10 cases of pulmonary mixed infections involving Mucor and Aspergillus, summarizing their characteristics and identifying commonalities.
The safety and efficacy of additional chest tube placement in patients with prolonged air leaks after pulmonary resection: a propensity score-matched analysis
Authors: Hua Qingwang , Liu Suyue , Shen Lu , Yang Zhenhua , Shen Haibo
Published: October 2024

Background

This study evaluates the symptomatic management of prolonged pleural air leaks following pulmonary resection, assesses the efficacy and safety of chest tube placement, and introduces experiences with high-positioned chest tube insertion.

Methods

We retrospectively reviewed 84 patients with prolonged pleural air leaks after lung surgery at Ningbo No.2 Hospital from January 2022 to December 2023. These patients were divided into a conservative treatment group (Group A, n = 64) and a chest tube placement group (Group B, n = 20). The propensity score matching method was applied to balance confounders between the two groups, resulting in 12 matched pairs. The study compared the time to chest tube removal, average hospital stays time, postoperative drainage volume, and facial visual analog pain score between the two groups.

Results

The average hospital stays and chest tube removal time of patients in group B were significantly lower than those of patients in group A (8.00 ± 1.12 vs. 9.75 ± 1.60 days, P = 0.003, 6.92 ± 1.08 vs. 8.58 ± 1.67 days, P = 0.005, respectively). However, the mean facial visual analog pain score in group B was higher than that in group A (1.58 ± 0.58 vs. 1.00 ± 0.01, P = 0.020). There were no significant differences between the two groups in terms of postoperative drainage volume.

Conclusions

For patients with prolonged air leaks, additional chest tube placement postoperatively significantly reduces both hospitals stay duration and chest tube indwelling time compared to conservative treatment. This method may be a potential treatment measure for prolonged air leak in selected patients.
Microbiota-derived short chain fatty acids in pediatric health and diseases: from gut development to neuroprotection
Authors: Hsu Chou-Yi , Khachatryan Lusine G. , Younis Nada Khairi , Mustafa Mohammed Ahmed , Ahmad Nabeel , Athab Zainab H. , Polyanskaya Angelina V. , Kasanave Elena Victorovna , Mirzaei Rasoul , Karampoor Sajad
Published: October 2024

The infant gut microbiota undergoes significant changes during early life, which are essential for immune system maturation, nutrient absorption, and metabolic programming. Among the various microbial metabolites, short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate, produced through the fermentation of dietary fibers by gut bacteria, have emerged as critical modulators of host-microbiota interactions. SCFAs serve as energy sources for colonic cells and play pivotal roles in regulating immune responses, maintaining gut barrier integrity, and influencing systemic metabolic pathways. Recent research highlights the potential neuroprotective effects of SCFAs in pediatric populations. Disruptions in gut microbiota composition and SCFA production are increasingly associated with a range of pediatric health issues, including obesity, allergic disorders, inflammatory bowel disease (IBD), and neurodevelopmental disorders. This review synthesizes current knowledge on the role of microbiota-derived SCFAs in pediatric health, emphasizing their contributions from gut development to neuroprotection. It also underscores the need for further research to unravel the precise mechanisms by which SCFAs influence pediatric health and to develop targeted interventions that leverage SCFAs for therapeutic benefits.
Bacterial metabolites influence the autofluorescence of Clostridioides difficile
Authors: Ticer Taylor D. , Tingler Anna M. , Glover Janiece S. , Dooley Sarah A. , Kendrick Jacob , Zackular Joseph P. , Devkota Suzanne , Wu Gary D. , Mahalak Karley , Engevik Amy , Engevik Melinda A.
Published: October 2024

Clostridioides difficile is a bacterial pathogen that has been implicated in severe gastrointestinal infections. C. difficile has intrinsic green autofluorescence and the level of this autofluorescence is known to be increased by growth time and oxygen. Currently, it is unclear if dietary compounds or metabolites from the gut microbiota are able to enhance C. difficile autofluorescence. Here, we aimed to determine potential factors that affect C. difficile autofluorescence. After screening a large repertoire of compounds, we identified several substances, like L-lysine and pantothenate, that led to an increased C. difficile autofluorescence. We also found that several members of the gut microbiota, such as Enterococcus faecalis, Klebsiella aerogenes and K. pneumoniae, can increase C. difficile autofluorescence through their secreted compounds. We further focused on the effect of K. pneumoniae on C. difficile autofluorescence and found that multiple enteric strains of K. pneumoniae could enhance C. difficile’s autofluorescence. We used this enhanced autofluorescence to identify C. difficile in K. pneumoniae co-cultures by flow cytometry. Our findings shed light on the relationship between C. difficile and other members of the gut microbiota, as well as different factors that can affect C. difficile autofluorescence.
Artificial intelligence in assisting pathogenic microorganism diagnosis and treatment: a review of infectious skin diseases
Authors: Han Renjie , Fan Xinyun , Ren Shuyan , Niu Xueli
Published: October 2024

The skin, the largest organ of the human body, covers the body surface and serves as a crucial barrier for maintaining internal environmental stability. Various microorganisms such as bacteria, fungi, and viruses reside on the skin surface, and densely arranged keratinocytes exhibit inhibitory effects on pathogenic microorganisms. The skin is an essential barrier against pathogenic microbial infections, many of which manifest as skin lesions. Therefore, the rapid diagnosis of related skin lesions is of utmost importance for early treatment and intervention of infectious diseases. With the continuous rapid development of artificial intelligence, significant progress has been made in healthcare, transforming healthcare services, disease diagnosis, and management, including a significant impact in the field of dermatology. In this review, we provide a detailed overview of the application of artificial intelligence in skin and sexually transmitted diseases caused by pathogenic microorganisms, including auxiliary diagnosis, treatment decisions, and analysis and prediction of epidemiological characteristics.
A review of proposed mechanisms for neurodegenerative disease
Authors: Kelser Benjamin M. , Teichner Eric M. , Subtirelu Robert C. , Hoss Kevin N.
Published: October 2024

Neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis (ALS) affect millions and present significant challenges in healthcare and treatment costs. The debate in the field pivots around two hypotheses: synaptic spread and selective vulnerability. Pioneers like Virginia Lee and John Trojanowski have been instrumental in identifying key proteins (tau, alpha-synuclein, TDP-43) central to these diseases. The synaptic spread hypothesis suggests a cell-to-cell propagation of pathogenic proteins across neuronal synapses, influencing disease progression, with studies highlighting the role of proteins like alpha-synuclein and amyloid-beta in this process. In contrast, the selective vulnerability hypothesis proposes inherent susceptibility of certain neurons to degeneration due to factors like metabolic stress, leading to protein aggregation. Recent advancements in neuroimaging, especially PET/MRI hybrid imaging, offer new insights into these mechanisms. While both hypotheses offer substantial evidence, their relative contributions to neurodegenerative processes remain to be fully elucidated. This uncertainty underscores the necessity for continued research, with a focus on these hypotheses, to develop effective treatments for these devastating diseases.
Organoid intelligence for developmental neurotoxicity testing
Authors: Alam El Din Dowlette-Mary , Shin Jeongwon , Lysinger Alexandra , Roos Matthew J. , Johnson Erik C. , Shafer Timothy J. , Hartung Thomas , Smirnova Lena
Published: October 2024

The increasing prevalence of neurodevelopmental disorders has highlighted the need for improved testing methods to determine developmental neurotoxicity (DNT) hazard for thousands of chemicals. This paper proposes the integration of organoid intelligence (OI); leveraging brain organoids to study neuroplasticity in vitro, into the DNT testing paradigm. OI brings a new approach to measure the impacts of xenobiotics on plasticity mechanisms – a critical biological process that is not adequately covered in current DNT in vitro assays. Finally, the integration of artificial intelligence (AI) techniques will further facilitate the analysis of complex brain organoid data to study these plasticity mechanisms.
Relationships of post-stroke fatigue with mobility, recovery, performance, and participation-related outcomes: a systematic review and meta-analysis
Authors: Usman Jibrin S. , Wong Thomson W. L. , Ng Shamay S. M.
Published: October 2024

Background

Effective post-stroke mobility, recovery, performance, and participation are key goals for stroke survivors. However, these outcomes may be hindered by post-stroke fatigue (PSF), which can affect numerous aspects of post-stroke mobility, recovery, performance, functioning, community participation, and return to work. This review aimed to assess the scientific evidence on the relationship between PSF and mobility function, functional recovery, functional performance, and participation-related outcomes among stroke survivors.

Method

A comprehensive search of Cochrane Central, PubMed, Embase, and Web of Science (WoS) databases was conducted from inception to December 2023. Observational, cross-sectional, and longitudinal studies were included. The methodological quality of the included studies was assessed using the National Institute of Health’s quality assessment tool, while the risk of bias was assessed using the Quality in Prognostic Studies tool. A total of 28 studies (n = 2,495 participants, 1,626 men, mean age ranging from 52.5 ± 9.5 to 71.1 ± 9.9 years) were included. The data analysis was conducted using narrative and quantitative synthesis. Fixed and random effects meta-analyses were conducted to explore the relationships between PSF and relevant outcomes.

Results

Chronic PSF was found to have significant negative correlations with mobility (meta r = −0.106, p < 0.001), balance performance (meta r = −0.172; 95%; p = 0.004), and quality of life (meta r = −0.647; p < 0.001). It also showed significant positive correlations with stroke impairment (meta r = 0.144, p < 0.001) and disability (meta r = 0.480, p < 0.001). Additionally, exertion/acute PSF had significantly negative correlations with walking economy (meta r = −0.627, p < 0.001) and walking endurance (meta r = −0.421, p = 0.022). The certainty of evidence was deemed moderate for these relationships.

Conclusion

Our findings indicate that higher levels of PSF are associated with poorer mobility, balance, and participation, as well as greater disability and stroke impairment. Future studies, especially prospective longitudinal and randomized controlled trials, are warranted to substantiate our findings.

Systematic review registration

PROSPERO, identifier: CRD42023492045.
Quantifying the association between stroke and dementia: a bibliometric study
Authors: Bian Xinyi , Zhao Zibin , Gao Xiaoping
Published: October 2024

Background

Stroke and dementia are two serious neurological disorders in modern medicine. Studies have revealed a significant link between the two, but there is still a lack of bibliometric analysis in this area. The objective of this study is to use bibliometric analysis to investigate the connection between stroke and dementia, as well as to assess the current state of research in this field and identify future trends.

Methods

The publications from the Web of Science were Collection and retrieved for the last 22 years (2002–2023). CiteSpace, VOSviewer, and the R package Bibliometrix were used to conduct bibliometric analysis. GraphPad Prism was used to plot.

Results

A total of 1,309 publications were included in the analysis. The number of articles on dementia and stroke has continued to grow steadily over the past 22 years. While China is the country with the most articles, the most influential and widely researched countries are England and the United States. The keyword analysis illustrates that the prevention of dementia through stroke prevention is a major focus and trend in this research area.

Conclusion

This study provides a visual analysis method for measuring the association between stroke and dementia, and examines the current state of research in this area and future research trends. In the future, dementia caused by stroke needs to be emphasized, and prevention of dementia through stroke prevention is a research priority.
Association between human herpes simplex virus and severe headache or migraine among aged 20–49 years: a cross-sectional study
Authors: Zheng Tao , Jiang Li , Li Guanglu , Zeng Na , Yu Binyang , Duan Shaojie , Wang Gesheng , Liu Zunjing
Published: October 2024

Background and purpose

Previous studies have shown that human herpes simplex virus (HSV) infection may be associated with the onset of headache or migraine. We aimed to investigate the association between HSV infection and severe headache or migraine.

Materials and methods

The cross-sectional data on 5,730 participants aged 20–49 years were obtained from the 1999–2004 National Health and Nutrition Examination Survey (NHANES). We used weighted logistic regression analysis to assess the association between HSV infection (HSV-1 gG-1 and HSV-2 gG-2) and severe headache or migraine, and performed subgroup analyses.

Results

Our study found that women, higher education, higher body mass index, better family conditions, smoking and alcohol consumption were all associated with severe headaches or migraines. After adjusting for confounding factors such as sex, age, race, and education, HSV-2 (+) was still significantly associated with severe headache or migraine (OR = 1.22, 95%CI:1.03–1.46, p = 0.0443). In subgroup analyses, we found that participants with HSV-1 (−) and HSV-2 (+) were also significantly associated with severe headache or migraine (OR = 1.41, 95%CI:1.04–1.91, p = 0.0281).

Conclusion

HSV-2 gG-2(+) was significantly associated with severe headache or migraine.
Commissural and monosynaptic inputs to medial vestibular nucleus GABAergic neurons in mice
Authors: Kong Dedi , Kong Lingxi , Liu Chengwei , Wu Qianru , Wang Jing , Dai Chunfu
Published: October 2024

Objective

MVN GABAergic neurons is involved in the rebalance of commissural system contributing to alleviating acute peripheral vestibular dysfunction syndrome. This study aims to depict monosynaptic inputs to MVN GABAergic neurons.

Methods

The modified rabies virus-based retrogradation method combined with the VGAT-IRES-Cre mice was used in this study. Moreover, the commissural connections with MVN GABAergic neurons were analyzed.

Results

We identified 60 nuclei projecting to MVN GABAergic neurons primarily distributed in the cerebellum and the medulla. The uvula-nodulus, gigantocellular reticular nucleus, prepositus nucleus, intermediate reticular nucleus, and three other nuclei sent dense inputs to MVN GABAergic neurons. The medial (fastigial) cerebellar nucleus, dorsal paragigantocellular nucleus, lateral paragigantocellular nucleus and 10 other nuclei sent moderate inputs to MVN GABAergic neurons. Sparse inputs to MVN GABAergic neurons originated from the nucleus of the solitary tract, lateral reticular nucleus, pedunculopontine tegmental nucleus and 37 other nuclei. The MVN GABAergic neurons were regulated by the contralateral MVN, lateral vestibular nucleus, superior vestibular nucleus, and inferior vestibular nucleus.

Conclusion

Our study contributes to further understanding of the vestibular dysfunction in terms of neural circuits and search for new strategies to facilitate vestibular compensation.
Subconscious vibrotactile stimulation improves mobility and balance in patients with bilateral vestibulopathy: adherence over 2 years
Authors: Kingma Herman , Hougaard Dan Dupont , van de Berg Raymond
Published: October 2024

Objective

To investigate the effect of daily use of subconscious vibrotactile stimulation in bilateral vestibulopathy (BVP) patients, who judged the effect of vestibular rehabilitation as insufficient.

Methods

BVP patients were asked to wear a subconscious vibrotactile stimulation belt for 2 h. Patients who reported benefit after 2 h of use, were instructed to wear a subconscious vibrotactile stimulation belt in daily life, for up to more than 2 years. Follow-up consultations (mostly by telephone calls) were scheduled after 2 weeks, 2 months, 1 year, and 2 years of use. During these consultations, adherence and the self-reported overall Balance and Mobility Score (BMS) were evaluated.

Results

One hundred twenty-one BVP patients were included. Regarding adherence, 74% of patients (n = 89) wanted to proceed with daily use at home after 2 h of try out. Of these patients, 90% (n = 80) was still wearing the belt daily after 2 months, and at least 81% (n = 72) after 1 year and 73% (n = 65) after 2 years. It should be noted that lack of adherence after 1 and 2 years resulted from a loss to follow-up. All patients responding to telephone consultations in the 2 years follow up were wearing a subconscious vibrotactile stimulation belt daily. The median BMS score significantly improved within 2 h of use, from 4 to 6 points (p < 0.0001). Compared to baseline, the median BMS score significantly improved with >=3 points after 2 weeks, 2 months, 1 year, and 2 years of daily use (p < 0.0001). Long-term adherence was high in patients who experienced an increase of two or more points on the BMS, after 2 weeks of daily use.

Conclusion

The Subconscious vibrotactile stimulation improves self-reported balance and mobility in a subgroup of motivated BVP patients in which vestibular rehabilitation is insufficient.
Revisiting the earliest hyperscanning study: power and functional connectivity in the alpha band may link brains far apart
Authors: Özkurt Tolga Esat
Published: October 2024

This brief report revisits the earliest known hyperscanning study published in 1965, which examined simultaneous EEG recordings of identical twins separated by six meters. The original study’s findings suggested that eye closure in one twin elicited alpha activity in the other, despite physical separation. Leveraging contemporary signal processing techniques, we reanalyzed the digitized data to validate their findings. Spectral analysis confirmed alpha activity in the twins’ EEG signals, aligning with the original observations. Multitapering along with background noise subtraction also revealed the alpha activity in the unrelated subject, which could not be observed by visual inspection alone. Coherence analysis revealed significant alpha band synchrony between a twin and an unrelated subject, differing from the initial study’s conclusions. Our findings indicate that even historical data can yield new insights when revisited with contemporary data analysis tools and highlight the potential for future large-scale studies using advanced techniques to explore nonlocal brain interactions.
Cardiovascular and vasomotor pulsations in the brain and periphery during awake and NREM sleep in a multimodal fMRI study
Authors: Tuunanen Johanna , Helakari Heta , Huotari Niko , Väyrynen Tommi , Järvelä Matti , Kananen Janne , Kivipää Annastiina , Raitamaa Lauri , Ebrahimi Seyed-Mohsen , Kallio Mika , Piispala Johanna , Kiviniemi Vesa , Korhonen Vesa
Published: October 2024

Introduction

The cerebrospinal fluid dynamics in the human brain are driven by physiological pulsations, including cardiovascular pulses and very low-frequency (< 0.1 Hz) vasomotor waves. Ultrafast functional magnetic resonance imaging (fMRI) facilitates the simultaneous measurement of these signals from venous and arterial compartments independently with both classical venous blood oxygenation level dependent (BOLD) and faster arterial spin-phase contrast.

Methods

In this study, we compared the interaction of these two pulsations in awake and sleep using fMRI and peripheral fingertip photoplethysmography in both arterial and venous signals in 10 healthy subjects (5 female).

Results

Sleep increased the power of brain cardiovascular pulsations, decreased peripheral pulsation, and desynchronized them. However, vasomotor waves increase power and synchronicity in both brain and peripheral signals during sleep. Peculiarly, lag between brain and peripheral vasomotor signals reversed in sleep within the default mode network. Finally, sleep synchronized cerebral arterial vasomotor waves with venous BOLD waves within distinct parasagittal brain tissue.

Discussion

These changes in power and pulsation synchrony may reflect systemic sleep-related changes in vascular control between the periphery and brain vasculature, while the increased synchrony of arterial and venous compartments may reflect increased convection of regional neurofluids in parasagittal areas in sleep.
Postoperative complications in the pediatric population. Malnutrition or phase angle? Which one do we use?
Authors: Díaz-Amaya María José , Rosales-Arreola Laura Fernanda , Hernández-Licona Jennifer , Pérez-Guillé Beatriz , Ignorosa-Arellano Karen , Carmona-Librado Silvio , González-Zamora José , González-Ortiz Ailema
Published: October 2024

Background and Aims

Malnutrition increases post-operative risks like infections and prolonged stays. Pediatric assessment challenges require using anthropometric measurements and phase angle, which reflects body cell mass and health outcomes. Phase angle varies by maturation stages, making it crucial for pre-surgical evaluations alongside BMI. This study aimed to determine the relationship between nutritional status, phase angle, and postoperative complications in pediatric patients who underwent surgery.

Methods

Prospective study with patients aged 3–17 undergoing major non-ambulatory surgery. Anthropometric measurements (weight, height, BMI Z-scores) hand grip strength, dietary intake and body composition via bioimpedance to assess phase angle were recorded. Postoperative complications were monitored, including surgical site infections, morbidity (pneumonia, inotropic support, infections, thromboembolism), and mortality. Surgical risks and pre- and postoperative conditions were documented.

Results

After the application of the selection criteria, a total of 391 patients who underwent surgery were included; 60% (n = 235) were within the range of the preschool and school-age groups. During the follow-up period, 51 (13%) patients developed at least one postoperative complication, with surgical site infections being the most common. Moreover, as phase angle decreased, the length of stay (LOS) increased in all the participants. Among children aged ≤12 years old, malnutrition was a risk factor for complications [OR 3.86 (1.61–9.27 95%CI)], whereas among adolescents, phase angle served as a protective factor [OR 0.63 (0.42–0.94 95%CI)].

Conclusion

Significant associations were observed between nutritional status, by BMI z-score, and post-surgical complications in younger patients. Additionally, in adolescents, the phase angle emerged as a protective factor against these complications.
Comparative long-term oncological outcomes of intraoperative radiotherapy vs. whole-breast irradiation in early breast cancer: a single institute study
Authors: Chi Mau-Shin , Ko Hui-Ling , Yang Tsen-Long , Liu Ya-Fang , Chi Kwan-Hwa , Cheng Fiona Tsui-Fen
Published: October 2024

Background

Intraoperative radiation therapy (IORT) and whole breast irradiation (WBI) are both effective adjuvant radiotherapy methods for ductal carcinoma in situ (DCIS) or early-stage breast cancer (BC) patients undergoing breast-conserving surgery (BCS). We aim to evaluate the long-term oncological efficacy and refine patient selection criteria based on our findings.

Methods

Female patients who underwent either IORT or WBI from January 2016 to December 2019, with a minimum follow-up of 12 months were collected. IORT was administered as a single fraction of 20 Gray (Gy) to the lumpectomy cavity using the Axxent electronic brachytherapy system, while WBI consisted of a standard fractionation of 50 Gy in 25 fractions, along with a reduced boost of 10 Gy. The clinicopathologic characteristics and oncological outcomes were retrospectively analyzed.

Results

A total of 247 patients were enrolled, comprising 164 with BC and 83 with DCIS. Among them, 112 underwent IORT, and 135 received WBI after BCS. The median age was 62.2 years, with median tumor sizes of 1.5 cm for BC and 1.2 cm for DCIS. At a median follow-up of 64.6 months, IORT demonstrated 11 locoregional recurrences (LRR), 1 metastasis, and 1 death, compared to 4 LRR, 5 metastases, and 2 deaths in the WBI group. WBI yielded significantly higher locoregional control (97.0% vs. 90.2%, p = 0.033), although metastasis-free (96.3% vs. 99.1%, p = 0.166) and overall survival rates (98.4% vs. 99%, p = 0.688) did not differ. The LRR rate was significantly higher in the IORT group among the DCIS or BC patients (p = 0.043). The hazard ratio for locoregional recurrence significantly increased in estrogen-receptor-negative (ER-) patients in both univariate analysis (HR = 4.98, 95% CI = 1.76-14.09, p = 0.002) and multivariate analysis (HR = 40.88, 95% CI = 1.29-1297.84, p = 0.035). Additionally, IORT was associated with increased LRR in the multivariate analysis (HR = 4.71, 95% CI = 1.16-19.06, p = 0.030).

Conclusion

At a long-term follow-up, the LRR rate was higher in the BCS followed by IORT, without significant differences in metastasis-free or overall survival rates. Our data confirmed the importance of exclusion ER- patients for IORT.
Effect of smoking status on immunotherapy for lung cancer: a systematic review and meta-analysis
Authors: Luo Dachen , Yang Dongmei , Cao Dan , Gong Zonglian , He Fang , Hou Yaqin , Lin Shan
Published: October 2024

Background

Recent studies have yielded conflicting results regarding the relationship between smoking history and the effectiveness of immune checkpoint inhibitors (ICIs) for advanced lung cancer. While some studies have suggested that smoking may enhance the response to immunotherapy in patients with lung cancer, other findings indicate the contrary. Therefore, we conducted a systematic review and meta-analysis to thoroughly examine this association.

Methods

We searched the PubMed, Embase, and Scopus databases for clinical trials comparing immunotherapy with conventional chemotherapy as the primary treatment for advanced lung cancer. A random effects model was used to synthesize hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS). We also conducted predefined subgroup analyses to investigate the efficacy disparities between never-smokers and smokers who were administered immunotherapy alone or in combination with chemotherapy, as well as the differences between former and current smokers under similar treatment modalities.

Results

Our analysis included data from 17 Phase III clinical trials involving 10,283 patients. The findings indicate that immunotherapy benefits both smokers and never-smokers with lung cancer or non-small cell lung cancer, yielding pooled HRs for OS of 0.74 (95% CI: 0.59–0.92) and 0.73 (95% CI: 0.67–0.80), respectively. A significant interaction effect was not observed (HR: 0.98, 95% CI: 0.77–1.24, pinteraction = 0.14), and the tumor type, immunotherapy combination, and type of immunotherapy did not differ among the groups in the subgroup analyses. Similarly, both former and current smokers experienced a significant survival benefit from immunotherapy, with pooled HRs for OS of 0.79 (95% CI: 0.68–0.91) and 0.71 (95% CI: 0.59–0.87), respectively. However, a significant interaction effect was also not observed (HR: 0.91, 95% CI: 0.74–1.11, pinteraction = 0.14).

Conclusion

Our findings suggest that smoking status does not affect the effectiveness of immunotherapy for lung cancer treatment. However, additional high-quality clinical trials are needed to confirm this conclusion.

Systematic review registration

https://inplasy.com/register/, identifier INPLASY2023110058.
Challenges and advances in glioblastoma targeted therapy: the promise of drug repurposing and biomarker exploration
Authors: Bae William Han , Maraka Stefania , Daher Ahmad
Published: October 2024

Glioblastoma remains the most prevalent and aggressive primary malignant brain tumor in adults, characterized by limited treatment options and a poor prognosis. Previous drug repurposing efforts have yielded only marginal survival benefits, particularly those involving inhibitors targeting receptor tyrosine kinase and cyclin-dependent kinase-retinoblastoma pathways. This limited efficacy is likely due to several critical challenges, including the tumor’s molecular heterogeneity, the dynamic evolution of its genetic profile, and the restrictive nature of the blood-brain barrier that impedes effective drug delivery. Emerging diagnostic tools, such as circulating tumor DNA and extracellular vesicles, offer promising non-invasive methods for real-time tumor monitoring, potentially enabling the application of targeted therapies to more selected patient populations. Moreover, innovative drug delivery strategies, including focused ultrasound, implantable drug-delivery systems, and engineered nanoparticles, hold potential for enhancing the bioavailability and therapeutic efficacy of treatments.
Reviewing the efficiency of photobiomodulation therapy in oncological treatment
Authors: Luitel Bibhus , Duggisani Tanush , Luitel Anuj , LaRocco John
Published: October 2024

The aim of the present systematic review is to evaluate the effects of different photobiomodulation therapy (PBMT) approaches in oncological treatment practices. The review follows the PRISMA guidelines. Specifically, the review is composed of laser PBMT and LED PBMT. A total of 23 studies were included, 14 investigating laser PBMT and 9 examining LED PBMT. In vitro studies demonstrated laser PBMT’s potential to induce apoptosis and cytotoxicity in various cancer cell lines while enhancing sensitivity to chemotherapeutics and natural compounds. However, some studies highlighted divergent effects between in vitro (promoted proliferation) and in vivo xenograft models (slowed tumor growth) for certain laser wavelengths. LED PBMT studies showed blue light inhibited melanoma and pancreatic cancer cell growth, potentially via ROS generation, while red light raised concerns about enhancing oral cancer invasiveness. Both modalities mitigated treatment side effects like oral mucositis, xerostomia, peripheral neuropathy, and improved quality of life. While promising, the outcomes varied based on light parameters, cancer type, and experimental setting, necessitating further optimization of PBMT protocols through well-designed studies to establish long-term safety and efficacy across clinical scenarios.
Automated mental health screening in pediatric lupus: associations with disease features and treatment
Authors: Harper Lauren , Ardoin Stacy P. , Leever Alana , Driest Kyla , Sivaraman Vidya , Taxter Alysha J.
Published: October 2024

Introduction

Patients with childhood-onset systemic lupus erythematosus (c-SLE) have higher rates of depression than their peers, which has been associated with worse medical outcomes. Therefore, it is imperative that their mental health be addressed. We utilized quality improvement (QI) methodology to automate mental health screening for patients with lupus within a pediatric rheumatology clinic. The retrospective cohort study aims to evaluate the association between mental health screening outcomes and demographics, medications, and disease activity measures in patients with childhood lupus.

Methods

The mental health QI team at a quaternary pediatric rheumatology center implemented an automated process for mental health screening in patients with c-SLE. Patients seen between 2017 and June 2023 with a diagnosis of c-SLE were identified using International Classification of Disease -Clinical Modification (ICD-CM) codes. Disease activity was assessed with the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K). Medications were identified on outpatient and inpatient orders for conventional synthetic and biologic disease-modifying anti-rheumatic drugs, hydroxychloroquine, corticosteroids, and aspirin. Mental health screening was accomplished with the Patient Health Questionnaire (PHQ). Descriptive statistics, univariate and multivariate linear regression were used.

Results

Between January 2017 and June 2023, 117 patients with c-SLE (41% with lupus nephritis) completed 534 total screenings. Each patient completed PHQ screenings, a median of 5 [interquartile range 2, 6] times. Screening increased when the screening process was automated. Those who were Black, female, or prescribed leflunomide, mycophenolate, and corticosteroids had higher PHQ scores.

Conclusions

Mental health support is essential for patients with chronic rheumatologic diseases such as SLE. Sustainable processes for quickly identifying depression are needed for optimal care of patients with SLE. Our process of automated, streamlined mental health screening successfully increased the screening of patients with SLE at every visit and led to timely interventions for positive PHQ scores. Higher PHQ scores were correlated with patients on leflunomide, mycophenolate, and corticosteroids. Future research should identify modifiable risk factors for high PHQ scores that the medical team can target.
Multiple cell-death patterns predict the prognosis and drug sensitivity of melanoma patients
Authors: Chen Zewei , Zhang Ruopeng , Zhao Zhoukai , Zhao Baiwei , Zhang Feiyang , Chen Guoming , Chen Xiaojiang , Wei Chengzhi , Lin Jun , Lin Feizhi , Zheng Ziqi , Jiang Kaiming , Nie Runcong , Chen Yingbo
Published: October 2024

Background

Melanoma, a malignant tumor of the skin, presents challenges in its treatment process involving modalities such as surgery, chemotherapy, and targeted therapy. However, there is a need for an ideal model to assess prognosis and drug sensitivity. Programmed cell death (PCD) modes play a crucial role in tumor progression and has the potential to serve as prognostic and drug sensitivity indicators for melanoma.

Methods

We analyzed 13 PCD modes including apoptosis, necroptosis, ferroptosis, pyroptosis, netotic cell death, entotic cell death, lysosome-dependent cell death, parthanatos, autophagy-dependent cell death, oxeiptosis, disulfidptosis, and alkaliptosis. These modes were used to construct a model that incorporated genes related to these 13 PCD modes to establish a cell death index (CDI) to conduct prognosis analysis. Transcriptomic, genomic, and clinical data were collected from cohorts including TCGA-SKCM, GSE19234, and GSE65904 to validate this model.

Results

A CDI consisting of ten gene signatures was established using machine learning algorithms and divided into two groups based on CDI values. The high CDI group exhibited relatively lower numbers of immune-infiltrating cells and showed resistance to commonly used drugs such as docetaxel and axitinib. Our validation results demonstrated good discrimination in PCA analysis between CDI groups, and melanoma patients with higher CDI values had worse postoperative prognoses (all p < 0.01).

Conclusion

The CDI model, incorporating multiple PCD modes, accurately predicts the clinical prognosis and drug sensitivity of melanoma patients.
T-cell engagers: model interrogation as a tool to quantify the interplay of relative affinity and target expression on trimer formation
Authors: Lai Massimo , Pichardo-Almarza Cesar , Verma Meghna , Shahinuzzaman Md , Zhu Xu , Kimko Holly
Published: October 2024

T-cell engagers (TCEs) represent a promising therapeutic strategy for various cancers and autoimmune disorders. These bispecific antibodies act as bridges, connecting T-cell receptors (TCRs) to target cells (either malignant or autoreactive) via interactions with specific tumour-associated antigens (TAAs) or autoantigens to form trimeric synapses, or trimers, that co-localise T-cells with target cells and stimulate their cytotoxic function. Bispecific TCEs are expected to exhibit a bell-shaped dose-response curve, with a defined optimal TCE exposure for maximizing trimer formation. The shape of the dose-response is determined by a non-trivial interplay of binding affinities, exposure and antigens expression levels. Furthermore, excessively low binding to the TCR may reduce efficacy, but mitigate risk of over-stimulating cytokine secretion or induce effector cell exhaustion. These inevitable trade-off highlights the importance of quantitatively understanding the relationship between TCE concentration, target expression, binding affinities, and trimer formation. We utilized a mechanistic target engagement model to show that, if the TCE design parameters are close to the recommended ranges found in the literature, relative affinities for TCR, TAA and target expression levels have qualitatively different, but predictable, effects on the resulting dose-response curve: higher expression levels shift the curve upwards, higher antigen affinity shifts the curve to the left, and higher TCR affinity shifts the curve upwards and to the left.
Resveratrol’s bibliometric and visual analysis from 2014 to 2023
Authors: Wei Haoyue , Fang Guowei , Song Weina , Cao Hongye , Dong Ruizhe , Huang Yanqin
Published: October 2024

Introduction

Resveratrol (RSV) is a natural polyphenolic compound derived from a variety of plants that possesses a wide range of biological activities, including antioxidant, anti-inflammatory, antitumor, antibacterial, antiviral, anti-aging, anti-radiation damage, anti-apoptosis, immune modulation, regulation of glucolipid metabolism, inhibition of lipid deposition, and anti-neuro. It is therefore considered a promising drug with the potential to treat a wide range of diseases.

Method

In this study, using Web of Science Core Collection (WoSCC) and CiteSpace bibliometric tool, VOSviewer quantitatively visualized the number of countries, number of authors, number of institutions, number of publications, keywords, and references of 16,934 resveratrol-related papers from 2014–2023 for quantitative and qualitative analysis.

Results

The results showed that an average of 1693.4 papers were published per year, with a general upward trend. China had the most publications with 5877. China Medical University was the institution with the largest number of publications and the highest number of citations in the field. The research team was mainly led by Prof. Richard Tristan, and the journal with the highest number of published papers was Molecular. Dietary polyphenols, oxidative stress, and antioxidant and anti-inflammatory effects are the most frequently cited articles. Oxidative stress, apoptosis, expression, and other keywords play an important role in connecting other branches of the field.

Discussion

Our analysis indicates that the integration of nanoparticles with RSV is poised to become a significant trend. RSV markedly inhibits harmful bacteria, fosters the proliferation of beneficial bacteria, and enhances the diversity of the intestinal flora, thereby preventing intestinal flora dysbiosis. Additionally, RSV exhibits both antibacterial and antiviral properties. It also promotes osteogenesis and serves a neuroprotective function in models of Alzheimer's disease. The potential applications of RSV in medicine and healthcare are vast. A future research challenge lies in modifying its structure to develop RSV derivatives with superior biological activity and bioavailability. In the coming years, innovative pharmaceutical formulations of RSV, including oral, injectable, and topical preparations, may be developed to enhance its bioavailability and therapeutic efficacy.