bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment outcomes of stereotactic body radiation therapy for pulmonary metastasis from sarcoma: a multicenter, retrospective study
Authors: Lee Tae Hoon , Kim Hak Jae , Kim Jin Ho , Kim Mi-Sook , Jang Won Il , Kim Eunji , Kim Kyung Su 
Published: April 2023

AbstractPurposeThe aim of this study was to evaluate the treatment outcomes and potential dose-response relationship of stereotactic body radiation therapy (SBRT) for pulmonary metastasis of sarcoma.Materials and methodsA retrospective review of 39 patients and 71 lesions treated with SBRT from two institutions was performed. The patients had oligometastatic or oligoprogressive disease, or were receiving palliation. Doses of 20–60 Gy were delivered in 1–5 fractions. The local control per tumor (LCpT) was evaluated according to the biologically effective dose with an α/β ratio of 10 (BED10) of the prescribed dose (BED10 ≥ 100 Gy vs. BED10 < 100 Gy). Clinical outcomes per patient, including local control per patient (LCpP), pulmonary progression-free rate (PPFR), any progression-free rate (APFR), and overall survival (OS) were investigated.ResultsThe median follow-up period was 27.2 months. The 1-, 2-, and 3-year LCpT rates for the entire cohort were 100.0%, 88.3%, and 73.6%, respectively. There was no observed difference in LCpT between the two BED10groups (p = 0.180). The 3-year LCpP, PPFR, APFR, and OS rates were 78.1%, 22.7%, 12.9%, and 83.7%, respectively. Five (12.8%) patients with oligometastasis had long-term disease-free intervals, with a median survival period of 40.7 months. Factors that were associated with a worse prognosis were oligoprogression (vs. oligometastasis), multiple pulmonary metastases, and simultaneous extrathoracic metastasis.ConclusionSBRT for pulmonary metastasis of sarcoma is effective. Some selected patients may achieve durable response. Considerations of SBRT indication and disease extent may be needed as they may influence the prognosis.
Research hotspots and trends of microRNAs in intervertebral disc degeneration: a comprehensive bibliometric analysis
Authors: Chen Shuang , Wang Yi , Wu Huanxi , Fang Xiaoyang , Wang Chenyu , Wang Nan , Xie Lin 
Published: April 2023

Abstract
Background
MicroRNAs (miRNAs) are involved in various pathological processes, such as proliferation, growth, and apoptosis, of intervertebral disc (IVD) cells and play an important role in the development of intervertebral disc degeneration (IDD). Although some studies have reported the role of miRNAs in IDD, scientific econometric analysis in this field is not available.

Objectives
We designed this study to describe the current research trends and potential mechanisms associated with the role of miRNAs in IDD and to provide new ideas for future research in this field.

Methods
We conducted a bibliometric analysis of the publications on the role of miRNAs in IDD included in the Web of Science core collection database to elucidate the current research trends in this field. The potential mechanisms were constructed using the Arrowsmith project.

Results
We found that the number of miRNAs and IDD-related publications increased over the years. China was the most important contributor to research in this field. The top three institutions in terms of number of articles published were Huazhong University of Science and Technology, Shanghai Jiao Tong University, and Xi’an Jiao Tong University. Shanghai Jiao Tong University had the highest number of citations. Experimental and thermal medicine had the maximum number of documents, and Cell promotion had the most citations. The journal with the most mean times cited per study was Annals of the Rheumatic Diseases. The author Wang K had the highest number of publications, and Wang HQ had the highest number of citations. These two authors made important contributions to the research in this field. The keyword analysis showed that recent studies have focused on miRNAs regulating nucleus pulposus cell apoptosis and proliferation. Moreover, we revealed the potential mechanisms of miRNAs associated with IDD, including miRNAs regulating the extracellular matrix (ECM) degradation, mediating cartilage endplate (CEP) degeneration, and participating in inflammatory responses.

Conclusion
We demonstrated the knowledge map of miRNAs and IDD-related research through bibliometric analysis and elucidated the current research status and hotspots in this field. The mechanisms by which miRNAs regulate the apoptosis and proliferation of degenerated IVDs, promote ECM degradation, mediate CEP degeneration, and participate in inflammatory responses should be explored in further studies.
Behavioral and emotional difficulties and HIV treatment outcomes among HIV-infected children in rural southwestern China
Authors: Zhou Yesheng , Tang Kailing , Lu Hongyan , Chen Hongli , Xie Haomin , Li Zeyu , Huang Jinghua , Fang Ningye , Chen Siya , Wang Hong , He Qin , Chen Huanhuan , Liu Xiu , Lan Guanghua , Zhu Qiuying , Chen Yi , Zhang Xiangjun , Ruan Yuhua , Liang Shujia 
Published: April 2023

Abstract
Background
Previous studies have not clearly demonstrated the impact of behavioral and emotional problems (BEDs) on treatment outcomes among HIV-infected children on antiretroviral therapy (ART). This study aimed to describe the prevalence of BEDs among this population and identify the factors associated with HIV treatment outcomes.

Methods
This cross-sectional study was conducted in Guangxi, China, between July and August 2021. HIV-infected children answered questionnaires about BEDs, physical health, social support, and whether they have missed doses in the past month. BEDs were assessed using the Chinese version of the self-reported Strengths and Difficulties Questionnaire (SDQ-C). The self-reported survey data were linked to participants’ HIV care information that was obtained from the national surveillance database. Univariate and multivariate logistic regression models were used to identify factors that were associated with missed doses in the past month and virological failure.

Results
The study sample was 325 HIV-infected children. HIV-infected children had a higher proportion of abnormal scores on SDQ-C total difficulties compared to their peers in the general population (16.9 vs 10.0%; P = 0.002). An abnormal SDQ-C total difficulties score (AOR = 2.06, 95%CI: 1.10–3.88) and infrequency of receiving assistance and support from parents over the past 3 months (AOR = 1.85, 95%CI: 1.12–3.06) were significantly associated with missed doses in the past month. Between the ages of 14–17 years (AOR = 2.66, 95% CI: 1.37–5.16), female (AOR = 2.21, 95% CI: 1.20–4.08), and suboptimal adherence (AOR = 2.45, 95% CI: 1.32–4.57) were significantly associated with virological failure.

Conclusions
Children’s mental health plays a role in HIV treatment outcomes. Psychological interventions should be promoted in pediatric HIV care clinics to improve children’s mental health status and HIV treatment outcomes.
Notch signaling is activated in knee-innervating dorsal root ganglia in experimental models of osteoarthritis joint pain
Authors: Wang Lai , Ishihara Shingo , Li Jun , Miller Rachel E. , Malfait Anne-Marie 
Published: April 2023

Abstract
Background
We aimed to explore activation of the Notch signaling pathway in knee-innervating lumbar dorsal root ganglia (DRG) in the course of experimental osteoarthritis (OA) in mice, and its role in knee hyperalgesia.

Methods
Cultured DRG cells were stimulated with the TLR4 agonist, lipopolysaccharide (LPS). Notch signaling in the cells was either inhibited with the γ-secretase inhibitor, DAPT, or with soluble Jagged1, or activated through immobilized Jagged1. CCL2 production was analyzed at mRNA and protein levels. In in vivo experiments, knee hyperalgesia was induced in naïve mice through intra-articular (IA) injection of LPS. The effect of inhibiting Notch signaling was examined by pre-injecting DAPT one hour before LPS. OA was induced through surgical destabilization of the medial meniscus (DMM) in male C57BL/6 mice. Gene expression in DRG was analyzed by qRT-PCR and RNAscope in situ hybridization. Activated Notch protein (NICD) expression in DRG was evaluated by ELISA and immunofluorescence staining. DAPT was injected IA 12 weeks post DMM to inhibit Notch signaling, followed by assessing knee hyperalgesia and CCL2 expression in the DRG.

Results
In DRG cell cultures, LPS increased NICD in neuronal cells. Inhibition of Notch signaling with either DAPT or soluble Jagged1 attenuated LPS-induced increases of Ccl2 mRNA and CCL2 protein. Conversely, activating Notch signaling with immobilized Jagged1 enhanced these LPS effects. In vivo, IA injection of LPS increased expression of Notch genes and NICD in the DRG. Pre-injection of DAPT prior to LPS alleviated LPS-induced knee hyperalgesia, and decreased LPS-induced CCL2 expression in the DRG. Notch signaling genes were differentially expressed in the DRG from late-stage experimental OA. Notch1, Hes1, and NICD were increased in the neuronal cell bodies in DRG after DMM surgery. IA administration of DAPT alleviated knee hyperalgesia post DMM, and decreased CCL2 expression in the DRG.

Conclusions
These findings suggest a synergistic effect of Notch signaling with TLR4 in promoting CCL2 production and mediating knee hyperalgesia. Notch signaling is activated in knee-innervating lumbar DRG in mice with experimental OA, and is involved in mediating knee hyperalgesia. The pathway may therefore be explored as a target for alleviating OA pain.
Steeper memory decline after COVID-19 lockdown measures
Authors: Bakker Els D. , van der Pas Stéphanie L. , Zwan Marissa D. , Gillissen Freek , Bouwman Femke H. , Scheltens Philip , van der Flier Wiesje M. , van Maurik Ingrid S. 
Published: April 2023

AbstractBackgroundDuring COVID-19 lockdown measures, memory clinic patients reported worries for faster cognitive decline, due to loss of structure and feelings of loneliness and depression. We aimed to investigate the impact of the COVID-19 lockdown on rate of cognitive decline in a mixed memory clinic population, compared to matched historical controls.MethodsWe included patients who visited Alzheimer Center Amsterdam 6 months to 1 week before the first Dutch COVID-19 lockdown, and had a second visit 1 year later, after this lockdown period (n = 113; 66 ± 7 years old; 30% female;n = 55 dementia,n = 31 mild cognitive impairment (MCI),n = 18 subjective cognitive decline (SCD),n = 9 postponed diagnosis). Historical controls (visit in 2016/2017 and second visit 1 year later (n = 640)) were matched 1:1 to lockdown patients by optimal Mahalanobis distance matching (both groupsn = 113). Groups were well matched. Differences between lockdown patients and historical controls over time in Mini-Mental State Examination, Trail Making Test part A and B, Rey-Auditory Verbal Learning Test (RAVLT) immediate and delayed recall, and category fluency scores were analyzed using linear mixed effect models with random intercepts. We examined differences in rate of cognitive decline between whole groups, and after stratification in SCD, MCI, and dementia separately.ResultsLockdown patients had a faster rate of memory decline compared to controls on both RAVLT immediate [B(SE) =  − 2.62 (1.07),p = 0.015] and delayed recall [B(SE) =  − 1.07 (0.34),p = 0.002]. Stratification by syndrome diagnosis showed that this effect was largely attributable to non-demented participants, as we observed faster memory decline during lockdown in SCD and MCI (RAVLT immediate [SCD:B(SE) =  − 6.85 (2.97),p = 0.027; MCI:B(SE) =  − 6.14 (1.78),p = 0.001] and delayed recall [SCD:B(SE) =  − 2.45 (1.11),p = 0.035; MCI:B(SE) =  − 1.50 (0.51),p = 0.005]), but not in dementia.ConclusionMemory clinic patients, specifically in pre-dementia stages, showed faster memory decline during COVID-19 lockdown, providing evidence that lockdown regulations had a deleterious effect on brain health. In individuals that may have been able to deal with accumulating, subclinical neuropathology under normal and structured circumstances, the additional stress of lockdown regulations may have acted as a “second hit,” resulting in less beneficial disease trajectory.
Cribriform adenocarcinoma of the minor salivary glands: a case report
Authors: Chen Tanya , Mamdani Mohammed , Vescan Allan , MacMillan Christina , Davies Joel 
Published: April 2023

Abstract
Background
Polymorphous adenocarcinoma is the third most common malignant salivary gland tumor. Within polymorphous adenocarcinoma, cribriform adenocarcinoma of salivary glands is a rare subtype and resembles papillary thyroid carcinoma histopathologically. Diagnostically, cribriform adenocarcinoma of salivary glands is challenging for pathologists and surgeons alike as initial presentation and cytologic nuclear features can be easily confused with papillary thyroid carcinoma arising from a thyroglossal duct remnant or lingual thyroid.

Case presentation
A healthy 64-year-old Caucasian woman presented to a community otolaryngologist with a 4-year history of progressive postnasal drip, globus sensation, and eventual dysphonia. Flexible fiberoptic laryngoscopy showed a large, smooth, vallecular lesion filling the oropharynx. Computed tomography imaging of the neck showed a rounded heterogeneous mass centered within the right aspect of the oropharynx measuring 4.2 × 4.4 × 4.5 cm. Fine needle aspiration biopsy was suspicious for papillary carcinoma due to microscopic findings of malignant cells, nuclear grooves, and a powdery chromatin pattern. In the operating room, the tumor was resected en bloc using a lateral pharyngotomy approach with partial resection of the right lateral hyoid. A limited cervical lymphadenectomy was performed to facilitate the lateral pharyngotomy approach and two out of three lymph nodes demonstrated regional metastatic disease. Nuclear grooves, nuclear membrane notching, and occasional intranuclear pseudoinclusions were identified, which are overlapping histopathological characteristics of papillary thyroid carcinoma and cribriform adenocarcinoma of salivary glands. It was negative for thyroglobulin and thyroid transcription factor-1, which was in keeping with cribriform adenocarcinoma of salivary glands rather than papillary thyroid carcinoma.

Conclusion
It is difficult to distinguish cribriform adenocarcinoma of salivary glands from papillary thyroid carcinoma solely by cytology, and the distinct characteristics of regional lymph node metastasis coupled with nuanced histologic differences should be emphasized in the evaluation of patients presenting with neck lymphadenopathy and an unknown primary or tongue mass. If sufficient fine needle aspiration biopsy material is available, thyroid transcription factor-1, thyroglobulin, or molecular testing may prove useful in differentiating cribriform adenocarcinoma of salivary glands from papillary thyroid carcinoma. A misdiagnosis of papillary thyroid carcinoma may lead to inappropriate treatment including unnecessary thyroidectomy. Therefore, it is critical for both pathologists and surgeons to be aware of this uncommon entity to avoid misdiagnosis and subsequent mismanagement.
Foodborne botulism and the importance of recognizing the disease in the emergency department: a case report
Authors: De Vet Seppe , Tackaert Thomas , Smet Mike , Raemen Hannelore 
Published: April 2023

Abstract
Background
Botulism is a rare neuroparalytic disease that has only presented itself 19 times in the last 30 years in Belgium. Patients present to emergency services with a wide range of complaints. Foodborne botulism is a forgotten yet life-threatening disease.

Case presentation
We describe a case of a Caucasian female in her 60s that presented to the emergency with reflux with nausea and spasmodic epigastric pain, no vomiting, dry mouth, and weakness in both legs. The symptoms started after ingestion of Atlantic wolffish. After exclusion of other more common causes, foodborne botulism was suspected. The patient was admitted to the intensive care unit for mechanical ventilation. Following treatment with trivalent botulinum antitoxin, she made a full neurologic recovery.

Conclusion
It is important to rapidly recognize the possible diagnosis of botulism even if the neurological symptoms are not dominant. Rapid neurologic dysfunction and respiratory difficulties starts between 6 and 72 hours after ingestion. The decision to administer antitoxins should, however, be based on the presumptive clinical diagnosis and diagnosis should not delay therapy.
ASAP2 interrupts c-MET-CIN85 interaction to sustain HGF/c-MET-induced malignant potentials in hepatocellular carcinoma
Authors: Ma Xiao-Lu , Nie Yan-Yan , Xie Su-Hong , Zheng Hui , Tong Ying , Wang Yan-Chun , Yan Tian-Qing , Meng Xin , Cao Jia-Zhen , Tang Wei-Guo , Guo Lin , Lu Ren-Quan 
Published: April 2023

Abstract
Background
Sustained activation of hepatocyte growth factor (HGF)/c-MET signaling is a major driver of hepatocellular carcinoma (HCC) progression, but underlying mechanism is unclear. ArfGAP With SH3 Domain, Ankyrin Repeat And PH Domain 2 (ASAP2) can reportedly activate GTPases and promote receptor tyrosine kinase signaling. However, the exact role of ASAP2 in HCC, especially for c-MET activation, also remains elusive.

Methods
ASAP2 expression levels in HCC tissues and cells were quantified using qRT-PCR, western blot (WB) analysis, and immunohistochemistry staining. Cell counting kit-8 (CCK-8) and colony formation assays were performed to evaluate cell proliferation rates. Flow cytometry assays were conducted to assess apoptosis rates. Wound healing and Transwell assays were performed to determine cell migration and invasion capacities. Epithelial-mesenchymal transition (EMT)-related marker expression levels were also examined. Subcutaneous implantation and tail vein injection models were applied for in vivo growth and metastasis evaluations, respectively. Bioinformatics analyses of The Cancer Genome Atlas and STRING datasets were performed to explore ASAP2 downstream signaling. Co-immunoprecipitation and Cycloheximide chasing experiments were performed to assess protein–protein interactions and protein half-life, respectively.

Results
ASAP2 had higher expression levels in HCC tissues than in normal liver, and also predicted poor prognosis. Knocking down ASAP2 significantly impaired cell proliferation, migration, and invasion capacities, but promoted apoptosis in HCC cells in vitro. However, overexpression of ASAP2 achieved the opposite effects. In vivo experiments confirmed that ASAP2 could promote HCC cell growth and facilitate lung metastasis. Interestingly, ASAP2 was essential for triggering EMT. Gene Set Enrichment Analysis demonstrated that c-MET signaling was greatly enriched in ASAP2-high HCC cases. Additionally, c-MET signaling activity was significantly decreased following ASAP knockdown, evidenced by reduced c-MET, p-AKT, and p-ERK1/2 protein levels. Importantly, ASAP2 knockdown effectively attenuated HGF/c-MET signaling-induced malignant phenotypes. c-MET and ASAP2 expression levels were positively correlated in our cohort. Mechanistically, ASAP2 can directly bind to CIN85, thereby disrupting its interaction with c-MET, and can thus antagonize CIN85-induced c-MET internalization and lysosome-mediated degradation. Notably, knocking down CIN85 can rescue the observed inhibitory effects caused by ASAP2 knockdown.

Conclusions
This study highlights the importance of ASAP2 in sustaining c-MET signaling, which can facilitate HCC progression.
Perinatal origins of bronchopulmonary dysplasia—deciphering normal and impaired lung development cell by cell
Authors: Mižíková I. , Thébaud B. 
Published: April 2023

AbstractBronchopulmonary dysplasia (BPD) is a multifactorial disease occurring as a consequence of premature birth, as well as antenatal and postnatal injury to the developing lung. BPD morbidity and severity depend on a complex interplay between prenatal and postnatal inflammation, mechanical ventilation, and oxygen therapy as well as associated prematurity-related complications. These initial hits result in ill-explored aberrant immune and reparative response, activation of pro-fibrotic and anti-angiogenic factors, which further perpetuate the injury. Histologically, the disease presents primarily by impaired lung development and an arrest in lung microvascular maturation. Consequently, BPD leads to respiratory complications beyond the neonatal period and may result in premature aging of the lung. While the numerous prenatal and postnatal stimuli contributing to BPD pathogenesis are relatively well known, the specific cell populations driving the injury, as well as underlying mechanisms are still not well understood. Recently, an effort to gain a more detailed insight into the cellular composition of the developing lung and its progenitor populations has unfold. Here, we provide an overview of the current knowledge regarding perinatal origin of BPD and discuss underlying mechanisms, as well as novel approaches to study the perturbed lung development.
Physics-informed deep learning framework to model intense precipitation events at super resolution
Authors: Teufel B. , Carmo F. , Sushama L. , Sun L. , Khaliq M. N. , Bélair S. , Shamseldin A. , Kumar D. Nagesh , Vaze J. 
Published: April 2023

AbstractPhysical modeling of precipitation at fine (sub-kilometer) spatial scales is computationally very expensive. This study develops a highly efficient framework for this task by coupling deep learning (DL) and physical modeling. This framework is developed and tested using regional climate simulations performed over a domain covering Montreal and adjoining regions, for the summers of 2015–2020, at 2.5 km and 250 m resolutions. The DL framework uses a recurrent approach and considers atmospheric physical processes, such as advection, to generate high-resolution information from low-resolution data, which enables it to recreate fine details and produce temporally consistent fields. The DL framework generates realistic high-resolution precipitation estimates, including intense short-duration precipitation events, which allows it to be applied in engineering problems, such as evaluating the climate resiliency of urban storm drainage systems. The results portray the value of the proposed DL framework, which can be extended to other resolutions, periods, and regions.
Progress and emerging techniques for biomaterial-based derivation of mesenchymal stem cells (MSCs) from pluripotent stem cells (PSCs)
Authors: Prakash Nityanand , Kim Jiseong , Jeon Jieun , Kim Siyeon , Arai Yoshie , Bello Alvin Bacero , Park Hansoo , Lee Soo-Hong 
Published: April 2023

Abstract
The use of mesenchymal stem cells (MSCs) for clinical purposes has skyrocketed in the past decade. Their multilineage differentiation potentials and immunomodulatory properties have facilitated the discovery of therapies for various illnesses. MSCs can be isolated from infant and adult tissue sources, which means they are easily available. However, this raises concerns because of the heterogeneity among the various MSC sources, which limits their effective use. Variabilities arise from donor- and tissue-specific differences, such as age, sex, and tissue source. Moreover, adult-sourced MSCs have limited proliferation potentials, which hinders their long-term therapeutic efficacy. These limitations of adult MSCs have prompted researchers to develop a new method for generating MSCs. Pluripotent stem cells (PSCs), such as embryonic stem cells and induced PSCs (iPSCs), can differentiate into various types of cells. Herein, a thorough review of the characteristics, functions, and clinical importance of MSCs is presented. The existing sources of MSCs, including adult- and infant-based sources, are compared. The most recent techniques for deriving MSCs from iPSCs, with a focus on biomaterial-assisted methods in both two- and three-dimensional culture systems, are listed and elaborated. Finally, several opportunities to develop improved methods for efficiently producing MSCs with the aim of advancing their various clinical applications are described.