bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of anticancer effect of colchicum autumnale L. Corm on breast cancer cell
Authors: Falahianshafiei Shiva , Akhtari Javad , Davoodi Ali , Pasha Hajar 
Published: October 2023

Abstract
Background
Breast cancer is the most common malignancy in women, and medicinal plants can prevent and play an inhibitory role for cancer. This study aims to evaluate the anticancer effect of colchicum autumnale L. Corm on breast cancer cell models.

Methods
In this study, the alkaloid-rich extract was prepared using the percolation method and with methanol/water solvent (70:30). HFF2 normal cell line and MCF-7 breast cancer cell line were cultured in microplates (96 wells). Then cells were treated with concentrations of 62.5 to 2000 ng/ml of extract and concentrations of 62 to 1000 ng/ml of doxorubicin at regular intervals of 48 and 72 h, and the percentage of cell growth inhibition was calculated. Cytotoxicity of drugs was measured by the MTT assay method. IC50 values were calculated by Calcusyn software. Also, the P-value of < 0.05 was considered significant.

Results
Alkaloid-rich extract of Colchicum autumnale plant inhibited breast cancer cell growth (MCF-7). The IC50 parameter showed more cytotoxic effects of Colchicum autumnale plant extract on the MCF-7 cancer cell line than HFF2 normal cell line for 48 and 72 h. In addition, with higher concentrations of the extract, cytotoxicity, and growth inhibitory effect increased significantly and in comparison to the doxorubicin was almost the same as cytotoxic.

Conclusion
This research provides a novel view into the development of new drugs for the treatment of cancer diseases. Colchicum autumnale plant extract had a significant cytotoxic effect like Doxorubicin drug on breast cancer cell line (MCF-7), which can alternatively treat and prevent breast cancer.
Some new insights into the biological activities of carboxymethylated polysaccharides from Lasiodiplodia theobromae
Authors: Pires Matheus Cerdeira , de Gois Andriolo Natalia , Lopes Bruno Rafael Pereira , Ruiz Ana Lucia Tasca Gois , do Nascimento Valeria Marta Gomes , Toledo Karina Alves , Santos Catarina dos 
Published: October 2023

Abstract
Background
Carboxymethylated Lasiodiplodan (LaEPS-C), Lasiodiplodia theobromae β-glucan exopolysaccharide derivative, has a well-known range of biological activities. Compared to LaEPS-C, its fractions, Linear (LLaEPS-C) and Branched (BLaEPS-C), have biological potentialities scarcely described in the literature. So, in this study, we investigate the immunomodulatory, antiviral, antiproliferative, and anticoagulant activities of LLaEPS-C and BLaEPS-C and compare them to the LaEPS-C.

Methods
LaEPS was obtained from L. theobromae MMBJ. After carboxymethylation, LaEPS-C structural characteristics were confirmed by Elementary Composition Analysis by Energy Dispersive X-Ray Detector (EDS), Fourier Transform Infrared (FTIR), and Nuclear Magnetic Resonance (NMR). The immunomodulatory activity on cytokine secretion was evaluated in human monocyte-derived macrophage cultures. The antiviral activity was evaluated by Hep-2 cell viability in the presence or absence of hRSV (human respiratory syncytial virus). In vitro antiproliferative activity was tested by sulforhodamine B assay. The anticoagulant activity was determined by APTT (Activated Partial Thromboplastin Time) and PT (Prothrombin Time).

Results
LaEPS-C showed low macrophage cell viability only at 100 µg/mL (52.84 ± 24.06, 48 h), and LLaEPS-C presented no effect. Conversely, BLaEPS-C showed cytotoxicity from 25 to 100 µg/mL (44.36 ± 20.16, 40.64 ± 25.55, 33.87 ± 25.16; 48 h). LaEPS-C and LLaEPS-C showed anti-inflammatory activity. LaEPS-C presented this at 100 µg/mL (36.75 ± 5.53, 48 h) for IL-10, and LLaEPS-C reduces TNF-α cytokine productions at 100 µg/mL (18.27 ± 5.80, 48 h). LLaEPS-C showed an anti-hRSV activity (0.7 µg/ml) plus a low cytotoxic activity for Hep-2 cells (1.4 µg/ml). LaEPS-C presented an antiproliferative activity for NCI-ADR/RES (GI50 65.3 µg/mL). A better PT was achieved for LLaEPS-C at 5.0 µg/mL (11.85 ± 0.87s).

Conclusions
These findings demonstrated that carboxymethylation effectively improves the biological potential of the LaEPS-C and their fractions. From those polysaccharides tested, LLaEPS provided the best results with low toxicity for anti-inflammatory, antiviral, and anticoagulant activities.
mRNA-based vaccines and therapeutics: an in-depth survey of current and upcoming clinical applications
Authors: Wang Yu-Shiuan , Kumari Monika , Chen Guan-Hong , Hong Ming-Hsiang , Yuan Joyce Pei-Yi , Tsai Jui-Ling , Wu Han-Chung 
Published: October 2023

AbstractmRNA-based drugs have tremendous potential as clinical treatments, however, a major challenge in realizing this drug class will promise to develop methods for safely delivering the bioactive agents with high efficiency and without activating the immune system. With regard to mRNA vaccines, researchers have modified the mRNA structure to enhance its stability and promote systemic tolerance of antigenic presentation in non-inflammatory contexts. Still, delivery of naked modified mRNAs is inefficient and results in low levels of antigen protein production. As such, lipid nanoparticles have been utilized to improve delivery and protect the mRNA cargo from extracellular degradation. This advance was a major milestone in the development of mRNA vaccines and dispelled skepticism about the potential of this technology to yield clinically approved medicines. Following the resounding success of mRNA vaccines for COVID-19, many other mRNA-based drugs have been proposed for the treatment of a variety of diseases. This review begins with a discussion of mRNA modifications and delivery vehicles, as well as the factors that influence administration routes. Then, we summarize the potential applications of mRNA-based drugs and discuss further key points pertaining to preclinical and clinical development of mRNA drugs targeting a wide range of diseases. Finally, we discuss the latest market trends and future applications of mRNA-based drugs.
Hardship financing, productivity loss, and the economic cost of illness and injury in Cambodia
Authors: Kolesar Robert John , Erreygers Guido , Van Damme Wim , Chea Vanara , Choeurng Theany , Leng Soklong 
Published: October 2023

Abstract
Background
Financial risk protection is a core dimension of universal health coverage. Hardship financing, defined as borrowing and selling land or assets to pay for healthcare, is a measure of last recourse. Increasing indebtedness and high interest rates, particularly among unregulated money lenders, can lead to a vicious cycle of poverty and exacerbate inequity.

Methods
To inform efforts to improve Cambodia’s social health protection system we analyze 2019–2020 Cambodia Socio-economic Survey data to assess hardship financing, illness and injury related productivity loss, and estimate related economic impacts. We apply two-stage Instrumental Variable multiple regression to address endogeneity relating to net income. In addition, we calculate a direct economic measure to facilitate the regular monitoring and reporting on the devastating burden of excessive out-of-pocket expenditure for policy makers.

Results
More than 98,500 households or 2.7% of the total population resorted to hardship financing over the past year. Factors significantly increasing risk are higher out-of-pocket healthcare expenditures, illness or injury related productivity loss, and spending of savings. The economic burden from annual lost productivity from illness or injury amounts to US$ 459.9 million or 1.7% of GDP. The estimated household economic cost related to hardship financing is US$ 250.8 million or 0.9% of GDP.

Conclusions
Such losses can be mitigated with policy measures such as linking a catastrophic health coverage mechanism to the Health Equity Funds, capping interest rates on health-related loans, and using loan guarantees to incentivize microfinance institutions and banks to refinance health-related, high-interest loans from money lenders. These measures could strengthen social health protection by enhancing financial risk protection, mitigating vulnerability to the devastating economic effects of health shocks, and reducing inequities.
Preservation vs. dissection of inferior pulmonary ligament for thoracoscopic upper lobectomy: a prospective randomized controlled trial
Authors: Qian Jiekun , Cai Shixian , Lin Pinghua , Chi Wanzhong , Chen Chun , Xu Guobin , Xu Chi , Wu Weidong , Zheng Wei , Zheng Bin 
Published: October 2023

Abstract
Objectives
The proper procedure for inferior pulmonary ligament (IPL) during upper lobectomy remains a topic of debate. To address this matter, we carried out a trial comparing the clinical outcomes of IPL preservation versus IPL dissection during thoracoscopic upper lobectomy (TUL).

Methods
Patients undergoing thoracoscopic left/right upper lobectomy (TLUL/TRUL) were assigned to either the dissection group (Group D) or the preservation group (Group P). Our primary objective was to quantify and compare the alterations in postoperative residual bronchial angle and lung volume changes between the two groups. Our secondary objective encompassed the assessment of various other intraoperative and postoperative outcomes.

Results
Following adherence to the inclusion and exclusion criteria, we enrolled 100 patients (41 left and 59 right) in Group P and 108 patients (41 left and 67 right) in Group D for the study. Our findings revealed that in TLUL, Group P was able to reduce the degree of postoperative residual bronchial angle change (P < 0.05). Conversely, the situation was distinct for TRUL. We found no notable disparity between the two groups (P > 0.05) with regard to alterations in lung volume or the occurrence of postoperative complications—except for the duration of postoperative hospital stay (P < 0.05).

Conclusions
Our study suggests IPL preservation especially for TLUL when compared to TRUL, which have important implications for the clinical management of patients undergoing upper lobectomy.
Supporting patients in the transition to the revised pexidartinib dosing regimen: perspectives from the multidisciplinary clinical and allied health professional team
Authors: McCabe Colleen , Wright Hillary , Polson Kathleen , Wagner Andrew J. 
Published: October 2023

AbstractPexidartinib is a colony-stimulating factor-1 receptor inhibitor approved in the United States for treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Because of the risk of severe and potentially fatal hepatotoxicity, pexidartinib is only available through a Risk Evaluation and Mitigation Strategy (REMS) program. Pexidartinib pharmacokinetics are influenced by the fat content of meals: compared with the fasted state, consuming a high-fat meal with pexidartinib increases pexidartinib absorption by 100%; a low-fat meal increases absorption by approximately 60%. Pexidartinib was initially authorized to be taken at 800 mg/day on an empty stomach; therefore, if this same dose of pexidartinib is taken with food, there is a risk of overexposure and potential toxicity. To reduce the risk of hepatotoxicity and improve patient compliance, pexidartinib has undergone a revised dosing regimen, from 800 mg/day (400 mg twice daily) fasted to 500 mg/day (250 mg twice daily) with a low-fat meal (approximately 11–14 g of total fat). The objective of this report is to educate clinical and allied health professionals on the revised dosing regimen and the importance of patient compliance with a low-fat meal. Healthcare professionals need to understand the rationale for the switch from pexidartinib dosing on an empty stomach to dosing with a low-fat meal and how meal composition and timing influence pharmacokinetics. Finally, we provide guidance for the healthcare team of prescribing providers, nurses, pharmacists, and dietitians who are caring for patients with TGCT on pexidartinib. It is important for healthcare providers to deliver consistent messaging on the low-fat meal requirement and help patients fit pexidartinib into their regular meal schedules. Consulting a dietitian may be helpful for patients, especially those with complex dietary needs. We provide an overview of the roles and responsibilities of each healthcare professional and outline steps to best support patients, including key questions and answers related to the revised dosing regimen. This report provides the information necessary to guide the multidisciplinary team caring for patients with TGCT and to support them through the pexidartinib dosing regimen change.
Integrative multi-omic sequencing reveals the MMTV-Myc mouse model mimics human breast cancer heterogeneity
Authors: Broeker Carson D. , Ortiz Mylena M. O. , Murillo Michael S. , Andrechek Eran R. 
Published: October 2023

Abstract
Background
Breast cancer is a complex and heterogeneous disease with distinct subtypes and molecular profiles corresponding to different clinical outcomes. Mouse models of breast cancer are widely used, but their relevance in capturing the heterogeneity of human disease is unclear. Previous studies have shown the heterogeneity at the gene expression level for the MMTV-Myc model, but have only speculated on the underlying genetics.

Methods
Tumors from the microacinar, squamous, and EMT histological subtypes of the MMTV-Myc mouse model of breast cancer underwent whole genome sequencing. The genomic data obtained were then integrated with previously obtained matched sample gene expression data and extended to additional samples of each histological subtype, totaling 42 gene expression samples. High correlation was observed between genetic copy number events and resulting gene expression by both Spearman’s rank correlation coefficient and the Kendall rank correlation coefficient. These same genetic events are conserved in humans and are indicative of poor overall survival by Kaplan–Meier analysis. A supervised machine learning algorithm trained on METABRIC gene expression data was used to predict the analogous human breast cancer intrinsic subtype from mouse gene expression data.

Results
Herein, we examine three common histological subtypes of the MMTV-Myc model through whole genome sequencing and have integrated these results with gene expression data. Significantly, key genomic alterations driving cell signaling pathways were well conserved within histological subtypes. Genomic changes included frequent, co-occurring mutations in KIT and RARA in the microacinar histological subtype as well as SCRIB mutations in the EMT subtype. EMT tumors additionally displayed strong KRAS activation signatures downstream of genetic activating events primarily ascribed to KRAS activating mutations, but also FGFR2 amplification. Analogous genetic events in human breast cancer showed stark decreases in overall survival. In further analyzing transcriptional heterogeneity of the MMTV-Myc model, we report a supervised machine learning model that classifies MMTV-Myc histological subtypes and other mouse models as being representative of different human intrinsic breast cancer subtypes.

Conclusions
We conclude the well-established MMTV-Myc mouse model presents further opportunities for investigation of human breast cancer heterogeneity.
Drosophila CASK regulates brain size and neuronal morphogenesis, providing a genetic model of postnatal microcephaly suitable for drug discovery
Authors: Tello Judith A. , Jiang Linan , Zohar Yitshak , Restifo Linda L. 
Published: October 2023

Abstract
Background
CASK-related neurodevelopmental disorders are untreatable. Affected children show variable severity, with microcephaly, intellectual disability (ID), and short stature as common features. X-linked human CASK shows dosage sensitivity with haploinsufficiency in females. CASK protein has multiple domains, binding partners, and proposed functions at synapses and in the nucleus. Human and Drosophila CASK show high amino-acid-sequence similarity in all functional domains. Flies homozygous for a hypomorphic CASK mutation (∆18) have motor and cognitive deficits. A Drosophila genetic model of CASK-related disorders could have great scientific and translational value.

Methods
We assessed the effects of CASK loss of function on morphological phenotypes in Drosophila using established genetic, histological, and primary neuronal culture approaches. NeuronMetrics software was used to quantify neurite-arbor morphology. Standard nonparametric statistics methods were supplemented by linear mixed effects modeling in some cases. Microfluidic devices of varied dimensions were fabricated and numerous fluid-flow parameters were used to induce oscillatory stress fields on CNS tissue. Dissociation into viable neurons and neurite outgrowth in vitro were assessed.

Results
We demonstrated that ∆18 homozygous flies have small brains, small heads, and short bodies. When neurons from developing CASK-mutant CNS were cultured in vitro, they grew small neurite arbors with a distinctive, quantifiable “bushy” morphology that was significantly rescued by transgenic CASK+. As in humans, the bushy phenotype showed dosage-sensitive severity. To overcome the limitations of manual tissue trituration for neuronal culture, we optimized the design and operation of a microfluidic system for standardized, automated dissociation of CNS tissue into individual viable neurons. Neurons from CASK-mutant CNS dissociated in the microfluidic system recapitulate the bushy morphology. Moreover, for any given genotype, device-dissociated neurons grew larger arbors than did manually dissociated neurons. This automated dissociation method is also effective for rodent CNS.

Conclusions
These biological and engineering advances set the stage for drug discovery using the Drosophila model of CASK-related disorders. The bushy phenotype provides a cell-based assay for compound screening. Nearly a dozen genes encoding CASK-binding proteins or transcriptional targets also have brain-development mutant phenotypes, including ID. Hence, drugs that improve CASK phenotypes might also benefit children with disorders due to mutant CASK partners.
Transurethral laser lithotripsy using the Mitrofanoff urethral conduit for bladder stones: a case report
Authors: Yamamoto Shotaro , Kawahara Takashi , Saito Tomoki , Hanai Takahiro , Takeshima Teppei , Teranishi Junichi , Makiyama Kazuhide , Uemura Hiroji 
Published: October 2023

Abstract
Background
The Mitrofanoff (appendicovesicostomy) procedure is a contraindicated urinary modification that maintains urinary continence by forming a flap-valve mechanism at the site of anastomosis between the appendage and bladder wall, which is used as a guide for urinary drainage. This technique has been used by intermittent self-catheterization patients who have difficulty voiding from the native urethra or in cases where voiding from the abdominal wall would improve quality of life. However, the risk of stone formation is high due to intermittent urinary catheterization using the Mitrofanoff conduit urethrostomy as a conduit.

Case presentation
The patient was a 22-year-old Asian-Japanese woman. At 6 years of age, she underwent bilateral vesicoureteral reflux surgery, Mitrofanoff urethrostomy using the appendix, abdominal wall plication, and vaginoplasty using the ileum. During follow-up, ultrasound performed due to persistent pain during urinary drainage revealed a 26 mm bladder stone. We performed ureteroscopic lithotripsy 6Fr using ureteral access sheath and made lithotripsy using Ho: YAG laser, then successfully removed the target stone.

Conclusions
We report a case of transurethral laser lithotripsy using the Mitrofanoff urethral conduit for bladder stones. Using with ureteral access sheath made lithotripsy and retrieved ureteral stone more effective.
Lung erosion following adjuvant immunotherapy with pembrolizumab: a case report
Authors: Leow Lowell , Anbudurai Manisha , Yue Li , Tam John Kit Chung 
Published: October 2023

Abstract
Background
Pembrolizumab as immunotherapy is increasingly used in adjuvant, neoadjuvant, and standalone therapy and has been described as safe. We share an experience of lung erosion post-thoracic surgery with the use of adjuvant pembrolizumab.

Case presentation
A 65-year-old Chinese gentleman with metastatic renal cell carcinoma underwent lung metastasis resection and presented with delayed onset pneumothorax while on adjuvant pembrolizumab. Failure of conservative management warranted repeat surgical intervention, and intraoperative findings showed erosion of staple lines possibly caused by poor healing associated with pembrolizumab.

Conclusion
Adjuvant pembrolizumab may impair wound healing, including stapler line healing. Presentation of delayed pneumothorax in a post-surgical patient undergoing immunotherapy should warrant early surgical intervention.
An acoustic echo canceller optimized for hands-free speech telecommunication in large vehicle cabins
Authors: Saremi Amin , Ramkumar Balaji , Ghaffari Ghazaleh , Gu Zonghua 
Published: October 2023

AbstractAcoustic echo cancelation (AEC) is a system identification problem that has been addressed by various techniques and most commonly by normalized least mean square (NLMS) adaptive algorithms. However, performing a successful AEC in large commercial vehicles has proved complicated due to the size and challenging variations in the acoustic characteristics of their cabins. Here, we present a wideband fully linear time domain NLMS algorithm for AEC that is enhanced by a statistical double-talk detector (DTD) and a voice activity detector (VAD). The proposed solution was tested in four main Volvo truck models, with various cabin geometries, using standard Swedish hearing-in-noise (HINT) sentences in the presence and absence of engine noise. The results show that the proposed solution achieves a high echo return loss enhancement (ERLE) of at least 25 dB with a fast convergence time, fulfilling ITU G.168 requirements. The presented solution was particularly developed to provide a practical compromise between accuracy and computational cost to allow its real-time implementation on commercial digital signal processors (DSPs). A real-time implementation of the solution was coded in C on an ARM Cortex M-7 DSP. The algorithmic latency was measured at less than 26 ms for processing each 50-ms buffer indicating the computational feasibility of the proposed solution for real-time implementation on common DSPs and embedded systems with limited computational and memory resources. MATLAB source codes and related audio files are made available online for reference and further development.