bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detachment-activated FAK-STAT3-NNMT inhibits anoikis by enhancing fatty acid oxidation in breast cancer
Authors: Tong Qingchao , Ma Yilei , Gao Yuzhen , Zhou Lin , Fang Qiang , Fang Sining , Zhao Ru , Zeng Jin , Li Guoli , Xie Xinyou , Wang Yanzhong , Zhang Jun 
Published: February 2024

Abstract
Purpose: Breast cancer metastasis claims the majority of breast cancer-related deaths. Anoikis resistance is a key prerequisite for tumor metastasis. Possible mechanism of evading anoikis in breast cancer remains unclear. Our previous research demonstrated that Nicotinamide N-methyltransferase (NNMT) has essential functions in cancer development and metastasis. However, the spercific functional mechanisms of NNMT in breast cancer anoikisp remain to be explored
Method: Immunofluorescence staining, confocal microscopy analysis, immunoblotting and qPCR were used to analyze NNMT expression. Flow cytometry and soft agar assay were used to analyze the proportion of breast cancer cells undergoing anoikis. ChIP assay and detached cell model were used to confirm the presence of FAK-STAT3-NNMT in detached breast cancer cells. BODIPY staining was used to visualize lipid deposit in the cytoplasm, and Seahorse analysis was used to directly measure FAO rate of attached and detached breast cancer cells.
Results: Detachment of breast cancer cells activates the FAK-STAT3 axis to increase the transcription of NNMT, which then protects breast cancer cells from anoikis by enhancing fatty acid oxidation (FAO). Mechanistically, NNMT promotes the expression of CPT1A, a FAO rate-limiting gene, by suppressing PP2A methylation. Furthermore, NNMT-induced FAO accelerates the clearance of reactive oxygen species (ROS), which triggers anoikis and hinders cancer metastasis, by maintaining NADP+/NADPH balance. In vivo experiments show that NNMT-knockdown breast cancer cells colonize the lung much less than that of NNMT high expression cells. Additionally, inhibitors of NNMT or FAO suppressed breast cancer cell metastasis, suggesting that NNMT-mediated FAO enhances the metastatic potential of breast cancer.
Conclusion: Our study identifies that NNMT, an enzyme upregulated during detachment via the FAK-STAT3 axis, activates the FAO pathway to resist anoikis of breast cancer cells.
The Effect of Constipation on Quality of Life in Child Patients Receiving Chemotherapy: Descriptive Cross-Sectional Study
Authors: BULUT Hacer KOBYA , YETIMOGLU Merve , Bahadır Aysenur 
Published: February 2024

Abstract
Purpose
This study was conducted to evaluate the effect of constipation on quality of life in paediatric patients receiving chemotherapy.
Methods
This study was carried out in a descriptive cross-sectional research design with 60 children and their parents in the outpatient chemotherapy unit of a university hospital. Data were collected face-to-face by means of questionnaires.
Results
It was determined that 70% of the children receiving chemotherapy experienced constipation. A significant correlation was found between having a female gender and experiencing constipation (p˂0.05). The quality of life of parents of children with constipation was low. At the same time, there is significance between experiencing constipation and parental quality of life (p˂0.05). Among children with constipation, 61.9% reported that they perceived constipation as a very important problem.
Evidence that chronic lymphocytic leukemia arises from a multiclonal selection process
Authors: Bagnara Davide , Cardente Niccolò , Vergani Stefano , Kasar Siddha , Fernandes Stacey , Mazzarello Andrea , Ferrer Gerardo , Ghiotto Fabio , Barrientos Jacqueline , Rai Kanti , Kolitz Jonathan , Allen Steven , Fais Franco , Brown Jennifer , Ferrarini Manlio , Chiorazzi Nicholas 
Published: February 2024

Abstract
Although chronic lymphocytic leukemia (CLL) is diagnosed by identifying in a patient’s blood a B-cell clone that exceeds 5x106/µL, additional clones have on occasion been identified. To characterize such clones in patients with CLL, we analyzed by NGS the IGHV-IGHD-IGHJ gene rearrangements in circulating CD5+ B cells from 57 untreated patients. In every patient, we identified additional distinct clonotypes (ADCs) from the clinically relevant clone (CRC). Even when defining clonal expansion using a rigorous threshold, 68% of patients had at least one expanded ADC. The predominant ADC (pADC) reached numbers qualifying as a CLL clone in two patients and qualifying as low/high-count monoclonal B-cell lymphocytosis in each other case. Over time, pADCs enlarged or shrank, suggesting an ongoing selection process. Stereotyped IGHV-D-J rearrangements were enriched in ADCs and IGHV usage and mutations revealed similarities specifically between pADCs and CRCs, while minor ADCs more closely resembled normal CD5+ B-cells. Thus, finding multiple expanded clones within the CD5+ B-cell population of patients with CLL is more the rule rather than the exception. Thus, leukemogenesis involves a competitive selection for dominance of more than one B-cell clone, with the process being influenced to some degree by the structure of the B-cell receptor.
Landing Style Influences Peak ‘ground’ Reaction Forces During Repeated Jumping Using a Supine Jump Sled in Microgravity
Authors: Price Phil DB , Kennett John E , Scott Jonathan PR , Green David A , Cleather Daniel J 
Published: February 2024

Abstract

Repeated jumping has been demonstrated as a feasible exercise countermeasure in microgravity and has been shown to reduce deconditioning in head down bed rest studies. However, varying landing stiffness may provide greater contribution of both axial and medio-lateral bone strain and muscle loading at greater muscle lengths, which may help minimize bone and muscle deconditioning. Therefore, this study investigated the effect of different landing styles on the force profile and ground contact time during repeated jumping using HIFIm in microgravity. Two participants performed repeated jumping on the HIFIm jump sled in microgravity during a parabolic flight campaign. ‘Ground’ forces and ground contact time were compared between landing styles where increased landing stiffness was instructed to the jumper, and increased spring resistance. The results show that the forces experienced when performing repeated jumps in microgravity are sensitive to the landing style employed. As greater stiffness was instructed, peak forces increased, and ground contact time decreased significantly. Peak forces and ground contact time also significantly increased when spring resistance increased. These results highlight that landing instructions and spring configurations could be used as training variables when developing an astronaut training program, which can use different jump styles to minimize bone and muscle deconditioning. Further research using bed rest analogs and repeated jumping using HIFIm is needed to demonstrate varied repeated jumping interventions as an effective exercise method for minimizing deconditioning in astronauts.
Therapeutic efficacy of artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria treatment in Metehara, Central-east Ethiopia
Authors: Tesfaye Mahelet , Assefa Ashenafi , Mamo Hassen 
Published: February 2024

Abstract
Malaria drug resistance presents a significant challenge to malaria control and elimination efforts. Therefore, it is crucial to conduct regular surveillance to assess the therapeutic efficacy of first-line antimalarial drugs, which informs policy decisions to manage this threat. This study aimed to evaluate the therapeutic efficacy of artemether-lumefantrine (AL), which is the first-line treatment for uncomplicated malaria in Ethiopia since 2004, for uncomplicated Plasmodium falciparum malaria in Metehara, central-east Ethiopia. Using a one-arm prospective evaluation design, the study assessed the clinical and parasitological responses of patients with uncomplicated P. falciparum malaria. Initially, 80 patients (50 males and 30 females) were screened, and a total of 73 participants (44 males, 29 females) successfully completed the follow-up. The results indicated rapid parasite clearance and resolution of clinical symptoms, with all patients achieving complete recovery from asexual parasitemia and fever by day 3. The prevalence of gametocytes decreased from 6.3% on day zero to 2.5% on days two, three, seven, and ultimately achieving complete clearance afterwards. The overall cure rate for AL treatment, without a polymerase chain reaction correction, was 100%, demonstrating its high efficacy in effectively eliminating the malaria parasite in patients. Importantly, no serious adverse events related to AL treatment were reported during the study, suggesting its safety and tolerability among the participants. These findings confirm that, even 20 years after its introduction in Ethiopia, AL remains an effective treatment for uncomplicated P. falciparum malaria in the study site.
Exploring the link between particulate matter pollution and type II Diabetes in Italy and Lombardy using clinical longitudinal data: a comparative analysis
Authors: Abbafati Cristiana , Nieddu Luciano 
Published: February 2024

Abstract
Background:
The association between particulate ambient air pollution and an increased risk of type II Diabetes (T2DM) is well-established. Air pollution, a significant public health concern globally, affects various non-communicable diseases, including T2DM. Italy faces significant challenges with both particulate air pollution and T2DM. No studies in Italy exist assessing the association of particulate and T2DM on a large dataset regarding clinically diagnosed T2DM.
Methods:
This study aims to assess the association between particulate matter (PM2.5 and PM10) and T2DM prevalence, and incidence rate in Lombardy compared to the rest of Italy from 2006 to 2019. The association with Years lived with disability (YLDs) rates has been assessed on data from 2006 to 2016. Data is obtained from the AMD dataset, a comprehensive outpatient longitudinal dataset, while particulate matter data is sourced from European Environment Agency and ARPA Lombardy. The association has been assessed via mixed-effects models.
Results:
The mixed-effects model revealed a significant positive association between particulate matter and T2DM incidence rates in Italy, with notable variations over time and between regions (Lombardy vs the rest of Italy). While no significant effect was observed of particulate on prevalence rates and YLDs rates, there is a positive significant connection between particulate and Incidence rate for Italy. The effect increases with time. The opposite tendency has been observed for Lombardy with a negative association of particulate and incidence. Said effect decreases with time opposing the trend for Italy.
Conclusions:
Particulate matter pollution, specifically PM2.5 and PM10, seems to be significantly associated with T2DM incidence rates in Italy. However, the impact varies between regions, with Lombardy exhibiting a complex relationship influenced by socioeconomic factors. This study underscores the importance of addressing air pollution as a public health priority, particularly in regions with high pollution levels like Lombardy, to mitigate the risk of T2DM and its associated burden.
MiR-223 Enhances Lipophagy by Suppressing CTSB in Microglia Following Lysolecithin-Induced Demyelination in Mice
Authors: Ma Hao , Ou Zhilin , Alaeiilkhchi Nima , Cheng Yongquan , Chen Kai , Chen Jiayu , Guo Ruqin , He Minyue , Tang Shiyi , Zhang Xin , Huang Zhiping , Liu Jie , Zhu Qinan , Huang Zu-cheng , Jiang Hui 
Published: February 2024

Abstract
Background
Lipid droplet (LD)-laden microglia are key pathological hallmarks of multiple sclerosis. The recent discovery of a novel microglial subtype, lipid-droplet-accumulating microglia (LDAM), is notable for increased inflammatory factor secretion and diminished phagocytic capability. Lipophagy, the autophagy-mediated selective degradation of LDs, plays a critical role in this context. This study investigates microRNA (miRNA) involvement in lipophagy during demyelinating diseases, assesses their capacity to modulate LDAM subtypes, and elucidates potential underlying mechanisms.
Methods
We conducted in vivo experiments using C57BL/6 mice. Two weeks post-demyelination induction at the cervical level 4 (C4), we performed histological assessments and confocal imaging to examine LD accumulation in microglia within the lesion site. Autophagic changes were observed using transmission electron microscopy. MiRNA and mRNA multi-omics analyses identified differentially expressed miRNAs and mRNAs under demyelinating conditions and the related autophagy target genes. We specifically explored the role of miR-223 in lipophagy in these conditions. In vitro studies, including miR-223 upregulation in BV2 cells via lentiviral transfection, validated bioinformatics findings. Immunofluorescence staining measured LD accumulation, autophagy levels, target gene expression, and inflammatory mediators, elucidating miR-223's mechanisms in LDAM.
Results
Oil Red O staining and confocal imaging revealed substantial LD accumulation in the demyelinated spinal cord. Transmission electron microscopy showed increased autophagic vacuoles at the injury site. Multi-omics analysis pinpointed miR-223 as a crucial regulatory gene in lipophagy during demyelination. Integrating miRNA, mRNA, and autophagy gene databases identified Cathepsin B (CTSB) as a miR-223 target in autophagy. In vitro, miR-223 upregulation suppressed CTSB expression in BV2 cells, augmented autophagy, alleviated LD accumulation, and decreased IL-1β, an inflammatory mediator.
Conclusion
These findings indicate miR-223's pivotal role in lipophagy during demyelinating conditions. By inhibiting CTSB, miR-223 promotes selective LD degradation, thereby reducing the lipid burden and inflammatory phenotype in LDAM. This study broadens our understanding of lipophagy's molecular mechanisms and proposes lipophagy induction as a potential therapeutic approach to mitigate inflammatory responses in demyelinating diseases.
TAG Synthesis and Oxidation Activated by YAP/TEAD Confers ROS Resistance in Cancer Stem Cells
Authors: Lin Jiun-Han , Hsu Tien-Wei , Cheng Wei-Chung , Liu Chen-Chi , Li Anna Fen-Yau , Hung Mien-Chie , Hsu Han-Shui , Hung Shih-Chieh 
Published: February 2024

Abstract
Background
Cancer stem cells (CSCs) are characterized by lower levels of reactive oxygen species (ROS), which contribute to radioresistance through mechanisms that remain unidentified.
Methods
Our study employed lipidomic analyses to investigate the lipid composition of lung CSCs, while concurrently utilizing RNA-seq analysis to assess the expression profile of CSCs. Gain and loss of functional studies were conducted to decipher the underlying molecular pathways. In addition, we performed immunohistochemical staining on clinical samples from human lung cancer patients and utilized transcriptome data to identify potential biomarkers for prognosis prediction.
Results
Lipidomic analyses unveiled that the predominant lipid in lung CSCs was triacylglycerol (TAG), which localized to peri-mitochondria lipid droplets. TAG acted as mitochondria-derived ROS scavengers, displaying higher oxidation levels compared to other lipids when exposed to H2O2. RNA-seq analysis revealed an upregulation of TAG synthesis enzymes (ACSL1/4, LPIN2, DGAT1/2, and PNPLA3) and the anti-ferroptosis arsenal GPX4 in CSCs. These molecular alterations were found to be relevant to CSC radioresistance, sphere formation, and tumor initiation. Furthermore, a six-gene TAG synthesis signature was identified, effectively predicting the prognosis and survival of lung cancer patients. Mechanistically, lung CSCs activated the YAP/TEAD pathway, enhancing the transcription of TAG synthesis genes, thereby playing a crucial role in both TAG synthesis and oxidation, ultimately conferring ROS resistance.
Conclusions
This comprehensive study enhances our understanding of the intricate mechanisms underlying CSC radioresistance. The identified pathways and signatures provide a promising foundation for the development of targeted therapies aimed at overcoming radioresistance in CSCs, with the potential to significantly improve patient outcomes in lung cancer treatment.
Graphic Abstract
Abscisic acid improves the phytoremediation ability of the aquatic accumulator plant Nasturtium officinale R. Br. in cadmium-contaminated soil
Authors: Peng Xuemei , Xiao Yunying , Tang Wanjia , Dai Zhen , Zhang Dilian , Zheng Yangxia , Lin Lijin 
Published: February 2024

Abstract

Previous studies report significant contamination of farmland soil by cadmium (Cd). Cadmium contamination increases the risk of diseases after consumption of grain crops with high Cd levels. Hyperaccumulators or accumulators have been widely used to bioremediate Cd-contaminated farmland soil. Studies report that aquatic hyperaccumulators or accumulators are rarely used in phytoremediation, or their phytoremediation efficiencies are low. A pot experiment was carried out to explore the effects of abscisic acid (ABA) on the cadmium (Cd) accumulation (phytoremediation) of emerged aquatic accumulator plant Nasturtium officinale R. Br. ABA application increased the shoot biomass, peroxidase (POD) activity, superoxide dismutase (SOD) activity, catalase (CAT) activity, and soluble protein content of N. officinale under Cd-contamination condition. The application of ABA at 5, 10, and 20 µmol/L increased the chlorophyll and carotenoid contents in N. officinale. The application of ABA also increased the shoot Cd content and shoot Cd extraction of N. officinale. The application of ABA at 1, 5, 10, and 20 µmol/L increased the shoot Cd extraction by 11.65, 25.27, 37.91, and 58.52%, respectively, compared with the control. In addition, ABA concentration had a linear regression relationship with the root biomass, shoot biomass, root Cd extraction, and shoot Cd extraction. Correlation, grey relational, and path analyses showed that the root biomass, shoot biomass, root Cd extraction, root Cd content, POD activity, SOD activity, and soluble protein content were significantly associated with the shoot Cd extraction. These findings indicate that ABA application can improve the phytoremediation ability of N. officinale under Cd-contaminated flooded fields.
Transcultural Adaptation and Psychometric Evaluation of the Serbian Ankylosing Spondylitis Quality of Life (Asqol) Questionnaire and Its Correlations With Disease Activity (Asdas, Basdai) and Functional Status Indexes
Authors: Mirjana Zlatkovic-Svenda , Dejan Dudok , Jeanette Thorpe , Jelena Milicevic , Dejana Petrovic , Marija Zdravkovic , Goran Radunovic 
Published: February 2024

Abstract
Background: The Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire gauges the impact of ankylosing spondylitis on individuals' overall well-being, shedding light on the quality of life challenges associated with this condition. The main goal of this study was to translate and adapt a Serbian version of the ASQoL questionnaire and to validate it with Serbian speaking AS patients.
Methods: Three stages were accomplished in this study. First, the ASQoL questionnaire was translated using transcultural adaptation and its linguistic intelligibility and naturalness were assessed by a bilingual and a lay panel. Second, cognitive debriefing interviews were implemented to determine face and content validity. Third, psychometric properties of the ASQoL were assessed by construct validity (convergent validity by using NHP as a comparator scale, and known group validity by correlating with disease activity and overall health state), and reliability through the internal consistency and test-retest reliability. Finally, correlations of the ASQoL were evaluated with disease activity and functional status indexes.
Results: The bilingual panel consisted of one male and five female Serbian professionals fluent in English, aged 25 to 35 years. The lay panel comprised two males and three females aged 28 to 65 years. Both panels were led by the same moderator. Cognitive debriefing interviews were conducted with 10 patients with a range of demographic backgrounds. The newly adapted questionnaire was evaluated as clear, precise and easy to understand and complete, and all of the questions were found to be valid and appropriate. Psychometric properties were tested on 60 randomly selected patients. Convergent validity was assessed by correlations of ASQoL and NHP domains of the pain (r =0.79), emotional reactions (r=0.78), physical activity (r=0.77) and energy (r=0.75) scales. Internal reliability measured by Cronbach’s alpha coefficient was 0.95 (1st administration) and 0.91 (2nd administration), test-retest reliability was 0.84, showing high correlations of the 1st and 2nd ASQoL administrations. Three independent regression analyses have shown significant relations (p<0.001) between ASQoL and ASDAS (R²=0.40), BASDAI (R²=0.56) and BASFI (R²=0.44).
Conclusion: The Serbian ASQoL has demonstrated excellent psychometric properties, indicating that it is a valid and veracious instrument for use both in clinical studies and clinical practice.
Neonatal ECMO in Severe Bronchiolitis: Our Experience in the Last 10 Years.
Authors: Merino-Hernández Amaia , Muñoz-Cutillas Agustín , Zeballos-Sarrato Susana , Bernardo-Atienza Belén , Sánchez-Luna Manuel 
Published: February 2024

Abstract

Introduction:
Bronchiolitis is the most common lower respiratory tract infection in infants less than 1 year of age, and the leading cause of hospitalization in this age group in developed countries. Neonates with bronchiolitis usually have a favorable prognosis, but preterm infants due their immaturity sometimes they undergo progressive and rapid deterioration with failure of the standard respiratory support and may require rescue treatment with extracorporeal membrane oxygenation (ECMO).
Materials and Methods
Observational, retrospective and single-center study conducted in the neonatology department of a high-complexity hospital (Level IIIC). The study included patients admitted to the Neonatal Intensive Care Unit who required ECMO for severe respiratory failure due to acute bronchiolitis between 2013 and 2022.
Results
6 patients were included, 83.3% preterm with a median gestational age of 28.6 weeks (IQR 27.1–29.6)). 3 patients (50%) presented with community bronchiolitis, and 3 (50%) with nosocomial bronchiolitis. RSV was isolated in 4 patients, rhinovirus in one and influenza A in another. The median duration of mechanical ventilation before ECMO was 2.5 days (IQR 1–4). At the beginning of ECMO support, the median age was 48.5 days (IQR 34–120), with a median postmenstrual age of 38 weeks (IQR 35-41.8) and a median weight of 2490 grams (IQR 1800–2900). The median duration of ECMO therapy was 14 days (IQR 9–24). 2 patients (33%) died, one from cardiac arrest due to hemopericardium and the other from liver failure with severe coagulopathy. All surviving patients were followed up by pulmonology and neurology. 2 (33.3%) required home oxygen therapy, and both had a respiratory admission in the first year of life. One required bronchodilator treatment, and the other has had a good evolution. One patient was diagnosed with attention deficit hyperactivity disorder, one with autism spectrum disorder and another with mild cognitive retardation and deafness.
Conclusion
Small infants are at high risk of developing severe bronchiolitis. Although they usually have good outcomes, some cases with the most severe respiratory failure may require rescue treatment with ECMO. When ECMO was needed, an increased mortality rate of 33% was observed, and it was associated with RSV-Bronchiolitis, prematurity, and prolonged ECMO .