bluuebunny/crossref_metadata_2025 huggingface dataset:
An in vitro model for Reactive Astrogliosis: Differentiated U-87 MG cells as biochemical analogues of reactive astrocytes
Authors: Arora Tania , Prashar Vikash , Singh Randeep , Sharma Arti , Changotra Harish , Parkash Jyoti
Published: June 2023

Reactive astrogliosis (RA) is a complex pathological condition where astrocytes undergo specific biochemical changes to attain hypertrophy and hyperplasia. RA is a mechanism being observed in various neurodegenerative disorders (ND) such as Alzheimer's disease (AD), Parkinson's Disease (PD) and traumatic brain Injury (TBI). Various models have been designed to understand the mechanism of activation as well as to determine therapeutics to reverse or attenuate the condition for major neurological disorders but the study is hampered due to the lack of a suitable in vitro model. In this study, we propose a new in vitro model by using U-87 MG (human glioblastoma cells) cells which are differentiated by using retinoic acid and transformed by using proinflammatory and anti-inflammatory cytokines to generate the A1/A2 phenotype. The model was further validated by using comparative expression analysis of marker proteins and profiling of a panel of miRNA. The purpose of this study was to understand the molecular switch mechanism for the interconversion of these cells that can be used in the development of new therapeutic interventions for multiple neurological conditions. Since multi targeted drugs are on the rise, it will be beneficial to design therapies that could direct both neuronal and astrocytic milieu towards neuroprotection.
Folic acid grafted mixed polymeric micelles as a targeted delivery strategy for tamoxifen citrate in treatment of breast cancer.
Authors: Nasr mohamed , Hashem Fahima , Teiama Mohammed , Tantawy Norhan , Abdelmoniem Raghda
Published: June 2023

The objective of this study was to develop folic acid (FA) grafted mixed polymeric micelles loaded with Tamoxifen citrate (TMXC) to enhance its antitumor activity in breast tissues. The conjugated FA-P123 micelles were prepared using carbonyl diimidazole cross-linker chemistry and confirmed using FTIR and 1HNMR. The micelles were examined for encapsulation efficiency, particle size, surface charge, in vitro release study, cytotoxic effect, and cellular uptake by a breast cancer cell line. The conjugated TMXC-loaded micelle exhibited a nanoparticle size of 35.01 ±1.20 nm, a surface charge of - 20.50 ± 0.95 mV, entrapped 87.83 ±5.10 % and released 67.58 ± 2.47 % of TMXC after 36 h. The conjugated micelles exhibited a significantly higher cellular uptake of TMXC by MCF-7 cell line and improved in vitro cytotoxicity by 2.48 folds compared to the TMXC-loaded unconjugated micelles. The results of in vivo studies indicated that TMXC-loaded FA-P123/P84 has a potential antitumor activity, as revealed by a significant reduction of tumor volume in tumor-bearing mice compared to TMXC-loaded unconjugated micelles. In conclusion, the obtained results suggested that conjugated FA-P123/P84 micelles could be an encouraging carrier for the treatment of breast cancer with TMXC.
Data-driven modeling for online fault pre-warning in thermal power plant using incremental Gaussian Mixture Regression
Authors: Jin Shengxiang , Si Fengqi , Dong Yunshan , Ren Shaojun
Published: June 2023

This study introduces a data-driven model for online fault pre-warning in thermal power plant using incremental Gaussian mixture regression. To tackle the issue of outdated parameters in existing fault pre-warning models, this study puts forth an incremental Gaussian mixture regression that leverages the merging of Gaussian components to reconstruct the model and enable online modeling. Due to its criticality, a forgetting factor is introduced during the merging process to efficiently manage the weight allocation between present and historical patterns, thereby guaranteeing the model’s accuracy. The results of the sine function case demonstrate that the IGMR model exhibits excellent pattern control performance and modeling efficiency. Furthermore, the IGMR model is employed to forecast parameter alterations in pulverizer blockages with mode switching, and experimental validation indicates that IGMR precisely anticipates parameter changes following mode switching. Compared to on-site solutions, the pre-warning of coal blockage has a clear advantage in advance warning.
Acanthopanax senticosus ameliorates steatohepatitis through HNF4 alpha pathway activation in mice
Authors: Kawano Yutaka , Tanaka Maki , Satoh Yasushi , Sugino Shigekazu , Suzuki Jun , Fujishima Masaki , Okumura Eri , Takekoshi Hideo , Uehara Osamu , Sugita Shintaro , Abiko Yoshihiro , Tomonari Tetsu , Tanaka Hironori , Takeda Hidekatsu , Takayama Tetsuji
Published: June 2023

Non-alcoholic fatty liver disease is a common liver disease worldwide, and is associated with dysregulation of lipid metabolism, leading to inflammation and fibrosis. Acanthopanax senticosus Harms (ASH) is widely used in traditional medicine as an adaptogen food. We examined the effect of ASH on steatohepatitis using a high-fat diet mouse model. Mice were fed a choline-deficient, L-amino acid-defined, high-fat diet with ASH extract (ASHE). After 6 weeks, liver RNA transcriptome sequencing (RNA-Seq) was performed, followed by Ingenuity Pathway Analysis (IPA). Our findings revealed that mice fed a high-fat diet with 5 % ASHE exhibited significantly reduced liver steatosis. These mice also demonstrated alleviated inflammation and reduced fibrosis in the liver. IPA of RNA-Seq indicated that hepatocyte nuclear factor 4 alpha (HNF4 alpha), a transcription factor, was the activated upstream regulator (P-value 0.00155, z score=2.413) in the liver of ASHE-fed mice. Adenosine triphosphate binding cassette transporter 8 and carboxylesterase 2, downstream targets of HNF4 alpha pathway, were upregulated. Finally, ASHE-treated HepG2 cells exposed to palmitate exhibited significantly decreased lipid droplet contents. Our study provides that ASHE can activate HNF4 alpha pathway and promote fat secretion from hepatocytes, thereby serving as a prophylactic treatment for steatohepatitis in mice.
Anticancer potential of furanocoumarins and flavonoids of Heracleum persicum fruit
Authors: Dehnoee Ali , Kalbasi Roozbeh Javad , Tavakoli Saeed , Zangeneh Mohammad Mahdi , Zangeneh Akram , Delnavazi Mohammad-Reza
Published: June 2023

Heracleum persicum Desf. ex Fischer (Umbelliferae) is a herbaceous perennial plant distributed in Iran and Turkey. The aromatic fruits of this plant are commonly used as food additive, carminative, antiseptic and tonic. The present study was designed to isolate non-volatile constituents of H. persicum fruits and evaluate their anti-tumor potentials against different cancer cells. Phytochemical analysis using chromatography on silica gel and Sephadex LH-20 columns resulted in the isolation of phellopterin (1), angelicin (2), pimpinellin (3), bergapten (4), isopimpinellin (5) and xanthotoxin (6) from dichloromethane fraction along with apterin (7), isorhamnetin 3-O-glucoside (8), isorhamnetin 3-O-rutinoside (narcissin) (9), and quercetin 3-O-rutinoside (rutin) from n-butanol fraction of H. persicum fruits extract. 1H-NMR and 13C-NMR spectral analyses were applied to characterize the chemical structures. In MTT assay all of the tested compounds demonstrated preferential cytotoxic activity against cancer cells (IC50; 40–370 µg/mL) in comparison with HUVEC normal cells (IC50; > 1000 µg/mL). Among the compounds phellopterin (1) showed the highest anti-tumor activity toward U-266, SK-MM-1 and RPMI-8226 multiple myeloma cells with IC50 values of 44.3 ± 1.4, 69.1 ± 1.2 and 85.7 ± 1.8 µg/mL, respectively.
Prevalence of bottle feeding practice and its associated factors among mothers of infant less than six months at Addis Ababa public health centers, Addis Ababa, Ethiopia, 2022
Authors: Birhan Gedifw , Mohammed Shikur , Tenia² Sisay , Belyneh Abebe , Alem Amanual , Alemante² Amlaku , Mengistu Belete
Published: June 2023

Introduction
Bottle feeding practice should be avoided due to its influence on optimal breastfeeding and its effect associated with morbidity and mortality resulting from diarrheal disease, infant and child illness, and malnutrition. This study is aimed to assess the prevalence of bottle-feeding practice and its associated factors among mothers of infants less than six months in Addis Ababa.
Methods
An institution-based cross-sectional study was conducted among 456 mothers who had infants less than six months in Addis Ababa public health facilities. Data were collected through interview, entered using Epi info version 7.1 and exported to statistical package for social science version 26 for analysis. Variables with p-value < 0.2 in bivariable binary logistic regression analysis were entered to multivariable logistic regression analysis. Finally, variables with p-value < 0.05 in multivariable logistic regression were taken as significant factor.
Results
The overall prevalence of bottle-feeding practice in this study was 39%. Being male infant (AOR = 0.589; 95%CI: 0.381, 0.911), infant hospitalization (AOR = 2.114; 95%CI 1.246, 3.588), cesarean section delivery (AOR = 2.817; 95%CI: 1.764, 4.496), late initiation of breastfeeding (AOR = 5.526; 95%CI: 3.121, 9.786) and not having information on breast feeding (AOR = 4.13; 95%CI 2.21, 7.73) were statistically significant factors associated with bottle feeding practice.
Conclusion
The magnitude of bottle-feeding practice is high in Addis Ababa. Being male infants, infants hospitalized, cesarean section delivery, late initiation of breastfeeding and not having information on breast feeding were significant factors for bottle feeding practice. Greater efforts to promote breastfeeding should be targeted towards women with sub-optimal breastfeed.
An elevated level of Interleukin-17A in a Senegalese malaria cohort is associated with rs8193038 IL-17A genetic variant
Authors: THIAM Fatou , DIOP Gora , COULONGES Cedric , DERBOIS Celine , THIAM Alassane , DIOUARA Abou Abdallah Malick , MBAYE Mame Ndew , DIOP Mamadou , NGUER Cheikh Momar , DIEYE Yakhya , MBENGUE Babacar , ZAGURY Jean-Francois , DELEUZE Jean-Francois , DIEYE Alioune
Published: June 2023

Malaria infection is a multifactorial disease partly modulated by host immuno-genetic factors. Recent evidence has demonstrated the importance of Interleukin-17 family proinflammatory cytokines and their genetic variants in host immunity. However, limited knowledge exists about their role in parasitic infections such as malaria. We aimed to investigate IL-17A serum levels in patients with severe and uncomplicated malaria and the gene polymorphism’s influence on the IL-17A serum levels. 125 severe (SM) and uncomplicated (UM) malaria patients and 48 free malaria controls were enrolled in this research. IL-17A serum levels were measured with ELISA. PCR and DNA sequencing were used to assess host genetic polymorphisms in IL-17A. We performed a multivariate regression to estimate the impact of human IL-17A variants on IL-17A serum level and malaria outcome. Elevated serum IL-17A levels accompanied by increased parasitemia were found in SM patients compared to UM and controls (P < 0.0001). Also, the IL-17A levels were lower in SM patients who were deceased than in those who survived. In addition, the minor allele frequencies (MAF) of two IL-17A polymorphisms (rs3819024 and rs3748067) were more prevalent in SM patients than UM patients indicating an essential role in SM. Interestingly, the heterozygous rs8193038 AG genotype was significantly associated with higher levels of IL-17A than the homozygous wild type (AA). According to our results, it can be concluded that the IL-17A gene rs8193038 polymorphism significantly affects IL-17A gene expression. Our results fill a gap in the implication of IL-17A gene polymorphisms on the cytokine level in a malaria cohort. IL-17A gene polymorphisms also may influence cytokine production in response to Plasmodium infections and may contribute to the hyperinflammatory responses during severe malaria outcomes.
A new step-wise surgical technique of knapsack-like uterine compression sutures for intractable postpartum hemorrhage in cesarean section
Authors: Han Lei , Zhang Baolin , Yin Hongmei , Xu Huishu , Pang Yiwei , Zhang Xianghui , Zhai Qingliang , Liu Xiaofeng , Wang Yanlin , Zhang Caiying , Liu Yanni , Xuemei Chen
Published: June 2023

Objectives
We aimed to explore the effectiveness and safety of a new type of uterine compression suture, the step-wise surgical technique of knapsack-like sutures for treating intractable postpartum hemorrhage (PPH) caused by uterine atony and placenta factors in cesarean section.
Methods
The step-wise surgical technique of knapsack-like sutures was established on the basis of the artful combination of vertical strap-like sutures and an annular suture-ligation technique. This novel surgical technique was applied to 34 patients diagnosed with PPH during cesarean section due to severe uterine atony and placental factors in our department. The hemostatic effects, clinical outcomes and follow-up visit results were all reviewed and analyzed.
Results
This new uterine compression suture successfully stopped bleeding in 33 patients, and the effective rate was 97.06%. Only 1 patient failed and was changed to use bilateral uterine arterial embolization and internal iliac artery embolization. The follow-up visits indicated that 33 patients restored menstruation except for 1 who was diagnosed with amenorrhea. The gynecological ultrasound tests of all the patients suggested good uterine involutions, and they had no obvious complaints such as hypogastralgia.
Conclusions
This step-wise surgical technique of knapsack-like uterine compression sutures can compress the uterus completely. It is a technique that can conserve the uterus and fertility function without special equipment in caesarean section for PPH, with the characteristics of being safe, simple and stable (3S) with rapid surgery, reliable hemostasis and resident doctor to operation (3R).
Regulating Neuroinflammatory Biomarkers in Nitroglycerine induced Migraine in Rats: A Therapeutic role of Chrysanthemum indicum extract
Authors: Rushendran Rapuru , Vellapandian Chitra , Kaliappan Ilango
Published: June 2023

Objective
Chronic migraine (CM) is characterised by unilateral/bilateral pulsatile headaches at least 15 days per month. Central sensitization can be demonstrated by a prolonged increase in trigeminal nucleus caudalis (TNC) neuron activity in response to painful stimuli. Scientists are continually researching migraine treatments, hoping herbal remedies may work better. Network pharmacological approach was used to assess Chrysanthemum indicum (CIHE) leaf hydroalcoholic extract to evaluate antimigraine activity.
Methods
We investigated specific genes involved in the migraine, extracted gene ontology, biological pathways, and protein-protein interaction analysis were determined with the screened 61 common genes by network pharmacological approach added with docking analysis. In vivo studies have been carried out with CD1 Mice (25-30g) randomly made into five groups. CIHE is prepared to evaluate antimigraine activity. MMP9, TNF-α, NFkB, IL-1β, CGRP, and iNOS were evaluated after administration of Nitroglycerine (10mg/kg; i.p).
Results
The elevated protein levels were significantly reduced with the treatment of CIHE (200mg/kg and 400mg/kg; p.o). Additionally histological and western blot analysis confirmed the reduction of specified proteins in the brain as well as blood. Docking analysis revealed that 1,5-Bis(4-dimethylaminophenyl)-1,4-pentadien-3-one (-10.3 KJ/mol), Naphthalene-1-carboxylic acid 4-formyl-phenyl ester (-9.7KJ/mol), and 3-(3-Nitrophenyl)-2'-acrylonaphthone (-9.7KJ/mol) are shown highest binding affinity.
Interpretation:
CIHE may attain antimigraine activity through suppression of neuroinflammatory cytokines by the natural extract of Chrysanthemum indicum in a dose dependent manner and isolation of hit molecules from the CIHE is required for further investigation.
Molecular Profiling reveals Tumor Immune Microenvironment Heterogeneity of Concurrent Lung Adenocarcinoma and Squamous Cell Carcinoma in Multiple Primary Lung Cancers
Authors: Zhang Yajie , Zhang Jiahao , Dong Dong , Cao Yuqin , Chen Xiang , Liu Di , Cheng Xueyan , Sun Debin , Li Hecheng
Published: June 2023

Background: Over the past decade, the annual incidence of multiple primary lung cancers (MPLC) has increased. There is a group of pathologically different patients with MPLC presenting as mostly having concurrent lung adenocarcinoma (ADC) and squamous cell carcinoma (SQCC). Their molecular profiles and tumor immune microenvironment (TIME) remain unknown. We aimed to clarify these factors in this patient group.
Methods: We performed mutational, biomarker, and neoantigen analyses using whole-exome sequencing (WES) and differential, enrichment,and TIME analyses using RNA sequencing (RNA-Seq) for five patients with concurrent ADC and SQCC to analyze their mutational profile, expression profile, and TIME features.
Results: WES of 10 lesions (five ADC and five SQCC) in five concurrent ADC and SQCC patients showed that the most frequently mutated genes in both groups were TTN, TP53, WDFY3, EGFR, ZFHX4 and TTC40, and there were no significantly different mutated genes in the comparative analysis of mutation frequencies between both groups. There were no significant differences inneoantigen analysis, including tumor mutational burden, tumor neoantigen burden, and mutant allele tumor heterogeneity. HLA genotype analysis indicated that three of five (60%) patients carried the HLA-I class B62 supertype, and seven of 10 (70%) lesions had loss of HLA heterozygosity (HLA-LOH).
RNA-Seq revealed that 2231 genes were differently expressed between the ADC and SQCC groups. GSVA based on the molecular signature database (MsigDB) showed that 12 gene sets were significantly differentially expressed between the ADC and SQCC groups (p < 0.05), with four gene sets relevant to squamous cell features upregulated in the SQCC group and eight metabolism-related gene sets upregulated in ADC. GO/KEGG analysis of immune function-related pathways showed that the interleukin-12 family-related signaling pathways, TP53 and TLR2/4 signaling pathways were upregulated in the ADC group. Co-expression analysis of TIME revealed that tumor infiltrating immune cells were significantly more enriched and diverse, with tumor-infiltrating lymphocytes scoring significantly higher (p = 0.047) in ADC. Specifically, CD8+ T cells, exhausted CD8+ cells, and macrophages infiltrated significantly more frequently in ADC (p < 0.05). Moreover, immunocostimulator expression (p = 0.034) and tertiary lymphoid structure score (p = 0.017) were significantly higher in ADC than in SQCC.
Conclusion: In patients with concurrent ADC and SQCC MPLC, the transcriptomic profiles and TIME features were quite different between ADC and SQCC lesions. ADC lesions exhibited a more active TIME than SQCC lesions.
SVPC-LDA: A Hybridised Feature Extraction Approach for Chronic Kidney Disease Dataset
Authors: Gulati Vineeta , Raheja Neeraj , Rana Arun Kumar , Islam Sardar M N , Alsubaie Najah , Alqahtani Mohammed S. , Abbas Mohamed , Soufiene Ben Othman
Published: June 2023

High-dimensional data is a major challenge for a high-quality machine learning model. Feature extraction is the most common technique offered in the literature to reduce the amount of data. Moreover, relevant feature extraction leads to a more efficient and reliable classification system through machine learning (ML). In this study, the authors introduce Singular Value Principal Component Linear Discriminant Analysis (SVPC-LDA), a hybrid dimensionality reduction technique that combines the three most popular feature extraction methods: Linear Discriminant Analysis (LDA), Singular Value Decomposition (SVD), and Principal Component Analysis (PCA). The proposed technique was evaluated using Gaussian NB (Naïve Bayes), K Neighbors, Gaussian Process, Linear SVC (Support Vector Classifier), SGD (Stochastic Gradient Descent), and Passive Aggressive Classifiers on the standard chronic kidney disease dataset. In addition, the efficiency of SVPC-LDA was compared with all features and with existing PCA, SVD, ICA, and LDA methods. In addition, the effectiveness of the hybridized SVPC-LDA technique was measured on a high scale, with achieved values of 98.75% accuracy, 98.07% sensitivity, 96.55% precision, 100% specificity, and 99.03% AUC. In addition, dimensionality was reduced by 15% and RMSE by 40.60%, which is better than the techniques found in the literature.
Rapid determination of warfarin in biological samples: Experimental and theoretical studies of Pt-doped CdTe QDs as fluorescent probes
Authors: Safari Meysam , Ehzari Hosna , Yousif Azeezah Yaseen , Samimi Mohsen
Published: June 2023

This research is focused on introducing a facile and safe fluorescence sensor for the sensitive and selective detection of warfarin in biological samples. The synthesis of the fluorescence sensor probe was easily performed with doping metal ions of the Pt to CdTe quantum dots (Pt:CdTe QDs). The morphological and optical properties of the synthesized Pt:CdTe quantum dots were characterized as FTIR spectroscopy, TEM, UV visible absorption and EDX. The interaction patterns of warfarin with CdTe QDs were investigated by the quantum chemical method and compared with experimental results. The proposed quantum dots exhibited a blue luminescence with a 28.8% quantum yield. Pt:CdTe QDs were used as the fluorescence probe to assay warfarin. This procedure is based on "off" fluorescence of quantum dots in the presence of different concentrations of warfarin. Under optimal conditions, the fluorescence sensor probe could detect the concentration of warfarin with a wide linear range of 2–100 µM and a detection limit (S/N = 3) of 0.75 µM. Results of real sample analysis by fluorescent nanoprobe displayed that this probe could be the potential alternative tool for warfarin drug detection in biological samples.
Association between early mobilization and functional outcomes in patients with aneurysmal subarachnoid hemorrhage: A Multicenter, retrospective, propensity score-matched study
Authors: Takara Hikaru , Suzuki Shota , Satoh Shuhei , Abe Yoko , Miyazato Shohei , Kohatsu Yoshiki , Minakata Shin , Moriya Masamichi
Published: June 2023

Background
Early mobilization is important for promoting functional recovery and preventing complications in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the efficacy of early mobilization in patients with aSAH remains unclear. This study aimed to investigate the association between early mobilization and functional outcomes in patients with aSAH.
Methods
This multicenter retrospective study was conducted in Japan, including patients with aSAH who received physical therapy, with or without occupational therapy, from April 2014 to March 2019. The primary outcome was the modified Rankin Scale (mRS) score, with a favorable functional outcome defined as an mRS score of 0–2 and an unfavorable outcome with an mRS score of 3–5. Patients initiating walking training within 14 days of aSAH onset were classified into the early mobilization group, whereas those initiating training after 14 days were classified into the delayed mobilization group. Propensity score matching analysis was performed to assess the association between early mobilization and favorable outcomes.
Results
A total of 718 patients were screened and 450 eligible patients were identified. Before matching, 229 patients (50.9%) were in the early mobilization group and 221 (49.1%) were in the delayed mobilization group. After matching, each group consisted of 122 patients, and the early mobilization group exhibited a higher proportion of favorable outcomes than did the delayed mobilization group (81.1% vs. 52.5%; risk difference, 28.7%; 95% CI, 17.4–39.9; p < 0.001).
Conclusions
This multicenter retrospective study suggests that initiating walking training within 14 days of aSAH onset is associated with favorable outcomes.
The design features of digital games and their impact on language learning for EFL college students
Authors: Klimova Blanka , Al-Obaydi Liqaa Habeb , Tawafak Ragad M , Pikhart Marcel
Published: June 2023

Background
Digital games have been recognized as an effective tool to enhance language learning, and their design features, such as interactivity, challenge, or immersion, have been linked to successful language acquisition. The purpose of this research study is to explore some design features of digital games and show their impact on learning English by EFL college students.
Methods
The methodology was based on a questionnaire survey that was conducted in two countries (Iraq and the Czech Republic) among 160 undergraduate students of English as a foreign language.
Results
The findings of this study reveal that digital games have the potential to be effective tools for improving English language proficiency among EFL college students and their effectiveness is especially affected by design features, such as personalization and interactivity. In addition, language skills development and perceived usefulness are also important factors despite the fact that students do not associate the intention to learn a language and perceived ease of use of the games with learning.
Conclusions
By understanding these factors and design features, educators and game designers can create games that are more engaging and effective in promoting language learning among EFL college students.
Association of Residual Ductal Carcinoma In Situ with Breast Cancer Treatment Outcomes after Neoadjuvant Chemotherapy according to Hormone Receptor Status
Authors: Shin Eunju , Yoo Tae-Kyung , Kim Jisun , Chung Il Yong , Ko Beom Seok , Kim Hee Jeong , Lee Jong Won , Son Byung Ho , Lee Sae Byul
Published: June 2023

Purpose
This research aimed to clarify the impact of residual DCIS in surgical specimens obtained after NAC for breast cancer on the associated prognosis outcomes.
Methods
This retrospective study was performed on a cohort of 1,009 patients who achieved pCR following NAC for breast cancer and underwent subsequent breast surgery at a single institution between January 2008 and December 2019. Overall survival, local recurrence-free survival, distant metastasis-free survival, and disease-free survival of the residual and non-residual DCIS groups were the outcomes compared, with further subgroup analysis performed according to breast cancer type.
Results
Among the 1,009 patients who achieved pCR, 260 individuals (25.8%) presented with residual DCIS. Based on a median follow-up of 54.0 months, no significant differences in outcomes were observed between the two groups.
Patients with residual DCIS and hormone receptor-negative (HR-) breast cancer demonstrated a significant decrease in distant metastasis-free survival (p=0.030) compared to those without residual DCIS. In the HR+ cohort, no significant difference was observed between the two groups.
Multivariate analysis of the HR- cohort demonstrated a significant association between residual DCIS and an elevated risk for distant recurrence (hazard ratio = 2.3, 95% confidence interval = 1.01–5.20, p=0.047).
Conclusions
Residual DCIS following NAC may impact breast cancer outcomes, particularly with respect to the occurrence of distant metastasis in HR- patients. Therefore, clinicians must vigilantly monitor patients with residual DCIS after NAC, and further research is needed to expand our understanding of the clinical implications of residual DCIS.
WITHDRAWN: Symbolic representation of district wise climate change scenarios of West Bengal state, India, using Thornthwaite classification scheme
Authors: MALLICK ANKITA , DAS LALU , AKHTER JAVED , SAHA GAUTAM
Published: June 2023

Now-a-days, multi-level stakeholders starting from grass-root level farming community to Government level policy makers need to have adequate climate change information before hand to implement appropriate adaptation and mitigation strategies towards combating climate change at local scale. However, availability of climate change data is not adequate at district and block level. The present study has attempted to reveal how the district level climate has changed in last 120 years over 23 districts of West Bengal in India using Thornthwaite classification scheme (TCS). The change of climate from moist to dry or vice-versa from mean climatological period of 1901–1930 to 1991–2020 has been assessed and represented through four different English letters based on the calculated values of TCS. The study of many indicators showed that symbolic representations remain same in some districts but in several districts these vary according to changes of time period. The B1A'a'w2 symbol was used to express climatic type of PurbaBardhaman during the first three climatological eras, but it was altered to C2A'a'w2 for the last period, showing a shift in moisture index (Im) value. This reveals how the climatic type is continuously changing in North Bengal and South Bengal districts of West Bengal through the passage of time. Furthermore, it has been noted that while the majority of North Bengal districts have changed to drier conditions as their Im value has decreased recently, several South Bengal districts indicate moist conditions compared to the previous climatological periods with increases in moisture index (Im) value.
Beyond the Impact of Electronic Health Record Execution Issues on its Utilization: Pragmatic Approaches
Authors: Abbassi Hajar , Rahimi Bahlol , Jebraeily Mohamad , Alinejad Vahid , Nourani Aynaz
Published: June 2023

The Electronic Health Record (EHR) is a repository for storing health data and a network for exchanging these data. Today, the EHR is one of the key elements in the health system and has brought many benefits. These benefits reach their maximum when the system is properly executed and used. The purpose of this study was to investigate the impact of Iranian EHR (SEPAS) execution issues on its utilization. This was a quantitative-analytical study conducted in 2022. The settings of the study were 28 hospitals in Iran. The participants (n = 70) included staff from discharge, HIM, and IT departments. The data were collected using a researcher-made questionnaire and analyzed using descriptive and analytical statistics. The study results indicated that financial factors (2.36 ± 1.15) have the most effect on the execution of SEPAS. Also, users' workload (3.76 ± 1.19) had the most effect on the utilization rate. In addition, the results showed that there is a correlation between technical, user-related, organizational, financial, and managerial factors with utilization factors (P < 0.05). Also, the linear-regression results showed that technical, organizational, and financial factors had positive effects and aligned with utilization factors (P < 0.05). SEPAS, after the initial stages, is now on the growth path and development. For better execution of this system and to increase the utilization capacity, attention should be paid to the factors affecting the execution and utilization of the system. The factors raised in this study can be important for decision and policy-making in this area, especially for developing countries.
Subconjunctival injection of human umbilical cord mesenchymal stem cells alleviates experimental allergic conjunctivitis via regulating T cell response
Authors: Li Dongli , Ou Qingjian , Shen Qi , Lu Michael Mingze , Xu Jing-Ying , Jin Caixia , Gao Furong , Wang Juan , Zhang Jingfa , Zhang Jieping , Li Jiao , Lu Lixia , Xu Guo-Tong , Tian Haibin
Published: June 2023

Background
T helper 2 (Th2) cells are thought to play critical roles in allergic conjunctivitis (AC). They release inflammatory cytokines to promote an allergic response in AC. Due to individual heterogeneity and long-term chronic management, current therapies do not always effectively control AC. Mesenchymal stem cells (MSCs) have been shown to be effective in treating allergy-related disorders, but it is unclear how exactly the Th2-mediated allergic response is attenuated. This study aims to elucidate the therapeutic effect and mechanism of the human umbilical cord MSCs (hUCMSCs) in a mouse model of experimental AC (EAC).
Methods
A mouse EAC model was established by inoculating short ragweed (SRW) pollen. After the SRW pollen challenge, the mice received a single subconjunctival or tail vein injection of 2 x 106 hUCMSCs; subsequent scratching behavior and clinical symptoms were assessed. Immunostaining and flow cytometry were carried out to show allergic reactions and the activation of CD4 + T cell subsets in the conjunctiva and cervical lymph nodes (CLNs). Gene expression was determined by RNA-seq and further verified by qRT-PCR and Western blot. Co-culture assays were performed to explore the regulatory role of hUCMSCs in the differentiation of CD4 + Th2 cells.
Results
Subconjunctival administration of hUCMSCs resulted in fewer instances of scratching and lower inflammation scores in EAC mice compared to the tail-vein delivery and control groups. Subconjunctival administration of hUCMSCs reduced the number of activated mast cells and infiltrated eosinophils in the conjunctiva, as well as decreased the number of Th2 cells in CLNs. After pretreatment with EAC mouse serum in vitro to mimic the in vivo milieu, hUCMSCs were able to inhibit the differentiation of naive T cells (Th0) into Th2 cells. Further evidence demonstrated that repression of Th2 cell differentiation by hUCMSCs is mediated by CRSPLD2 through downregulation of STAT6 phosphorylation. Additionally, hUMCSCs were able to promote the differentiation of Th0 cells into regulatory T cells (Treg) in CLNs of EAC mice.
Conclusions
Subconjunctival injection of hUCMSCs suppressed the Th2-allergic response and alleviated clinical symptoms. This study provides not only a potential therapeutic target for the treatment of AC but also other T cell-mediated diseases.
Knowledge, Attitude, and Concerns related to Next Generation Sequencing in General Population in India: A Pilot Study
Authors: Phadke Shubha , Shambhavi Arya , Moirangthem Amita , Mishra Prabhaker
Published: June 2023

Next Generation Sequencing (NGS) technology is being widely used for preconception carrier screening of couples with or without family history of a genetic disorder, newborn screening, and for personalized and preventive treatments although its knowledge is still limited in general population and health care workers. In this pilot study, we have assessed the knowledge, attitude and concerns related to next generation sequencing in the general population in India. The present prospective cross-sectional survey was performed between June 2022 and September 2022. The predesigned semi structures questionnaire was used to collect the data. A total of 103 apparently healthy individuals completed the questionnaires related to basic understanding assessment, personal utility, information sharing with family members, concerns surrounding NGS and positive impact. The participants in this study demonstrated relatively good general understanding of the information sheet (78% average correct response). We also observed that the majority wished to know the results of secondary findings for treatable conditions, untreatable conditions and also variants of uncertain significance. The public also wanted to sequence all the genes in their body, given a chance, and based on the results- carrier status, drug response, or susceptibility to various conditions, plan of action would be decided. They had a general willingness to share the results with their relatives. About half of them also wished to undergo prenatal testing based on the VUS result.
Exploring the effects of dietary inulin in rainbow trout fed a high-starch, 100% plant-based diet
Authors: Defaix Raphaël , Lokesh Jep , Frohn Laura , Bechec Mickael Le , Pigot Thierry , Véron Vincent , Surget Anne , Biasutti Sandra , Terrier Frédéric , Skiba-Cassy Sandrine , Roy Jérôme , Panserat Stéphane , Ricaud Karine Brugirard
Published: June 2023

Background
High dietary carbohydrates can spare protein in rainbow trout but may affect growth and health. Inulin, a prebiotic, could have nutritional and metabolic effects, along with anti-inflammatory properties in teleosts, improving growth and welfare. We tested this hypothesis in rainbow trout by feeding them a 100% plant-based diet, which is a viable alternative to fishmeal and fish oil in aquaculture feeds. In a two-factorial design, we examined the impact of inulin (2%) as well as the variation in the CHO/plant protein ratio on rainbow trout. We assessed the influence of these factors on zootechnical parameters, plasmatic metabolites, gut microbiota, production of Short-Chain Fatty Acid and lactic acid, as well as the expression of free-fatty acid receptors genes in the mid-intestine, intermediary liver metabolism, and immune markers.
Results
The use of 2% inulin did not change significantly the fish intestinal microbiota, while interestingly, the high CHO/Protein ratio group shows modification of intestinal microbiota and in particular the beta diversity, with 21 bacterial genera affected, including Ralstonia, Bacillus, and 11 lactic-acid producing bacteria. There were higher levels of butyric, and valeric acid in groups fed with high CHO/protein diet but not with inulin. The high CHO/Protein group shows a decrease in the expression of pro-inflammatory cytokines (il1b, il8, tnfa) in liver and a lower expression of the genes coding for tight-junction proteins in mid-intestine (tjp1a, tjp3). However, the 2% inulin did not modify the expression of plasma immune markers. Finally, inulin induced a negative effect on rainbow trout growth performance irrespective of the dietary carbohydrates.
Conclusions
with a 100% plant-based diet, inclusion of high levels of carbohydrates could be a promising way for fish nutrition in aquaculture through a protein sparing effect whereas the supplementation of inulin in combination with such alternative diets needs further investigations.
SNP Markers Revealing the uniqueness of Gushan semi-rock tea in the tea germplasm resources of Fujian, China
Authors: Wang Pan , Lv Shuiyuan , Yu Wentao , Lin Cheng , Zhu Yanyu , Gui Wenjing , Liu Caiguo , Ye Naixing
Published: June 2023

As a renowned tea with a historical significance in China, Gushan semi-rock tea originated from the Gushan Mountain in Fujian, China. This study describes the genetic diversity, population structure, and distribution characteristics of 76 tea samples collected from Gushan Mountain and neighboring regions, using single nucleotide polymorphism (SNP) markers. The results show that the average information index (I) is 0.490, the average observed heterozygosity (Ho) is 0.384, the average expected heterozygosity (He) is 0.329, and the average fixation index (F) is -0.132. The genetic variation mainly comes from intraregional variation, which accounts for 82% of the total variation. Furthermore, there is a closer connection between tea plants in Southern, Northern, and Eastern Fujian. The frequency of genetic exchange between tea plants in the Gushan semi-rock tea and those in Southern, Northern, and Eastern Fujian is relatively low, showing obvious uniqueness. The findings of this study help fill the gap in tea genome research in the Gushan semi-rock tea and provide valuable information on the genetic diversity of tea resources in Gushan area. The results can be utilized in future genomics, phylogeny, and artificial breeding programs aimed at developing new tea varieties.
Excitation of tunable dual quasi-bound states in the continuum in graphene metasurface and terahertz sensing application
Authors: Huang Zhong , Chen Qing , Cao Xiaoxiao , Ding Ji , Tang Chaojun , Yan Zhendong , Chen Jing
Published: June 2023

This study proposes an all-graphene metasurface supporting dual band symmetric bound state in the continuum (BIC) in the terahertz (THz) range for the first time. The structure consists of a unit cell containing a double-gap split ring resonator periodically on a dielectric substrate. By introducing symmetry breaking, two plasmonic quasi-BICs (Q-BICs) transmission dips are observed with finite Q-factors and high modulation depth. Simulation and analysis results simultaneously exhibit that the Q-factors of Q-BICs follow an inverse square dependency with the asymmetry degree. Via changing the graphene’s chemical potential, the Q-BICs’ operating frequency range can be actively expanded. The dual Q-BICs are immune to the variation of incident angle and has a significant slow light effect with time delay up to 23.8 ps. In addition, the sensing performance in THz region is investigated. A maximum sensitivity of 267.5 GHz/RIU is obtained with a FOM of 24.08 RIU− 1. Our work shows an alternative way to design the class of tunable Q-BIC metasurface, which will provide a valuable reference for future dynamic sensor and other fields.
Optimizing the Cumulative Cisplatin Dose for Concurrent Chemoradiotherapy Beneficiaries Among Elderly Nasopharyngeal Carcinoma Patients: A Real World Study
Authors: Wu Yan-Ling , He Shuiqing , He Danjie , Gao Yongxiang , Huang Ying , Jin Jing
Published: June 2023

Objective
This study aimed to find a safe and effective cumulative cisplatin dose (CCD) for concurrent chemoradiotherapy (CCRT) beneficiaries among elderly nasopharyngeal carcinoma (NPC) patients.
Materials and methods
A total of 765 elderly (≥ 60 years old) NPC patients treated with cisplatin-based CCRT and IMRT-alone from 2007 to 2018 were included in this study. RPA-generated risk stratification was used to identify CCRT beneficiaries. CCDs were divided into CCD = 0, 0 < CCD ≤ 80, 80 < CCD ≤ 160 and 160 < CCD ≤ 300 mg/m2 and their OS and nephrotoxicity compared.
Results
Pre-treatment plasma EBV DNA and clinical Stage were incorporated into the RPA model to perform risk stratification. All patients were classified into either a high-risk group (n = 158, Stage IV), an intermediate-risk group (n = 193, EBV DNA > 2000 copy/mL & Stage I, II, III) or a low-risk group (n = 414, EBV DNA ≤ 2000 copy/mL & Stage I, II, III). The 5-yearOS of CCRT vs. IMRT alone in the high-, intermediate- and low-risk groups after balancing covariate bias were 60.1% vs 46.6% (p = 0.02), 77.8% vs 64.6% (p = 0.03) and 86.2% vs 85.0% (p = 0.81), respectively. The 5-year OS of patients receiving CCD = 0, 0 < CCD ≤ 80, 80 < CCD ≤ 160 and 160 < CCD ≤ 300 mg/m2 after balancing covariate bias in the high-risk group were 45.2%, 48.9%, 73.4% and 58.3% (p = 0.029), in the intermediate-risk group they were 64.6%, 65.2%, 76.8% and 83.6% (p = 0.038), and in the low-risk group they were 85.0%, 68.1%, 84.8% and 94.0% (p = 0.029), respectively. In the low-risk group, the 5-year OS of Stage III patients receiving CCD = 0, 0 < CCD ≤ 80, 80 < CCD ≤ 160 and 160 < CCD ≤ 300 mg/m2 were 83.5%, 76.9%, 85.5% and 95.5% (p = 0.044), respectively. No Grade 3–4 nephrotoxicity occurred.
Conclusions
In our study, Stage I, II & EBV DNA > 2000copy/ml and Stage III, IV elderly NPC patients may be CCRT beneficiaries. 80 < CCD ≤ 300 mg/m2 is recommended for the high-risk (Stage IV) group, and 160 < CCD ≤ 300 mg/m2 for the intermediate-risk (Stage I, II, III & EBV DNA > 2000copy/ml) and low-risk (Stage III&EBV DNA ≤ 2000 copy/ml) groups. No Grade 3–4 nephrotoxicity occurred in any of the CCD groups.
Identification of Ferroptosis-related genes in sepsis-induced acute respiratory distress syndrome
Authors: Zhang Xiao , Ma Yuan , Qin Weiwei , Dai Yuting , Ma Fuguo , Sun Lixin
Published: June 2023

Objective:The objective of this investigation was to examine the association between genes related to ferroptosis (FAGs) and acute respiratory distress syndrome (ARDS) induced by sepsis in individuals.Methods:Microarray profiles (GSE332707) from the GEO database were utilized to screen for differential genes. FAGs were derived from three gene pools (KEGG database, NCBI, FerrDb database). The co-expression genes were obtained through the intersection of differential genes (DEGs) in GSE332707 and FAGs. Subsequently, hub genes were discerned by means of GO, KEGG, and PPI network analysis. The validation of these hub genes was carried out experimentally using the RT-qPCR technique and a separate dataset (GSE66890). Ultimately, target gene prediction was conducted through the utilization of GeneCard and StarBase 3.0.Results:A total of 565 DEGs were identified between sepsis-induced ARDS and control samples, with 30 co-differential genes being detected. Then, the protein interaction network of 30 co-differential genes unearthed 5 hub genes (CTSB, LCN2, ZFP36, KLF2, and IRF1). Validation of the 5 hub genes was performed using RT-qPCR and GSE66890, which confirmed LCN2 as a potential prognostic candidate gene. The hsa-miR-374b-3p emerged as the most strongly supported candidate miRNA of LCN2.Conclusion:Based on our findings, we conclude that LCN2, a potential biomarker associated with FAGs, may play a role in the pathogenesis of sepsis-induced ARDS.
Broad Protection Against Clade 1 Sarbecoviruses After a Single Immunization with Cocktail Spike-Protein-Nanoparticle Vaccine
Authors: Kane Ravi , Halfmann Peter , Loeffler Kathryn , Duffy Augustine , Kuroda Makoto , Kawaoka Yoshihiro
Published: June 2023

The 2002 SARS outbreak, the 2019 emergence of COVID-19, and the continuing evolution of immune-evading SARS-CoV-2 variants together highlight the need for a broadly protective vaccine against ACE2-utilizing sarbecoviruses. While updated variant-matched formulations such as Pfizer-BioNTech’s bivalent vaccine are a step in the right direction, protection needs to extend beyond SARS-CoV-2 and its variants to include SARS-like viruses. Here, we introduce bivalent and trivalent vaccine formulations using our spike protein nanoparticle platform that completely protected hamsters against BA.5 and XBB.1 challenges with no detectable virus in the lungs. The trivalent cocktails elicited highly neutralizing responses against all tested Omicron variants and the bat sarbecoviruses SHC014 and WIV1. Finally, our 614D/SHC014/XBB trivalent spike formulation completely protected human ACE2-transgenic hamsters against challenges with WIV1 and SHC014 with no detectable virus in the lungs. Collectively, these results illustrate that our trivalent protein-nanoparticle cocktail can provide broad protection against SARS-CoV-2-like and SARS-CoV-1-like sarbecoviruses.
Public Perception Towards Children's COVID-19 Vaccination with Natural Language Processing
Authors: DELİCE Elif , TOZAN Hakan , POLATLI L. Özge , KARADAYI Melis A.
Published: June 2023

In 2019, Coronavirus manifested itself in China and caused numerous deaths. Vaccines developed against COVID-19 are seen as a way to end or mitigate the pandemic. Many debates arose about the vaccination of children through social media. The main target of this study is to present a model that reveals the perception of parents about getting their children vaccinated, extracts the main themes, and determines the emotional changes. With the support of the Octoparse web scraping tool, data was extracted from Twitter when the epidemic turned into a global problem and the discussions about vaccines intensified. Then, using the topic modeling and sentiment analysis techniques under the umbrella of (Natural Language Processing) NLP, main, sub-topics about parents' attitudes were revealed, also vaccine perceptions were detected by performing sentiment analysis. As a result, four topic clusters were determined: “the opinion of the need for the first dose of vaccination according to age”, “the effectiveness of the first dose of vaccine”, “the opinion of the need for vaccination of school-age children”, and “the need for vaccination arising from the protection of unvaccinated children with only mask protection”. With sentiment analysis, it was seen that positive emotions were dominant, and three emotions, namely trust, expectation, and fear, came to the fore. In conclusion, it has been determined that families trust the states and their announcements about getting their children vaccinated, they anticipate new vaccines to be developed, but they are also afraid of the risks that the vaccine will bring to their children.