bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized, open-label phase II study of brigatinib and carboplatin plus pemetrexed and brigatinib alone for chemotherapy-naive patients with ALK-rearranged non-squamous non-small cell lung cancer: Treatment Rationale and Protocol Design of the B-DASH Study (WJOG 14720 L)
Authors: Wakuda Kazushige , Kenmotsu Hirotsugu , Sato Yuki , Nakamura Atsushi , Akamatsu Hiroaki , Tachihara Motoko , Miura Satoru , Yokoyama Toshihide , Mori Keita , Nakagawa Kazuhiko , Yamamoto Nobuyuki
Published: March 2023

Background

The ALTA-1L study compared brigatinib with crizotinib in untreated ALK-rearranged non-small cell lung cancer (NSCLC) patients, demonstrating the efficacy of brigatinib. Although the median progression-free survival (PFS) of brigatinib group was 24.0 months, the one-year PFS rate was 70%. In the NEJ009 study, patients with EGFR mutations showed improved outcomes with gefitinib plus chemotherapy compared with gefitinib monotherapy. To evaluate the efficacy of the combination of brigatinib with chemotherapy for patients with ALK-rearranged NSCLC, we designed B-DASH study (WJOG 14720L).

Methods

B-DASH study is a multicenter, two-arm, phase II study. Eligible patients have untreated stage IV ALK-rearranged nonsquamous NSCLC. Patients will be randomized in a 1:1 ratio to receive brigatinib (180 mg once daily with a 7-day lead-in period at 90 mg) monotherapy or carboplatin (area under the curve = 5 on day 1) plus pemetrexed (500 mg/m2 on day 1) and brigatinib in a 3-week cycle for up to four cycles, followed by pemetrexed and brigatinib as maintenance therapy. The target hazard ratio of 0.62 is set based on the NEJ009 study. With one-sided alpha = 0.20 and power = 0.8, the sample size for the B-DASH study was calculated to be 110, considering the possibility of patients dropping out. The primary endpoint is PFS. The key secondary endpoints are the overall response rate and overall survival. We will evaluate tumor-derived DNA from plasma specimens before treatment, 42 days after administering the study drug, and on the day of progressive disease. Recruitment began in November 2021 and is ongoing.

Discussion

The efficacy of combination therapy with tyrosine kinase inhibitors and cytotoxic chemotherapy was demonstrated in patients with EGFR mutations but remains unclear in patients with ALK-rearranged NSCLC. The B-DASH study is the only trial of brigatinib combined with chemotherapy in patients with untreated ALK-rearranged NSCLC.

Trial registration

jRCT identifier: jRCTs041210103
Database task processing optimization based on Performance evaluation and machine learning algorithm
Authors: Deng Aqin
Published: March 2023

One of the key components of artificial intelligence algorithms is machine learning, involving a variety of fields, and has been applied in many artificial intelligence systems, including computer vision algorithm, radio network algorithm, medical diagnosis algorithm and intelligent robot system algorithm. In the form of machine learning algorithm, the machine learning module of the algorithm is first used to calculate the consumption, the main performance modules are optimized and improved, and the system data under database optimization is obtained, and select the optimized structure of the database for calculation, data analysis for the calculation results. Finally, in the design of the database optimization system, the separation of the database system storage engine is studied, and the database optimization form under the data processing structure is proposed. In terms of performance and functionality and reliability, it helps to solve the loss problem caused by big data processing in transmission. In the research of data intensive downward moving calculation process, the optimized solution of data processing is estimated. The results show that using computer terminal sampling comparison to select the executable data processing scheme. The result of this paper shows it can improve the calculation efficiency of data optimization system query.
Surveillance of multiple congenital anomalies; searching for new associations
Authors: Morris Joan , Bergman Jorieke , Barisic Ingeborg , Wellesley Diana , Tucker David , Limb Elisabeth , Addor Marie-Claude , Cavero-Carbonell Clara , Dias Carlos , Draper Elisabeth , De Garibay Luis Echevarría González , Gatt Miriam , Klungsoyr Kari , Lelong Nathalie , Luyt Karen , Materna-Kiryluk Anna , Nelen Vera , Neville Amanda , PERTHUS Isabelle , Pierini Anna , RANDRIANAIVO Hanitra , Rankin Judith , Rissmann Anke , Rouget Florence , Sayers Geraldine , Wertelecki Wladimir , Kinsner-Ovaskainen Agnieszka , Garne Ester
Published: March 2023

Many human teratogens are associated with a spectrum of congenital anomalies rather than a single defect, and therefore the identification of congenital anomalies occurring together more frequently than expected may improve the detection of teratogens. Thirty-two EUROCAT congenital anomaly registries covering 6,599,765 births provided 123,566 cases with one or more major congenital anomaly (excluding chromosomal and genetic syndromes) for the birth years 2008 to 2016. The EUROCAT multiple congenital anomaly algorithm identified 8,804 cases with two or more major congenital anomalies in different organ systems, that were not recognised as part of a syndrome or sequence. For each pair of anomalies, the odds of a case having both anomalies relative to having only one anomaly was calculated and the p-value estimated using a two-sided Fisher’s exact test. The Benjamini-Hochberg procedure adjusted p-values to control the false discovery rate and pairs of anomalies with adjusted p-values < 0.05 were identified. A total of 1,386 combinations of two anomalies were analysed. Out of the 31 statistically significant positive associations identified, 20 were found to be known associations or sequences already described in the literature and 11 were considered “potential new associations” by the EUROCAT Coding and Classification Committee. After review of the literature and detailed examination of the individual cases with the anomaly pairs, six pairs remained classified as new associations. In summary, systematically searching for congenital anomalies occurring together more frequently than expected using the EUROCAT database is worthwhile and has identified six new associations that merit further investigation.
Hematologic Toxicities and its Determinants among Breast Cancer Patients Treated with Doxorubicin-Cyclophosphamide Followed by Paclitaxel Regimen in Cancer Centers: Retrospective Cohort Study
Authors: Tesfaye Tegenu Chanie , Mekonnen Gashaw Binega , Abebe Rahel Belete , Teferi Ephrame Tafesse , Alemu Belete Kassa , Bizuneh Mekonnen Melkie
Published: March 2023

Background
Clinically, chemotherapy induced neutropenia, febrile neutropenia, thrombocytopenia and anemia were the common toxicities among breast cancer patients treated with doxorubicin-cyclophosphamide followed by paclitaxel regimen. Those toxicities may lead to chemotherapy dose modification, delay and discontinuation that may substantially compromise therapeutic outcomes.
Objective
To assess hematologic toxicities and its determinants among breast cancer patients treated with doxorubicin-cyclophosphamide followed by paclitaxel regimen in cancer centers, Northwest Ethiopia.
Method
Retrospective cohort study design was used to collect data among 422 breast cancer patients from Felege-Hiwot Comprehesnsive and Specialized Hospital and University Of Gondar Comprehensive and Specialized Hospital using a structured data abstraction format by employing systematic random sampling technique. The collected data were entered into EPI-data version 3.1 and analysed using IBM SPSS version 26. Association between dependent and independent variables was determined by using bivariate and multivariate logistic regression analysis where p < 0.05 was considered to be statistically significant.
Results
Among the study participants, more than half (76.1%) and (51.4%) patients had ductal type histology and stage III cancer, respectively, and almost all (98.9%) breast cancer patients performed modified radical mastectomy. Besides, nearly half of patients (46%) had poor ECOG PS. In the current study, the occurrence of neutropenia, anemia, thrombocytopenia and febrile neutropenia were 61.8%, 44.1%, 16.4% and 10%, respectively. Significant association with neutropenia was seen in patients; age ≥ 43years [AOR = 1.68, 95%CI (1.13,2.52)] and rular residency [AOR = 1.76,95%CI (1.16,2.67)]. Whereas stage III and IV cancer [AOR = 2.40,95%CI (1.17,4.94)] was significantly associated with febrile neutropenia. Furthermore, association with anemia was also seen in patients with mixed type histology [AOR = 4.71, 95%CI (1.43,15.53)], lobular type histology [AOR = 0.51,95%CI (0.29,0.87)], stage III and IV cancer [AOR = 1.73,95%CI (1.14,2.63) and disease comorbidity [AOR = 2.11,95%CI (1.04,4.30)]. Likewise, rular residency [AOR = 1.72,95%CI (1.01,2.91)], age ≥ 43years [AOR = 1.75,95%CI (1.02,3.02)] and stage III and IV cancer [AOR = 2.13,95%CI (1.22,3.74) were significantly associated with thrombocytopenia.
Conclusion
The magnitude of hematologic toxicities in patients treated with doxorubicin-cyclophosphamide followed by paclitaxel was high in the study setting. Age, rular residence, stage of cancer, disease comorbidity, mixed and lobular type histology were factors associated with chemotherapy induced hematologic toxicities.
Incorporating winter mixed cover crops into spring maize improves nitrogen-utilization efficiency and environmental benefits on the North China Plain
Authors: Ma Bowen , Lambers Hans , Lakshmanan Prakash , Huang Wenfeng , Liang Zhengyuan , Mudare Shingirai , Ying Jingjing , Cong Wen-Feng
Published: March 2023

Background and aims Understanding the contributions of winter cover crops (CCs) to nitrogen (N) uptake of succeeding spring maize will help achieve more efficient soil N use.
Methods A single-factor field experiment was conducted to quantify residual N effects of contrasting CC tops on spring maize N utilization and environmental benefits. 15N-labeled fertilizers were applied at the time of CC establishment in a microplot experiment to determine the contribution of aboveground residue N of winter cover crops (hairy vetch (HV), February orchid (OV), hairy vetch/ February orchid mixture (HO)) to the following spring maize.
Results Compared with the winter fallow, HV, OV and HO treatments significantly increased the partial factor productivity of N fertilizer by 43%, 16%, and 23%, respectively. The spring maize N derived from the residues was 27 (HV), 6 (OV) and 22 (HO) kg ha−1 and the total contribution to the N uptake of spring maize from the aboveground residues was 2.2~10.3%. Net N surplus was defined as total N input minus N output, and the value of OV (112 kg N ha−1) was significantly lower than that of OV (182 kg N ha−1) and HO (197 kg N ha−1). The HO was the most environmental-friendly cropping system with the lowest carbon footprint, which decreased greenhouse gas (GHG) emissions by 30%.
Conclusions The introduction of winter mixed CCs in the rotation system of three crops across two years on the North China Plain had a higher N-use efficiency, maintained yields with higher net profits, and lowered emissions.
Coordinated and communal hunting behaviours by Erabu sea krait Laticauda semifactiata
Authors: Somaweera Ru , Udyawer Vinay , Amarasinghe Thasun , de Fresnes Joe , Catherall Jay , Molchanova Galina
Published: March 2023

Opportunistic observation of Erabu sea snakes (Laticauda semifaciata) provide evidence that these species undertake a novel foraging tactic; coordinated communal hunting. Erabu sea snakes prey on cryptic fish species in highly complex reef habitats. Intra- and interspecific cooperative hunting strategies may increase chances for all members of the hunting party to encounter and capture prey in these complex habitats. Here we observed 52 instances of communal hunting by Erabu sea snakes with conspecifics and other predatory fishes at recreational dive sites in Southern Lombok, Indonesia. These observations highlight the potential higher cognitive capacity of sea snakes to coordinate activities around communal hunting events.
Statistical Information of Low-Dimensional Processes Hidden in Random State Data
Authors: Tian Yanping , Huang Zhanchao , Li Junyin , Wang Yong , Huang Zhilong , Elishakoff Isaac
Published: March 2023

For stochastically excited dissipative dynamical systems, the low-dimensional slowly varying processes act as the essential and simplified description of the apparent high-dimensional fast-varying processes (i.e., state variables). Deriving the statistical information of low-dimensional processes has a great significance, which inflects almost all the statistical information of concerned. This work is devoted to an equation-free, data-driven method, which starts from random state data, automatically extracts the slowly varying processes and automatically identifies its stationary probability density. The independent slowly varying processes are extracted by combining the identification of Lagrangian and Legendre transformations; the probability density is identified by the assumption of exponential form and the comparison with calculated data at lattices; both steps are implemented in the framework of linear regression. This method is universally valid for general nonlinear systems with arbitrary parameter values; for systems with heavy damping and/or strong excitations, it provides sparse results with high precision, while the results from stochastic averaging are incorrect even in function property.
SupportPrim – A computerized clinical decision support system for stratified care for patients with musculoskeletal pain complaints in general practice – Study Protocol for a randomized controlled trial
Authors: Lervik Lars Christian Naterstad , Vasseljen Ottar , Austad Bjarne , Bach Kerstin , Bones Anita Formo , Granviken Fredrik , Hill Jonathan C. , Jørgensen Pål , Øien Torbjørn , Veites Paola Marin , Windt Danielle A. Van der , Meisingset Ingebrigt
Published: March 2023

Background: Musculoskeletal disorders represented 149 million years lived with disability world-wide in 2019 and are the main cause of years lived with disability worldwide. Current treatment recommendations are based on “one-size fits all” principle, which does not take into account the large degree of biopsychosocial heterogeneity in this group of patients. To compensate for this, we developed a stratified care computerized clinical decision support system for general practice based on patient biopsychosocial phenotypes, further, we added personalized treatment recommendations based on specific patient factors to the system. In this study protocol we describe the randomized controlled trial for evaluating the effectiveness of computerized clinical decision support system for stratified care for patients with common musculoskeletal pain complaints in general practice. The aim of this study is to test the effect of a computerized clinical decision support system for stratified care in general practice on subjective patient outcome variables compared to current care.Methods: We will perform a cluster-randomized controlled trial with 44 general practitioners including 748 patients seeking their general practitioner due to pain in the neck, back, shoulder, hip, knee or multisite. The intervention group will use the computerized clinical decision support system while the control group will provide current care for their patients. The primary outcomes assessed at 3 months are global perceived effect and clinically important improvement in function measured by the Patient Specific Function Scale (PSFS), while secondary outcomes include change in pain intensity measured by the Numeric Rating Scale (0-10), health related quality of life (EQ-5D), general musculoskeletal health (MSK-HQ), number of treatments, use of painkillers, sick-leave grading and duration, referral to secondary care and use of imaging.Discussion: The use of biopsychosocial profile to stratify patients and implement it in a computerized clinical decision support system for general practitioners is a novel method of providing decision support for this patient group. The study aim to recruit patients from may 2022 to march 2023, and the first results from the study will be available late 2023.Trial registration: The trial is registered in ISRCTN: 14067965
Impact of environmental factors on two prominent diseases prevalent in New South Wales, Australia
Authors: Dissanayake Gnanadarsha Sanjaya , Duck Gerard
Published: March 2023

Background: Changing disease prevalence over time is an important factor in projecting for future health system requirements. Case studies and analysis of the impact of environmental and climate change on diseases affecting humans have been done in various parts of the world, providing a range of data points and interpretations. A unique subset of the published literature are statistical causality studies that infer the impact of certain environmental factors on incidence frequencies of some diseases that afflict humans. Occurrence of such frequencies in a periodic manner generate time series that could be utilised to develop future forecast predictions known as projections.
Methods: This study uses the Granger’s statistical causality method to assess the relationship between environmental variables and the prevalence of two diseases (Asthma and Melanoma) and presents projections using appropriate time series methodology to inform the health service planning requirements of the state of New South Wales (NSW).
Results: Causality between Air quality and Asthma incidence as well as Solar irradiance and Melanoma incidence are established through statistical significance measures as a contribution. Thereafter time series based forecast projections are provided for both the diseases as another contribution.
Conclusion: Statistical causality between environmental and health disease related linked variables have been established for Asthma and Melanoma, and subsequently disease incidence frequency projections in the form of point and interval estimates for the NSW state in Australia have been provided.
Identifying metastatic biomarkers of colorectal cancer: Machine learning modeling and experimental validation
Authors: Ahmadieh-Yazdi Amirhossein , Mahdavinezhad Ali , Tapak Leili , Nouri Fatemeh , Taherkhani Amir , Afshar Saeid
Published: March 2023

Background
Colorectal cancer (CRC) liver metastasis is responsible for the majority of CRC-related deaths. Early detection of metastasis is crucial for improving patient outcomes but can be delayed due to a lack of symptoms. In this research, we aimed to investigate for CRC metastasis related biomarkers by employing machine learning (ML) approach and experimental validation.
Methods
Gene expression profile of CRC patients with liver metastasis was obtained using GSE41568 dataset and the differentially expressed genes between primary and metastatic samples were screened. Subsequently, we carried out feature selection to identify most relevant DEGs using LASSO and Penalized-SVM methods. DEGs commonly selected by these methods were selected for further analysis. Finally, the experimental validation was done through qRT-PCR.
Results
11 genes were commonly selected by SCAD and P-SVM algorithms among which seven had prognostic value in colorectal cancer. It was found that the expression of MMP3 gene decreases in stage IV of colorectal cancer compared to other stages (p-value < 0.01). Also, the expression of WNT11gene increases significantly in this stage(p-value < 0.001). It was also found that expression of WNT5a, TNFSF11 and MMP3 is significantly lower, and the expression level of WNT11 is significantly higher in liver metastasis samples compared to primary tumors.
Conclusion
In summary, this study has identified a set of potential biomarkers for CRC metastasis using ML algorithms. The findings of this research may provide new insights into the identification of biomarkers for CRC metastasis and may lead to new therapeutic strategies for the treatment of this disease.
Downregulation of ubiquitin-specific protease 15 (USP15) does not provide therapeutic benefit in experimental mesial temporal lobe epilepsy
Authors: Häussler Ute , Neres João , Vandenplas Catherine , Eykens Caroline , Kadiu Irena , Schramm Carolin , Fleurance Renaud , Stanley Phil , Godard Patrice , de Mot Laurane , Eyll Jonathan van , Knobeloch Klaus-Peter , Haas Carola A. , Dedeurwaerdere Stefanie
Published: March 2023

Structural epilepsies display complex immune activation signatures; however, it is unclear which neuroinflammatory pathways drive disease pathobiology. Transcriptome studies of brain resections from mesial temporal lobe epilepsy (mTLE) patients revealed a dysregulation of transforming growth factor β, interferon α/β and nuclear factor erythroid 2-related factor 2 pathways among other neuroinflammatory mechanisms. Since these pathways are regulated by ubiquitin-specific proteases (USP), in particular USP15, we hypothesized that USP15 blockade may provide therapeutic relief in treatment-resistant epilepsies. For validation, transgenic mice which either constitutively or inducibly lack USP15 underwent intrahippocampal kainate injections to induce mTLE and to investigate the impact of USP15 downregulation at the molecular and phenotypic levels. We show that the severity of status epilepticus is unaltered in mice constitutively lacking Usp15 compared to wildtype littermates. Cell death, reactive gliosis and changes in the inflammatory transcriptome were pronounced at 4 days after kainate injection. However, the lack of USP15 did not alter brain inflammation signatures. Likewise, induced deletion of Usp15 in chronic epilepsy neither affected seizure generation, nor cell death, gliosis or the transcriptome. Concordantly, siRNA-mediated knockdown of Usp15 in a microglial cell line did not impact inflammatory responses in form of cytokine release. Our data show that a lack of USP15 is insufficient to modulate the expression of relevant neuroinflammatory pathways in mTLE and has no impact on epileptic activity in a mouse model. Although previous reports implicated a checkpoint function for USP15 in inflammation, our results do not support targeting USP15 as a therapeutic approach for pharmacoresistant epilepsy.
Square-Wave Voltammetry of Human Blood Serum
Authors: Kokoskarova Pavlinka , Stojanov Leon , Najkov Kosta , Ristovska Natasa , Ruskovska Tatjana , Skrzypek Sławomira , Mirceski Valentin
Published: March 2023

A study on voltammetric analysis of whole blood serum is presented using advanced square-wave voltammetry at an edge plane pyrolytic graphite electrode. The results demonstrate that even in a complex medium like human blood serum, electrochemical characterization can be achieved through the use of advanced voltammetric techniques in conjunction with an appropriate commercially available electrode, such as the edge plane pyrolytic graphite electrode, which boasts superior electrocatalytic properties. Without undergoing any chemical treatment of the serum sample, the square-wave voltammetry technique reveals, for the first time, the electrode reactions of uric acid, bilirubin, and albumin in a single experiment, as represented by well-defined, separated, and intense voltammetric signals. All electrode processes are surface-confined, indicating that the edge plane sites of the electrode serve as an ideal platform for the competitive adsorption of electroactive species, despite the extensive chemical complexity of the serum samples. The speed and differential nature of square-wave voltammetry are crucial for obtaining an outstanding resolution of the voltammetric peaks, maintaining the quasi-reversible nature of the underlying electrode processes, while reducing the impact of follow-up chemical reactions that are coupled to the initial electron transfer for all three detected species, and minimizing fouling of the electrode surface.
Determining what happens to the genes FOXP3, RORγt, SOCS1, STAT3, STAT5, and SMAD3 in patients with ankylosing spondylitis who received anti-TNF therapy
Authors: Aldaoseri Husham A. , Ali Naael Hussein , Al-Mubarak Fires
Published: March 2023

Background/Objective: Ankylosing spondylitis (AS) is a common inflammatory rheumatic disease that affects the axial skeleton, causing characteristic inflammatory back pain. We aim to examine the genes FOXP3, RORγt, SOCS1, STAT3, STAT5, and SMAD3 in patients with ankylosing spondylitis who receive anti-TNF therapy to understand the progression of the disease in a clinically improved or failed response to anti-TNF treatment.
Method: A prospective case-control study was conducted at Basrah Teaching Hospital in southern Iraq. Eighty-one AS patients were divided into two groups: 67 were treated with anti-TNF therapy; 14 were newly diagnosed patients as positive controls, and 65 were healthy individuals. Disease activity was assessed using the AS Bath Disease Activity Index (BASDAI). Conventional radiography and MRI are used to measure the severity of the disease. Blood samples were homogenized, and mRNA was isolated using a total RNA extraction kit. Reverse transcription (RT) was performed. The gene expression of RORγt, FOXP3, SOCS1, SAMD1, SMAD3, STAT3, and STAT5 was detected by implementing a real-timePCR system.
Result: There was significant downregulation of the FOXP3 gene in anti-TNF-treated AS patients and biologically naïve AS patients compared to healthy control people, which may be due to how the disease affects the expression and activity of the FOXP3 gene, which does not change with the type of therapy (P = 0.001). RORγt expression was higher in both established and newly diagnosed AS patients (p 0.001) than in healthy controls. The SOCS1 gene was expressed at a low level in patients with AS and positive control patients compared to the SOCS1 gene in healthy control individuals (p 0.780). STAT3 expression was lower in established and biologically naïve AS patients than in healthy subjects. Simultaneously, biologically normal AS patients had higher levels of STAT5 in this group. SMAD3 was underexpressed in established and biologically naïve AS patients compared to healthy subjects.
Conclusion: The progression of AS in patients treated with anti-TNF therapy is linked to a secondary change in the expression of the genes FOXP3, RORγt, SOCS1, STAT3, STAT5, and SMAD3 that leads to the induction of exTh17cells.
Association of social support before ICU admission with post-discharge mental health symptoms in ICU patients: A prospective cohort study
Authors: Yoshino Yasuyo , Unoki Takeshi , Hata Kimiko , Ito Kiyoe
Published: March 2023

Mental health problems after discharge from ICU interfere with physical recovery and seriously affect daily life. Social support has been suggested to be associated with mental health but has not been sufficiently characterized. This study aimed to evaluate the association of social support before ICU admission with mental health after ICU discharge. In this prospective cohort study, patients who admitted to the ICU for more than 48 h were surveyed on social support prior to ICU admission, and 3 months after discharge from the ICU, mental health questionnaires were mailed. 153 patients were enrolled; the prevalence of PTSD, anxiety, and depression, 3 months after discharge from the ICU was 11.3, 14.0, and 24.6%, respectively. Multivariate analysis using linear regression models adjusted for confounding by age, sex, and years of education for PTSD, anxiety, and depression revealed that social support women were independent factors associated with depressive symptoms. Additionally, gender differences were observed in depressive symptoms and social support associations. Social support prior to ICU admission was not associated with PTSD symptoms after ICU discharge. Higher social support before ICU admission may be associated with lower depressive symptoms after ICU discharge. It is important to provide necessary social support when needed.
Evaluation of the Effects of processing on Physicochemical Properties of the Freshly Extracted Crude Groundnut Oil
Authors: Afolabi Funmilayo Patricia , Ogundele Olamide Rachael , Raji Rofiat Oyebisi , Aderogba Mutalib Adeniran , Falade Olumuyiwa Sunday
Published: March 2023

The effect of processing on physicochemical properties of freshly extracted crude groundnut oil was determined. Crude groundnut oil was extracted following the traditional method and half of it was processed as done industrially. Chemical properties [acid value, free fatty acid, peroxide value, saponification value, ester value, iodine value, total phenol (TP), p-Anisidine value, total tocopherol (TT), and total antioxidant capacity (TAC) and thiobarbituric acid reactive species (TBARS)] and physical properties (refractive index, surface tension, smoke point, flash point, viscosity and specific gravity) were determined following the AOAC and other standard methods. Analysis of the results indicated that the processing of the crude groundnut oil, although improved the physical appearance and reduced free fatty acid by 56% hence, could improve its stability but it also compromised the levels of antioxidant compounds such as tocopherols in the oil that reduced by 16.4%. TAC, an antioxidant parameter also reduced by 92% while TBARS increased by 15.1%. It can be concluded that processing of groundnut oil could either improve its stability or compromise it, hence, there is need for the stability study of processed groundnut oil.
Quercetin-loaded Solid Lipid Nanoparticles Effectively Inhibit the Growth of Invasive Breast Cancer Cell Line MDA-MB 231
Authors: Hatami Mahdi , Kouchak Maryam ,   Alireza Kheirollah2, Khorsandi Layasadat , Rashidi Mojtaba
Published: March 2023

Background: Quercetin (QC) is a natural flavonoid abundant in fruits and vegetables. The anticancer and anti-inflammatory effects of quercetin have been reported previously, but the clinical application has been limited because of its low bioavailability. Triple-negative breast cancer is a type of breast cancer that responds poorly to chemotherapy. This study aims to determine the anti-cancer impact of quercetin-solid lipid nanoparticles (QC-SLN) on the triple-negative breast cancer cell line MDA-MB231.
Materials and Methods: Following a 48-hour treatment with 18.9 µM of QC and QC-SLN for MCF-7 and 13.4 µM for MDA-MB231, cell viability, apoptosis, the colony formation assay, and the anti-angiogenic effect of treatment were assessed.
Results: QC-SLN was constructed with the best properties (particle size of 154 nm, zeta potential of -27.7 mV, and encapsulation efficacy of 99.6%) and continuously released QC in 72 h .in QC-SLN group compared to the QC group, There was a significant decrease in cell viability, colony formation, angiogenesis and in addition, a significant increase in apoptosis, throughout modulation in Bax and Bcl-2 at gene and protein level.
Conclusions: Our findings indicated that SLN enhanced the cytotoxic effect of QC in MDA-MB231 cells by improving bioavailability and apoptotic intrinsic pathways. It may be a promising therapy for the future, but more in vivo study is needed.
Relationship between sarcopenia and cachexia with prognostic markers of middle-aged and older inpatients with COVID-19: a case-control study
Authors: Júnior José Reginaldo Alves de Queiroz , Pereira Jarson Pedro da Costa , Benjamim Raquel de Arruda Campos , Silva Nahara Oliveira Lima da , Silva Maria Eduarda de Paiva , Ramiro Claudia Porto Sabino Pinho
Published: March 2023

Purpose:SARS-CoV-2 infection can lead to various manifestations beyond an inflammatory response, such as anorexia, hyposmia, and other symptoms that may increase the risk of nutritional disorders. Sarcopenia and cachexia (nutritional disorders) are conditions that appear to influence COVID-19 evolution. Thus, this study aimed to evaluate sarcopenia and cachexia in hospitalized patients with COVID-19, verifying their clinical impacts and relationship with prognostic markers.
Methods: This is a case-control study involving inpatients with and without a COVID-19 diagnosis. The occurrence of sarcopenia was evaluated according to European Working Group on Sarcopenia 2 criteria, and cachexia was also evaluated. Inflammatory markers and the 4C Mortality Score were evaluated.
Results: The groups were similar regarding age (p = 0.656), sex (p = 0.777), presence of comorbidities (type 2 diabetes p = 0.659; systemic arterial hypertension p = 0.427), and Body Mass Index (p = 0.657). The frequency of sarcopenia and cachexia in patients with COVID-19 was 21.9% and 28.1%, respectively. Sarcopenic patients with COVID-19 had a higher risk of death (4C Mortality Score) (p = 0.038). The occurrence of sarcopenia or cachexia within the COVID-19 group was not associated with inflammatory biomarkers or a higher number of COVID-19 symptoms (p > 0.05).
Conclusion: The presence of sarcopenia among COVID-19 patients increased the risk of mortality.
Common Variable Immunodeficiency Patient Fecal Microbiota Transplant Recapitulates Gut Dysbiosis
Authors: Hajjar Joud , Voigt Anita , Conner Margaret , Swennes Alton , Fowler Stephanie , Calarge Chadi , Mendonca Danielle , Armstrong Dominique , Chang Cheng-Yen , Walter Jolan , Butte Manish , Savidge Tor , Oh Julia , Kheradmand Farrah , Petrosino Joseph
Published: March 2023

Purpose
Patients with non-infectious complications have worse clinical outcomes in common variable immunodeficiency (CVID) than those with infections-only. Non-infectious complications are associated with gut microbiome aberrations, but there are no reductionist animal models that emulate CVID. Our aim in this study was to uncover potential microbiome roles in the development of non-infectious complications in CVID.
Methods
We examined fecal whole genome shotgun sequencing from patients CVID, and non-infectious complications, infections-only, and their household controls. We also performed Fecal Microbiota transplant from CVID patients to Germ-Free Mice.
Results
We found potentially pathogenic microbes Streptococcus parasanguinis and Erysipelatoclostridium ramosum were enriched in gut microbiomes of CVID patients with non-infectious complications. In contrast, Fusicatenibacter saccharivorans and Anaerostipes hadrus, known to suppress inflammation and promote healthy metabolism, were enriched in gut microbiomes of infections-only CVID patients. Fecal microbiota transplant from non-infectious complications, infections-only, and their household controls into germ-free mice revealed gut dysbiosis patterns in recipients from CVID patients with non-infectious complications, but not infections-only CVID, or household controls recipients.
Conclusion
Our findings provide a proof of concept that fecal microbiota transplant from CVID patients with non-infectious complications to Germ-Free mice recapitulates microbiome alterations observed in the donors.
Computational modeling of AMPK and mTOR crosstalk in glutamatergic synapse calcium signaling
Authors: Rangamani Padmini , Leung Allen
Published: March 2023

Neuronal energy consumption is vital for information processing and memory formation in synapses. The brain consists of just 2% of the human body’s mass, but consumes almost 20% of the body’s energy budget. Most of this energy is attributed to active transport in ion signaling, with calcium being the canonical second messenger of synaptic transmission. Here, we develop a computational model of synaptic signaling resulting in the activation of two protein kinases critical in metabolic regulation and cell fate, AMP-Activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) and investigate the effect of glutamate stimulus frequency on their dynamics. Our model predicts that frequencies of glutamate stimulus over 10 Hz perturb AMPK and mTOR oscillations at higher magnitudes by up to 70% and area under curve (AUC) by 10%. This dynamic difference in AMPK and mTOR activation trajectories potentially differentiates high frequency stimulus bursts from basal neuronal signaling leading to a downstream change in synaptic plasticity. Further, we also investigate the crosstalk between insulin receptor and calcium signaling on AMPK and mTOR activation and predict that the pathways demonstrate multistability dependent on strength of insulin signaling and metabolic consumption rate. Our predictions have implications for improving our understanding of neuronal metabolism, synaptic pruning, and synaptic plasticity.
Methylene Orange and Methyl Blue Adsorption Behavior on Pine Leaves Biomass (Pinus kesiya)
Authors: Huynh Phuong Thao , Nguyen Duy-Khoi , Duong Bich-Ngoc , Nguyen Phi-Ho , Dinh Van-Phuc
Published: March 2023

The uptake of Methyl Orange (MO) and Methylene Blue (MB) from aqueous solutions onto Pine leaves (Pinus kesiya) was investigated in this work. Factors including pH solution, contact time, initial dye concentration were discovered to be relevant in the removal of dyes. Among four isotherm models (Langmuir, Sips, Freundlich, and Temkin), the experimental data was fitted the Langmuir model better than others. For MO and MB, the maximum Langmuir adsorption capacities were 136.99 mg.g − 1 and 140.85 mg.g − 1 , respectively. The kinetic studies demonstrated that the biosorption of MO and MB onto biomass of pine leaves was compatible with Elovich, pseudo-first-order, pseudo-second-order and intra-particle diffusion models. The thermodynamic studies showed that the uptake of the two dyes was regulated by physisorption, spontaneous, and endothermic in nature. Electrostatic interactions, as well as other non-covalent forces such as π–π interactions and hydrogen bonds, are mechanisms of dyes adsorption on pine leaf biomass. The current study found that pine leaves (Pinus kesiya) might be a potential biosorbent for the wastewater treatment due to their high availability and production, resulting in various environmental advantages.
The role of OXGR1 on gut smooth muscle to regulate intestinal motility and health
Authors: Xu Guli , Zhou Jingjing , Gyawali Ishwari , Feng Jinlong , Yuan Yexian , Xu Chang , Yang Jinping , Ma Zewei , Li Penglin , Sui Chengrong , Jiang Qingyan , Shu Gang , Zhu Canjun
Published: March 2023

Background
A stable intestinal microenvironment determines the balance of intestinal flora and body health, which is influenced by intestinal motility. 2-Oxoglutarate receptor 1 (OXGR1) is a G-protein-coupled receptor whose endogenous ligand is the resistance exercise metabolic intermediate α-ketoglutarate (AKG). Here, we aimed to determine the function of OXGR1 in intestinal motility, which modulate intestinal microenvironment.
Results
Through intestinal co-location, we found OXGR1 was highly expressed in intestinal smooth muscle. The model of OXGR1 lose-of-function mice showed enhanced intestinal barrier and motility, as well as improved intestinal flora. We further found that in gastrointestinal smooth muscle cells (GSMCs), AKG downregulates Car2 expression and modulates cellular acid-base balance by OXGR1, ultimately leading to the relaxation and reduction of motility of intestinal smooth muscle.
Conclusions
OXGR1 deletion improves intestinal microenvironment by enhanced intestinal motility; and these results provide a new target for intestinal motility regulation, OXGR1 may be developed for the treatment of some diseases such as microbiota disorders and enteritis.
Electrochemical property based on the structural control of pitch-based carbon anode
Authors: HWANG JINUNG , Lee Jong dae , Im Ji Sun
Published: March 2023

The charge/discharge characteristics of a carbon anode is studied in a lithium ion battery system based on the effects of a graphite structure developed by heat energy. A carbon precursor (pitch) is synthesized from pyrolysis of fuel oil, after which a carbonization/graphitization treatment at 1000–2400 ℃ is carried out on the carbon anode. The lithium storage mechanism of carbonized materials treated under 1300 ℃ is noted not by the space between the graphite layers but the cavity in the carbon materials. This indicates higher capacity and high speed charge-discharge performance capabilities than graphite. For graphitized materials treated at 2400 ℃, lithium ions are mainly inserted between the layers of the graphite, forming an interlayer structure. Based on the suggested mechanisms, it is noted that the charge/discharge of lithium ions can be controlled based on control of the graphite structure.
From molecule to device: DFT and SCAPS-1D simulations on the effect of aromaticity of π-linkers on enhancing the performance of anthanthrene-based dyes with D-π-A configuration in dye‐sensitized solar cells
Authors: Wazzan Nuha , Soliman Kamal A. , Jha Prafulla K.
Published: March 2023

It is essential to interpret and analyze the performance and effectiveness of dye which acts as the photon harvester component in dye-sensitized solar cells (DSSCs) applications with a molecular level insight. D2 dye was tested experimentally and proved to perform better than other investigated dyes. D2 in the fabricated solar cell achieved 690 mV of open-circuit voltage (\({\text{V}}_{\text{o}\text{c}}\)), 0.73 fill factor (\(\text{F}\text{F})\), 10.40 mA.cm− 2 of sort-circuit current (\({\text{J}}_{\text{s}\text{c}}\)), and a 5.27% of power conversion efficiency (\({\eta }\)). D2 is E)-2-cyano-3-(5-(10-(4-(di-p-tolylamino)phenyl)-6,12-bis(octyloxy)naphtho[7,8,1,2,3-nopqr]tetraphen-4-yl)thiophen-2-yl)acrylic acid compound with anthanthrene core as a π-linker substituted at 6–12 positions with nonane alkyl groups. The chemical structure engineering of D2 photosensitizer is predicted to have a significant role in DSSC devices. This work replaced the anthanthrene core with 694 kJ/mol resonance energy with other aromatic cores with different resonance energies (ranging from 255 to 529 kJ/mol). Seven dyes were designed to examine the effects of resonance energies of π-aromatic linker on the geometrical, optical, and photovoltaic parameters in the isolated and adsorbed (on TiO2 semiconductor) dyes forms. Comparison between the experimental data of D2 allow the validation of the theoretical approach and is used as a reference to evaluate the potential of the designed dyes in this application. In addition, the DSSC device was optimized using the SCAPS-1D software and successfully simulated the main electrochemical parameters.
Design and synthesis of graphene nanoribbons from organic precursors
Authors: Debnath Ranjit , Debbarma Jhuma , Saha Mitali
Published: March 2023

The strategies of synthesis of graphene nanoribbons (GNRs) with different geometries and edge structures have been investigated by various researchers but their bulk production with structural uniformity maintaining appreciable length is still a great challenge for everyone. In terms of chemistry, preparation of GNR is actually the synthesis of a conjugated polymer which may be possible via rational assembly of small organic blocks using covalent or non-covalent bonding. In this work, two organic precursors viz., p-amino benzoic acid and o-amino phenol were selected for their transformation to graphene nanoribbons. The synthesis process was designed in such a way that functional groups attached at different positions of the aromatic moieties can produce graphenic ribbon like structures. Interestingly, the FE-SEM and TEM images confirmed that intermolecular condensation might have taken place between -NH2 and -COOH groups of p-amino benzoic acid and due to simultaneous dehydration and dehydrogenation, ribbon like structures was formed. Similarly, intermolecular condensation between -NH2 and -OH groups in o-amino phenol was found to be responsible for production of ribbons like structures within the graphenic lattice. The chemistry and mechanism concluded that designing the organic precursors with functional groups at suitable positions, optimization of time and temperature can lead to the formation graphene nanoribbons even at low temperatures.
Extra-nodal Follicular dendritic cell sarcoma in a young male showing marked response to gemcitabine and docetaxel: a case study and literature review
Authors: Sarwar Kashif Ali
Published: March 2023

Follicular dendritic cell sarcoma (FDCS) is a rare tumor of dendritic cells located in B-follicles, which play a pivotal role in adaptive immune response. Surgery is the mainstay of treatment in localized disease but the management of unresectable or advanced disease is less well-defined. There is no established or preferred chemotherapy regimen to date, though many (primarily used in lymphomas) have been utilized with suboptimal outcomes. This case study reports a young male patient with advanced unresectable FDCS that progressed on doxorubicin/ifosfamide chemotherapy. The patient was subsequently advised gemcitabine/docetaxel combination chemotherapy, to which he showed marked objective as well as subjective response, and improvement of performance status. This observation, while having a potential therapeutic bearing, also supports the mesenchymal behavior of this rare tumor type. With few other reports of such marked response to gemcitabine/docetaxel and growing body of literature showing its mesenchymal origin and behavior, an accumulation of such case reports can help establish the preferred treatment regimen in advanced FDCS.
In-operando Lithium Evaporation Inducing Helium Retention in Long-Pulse HIDRA Helium Plasmas
Authors: Shone Andrew , Rizkallah Rabel , O'Dea Daniel , Kamiyama Brandon , Andruczyk Daniel
Published: March 2023

The Lithium Evaporation EXperiment (LEEX) investigated helium retention effects induced by in-operando lithium evaporations into the Hybrid Illinois Device for Research and Applications (HIDRA) at the University of Illinois Urbana-Champaign (UIUC). Lithium droplets were applied to tungsten samples and then exposed to a 600s helium plasma at different distances from the plasma edge (D=0mm, D=25mm, D=47.5mm). Spectrometers, residual gas analyzers (RGAs), and pressure gauges were employed to characterize the plasma throughout the plasma discharge. LEEX data has confirmed previous results at UIUC of in-operando lithium evaporations producing a low-recycling regime for HIDRA helium plasmas and additionally proves the retained specie is helium. The lithium evaporation from the D=25mm case had an 85.3% ± 1% increase in helium retention in the low recycling regime when compared to the steady state plasma of the LEEX control shot. Data presented substantiates previous helium retention claims and advances research surrounding liquid metal PFCs. A retention mechanism has not been identified, but further research utilizing HIDRA and HIDRA-MAT aims to investigate this. This study's outcomes are thoroughly presented and provide an additional justification for conducting further research on lithium's behavior in fusion environments, given its substantial potential impact on the development of plasma-facing components (PFCs).