bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting tumor repopulation through the gene panel derived from radiation resistant colorectal cancer cells
Authors: Song Yanwei , Deng Zheng , Sun Haoran , Zhao Yucui , Zhao Ruyi , Cheng Jin , Huang Qian 
Published: June 2023

Abstract
Background
Tumor cells with the capability of radiation resistance can escape the fate of cell death after radiotherapy, serving as the main cause of treatment failure. Repopulation of tumors after radiotherapy is dominated by this group of residual cells, which greatly reduce the sensitivity of recurrent tumors to the therapy, resulting in poor clinical outcomes. Therefore, revealing the mechanism of radiation resistant cells participating in tumor repopulation is of vital importance for cancer patients to obtain a better prognosis.

Methods
Co-expressed genes were searched by using genetic data of radiation resistant cells (from GEO database) and TCGA colorectal cancer. Univariate and multivariate Cox regression analysis were performed to define the most significant co-expressed genes for establishing prognostic indicator. Logistic analysis, WGCNA analysis, and other types of tumors were included to verify the predictive ability of the indicator. RT-qPCR was carried out to test expression level of key genes in colorectal cancer cell lines. Colongenic assay was utilized to test the radio-sensitivity and repopulation ability of key gene knockdown cells.

Results
Prognostic indicator based on TCGA colorectal cancer patients containing four key radiation resistance genes (LGR5, KCNN4, TNS4, CENPH) was established. The indicator was shown to be significantly correlated with the prognosis of colorectal cancer patients undergoing radiotherapy, and also had an acceptable predictive effect in the other five types of cancer. RT-qPCR showed that expression level of key genes was basically consistent with the radiation resistance level of colorectal cancer cells. The clonogenic ability of all key gene knockdown cells decreased after radiation treatment compared with the control groups.

Conclusions
Our data suggest that LGR5, KCNN4, TNS4 and CENPH are correlated with radiation sensitivity of colorectal cancer cells, and the indicator composed by them can reflect the prognosis of colorectal cancer patients undergoing radiation therapy. Our data provide an evidence of radiation resistant tumor cells involved in tumor repopulation, and give patients undergoing radiotherapy an approving prognostic indicator with regard to tumor progression.
Proteins from toad’s parotoid macroglands: do they play a role in gland functioning and chemical defence?
Authors: Kowalski Krzysztof , Marciniak Paweł , Rychlik Leszek 
Published: June 2023

Abstract
Background
Parotoid gland secretion of bufonid toads is a rich source of toxic molecules that are used against predators, parasites and pathogens. Bufadienolides and biogenic amines are the principal compounds responsible for toxicity of parotoid secretion. Many toxicological and pharmacological analyses of parotoid secretions have been performed, but little is known about the processes related to poison production and secretion. Therefore, our aim was to investigate protein content in parotoids of the common toad, Bufo bufo, to understand the processes that regulate synthesis and excretion of toxins as well as functioning of parotoid macroglands.

Results
Applying a proteomic approach we identified 162 proteins in the extract from toad’s parotoids that were classified into 11 categories of biological functions. One-third (34.6%) of the identified molecules, including acyl-CoA-binding protein, actin, catalase, calmodulin, and enolases, were involved in cell metabolism. We found many proteins related to cell division and cell cycle regulation (12.0%; e.g. histone and tubulin), cell structure maintenance (8.4%; e.g. thymosin beta-4, tubulin), intra- and extracellular transport (8.4%), cell aging and apoptosis (7.3%; e.g. catalase and pyruvate kinase) as well as immune (7.0%; e.g. interleukin-24 and UV excision repair protein) and stress (6.3%; including heat shock proteins, peroxiredoxin-6 and superoxide dismutase) response. We also identified two proteins, phosphomevalonate kinase and isopentenyl-diphosphate delta-isomerase 1, that are involved in synthesis of cholesterol which is a precursor for bufadienolides biosynthesis. STRING protein-protein interaction network predicted for identified proteins showed that most proteins are related to metabolic processes, particularly glycolysis, stress response and DNA repair and replication. The results of GO enrichment and KEGG analyses are also consistent with these findings.

Conclusion
This finding indicates that cholesterol may be synthesized in parotoids, and not only in the liver from which is then transferred through the bloodstream to the parotoid macroglands. Presence of proteins that regulate cell cycle, cell division, aging and apoptosis may indicate a high epithelial cell turnover in parotoids. Proteins protecting skin cells from DNA damage may help to minimize the harmful effects of UV radiation. Thus, our work extends our knowledge with new and important functions of parotoids, major glands involved in the bufonid chemical defence.
Acute and post-acute sequelae of SARS-CoV-2 infection: a review of risk factors and social determinants
Authors: Wang Chumeng , Ramasamy Akshara , Verduzco-Gutierrez Monica , Brode W. Michael , Melamed Esther 
Published: June 2023

AbstractSARS-CoV-2 infection leading to Coronavirus Disease 2019 (COVID-19) has caused more than 762 million infections worldwide, with 10–30% of patients suffering from post-acute sequelae of SARS-CoV-2 infections (PASC). Initially thought to primarily affect the respiratory system, it is now known that SARS-CoV-2 infection and PASC can cause dysfunction in multiple organs, both during the acute and chronic stages of infection. There are also multiple risk factors that may predispose patients to worse outcomes from acute SARS-CoV-2 infection and contribute to PASC, including genetics, sex differences, age, reactivation of chronic viruses such as Epstein Barr Virus (EBV), gut microbiome dysbiosis, and behavioral and lifestyle factors, including patients’ diet, alcohol use, smoking, exercise, and sleep patterns. In addition, there are important social determinants of health, such as race and ethnicity, barriers to health equity, differential cultural perspectives and biases that influence patients’ access to health services and disease outcomes from acute COVID-19 and PASC. Here, we review risk factors in acute SARS-CoV-2 infection and PASC and highlight social determinants of health and their impact on patients affected with acute and chronic sequelae of COVID-19.
Role and clinical implication of autophagy in COVID-19
Authors: Shan Tianjiao , Li Lan-ya , Yang Jin-Ming , Cheng Yan 
Published: June 2023

AbstractThe ongoing coronavirus disease 2019 (COVID-19) pandemic constitutes a serious public health concern worldwide. Currently, more than 6 million deaths have occurred despite drastic containment measures, and this number is still increasing. Currently, no standard therapies for COVID-19 are available, which necessitates identifying effective preventive and therapeutic agents against COVID-19. However, developing new drugs and vaccines is a time-consuming process, and therefore, repurposing the existing drugs or redeveloping related targets seems to be the best strategy to develop effective therapeutics against COVID-19. Autophagy, a multistep lysosomal degradation pathway contributing to nutrient recycling and metabolic adaptation, is involved in the initiation and progression of numerous diseases as a part of an immune response. The key role of autophagy in antiviral immunity has been extensively studied. Moreover, autophagy can directly eliminate intracellular microorganisms by selective autophagy, that is, “xenophagy.” However, viruses have acquired diverse strategies to exploit autophagy for their infection and replication. This review aims to trigger the interest in the field of autophagy as an antiviral target for viral pathogens (with an emphasis on COVID-19). We base this hypothesis on summarizing the classification and structure of coronaviruses as well as the process of SARS-CoV-2 infection and replication; providing the common understanding of autophagy; reviewing interactions between the mechanisms of viral entry/replication and the autophagy pathways; and discussing the current state of clinical trials of autophagy-modifying drugs in the treatment of SARS-CoV-2 infection. We anticipate that this review will contribute to the rapid development of therapeutics and vaccines against COVID-19.
Age-appropriate potassium clearance from perinatal cerebrospinal fluid depends on choroid plexus NKCC1
Authors: Fame Ryann M. , Xu Huixin , Pragana Aja , Lehtinen Maria 
Published: June 2023

AbstractRegulation of the volume and electrolyte composition of the cerebrospinal fluid (CSF) is vital for brain development and function. The Na-K-Cl co-transporter NKCC1 in the choroid plexus (ChP) plays key roles in regulating CSF volume by co-transporting ions and mediating same-direction water movements. Our previous study showed ChP NKCC1 is highly phosphorylated in neonatal mice as the CSF K+ level drastically decreases and that overexpression of NKCC1 in the ChP accelerates CSF K+ clearance and reduces ventricle size [1]. These data suggest that NKCC1 mediates CSF K+ clearance following birth in mice. In this current study, we used CRISPR technology to create a conditional NKCC1 knockout mouse line and evaluated CSF K+ by Inductively Coupled Plasma Optical Emission spectroscopy (ICP-OES). We demonstrated ChP-specific reduction of total and phosphorylated NKCC1 in neonatal mice following embryonic intraventricular delivery of Cre recombinase using AAV2/5. ChP-NKCC1 knockdown was accompanied by a delayed perinatal clearance of CSF K+. No gross morphological disruptions were observed in the cerebral cortex. We extended our previous results by showing embryonic and perinatal rats shared key characteristics with mice, including decreased ChP NKCC1 expression level, increased ChP NKCC1 phosphorylation state, and increased CSF K+ levels compared to adult. Collectively, these follow up data support ChP NKCC1’s role in age-appropriate CSF K+ clearance during neonatal development.
A cluster-randomized trial of a brief multi-component intervention to improve tobacco outcomes in substance use treatment
Authors: Guydish Joseph , McCuistian Caravella , Hosakote Sindhushree , Le Thao , Masson Carmen L. , Campbell Barbara K. , Delucchi Kevin 
Published: June 2023

Abstract
Background
Smoking prevalence is high among people in substance use disorder (SUD) treatment, and program interventions to address smoking are often complex and lengthy. This cluster-randomized trial tested whether a brief multi-component intervention impacted tobacco outcomes among staff and clients.

Methods
Seven SUD treatment programs were randomly assigned to the multi-component intervention or to waitlist control. The 6-month intervention included a leadership motivation assessment, program incentives, 4 staff training sessions and a leadership learning community session. Survey data were collected from staff and clients at pre- and post-intervention. Outcomes were first compared across condition (intervention vs waitlist control), and then examined pre- to post-intervention with condition collapsed.

Results
Staff in the intervention (n = 48) and control conditions (n = 26) did not differ at post-intervention on smoking prevalence, self-efficacy to help clients quit, or practices used to help clients quit smoking. Intervention clients (n = 113) did not differ from controls (n = 61) in smoking prevalence or receipt of tobacco services. Pre-post comparisons collapsed across condition showed a decrease in client and staff smoking prevalence, which could not be attributed to the intervention, and a decrease in client receipt of cessation medication.

Conclusion
The brief multi-component intervention did not support changes in smoking prevalence or in tobacco-related services received by clients. Other intervention features are needed to reduce smoking among SUD clients.

Trial registration
Randomization occurred at the program level and outcomes measured are program-level measures. Accordingly, the trial is not registered.
Prenatal antidepressant exposure and emotional disorders until age 22: a danish register study
Authors: Bliddal Mette , Wesselhoeft Rikke , Strandberg-Larsen Katrine , Ernst Martin T. , Weissman Myrna M. , Gingrich Jay A. , Talati Ardesheer , Pottegård Anton 
Published: June 2023

Abstract
Background
Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed antidepressants in pregnancy. Animal and some clinical studies have suggested potential increases in depression and anxiety following prenatal SSRI exposure, but the extent to which these are driven by the medication remains unclear. We used Danish population data to test associations between maternal SSRI use during pregnancy and children outcomes up to age 22.

Methods
We prospectively followed 1,094,202 single-birth Danish children born 1997–2015. The primary exposure was ≥ 1 SSRI prescription filled during pregnancy; the primary outcome, first diagnosis of a depressive, anxiety, or adjustment disorder, or redeemed prescription for an antidepressant medication. We used propensity score weights to adjust potential confounders, and incorporated data from the Danish National Birth Cohort (1997–2003) to further quantify potential residual confounding by subclinical factors.

Results
The final dataset included 15,651 exposed and 896,818 unexposed, children. After adjustments, SSRI-exposed had higher rates of the primary outcome than those of mothers who either did not use an SSRI (HR = 1.55 [95%CI:1.44,1.67] or discontinued the SSRI use ≥ 3 months prior to conception (HR = 1.23 [1.13,1.34]). Age of onset was earlier among exposed (9 [IQR:7–13] years) versus unexposed (12 [IQR:12–17] years) children (p < 0.01). Paternal SSRI use in the absence of maternal use during the index pregnancy (HR = 1.46 [1.35,1.58]) and maternal SSRI use only after pregnancy (HR = 1.42 [1.35,1.49]) were each also associated with these outcomes.

Conclusions
While SSRI exposure was associated with increased risk in the children, this risk may be driven at least partly by underlying severity of maternal illness or other confounding factors.
Intermittent theta-burst stimulation combined with physical therapy as an optimal rehabilitation in Parkinson’s disease: study protocol for a randomised, double-blind, controlled trial
Authors: Jin Zhao-hui , Wang Yi-xuan , Meng De-tao , Qin Yi , Duan Yi-nan , Fang Jin-ping , Wang Rui-dan , Liu Yan-jun , Liu Cui , Wang Ping , Yan Hong-jiao , Zhen Yi , An Xia , Chen Ke-ke , Yu Xin , Lyu Diyang , Yan Xiao-Yan , Fang Bo-yan 
Published: June 2023

AbstractBackgroundFirst-line rehabilitative strategies to improve motor deficits are based on functional training (physical or occupational therapy), which has been demonstrated to facilitate neural reorganisation. Accumulating evidence suggests that non-invasive brain stimulation techniques, such as repetitive TMS (rTMS), may enhance neuroplasticity, thereby facilitating neural reorganisation and recovery from Parkinson’s disease. Evidence also shows that intermittent theta-burst stimulation (iTBS) can improve motor function and quality of life in patients by promoting the excitability and neural remodelling of cerebral cortex. We aimed to combine iTBS stimulation with physiotherapy to improve the rehabilitation effect compared to physiotherapy alone in patients with Parkinson’s disease.MethodsThis randomised, double-blind clinical trial will enrol 50 Parkinson’s disease patients aged 45–70 years with Hoehn and Yahr scale scores of 1–3. Patients are randomly assigned to either the iTBS + physiotherapy or sham-iTBS + physiotherapy group. The trial consists of a 2-week double-blind treatment period and a 24-week follow-up period. iTBS and sham-iTBS will be administered twice daily for 10 days based on physiotherapy. The primary outcome will be the third part of Movement Disorders–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS III) from the baseline to the first 2 days following completion hospitalised intervention. The secondary outcome will be 39-item Parkinson’s Disease Questionnaire (PDQ-39) at 4 weeks, 12 weeks and 24 weeks after intervention. Tertiary outcomes are clinical evaluations and mechanism study outcomes such as NMSS, 6MWD, 10MT, TUG, BBS, MRI, and EEG, the length of time between the drug needs to be adjusted when symptoms fluctuate.DiscussionThe aim of this study is to demonstrate that iTBS can promote overall function and quality of life in Parkinson’s disease patients using physiotherapy and that this efficacy may be associated with altered neuroplasticity in exercise-related brain regions. The iTBS combined with physiotherapy training model will be evaluated during a 6-month follow-up period. With significant improvement in quality of life and motor function, iTBS combined with physiotherapy can be considered as a first-line rehabilitation option for Parkinson’s disease. The potential of iTBS to enhance neuroplasticity in the brain should have a more positive impact in increasing the generality and efficiency of physiotherapy, improving the quality of life and overall functional status of patients with Parkinson’s disease.Trial registrationChinese Clinical Trial Registry ChiCTR2200056581. Registered on 8 February 2022.
Quantitative analysis of two COVID-19 antiviral agents, favipiravir and remdesivir, in spiked human plasma using spectrophotometric methods; greenness evaluation
Authors: Batubara Afnan S. , Abdelazim Ahmed H. , Almrasy Ahmed A. , Gamal Mohammed , Ramzy Sherif 
Published: June 2023

AbstractFavipiravir and remdesivir have been included in the COVID-19 treatment guidelines panel of several countries. The main objective of the current work is to develop the first validated green spectrophotometric methods for the determination of favipiravir and remdesivir in spiked human plasma. The UV absorption spectra of favipiravir and remdesivir have shown some overlap, making simultaneous determination difficult. Due to the considerable overlap, two ratio spectra manipulating spectrophotometric methods, namely, ratio difference and the first derivative of ratio spectra, enabled the determination of favipiravir and remdesivir in their pure forms and spiked plasma. The ratio spectra of favipiravir and remdesivir were derived by dividing the spectra of each drug by the suitable spectrum of another drug as a divisor to get the ratio spectra. Favipiravir was determined by calculating the difference between 222 and 256 nm of the derived ratio spectra, while calculating the difference between 247 and 271 nm of the derived ratio spectra enabled the determination of remdesivir. Moreover, the ratio spectra of every drug were transformed to the first order derivative using ∆λ = 4 and a scaling factor of 100. The first-order derivative amplitude values at 228 and 251.20 nm enabled the determination of favipiravir and remdesivir, respectively. Regarding the pharmacokinetic profile of favipiravir (Cmax 4.43 µg/mL) and remdesivir (Cmax 3027 ng/mL), the proposed methods have been successfully applied to the spectrophotometric determination of favipiravir and remdesivir in plasma matrix. Additionally, the greenness of the described methods was evaluated using three metrics systems: the national environmental method index, the analytical eco-scale, and the analytical greenness metric. The results demonstrated that the described models were in accordance with the environmental characteristics.
Physiochemical and molecular responses of the diatom Phaeodactylum tricornutum to illumination transitions
Authors: Ding Wei , Ye Ying , Yu Lihua , Liu Meijing , Liu Jin 
Published: June 2023

AbstractBackgroundLight is a key regulatory factor for photosynthesis and metabolism of microalgae. The diatomPhaeodactylum tricornutumis capable of exhibiting metabolic flexibility in response to light fluctuations. However, the metabolic switching and underlying molecular mechanisms upon illumination transitions remain poorly understood for this industrially relevant marine alga. To address these, the physiochemical and molecular responses ofP. tricornutumupon high light (HL) and recovery (HLR) were probed.ResultsUpon HL,P. tricornutumexhibited quick responses, including decreases in cell division, major light harvesting pigments (e.g., chlorophylla,β-carotene, and fucoxanthin), chloroplastidic membrane lipids (e.g., monogalactosyldiacylglycerol, digalactosyldiacylglycerol, and sulfoquinovosyldiacylglycerol), and long-chain polyunsaturated fatty acids (e.g., C20:5), as well as increases in carbohydrates and neutral lipids particularly triacylglycerol. During HLR stage when the stress was removed, these physiochemical phenotypes were generally recovered, indicative of a rapid and reversible changes ofP. tricornutumto cope with illumination transitions for survival and growth. Through the integrated analysis with time-resolved transcriptomics, we revealed the transcriptional control of photosynthesis and carbon metabolism inP. tricornutumresponding to HL, which could be reversed more or less during the HLR stage. Furthermore, we highlighted key enzymes involved in carotenoid biosynthesis and lipid metabolism ofP. tricornutumand identified monooxygenases putatively responsible for catalyzing the ketolation step towards fucoxanthin synthesis from neoxanthin.ConclusionsThe detailed profiling of physiochemical and transcriptional responses ofP. tricornutumto HL-HLR treatments advances our understanding on the adaption of the alga to illumination transitions and provides new insights into engineering of the alga for improved production of value-added carotenoids and lipids.