Miracle-dz/UniFAR-FTUs huggingface dataset:
Challenges and Novel Opportunities of Radiation Therapy for Brain Metastases in Non-Small Cell Lung Cancer

Simple Summary Lung cancer is the most common primary malignancy that tends to metastasize to the brain. Owing to improved survival of lung cancer patients, the prevalence of brain metastases is a matter of growing concern. Brain radiotherapy remains the mainstay in the management of metastatic CNS disease. However, new targeted therapies such as the tyrosine kinase or immune checkpoint inhibitors have demonstrated intracranial activity and promising tumor response rates. Here, we review the current and emerging therapeutical strategies for brain metastases from non-small cell lung cancer, both brain-directed and systemic, as well as the uncertainties that may arise from their combination. Abstract Approximately 20% patients with non-small cell lung cancer (NSCLC) present with CNS spread at the time of diagnosis and 25–50% are found to have brain metastases (BMs) during the course of the disease. The improvement in the diagnostic tools and screening, as well as the use of new systemic therapies have contributed to a more precise diagnosis and prolonged survival of lung cancer patients with more time for BMs development. In the past, most of the systemic therapies failed intracranially because of the inability to effectively cross the blood brain barrier. Some of the new targeted therapies, especially the group of tyrosine kinase inhibitors (TKIs) have shown durable CNS response. However, the use of ionizing radiation remains vital in the management of metastatic brain disease. Although a decrease in CNS-related deaths has been achieved over the past decade, many challenges arise from the need of multiple and repeated brain radiation treatments, which carry along not insignificant risks and toxicity. The combination of stereotactic radiotherapy and systemic treatments in terms of effectiveness and adverse effects, such as radionecrosis, remains a subject of ongoing investigation. This review discusses the challenges of the use of radiation therapy in NSCLC BMs in view of different systemic treatments such as chemotherapy, TKIs and immunotherapy. It also outlines the future perspectives and strategies for personalized BMs management.
Deep Transcranial Magnetic Stimulation Affects Gut Microbiota Composition in Obesity: Results of Randomized Clinical Trial

Growing evidence highlights the crucial role of gut microbiota in affecting different aspects of obesity. Considering the ability of deep transcranial magnetic stimulation (dTMS) to modulate the cortical excitability, the reward system, and, indirectly, the autonomic nervous system (ANS), we hypothesized a potential role of dTMS in affecting the brain-gut communication pathways, and the gut microbiota composition in obesity. In a hospital setting, 22 subjects with obesity (5 M, 17 F; 44.9 ± 2.2 years; BMI 37.5 ± 1.0 kg/m2) were randomized into three groups receiving 15 sessions (3 per week for 5 weeks) of high frequency (HF), low frequency (LF) dTMS, or sham stimulation. Fecal samples were collected at baseline and after 5 weeks of treatment. Total bacterial DNA was extracted from fecal samples using the QIAamp DNA Stool Mini Kit (Qiagen, Italy) and analyzed by a metagenomics approach (Ion Torrent Personal Genome Machine). After 5 weeks, a significant weight loss was found in HF (HF: −4.1 ± 0.8%, LF: −1.9 ± 0.8%, sham: −1.3 ± 0.6%, p = 0.042) compared to LF and sham groups, associated with a decrease in norepinephrine compared to baseline (HF: −61.5 ± 15.2%, p < 0.01; LF: −31.8 ± 17.1%, p < 0.05; sham: −35.8 ± 21.0%, p > 0.05). Furthermore, an increase in Faecalibacterium (+154.3% vs. baseline, p < 0.05) and Alistipes (+153.4% vs. baseline, p < 0.05) genera, and a significant decrease in Lactobacillus (−77.1% vs. baseline, p < 0.05) were found in HF. Faecalibacterium variations were not significant compared to baseline in the other two groups (LF: +106.6%, sham: +27.6%; p > 0.05) as well as Alistipes (LF: −54.9%, sham: −15.1%; p > 0.05) and Lactobacillus (LF: −26.0%, sham: +228.3%; p > 0.05) variations. Norepinephrine change significantly correlated with Bacteroides (r2 = 0.734; p < 0.05), Eubacterium (r2 = 0.734; p < 0.05), and Parasutterella (r2 = 0.618; p < 0.05) abundance variations in HF. In conclusion, HF dTMS treatment revealed to be effective in modulating gut microbiota composition in subjects with obesity, reversing obesity-associated microbiota variations, and promoting bacterial species representative of healthy subjects with anti-inflammatory properties.
Textural, Sensory, and Chemical Characteristic of Threadfin Bream (Nemipterus sp.) Surimi Gel Fortified with Bio-Calcium from Bone of Asian Sea Bass (Lates calcarifer)

The effects of Asian sea bass (Lates calcarifer) bio-calcium (ASBB) at different levels (0, 2, 4, 6, 8, and 10%) (w/w) on properties of threadfin bream (Nemipterus sp.) surimi gel were investigated. ASBB addition increased breaking force and deformation, while reduced expressible moisture content (p < 0.05) of surimi gel. L* (lightness), a* (redness), and b* (yellowness) values were increased with augmenting ASBB levels; however, whiteness slightly decreased in surimi gel incorporated with ASBB (p < 0.05). Higher likeness scores were noticed in surimi gel containing ASBB, compared to that of the control. However, a slight decrease in the likeness score was noticed in surimi gel with 10% (w/w) ASBB (p < 0.05). Surimi gel added with 8% (w/w) ASBB possessed the increase in breaking force by 80% from the control and had the highest likeness score. Texture profile analysis of surimi gel added with ASBB showed the improved texture characteristics with coincidentally higher storage modulus of surimi paste. Surimi gel with 8% (w/w) ASBB had a denser and finer microstructure with higher ash, calcium, and phosphorous contents, compared to the control. Thus, incorporation of bio-calcium up to 8% (w/w) not only increased mineral content, but also improved textural, sensory, and microstructural properties of surimi gel.
Cardiovascular disease (CVD) risk scores, age, or years since menopause to predict cardiovascular disease in the Women's Health Initiative

Supplemental Digital Content is available in the text Abstract Objective: To assess the utility of cardiovascular disease (CVD) risk scores compared to age or years since menopause for prediction of CVD events in the WHI clinical trials. Methods: Briefly, in the randomized clinical trial 27,347 postmenopausal women age 50 to 79 years entered from 1993 to 1998. Women with a uterus (16,608) were randomized to receive daily oral conjugated equine estrogen (CEE) (0.625 mg) plus medroxyprogesterone acetate (2.5 mg) (5.7 years or placebo), while women with a hysterectomy (10,739) were randomized to receive daily oral CEE (0.625 mg) alone or placebo (7.2 y). CVD risk scores were assessed at baseline and CVD events were adjudicated throughout the follow-up period to the end of the main study phase and to the end of cumulative follow-up. The median follow-up time after the start of the randomized clinical trial to the end of the main study phase was 8.2 years. The median follow-up time to the end of cumulative follow-up was 17.6 years. We compared The American Heart Association/American College of Cardiology (AHA/ACC) and Framingham Heart Study risk scores to age or years since menopause all obtained at baseline to predict subsequent CVD events. The absolute event rates, hazard ratios, and C-statistics (Uno Concordance from Cox proportional models) were compared. Results: Overall, the hazard ratios for CVD events were highest with calculated CVD scores calculated at trial onset both at the end of the main study (ranging from 2.02 to 10.8 for Q2-Q5, compared to Q1) and at cumulative follow-up (ranging from 1.76 to 8.86 for Q2-Q5, compared to Q1). While older age and years since menopause at baseline were also associated with higher CVD event rates, better risk prediction was accomplished by using CVD risk scores. The Framingham Heart Study BMI score had the highest C-statistic at the end of the main study (0.711) and after 17.6 years through the end of follow-up (0.689). Conclusions: CVD risk scores can help identify postmenopausal women at higher risk for CVD beyond age or time since menopause. Risk scoring that better estimates vascular aging may facilitate CVD risk prevention. When performed prior to initiation of menopausal hormone therapy, scores can better inform HT risk/benefit discussions. Video Summary:http://links.lww. com/MENO/A717.
Determinants of IgG antibodies kinetics after severe and critical COVID‐19

The kinetics of IgG antibodies after coronavirus disease 2019 (COVID‐19) remain poorly understood. We investigated factors influencing severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) IgG antibody levels and time to seronegativation during the follow‐up of severe and critically ill patients. We retrospectively reviewed serological evaluations drawn during the follow‐up of severe or critical laboratory‐proven COVID‐19 patients hospitalized at a large academic hospital. Specific IgG titers were measured using a chemiluminescent assay targeting anti‐spike and anti‐nucleocapsid protein IgG. The influence of time, demographic factors, clinical and paraclinical characteristics, and COVID‐19 therapeutics on IgG levels were assessed through linear regression using a mixed‐effect model, and delay until IgG negativation through a Weibull regression model. The cohort included 116 patients with a total of 154 IgG measurements drawn at a median of 79 days after diagnosis. IgG antibodies were increased with age (p = 0.005) and decreased significantly over time (p = 0.0002). Using elapsed time and age as covariates, we demonstrated higher IgG levels in patients with a higher body mass index (BMI) (p = 0.0026) and lower IgG levels in immunocompromised patients (p = 0.032). A high BMI was further found to delay and immunodeficiency to hasten significantly seronegativation, whereas no significant effect was observed with corticosteroids. These data highlight the waning over time of IgG antibodies after severe or critical COVID‐19. Age, BMI, and immunosuppression also appear to influence the IgG kinetics, while short‐term corticotherapy does not. Those data improve the understanding of SARS‐CoV‐2 serology while further research should determine the determinants of long‐term seroprotection.
Consumption of sugar‐sweetened and artificially sweetened beverages and breast cancer survival

The activation of insulin pathways is hypothesized to promote tumor growth and worsen breast cancer survival. Sugar‐sweetened beverages (SSBs) can lead to a higher risk of insulin resistance and may affect survival. The authors prospectively evaluated the relation of postdiagnostic SSB and artificially sweetened beverage (ASB) consumption with mortality among women with breast cancer.
Dynamics of Specific cfDNA Fragments in the Plasma of Full Marathon Participants

Plasma cell-free DNA (cfDNA) is frequently analyzed using liquid biopsy to investigate cancer markers. We hypothesized that this concept might be applicable in exercise physiology. Here, we aimed to identify specific cfDNA (spcfDNA) sequences in the plasma of healthy humans using next-generation sequencing (NGS) and clearly define the dynamics regarding spcfDNA-fragment levels upon extreme exercises, such as running a full marathon. NGS analysis was performed using cfDNA of pooled plasma collected from healthy participants. We confirmed that the TaqMan-qPCR assay had high sensitivity and found that the spcfDNA sequence abundance was 16,600-fold higher than that in a normal genomic region. We then used the TaqMan-qPCR assay to investigate the dynamics of spcfDNA-fragment levels upon running a full marathon. The spcfDNA fragment levels were significantly increased post-marathon. Furthermore, spcfDNA fragment levels were strongly correlated with white blood cell and plasma myoglobin concentrations. These results suggest the spcfDNA fragments identified in this study were highly sensitive as markers of extreme physical stress. The findings of this study may provide new insights into exercise physiology and genome biology in humans.
Changes in aqueous and vitreous inflammatory cytokine levels in diabetic macular oedema: a systematic review and meta‐analysis

Diabetic macular oedema (DME) is considered a chronic inflammatory disease associated with aberrations in many intraocular cytokines. Studies assessing the role of these cytokines as biomarkers in the diagnosis and management of DME have demonstrated inconsistent findings. We quantitatively summarized data related to 116 candidate aqueous and vitreous inflammatory cytokines as biomarkers in DME. A systematic search without year limitation was performed up to 19 October 2020. Studies were included if they provided data on aqueous or vitreous cytokine concentrations in patients with DME. Effect sizes were generated as standardized mean differences (SMDs) of cytokine concentrations between patients with DME and controls. Data were extracted from 128 studies that included 4163 study eyes with DME and 1281 control eyes. Concentrations (standard mean difference, 95% confidence interval and p‐value) of aqueous IL‐6 (1.28, 0.57–2.00, p = 0.004), IL‐8 (1.06, 0.74–1.39, p < 0.00001), MCP‐1 (1.36, 0.57–2.16, p = 0.0008) and VEGF (1.31, 1.01–1.62, p < 0.00001) and vitreous VEGF (2.27, 1.55–2.99, p < 0.00001) were significantly higher in patients with DME (n = 4163) compared to healthy controls (n = 1281). No differences, failed sensitivity analyses or insufficient data were found between patients with DME and healthy controls for the concentrations of the remaining cytokines. This analysis implicates multiple cytokine biomarker candidates other than VEGF in DME and clarifies previously reported inconsistent associations. As the therapeutic options for DME expand to include multiple agents with multiple targets, it will be critical to manage the treatment burden with tailored therapy that optimizes outcomes and minimizes treatment burden. Intraocular cytokines have the promise of providing a robust individualized assessment of disease status and response to therapy. We have identified key candidate cytokines that may serve as biomarkers in individualized treatment algorithms.
Water Electrolysis Using a Porous IrO2/Ti/IrO2 Catalyst Electrode and Nafion Membranes at Elevated Temperatures

Porous IrO2/Ti/IrO2 catalyst electrodes were obtained by coating IrO2 on both sides of three types of porous Ti powder sheets (sample 1, sample 2, and sample 3) using different surface treatment methods, and a hydrogen evolution catalyst electrode was obtained by coating Pt/C on carbon gas diffusion layers. A Nafion115 membrane was used as an electrolyte for the membrane electrode assemblies (MEA). Water electrolysis was investigated at cell temperatures up to 150 °C, and the electrical characteristics of the three types of porous IrO2/Ti/IrO2 catalyst electrodes were investigated. The sheet resistance of sample 1 was higher than those of samples 2 and 3, although during water electrolysis, a high current density was observed due to the nanostructure of the IrO2 catalyst. In addition, the structural stabilities of Nafion and Aquivion membranes up to 150 °C were investigated by using small angle X-ray scattering (SAXS). The polymer structures of Nafion and Aquivion membranes were stable up to 80 °C, whereas the crystalline domains grew significantly above 120 °C. In other words, the initial polymer structure did not recover after the sample was heated above the glass transition temperature.
Life‐history traits are poor predictors of species responses to flow regime change in headwater streams

Recent climate change is altering the timing, duration and volume of river and stream flows globally, and in many regions, perennially flowing rivers and streams are drying and switching to intermittent flows. Profound impacts on aquatic biota are becoming apparent, due in part to the strong influence of flow regime on the evolution of life history. We made predictions of life‐history responses for 13 common aquatic invertebrate species (four caddisflies, five mayflies, two stoneflies, a dragonfly and an amphipod), to recent flow regime change in Australian mediterranean climate streams, based on historic studies in the same streams. Size distributions, phenology, voltinism and synchrony were compared, revealing five main responses. More than half of the species were restricted to perennially flowing streams and were absent from those that had switched to intermittent flows (including all four caddisfly species). These formerly common species are at risk of extinction as climate change progresses. Two mayfly species had divergent responses in voltinism and synchrony, and one relied on drought micro‐refuges to persist. One stonefly species changed development timing to suit the new flow regime, and the amphipod species retreated to subterranean refuges. Two formerly common species were not detected at all during 2016–2017. In addition, a new mayfly species and a caddisfly species proliferated under new flow regimes, because they had life histories suited to brief hydroperiods. Importantly, previous life history rarely predicted species’ actual responses to climate‐driven flow regime change, raising doubts about the veracity of predictions based on species traits. This is because a species’ potential for flexible phenology or growth rate is not necessarily indicated by life‐history traits.
Theoretical Mediators of Diabetes Risk and Quality of Life Following a Diabetes Prevention Program for Latino Youth With Obesity

Purpose: This study tested self-efficacy and social support for activity and dietary changes as mediators of changes in type 2 diabetes related outcomes following a lifestyle intervention among Latino youth. Setting and Intervention: Latino adolescents (14-16 years) with obesity (BMI% = 98.1 ± 1.4) were randomized to a 3-month intervention (n = 67) that fostered self-efficacy and social support through weekly, family-centered sessions or a comparison condition (n = 69). Measures: Primary outcomes included insulin sensitivity and weight specific quality of life. Mediators included self-efficacy, friend, and family social support for health behaviors. Data was collected at baseline, 3-months, 6-months, and 12-months. Analysis: Sequential path analysis was used to examine mediators as mechanisms by which the intervention influenced primary outcomes. Results: The intervention had a direct effect on family (β = 0.33, P < .01) and friend social support (β = 0.22, P < .001) immediately following the intervention (3-months). Increased family social support mediated the intervention’s effect on self-efficacy at 6-months (β = 0.09, P < .01). However, social support and self-efficacy did not mediate long-term changes in primary outcomes (P > .05) at 12-months. Conclusions: Family social support may improve self-efficacy for health behaviors in high-risk Latino youth, highlighting the important role of family diabetes prevention. Fostering family social support is a critical intervention target and more research is needed to understand family-level factors that have the potential to lead to long-term metabolic and psychosocial outcome in vulnerable youth.
Immunological analysis of the murine anti‐CD3‐induced cytokine release syndrome model and therapeutic efficacy of anti‐cytokine antibodies

The aberrant release of inflammatory mediators often referred to as a cytokine storm or cytokine release syndrome (CRS), is a common and sometimes fatal complication in acute infectious diseases including Ebola, dengue, COVID‐19, and influenza. Fatal CRS occurrences have also plagued the development of highly promising cancer therapies based on T‐cell engagers and chimeric antigen receptor (CAR) T cells. CRS is intimately linked with dysregulated and excessive cytokine release, including IFN‐γ, TNF‐α, IL 1, IL‐6, and IL‐10, resulting in a systemic inflammatory response leading to multiple organ failure. Here, we show that mice intravenously administered the agonistic hamster anti‐mouse CD3ε monoclonal antibody 145‐2C11 develop clinical and laboratory manifestations seen in patients afflicted with CRS, including body weight loss, hepatosplenomegaly, thrombocytopenia, increased vascular permeability, lung inflammation, and hypercytokinemia. Blood cytokine levels and gene expression analysis from lung, liver, and spleen demonstrated a hierarchy of inflammatory cytokine production and infiltrating immune cells with differentiating organ‐dependent kinetics. IL‐2, IFN‐γ, TNF‐α, and IL‐6 up‐regulation preceded clinical signs of CRS. The co‐treatment of mice with a neutralizing anti‐cytokine antibody cocktail transiently improved early clinical and laboratory features of CRS. We discuss the predictive use of this model in the context of new anti‐cytokine strategies to treat human CRS.
Exploring the Impact of Corporate Social Responsibility Communication through Social Media on Banking Customer E-WOM and Loyalty in Times of Crisis

Previous studies have largely explored corporate social responsibility (CSR) for organization-centric outcomes to achieve organizational performance, organizational commitment, or organizational citizenship behavior. However, the importance of CSR to achieve customer-centric outcomes is underexplored to date. Contemporary researchers have recently turned their attention toward CSR from the viewpoint of customer-centric outcomes. Therefore, the present study attempts to test the influence of CSR communication on social media and customer loyalty in the banking sector of a developing economy in times of crisis. This study also investigates the mediating effect of electronic word of mouth (E-WOM) with this relationship. The data of the present study were collected from different banking customers using a self-administered questionnaire. The empirical findings of this study validated that the CSR communication of a bank on social media increases customer loyalty, and E-WOM partially mediates this relationship. This study will be helpful for the banking sector to understand the importance of CSR communication to increase customer loyalty, which is very important for every bank in times of crisis.
Investigation of Neuropathology after Nerve Release in Chronic Constriction Injury of Rat Sciatic Nerve

Peripheral compressive neuropathy causes significant neuropathic pain, muscle weakness and prolong neuroinflammation. Surgical decompression remains the gold standard of treatment but the outcome is suboptimal with a high recurrence rate. From mechanical compression to chemical propagation of the local inflammatory signals, little is known about the distinct neuropathologic patterns and the genetic signatures after nerve decompression. In this study, controllable mechanical constriction forces over rat sciatic nerve induces irreversible sensorimotor dysfunction with sustained local neuroinflammation, even 4 weeks after nerve release. Significant gene upregulations are found in the dorsal root ganglia, regarding inflammatory, proapoptotic and neuropathic pain signals. Genetic profiling of neuroinflammation at the local injured nerve reveals persistent upregulation of multiple genes involving oxysterol metabolism, neuronal apoptosis, and proliferation after nerve release. Further validation of the independent roles of each signal pathway will contribute to molecular therapies for compressive neuropathy in the future.