Miracle-dz/UniFAR-FTUs huggingface dataset:
Neoadjuvant Chemotherapy of Triple-Negative Breast Cancer: Evaluation of Early Clinical Response, Pathological Complete Response Rates, and Addition of Platinum Salts Benefit Based on Real-World Evidence

Simple Summary Neoadjuvant chemotherapy (NACT) is the standard treatment for early-stage triple-negative breast cancer (TNBC). Achieving pathological complete response (pCR) is considered an essential prognostic factor with favorable long-term outcomes. The administration of NACT regimens with platinum salts is associated with a higher pCR rate. However, with unclear treatment guidelines and at the expense of a higher incidence of adverse events. Identifying patients and circumstances in which the benefits of platinum NACT outweigh inconveniences is still an ongoing challenge. Considering early clinical response (ECR) after the initial standard NACT cycles together with other suitable predictors could be useful to decide about the administration of platinum salts in clinical practice. The results of this large single institutional retrospective study of consecutive patients showed the significant role of adding platinum salts in older patients with high-proliferative early responded tumors and persisted lymph nodes involvement regardless of BRCA1/2 status. Abstract Pathological complete response (pCR) achievement is undoubtedly the essential goal of neoadjuvant therapy for breast cancer, directly affecting survival endpoints. This retrospective study of 237 triple-negative breast cancer (TNBC) patients with a median follow-up of 36 months evaluated the role of adding platinum salts into standard neoadjuvant chemotherapy (NACT). After the initial four standard NACT cycles, early clinical response (ECR) was assessed and used to identify tumors and patients generally sensitive to NACT. BRCA1/2 mutation, smaller unifocal tumors, and Ki-67 ≥ 65% were independent predictors of ECR. The total pCR rate was 41%, the achievement of pCR was strongly associated with ECR (OR = 15.1, p < 0.001). According to multivariable analysis, the significant benefit of platinum NACT was observed in early responders ≥45 years, Ki-67 ≥ 65% and persisted lymph node involvement regardless of BRCA1/2 status. Early responders with pCR had a longer time to death (HR = 0.28, p < 0.001) and relapse (HR = 0.26, p < 0.001). The pCR was achieved in only 7% of non-responders. However, platinum salts favored non-responders’ survival outcomes without statistical significance. Toxicity was significantly often observed in patients with platinum NACT (p = 0.003) but not for grade 3/4 (p = 0.155). These results based on real-world evidence point to the usability of ECR in NACT management, especially focusing on the benefit of platinum salts.
Gender Differences in Risk Factor Profile and Clinical Characteristics in 89 Consecutive Cases of Cerebral Venous Thrombosis

Gender has been shown to be an important variable in cerebral venous thrombosis (CVT) risk and significantly influences its clinical manifestations and outcome. The aim of our study was to investigate the gender-specific risk factor profile and clinical picture of this rare cerebrovascular disorder. Materials and methods: We retrospectively reviewed the medical records of 89 consecutive cases of CVT at a tertiary neurology clinic in Târgu Mures, Romania, between June 2009 and January 2021 to analyze the gender-related differences in etiology, clinical presentation, and outcome. Results: Women comprised 62.5% of the cohort. Females were significantly younger than males (37.3 years versus 48.8 years, respectively, p = 0.001), and the main risk factors were hormone related in 37.9% of the cases, followed by primary thrombophilia (34.4%), smoking (25.8%), obesity (17.2%), infections (17.2%), mechanical factors (17.2%), cancer (8.6%), systemic autoimmune disorders (8.6%), and hematological disorders (8.6%). In male patients, the main risk factors were smoking (41.9%), primary thrombophilia (29%), infections (22.6%), heavy alcohol consumption (16.1%), and venous thromboembolism in the medical history (12.9%). Frequency of headache was higher in females than in males (75.9% versus 67.7%), whereas frequency of coma (6.5% in males versus 1.7% in females) and dizziness (19.4% in males versus 10.3% in females) was higher in males. CVT onset was acute in 41.4% of females and 38.7% of males. The Rankin score at discharge was significantly lower in females compared with males (0.6 versus 1.6), reflecting a more favorable short-term outcome. Mortality was 6.4% in males and 1.7% in females. Conclusions: CVT is a multifactorial disorder that has a broad spectrum of risk factors with important gender-related differences in clinical manifestation and prognosis. Female patients, especially those with hormone-related risk factors, have a more favorable outcome than male patients.
Hepatic Stellate Cell Activation and Inactivation in NASH-Fibrosis—Roles as Putative Treatment Targets?

Hepatic fibrosis is the primary predictor of mortality in patients with non-alcoholic steatohepatitis (NASH). In this process, the activated hepatic stellate cells (HSCs) constitute the principal cells responsible for the deposition of a fibrous extracellular matrix, thereby driving the hepatic scarring. HSC activation, migration, and proliferation are controlled by a complex signaling network involving growth factors, lipotoxicity, inflammation, and cellular stress. Conversely, the clearance of activated HSCs is a prerequisite for the resolution of the extracellular fibrosis. Hence, pathways regulating the fate of the HSCs may represent attractive therapeutic targets for the treatment and prevention of NASH-associated hepatic fibrosis. However, the development of anti-fibrotic drugs for NASH patients has not yet resulted in clinically approved therapeutics, underscoring the complex biology and challenges involved when targeting the intricate cellular signaling mechanisms. This narrative review investigated the mechanisms of activation and inactivation of HSCs with a focus on NASH-associated hepatic fibrosis. Presenting an updated overview, this review highlights key cellular pathways with potential value for the development of future treatment modalities.
Melatonin Regulates Chloroplast Protein Quality Control via a Mitogen-Activated Protein Kinase Signaling Pathway

Serotonin N-acetyltransferase 1 (SNAT1), the penultimate enzyme for melatonin biosynthesis has shown N-acetyltransferase activity toward multiple substrates, including histones, serotonin, and plastid proteins. Under two different light conditions such as 50 or 100 μmol m−2 s−1, a SNAT1-knockout (snat1) mutant of Arabidopsis thaliana ecotype Columbia (Col-0) exhibited small size phenotypes relative over wild-type (WT) Arabidopsis Col-0. Of note, the small phenotype is stronger when growing at the 50 μmol m−2 s−1, exhibiting a dwarfism phenotype and delayed flowering. The snat1 Arabidopsis Col-0 accumulated less starch than the WT Col-0. Moreover, snat1 exhibited lower Lhcb1, Lhcb4, and RBCL protein levels, compared with the WT Col-0, but no changes in the corresponding transcripts, suggesting the involvement of melatonin in chloroplast protein quality control (CPQC). Accordingly, caseinolytic protease (Clp) and chloroplast heat shock proteins (CpHSPs), two key proteins involved in CPQC, as well as ROS defense were suppressed in snat1. In contrast, exogenous melatonin treatment induced expression of Clp, CpHSP, APX1, and GST, but not other growth-related genes such as DWF4, KS, and IAA1. Finally, the induction of ClpR1, APX1, and GST1 in response to melatonin was inhibited in the mitogen-activated protein kinase (MAPK) knockdown Arabidopsis (mpk3/6), suggesting that melatonin-mediated CPQC was mediated, in part, by the MAPK signaling cascade. These results suggest that melatonin is involved in CPQC, which plays a pivotal role in starch synthesis in plants.
Essential oil from the fruits of Schinus molle L. from Peru

Abstract The essential oil from the fruits of Schinus molle L. was investigated, in order to establish the enantiomeric distribution of its main chiral compounds. Three samples were collected between September 2001 and February 2003. The essential oils were obtained by steam distillation and analysed by GC-MS. The main components were: α-pinene (3.1 -5.7%), myrcene (26.4 – 42.0%), α-phellandrene (4.0–25.0%), limonene (9.8–19.0%), β-phellandrene (7.7–9.7%), p-cymene (3.2–19.8%), methyl octanoate (0.7–1.9%) and (Z)-β-caryophyllene (0.5 – 0.9%). The 31 compounds identified represent 94,9 – 98,2% of the total oil content. The enantiomeric distribution of the main chiral hydrocarbons showed that α-and β-phellandrene were present with only one enantiomer, while α-pinene and limonene were found to be mixtures of both enantiomers in variable concentrations.
Approaches for Mitigating Microbial Biofilm-Related Drug Resistance: A Focus on Micro- and Nanotechnologies

Biofilms play an essential role in chronic and healthcare-associated infections and are more resistant to antimicrobials compared to their planktonic counterparts due to their (1) physiological state, (2) cell density, (3) quorum sensing abilities, (4) presence of extracellular matrix, (5) upregulation of drug efflux pumps, (6) point mutation and overexpression of resistance genes, and (7) presence of persister cells. The genes involved and their implications in antimicrobial resistance are well defined for bacterial biofilms but are understudied in fungal biofilms. Potential therapeutics for biofilm mitigation that have been reported include (1) antimicrobial photodynamic therapy, (2) antimicrobial lock therapy, (3) antimicrobial peptides, (4) electrical methods, and (5) antimicrobial coatings. These approaches exhibit promising characteristics for addressing the impending crisis of antimicrobial resistance (AMR). Recently, advances in the micro- and nanotechnology field have propelled the development of novel biomaterials and approaches to combat biofilms either independently, in combination or as antimicrobial delivery systems. In this review, we will summarize the general principles of clinically important microbial biofilm formation with a focus on fungal biofilms. We will delve into the details of some novel micro- and nanotechnology approaches that have been developed to combat biofilms and the possibility of utilizing them in a clinical setting.
Silicon in the Soil–Plant Continuum: Intricate Feedback Mechanisms within Ecosystems

Plants’ ability to take up silicon from the soil, accumulate it within their tissues and then reincorporate it into the soil through litter creates an intricate network of feedback mechanisms in ecosystems. Here, we provide a concise review of silicon’s roles in soil chemistry and physics and in plant physiology and ecology, focusing on the processes that form these feedback mechanisms. Through this review and analysis, we demonstrate how this feedback network drives ecosystem processes and affects ecosystem functioning. Consequently, we show that Si uptake and accumulation by plants is involved in several ecosystem services like soil appropriation, biomass supply, and carbon sequestration. Considering the demand for food of an increasing global population and the challenges of climate change, a detailed understanding of the underlying processes of these ecosystem services is of prime importance. Silicon and its role in ecosystem functioning and services thus should be the main focus of future research.
Efficacy of toric intraocular lens and prevention of axis misalignment by optic capture in pediatric cataract surgery

The use of toric IOL in combination with OC seemed to be effective in reducing ocular aberration with less AM in pediatric cataract eyes with severe astigmatism. Purpose: To compare the outcomes of intraocular lens (IOL) implantation using toric (T)-IOL and nontoric (N)-IOL in pediatric cataract patients with astigmatism and to examine the effect of optic capture (OC) on the axis misalignment (AM) of the T-IOLs. Setting: Department of Ophthalmology, Kindai University Hospital, Osaka, Japan. Design: Interventional, comparative case study. Methods: Consecutive pediatric patients implanted with T-IOLs or N-IOLs were retrospectively reviewed. In the T-IOL group, the preoperative and postoperative corrected distance visual acuity (CDVA) and AM were compared in patients with and without OC. Results: The T-IOL group included 14 eyes of 11 patients, whereas the N-IOL group included 22 eyes of 15 patients. One year postoperatively, the mean ocular cylinder (1.38 ± 0.80 diopters [D]) was significantly smaller than the mean corneal cylinder (3.33 ± 1.24 D) in the T-IOL group (P = .00012, Wilcoxon signed-rank test). The mean preoperative and 1-year postoperative CDVA (logMAR) were 0.57 and 0.003 (T-IOL) and 0.71 and 0.09 (N-IOL), respectively. The AM at 1 week and 1 year postoperatively was 2.6 ± 3.7 degrees and 4.4 ± 3.1 degrees for the OC group, and 13.3 ± 8.8 degrees and 18.5 ± 14.8 degrees, for the non-OC group, respectively. The AM was significantly smaller in the OC group than that in the non-OC group (P = .009, Mann-Whitney U test) at postoperative 1 week. Conclusions: T-IOL implantation is effective in correcting astigmatism in pediatric cataract patients with astigmatism, and the OC technique is likely to achieve lower AM of the T-IOL.
Paving the Way for Outdoor Play: Examining Socio-Environmental Barriers to Community-Based Outdoor Play

Outdoor play and independent, neighborhood activity, both linked with healthy childhood development, have declined dramatically among Western children in recent decades. This study examines how social, cultural and environmental factors may be hindering children’s outdoor and community-based play. A comprehensive survey was completed by 826 children (aged 10–13 years) and their parents from 12 schools (four each urban, suburban and rural) from a large county in Ontario, Canada. Five multilevel regression models, controlling for any school clustering effect, examined associations between outdoor play time per week and variable sets representing five prevalent factors cited in the literature as influencing children’s outdoor play (OP). Models predicted that younger children and boys were more likely to spend time playing outdoors; involvement in organized physical activities, other children nearby to play with, higher perception of benefits of outdoor play, and higher parental perceptions of neighborhood social cohesion also predicted more time in outdoor play. Time outdoors was less likely among children not allowed to play beyond home without supervision, felt they were ‘too busy’ with screen-based activities, and who reported higher fears related to playing outdoors. Study findings have important implications for targeting environmental, cultural and policy changes to foster child-friendly communities which effectively support healthy outdoor play.
Horse Preferences for Insolation, Shade or Mist Curtain in the Paddock under Heat Conditions: Cardiac and Behavioural Response Analysis

Simple Summary Most housing guidelines for horses recommend providing access to shade in paddocks and pastures on hot days. Some paddocks are equipped with mist curtains to enable horse cooling. However, earlier studies on horse behaviours have shown that the provision of shade is not an absolute care requirement. The use of mist curtains by horses has not been scientifically studied until now. The objective of the current study was to determine which area in a paddock (insolated, shaded, or water sprayed) is most often chosen by horses during a short, 45 min stay in a hot environment (29–32 °C, 42.0% humidity) and whether horses’ behaviour and emotional arousal (expressed by cardiac variables) are related to exposure to factors prevailing in these places. The study found that the horses’ preferences regarding the conditions in the paddock were not evident, although particular horses differed in this respect. The horses did not show symptoms of overheating while staying in the sun. They were more relaxed in insolated and water sprayed areas than in the shade. The free choice of different areas provided in paddocks seems to enable horses to maintain body temperature and emotional arousal at similar levels. Abstract The horse’s welfare and, consequently, the emotional arousal may be connected with stressful environmental conditions. This study aimed to determine whether horses show behavioural or physiological symptoms of thermal discomfort and if their behaviour and cardiac parameters are related to freely chosen insolated (IS), shaded (SH), or water sprayed (with a mist curtain (MC)) areas in a paddock under heat conditions (29–32 °C, 42.0 ± 1.5% humidity). Twelve adult horses freely moving in the paddock were studied during a 45 min solitary turnout. Six cardiac variables, locomotor, and non-locomotor activities as well as rectal temperature before and after the test were monitored with regard to the area of staying. Horses did not show clear preferences regarding the time spent in IS, SH, and MC, although preferences of particular horses differed considerably. When staying under IS and MC conditions, the horses showed a higher level of relaxation compared to SH. Horses did not exhibit symptoms of thermal discomfort while staying in the sun. Free choice between the three areas differing in environmental conditions could be a crucial factor in maintaining body temperature as well as emotional arousal at similar levels. Thus, the provision of a shade and mist curtain in paddocks seems to be reasonable.
Validation of a Physical Activity and Health Questionnaire Evaluating Knowledge of WHO Recommendations among Colombians

Knowledge of physical activity (PA) can be considered a predictor of public health for society. Thus, this study aims to show content validity of the “Knowledge Questionnaire on World Health Organization (WHO) Recommendations on PA and Health” (CUAFYS-A) and reference values on adults’ knowledge of the WHO recommendations on PA. This is a quantitative, non-experimental, descriptive, and cross-sectional study, in which 579 adults completed an online questionnaire with demographic data. The questionnaire was made up of 9 items to measure PA related to knowledge. For the elaboration of the items of the questionnaire a disciplinary team formed it and for the analysis of results, a descriptive analysis of these was applied. Then an inferential analysis was performed, content validity, construct validity, and reliability were analyzed. The CUAFYS-A after its content analysis, obtained appropriate results in terms of pertinence and relevance; additionally, it showed Cronbach’s alpha coefficient of 0.62. Thereby, it was concluded the CUAFYS-A questionnaire proved to be a valid and reliable instrument to show reference values and to evaluate the knowledge of adults of PA and health according to the WHO recommendations.
Visualizing Glioma Infiltration by the Combination of Multimodality Imaging and Artificial Intelligence, a Systematic Review of the Literature

The aim of this study was to systematically review the literature concerning the integration of multimodality imaging with artificial intelligence methods for visualization of tumor cell infiltration in glioma patients. The review was performed in accordance with the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. The literature search was conducted in PubMed, Embase, The Cochrane Library and Web of Science and yielded 1304 results. 14 studies were included in the qualitative analysis. The reference standard for tumor infiltration was either histopathology or recurrence on image follow-up. Critical assessment was performed according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS2). All studies concluded their findings to be of significant value for future clinical practice. Diagnostic test accuracy reached an area under the curve of 0.74–0.91 reported in six studies. There was no consensus with regard to included image modalities, models or training and test strategies. The integration of artificial intelligence with multiparametric imaging shows promise for visualizing tumor cell infiltration in glioma patients. This approach can possibly optimize surgical resection margins and help provide personalized radiotherapy planning.
Hepatoprotective activity of Chenopodium album Linn: in vitro and in vivo studies -

Objective: The hepatoprotective activity of Chenopodium album Linn leaves against carbon tetrachloride (CCl4)-induced hepatotoxicity was investigated. Methods: Rat hepatocyte monolayer culture and rats were used as in vitro and in vivo hepatoprotective screening models. In the in vitro studies, different extracts and fractions of C.album were screened. Silymarin was taken as reference drug. In vitro antioxidant activity was also assessed. In the in vivo studies, hepatotoxicity was induced in wistar rats by administering a mixture of CCl4: olive oil (1:1, 2 ml/kg, s.c.). The extent of hepatotoxicity was assessed by measuring the serum enzyme levels. The antioxidant parameters, malondialdehyde, reduced glutathione, superoxide dismutase and catalase of the liver tissue were also assessed. Results: In the in vitro studies, ethanol extract of C.album was found to be most active than other screened extracts/fractions. Furthermore, ethanol extract was found to be rich in phenolic and flavonoids and showed significant free radical scavenging activity against diphenylpicryl hydrazyl (DPPH) and superoxide ion radicals. In the in vivo studies, ethanol extract at a dose of 100, 200 and 400 mg/kg b.w. exhibited significant protection against CCl4-induced hepatotoxicity as evident by prevention of CCl4-induced biochemical changes.
Contributions From Resting State Functional Connectivity and Familial Risk to Early Adolescent-Onset MDD: Results From the Adolescent Brain Cognitive Development Study

BACKGROUND Family history of Major Depressive Disorder (MDD) is a robust predictor of MDD onset, especially in early adolescence. We examined the relationships between familial risk for depression and alterations to resting state functional connectivity (rsFC) within the default mode network (wDMN) and between the DMN and the left/right hippocampus (DMN-LHIPP/DMN-RHIPP) to the risk for early adolescent MDD onset. METHODS We examined 9403 youth aged nine to eleven from the Adolescent Brain Cognitive Development study. Depressive symptoms were measured with the parent-reported Child Behavior Checklist. Both youth and their parents completed the Kiddie Schedule for Affective Disorders and Schizophrenia, which provided MDD diagnoses. A family history screen was administered to determine familial risk for depression. Youth underwent a resting state functional magnetic resonance imaging scan, providing us with rsFC data. RESULTS Negative wDMN rsFC was associated with child-reported current depression, both child- and parent-reported past depression, and parent-reported current depressive symptoms. No difference was found in wDMN, DMN-LHIPP or DMN-RHIPP rsFC in children with or without familial risk for depression. Familial risk for depression interacted with wDMN rsFC in association with child-reported past MDD diagnosis and parent-reported current depressive symptoms. LIMITATIONS Information such as length of depressive episodes and age of onset of depression was not collected. CONCLUSIONS Altered wDMN rsFC in youth at familial risk for depression may be associated with increased risk for MDD onset in adolescence, but longitudinal studies are needed to test this hypothesis.