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Background: While autopsy-repository programs with a variety of pediatric central nervous system (CNS) tumor types are a critical resource for preclinical neuro-oncology research, few exist and there is no published guidance on how to develop one. The goal of this prospective Pediatric Brain Tumor Repository (PBTR) study was to develop such a program at Cincinnati Children's Hospital Medical Center (CCHMC) and then publish the quantitative and experiential data as a guide to support the development of similar programs., Methods: Protocols and infrastructure were established-to educate oncologists and families, establish eligibility, obtain consent, address pre- and post-autopsy logistics (e.g., patient and tissue transportation), process and authenticate tissue samples, and collect and analyze data., Results: Of the 129 pediatric CNS tumor patients at CCHMC who died between 2013 and 2018, 109 were eligible for our study. Of these, 74% (81 of 109) were approached for PBTR donation, and 68% (55 of 81) consented. In the final year of the study, approach and consent rates were 93% and 85%, respectively. Median time from death to autopsy (postmortem interval, PMI) was 10 h (range, 1.5-30). In the outpatient setting, PMI increased with distance (from the hospice/home where the patient died to CCHMC). In all patients, PMI appeared to be lower, when consent was obtained more than 24 h before death., Conclusions: Procurement of autopsy specimens need not be a barrier in neuro-oncology research. Regional centers, strict timing-of-consent, patient education, and dedicated staff are all needed to minimize PMI and, thereby, increase the value of the procured tissue for an array of basic and translational research applications.

Rice is a critical staple crop that feeds more than half of the world's population. Still, its production confronts various biotic risks, notably the severe bacterial blight disease produced by Xanthomonas oryzae. Understanding the possible effects of climate change on the geographic distribution of this virus is critical to ensuring food security. This work used ecological niche modeling and the Maxent algorithm to create future risk maps for the range of X. oryzae under several climate change scenarios between 2050 and 2070. The model was trained using 93 occurrence records of X. oryzae and five critical bioclimatic variables. It has an excellent predictive performance, with an AUC of 0.889. The results show that X. oryzae's potential geographic range and habitat suitability are expected to increase significantly under low (RCP2.6) and high (RCP8.5) emission scenarios. Key climatic drivers allowing this development include increased yearly precipitation, precipitation during the wettest quarter, and the wettest quarter's mean temperature. These findings are consistent with broader research revealing that climate change is allowing many plant diseases and other dangerous microbes to spread across the globe. Integrating these spatial predictions with data on host susceptibility, agricultural practices, and socioeconomic vulnerabilities can help to improve targeted surveillance, preventative, and management methods for reducing the growing threat of bacterial blight to rice production. Proactive, multidisciplinary efforts to manage the changing disease dynamics caused by climate change will be critical to assuring global food security in the future decades., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Sibling relationships provide unique social experiences that can vary across the lifespan. Early sibling social interactions (ESSI) have been associated with children's own relationship and developmental outcomes, highlighting the essential role that sibling encounters play, even from a young age. Understanding how these social exchanges occur and unfold and the range of opportunities they provide can shed light on critical aspects of early childhood development and family life. However, the methodological approach used in studying ESSI can influence our understanding of these early experiences. This systematic review aims to delineate the methodological framework adopted in observational studies of ESSI. Through a systematic search of psychology and domain-general databases until March 2023, we focused on studies that addressed bidirectional naturalistic interactions in young sibling dyads (at least one child aged 0-36 months). Of the 713 articles screened, only 63 met the inclusion criteria. Findings regarding three main issues are examined, including sample characteristics, study designs and procedures, and sibling interactive behaviours targeted. Previous research has focused on a diverse range of sibling behavioral exchanges, including cues of children's social skills and relationship quality within mainly ecological contexts. However, limitations in representativeness and standardization have been identified. Future studies should incorporate sequential analyses to fully comprehend the interactive nature of early sibling social encounters., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We aimed to perform external validation of the recently developed survival prediction model for diffuse intrinsic pontine glioma (DIPG), and discuss its utility. The DIPG survival prediction model was developed in a cohort of patients from the Netherlands, United Kingdom and Germany, registered in the SIOPE DIPG Registry, and includes age <3 years, longer symptom duration and receipt of chemotherapy as favorable predictors, and presence of ring-enhancement on MRI as unfavorable predictor. Model performance was evaluated by analyzing the discrimination and calibration abilities. External validation was performed using an unselected cohort from the International DIPG Registry, including patients from United States, Canada, Australia and New Zealand. Basic comparison with the results of the original study was performed using descriptive statistics, and univariate- and multivariable regression analyses in the validation cohort. External validation was assessed following a variety of analyses described previously. Baseline patient characteristics and results from the regression analyses were largely comparable. Kaplan-Meier curves of the validation cohort reproduced separated groups of standard (n = 39), intermediate (n = 125), and high-risk (n = 78) patients. This discriminative ability was confirmed by similar values for the hazard ratios across these risk groups. The calibration curve in the validation cohort showed a symmetric underestimation of the predicted survival probabilities. In this external validation study, we demonstrate that the DIPG survival prediction model has acceptable cross-cohort calibration and is able to discriminate patients with short, average, and increased survival. We discuss how this clinico-radiological model may serve a useful role in current clinical practice.

Diffuse intrinsic pontine glioma (DIPG), a rare, often fatal childhood brain tumor, remains a major therapeutic challenge. In 2012, investigators, funded by the DIPG Collaborative (a philanthropic partnership among 29 private foundations), launched the International DIPG Registry (IDIPGR) to advance understanding of DIPG. Comprised of comprehensive deidentified but linked clinical, imaging, histopathological, and genomic repositories, the IDIPGR uses standardized case report forms for uniform data collection; serial imaging and histopathology are centrally reviewed by IDIPGR neuro-radiologists and neuro-pathologists, respectively. Tissue and genomic data, and cell cultures derived from autopsies coordinated by the IDIPGR are available to investigators for studies approved by the Scientific Advisory Committee. From April 2012 to December 2016, 670 patients diagnosed with DIPG have been enrolled from 55 participating institutions in the US, Canada, Australia and New Zealand. The radiology repository contains 3558 studies from 448 patients. The pathology repository contains tissue on 81 patients with another 98 samples available for submission. Fresh DIPG tissue from seven autopsies has been sent to investigators to develop primary cell cultures. The bioinformatics repository contains next-generation sequencing data on 66 tumors. Nine projects using data/tissue from the IDIPGR by 13 principle investigators from around the world are now underway. The IDIPGR, a successful alliance among philanthropic agencies and investigators, has developed and maintained a highly collaborative, hypothesis-driven research infrastructure for interdisciplinary and translational projects in DIPG to improve diagnosis, response assessment, treatment and outcome for patients.

The aim of this qualitative study was to explore the perception of women regarding long-term effects of childbirth education on future health-care decision making. This qualitative study used a purposive sample of 10 women who participated in facilitated focus groups. Analysis of focus group narratives provided themes in order of prevalence: (a) self-advocacy, (b) new skills, (c) anticipatory guidance, (d) control, (e) informed consent, and (f) trust. This small exploratory study does not answer the question of whether childbirth education influences future health-care decision making, but it demonstrates that the themes and issues from participants who delivered 15-30 years ago were comparable to current findings in the literature.

Although bevacizumab has not proven effective in adults with newly diagnosed high-grade gliomas (HGG), feasibility in newly diagnosed children with diffuse intrinsic pontine gliomas (DIPG) or HGG has not been reported in a prospective study. In a safety and feasibility study, children and young adults with newly diagnosed HGG received radiotherapy (RT) with bevacizumab (10 mg/kg: days 22, 36) and temozolomide (75-90 mg/m(2)/day for 42 days) followed by bevacizumab (10 mg/kg, days 1, 15), irinotecan (125 mg/m(2), days 1, 15) and temozolomide (150 mg/m(2)/day days 1-5). DIPG patients did not receive temozolomide. Telomerase activity, quality of life (QOL), and functional outcomes were assessed. Among 27 eligible patients (15 DIPG, 12 HGG), median age 10 years (range 3-29 years), 6 discontinued therapy for toxicity: 2 during RT (grade 4 thrombocytopenia, grade 3 hepatotoxicity) and 4 during maintenance therapy (grade 3: thrombosis, hypertension, skin ulceration, and wound dehiscence). Commonest ≥grade 3 toxicities included lymphopenia, neutropenia and leukopenia. Grade 3 hypertension occurred in 2 patients. No intracranial hemorrhages occurred. For DIPG patients, median overall survival (OS) was 10.4 months. For HGG patients, 3-year progression free survival and OS were 33 % (SE ± 14 %) and 50 % (SE ± 14 %), respectively. All 3 tested tumor samples, demonstrated histone H3.3K27M (n = 2 DIPG) or G34R (n = 1 HGG) mutations. QOL scores improved over the course of therapy. A bevacizumab-based regimen is feasible and tolerable in newly diagnosed children and young adults with HGG and DIPG.

MRI is a powerful tool to evaluate brain anatomy and function in normal children and its use in research applications has steadily increased. As imaging technology improves, and sensitivity to brain pathology increases, unanticipated (and potentially clinically important) findings on research neuroimaging studies will also increase. We evaluated the prevalence and type of unanticipated and potentially clinically significant imaging findings in a group of 114 normal children enrolled in an ongoing MRI imaging study of normal brain development for the Pediatric Functional Neuroimaging Research Network. Brain imaging findings were classified using standardized scales developed for the Network and findings were reported to participants and their primary healthcare provider according to a standard reporting pathway. Classification scales, reporting processes, and illustrated examples of findings are included and discussed. Unanticipated imaging findings were identified in approximately 12.5 % of children participating in this study.

There is a paucity of data regarding patterns of progression in children with high-grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG) treated with bevacizumab (BVZ) at diagnosis. We performed a retrospective study of 20 children with HGG or DIPG who received BVZ-based therapy at diagnosis on, or according to, a bi-institutional study. Magnetic resonance imaging (MRI) characteristics of first and most recent progressions were reviewed. Comparison was made to a control group of 19 patients who never received BVZ. Imaging definitions of progressive disease (PD) were local: at primary site or within 2 cm, contiguous; diffuse: >2 cm away but contiguous with primary site, ill-defined and infiltrative; distant: new, non-contiguous disease. In the BVZ-treated group, 14 patients had DIPG, six patients had HGG. Median age was 7 years (range: 3-21). Median time to PD and follow-up were 8.8 months (range 4-21) and 11 months (range: 6-25), respectively. Among 14 patients with PD, 8 (57.1 %) had local PD, 6 (42.9 %) had local and diffuse/distant PD, at initial progression. At most recent progression, a median of 10.8 months (range 6-25) from diagnosis, 10 of 14 (71.4 %) had at least diffuse (n = 8), or distant (n = 6) PD. In the comparable control group, 15 patients had PD: 11(73.3 %) local, 4 (26.7 %) local and diffuse/distant PD at first and most recent progressions. Based on these data, we postulate that BVZ may lead to a higher incidence of distant and diffuse disease in newly-diagnosed children with HGG or DIPG who received BVZ-based therapy.

Although medical and technological advances in maternity care have drastically reduced maternal and infant mortality, these interventions have become commonplace if not routine. Used appropriately, they can be life-saving procedures. Routine use, without valid indications, can transform childbirth from a normal physiologic process and family life event into a medical or surgical procedure. Every intervention presents the possibility of untoward effects and additional risks that engender the need for more interventions with their own inherent risks. Unintended consequences to intrapartum interventions make it imperative that nurse educators work with other professionals to promote natural childbirth processes and advocate for policies that focus on ensuring informed consent and alternative choices. Interdisciplinary collaboration can ensure that intrapartum caregivers "first do no harm."

On a medical mission into rural mountainous regions of Haiti, the authors were charged with teaching safer childbirth practices to untrained, mostly illiterate traditional birth attendants (TBA) who spoke Haitian Creole. In this isolated region with no physician or accessible hospital, almost all births occur at home. With no electricity, safe water supply, or sanitation facilities, childbirth education was a challenge. Accustomed to electronic, high-tech teaching aids, these childbirth educators had to modify educational strategies for these extraordinary circumstances. A successful solution was to revive decades-old teaching techniques and visual aids once used in Lamaze classes. The purpose of this article is to describe the teaching environment, the target audience, and the low-tech approach to childbirth education in Haiti.

Background: Cancer risk assessment is an important decision-making tool for women considering irreversible risk-reducing surgery. Our objective was to determine the prevalence of BRCA testing among women undergoing bilateral prophylactic mastectomy (BPM) and to review the characteristics of women who choose BPM within a metropolitan setting., Methods: We retrospectively reviewed records of women who underwent BPM in the absence of cancer within 2 health care systems that included 5 metropolitan hospitals. Women with invasive carcinoma or ductal carcinoma in situ (DCIS) were excluded; neither lobular carcinoma in situ (LCIS) nor atypical hyperplasia (AH) were exclusion criteria. We collected demographic information and preoperative screening and risk assessment, BRCA testing, reconstruction, and associated cancer risk-reducing surgery data. We compared women who underwent BRCA testing to those not tested., Results: From January 2002 to July 2009, a total of 71 BPMs were performed. Only 25 women (35.2%) had preoperative BRCA testing; 88% had a BRCA mutation. Compared with tested women, BRCA nontested women were significantly older (39.1 vs. 49.2 years, P < 0.001), had significantly more preoperative biopsies and mammograms and had fewer previous or simultaneous cancer risk-reducing surgery (oophorectomy). Among BRCA nontested women, common indications for BPM were family history of breast cancer (n = 21, 45.6%) or LCIS or AH (n = 16, 34.8%); 9 nontested women (19.6%) chose BPM based on exclusively on cancer-risk anxiety or personal preference., Conclusion: Most women who underwent BPM did not receive preoperative genetic testing. Further studies are needed to corroborate our findings in other geographic regions and practice settings.

SHZ-2 is an indica rice cultivar that exhibits broad-spectrum resistance to rice blast; it is widely used as a resistance donor in breeding programs. To dissect the QTL responsible for broad-spectrum blast resistance, we crossed SHZ-2 to TXZ-13, a blast susceptible indica variety, to produce 244 BC(4)F(3) lines. These lines were evaluated for blast resistance in greenhouse and field conditions. Chromosomal introgressions from SHZ-2 into the TXZ-13 genome were identified using a single feature polymorphism microarray, SSR markers and gene-specific primers. Segregation analysis of the BC(4)F(3) population indicated that three regions on chromosomes 2, 6, and 9, designated as qBR2.1, qBR6.1, and qBR9.1, respectively, was associated with blast resistance and contributed 16.2, 14.9, and 22.3%, respectively, to the phenotypic variance of diseased leaf area (DLA). We further narrowed the three QTL regions using pairs of sister lines extracted from heterogeneous inbred families (HIF). Pairwise comparison of these lines enabled the determination of the relative contributions of individual QTL. The qBR9.1 conferred strong resistance, whereas qBR2.1 or qBR6.1 individually did not reduce disease under field conditions. However, when qBR2.1 and qBR6.1 were combined, they reduced disease by 19.5%, suggesting that small effect QTLs contribute to reduction of epidemics. The qBR6.1 and qBR9.1 regions contain nucleotide-binding sites and leucine rich repeats (NBS-LRR) sequences, whereas the qBR2.1 did not. In the qBR6.1 region, the patterns of expression of adjacent NBS-LRR genes were consistent in backcross generations and correlated with blast resistance, supporting the hypothesis that multiple resistance genes within a QTL region can contribute to non-race-specific quantitative resistance.

Multicellular tumor spheroids are rapidly emerging as an improved in vitro model with respect to more traditional 2D culturing. Microwell culturing is a simple and accessible method for generating a large number of uniformly sized spheroids, but commercially available systems often do not enable researchers to perform complete culturing and analysis pipelines and the mechanical properties of their culture environment are not commonly matching those of the target tissue. We herein report a simple method to obtain custom-designed self-built microwell arrays made of polydimethylsiloxane or agarose for uniform 3D cell structure generation. Such materials can provide an environment of tunable mechanical flexibility. We developed protocols to culture a variety of cancer and non-cancer cell lines in such devices and to perform molecular and imaging characterizations of the spheroid growth, viability, and response to pharmacological treatments. Hundreds of tumor spheroids grow (in scaffolded or scaffold-free conditions) at homogeneous rates and can be harvested at will. Microscopy imaging can be performed in situ during or at the end of the culture. Fluorescence (confocal) microscopy can be performed after in situ staining while retaining the geographic arrangement of spheroids in the plate wells. This platform can enable statistically robust investigations on cancer biology and screening of drug treatments., (© 2023. The Author(s).)

Bone defects from accidents, congenital conditions, and age-related diseases significantly impact quality of life. Recent advancements in bone tissue engineering (TE) involve biomaterial scaffolds, patient-derived cells, and bioactive agents, enabling functional bone regeneration. Stem cells, obtained from numerous sources including umbilical cord blood, adipose tissue, bone marrow, and dental pulp, hold immense potential in bone TE. Induced pluripotent stem cells and genetically modified stem cells can also be used. Proper manipulation of physical, chemical, and biological stimulation is crucial for their proliferation, maintenance, and differentiation. Stem cells contribute to osteogenesis, osteoinduction, angiogenesis, and mineralization, essential for bone regeneration. This review provides an overview of the latest developments in stem cell-based TE for repairing and regenerating defective bones., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The field of EEG-Neurofeedback (EEG-NF) training has showcased significant promise in treating various mental disorders, while also emerging as a cognitive enhancer across diverse applications. The core principle of EEG-NF involves consciously guiding the brain in desired directions, necessitating active engagement in neurofeedback (NF) tasks over an extended period. Music listening tasks have proven to be effective stimuli for such training, influencing emotions, mood, and brainwave patterns. This has spurred the development of musical NF systems and training protocols. Despite these advancements, there exists a gap in systematic literature that comprehensively explores and discusses the various modalities of feedback mechanisms, its benefits, and the emerging applications. Addressing this gap, our review article presents a thorough literature survey encompassing studies on musical NF conducted over the past decade. This review highlights the several benefits and applications ranging from neurorehabilitation to therapeutic interventions, stress management, diagnostics of neurological disorders, and sports performance enhancement. While acknowledged for advantages and popularity of musical NF, there is an opportunity for growth in the literature in terms of the need for systematic randomized controlled trials to compare its effectiveness with other modalities across different tasks. Addressing this gap will involve developing standardized methodologies for studying protocols and optimizing parameters, presenting an exciting prospect for advancing the field., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The proper measurement of emotion is vital to understanding the relationship between emotional expression in social media and other factors, such as online information sharing. This work develops a standardized annotation scheme for quantifying emotions in social media using recent emotion theory and research. Human annotators assessed both social media posts and their own reactions to the posts' content on scales of 0 to 100 for each of 20 (Study 1) and 23 (Study 2) emotions. For Study 1, we analyzed English-language posts from Twitter (N = 244) and YouTube (N = 50). Associations between emotion ratings and text-based measures (LIWC, VADER, EmoLex, NRC-EIL, Emotionality) demonstrated convergent and discriminant validity. In Study 2, we tested an expanded version of the scheme in-country, in-language, on Polish (N = 3648) and Lithuanian (N = 1934) multimedia Facebook posts. While the correlations were lower than with English, patterns of convergent and discriminant validity with EmoLex and NRC-EIL still held. Coder reliability was strong across samples, with intraclass correlations of .80 or higher for 10 different emotions in Study 1 and 16 different emotions in Study 2. This research improves the measurement of emotions in social media to include more dimensions, multimedia, and context compared to prior schemes., (© 2023. The Psychonomic Society, Inc.)

The present study aimed to evaluate transcriptional activator-like effector (TALE) genes in 86 Xanthomonas oryzae pv. oryzicola strains collected from 8 rice-growing regions in Yunnan, and to examine the relationship between TALE genotypes and virulence in 6 differential rice lines. Besides, the geographical areas, distribution of these genotypes were studied in detail. Genetic diversity was analyzed through the number and size of putative TALE genes based on TALE gene avrXa3 as a probe. We found that X. oryzae pv. oryzicola strains consist of variable number (13-27) of avrXa3-hybridizing fragments (putative TALE genes). Test strains were classified into 8 genotypes (G1-G8) with major genotypes G3 and G7 widely distributed in Yunnan. Pathogenicity of X. oryzae pv. oryzicola was evaluated by inoculating 6 differential rice lines with a single resistance gene into 9 pathotypes clusters (I-IX), the dominant Genotypes G3 and G7 consist of pathotypes I, II, and IV. Furthermore, we also detected the known TALE target genes expression in susceptible rice cultivar (cv. nipponbare) after inoculating 8 genotypes-representative X. oryzae pv. oryzicola strain. Correlation between the numbers of putative TALE genes of X. oryzae pv. oryzicola and relevant target genes in nipponbare confirmed up-regulation. Altogether, this study has given insights into the population structure of X. oryzae pv. oryzicola that may inform strategies to control BLS in rice., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Examine the effect of subconcussive impact accumulation on cognitive/functional, imaging, and biomarker outcomes over the course of a single season, specifically in contact sport athletes at collegiate level or younger. Systematic review following PRISMA guidelines and using Oxford Center for Evidence-Based Medicine 2011 Levels of Evidence and Newcastle Ottawa Assessment Scale. PubMed MEDLINE, PsycInfo, SPORT-Discus, Web of Science. Original research in English that addressed the influence of subconcussive impacts on outcomes of interest with minimum preseason and postseason measurement in current youth, high school, or college-aged contact sport athletes. 796 articles were initially identified, and 48 articles were included in this review. The studies mostly involved male football athletes in high school or college and demonstrated an underrepresentation of female and youth studies. Additionally, operationalization of previous concussion history and concussion among studies was very inconsistent. Major methodological differences existed across studies, with ImPACT and diffusion tensor imaging being the most commonly used modalities. Biomarker studies generally showed negative effects, cognitive/functional studies mostly revealed no effects, and advanced imaging studies showed generally negative findings over the season; however, there was variability in the findings across all types of studies. This systematic review revealed growing literature on this topic, but inconsistent methodology and operationalization across studies makes it challenging to draw concrete conclusions. Overall, cognitive measures alone do not seem to detect changes across this timeframe while imaging and biomarker measures may be more sensitive to changes following subconcussive impacts., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Non-coding RNAs (ncRNAs) have key roles in the etiology of many illnesses, including heart failure, myocardial infarction, stroke, and in physiological processes like angiogenesis. In transcriptional regulatory circuits that control heart growth, signaling, and stress response, as well as remodeling in cardiac disease, ncRNAs have become important players. Studies on ncRNAs and cardiovascular disease have made great progress recently. Here, we go through the functions of non-coding RNAs (ncRNAs) like circular RNAs (circRNAs), and microRNAs (miRNAs) as well as long non-coding RNAs (lncRNAs) in modulating cardiovascular disorders., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Botrytis cinerea is a severe threat in agriculture, as it can infect over 200 different crop species with gray mold affecting food yields and quality. The conventional treatment using fungicides lead to emerging resistance over the past decades. Here, we introduce Photodynamic Inactivation (PDI) as a strategy to combat B. cinerea infections, independent of fungicide resistance. PDI uses photoactive compounds, which upon illumination create reactive oxygen species toxic for killing target organisms. This study focuses on different formulations of sodium-magnesium-chlorophyllin (Chl, food additive E140) as photoactive compound in combination with EDTA disodium salt dihydrate (Na 2 EDTA) as cell-wall permeabilizer and a surfactant. In an in vitro experiment, three different photosensitizers (PS) with varying Chl and Na 2 EDTA concentrations were tested against five B. cinerea strains with different resistance mechanisms. We showed that all B. cinerea mycelial spheres of all tested strains were eradicated with concentrations as low as 224 µM Chl and 3.076 mM Na 2 EDTA (LED illumination with main wavelength of 395 nm, radiant exposure 106 J cm -2 ). To further test PDI as a Botrytis treatment strategy in agriculture a greenhouse trial was performed on B. cinerea infected bell pepper plants (Capsicum annum L). Two different rates (560 or 1120 g Ha -1 ) of PS formulation (0.204 M Chl and 1.279 M Na 2 EDTA) and a combination of PS formulation with 0.05% of the surfactant BRIJ L4 (560 g Ha -1 ) were applied weekly for 4 weeks by spray application. Foliar lesions, percentage of leaves affected, percentage of leaf area diseased and AUDPC were significantly reduced, while percentage of marketable plants were increased by all treatments compared to a water treated control, however, did not statistically differ from each other. No phytotoxicity was observed in any treatment. These results add to the proposition of employing PDI with the naturally sourced PS Chl in agricultural settings aimed at controlling B. cinerea disease. This approach seems to be effective regardless of the evolving resistance mechanisms observed in response to conventional antifungal treatments., (© 2024. The Author(s).)

Myocardial infarction leads to cardiomyocyte loss, ensuing ventricular pathological remodeling, dramatic impairment of cardiac function, and ultimately heart failure. Unfortunately, the existing therapeutical treatments cannot directly replenish the lost myocytes in the injured myocardium and the long-term prognosis of heart failure after myocardial infarction remains poor. Growing investigations have demonstrated that the adult mammalian cardiomyocytes possess very limited proliferation capacity, and that was not enough to restore the injured heart. Recently, many studies were targeting to promote cardiomyocyte proliferation via inducing cardiomyocyte cell cycle re-entry for cardiac repair after myocardial infarction. Indeed, these results showed it is a feasible way to stimulate terminally differentiated cardiomyocyte proliferation. Here, we reviewed the major mechanisms and the potential targets for stimulating mammalian adult cardiomyocyte proliferation specifically. This will provide a new therapeutic strategy for the clinical treatment of myocardial infarction by activating the endogenous regeneration. Graphical abstract.

Introduction: This study investigates the safety, tolerability, and preliminary efficacy of combined treatment with VEGF inhibitor bevacizumab, topoisomerase I inhibitor irinotecan, and EGFR inhibitor erlotinib in children with progressive diffuse intrinsic pontine glioma (DIPG)., Methods: Biweekly bevacizumab (10 mg/kg) and irinotecan (125 mg/m 2 ) were combined with daily erlotinib. Two cohorts received increasing doses of erlotinib (65 and 85 mg/m 2 ) following a 3 + 3 dose-escalation schedule, until disease progression with a maximum of one year. Dose-limiting toxicities (DLT) were monitored biweekly. Secondary progression free survival (sPFS) and overall survival (OS) were determined based on clinical and radiological response measurements. Quality of life (QoL) during treatment was also assessed., Results: Between November 2011 and March 2018, nine patients with disease progression after initial radiotherapy were enrolled. Median PFS at start of the study was 7.3 months (range 3.5-10.0). In the first dose cohort, one patient experienced a DLT (grade III acute diarrhea), resulting in enrollment of three additional patients in this cohort. No additional DLTs were observed in consecutive patients receiving up to a maximum dose of 85 mg/m 2 . Median sPFS was 3.2 months (range 1.0-10.9), and median OS was 13.8 months (range 9.3-33.0). Overall QoL was stable during treatment., Conclusions: Daily erlotinib is safe and well tolerated in doses up to 85 mg/m 2 when combined with biweekly bevacizumab and irinotecan in children with progressive DIPG. Median OS of the study patients was longer than known form literature.

Purpose: Cyclin-dependent kinase-retinoblastoma (CDK-RB) pathway is dysregulated in some diffuse intrinsic pontine gliomas (DIPG). We evaluated safety, feasibility, and early efficacy of the CDK4/6-inhibitor ribociclib, administered following radiotherapy in newly-diagnosed DIPG patients., Methods: Following radiotherapy, eligible patients received ribociclib in 28-day cycles (350 mg/m 2 ; 21 days on/7 days off). Feasibility endpoints included tolerability for at least 6 courses, and a less than 2-week delay in restarting therapy after 1 dose reduction. Early efficacy was measured by 1-year and median overall survival (OS). Patient/parent-by-proxy reported outcomes measurement information system (PROMIS) assessments were completed prospectively., Results: The study included 10 evaluable patients, 9 DIPG and 1 diffuse midline glioma (DMG)-all 3.7 to 19.8 years of age. The median number of courses was 8 (range 3-14). Three patients required dose reduction for grade-4 neutropenia, and 1 discontinued therapy for hematological toxicity following course 4. The most common grade-3/4 toxicity was myelosuppression. After 2 courses, MRI evaluations in 4 patients revealed increased necrotic volume, associated with new neurological symptoms in 3 patients. The 1-year and median OS for DIPG was 89% and 16.1 months (range 10-30), respectively; the DMG patient died at 6 months post-diagnosis. Five patients donated brain tissue and tumor; 3 were RB+ ., Conclusions: Ribociclib administered following radiotherapy is feasible in DIPG and DMG. Increased tumor necrosis may represent a treatment effect. These data warrant further prospective volumetric analyses of tumors with necrosis. Feasibility and stabilization findings support further investigation of ribociclib in combination therapies., Trial Registration: NCT02607124.

Introduction: Beyond focal radiation, there is no consensus standard therapy for pediatric high-grade glioma (pHGG) and outcomes remain dismal. We describe the largest molecularly-characterized cohort of children with pHGG treated with a 3-drug maintenance regimen of temozolomide, irinotecan, and bevacizumab (TIB) following radiation., Methods: We retrospectively reviewed 36 pediatric patients treated with TIB at Seattle Children's Hospital from 2009 to 2018 and analyzed survival using the Kaplan-Meier method. Molecular profiling was performed by targeted DNA sequencing and toxicities, steroid use, and palliative care utilization were evaluated., Results: Median age at diagnosis was 10.9 years (18 months-18 years). Genetic alterations were detected in 26 genes and aligned with recognized molecular subgroups including H3 K27M-mutant (12), H3F3A G34-mutant (2), IDH-mutant (4), and hypermutator profiles (4). Fifteen patients (42%) completed 12 planned cycles of maintenance. Side effects associated with chemotherapy delays or modifications included thrombocytopenia (28%) and nausea/vomiting (19%), with temozolomide dosing most frequently modified. Median event-free survival (EFS) and overall survival (OS) was 16.2 and 20.1 months, with shorter survival seen in DIPG (9.3 and 13.3 months, respectively). Survival at 1, 2, and 5 years was 80%, 10% and 0% for DIPG and 85%, 38%, and 16% for other pHGG., Conclusion: Our single-center experience demonstrates tolerability of this 3-drug regimen, with prolonged survival in DIPG compared to historical single-agent temozolomide. pHGG survival was comparable to analogous 3-drug regimens and superior to historical agents; however, cure was rare. Children with pHGG remain excellent candidates for the study of novel therapeutics combined with standard therapy.

Background: Severe COVID-19, with the need in supplemental oxygen and hospitalization, leads to major burden on patients and healthcare systems. As a result, safe and effective ambulatory treatment strategies for severe COVID-19 are of urgent need. In this systematic review, we aimed to evaluate interventions to transition care to the ambulatory setting for patients with active severe COVID-19 that required supplemental oxygen., Methods: We searched Medline, Scopus, Web of Science, and DOAJ databases to identify articles with original data published until the 1st of April 2023. Characteristics and outcomes of interventions to transition care to home management were reviewed. Given the heterogeneous settings and outcomes studied, a meta-analysis was not performed., Results: Of the 235 studies identified, 11 observational studies, with 2645 patients, were included. The interventions were initiated from the emergency department, observation units or inpatient units, and included continuous home telemonitoring (n = 8), mobile applications (n = 2), and patient-initiated medical contact (n = 3). Included patients had an overall short length of hospital stay, high readmission rates, and positive patients' feedback. There was a lack of prospective controlled data and cost-effectiveness analyses., Conclusion: Our findings highlight the potential in treating severe COVID-19 at the ambulatory setting and the lack of high-quality data in this field. Dedicated medical teams, adjusted monitoring methods, improving clinical trajectory, and correct inclusion settings are needed for safe and effective transition of care., (© 2023. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Susceptibility-weighted imaging (SWI) is a magnetic resonance imaging (MRI) technique able to depict the magnetic susceptibility produced by different substances, such as deoxyhemoglobin, calcium, and iron. The main application of SWI in clinical neuroimaging is detecting microbleedings and venous vasculature. Quantitative analyses of SWI have been developed over the last few years, aimed to offer new parameters, which could be used as neuroimaging biomarkers. Each technique has shown pros and cons, but no gold standard exists yet. The fractal dimension (FD) has been investigated as a novel potential objective parameter for monitoring intratumoral space-filling properties of SWI patterns. We showed that SWI patterns found in different tumors or different glioma grades can be represented by a gradient in the fractal dimension, thereby enabling each tumor to be assigned a specific SWI fingerprint. Such results were especially relevant in the differentiation of low-grade versus high-grade gliomas, as well as from high-grade gliomas versus lymphomas.Therefore, FD has been suggested as a potential image biomarker to analyze intrinsic neoplastic architecture in order to improve the differential diagnosis within clinical neuroimaging, determine appropriate therapy, and improve outcome in patients.These promising preliminary findings could be extended into the field of neurotraumatology, by means of the application of computational fractal-based analysis for the qualitative and quantitative imaging of microbleedings in traumatic brain injury patients. In consideration of some evidences showing that SWI signals are correlated with trauma clinical severity, FD might offer some objective prognostic biomarkers.In conclusion, fractal-based morphometrics of SWI could be further investigated to be used in a complementary way with other techniques, in order to form a holistic understanding of the temporal evolution of brain tumors and follow-up response to treatment, with several further applications in other fields, such as neurotraumatology and cerebrovascular neurosurgery as well., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Soil erosion is a destructive consequence of land degradation caused by deforestation, improper farming practices, overgrazing, and urbanization. This irreversible effect negatively impacts the limited renewable soil resource, causing soil truncation, reduced fertility, and unstable slopes. To address the anticipation of erosion modulus resulting from long-term land use and land cover (LULC) changes, a study was conducted in the Swat District of Khyber Pakhtunkhwa (Kpk), Pakistan. The study aimed to predict and evaluate soil erosion concerning these changes using remote sensing (RS), geographic information systems (GIS), and the Revised Universal Soil Loss Equation (RUSLE) model. We also evaluated the impact of the Billion Tree Tsunami Project (BTTP) on soil erosion in the region. Model inputs, such as rainfall erosivity factor, topography factor, land cover and management factor, and erodibility factor, were used to calculate soil erosion. The results revealed that significant soil loss occurred under 2001, 2011, and 2021 LULC conditions, accounting for 67.26%, 61.78%, and 65.32%, falling within the category of low erosion potential. The vulnerable topographical features of the area indicated higher erosion modulus. The maximum soil loss rates observed in 2001, 2011, and 2021 were 80 t/ha -1 /year -1 , 120 t/ha -1 /year -1 , and 96 t/ha -1 /year -1 , respectively. However, the observed reduction in soil loss in 2021 as compared to 2001 and 2011 suggests a positive influence of the BTTP on soil conservation efforts. This study underscores the potential of afforestation initiatives like the BTTP in mitigating soil erosion and highlights the significance of environmental conservation programs in regions with vulnerable topography., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Our main objective is to investigate how the structural information of intraluminal thrombus (ILT) can be used to predict abdominal aortic aneurysms (AAA) growth status through an automated workflow. Fifty-four human subjects with ILT in their AAAs were identified from our database; those AAAs were categorized as slowly- (< 5 mm/year) or fast-growing (≥ 5 mm/year) AAAs. In-house deep-learning image segmentation models were used to generate 3D geometrical AAA models, followed by automated analysis. All features were fed into a support vector machine classifier to predict AAA's growth status.The most accurate prediction model was achieved through four geometrical parameters measuring the extent of ILT, two parameters quantifying the constitution of ILT, antihypertensive medication, and the presence of co-existing coronary artery disease. The predictive model achieved an AUROC of 0.89 and a total accuracy of 83%. When ILT was not considered, our prediction's AUROC decreased to 0.75 (P-value < 0.001)., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A trace element, known as a minor element, is a chemical element whose concentration is very low. They are divided into essential and non-essential classes. Numerous physiological and metabolic processes in both plants and animals require essential trace elements. These essential trace elements are so directly related to the metabolic and physiologic processes of the organism that either their excess or deficiency can result in severe bodily malfunction or, in the worst situations, death. Elements can be found in nature in various forms and are essential for the body to carry out its varied functions. Trace elements are crucial for biological, chemical, and molecular cell activity. Nutritional deficits can lead to weakened immunity, increased susceptibility to oral and systemic infections, delayed physical and mental development, and lower productivity. Trace element enzymes are involved in many biological and chemical processes. These compounds act as co-factors for a number of enzymes and serve as centers for stabilizing the structures of proteins and enzymes, allowing them to mediate crucial biological processes. Some trace elements control vital biological processes by attaching to molecules on the cell membrane's receptor site or altering the structure of the membrane to prevent specific molecules from entering the cell. Some trace elements are engaged in redox reactions. Trace elements have two purposes. They are required for the regular stability of cellular structures, but when lacking, they might activate alternate routes and induce disorders. Therefore, thoroughly understanding these trace elements is essential for maintaining optimal health and preventing disease., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aims to simulate beta blockers' (BB) effects on coronary artery aneurysms' (CAA) hemodynamics and thrombotic risk in Kawasaki disease (KD). BB are recommended in cases of large aneurysms due to their anti-ischemic effect. Coronary blood flow (CBF) was simulated in KD patient-specific CAA models using computational fluid dynamics. Hemodynamic indices that correlate with thrombotic risk were calculated following two possible responses to BB: (1) preserved coronary flow (third BB generation) and (2) reduction in coronary flow (first and second BB generations) at reduced heart rate. Following CBF reduction scenario, mean TAWSS and HOLMES significantly decreased compared to normal conditions, leading to a potential increase in thrombotic risk. Preserved CBF at lower heart rates, mimicking the response to vasodilating BBs, does not significantly affect local CAA hemodynamics compared with baseline, while achieving the desired anti-ischemic effects. Different BB generations lead to different hemodynamic responses in CAA., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Neutrophils are the most abundant white blood cells in circulation and constitute up to 60% of circulating leukocytes. Neutrophils play a significant role in host defense against pathogens through various mechanisms, including phagocytosis, production of antimicrobial proteins, and formation of neutrophil extracellular traps (NETs). Recently, the role of neutrophils and NETs in cancer has generated significant interest, as accumulating evidence suggests that neutrophils and NETs contribute to cancer progression and are associated with adverse patient outcomes. In this review, we will first highlight the roles of neutrophils and NETs in cancer progression and metastasis and discuss new drug delivery approaches to target and modulate neutrophils and NETs for cancer therapeutics., (© 2022. Controlled Release Society.)

Background: The ongoing COVID-19 pandemic has revealed gender-specific differences between general practitioners in adapting to the posed challenges. As primary care workforce is becoming increasingly female, in many countries, it is essential to take a closer look at gender-specific influences when the global health care system is confronted with a crisis., Objective: To explore gender-specific differences in the perceived working conditions and gender-specific differences in challenges facing GPs at the beginning of the COVID-19 pandemic in 2020., Design: Online survey in seven countries., Participants: 2,602 GPs from seven countries (Austria, Australia, Switzerland, Germany, Hungary, Italy, Slovenia). Of the respondents, 44.4% (n = 1,155) were women., Main Measures: Online survey. We focused on gender-specific differences in general practitioners' perceptions of working conditions at the beginning of the COVID-19 pandemic in 2020., Key Results: Female GPs rated their skills and self-confidence significantly lower than male GPs (f: 7.1, 95%CI: 6.9-7.3 vs. m: 7.6, 95%CI 7.4-7.8; p < .001), and their perceived risk (concerned about becoming infected or infecting others) higher than men (f: 5.7, 95%CI: 5.4-6.0 vs. m: 5.1, 95%CI: 4.8-5.5; p = .011). Among female GPs, low self-confidence in the treatment of COVID-19 patients appear to be common. Results were similar in all of the participating countries., Conclusions: Female and male GPs differed in terms of their self-confidence when dealing with COVID-19-related issues and their perceptions of the risks arising from the pandemic. To ensure optimal medical care, it is important that GPs realistically assess their own abilities and overall risk., (© 2023. The Author(s).)

Sensitivity to ultraviolet-B (UVB, 280-315 nm) radiation varies widely among rice (Oryza sativa) cultivars due to differences in the activity of cyclobutane pyrimidines dimer (CPD) photolyase. Interestingly, cultivars with high UVB sensitivity and low CPD photolyase activity have been domesticated in tropical areas with high UVB radiation. Here, we investigated how differences in CPD photolyase activity affect plant resistance to the rice blast fungus, Magnaporthe oryzae, which is one of the other major stresses. We used Asian and African rice cultivars and transgenic lines with different CPD photolyase activities to evaluate the interaction effects of CPD photolyase activity on resistance to M. oryzae. In UVB-resistant rice plants overexpressing CPD photolyase, 12 h of low-dose UVB (0.4 W m -2 ) pretreatment enhanced sensitivity to M. oryzae. In contrast, UVB-sensitive rice (transgenic rice with antisense CPD photolyase, A-S; and rice cultivars with low CPD photolyase activity) showed resistance to M. oryzae. Several defense-related genes were upregulated in UVB-sensitive rice compared to UVB-resistant rice. UVB-pretreated A-S plants showed decreased multicellular infection and robust accumulation of reactive oxygen species. High UVB-induced CPD accumulation promoted defense responses and cross-protection mechanisms against rice blast disease. This may indicate a trade-off between high UVB sensitivity and biotic stress tolerance in tropical rice cultivars., (© 2023. The Author(s).)

In recent years, within tissue engineering, cell growth on patterned surfaces have gained significant attention. Growing cells in patterns is important to manufacture polymeric tissues that can be used within the medical field. For this reason, the main focus of this study was to prepare patterned scaffolds using Titanium (Ti) and polyvinyl chloride (PVC) covered on microscope lamellas and examine their liability for cell growth. A polydimethylsiloxane stamp was initially prepared which was then used to transfer a predefined pattern onto PVC- and Ti-covered surfaces. Cell growth experiments were performed on the prepared materials by seeding L929 mouse fibroblasts. The growth of cells seeded on the surface of the scaffolds were spectroscopically followed using Neutral Red uptake assay. The results showed cell proliferation on both patterned surfaces, however, it was higher on Ti-covered samples. In addition, three different alkanethiols were tested for cell adhesion on patterned surfaces. A higher number of cell proliferation was observed with undecanethiol, which has a shorter alkane group among them. The morphological properties of the samples before and after cell-seeding were analyzed via scanning electron microscope and optical microscopy. Significant amount of cell proliferation was observed on all of the prepared samples., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Wheat (Triticum aestivum) is one of the major crops worldwide and a primary source of calories for human food. Biotic stresses such as fungi, bacteria, and diseases limit wheat production. Although plant breeding and genetic engineering for biotic stress resistance have been suggested as promising solutions to handle losses caused by biotic stress factors, a comprehensive understanding of molecular mechanisms and identifying key genes is a critical step to obtaining success. Here, a network-based meta-analysis approach based on two main statistical methods was used to identify key genes and molecular mechanisms of the wheat response to biotic stress. A total of 163 samples (21,792 genes) from 10 datasets were analyzed. Fisher Z test based on the p-value and REM method based on effect size resulted in 533 differentially expressed genes (p < 0.001 and FDR < 0.001). WGCNA analysis using a dynamic tree-cutting algorithm was used to construct a co-expression network and three significant modules were detected. The modules were significantly enriched by 16 BP terms and 4 KEGG pathways (Benjamini-Hochberg FDR < 0.001). A total of nine hub genes (a top 1.5% of genes with the highest degree) were identified from the constructed network. The identification of DE genes, gene-gene co-expressing network, and hub genes may contribute to uncovering the molecular mechanisms of the wheat response to biotic stress., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: As there is no standard of care treatment for recurrent/progressing pediatric high-grade gliomas (pHGG), we aimed to gain an overview of different treatment strategies., Methods: In a web-based questionnaire, members of the SIOPE-BTG and the GPOH were surveyed on therapeutic options in four case scenarios (children/adolescents with recurrent/progressing HGG)., Results: 139 clinicians with experience in pediatric neuro-oncology from 22 European countries participated in the survey. Most respondents preferred further oncological treatment in three out of four cases and chose palliative care in one case with marked symptoms. Depending on the case, 8-92% would initiate a re-resection (preferably hemispheric pHGG), combined with molecular diagnostics. Throughout all case scenarios, 55-77% recommended (re-)irradiation, preferably local radiotherapy > 20 Gy. Most respondents would participate in clinical trials and use targeted therapy (79-99%), depending on molecular genetic findings (BRAF alterations: BRAF/MEK inhibitor, 64-88%; EGFR overexpression: anti-EGFR treatment, 46%; CDKN2A deletion: CDK inhibitor, 18%; SMARCB1 deletion: EZH2 inhibitor, 12%). 31-72% would administer chemotherapy (CCNU, 17%; PCV, 8%; temozolomide, 19%; oral etoposide/trofosfamide, 8%), and 20-69% proposed immunotherapy (checkpoint inhibitors, 30%; tumor vaccines, 16%). Depending on the individual case, respondents would also include bevacizumab (6-18%), HDAC inhibitors (4-15%), tumor-treating fields (1-26%), and intraventricular chemotherapy (4-24%)., Conclusion: In each case, experts would combine conventional multimodal treatment concepts, including re-irradiation, with targeted therapy based on molecular genetic findings. International cooperative trials combining a (chemo-)therapy backbone with targeted therapy approaches for defined subgroups may help to gain valid clinical data and improve treatment in pediatric patients with recurrent/progressing HGG., (© 2023. The Author(s).)

Purpose: In this study we report our 30-year experience in stereotactic radiosurgery (SRS) treatment of lung squamous cell carcinoma (LUSC) brain metastases (BMs). It will serve to provide detailed longitudinal outcomes and predictors of efficacy in treating LUSC-BMs with SRS., Method: We retrospectively reviewed 51 patients and 109 tumors treated with SRS at our center between 1993 and 2022. Patient demographics, PDL1 genotype, immunotherapy use and mortality cause were recorded. Radiological and clinical outcomes were followed at 1-3-month intervals post-SRS. Cox-regression analysis and Kaplan-Meier survival curves were performed in statistical analysis., Results: We included 37 male and 14 female patients (median age 62.7 years at BM diagnosis). Median overall survival (OS) time was 6.9 months, 6-month OS rate was 62.1%, and Karnofsky performance scale (KPS) was the only independent predictor. Median time for local control maintenance was 7.6 months, 6-month local control rate was 69.1%, with TKI as the only independent predictor. Median time to distant failure was 5.13 months, 6-month distant failure rate was 51.1%, and factors with significant impact included gender (p = 0.002), presence of extracranial metastases (p < 0.001), use of immunotherapy(p < 0.001), PDL1 genotype (p = 0.034), and total intracranial metastases number (p = 0.008). However, no definitive benefits of immunotherapy were identified in patients with higher PDL1 mutational tumors., Conclusion: In this study we defined the natural history of disease progression and outcomes in SRS-treated LUSC-BM patients. We also identified predictors of OS and tumor control among these patients. The findings of this study will serve as a guide when counseling these patients for SRS., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alternative splicing (AS) plays a major role in the generation of transcript diversity. In the heart, roles have been described for some AS variants, but the global impact and regulation of AS patterns are poorly understood. Here, we studied the AS profiles in heart disease, their relationship with heart development, and the regulatory mechanisms controlling AS dynamics in the mouse heart. We found that AS profiles characterized the different groups and that AS and gene expression changes affected independent genes and biological functions. Moreover, AS changes, specifically in heart disease, were associated with potential protein-protein interaction changes. While developmental transitions were mainly driven by the upregulation of MBNL1, AS changes in disease were driven by a complex regulatory network, where PTBP1 played a central role. Indeed, PTBP1 over-expression was sufficient to induce cardiac hypertrophy and diastolic dysfunction, potentially by perturbing AS patterns., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Maximizing tendency is a central decision-making concept that has increasingly drawn attention from the scientific community. It refers to individuals' predisposition to look for the best option instead of settling for something that merely passes an internal threshold of acceptability. Although this maximizing strategy intuitively increases individual benefits, it also has been linked to various negative outcomes, including decreased well-being and low life satisfaction, and it varies considerably across populations. However, the neuroanatomical characteristics underlying this heterogeneity remain poorly understood. To address this knowledge gap, a 13-item Maximization Scale and magnetic resonance imaging technique were respectively used in this study to estimate individual maximizing tendency and structural morphological information on a sample of healthy adults (n = 69). Furthermore, voxel-based morphometry (VBM) analysis was conducted to investigate the associations between gray matter volume (GMV) and maximizing tendency through univariate and multivariate pattern analysis (MVPA). Univariate analysis did not determine an association between maximizing tendency and whole-brain GMV; by contrast, MVPA revealed that maximizing tendency could be successfully predicted by the GMVs of the right inferior frontal gyrus (IFG), right insula, and right cerebellum. These findings suggest the critical role of the morphological characteristics of the cortical-subcortical circuitry in individuals' maximizing tendency., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The upper Mississippi River basin has been identified as the most significant contributor of excessive nutrients to the hypoxic zone in the Gulf of Mexico. The land-use changes from an internally drained prairie-wetland complex to an intensively managed corn-soybean production system drained by subsurface tile drainage system in the north-central Iowa and south-central Minnesota are the primary cause of nutrient loads into the Mississippi River and many other environmental stresses. The present study summarizes the water-quality degradation from land-use change and offers a fuzzy logic-based decision support for assessing degree of suitability of the four recommended perennial plant options for managing water and nitrate-nitrogen export. These options are designed based on landscape position that currently fails to produce high yielding row crops and scale: (1) marginal upland depressions for water storage by planting deep-rooted perennial grasses and fast-growing woody poplar, willow, and alder in poorly drained swales; (2) saturated buffers and/or subtle changes in landscape slope for draining high nitrate-nitrogen subsurface (through multi-species phytoremediation treatment buffers or strips of perennial vegetation); (3) two-stage ditches with linear floodplains planted with perennial grasses; and (4) riparian and in-channel ecologically engineered trees, shrubs, and grasses to better connect meander belt width to frequent peak stream flows at larger scales. When applied throughout a typical (Des Moines Lobe Till) DMLT watershed, each option can have positive cumulative environmental effects. Fuzzy logic enhanced the precision in watershed decision-making by incorporating the uncertainty associated with factors like cost effectiveness, nitrate reduction potential, water quality improvement, and level of acceptance., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Ionizing irradiation induces positive or negative changes in plant growth (M1) depending on the amount of irradiation applied to seeds or plant parts. The effect of 50-350 Gy gamma irradiation of kernels on nucleolar activity, as an indicator of metabolic activity, in root tip cells of tetraploid wheat Triticum turgidum ssp. durum L. cv. Orania (AABB) was investigated. The number of nucleoli present in nuclei and micronuclei as well as the mitotic index in the different irradiation dosages was used as an indicator of the cells entering mitosis, the chromosomes with nucleolar organizer regions that are active as well as chromosome doubling in the event of unsuccessful mitotic division. Nucleolar activity was investigated from 17.5 to 47.5 h after the onset of imbibition to study the first mitotic division and its consequences on the cells that were in G 2 and G 1 phases at the time of gamma irradiation. Untreated material produced a maximum of four nucleoli formed by the nucleolar organizing regions (NORs) on chromosomes 1B and 6B. In irradiated material, additional nucleoli were noted that are due to the activation of the NORs on chromosome 1A in micronuclei. The onset of mitosis was highly significantly retarded in comparison to the control due to checkpoints in the G 2 phase for the repairing of damaged DNA. This study is the first to report on the appearance of nucleoli in micronuclei as well as activation of NORs in the micronuclei that are inactive in the nucleus and the effect of chromosome doubling on nucleolar activity in the event of unsuccessful mitotic division., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Traumatic brain injury (TBI) is a neurological disorder which represents a major health issue worldwide. It causes mortality and disability among all group ages, caused by external force, sports-related events or violence and road traffic accidents. In the USA, approximately one-third people die annually due to injury and 1.7 million people suffer from traumatic brain injury. Every year in India around 1.6 million individuals suffer from sustain brain injury with 200,000 deaths and approximately one million person needed recovery treatment at any stage of time. Sports-related head impact and trauma has become an extremely controversial public health and medico-legal problem that accounts for 20% of all brain injury (including concussion). It is difficult to reverse the primary injury but the secondary injury can be minimized by using proper pharmacological intervention during the initial hours of injury. This article highlights the pathophysiology and types of TBI along with treatment therapies. Till date, there is no single medication that can decrease the progression of the disease so that symptomatic treatment is given to the patient by determining proper pathology. Recently various herbal medicine therapies and traditional supplements have been developed for TBI. Nutritional supplementation and nutraceuticals have exposed potential in the treatment of TBI when used before and after TBI. The compiled data will enable the readers to know the pathophysiology as well as the allopathic and natural remedies to treat the TBI., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The optimal second and subsequent lines of chemotherapy for patients with non-small cell lung cancer (NSCLC) who have preexisting interstitial lung disease (ILD) are unclear. Hence, we examined the clinical efficacy and safety of second-line chemotherapy in such patients, including any exacerbation of preexisting ILD., Methods: The medical records of patients with NSCLC and preexisting ILD who received both first- and second-line chemotherapy were retrospectively reviewed., Results: Twenty-four patients with a median age of 71 years who were treated between April 2013 and March 2021 were included. The response rate after second-line chemotherapy with S-1 (n = 13), docetaxel (n = 8), pemetrexed (n = 2), or docetaxel plus ramucirumab (n = 1) was 12.5%, with a median progression-free survival (2nd line PFS) of 3.8 months. The overall survival from a start of first-line chemotherapy (1 st line OS) and post-progression survival (PPS) post-first-line chemotherapy were 18.7 and 9.7 months, respectively. Spearman rank correlation and linear regression analyses showed that PPS was strongly correlated with 1st line OS (R = 0.85, P < 0.00001). Importantly, the 2nd line PFS was also significantly correlated with 1st line OS (R = 0.71, P = 0.0001). While second-line chemotherapy-related acute exacerbation of ILD was observed in 7 patients (29.2%), there were no treatment-related fatalities. Conslusions. Second-line chemotherapy has a strong positive impact on the OS of patients with NSCLC who have preexisting ILD. Given the findings of this study, second-line chemotherapy may be valuable in terms of prolonging long-term OS., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Heart failure (HF) following ischemic heart disease (IHD) remains a hard nut to crack and a leading cause of death worldwide. Cardiac regeneration aims to promote cardiomyocyte (CM) proliferation by transitioning the cell cycle state of CMs from arrest to re-entry. Protein posttranslational modifications (PTMs) have recently attracted extensive attention in the field of cardiac regeneration due to their reversibility and effects on the stability, activity, and subcellular localization of target proteins. The balance of PTMs is disrupted when neonatal CMs withdraw from the cell cycle, resulting in significant dysfunction of downstream substrate protein localization, expression, and activity, ultimately limiting the maintenance of cardiac regeneration ability. In this review, we summarize recent research concerning the role of PTMs in cardiac regeneration, while focusing on phosphorylation, acetylation, ubiquitination, glycosylation, methylation, and neddylation, and the effects of these modifications on CM proliferation, which may provide potential targets for future treatments for IHD., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In our previous study, a 3D structure of LNAA66 model protein containing 4-5 α-helices, high large neutral amino acids (LNAA) and lacking phenylalanine was designed, refined, expressed in Pichia pastoris and confirmed by Western blotting. Here the study is focused on the characterization of the expressed and purified recombinant LNAA66 protein. The results revealed that the expressed protein had 68.59% of LNAA enrichment, containing 41.6% of α-helix, 50.4% turns and 8% β-sheet, which are as per the in silico designed protein. The LC-ESI-MS/MS results confirmed the recombinant protein by identifying the first 30 N-terminal amino acids with a sequence coverage of ~ 29%. The protein was digested entirely into smaller molecular weight fragments when treated with digestive enzymes mimicking the human GI tract digestion, which indicated complete digestibility of the protein. These results suggest that the protein can be utilized for the envisioned application of dietary treatment for phenylketonuria., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

For a recirculating aquaculture system (RAS), a passive water treatment system was designed for efficient discharge nutrient removal and water reuse in RAS production. Denitrification in a woodchip bioreactor filled with birch wood (Betula pendula) followed by sand filtration was introduced into a side-loop of an experimental RAS rearing rainbow trout (Oncorhynchus mykiss). Denitrification efficiency remained high (96%) throughout the experiment and reached a nitrogen removal rate of 15 g NO 3 -N m -3 per day. Sand filtration was used to remove dissolved and particulate matter and improve water quality before being returned to water circulation. To ensure the absence of harmful substances in the system, heavy metals were quantified. Additionally, off-flavor-inducing compounds were quantified in the circulating water and in fish flesh. Significantly higher concentrations of geosmin (GSM) (p<0.05) were observed in the controls compared to side-looped systems, but a similar effect was not observed in the case of 2-methylisoborneol (MIB). Among heavy metals, concentrations of Co (30 μg L -1 ), Ni (40 μg L -1 ), and Pb (140 μg L -1 ) decreased to below 10 μg L -1 in the side-loop water after the start-up of the system. Only low concentrations of Cu (5-30 μg L -1 ) were found in the rearing tank water, in both the side-loop and controls. The results indicated that this type of process design is suitable for safely producing fish of high quality., (© 2021. The Author(s).)

Introduction: H3K27M-mutated diffuse midline gliomas (H3-DMGs) are aggressive tumors with a fatal outcome. This study integrating individual patient data (IPD) from published studies aimed to investigate the prognostic impact of different genetic alterations on survival of these patients., Methods: We accessed PubMed and Web of Science to search for relevant articles. Studies were included if they have available data of follow-up and additional molecular investigation of H3-DMGs. For survival analysis, Kaplan-Meier analysis and Cox regression models were utilized, and corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of genetic events on overall survival (OS)., Result: We included 30 studies with 669 H3-DMGs. TP53 mutations were the most common second alteration among these neoplasms. In univariate Cox regression model, TP53 mutation was an indicator of shortened survival (HR 1.446; 95% CI 1.143-1.829) whereas ACVR1 (HR 0.712; 95% CI 0.518-0.976) and FGFR1 mutations (HR 0.408; 95% CI 0.208-0.799) conferred prolonged survival. In addition, ATRX loss was also associated with a better OS (HR 0.620; 95% CI 0.386-0.996). Adjusted for age, gender, and tumor location, the presence of TP53 mutations, the absence of ACVR1 or FGFR1 mutations remained significantly poor prognostic factors., Conclusions: We outlined the prognostic importance of additional genetic alterations in H3-DMGs and recommended that these neoplasms should be further molecularly segregated. This may aid neuro-oncologists in appropriate risk stratification., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Wide-spread visualization methods which are computed tomography (CT) and magnetic resonance imaging (MRI) are not sensitive to mild traumatic brain injury (mTBI). However, mTBI may cause changes of cerebral microstructure that could be found using diffusion-tensor imaging. The aim of this study is to reveal the impact of acute mTBI (no more than 3 days after trauma) on diffusion parameters in corpus callosum, corticospinal tract, and thalamus in children (aged 14-18). Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were analyzed. Significant increase in FA and decrease in ADC were observed in thalamus. The trend to an increase in FA is observed in corpus callosum., (© 2020. Belgian Neurological Society.)

Immunotherapy has emerged as an unprecedented hope for the treatment of notoriously refractory cancers. Numerous investigational drugs and immunotherapy-including combination regimens are under preclinical and clinical investigation. However, only a small patient subpopulation across different types of cancer responds to the therapy due to the presence of several mechanisms of resistance. There have been extensive efforts to overcome this limitation and to expand the patient population that could be benefited by this state-of-the-art therapeutic modality. Among various causes of the resistance, we here focus on physical stromal barriers that impede the access of immunotherapeutic drug molecules and/or native and engineered immune cells to cancer tissues and cells. Two primary stromal barriers that contribute to the resistance include aberrant tumor vasculatures and excessive extracellular matrix build-ups that restrict extravasation and infiltration, respectively, of molecular and cellular immunotherapeutic agents into tumor tissues. Here, we review the features of these barriers that limit the efficacy of immunotherapy and discuss recent advances that could potentially help immunotherapy overcome the barriers and improve therapeutic outcomes., (© 2021. Controlled Release Society.)