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The spontaneous regression of cancer is the partial or complete remission of a tumor without treatment, and this has been linked to trauma and infection. The present case details the rare spontaneous regression of a triple negative Grade III ductal carcinoma in the breast. The findings suggest that in our case, this may have been triggered by biopsy and marker clip deployment, and it highlights the importance of being aware of this unusual occurrence so timely diagnosis can be made without causing undue anxiety in patients.

Background The use of so-called “red flags” may be beneficial in identifying patients with metastatic spinal disease. This study examined the utility and efficacy of these red flags in the referral chain of patients surgically treated for spinal metastases. Methods The referral chains from the onset of symptoms until surgical treatment for all patients receiving surgery for spinal metastases between March 2009 and December 2020 were reconstructed. The documentation of red flags, as defined by the Dutch National Guideline on Metastatic Spinal Disease, was assessed for each healthcare provider involved. Results A total of 389 patients were included in the study. On average, 33.3% of red flags were documented as present, 3.6% were documented as absent, and 63.1% were undocumented. A higher rate of red flags documented as present was associated with a longer time to diagnosis, but a shorter time to definitive treatment by a spine surgeon. Moreover, red flags were documented as present more often in patients who developed neurological symptoms at any point during the referral chain than those who remained neurologically intact. Conclusions The association of red flags with developing neurological deficits highlights their significance in clinical assessment. However, the presence of red flags was not found to decrease delays prior to referral to a spine surgeon, indicating that their relevance is currently not sufficiently recognized by healthcare providers. Raising awareness of symptoms indicative of spinal metastases may expedite timely (surgical) treatment and thus improve treatment outcome.

International audience; Metal complexes with a 3d6 electron count are emerging as an alternative to 4d6-based photosensitizers, emitters, or photoredox catalysts. In recent years several Fe(II) potential emitters have been proposed, based on strongly donating ligand sets. Those tend to facilitate oxidation to their 3d5 species, whose photophysics is based on low-lying ligand-to-metal charge transfer (LMCT) states. The geometry and electronic structure of 2LMCT states are unveiled in this work.

Chromoanagenesis is a single catastrophic event that involves, in most cases, localized chromosomal shattering and reorganization, resulting in a dramatically restructured chromosome. First discovered in cancer cells, it has since been observed in various other systems, including plants. In this review, we discuss the origin, characteristics, and potential mechanisms underlying chromoanagenesis in plants. We report that multiple processes, including mutagenesis and genetic engineering, can trigger chromoanagenesis via a variety of mechanisms such as micronucleation, breakage-fusion-bridge (BFB) cycles, or chain-like translocations. The resulting rearranged chromosomes can be preserved during subsequent plant growth, and sometimes inherited to the next generation. Because of their high tolerance to genome restructuring, plants offer a unique system for investigating the evolutionary consequences and potential practical applications of chromoanagenesis.

We present the results of our 14th horizon scan of issues we expect to influence biological conservation in the future. From an initial set of 102 topics, our global panel of 30 scientists and practitioners identified 15 issues we consider most urgent for societies worldwide to address. Issues are novel within biological conservation or represent a substantial positive or negative step change at global or regional scales. Issues such as submerged artificial light fisheries and accelerating upper ocean currents could have profound negative impacts on marine or coastal ecosystems. We also identified potentially positive technological advances, including energy production and storage, improved fertilisation methods, and expansion of biodegradable materials. If effectively managed, these technologies could realise future benefits for biological diversity.

International audience; Ruthenium(II) complexes feature prominently in the development of agents for photoactivated chemotherapy, however, the excited state mechanisms by which photochemical ligand release operate remain unclear. We report here a systematic experimental and computational study of a series of complexes [Ru(bpy)2(N^N)]2+ (bpy = 2,2'-bipyridyl; N^N = bpy (1), 6-methyl-2,2'-bipyridyl (2), 6,6'-dimethyl-2,2'-bipyridyl (3), 1-benzyl-4-(pyrid-2-yl)-1,2,3-triazole (4), 1-benzyl-4-(6-methylpyrid-2-yl)-1,2,3-triazole (5), 1,1'-dibenzyl-4,4'-bi-1,2,3-triazolyl (6)) in which we probe the contribution to the promotion of photochemical N^N ligand release of the introduction of sterically encumbering methyl substituents and the electronic effect of replacement of pyridine by 1,2,3-triazole donors in the N^N ligand. Complexes 2 to 6 all release the ligand N^N on irradiation in acetonitrile solution to yield cis-[Ru(bpy)2(NCMe)2]2+ with resultant photorelease quantum yields that at first seem counter-intuitive and span a broad range. The data show that incorporation of a single sterically encumbering methyl substituent on the N∧N ligand (2 and 5) leads to a significantly enhanced rate of triplet metal-to-ligand charge-transfer (3MLCT) state deactivation but with little promotion of photoreactivity, whereas replacement of pyridine by triazole donors (4 and 6) leads to a similar rate of 3MLCT deactivation but with much greater photochemical reactivity. The data reported here, discussed in conjunction with previously reported data on related complexes, suggest that monomethylation in 2 and 5 sterically inhibits the formation of a 3MCcis state but promotes the population of 3MCtrans states which rapidly deactivate 3MLCT states and are prone to mediating ground-state recovery. On the other hand, increased photochemical reactivity in 4 and 6 seems to stem from the accessibility of 3MCcis states. The data provide important insights into the excited-state mechanism of photochemical ligand release by Ru(II) tris-bidentate complexes.

Background Among neonates with hemolytic disease of the fetus and newborn (HDFN), we aimed to describe the frequency of central-line use, indications for insertion, and incidence of confirmed and suspected sepsis, including antibiotic treatment over a 10-year surveillance period. Study Design and Methods All neonates with HDFN admitted to our neonatal intensive care unit between January 2012 and December 2021 were included in this retrospective, cohort study. Annual proportions of infants with a central-line and central-line-associated bloodstream infection (CLABSI) rates (per 1000 central-line days and per 100 infants) were evaluated. Numbers of confirmed and suspected early- and late-onset sepsis episodes were assessed over the entire study period. Results Of the 260 included infants, 25 (9.6%) were evaluated for suspected sepsis, with 16 (6.2%) having >= 1 confirmed sepsis episode. A total of 123 central-lines were placed in 98 (37.7%) neonates, with impending exchange transfusion (ET) being the most frequent indication. Of the 34 (34.7%) neonates in whom a central-line was placed due to impending ET, 11 (32.4%) received no ET. Overall CLABSI incidence was 13.58 per 1000 central-line days. Neonates with a central-line had a higher risk for confirmed late-onset infection (RR 1.11, 95% CI: 1.04-1.20) and sepsis work-up (RR 1.10, 95% CI: 1.03-1.17) compared to infants without a central-line. Conclusions Sepsis incidence among neonates with HDFN remains high, in particular in those with a central-line. Considering the substantial proportion of neonates with a central-line without eventual ET, central-line placement should be delayed until the likelihood of ET is high.

Academic neurosurgeons with international medical training play a large role in the U.S. neurosurgical workforce. We aimed to compare U.S.-trained neurosurgeons with internationally trained neurosurgeons to reveal differences in subspecialty preferences and training opportunities abroad.We identified 1671 neurosurgeons from 115 Accreditation Council for Graduate Medical Education (ACGME)-accredited neurosurgical residency programs. Data on demographics, institution characteristics, and chosen subspecialty were collected, and faculty were divided based on location of training. Univariate analysis and multivariable logistic regression compared faculty characteristics between training locations.Compared with the U.S. medical school + U.S. residency group, the international medical graduate + U.S. residency group was more likely to subspecialize in oncology/skull base and vascular neurosurgery and complete a fellowship in the United States or internationally (P0.05). The international medical graduate + international residency group was more likely to subspecialize in oncology/skull base neurosurgery, more likely to complete an international fellowship, and less likely to practice general neurosurgery (P0.05). Neurosurgeons in pediatrics, radiosurgery, and vascular subspecialties were more likely to receive fellowship training in any location (P 0.05). Additionally, functional neurosurgeons were more likely to complete fellowships internationally, spinal neurosurgeons were less likely to pursue international fellowships, and peripheral nerve neurosurgeons were more likely to have dual fellowship training in both the United States and abroad (P0.05).International medical training affected subspecialty choice and fellowship training. Internationally trained neurosurgeons more often specialized in oncology and vascular neurosurgery. Functional neurosurgeons were more likely to complete international fellowships, spine neurosurgeons were less likely to complete international fellowships, and peripheral nerve neurosurgeons more often had both U.S. and international fellowships.

BACKGROUND Endometriosis remains a poorly understood disease, despite its high prevalence and debilitating symptoms. The overlap in symptoms and the increased risk of multiple other traits in women with endometriosis is becoming increasingly apparent through epidemiological data. Genetic studies offer a method of investigating these comorbid relationships through the assessment of causal relationships with Mendelian randomization (MR), as well as identification of shared genetic variants and genes involved across traits. This has the capacity to identify risk factors for endometriosis as well as provide insight into the aetiology of disease. OBJECTIVE AND RATIONALE We aim to review the current literature assessing the relationship between endometriosis and other traits using genomic data, primarily through the methods of MR and genetic correlation. We critically examine the limitations of these studies in accordance with the assumptions of the utilized methods. SEARCH METHODS The PubMed database was used to search for peer-reviewed original research articles using the terms ‘Mendelian randomization endometriosis’ and ‘“genetic correlation” endometriosis’. Additionally, a Google Scholar search using the terms ‘“endometriosis” “mendelian randomization” “genetic correlation”’ was performed. All relevant publications (n = 21) published up until 7 October 2022 were included in this review. Upon compilation of all traits with published MR and/or genetic correlation with endometriosis, additional epidemiological and genetic information on their comorbidity with endometriosis was sourced by searching for the trait in conjunction with ‘endometriosis’ on Google Scholar. OUTCOMES The association between endometriosis and multiple pain, gynaecological, cancer, inflammatory, gastrointestinal, psychological, and anthropometric traits has been assessed using MR analysis and genetic correlation analysis. Genetic correlation analyses provide evidence that genetic factors contributing to endometriosis are shared with multiple traits: migraine, uterine fibroids, subtypes of ovarian cancer, melanoma, asthma, gastro-oesophageal reflux disease, gastritis/duodenitis, and depression, suggesting the involvement of multiple biological mechanisms in endometriosis. The assessment of causality with MR has revealed several potential causes (e.g. depression) and outcomes (e.g. ovarian cancer and uterine fibroids) of a genetic predisposition to endometriosis; however, interpretation of these results requires consideration of potential violations of the MR assumptions. WIDER IMPLICATIONS Genomic studies have demonstrated that there is a molecular basis for the co-occurrence of endometriosis with other traits. Dissection of this overlap has identified shared genes and pathways, which provide insight into the biology of endometriosis. Thoughtful MR studies are necessary to ascertain causality of the comorbidities of endometriosis. Given the significant diagnostic delay of endometriosis of 7–11 years, determining risk factors is necessary to aid diagnosis and reduce the disease burden. Identification of traits for which endometriosis is a risk factor is important for holistic treatment and counselling of the patient. The use of genomic data to disentangle the overlap of endometriosis with other traits has provided insights into the aetiology of endometriosis.

The pituitary adenylate cyclase-activating polypeptide (PACAP) system is implicated in posttraumatic stress disorder (PTSD) and related amygdala-mediated arousal and threat reactivity. PTSD is characterized by increased amygdala reactivity to threat and, more recently, aberrant intrinsic connectivity of the amygdala with large-scale resting state networks, specifically the default mode network (DMN). While the influence of PACAP on amygdala reactivity has been described, its association with intrinsic amygdala connectivity remains unknown. To fill this gap, we examined functional connectivity of resting-state functional magnetic resonance imaging (fMRI) in eighty-nine trauma-exposed adults (69 female) screened for PTSD symptoms to examine the association between blood-borne (circulating) PACAP levels and amygdala-DMN connectivity. Higher circulating PACAP levels were associated with increased amygdala connectivity with posterior DMN regions, including the posterior cingulate cortex/precuneus (PCC/Precun) and left angular gyrus (lANG). Consistent with prior work, this effect was seen in female, but not male, participants and the centromedial, but not basolateral, subregions of the amygdala. Clinical association analyses linked amygdala-PCC/Precun connectivity to anxious arousal symptoms, specifically exaggerated startle response. Taken together, our findings converge with previously demonstrated effects of PACAP on amygdala activity in PTSD-related processes and offer novel evidence for an association between PACAP and intrinsic amygdala connectivity patterns in PTSD. Moreover, these data provide preliminary evidence to motivate future work ascertaining the sex- and subregion-specificity of these effects. Such findings may enable novel mechanistic insights into neural circuit dysfunction in PTSD and how the PACAP system confers risk through a disruption of intrinsic resting-state network dynamics.

Although the role of RNA binding proteins (RBPs) in extracellular RNA (exRNA) biology is well established, their exRNA cargo and distribution across biofluids are largely unknown. To address this gap, we extend the exRNA Atlas resource by mapping exRNAs carried by extracellular RBPs (exRBPs). This map was developed through an integrative analysis of ENCODE enhanced crosslinking and immunoprecipitation (eCLIP) data (150 RBPs) and human exRNA profiles (6,930 samples). Computational analysis and experimental validation identified exRBPs in plasma, serum, saliva, urine, cerebrospinal fluid, and cell-culture-conditioned medium. exRBPs carry exRNA transcripts from small non-coding RNA biotypes, including microRNA (miRNA), piRNA, tRNA, small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), Y RNA, and lncRNA, as well as protein-coding mRNA fragments. Computational deconvolution of exRBP RNA cargo reveals associations of exRBPs with extracellular vesicles, lipoproteins, and ribonucleoproteins across human biofluids. Overall, we mapped the distribution of exRBPs across human biofluids, presenting a resource for the community.

Chromatin is the physical substrate of the genome that carries the DNA sequence and ensures its proper functions and regulation in the cell nucleus. While a lot is known about the dynamics of chromatin during programmed cellular processes such as development, the role of chromatin in experience-dependent functions remains not well defined. Accumulating evidence suggests that in brain cells, environmental stimuli can trigger long-lasting changes in chromatin structure and tri-dimensional (3D) organization that can influence future transcriptional programs. This review describes recent findings suggesting that chromatin plays an important role in cellular memory, particularly in the maintenance of traces of prior activity in the brain. Inspired by findings in immune and epithelial cells, we discuss the underlying mechanisms and the implications for experience-dependent transcriptional regulation in health and disease. We conclude by presenting a holistic view of chromatin as potential molecular substrate for the integration and assimilation of environmental information that may constitute a conceptual basis for future research., Translational Psychiatry, 13 (1), ISSN:2158-3188

Sex as a variable of survival

One-way ANOVA analysis comparing expression of cytokines between Avelumab treated and Avelumab combined with Bevacizumab

Table S2. Key Antibodies Resource

Chromogenic multiplex expression analysis of different biomarkers in formalin-fixed paraffin-embedded tissue of a patient's tumor when diagnosed with glioblastoma (34369), before treated with LITT (34370) and after treatment with LITT and avelumab (34371) and quantitative analysis using Halo® Image Analysis Platform.

Table S1. Representativeness of Study Participants

Tumor molecular characteristics

Chromogenic multiplex expression analysis of different biomarkers in formalin-fixed paraffin-embedded tissue of 34364, 34368, 34369, 34370, and 34371 tumors and quantitative analysis using Halo® Image Analysis Platform

Purpose:The treatment of glioblastoma (GBM) poses challenges. The use of immune checkpoint inhibition (ICI) has been disappointing as GBM is characterized by low mutational burden and low T-cell infiltration. The combination of ICI with other treatment modalities may improve efficacy.Patient and Methods:Patients with recurrent GBM were treated with avelumab, a human IgG1 antibody directed against PD-L1 (part A), or avelumab within a week after laser interstitial thermal therapy (LITT) and continuation of avelumab (part B). Bevacizumab was allowed to be combined with ICI to spare steroid use. The primary objective was to characterize the tolerability and safety of the regimens. The secondary objectives included overall survival, progression-free survival (PFS), signatures of plasma analytes, and immune cells.Results:A total of 12 patients (median age 64; range, 37–73) enrolled, five in part A and seven in part B. Two serious adverse events occurred in the same patient, LITT treated, not leading to death. The median survival from enrollment was 13 months [95% confidence interval (CI), 4–16 months] with no differences for part A or B. The median PFS was 3 months (95% CI, 1.5–4.5 months). The decrease in MICA/MICB, γδT cells, and CD4+ T cell EMRA correlated with prolonged survival.Conclusions:Avelumab was generally well tolerated. Adding bevacizumab to ICI may be beneficial by lowering cytokine and immune cell expression. The development of this combinatorial treatment warrants further investigation. Exploring the modulation of adaptive and innate immune cells and plasma analytes as biomarker signatures may instruct future studies in this dismal refractory disease.Significance:Our phase I of PD-L1 inhibition combined with LITT and using bevacizumab to spare steroids had a good safety profile for recurrent GBM. Developing combinatory treatment may help outcomes. In addition, we found significant immune modulation of cytokines and immune cells by bevacizumab, which may enhance the effect of ICI.

Supplementary Slide 3 from Disruption of the Y-Box Binding Protein-1 Results in Suppression of the Epidermal Growth Factor Receptor and HER-2

Supplementary Figure 1 from Disruption of the Y-Box Binding Protein-1 Results in Suppression of the Epidermal Growth Factor Receptor and HER-2

The overexpression of the epidermal growth factor receptor (EGFR) and HER-2 underpin the growth of aggressive breast cancer; still, it is unclear what governs the regulation of these receptors. Our laboratories recently determined that the Y-box binding protein-1 (YB-1), an oncogenic transcription/translation factor, induced breast tumor cell growth in monolayer and in soft agar. Importantly, mutating YB-1 at Ser102, which resides in the DNA-binding domain, prevented growth induction. We reasoned that the underlying cause for growth attenuation by YB-1(Ser102) is through the regulation of EGFR and/or HER-2. The initial link between YB-1 and these receptors was sought by screening primary tumor tissue microarrays. We determined that YB-1 (n = 389 cases) was positively associated with EGFR (P < 0.001, r = 0.213), HER-2 (P = 0.008, r = 0.157), and Ki67 (P < 0.0002, r = 0.219). It was inversely linked to the estrogen receptor (P < 0.001, r = −0.291). Overexpression of YB-1 in a breast cancer cell line increased HER-2 and EGFR. Alternatively, mutation of YB-1 at Ser102 > Ala102 prevented the induction of these receptors and rendered the cells less responsive to EGF. The mutant YB-1 protein was also unable to optimally bind to the EGFR and HER-2 promoters based on chromatin immunoprecipitation. Furthermore, knocking down YB-1 with small interfering RNA suppressed the expression of EGFR and HER-2. This was coupled with a decrease in tumor cell growth. In conclusion, YB-1(Ser102) is a point of molecular vulnerability for maintaining the expression of EGFR and HER-2. Targeting YB-1 or more specifically YB-1(Ser102) are novel approaches to inhibiting the expression of these receptors to ultimately suppress tumor cell growth. (Cancer Res 2006; 66(9): 4872-9)

Supplementary Methods and Materials, Figures 1-6 from Y-Box Binding Protein-1 Induces the Expression of CD44 and CD49f Leading to Enhanced Self-Renewal, Mammosphere Growth, and Drug Resistance

Sertoli cells are somatic cells that are in close contact with germ cells in the mammalian testes. They have multiple functions and fulfill key roles for the development and proper maturation of spermatogenic cells into functional spermatozoa. One of their most important properties is to release trophic factors and supply nutrients to germ cells. But they are also involved in the regulation of the immune system in testis, and provide an immunologically privileged environment for developing germ cells. Because they are so essential for reproductive cells, their alterations can have detrimental consequences for fertility. Many environmental factors and exposures such as high caloric diet, toxins, and pollutants are thought to compromise Sertoli cells physiology. This review describes the discovery of Sertoli cells and the methods used for their study, summarizes their major properties and functions, and describes their dysfunctions in pathologies, particularly associated with environmental stressors., Andrology, 11 (5), ISSN:2047-2919, ISSN:2047-2927

Chromoanagenesis is a catastrophic event that involves localized chromosomal shattering and reorganization. In this study, we report a case of chromoanagenesis resulting from defective meiosis in the MEIOTIC ASYNAPTIC MUTANT 1 (asy1) background in Arabidopsis thaliana. We provide a detailed characterization of the genomic structure of this individual with a severely shattered segment of chromosome 1. We identified 260 novel DNA junctions in the affected region, most of which affect gene sequence on 1 or both sides of the junction. Our results confirm that asy1-related defective meiosis is a potential trigger for chromoanagenesis. This is the first example of chromoanagenesis associated with female meiosis and indicates the potential for genome evolution during oogenesis. Chromoanagenesis is a complex and catastrophic event that results in severely restructured chromosomes. It has been identified in cancer cells and in some plant samples, after specific triggering events. Here, we identified this kind of genome restructuring in a mutant that exhibits defective meiosis in the model plant system Arabidopsis thaliana.

This Marine and Coastal Horizon Scan was funded by Oceankind. S.N.R.B. is supported by EcoStar (DM048) and Cefas (My time). R.C. acknowledges FCT/MCTES for the financial support to CESAM (UIDP/50017/2020, UIDB/50017/2020, LA/P/0094/2020) through national funds. O.D. is supported by CSIC Uruguay and Inter-American Institute for Global Change Research. J.E.H.-R. is supported by the Whitten Lectureship in Marine Biology. S.A.K. is supported by a Natural Environment Research Council grant (NE/S00050X/1). P.I.M. is supported by an Australian Research Council Discovery Grant (DP200100575). D.M.P. is supported by the Marine Alliance for Science and Technology for Scotland (MASTS). A.R.P. is supported by the Inter-American Institute for Global Change Research. W.J.S. is funded by Arcadia. A.T. is supported by Oceankind. M.Y. is supported by the Deep Ocean Stewardship Initiative and bioDISCOVERY. The biodiversity of marine and coastal habitats is experiencing unprecedented change. While there are well-known drivers of these changes, such as overexploitation, climate change and pollution, there are also relatively unknown emerging issues that are poorly understood or recognized that have potentially positive or negative impacts on marine and coastal ecosystems. In this inaugural Marine and Coastal Horizon Scan, we brought together 30 scientists, policymakers and practitioners with transdisciplinary expertise in marine and coastal systems to identify new issues that are likely to have a significant impact on the functioning and conservation of marine and coastal biodiversity over the next 5–10 years. Based on a modified Delphi voting process, the final 15 issues presented were distilled from a list of 75 submitted by participants at the start of the process. These issues are grouped into three categories: ecosystem impacts, for example the impact of wildfires and the effect of poleward migration on equatorial biodiversity; resource exploitation, including an increase in the trade of fish swim bladders and increased exploitation of marine collagens; and new technologies, such as soft robotics and new biodegradable products. Our early identification of these issues and their potential impacts on marine and coastal biodiversity will support scientists, conservationists, resource managers and policymakers to address the challenges facing marine ecosystems. Postprint

Cardiorespiratory fitness (CRF) has recently been recognized as a risk factor for mortality, but it is not routinely measured in clinical settings. The purpose of this study was to assess a nonexercise method to estimate CRF (eCRF) and its association with mortality in a clinically referred population.A symptom tool, termed the Veterans Specific Activity Questionnaire (VSAQ), and nonexercise clinical variables were obtained from 1545 clinically referred subjects (60 ± 13 yr), and followed for a mean of 5.6 ± 4.2 yr. The VSAQ along with nonexercise clinical and historical variables was used to develop a multivariate model to predict achieved CRF from maximal exercise testing. Proportional hazards analysis was used to assess the association between measured and eCRF and all-cause mortality.The eCRF model was significantly associated with achieved CRF (multiple R = 0.67, P.001). Mean achieved CRF from maximal treadmill testing and eCRF were similar (8.6 ± 5.0 metabolic equivalents [METs] vs 8.7 ± 4.7 METs respectively, P = .27). Achieved CRF and eCRF performed similarly for predicting mortality. After full adjustment, each 1 MET higher increment in achieved CRF and eCRF was associated with 19% and 26% reductions in mortality risk, respectively. Compared with the lowest fit group (5 METs), the highest CRF groups (11 METs) had 88% and 87% lower risks for mortality for achieved CRF and eCRF, respectively.A multivariable nonexercise model featuring a symptom questionnaire combined with clinical variables that are readily available during a typical clinical encounter had a reasonably strong association with achieved CRF and exhibited prognostic characteristics that were similar to achieved CRF.

The Institute of Medicine best practice recommendation to review guidelines every 5 years is followed by the Congress of Neurological Surgeons Guidelines Committee. The aim of this work was to provide an updated literature review and evidence-based recommendations on the topic of diagnosis and treatment of patients with progressive glioblastoma (pGBM).To review the literature published since the last guidelines on pGBM dated 2014, with literature search ending in June 2012.PubMed, Embase, and Cochrane were searched for the period July 1, 2012, to March 31, 2019, using search terms and search strategies to identify pertinent abstracts. These were then screened using published exclusion/inclusion criteria to identify full-text review articles. Evidence tables were constructed using data derived from full-text reviews and recommendations made from the evidence derived.From the total 8786 abstracts identified by the search, 237 full-text articles met inclusion/exclusion criteria and were included in this update. Two new level II recommendations derived from this work. For the diagnosis of patients with GBM, the use of diffusion-weighted images is recommended to be included in the magnetic resonance images with and without contrast used for surveillance to detect pGBM. For the treatment of patients with pGBM, repeat cytoreductive surgery is recommended to improve overall survival. An additional 21 level III recommendations were provided.Recent published literature provides new recommendations for the diagnosis and treatment of pGBM. The Central Nervous System Guidelines Committee will continue to pursue timely updates to further improve the care of patients with diagnosis.https://www.cns.org/guidelines/browse-guidelines-detail/guidelines-management-of-progressive-glioblastoma.

Adolescents experiencing anxiety or depression exhibit cognitive biases favoring the processing of negative emotional information. It remains unknown whether common neurobiological processes underlie these biases across anxiety and depression. Here, brain imaging was acquired from typical, anxious, and depressed adolescents during an emotional-interference task. Functional connectivity patterns were assessed while adolescents were cued to attend to or ignore faces. Results revealed a shared dimension of anxious and depressive symptoms was associated with reduced changes in connectivity patterns between conditions in which adolescents needed to ignore or attend to fearful faces. These findings were exclusive to fearful faces and observed only for functional connections with a primary face-representation area (fusiform gyrus). Results suggested a failure to flexibly adapt communication patterns with sensory-representation areas in the presence of negative emotional information, which may reflect a common neurobiological mechanism explaining biases favoring such information shared among adolescent anxiety and depression.

Growing national concern about the increase in Black youth's suicide rates has led to calls for closer examinations of disparities in young people's mental health outcomes and their underlying causes, including differences in access to healthcare and willingness to use mental health services, and systemic inequities. The present research brief answers this call through a critical analysis of racial discrimination and other adverse mechanisms that perpetuate negative mental health outcomes for Black youth. Our approach draws from principles of developmental psychology and intersectional theory. We begin by arguing for a biopsychosocial consideration of the effects of discrimination on Black youth's development. Then, we review the multilevel impact of racism on mental health outcomes. Although examining global patterns for Black youth as a group has value, our paper will instead focus on within-group differences and the intersecting social factors that shape them. Finally, we end with research-based proposals for policies that prioritize Black youth's well-being.

Target populationThese recommendations apply to adult patients diagnosed with progressive glioblastoma (pGBM).Question (Q1):In adult patients with pGBM does the use of temozolomide (TMZ) with alternative dosing or the use of TMZ in combination with other cytotoxic treatments result in increased overall survival compared to other chemotherapy?Recommendation:Level III: Adult patients with pGBM might derive benefit in treatment with TMZ especially those who progress after more than 5 months of TMZ-treatment free interval. Level III: Combination of TMZ with other cytotoxic agents such as nitrosourea, cisplatin, electrohypothermia, or tamoxifen is not suggested in adult patients with pGBM as a stand-alone therapy.There is insufficient data to make a recommendation about which alternative TMZ dosing provides the best benefits.Question (Q2):In adult patients with pGBM does the use of systemic or in situ nitrosourea result in increased overall survival compared to other chemotherapy?Recommendation:Level III: In the setting of pGBM, fotemustine is suggested in elderly patients with methylated MGMT promoter status. There is insufficient evidence to compare fotemustine to other nitrosoureas. There is insufficient evidence to make a suggestion about the use of in situ nitrosourea in patients with pGBM who underwent the Stupp regimen.Question (Q3):In adult patients with pGBM does the use of platinum compounds and topoisomerase result in increased survival compared to other chemotherapy?Recommendation:Level III: Other chemotherapy including platinum compounds and topoisomerase inhibitors are not suggested to be used in adult patients with pGBM.Level III: Other cytotoxic therapies like perillyl acohol and ketogenic diet are not suggested for use in adult patients with pGBM as a stand-alone therapy.Question (Q4):In adult patients with pGBM does the use of tumor treating field (TTF) result in increased overall survival compared to chemotherapy?Recommendation:Level III: The use of TTF with other chemotherapy may be considered when treating adult patients with pGBM.There is insufficient evidence to recommend TTF to increase overall survival in adult patients with pGBM.Question (Q5):In adult patients with pGBM does the use of oncolytic virotherapy result in increased survival compared to chemotherapy?Recommendation:Level III: Oncolytic virotherapy is not suggested in patients with pGBM.

A simple and fast aqueous synthesis of silver selenide quantum dots is proposed with the aid of multivariate optimization.

Cholesterol synthesis is both energy- and oxygen-intensive, yet relatively little is known of the regulatory effects of hypoxia on pathway enzymes. We previously showed that the rate-limiting and first oxygen-dependent enzyme of the committed cholesterol synthesis pathway, squalene monooxygenase (SM), can undergo partial proteasomal degradation that renders it constitutively active. Here, we show hypoxia is a physiological trigger for this truncation, which occurs through a two-part mechanism: (1) increased targeting of SM to the proteasome via stabilization of the E3 ubiquitin ligase MARCHF6 and (2) accumulation of the SM substrate, squalene, which impedes the complete degradation of SM and liberates its truncated form. This preserves SM activity and downstream pathway flux during hypoxia. These results uncover a feedforward mechanism that allows SM to accommodate fluctuating substrate levels and may contribute to its widely reported oncogenic properties.