tbuckley/cabot-search huggingface dataset:
Building resilience through family planning and climate adaptation finance: systematic review and opportunity analysis
Authors: Kristen P Patterson, Kathleen Mogelgaard, Charles Kabiswa, Raymond Ruyoka
Journal: The Lancet Planetary Health (2019)

BackgroundClimate change adaptation is on the forefront of the global agenda, and momentum for international financing for climate change adaptation projects is growing. This growth provides an opportunity to engage with adaptation decision makers and processes to include women's empowerment as part of multisectoral climate adaptation projects.MethodsA growing evidence base links women's met needs for family planning with reduced human vulnerability to climate change and enhanced resilience in the face of climate change impacts. Yet, population and family planning have been largely left out of adaptation proposals and projects. Through key informant interviews, a literature review, and research, the Population Reference Bureau identified how to promote the inclusion of family planning in climate adaptation strategies in ways that build resilience, improve health, and enhance women's economic empowerment.FindingsWays to integrate family planning into climate adaptation strategies included drawing the connections to and building the evidence base for including family planning in multisectoral adaptation approaches; reaching out to a country's designated authority to identify main climate change adaptation decision makers and develop an understanding of how adaptation finance flows; engaging in a country's National Adaptation Plan process to connect with stakeholders and identify country-driven adaptation priorities; and considering partnering with others in developing multisectoral proposals that include family planning and help to implement those proposals.InterpretationThe best opportunity for funding family planning and reproductive health within adaptation projects is to integrate women's empowerment—including family planning—within multisectoral proposals. The research includes an example of how to apply these key strategies, showing how the women's empowerment community could seize opportunities created by the importance of adapting to climate change and the growing availability of international climate financing to strengthen prospects for including women's health in climate adaptation projects. The Ecological Christian Organization of Uganda and Reproductive Health Uganda are following the Population Reference Bureau's research with a country-level strategy to advocate for the adoption of a multisectoral approach to climate adaptation in Uganda.FundingUnited States Agency for International Development (USAID).
Use of DNA copy number analysis of grade 2-4 gliomas to reveal differences in molecular ontogeny associated with IDH mutation status.
Authors: Mariko Sato, Kenneth D. Aldape, Clinton C Mason, Kristin Diefes, Lindsey Heathcock, Lisa Abegglen, Joshua David Schiffman, Howard Colman
Journal: Journal of Clinical Oncology (2013)

2026 Background: The genetic alterations of glioma have been studied extensively. IDH1 mutation is associated with younger age and better survival. However, differences in molecular ontogeny within glioma related to IDH1 mutation remain unknown. Here we describe a detailed analysis of copy number alterations (CNA) between IDH1 mut vs IDH1 wt gliomas of grade 2-3 and 4. Methods: CNA were detected by molecular inversion probes (Affymetrix) and analyzed with Nexus Copy Number Software (BioDiscovery). DNA was extracted from 94 patient FFPE samples including grade 2-3: IDH1 wt (n = 17) and IDH1 mut (n = 28), and grade IV: IDH1 wt ( n = 25) and IDH1 mut (n = 24). Chromothripsis was detected using a stringent criteria of at least ten switches of CNA in individual chromosomes. Results: We validated prior findings that IDH1 wt GBM have higher frequency of Chr7 amplification (including EGFR) and loss of Chr10 (including PTEN). Other CNA across all grades were: gain of 19q12 and loss of 14q11 in IDH1 wt , and gain of 11q21, 10p11, 8q21 and loss of 11p15, 19q13 in IDH1 mut . Within grade 2-3 samples, few CNA were associated with mutation status: 2-3 wt demonstrated higher frequencies of gain of 7q and loss of 10q, 14q11, and 22q13, while 2-3 mut demonstrated higher frequencies of 11q21 gain and 19q13 loss. Grade 4 tumors demonstrated more CNA that differed by mutation status, with 4 wt tumors demonstrating gain of 7 and loss of 10 and 14q11, while 4 mut demonstrated gains of 8q, 10p, 12p13, 1q23, and loss of 11p15, 3p, 19q13, among others. Comparison of grade 2-3 mut vs grade 4 mut tumors demonstrated larger number of CNA in the grade 4 mut tumors including gain of 1p, 14q, 13q33, 9p, 8q and loss of 22q, 11p15, 10q, and 3p, among others. A significantly higher incidence of chromothripsis events was observed in grade 4 mut compared to grade 4 wt (p = 0.0374). Conclusions: CNA analysis showed significant differences in molecular ontogeny between IDH1 wt and IDH1 mut , some of which may further elucidate pathogenesis. Significant CNA increases and increased chromthripsis in grade 4 mut support malignant transformation of low grade gliomas through accumulation of genomic instability and genomic catastrophe.
Detection of Various Microplastics in Human Stool
Authors: Philipp Schwabl, Sebastian Köppel, Philipp Königshofer, Theresa Bucsics, Michael Trauner, Thomas Reiberger, Bettina Liebmann
Journal: Annals of Internal Medicine (2019)

Microplastics are ubiquitous in natural environments. Ingestion of microplastics has been described in marine organisms, whereby particles may enter the food chain.To examine human feces for the presence of microplastics to determine whether humans involuntarily ingest them.Prospective case series in which participants completed a food diary and sampled stool according to step-by-step instructions.Europe and Asia.Eight healthy volunteers aged 33 to 65 years.After chemical digestion, Fourier-transform infrared microspectroscopy was used to analyze the presence and shape of 10 common types of microplastic in stool samples.All 8 stool samples tested positive for microplastics. A median of 20 microplastics (50 to 500 µm in size) per 10 g of human stool were identified. Overall, 9 plastic types were detected, with polypropylene and polyethylene terephthalate being the most abundant.There were few participants, and each provided only 1 sample. The origin and fate of microplastics in the gastrointestinal tract were not investigated.Various microplastics were detected in human stool, suggesting inadvertent ingestion from different sources. Further research on the extent of microplastic intake and the potential effect on human health is needed.None.
Type I IFN protects cancer cells from CD8+ T cell–mediated cytotoxicity after radiation
Authors: Jianzhou Chen, Yunhong Cao, Bostjan Markelc, Jakob Kaeppler, Jenny A.F. Vermeer, Ruth J. Muschel
Journal: Journal of Clinical Investigation (2019)

Treatment of tumors with ionizing radiation stimulates an antitumor immune response partly dependent on induction of IFNs. These IFNs directly enhance dendritic cell and CD8+ T cell activity. Here we show that resistance to an effective antitumor immune response is also a result of IFN signaling in a different cellular compartment of the tumor, the cancer cells themselves. We abolished type I IFN signaling in cancer cells by genetic elimination of its receptor, IFNAR1. Pronounced immune responses were provoked after ionizing radiation of tumors from 4 mouse cancer cell lines with Ifnar1 knockout. This enhanced response depended on CD8+ T cells and was mediated by enhanced susceptibility to T cell-mediated killing. Induction of Serpinb9 proved to be the mechanism underlying control of susceptibility to T cell killing after radiation. Ifnar1-deficient tumors had an augmented response to anti-PD-L1 immunotherapy with or without radiation. We conclude that type I IFN can protect cancer cells from T cell-mediated cytotoxicity through regulation of Serpinb9. This result helps explain why radiation of tumors can stimulate antitumor immunity yet also result in resistance. It further suggests potential targets for intervention to improve therapy and to predict responses.
Regulating Decisions for Incapacitated Pregnant Women—Reply
Authors: Erin S. DeMartino, Cavan K. Doyle, Paul S. Mueller
Journal: JAMA (2019)

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P14.23 Risk of venous thromboembolism (VTE) in grade II-IV gliomas as a function of molecular subtype
Authors: M Diaz, J Jo, D Schiff
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND VTE affects up to 30% of patients with glioblastoma (GBM, WHO grade IV), but little is known about its incidence in lower-grade gliomas (LGG, WHO grade II-III). It has been suggested that isocitrate dehydrogenase (IDH) mutation status dramatically decreases the incidence of VTE in glioma patients, through a combination of F3 promoter hypermethylation leading to lower expression of the procoagulant protein tissue factor, and an increased production of D-2-hydroxyglutarate, which has anticoagulant properties (Unruh et al, 2016). Our objective was to determine the incidence of VTE in LGG and stratify VTE risk by molecular subtype in gliomas grade II-IV. MATERIAL AND METHODS We performed a retrospective analysis of 590 glioma patients with molecular testing seen at our institution (UVa) from January 2005 to August 2017. We divided LGG patients into 3 groups: IDH-wildtype (IDHwt); IDH-mutant (IDHmt), 1p/19q-codeleted; and IDHmt, 1p/19q-intact. GBM patients were divided according to MGMT methylation status. Estimates of cumulative incidence of VTE were calculated with death as competing risk, and significance testing was determined using the Fine and Gray model. RESULTS Of 256 LGG patients (147 grade II and 109 grade III), 81 were IDHwt, 113 IDHmt and 1p/19q-codeleted, and 62 IDHmt and 1p/19q-intact. There were 334 GBM patients, with MGMT methylation status available in 263 (98 (37%) methylated and 165 (63%) unmethylated). With a median follow-up of 545 days, the overall incidence of VTE was 8.2% for grade II, 9.2% for grade III and 30.5% for grade IV. The 6-, 12- and 24-month VTE incidence was 4.1%, 4.8% and 5.4% respectively for grade II, 4.6%, 7.3% and 9.2% for grade III and 23.1%, 26.6% and 29% for grade IV. In LGG patients, VTE incidence was slightly higher in IDHwt tumors (11.1%) vs IDHmt, 1p/19q-codeleted (8.8%) and IDHmt, 1p/19q-intact tumors (4.8%). However, this difference was not statistically significant (IDHwt vs IDHmt, 1p/19q-codeleted, sub-distribution hazard ratio (SHR)=1.67, 95% CI=0.59–4.72; IDHwt vs IDHmt, 1p/19q-intact, SHR=1.87, 95% CI=0.54–6.53). In GBM patients, there was no difference in the VTE incidence according to MGMT methylation status (SHR=0.99, 95% CI=0.64–1.54). CONCLUSION In our cohort, the risk of VTE in GBM patients was consistent with historical data; patients with LGG also had a higher VTE risk compared to the general population. In contrast to other retrospective studies in which the incidence of VTE for grade II-IV IDHmt gliomas was 0% (Unruh et al, 2016; Nazari et al, 2018), our data suggest that VTEs do occur in IDHmt LGG patients, although at a lower rate than in IDHwt. MGMT methylation does not seem to influence the incidence of VTE. VTE risk stratification in GBM patients based on IDH mutation is forthcoming.
P14.31 CMV reactivation in a cohort of newly-diagnosed glioblastoma patients treated with temozolomide chemoradiotherapy. A single center analysis
Authors: R URSU, J Doridam, E Chaugne, H Zannou, C Belin, S Cuzzubbo, L Sirven-Villaros, S Brichler, C Levy-Piedbois, A Carpentier
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND The Cytomegalovirus (CMV) is a ubiquitous herpes virus which infects 60–80 % of the population in Europe. Although the CMV usually remains latent, reactivation can occur in the context of an immunodepression, such as low CD4-lymphocyte levels in HIV patients. Glioblastoma (GBM) patients frequently show lymphopenia, which is related to both the immunosuppressive nature of the tumor and to the treatment with concomitant temozolomide (TMZ) and radiotherapy (RT). Surprisingly, the incidence of CMV reactivation in GBM patients has not been clearly studied so far. We report here our experience on CMV reactivation in a cohort of newly-diagnosed GBM patients, treated with RT and TMZ. We assessed the incidence of CMV reactivation in these patients and tried to identify risk factors for such reactivation. MATERIAL AND METHODS All consecutive patients with histologically confirmed malignant GBM recommended for temozolomide chemoradiotherapy in our institution from October 2013 to December 2015 were reviewed. In all patients, sex, age, Karnofsky performance status (KPS), lymphocyte level, serological CMV status and steroid dosages were recorded at the onset, and one month after completion of the concomitant radio-chemotherapy regimen. A CMV reactivation was defined by a detection of CMV DNA &gt; 1000 copies/ml in the patient’s serum. RESULTS 103 patients meeting the analysis criteria were reviewed. Within these 103 patients, 34 patients (33%) had initial negative serology for CMV, and none of them developed a seroconversion after treatment with concomitant RT + TMZ. Among patients with positive IgG (n=69), 16 patients (23%) developed a positive viremia at one point during treatment with concomitant RT + TMZ. Age (&gt;60 years), lymphocyte count before RT (&lt;1500/mm3) and use of steroids were correlated with CMV reactivation (p&lt;0.05 in univariate analysis). A positive CMV viremia during RT+TMZ did not impact the progression free survival (PFS) but was associated with a shorter overall survival (OS) when compared to the others patients (median: 12 months vs 15 months; p=0.04). No clinical symptoms suggestive of CMV infection were reported. CONCLUSION In this single center series, we showed that CMV reactivation occurs in 23% of the GBM patients having a positive serology for CMV. Reactivation was more frequent in older patients, with low lymphocyte counts and treated with steroids. A positive viremia was not associated with poor PFS, a fact that does not support a promoting role of CMV in glioma oncogenesis, which has been sometimes suggested. Yet, the group of patients with CMV reactivation showed a shorter OS, which might be related to an older age and /or poorer clinical conditions in this group.
P14.55 FOXP2 as a prognostic biomarker in glioblastoma
Authors: J Plata-Bello, H Fariña, I Betancor, Y Quintero, E Salido, V Garcia-Marin
Journal: Neuro-Oncology (2019)

Abstract Background FOXP2 is an essential transcription factor for the development of language. It has also a high expression in some neosplasm, with a differential role as a prognostic biomarker. However, the role of FOXP2 in glioblastoma (GBM) has not been studied until now. AIM To study the role of FOXP2 as a prognostic biomarker in GBM. METHODS This is a retrospective observational case series study in which the expression of FOXP2 has been analyzed at the protein level (immunochemistry, in probes from patients treated in our Center) and at the level of mRNA (RNAseq, in a cohort of GBM patients from The Cancer Genome Atlas [TCGA] database). The expression of some target genes of FOXP2 (RNAseq) has also been studied in the TCGA cohort. Survival analysis using Log-Rank test and COX regression (uni- and multivariate) have been used. The analysis included also other molecular and clinical features of interest in GBM. RESULTS At protein level, FOXP2 was expressed in more than 90% of patients, with a mean positivity of 28.33% (SD=32.29). At mRNA level, FOXP2 was expressed in 79% of patients, with a mean expression of 29.72 RPKM (SD=63.77). Patients with a high expression of FOXP2 at protein level showed a worse prognosis than those patients with low expression in both, progression free survival (HR=1.711; p=.034) and overall survival (HR=1.809; p=.014). These associations maintained their significance in multivariate analysis. Nevertheless, no prognostic association was found with mRNA FOXP2 expression. Interestingly, FOXP2 target genes did not show the expected regulation described in previous works. Some of these genes has been involved in oncogenesis. CONCLUSION FOXP2 is expressed in many GBM patients. Higher expression of FOXP2 protein may be associated with a worse prognosis, but this has not been confirmed at mRNA. Furthermore, a dysregulation of FOXP2 function may be present in tumoral cells.
P14.07 Complete response under treatment with proton therapy followed by chemotherapy together with Tumor Treating Fields in a biopsied IDH wildtype glioblastoma patient
Authors: M Stein, H Dohmen, B Woelk, E Uhl, M Kolodziej, A Jensen
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Proton therapy is able to apply high radiation doses to the tumor while sparing healthy tissues by reducing integral dose. Tumor Treating Fields (TTFields) are low intensity (1–3 V/cm) and intermediate frequency (100–300 kHz) alternating electric fields that demonstrated significantly increased survival rates in combination with adjuvant temozolomide (TMZ) in patients with newly diagnosed glioblastoma (ndGBM). Especially in ndGBM IDH wildtype with unmethylated MGMT promotor therapeutic options are restricted. Here, we report on a patient with biopsied ndGBM IDH wildtype with complete radiological response. MATERIAL AND METHODS Brain MRI demonstrated an occlusive hydrocephalus and a ring enhancing lesion in the right posterior thalamus in a 42 year old male. Endoscopic third ventriculostomy and stereotactic biopsy of the lesion were performed. Histopathological examination resulted in the diagnosis of a glioblastoma (WHO grade IV), IDH 1 wildtype (R132), IDH 2 wildtype (R172), HIST1H3B/C wildtype, TERT wildtype (C228 and C250), BRAF wildtype, and unmethylated MGMT promotor. In view of the tumor site, resection was not feasible. Consequently, the patient received definitive chemoradiation with TMZ to a total dose of 60Gy incl. proton boost of 5x2 GyRBE. TTFields therapy in combination with TMZ was initiated 4 weeks after completion of chemoradiation, TMZ maintenance was completed per protocol after 6 cycles. TTFields therapy was continued for more than 13 month and to-date the patient is still on therapy. RESULTS Current follow up time is 20 months after initial diagnosis with the patient showing a radiological complete response. The first MRI following chemoradiation with TMZ and protons (showed pseudoprogression. After 3 months, the MRI again showed slightly increasing contrast enhancement. However, no clinical symptoms of tumor progression were present. The TTFields usage (compliance) rate, i.e. the rate per time the patient is applying the therapy, of the patient was 86 %. This was well above the independent prognostic threshold of 75 % and supports the feasibility of this approach. A further MRI after 8 weeks showed a stable disease. In a MRI 4 months later, partial response with decreased contrast enhancement plus perfusion restriction in the tumor area was observed. Another MRI after 3 months showed a complete response without perfusion signal in the tumor area. In the clinical examination the patient had no neurological deficits and to-date the patient is still stable CONCLUSION Complete response was observed following combination treatment of chemoradiation with TMZ including proton boost, TMZ maintenance and TTFields in a patient with pathologically confirmed GBM IDH wildtype. To our knowledge, this is the first report on a ndGBM patient receiving proton therapy followed by TTFields therapy.
OS10.5 Outcome of unresectable de novo IDH wild-type GBM: A decade analysis of factors influencing survival
Authors: A Hamdan, K Homyer, G Swan, G Bankov, S Alfadhel, L Sinan, A Aw, A Grivas
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Patients with unresectable GBM represent an understudied and underpowered disease subgroup for which limited outcome data exist to support treatment recommendations. In this study, we present a ten-year analysis on outcome of unresectable GBM patients at our unit. MATERIAL AND METHODS We collected data for all consecutive adult de novo IDH wild-type (IDHwt) GBM patients who had undergone biopsy at our unit (2009–18, N= 177) and analysed those that had complete data on performance status, radiology, MGMT status, and adjuvant treatment (N= 156). We used step-wise cox proportional hazards regression to analyse factors associated with survival and outcomes. RESULTS Of 156 patients, mean age was 60.8 years old (range 19–89, 34/21.8% &gt;69 years old), 63 (40.4%) were females, and 50 (32.1%), 26 (16.7%) and 12 (7.7%) had multifocal, butterfly or both lesion types respectively. 101 (64.7%) patients had good performance status (ECOG 0–1), and 49 (31.4%) had methylated MGMT lesions. Adjuvant treatment modalities were best supportive care (41, 26.3%), RT only (33, 21.2%), TMZ only (20, 12.8%), RT and TMZ (10, 6.4%), concurrent TMZ/RT only (29, 18.6%) and concurrent TMZ/RT plus adjuvant TMZ [TMZ/RT+TMZ] (23, 14.7%). Median OS was 6.1 months (range 0–50.7), with 22% and 2% 1- and 2-year OS respectively. Patients who were MGMT methylated, had good performance status, and received TMZ/RT+TMZ had the highest survival (median OS 18.7 vs 5.5 months, P&lt;0.0001). Multivariate analysis revealed factors associated with worse OS; these include male sex (HR 1.6, 95%CI 1.1–2.2), unmethylated MGMT (1.8, 1.3–2.8), poor performance status ie ECOG&gt;1 (2.4, 1.6–3.3), not receiving TMZ/RT+TMZ (3.1, 1.8–5.1). In addition, univariate analysis initially revealed that older age (&gt;69yrs) was significantly associated with poorer outcome, however in multivariate analysis, this effect was obliterated (HR 1.3, 95%CI 0.9–2.1). CONCLUSION In this study, we provide one of the largest series of unresectable IDHwt GBM outcome in the literature. Survival of patients harbouring unresectable IDHwt GBM can be unexpectedly long, and may even reach nearly twice that of the unselected, biopsy-only GBM patients receiving TMZ/RT+TMZ studied in the original Stupp trial (median OS of 9.4 months). For this subgroup of IDHwt GBM patients, advanced age may not necessarily predict poor outcome, once adjusted for other outcome predictors. Future randomised trials looking into unresectable IDHwt GBM should stratify patients according to the factors revealed above.
I’m Worried About Depression—What Should I Know?
Authors: Michael A. Incze
Journal: JAMA Internal Medicine (2019)

What Is Depression?Depression is a common medical illness that causes feelings of sadness and a loss of interest in things that usually bring joy.While everyone experiences sad feelings at times, clinical depression is when these symptoms last 2 or more weeks.For many, depression happens in a cycle of recurrent episodes.Depression leads to life problems, such as trouble at work, school, and in relationships.Depression can be treated; however, untreated depression increases the risk of self-harm and suicide.