bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upper Ordovician Juniata Formation, Central Appalachian Basin, USA: A record of Milankovitch-forced eustatic oscillations originating from glaciations in polar Gondwana
Authors: Hinnov Linda A. , Diecchio Richard J. 
Published: June 2020

ABSTRACT
The Upper Ordovician Juniata Formation, Central Appalachian Basin, USA, is a thick succession of cyclically bedded arenites, wackes, and mudrocks. Sedimentary facies of the formation in West Virginia, Virginia, and Maryland indicate cyclic peritidal deposition along the northern shoreline of the basin. The subsurface Juniata Formation has been drilled throughout the basin, and long, continuous well logs are available for analysis of the cyclic deposition. A 2400-ft-long (731.52-m-long) gamma-ray (GR) log from the Preston 119 well, northern West Virginia, provides a proxy of terrigenous siliciclastic fluxes originating from the Taconic highlands, from the early Ashgillian to the Ordovician–Silurian transition. Strong cycling in the GR log shows evidence for Milankovitch-forced sea-level oscillations, hypothesized to have been produced by dynamic Late Ordovician glaciation in polar (southern) Gondwana. Juniata cycle frequencies are different from those of Quaternary Milankovitch cycles, with significantly higher obliquity and precession index frequencies, consistent with a 21.5 h Ordovician day and an Earth-Moon distance that was 95% of present day. These results support John Dennison’s long-held view that Milankovitch forcing of sedimentation took place in the early Paleozoic Appalachian Basin by action of remotely generated glacio-eustatic oscillations powered by glaciation on southern Gondwana, and that this sedimentary record has tracked “Earth’s movement through space.”
Voices from the frontline: findings from a thematic analysis of a rapid online global survey of maternal and newborn health professionals facing the COVID-19 pandemic
Authors: Semaan Aline , Audet Constance , Huysmans Elise , Afolabi Bosede , Assarag Bouchra , Banke-Thomas Aduragbemi , Blencowe Hannah , Caluwaerts Séverine , Campbell Oona Maeve Renee , Cavallaro Francesca L , Chavane Leonardo , Day Louise Tina , Delamou Alexandre , Delvaux Therese , Graham Wendy Jane , Gon Giorgia , Kascak Peter , Matsui Mitsuaki , Moxon Sarah , Nakimuli Annettee , Pembe Andrea , Radovich Emma , van den Akker Thomas , Benova Lenka 
Published: June 2020

IntroductionThe COVID-19 pandemic has substantially impacted maternity care provision worldwide. Studies based on modelling estimated large indirect effects of the pandemic on services and health outcomes. The objective of this study was to prospectively document experiences of frontline maternal and newborn healthcare providers.MethodsWe conducted a global, cross-sectional study of maternal and newborn health professionals via an online survey disseminated through professional networks and social media in 12 languages. Information was collected between 24 March and 10 April 2020 on respondents’ background, preparedness for and response to COVID-19 and their experience during the pandemic. An optional module sought information on adaptations to 17 care processes. Descriptive statistics and qualitative thematic analysis were used to analyse responses, disaggregating by low-income and middle-income countries (LMICs) and high-income countries (HICs).ResultsWe analysed responses from 714 maternal and newborn health professionals. Only one-third received training on COVID-19 from their health facility and nearly all searched for information themselves. Half of respondents in LMICs received updated guidelines for care provision compared with 82% in HICs. Overall, 47% of participants in LMICs and 69% in HICs felt mostly or completely knowledgeable in how to care for COVID-19 maternity patients. Facility-level responses to COVID-19 (signage, screening, testing and isolation rooms) were more common in HICs than LMICs. Globally, 90% of respondents reported somewhat or substantially higher levels of stress. There was a widespread perception of reduced use of routine maternity care services, and of modification in care processes, some of which were not evidence-based practices.ConclusionsSubstantial knowledge gaps exist in guidance on management of maternity cases with or without COVID-19. Formal information-sharing channels for providers must be established and mental health support provided. Surveys of maternity care providers can help track the situation, capture innovations and support rapid development of effective responses.
IL-6 promotes PD-L1 expression in monocytes and macrophages by decreasing protein tyrosine phosphatase receptor type O expression in human hepatocellular carcinoma
Authors: Zhang Wenjie , Liu Yang , Yan Zhongyi , Yang Hui , Sun Wei , Yao Yongliang , Chen Yun , Jiang Runqiu 
Published: June 2020

BackgroundWe have previously discovered a relationship between the low expression of protein tyrosine phosphatase, receptor type O (PTPRO) in tumor-infiltrating T cells and immunosuppression. The aim of the present study was to investigate the relationship between decreased PTPRO and increased programmed death ligand 1 (PD-L1) in both the peripheral monocytes and tumor-infiltrating macrophages of human hepatocellular carcinoma (HCC).MethodsThe expression and correlation of all the indices were explored in monocytes and tumor-infiltrating macrophages within both human and mice HCC. The mechanic regulations were studied by using both in vitro and in vivo studies.ResultsWe found a significant decrease in PTPRO in HCC peripheral monocytes that was associated with increased PD-L1 expression in peripheral monocytes and tumor-associated macrophages (TAMs) in HCC. Monocyte PD-L1 and PTPRO therefore could serve as valuable prognostic indicators for post-surgery patients with HCC and were associated with increased T-cell exhaustion (Tim3+T cells). A depletion of PTPRO promoted PD-L1 secretion in both monocytes and macrophages through the JAK2/STAT1 and JAK2/STAT3/c-MYC pathways. Increased IL-6 expression was associated with activation of JAK2/STAT3/c-MYC and with decreased PTPRO expression through the STAT3/c-MYC/miR-25–3 p axis. Monocytes and TAMs showed significantly increased miR-25–3 p expression, which could target the 3′ untranslated region of PTPRO. The miR-25–3 p expression positively correlated with serum IL-6 levels, but inversely correlated with PTPRO in HCC monocytes. IL-6/STAT3/c-MYC activation enhanced in vitro miR-25–3 p transcription and decreased PTPRO, while further promoting PD-L1 secretion. Adoptive cell transfer of c-MYC/miR-25–3 p–modified monocytes promoted tumor growth by downregulating PTPRO and causing a PD-L1–induced immunosuppression in an orthotopic tumor transplantation model.ConclusionsIncreased serum IL-6 downregulated PTPRO expression in HCC monocytes and macrophages by activating STAT3/c-MYC/miR-25–3 p and by further enhancing PD-L1 expression through JAK2/STAT1 and JAK2/STAT3/c-MYC signaling.
Combination treatment with radiotherapy and a novel oxidative phosphorylation inhibitor overcomes PD-1 resistance and enhances antitumor immunity
Authors: Chen Dawei , Barsoumian Hampartsoum B , Fischer Grant , Yang Liangpeng , Verma Vivek , Younes Ahmed I , Hu Yun , Masropour Fatemeh , Klein Katherine , Vellano Christopher , Marszalek Joseph , Davies Michael , Cortez Maria Angelica , Welsh James 
Published: June 2020

BackgroundDespite outstanding responses to anti-PD-1 agents in a subset of non-small cell lung cancer (NSCLC) patients, approximately 80% of patients fail to have prolonged favorable response. Recent studies show that tumor cell oxidative metabolism is a barrier to PD-1 immunotherapy and radiotherapy could overcome PD-1 resistance, so it is urgent to determine if combination treatment with radiotherapy and a novel oxidative phosphorylation (OXPHOS) inhibitor (IACS-010759) is an effective strategy against PD-1 resistance in NSCLC.MethodsThe antitumor effect of this combinational treatment was evaluated in vitro and in vivo. For in vivo experiments, we treated 129Sv/Ev mice with anti-PD1-sensitive and anti-PD1-resistant 344SQ NSCLC adenocarcinoma xenografts with oral IACS-010759 combined with radiotherapy (XRT). In vitro experiments included PCR, seahorse bioenergetic profiling, flow cytometry phenotyping, and clonogenic survival assay.ResultsIn the current study, we found that our PD-1-resistant model utilized OXPHOS to a significantly greater extent than the PD-1-sensitive model and XRT increased OXPHOS in vitro and in vivo. Thus, we explored the effect of the novel OXPHOS inhibitor IACS-010759 on PD-1-resistant NSCLC in an effort to overcome XRT-induced immunosuppression and maximize response to PD-1. Additionally, combined XRT and IACS-010759 promoted antitumor effects in the PD-1-resistant model, but not in the sensitive model. After elucidation of the most optimal dose/fractionation scheme of XRT with IACS-010759, the combinatorial therapy with this regimen did not increase the abscopal antitumor effect, although IACS-010549 did not decrease CD45+, CD4+, and CD8+ immune cells. Finally, triple therapy with IACS-010759, XRT, and anti-PD-1 promoted abscopal responses and prolonged survival time.ConclusionOXPHOS inhibition as part of a combinatorial regimen with XRT is a promising strategy to address PD-1-resistant NSCLC, and this combination is being tested clinically.
Sequential ctDNA whole-exome sequencing in advanced lung adenocarcinoma with initial durable tumor response on immune checkpoint inhibitor and late progression
Authors: Giroux Leprieur Etienne , Hélias-Rodzewicz Zofia , Takam Kamga Paul , Costantini Adrien , Julie Catherine , Corjon Alexandre , Dumenil Coraline , Dumoulin Jennifer , Giraud Violaine , Labrune Sylvie , Garinet Simon , Chinet Thierry , Emile Jean-François 
Published: June 2020

BackgroundDespite prolonged tumor response to immune checkpoint inhibitors (ICIs) for a subset of patients with advanced non-small cell lung cancer (NSCLC), a secondary resistance will occur for a majority of these patients. The understanding of late progression mechanisms with ICIs is important to improve future treatment strategies.MethodsWe performed whole-exome sequencing (WES) on circulating tumor DNA and compared molecular profiles between the beginning of ICI treatment and tumor progression in patients with advanced NSCLC treated with ICIs and who had initial and prolonged tumor response with secondary progression, after at least 6 months of treatment.ResultsWe identified eight patients who experienced initial and durable tumor response, and secondary tumor progression after 6 months of treatment, with available paired blood samples (diagnosis and progression). All had lung adenocarcinoma, three had programmed-death ligand-1 expression ≥50% in immunohistochemistry and all presented low blood tumor mutational burden (bTMB). Seven patients received nivolumab in second-line or more, and one received pembrolizumab as first-line treatment. WES at progression showed clonal selection with molecular alterations of Wnt pathway-related genes, increase of copy number aberrations in cancer-related genes and loss of tumor-suppressor genes (such asPTEN) or of genes associated with immune response (such asB2M). No difference in term of bTMB was observed at progression.ConclusionsThis is the first study describing putative molecular mechanisms associated with late progression under ICI in lung cancer. Studies on treatment strategies adapted to these mechanisms are needed.
Calcium-sensing receptor autoantibody-mediated hypoparathyroidism associated with immune checkpoint inhibitor therapy: diagnosis and long-term follow-up
Authors: Dadu Ramona , Rodgers Theresa E , Trinh Van A , Kemp Elizabeth Helen , Cubb Trisha D , Patel Sapna , Simon Julie M , Burton Elizabeth M , Tawbi Hussein 
Published: June 2020

BackgroundImmune checkpoint inhibitors (ICIs) have produced significant survival benefit across many tumor types. However, immune-related adverse events are common including autoimmune responses against different endocrine organs. Here, a case of ICI-mediated hypoparathyroidism focusing on long-term follow-up and insights into its etiology is presented.Case and methodsA 73-year-old man developed severe symptomatic hypocalcemia after the initiation of ipilimumab and nivolumab for the treatment of metastatic melanoma. Hypoparathyroidism was diagnosed with undetectable intact parathyroid hormone (PTH). Immunoprecipitation assays, ELISAs, and cell-based functional assays were used to test the patient for antibodies against the calcium-sensing receptor (CaSR). NACHT leucine-rich repeat protein 5 (NALP5) and cytokine antibodies were measured in radioligand binding assays and ELISAs, respectively.ResultsThe patient’s symptoms improved with aggressive calcium and vitamin D supplementation. At 3 years and 3 months since the diagnosis of hypoparathyroidism, PTH was still inappropriately low at 7.6 pg/mL, and attempted discontinuation of calcium and calcitriol resulted in recurrent symptomatic hypocalcemia. Analysis for an autoimmune etiology of the patient’s hypoparathyroidism indicated that CaSR antibodies were negative before treatment and detected at multiple time points afterwards, and corresponded to the patient’s clinical course of hypoparathyroidism. CaSR antibodies purified from the patient’s serum activated the human CaSR. The patient was seronegative for NALP5 and cytokine antibodies, indicating that their hypoparathyroidism was not a manifestation of autoimmune polyendocrine syndrome type 1.ConclusionThe etiology of hypocalcemia is likely autoimmune hypoparathyroidism caused by the development of CaSR-activating antibodies that might prevent PTH release from the parathyroid.
Development of classification criteria for hand osteoarthritis: comparative analyses of persons with and without hand osteoarthritis
Authors: Haugen Ida K , Felson David T , Abhishek Abhishek , Berenbaum Francis , Bierma-Zeinstra Sita , Borgen Tove , Herrero Beaumont Gabriel , Ishimori Mariko , Jonsson Helgi , Kroon Féline PB , Maheu Emmanuel , Ramonda Roberta , Ritschl Valentin , Stamm Tanja A , van der Heijde Desirée , Wittoek Ruth , Greibrokk Elsie , Smeets Wilma , Kloppenburg Margreet 
Published: June 2020

ObjectivesFurther knowledge about typical hand osteoarthritis (OA) characteristics is needed for the development of new classification criteria for hand OA.MethodsIn a cross-sectional multi-centre international study, a convenience sample of patients from primary and secondary/tertiary care with a physician-based hand OA diagnosis (n = 128) were compared with controls with hand complaints due to inflammatory or non-inflammatory conditions (n = 70). We examined whether self-reported, clinical, radiographic and laboratory findings were associated with hand OA using logistic regression analyses. Discrimination between groups was assessed by calculating the area under receiver operating curves (AUC).ResultsStrong associations with hand OA were observed for radiographic osteophytes (OR = 1.62, 95% CI 1.40 to 1.88) and joint space narrowing (JSN) (OR = 1.57, 95% CI 1.36 to 1.82) in the distal interphalangeal (DIP) joints with excellent discrimination (AUC = 0.82 for both). For osteophytes and JSN, we found acceptable discrimination between groups in the proximal interphalangeal joints (AUC = 0.77 and 0.78, respectively), but poorer discrimination in the first carpometacarpal joints (AUC = 0.67 and 0.63, respectively). Painful DIP joints were associated with hand OA, but were less able to discriminate between groups (AUC = 0.67). Age and family history of OA were positively associated with hand OA, whereas negative associations were found for pain, stiffness and soft tissue swelling in metacarpophalangeal joints, pain and marginal erosions in wrists, longer morning stiffness, inflammatory biomarkers and autoantibodies.ConclusionsDifferences in symptoms, clinical findings, radiographic changes and laboratory tests were found in patients with hand OA versus controls. Radiographic OA features, especially in DIP joints, were best suited to discriminate between groups.
Courant bracket found out to be T-dual to Roytenberg bracket
Authors: Ivanišević I. , Davidović Lj. , Sazdović B. 
Published: June 2020

AbstractBosonic string moving in coordinate dependent background fields is considered. We calculate the generalized currents Poisson bracket algebra and find that it gives rise to the Courant bracket, twisted by a 2-form $$2B_{\mu \nu }$$2Bμν. Furthermore, we consider the T-dual generalized currents and obtain their Poisson bracket algebra. It gives rise to the Roytenberg bracket, equivalent to the Courant bracket twisted by a bi-vector $$\Pi ^{\mu \nu }$$Πμν, in case of $$\Pi ^{\mu \nu } = 2 {^\star B}^{\mu \nu } = \kappa \theta ^{\mu \nu }$$Πμν=2⋆Bμν=κθμν. We conclude that the twisted Courant and Roytenberg brackets are T-dual, when the quantities used for their deformations are mutually T-dual.
Constraints on Newton’s constant from cosmological observations
Authors: Wang Ke , Chen Lu 
Published: June 2020

AbstractNewton’s constant has observational effects on both the CMB power spectra and the light curves of SNIa. We use Planck data, BAO data and the SNIa measurement to constrain the varying Newton’s constant G during the CMB epoch and the redshift ranges of PANTHEON samples, and find no evidence indicating that G is varying with redshift. By extending the $$\Lambda $$ΛCDM model with one free parameter G, we get $$G =(6.65635_{-0.18560}^{+0.18766} ) \times 10^{-11} \text {m}^3\,\text {kg}^{-1}\,\text {s}^{-2}$$G=(6.65635-0.18560+0.18766)×10-11m3kg-1s-2 and $$H_0=67.62^{+1.24}_{-1.25}$$H0=67.62-1.25+1.24 km s$$^{-1}$$-1 Mpc$$^{-1}$$-1 at 68$$\%$$% CL from Planck$$+$$+BAO$$+$$+uncalibrated PANTHEON. The results show the value of G is consistent with CODATA 2018, but the $$H_0$$H0 tension can’t be solved in this way.
MANAGEMENT INNOVATION, DRIVERS AND OUTCOMES: THE MODERATING ROLE OF ORGANISATIONAL SIZE
Authors: KAFETZOPOULOS DIMITRIOS , GOTZAMANI KATERINA , VOUZAS FOTIS 
Published: June 2020

This article proposes a conceptual model to analyse the role of quality orientation and collaborations in firms’ management innovation, and also the impact of management innovation to product, process and marketing innovation. Moreover, the analysis considers organisational size as a key moderating factor in order to investigate whether the relationships among the model factors vary between small and medium size firms. To achieve these objectives an empirical survey was conducted among 429 firms. The structural relationships among the latent factors were determined through SEM. The findings show that the probability of success increases when firms use quality orientation and collaboration to support management innovation efforts. In addition, the findings suggest that management innovation positively affects product, process and marketing innovation while the organisational size acts as a moderator in the relationships among quality orientation, collaborations, management innovation, — product, process and marketing innovation, respectively.
Female medal and fund recipients of the Geological Society of London: a historical perspective
Authors: Burek Cynthia V. 
Published: June 2020

Abstract
The Geological Society of London has historically awarded medals and funds to early career geologists and for career achievement recognition. Mid-career and outreach awards were later added as categories. This paper will concentrate on early recipients of funds and medal winners mainly during the nineteenth and twentieth centuries.
In the nineteenth century, only two women received recognition by the Geological Society for their work through early career funds (not medals): Catherine Raisin in 1893 and Jane Donald in 1898.
From 1900 to 1919, no woman received a medal but funds were collected by men on behalf of Gertrude Elles, Elizabeth Gray, Ethel Wood, Helen Drew, Ida Slater and Ethel Skeat. The first woman to collect her own Fund was Ethel Skeat in 1908.
Pre-World War II, only four women received career recognition in the form of a medal. Gertrude Elles in 1919 and Ethel Shakespear in 1920 received the Murchison Medal. No further medals were awarded to women until Maria Ogilvie Gordon in 1932 and Eleanor Mary Reid in 1936. It was not until the end of the 1990s and into the twenty-first century that a significant number of women received medals. It is noted that the William Smith Medal was only received by a woman in 2019 and the Dewey Medal has yet to be received by a woman. An analysis of the different medals and funds awarded to females through the Geological Society is discussed in detail with snapshots of the women who were so recognized. As we move into the twenty-first century we see an increase in these awards to women.
Mogamulizumab in Combination with Durvalumab or Tremelimumab in Patients with Advanced Solid Tumors: A Phase I Study
Authors: Zamarin Dmitriy , Hamid Omid , Nayak-Kapoor Asha , Sahebjam Solmaz , Sznol Mario , Collaku Agron , Fox Floyd E. , Marshall Margaret A. , Hong David S. 
Published: June 2020

AbstractPurpose:The study goal was to determine safety, antitumor activity, and pharmacodynamic profile of mogamulizumab, an anti–C-C chemokine receptor 4 (anti-CCR4) mAb targeting effector regulatory T cells (eTreg), in combination with mAb checkpoint inhibitors durvalumab or tremelimumab.Patients and Methods:This was a multicenter, phase I, dose escalation study, followed by disease-specific cohort expansion (NCT02301130). Mogamulizumab dose escalation proceeded with concurrent dose escalation of durvalumab or tremelimumab in patients with advanced solid tumors. Cohort expansion occurred with mogamulizumab 1 mg/kg plus durvalumab 10 mg/kg or tremelimumab 10 mg/kg in patients with advanced pancreatic cancer.Results:Forty patients were enrolled during dose escalation, followed by 24 patients during dose expansion. No dose-limiting toxicities occurred during dose escalation. No new or unexpected toxicities were seen. Tolerability, the primary endpoint, was acceptable utilizing mogamulizumab 1 mg/kg plus durvalumab or tremelimumab 10 mg/kg in the combined dose escalation and dose expansion cohorts (each n = 19). At these doses, the objective response rate was 5.3% (95% confidence interval, 0.1%–26.0%; one partial response) with each combination treatment. At all doses, mogamulizumab treatment led to almost complete depletion of peripheral eTregs, as well as reduction of intratumoral Tregs in the majority of patients. There was no clear correlation of clinical response with peripheral or intratumoral reduction in CCR4+ eTregs or with baseline degree of CCR4+ expression.Conclusions:Mogamulizumab in combination with durvalumab or tremelimumab did not result in potent antitumor efficacy in patients with advanced solid tumors. Tolerability of mogamulizumab 1 mg/kg combined with durvalumab or tremelimumab 10 mg/kg was acceptable.