bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mesozoic–Cenozoic tectonic controls on the formation of large‐scale metamorphic rock buried‐hill reservoirs in Bozhong Sag, eastern China
Authors: Liu Xiaojian , Hou Mingcai , Niu Chengmin , Wang Qingbin , Zhang Xintao , Ye Tao , Cui Puyuan , Hao Yiwei 
Published: August 2021

Buried‐hill reservoirs are important targets for petroleum exploration. The number of buried‐hill oil–gas fields with reservoirs hosted in metamorphic rock is low, and metamorphic rock buried‐hill reservoirs deeper than 4,500 m (ultra‐deep) are even rarer. Ultra‐deep metamorphic rock buried‐hill reservoirs are characterized by highly heterogeneous lithologies and structure and have complex formation mechanisms, but such reservoirs have received relatively little research attention compared with reservoirs hosted in other rock types and at shallower depths. In the Bozhong Sag in the Bohai Bay Basin, Archean metamorphic rocks are buried at depths of 4,500–6,000 m, and their anticlinal structures are thus defined as ultra‐deep buried hills. Owing to their burial depth and compacted overburden, tectonism has been a key control on the formation of high‐quality reservoirs by causing deformation such as fractures. In this study, using results of drill‐core analyses, thin‐section imaging, and rock mechanical tests, we investigated the distribution and formation mechanisms of high‐quality reservoirs within the Bozhong 19‐A metamorphic rock buried hill. We also examined the formation mechanism of fractures in the Bozhong 19‐A buried hill with respect to early‐stage initiation by compression and late‐stage reactivation by transpression. Results show that intense compression‐related overthrusting caused by collision between the South China and North China plates during the Indosinian (252–237 Ma) orogeny generated initial fractures in the metamorphic rock buried hill and the formation of numerous NW‐trending nappe structures. Subsequent Yanshanian (163–66 Ma) sinistral transpression not only reactivated pre‐existing fractures, but also resulted in the development of numerous new fractures. In addition, in low‐stress regions such as anticline flanks and the lower parts of structures, compression closed the pre‐existing fractures, leading to lower fracture densities. Results of acoustic emission mechanical testing indicate that Himalayan (66–0 Ma) extensional stress was insufficient to produce large‐scale fracture systems in the Archean metamorphic rock, but was crucial for reactivating pre‐existing early‐stage fractures. Thus, the Himalayan period was a key interval for the formation of effective fractures. Therefore, rocks that underwent large‐scale overthrusting during early‐stage (Indosinian) fracturing and subsequent late‐stage (Yanshanian and Himalayan) reactivation favoured the development of ultra‐deep metamorphic rock buried‐hill reservoirs. This study should provide guidance for petroleum exploration in buried hills in superimposed basins that underwent early‐stage compression, late‐stage transpression, and final extension.
Adenosine A2B receptor down‐regulates metabotropic glutamate receptor 5 in astrocytes during postnatal development
Authors: Tanaka Masayoshi , Shigetomi Eiji , Parajuli Bijay , Nagatomo Hiroaki , Shinozaki Youichi , Hirayama Yuri , Saito Kozo , Kubota Yuto , Danjo Yosuke , Lee Ji Hwan , Kim Sun Kwang , Nabekura Junichi , Koizumi Schuichi 
Published: August 2021

AbstractMetabotropic glutamate receptor 5 (mGluR5) in astrocytes is a key molecule for controlling synapse remodeling. Although mGluR5 is abundant in neonatal astrocytes, its level is gradually down‐regulated during development and is almost absent in the adult. However, in several pathological conditions, mGluR5 re‐emerges in adult astrocytes and contributes to disease pathogenesis by forming uncontrolled synapses. Thus, controlling mGluR5 expression in astrocyte is critical for several diseases, but the mechanism that regulates mGluR5 expression remains unknown. Here, we show that adenosine triphosphate (ATP)/adenosine‐mediated signals down‐regulate mGluR5 in astrocytes. First, in situ Ca2+ imaging of astrocytes in acute cerebral slices from post‐natal day (P)7‐P28 mice showed that Ca2+ responses evoked by (S)‐3,5‐dihydroxyphenylglycine (DHPG), a mGluR5 agonist, decreased during development, whereas those evoked by ATP or its metabolite, adenosine, increased. Second, ATP and adenosine suppressed expression of the mGluR5 gene, Grm5, in cultured astrocytes. Third, the decrease in the DHPG‐evoked Ca2+ responses was associated with down‐regulation of Grm5. Interestingly, among several adenosine (P1) receptor and ATP (P2) receptor genes, only the adenosine A2B receptor gene, Adora2b, was up‐regulated in the course of development. Indeed, we observed that down‐regulation of Grm5 was suppressed in Adora2b knockout astrocytes at P14 and in situ Ca2+ imaging from Adora2b knockout mice indicated that the A2B receptor inhibits mGluR5 expression in astrocytes. Furthermore, deletion of A2B receptor increased the number of excitatory synapse in developmental stage. Taken together, the A2B receptor is critical for down‐regulation of mGluR5 in astrocytes, which would contribute to terminate excess synaptogenesis during development.
Improvement of patient stratification in human papilloma virus‐associated oropharyngeal squamous cell carcinoma by defining a multivariable risk score
Authors: Oberste Maximilian , Riders Armands , Abbaspour Bektasch , Kerschke Laura , Beule Achim G. , Rudack Claudia 
Published: August 2021

AbstractBackgroundPrecise risk stratification models are necessary to determine patient selection for deintensifying treatment trials in human papilloma virus (HPV)‐associated oropharyngeal squamous cell cancer (HPV+ OPSCC).MethodsWe examined 526 cases with OPSCC treated at our department between 2002 and 2017. Every patient was classified after the 7th and 8th edition UICC staging manual. For HPV+ OPSCC, we calculated a simple risk score with four risk groups based on multivariable Cox regression analysis of clinical and lifestyle parameters (UICC 8th edition stage, tobacco/alcohol abuse, age, gender).ResultsTwo hundred and thirty‐nine patients with OPSCC (45.4%) showed a positive histological HPV status. In comparison to UICC 8th edition stages, our proposed risk model showed a tendency for better stratification between risk strata I/III, I/IV, and II/IV (each p < 0.002) and I/II, II/III, and III/IV (each p < 0.09).ConclusionAge, gender, tobacco, and alcohol abuse should be added to the current UICC staging system in order to improve risk stratification in HPV+ OPSCC.
Missed opportunities for improving oral health in rural Victoria: The role of municipal public health planning in improving oral health
Authors: Dickson‐Swift Virginia , Crocombe Leonard 
Published: August 2021

AbstractIssue addressedPeople in rural areas have poorer oral health than their urban counterparts due to a range of factors. Local governments (LGs) have a key role in addressing health issues that impact on local communities.MethodsPublicly available oral health profile (OHP) data and Municipal Public Health and Wellbeing Plans (MPHWPs) (2017‐2021) were downloaded from Dental Health Services Victoria and LG websites for 48 Victorian local government areas (LGAs) containing predominately rural areas. OHP data were collated to provide an overview of the oral health status of the communities and a content analysis of the MPHWPs undertaken.ResultsDespite poor oral health in rural Victorian LGAs, oral health was not often in MPHWPs. Twenty of the MPHWPs had some mention of oral health but only four included specific actions or strategies that would be used to improve oral health. None of the plans contained any specific targets for action or details of evaluations that might be used to assess success.ConclusionsPoor oral health in rural Victorian communities continues to be demonstrated through local OHPs and is due to modifiable risk factors and poor access to water fluoridation. LGs have a key role to play in improving oral health through utilisation of OHP data in their MPHWPs.So what?Oral health remains a low priority for LG action. This represents a missed opportunity for prioritising oral health prevention and promotion activities that improve oral health in rural Victoria.
Polydatin gold nanoparticles potentiate antitumor effect of doxorubicin in Ehrlich ascites carcinoma‐bearing mice
Authors: Samra Yara A. , Abdelghany Amr M. , Zaghloul Randa A. 
Published: August 2021

AbstractBreast cancer is a leading cause of death. Anticancer treatment such as gold nanoparticles (AuNP) seems highly promising in this regard. Therefore, this study aimed to assess the beneficial effect of doxorubicin (Dox) and polydatin (PD) AuNP in Ehrlich ascites carcinoma (EAC) and the ability of PD–AuNP to protect the heart from Dox's deteriorating effects. EAC was induced in mice. The mice were divided into nine groups: normal, EAC, PD: received PD (20 mg/kg), Dox: received Dox (2 mg/kg), PD–AuNPH: received 10 ppm AuNP of PD, PD–AuNPL: received 5 ppm AuNP of PD, Dox–AuNP: received Dox–AuNP, PD–Dox–AuNP: received PD–Dox–AuNP, AuNP: received AuNP. On the 21st day from tumor inoculation, the mice were sacrificed and tumor and heart tissues were removed. Tumor β‐catenin/Cyclin D1 and p53 were assessed by immunohistochemistry. IL‐6 was determined by enzyme‐linked immunosorbent assay. PD–AuNP and Dox–AuNP showed a significant reduction in tumor volume and weight more than their free forms. Also, PD–AuNP and Dox–AuNP showed markedly less dense tumor cells. β‐catenin and Cyclin D1 were markedly decreased and p53 was highly upregulated by PD–AuNP and Dox–AuNP. Moreover, PD–AuNP and Dox–AuNP have the ability to decrease IL‐6 production. PD–AuNP protected the heart from Dox‐induced severe degeneration. Therefore, PD–AuNP could be a tool to decelerate the progression of breast cancer.
Identification of steroidal saponins from Tribulus terrestris and their in silico docking studies
Authors: Patel Apurva , Bhatt Mital , Soni Anjali , Sharma Preeti 
Published: August 2021

AbstractTribulus terrestris is known to possess many pharmacological properties, most notably its anticancer activities, owing to its rich steroidal saponin contents. Even though many reports are available elucidating the anticancer potential of the herb, we, for the very first time have attempted to isolate and identified the active compound present in seed crude saponin extract and confers its in silico docking ability with various cellular targets proteins. High performance thin layer chromatography confirms the presence of active saponins in leaf and seed saponin extracts which were further fractionated by silica gel column chromatography. Fractions collected were assessed for cytotoxicity on human breast cancer cells. High resolution liquid chromatography and mass spectroscopy was employ to identify the active components present in fraction with highest cytotoxicity. Intriguingly, Nautigenin type of steriodal saponin was identified to present in the active fraction of seed extract (SF11) and the identified compound was further analyzed for its in silico docking interaction using PyRx AutodockVina. Docking studies revealed the high binding affinity of Nuatigenin at significant sites with apoptotic proteins Bcl‐2, Bax, caspase‐3, caspase‐8, p53 and apoptosis inducing factor along with cell surface receptors estrogen receptor, projesterone receptor, epidermal growth factor receptor, and human epidermal growth factor receptor‐2. Thus, the conclusions were drawn that saponin fraction of Tribulus terrestis possesses active compounds having anticancer property and specifically, Nuatigenin saponin can be considered as an important therapeutic drug for the breast cancer treatment.
What's in the BAGs? Intrinsic disorder angle of the multifunctionality of the members of a family of chaperone regulators
Authors: Marzullo Liberato , Turco Maria C. , Uversky Vladimir N. 
Published: August 2021

AbstractIn humans, the family of Bcl‐2 associated athanogene (BAG) proteins includes six members characterized by exceptional multifunctionality and engagement in the pathogenesis of various diseases. All of them are capable of interacting with a multitude of often unrelated binding partners. Such binding promiscuity and related functional and pathological multifacetedness cannot be explained or understood within the frames of the classical “one protein–one structure–one function” model, which also fails to explain the presence of multiple isoforms generated for BAG proteins by alternative splicing or alternative translation initiation and their extensive posttranslational modifications. However, all these mysteries can be solved by taking into account the intrinsic disorder phenomenon. In fact, high binding promiscuity and potential to participate in a broad spectrum of interactions with multiple binding partners, as well as a capability to be multifunctional and multipathogenic, are some of the characteristic features of intrinsically disordered proteins and intrinsically disordered protein regions. Such functional proteins or protein regions lacking unique tertiary structures constitute a cornerstone of the protein structure‐function continuum concept. The aim of this paper is to provide an overview of the functional roles of human BAG proteins from the perspective of protein intrinsic disorder which will provide a means for understanding their binding promiscuity, multifunctionality, and relation to the pathogenesis of various diseases.
Risk stratification using sarcopenia status among subjects with metabolic dysfunction‐associated fatty liver disease
Authors: Chun Ho Soo , Kim Mi Na , Lee Jae Seung , Lee Hye Won , Kim Beom Kyung , Park Jun Yong , Kim Do Young , Ahn Sang Hoon , Kim Seung Up 
Published: August 2021

AbstractBackgroundSarcopenia is a significant indicator of the severity of non‐alcoholic fatty liver disease. We investigated whether sarcopenia could identify subgroups with different risk of liver fibrosis and atherosclerotic cardiovascular disease (ASCVD) among subjects with metabolic dysfunction‐associated fatty liver disease (MAFLD).MethodsSubjects from the Korea National Health and Nutrition Examination Survey 2008–2011 were selected (n = 8361). Sarcopenia was defined using the sarcopenia index. Hepatic steatosis was defined as a fatty liver index ≥30. Significant liver fibrosis was defined as a fibrosis‐4 index (FIB‐4) ≥2.67 or the highest quartile of non‐alcoholic fatty liver disease fibrosis score (NFS). High probability of ASCVD was defined as ASCVD risk score >10%.ResultsThe mean age was 48.5 ± 15.6 years, and 42.6% of subjects were male. The prevalence of MAFLD was 37.3% (n = 3116 of 8361), and the proportion of sarcopenic subjects was 9.9% among those with MAFLD. After adjusting for confounders, the risk of significant liver fibrosis significantly increased from non‐sarcopenic subjects with MAFLD [odds ratio (OR) = 1.57 by FIB‐4 and 2.13 by NFS] to sarcopenic subjects with MAFLD (OR = 4.51 by FIB‐4 and 5.72 by NFS), compared with subjects without MAFLD (all P < 0.001). The risk for high probability of ASCVD significantly increased from non‐sarcopenic subjects with MAFLD (OR = 1.47) to sarcopenic subjects with MAFLD (OR = 4.08), compared with subjects without MAFLD (all P < 0.001).ConclusionsThe risks of significant liver fibrosis and ASCVD differed significantly according to sarcopenic status among subjects with MAFLD. An assessment of sarcopenia might be helpful in risk stratification among subjects with MAFLD.
Predictive impact of sarcopenia in solid cancers treated with immune checkpoint inhibitors: a meta‐analysis
Authors: Takenaka Yukinori , Oya Ryohei , Takemoto Norihiko , Inohara Hidenori 
Published: August 2021

AbstractSarcopenia, which is characterized by a decrease in muscle quantity or quality, is commonly observed in patients with cancer. Recent research has reported contradictory results on the association between sarcopenia and the efficacy of immune checkpoint inhibitors (ICIs). We conducted a systematic review and meta‐analysis to investigate this discrepancy. We systematically searched three electronic databases to identify articles reporting on the association between sarcopenia and treatment outcomes in patients with solid cancers who received ICIs. The outcomes assessed were hazard ratios (HRs) for overall survival (OS) and progression‐free survival (PFS), and odds ratios (ORs) for objective response rate (ORR), disease control rate (DCR), and toxicity. Pooled estimates and their 95% confidence intervals (CIs) were calculated. A total of 2501 patients from 26 studies were analysed. Sarcopenia was observed in 44.7% (95% CI: 38.2–51.3) of the patients and was significantly associated with poor survival (HR = 1.55, 95% CI = 1.32–1.82 for OS and HR = 1.61, 95% CI = 1.35 to 1.93 for PFS). The HRs (95% CIs) for OS according to the diagnostic measures used were 1.97 (0.88–4.41) for psoas muscle index (PMI), 1.41 (0.87–2.28) for skeletal muscle density (SMD), and 1.43 (1.23–1.67) for skeletal mass index (SMI). The HRs (95% CIs) for PFS were 1.86 (1.08–3.21) for PMI, 1.27 (0.94–1.71) for SMD, and 1.38 (1.11–1.71) for SMI. Poor radiological response to ICI therapy was observed in patients with sarcopenia (OR = 0.52, 95% CI = 0.34–0.80 for ORR and OR = 0.45, 95% CI = 0.30–0.67 for DCR). The ORs for ORR (95% CIs) were 0.56 (0.15–2.05) for PMI and 0.78 (0.56–1.09) for SMI. The oncologic outcomes associated with melanoma and non‐small cell lung cancer (NSCLC) were comparable with those observed overall (HR for OS = 2.02, 95% CI = 1.26–3.24 for melanoma and HR for OS = 1.61, 95% CI = 1.19–2.18 for NSCLC). In contrast, the occurrence of severe toxicity was not associated with sarcopenia (OR = 1.13, 95% CI = 0.51–2.52). Poor survival and poor response in patients with sarcopenia indicate a negative association between sarcopenia and efficacy of ICIs. Sarcopenia's predictive ability is consistent across various tumour types. For the selection of patients who may respond to ICIs pre‐therapeutically, the presence of sarcopenia should be assessed in clinical practice.
Vitamin D supplementation and risk of falling: outcomes from the randomized, placebo‐controlled D‐Health Trial
Authors: Waterhouse Mary , Sanguineti Emma , Baxter Catherine , Duarte Romero Briony , McLeod Donald S.A. , English Dallas R. , Armstrong Bruce K. , Ebeling Peter R. , Hartel Gunter , Kimlin Michael G. , O'Connell Rachel L. , Pham Hai , van der Pols Jolieke C. , Venn Alison J. , Webb Penelope M. , Whiteman David C. , Neale Rachel E. 
Published: August 2021

AbstractBackgroundFalls cause considerable morbidity and mortality in older people. It is unclear how vitamin D supplementation affects falls risk, particularly when taken at high doses. We sought to determine whether monthly high‐dose vitamin D supplementation reduces risk and incidence of falls.MethodsWe used data from the randomized, double‐blind, placebo‐controlled D‐Health Trial conducted in Australia. Between February 2014 and May 2015, 21 315 participants aged 60–84 years were randomized (1:1) to monthly doses of either 60 000 IU of colecalciferol or placebo for a maximum of 5 years. People who reported a history of osteomalacia, sarcoidosis, hyperparathyroidism, hypercalcaemia or kidney stones or who were taking >500 IU/day supplementary vitamin D were ineligible. Each year, we collected blood samples from ~450 randomly sampled participants from each trial arm and measured 25‐hydroxyvitamin D [25(OH)D]. Falls, a prespecified tertiary outcome, were ascertained using annual surveys and, for a subset of participants, 3‐month falls diaries. The primary outcome for this analysis was any fall in the month before completing an annual survey. As part of our process to maintain blinding, we used random samples of participants (surveys, n = 16 000; diaries, n = 2400), with equal numbers per group. Participants with no outcome data were excluded. Following an intention‐to‐treat approach, we analysed outcomes using logistic, ordinal and negative binomial regression. Registration: Australian New Zealand Clinical Trials Registry (ACTRN12613000743763); registered 4 July 2013.ResultsMean treatment duration was 4.3 years (standard deviation [SD] = 1.4 years). Mean serum 25(OH)D concentrations during the trial were 114.8 (SD 30.3) nmol/L and 77.5 (SD 25.2) nmol/L in the vitamin D and placebo groups, respectively. Survey and diary analytic sets included 15 416 and 2200 participants, respectively; approximately half were randomized to vitamin D (surveys: 50.1%; diaries: 50.4%). Vitamin D had no effect on falling in the past month (odds ratio [OR] 1.02, 95% confidence interval [CI] 0.95–1.10). There was an interaction with body mass index (BMI) (P‐interaction = 0.001); vitamin D increased risk in participants with BMI < 25 kg/m2 (OR 1.25, 95% CI 1.09–1.43), but there was no effect in those with BMI ≥ 25 kg/m2 (OR 0.95, 95% CI 0.87–1.04). Analyses of diary data were consistent with these findings. The incidence of hypercalcaemia and kidney stones did not differ between groups.ConclusionsMonthly high‐dose vitamin D supplementation did not reduce risk of falling. A possible increased risk of falling with vitamin D supplementation in people with normal BMI warrants further investigation.
Cryptococcus extracellular vesicles properties and their use as vaccine platforms
Authors: Rizzo Juliana , Wong Sarah Sze Wah , Gazi Anastasia D. , Moyrand Frédérique , Chaze Thibault , Commere Pierre‐Henri , Novault Sophie , Matondo Mariette , Péhau‐Arnaudet Gérard , Reis Flavia C. G. , Vos Matthijn , Alves Lysangela R. , May Robin C. , Nimrichter Leonardo , Rodrigues Marcio L. , Aimanianda Vishukumar , Janbon Guilhem 
Published: August 2021

AbstractWhereas extracellular vesicle (EV) research has become commonplace in different biomedical fields, this field of research is still in its infancy in mycology. Here we provide a robust set of data regarding the structural and compositional aspects of EVs isolated from the fungal pathogenic species Cryptococcus neoformans, C. deneoformans and C. deuterogattii. Using cutting‐edge methodological approaches including cryogenic electron microscopy and cryogenic electron tomography, proteomics, and flow cytometry, we revisited cryptococcal EV features and suggest a new EV structural model, in which the vesicular lipid bilayer is covered by mannoprotein‐based fibrillar decoration, bearing the capsule polysaccharide as its outer layer. About 10% of the EV population is devoid of fibrillar decoration, adding another aspect to EV diversity. By analysing EV protein cargo from the three species, we characterized the typical Cryptococcus EV proteome. It contains several membrane‐bound protein families, including some Tsh proteins bearing a SUR7/PalI motif. The presence of known protective antigens on the surface of Cryptococcus EVs, resembling the morphology of encapsulated virus structures, suggested their potential as a vaccine. Indeed, mice immunized with EVs obtained from an acapsular C. neoformans mutant strain rendered a strong antibody response in mice and significantly prolonged their survival upon C. neoformans infection.