bluuebunny/crossref_metadata_2025_split huggingface dataset:
Illite
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Ar dating of Eocene deformation in the Chiapas Fold and Thrust Belt, southern Mexico
Authors: Hernández-Vergara Rogelio , Fitz-Díaz Elisa , Brocard Gilles , Morán-Zenteno Dante Jaime 
Published: July 2020

Abstract

The Chiapas Fold and Thrust Belt (CFTB) of southern Mexico underwent widespread contraction during the well-documented middle Miocene ‘Chiapanecan’ Orogeny. However, earlier phases of folding have been documented in the region and might have affected the belt before the Miocene. We carried out a stratigraphic review and a structural analysis of the belt, complemented by
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Ar dating of synorogenic illite to identify the successive pulses of deformation. Reliable radiometric ages were obtained in three folds from the southern portion of the belt, and in one thrust gouge near the front of the belt. Authigenic illite-rich samples were located in Upper Cretaceous limestone successions that experienced bed-parallel shear during folding and thrusting. They yielded ages ranging from 35 to 40 Ma in the folds and 54.5 ± 7 Ma in the thrust, documenting thin-skinned folding and thrusting in the belt mostly in Eocene time. Some of the basement faults of the belt may have been active during this phase. However, most of the pervasive lateral faults that cross-cut the regional folds in the belt were mostly active from the Miocene onwards, causing transpression and fold amplification.
Women at the dawn of diamond discovery in Siberia or how two women discovered the Siberian diamond province
Authors: Kiseeva Ekaterina S. , Yuzmukhametov Rishat N. 
Published: July 2020

Abstract
Exploration for diamonds in the Soviet Union started in the 1940s; however, it was not until the beginning of 1950s that the government acknowledged a strong need for locally mined diamonds. In this paper, based on publications from Russian literature, we recount a story of two female geologists, Larisa Popugaeva and Natalia Sarsadskhih.
Natalia was the head of the mineralogical laboratory who implemented a new methodology to search for mineral indicators of primary diamond deposits. Larisa was a young geologist who joined Natalia's team in 1953.
The work of these women led to the discovery, in 1954, of the first diamond deposit in the country – the kimberlite pipe ‘Zarnitsa’. In 1954, Natalia was unable to go into the field and, therefore, the discovery was made by Larisa. Credit for this discovery, however, was claimed by the higher officials from the Amakinskaya expedition, one of the largest diamond exploration organizations in the country. Multiple efforts to restore justice did not succeed, with Larisa only being awarded the title of the ‘Discoverer’ in 1970 and Natalia not until 1990. This paper provides a description of Larisa's and Natalia's lives up until the discovery of Zarnitsa, and a few significant events after.
Human Cancers Express TRAILshort, a Dominant Negative TRAIL Splice Variant, Which Impairs Immune Effector Cell Killing of Tumor Cells
Authors: Aboulnasr Fatma , Krogman Ashton , Graham Rondell P. , Cummins Nathan W. , Misra Anisha , Garcia-Rivera Enrique , Anderson Jeff R. , Natesampillai Sekar , Kogan Nicole , Aravamudan Murali , Nie Zilin , Chung Thomas D.Y. , Buick Richard , Feldman Andrew L. , King Rebecca L. , Novak Anne J. , Ansell Stephen M. , Kenderian Saad , Badley Andrew D. 
Published: July 2020

Abstract

Purpose:
TNF-related apoptosis inducing ligand (TRAIL) expression by immune cells contributes to antitumor immunity. A naturally occurring splice variant of TRAIL, called TRAILshort, antagonizes TRAIL-dependent cell killing. It is unknown whether tumor cells express TRAILshort and if it impacts antitumor immunity.

Experimental Design:
We used an unbiased informatics approach to identify TRAILshort expression in primary human cancers, and validated those results with IHC and ISH. TRAILshort-specific mAbs were used to determine the effect of TRAILshort on tumor cell sensitivity to TRAIL, and to immune effector cell dependent killing of autologous primary tumors.

Results:
As many as 40% of primary human tumors express TRAILshort by both RNA sequencing and IHC analysis. By ISH, TRAILshort expression is present in tumor cells and not bystander cells. TRAILshort inhibition enhances cancer cell lines sensitivity to TRAIL-dependent killing both in vitro and in immunodeficient xenograft mouse models. Immune effector cells isolated from patients with B-cell malignancies killed more autologous tumor cells in the presence compared with the absence of TRAILshort antibody (P &lt; 0.05).

Conclusions:
These results identify TRAILshort in primary human malignancies, and suggest that TRAILshort blockade can augment the effector function of autologous immune effector cells.
See related commentary by de Miguel and Pardo, p. 5546
A Diagnostic Biopsy-Adapted Immunoscore Predicts Response to Neoadjuvant Treatment and Selects Patients with Rectal Cancer Eligible for a Watch-and-Wait Strategy
Authors: El Sissy Carine , Kirilovsky Amos , Van den Eynde Marc , Muşină Ana-Maria , Anitei Maria-Gabriela , Romero Alfredo , Marliot Florence , Junca Audelaure , Doyen Jérôme , Mlecnik Bernhard , Haicheur Nacilla , Fredriksen Tessa , Lagorce Christine , Jouret-Mourin Anne , Leonard Daniel , Bibeau Frédéric , Iseas Soledad , Roca Enrique L. , Cabanne Ana M. , Vaccaro Carlos A. , Santino Juan P. , Huertas Eduardo , Tougeron David , Carvalho Carlos , Figueiredo Nuno , Perez Rodrigo O. , Habr-Gama Angelita , Scripcariu Viorel , Gerard Jean-Pierre , Galon Jérôme , Zeitoun Guy , Pagès Franck 
Published: July 2020

Abstract

Purpose:
No biomarker to personalize treatment in locally advanced rectal cancer (LARC) is currently available. We assessed in LARC whether a diagnostic biopsy-adapted immunoscore (ISB) could predict response to neoadjuvant treatment (nT) and better define patients eligible to an organ preservation strategy (“Watch-and-Wait”).

Experimental Design:
Biopsies from two independent cohorts (n1 = 131, n2 = 118) of patients with LARC treated with nT followed by radical surgery were immunostained for CD3+ and CD8+ T cells and quantified by digital pathology to determine ISB. The expression of immune-related genes post-nT was investigated (n = 64 patients). Results were correlated with response to nT and disease-free survival (DFS). The ISB prognostic performance was further assessed in a multicentric cohort (n = 73 patients) treated by Watch-and-Wait.

Results:
ISB positively correlated with the degree of histologic response (P &lt; 0.001) and gene expression levels for Th1 orientation and cytotoxic immune response, post-nT (P = 0.006). ISB high identified patients at lower risk of relapse or death compared with ISB low [HR, 0.21; 95% confidence interval (CI), 0.06–0.78; P = 0.009]. Prognostic performance of ISB for DFS was confirmed in a validation cohort. ISB was an independent parameter, more informative than pre- (P &lt; 0.001) and post-nT (P &lt; 0.05) imaging to predict DFS. ISB combined with imaging post-nT discriminated very good responders that could benefit from organ preservation strategy. In the “Watch-and-Wait” cohort (n = 73), no relapse was observed in patients with ISB high (23.3%).

Conclusions:
ISB predicts response to nT and survival in patients with LARC treated by surgery. Its usefulness in the selection of patients eligible for a Watch-and-Wait strategy is strongly suggested.
The Role of Specific ATP-Binding Cassette Transporters in the Acquired Resistance to Pyrrolobenzodiazepine Dimer–Containing Antibody–Drug Conjugates
Authors: Corbett Simon , Huang Shiran , Zammarchi Francesca , Howard Philip W. , van Berkel Patrick H. , Hartley John A. 
Published: July 2020

Abstract
Antibody–drug conjugates (ADC) containing pyrrolobenzodiazepine (PBD) dimers are being evaluated clinically in both hematologic and solid tumors. These include ADCT-301 (camidanlumab tesirine) and ADCT-402 (loncastuximab tesirine) in pivotal phase II trials that contain the payload tesirine, which releases the PBD dimer warhead SG3199. An important consideration in future clinical development is acquired resistance. The aim was to generate and characterize PBD acquired resistant cell lines in both hematologic and solid tumor settings. Human Karpas-299 (ALCL) and NCI-N87 (gastric cancer) cells were incubated with increasing IC50 doses of ADC (targeting CD25 and HER2, respectively) or SG3199 in a pulsed manner until stable acquired resistance was established. The level of resistance achieved was approximately 3,000-fold for ADCT-301 and 3-fold for SG3199 in Karpas-299, and 8-fold for ADCT-502 and 4-fold for SG3199 in NCI-N87. Cross-resistance between ADC and SG3199, and with an alternative PBD-containing ADC or PBD dimer was observed. The acquired resistant lines produced fewer DNA interstrand cross-links, indicating an upstream mechanism of resistance. Loss of antibody binding or internalization was not observed. A human drug transporter PCR Array revealed several genes upregulated in all the resistant cell lines, including ABCG2 and ABCC2, but not ABCB1(MDR1). These findings were confirmed by RT-PCR and Western blot, and inhibitors and siRNA knockdown of ABCG2 and ABCC2 recovered drug sensitivity. These data show that acquired resistance to PBD-ADCs and SG3199 can involve specific ATP-binding cassette drug transporters. This has clinical implications as potential biomarkers of resistance and for the rational design of drug combinations.
Fatty Acid Oxidation Is an Adaptive Survival Pathway Induced in Prostate Tumors by HSP90 Inhibition
Authors: Nassar Zeyad D. , Mah Chui Yan , Centenera Margaret M. , Irani Swati , Sadowski Martin C. , Scott Julia S. , Nguyen Elizabeth V. , Nagarajan Shilpa R. , Moldovan Max , Lynn David J. , Daly Roger J. , Hoy Andrew J. , Butler Lisa M. 
Published: July 2020

Abstract

HSP90 is a molecular chaperone required for stabilization and activation of hundreds of client proteins, including many known oncoproteins. AUY922 (luminespib), a new-generation HSP90 inhibitor, exhibits potent preclinical efficacy against several cancer types including prostate cancer. However, clinical use of HSP90 inhibitors for prostate cancer has been limited by toxicity and treatment resistance. Here, we aimed to design an effective combinatorial therapeutic regimen that utilizes subtoxic doses of AUY922, by identifying potential survival pathways induced by AUY922 in clinical prostate tumors. We conducted a proteomic analysis of 30 patient-derived explants (PDE) cultured in the absence and presence of AUY922, using quantitative mass spectrometry. AUY922 significantly increased the abundance of proteins involved in oxidative phosphorylation and fatty acid metabolism in the PDEs. Consistent with these findings, AUY922-treated prostate cancer cell lines exhibited increased mitochondrial mass and activated fatty acid metabolism processes. We hypothesized that activation of fatty acid oxidation is a potential adaptive response to AUY922 treatment and that cotargeting this process will sensitize prostate cancer cells to HSP90 inhibition. Combination treatment of AUY922 with a clinical inhibitor of fatty acid oxidation, perhexiline, synergistically decreased viability of several prostate cancer cell lines, and had significant efficacy in PDEs. The novel drug combination treatment induced cell-cycle arrest and apoptosis, and attenuated the heat shock response, a known mediator of HSP90 treatment resistance. This combination warrants further preclinical and clinical investigation as a novel strategy to overcome resistance to HSP90 inhibition.

Implications:
Metabolic pathways induced in tumor cells by therapeutic agents may be critical, but targetable, mediators of treatment resistance.
<p><strong><em>Camellia ngheanensis </em></strong><strong>(Sect. <em>Chrysantha</em>: Theaceae), a new species from Central Vietnam</strong></p>
Authors: DO NGOC-DAI , LUONG VAN-DUNG , LE THI-HUONG , NGUYEN DANH-HUNG , NGUYEN THANH-NHAN , LY NGOC-SAM 
Published: July 2020

Camellia ngheanensis, a new species of Theaceae, is described and illustrated from Nghe An Province, Central Vietnam. It is most similar to C. ninhii in pubescent hairs on twigs and abaxial leaf blades, colour of flowers, pubescent ovary, glabrous filament, free styles from the base but differing by the glabrous petioles, pubescent bracteoles, 5-pubesncent sepals, 12 or 13 pubescent petals, and pubescent styles. The comparison between the new species and C. euphlebia, C. petelotii, and C. velutina is presented. Data on ecology, phenology, vernacular name and uses, expected conservation status are given along with an illustration and a coloured plate.
Complementary therapy in palliative care: A synthesis of qualitative and quantitative systematic reviews
Authors: Armstrong Megan , Kupeli Nuriye , Flemming Kate , Stone Patrick , Wilkinson Susie , Candy Bridget 
Published: July 2020

Background: Interventions delivered in palliative care are complex and their evaluation through qualitative and quantitative research can lead to contrasting results. In a systematic review of trials, the effectiveness results of complementary therapies in palliative care were inconclusive; however, our qualitative synthesis showed participants perceived them to be beneficial. Aim: Use a novel methodology to synthesise evidence from qualitative and quantitative systematic reviews on complementary therapy in palliative care to explore the following: (1) If interventions delivered in trials reflect how participants in qualitative studies report they are delivered in real-life settings and (2) whether quality of life measures used in trials capture perceived benefits that are reported in qualitative studies. Methods: Two matrix tables were formulated. In one, key components in delivery of the complementary therapy from the qualitative synthesis which are as follows: (1) relationship with therapist, (2) comfortable environment, (3) choices (e.g. area of massage) and (4) frequent sessions, were plotted against intervention description, to explore matches and mismatches. In the other, items included in quality of life scales were compared with perceived benefits of complementary therapy. Results: None of the trials included all four key delivery components. The five quality of life scales used in the trials failed to capture the range of perceived benefits from the complementary therapies and many included inappropriate or redundant items. Conclusions: By integrating qualitative and quantitative review data, we determined the reasons trials may be inconclusive. This methodological exemplar provides a framework for understanding complexity in outcomes across trials and a direction for future research.
A surgical decompression procedure for effective treatment of calcified lumbar disc herniation
Authors: Wang Dawei , Xing Jianqiang , Shao Bin , Su Hongmin , Zhang Xiaomei , Zhao Wei , Fang Qingmin , Sun Jinchuan , Zhang Zheng , Zhang Daijie , Zhang Tianqi 
Published: July 2020

Objective To present our experience in managing calcified lumbar disc herniation (cLDH) using a surgical decompression procedure. Methods Patients who had low back pain radiating to the leg, were preoperatively diagnosed with cLDH by computed tomography and/or magnetic resonance imaging, and were treated with a surgical decompression procedure were studied. Those without cLDH or who were treated with a method other than decompression were excluded. The treatment outcome was analyzed using the visual analog scale (VAS) score, Oswestry Disability Index, and modified Macnab criteria. Results Thirty-seven patients aged 60.5 ± 9.6 years were evaluated. The VAS scores were significantly decreased 1 day after surgery and remained low at the 3-month and 1-year follow-ups. The Oswestry Disability Index was also significantly lower at the 3-month and 1-year follow-ups. Ninety-four percent of patients rated the results as “excellent” or “good” according to the modified Macnab criteria at the 3-month follow-up. The patients developed few postoperative complications and no recurrence during 1 year of follow-up. Conclusion Our data suggest that the decompression approach is effective for management of cLDH at least in the short term (1 year) with respect to reducing pain and improving patient satisfaction with few complications.
Frailty Is Associated With Decreased Time Spent at Home After Critical Illness: A Population-Based Study
Authors: Hendin Ariel , Tanuseputro Peter , McIsaac Daniel I. , Hsu Amy T. , Smith Glenys A. , Begum Jahanara , Thompson Laura Hilary , Stelfox Henry T. , Reardon Peter , Herritt Brent , Chaudhuri Dipayan , Rosenberg Erin , Kyeremanteng Kwadwo 
Published: July 2020

Background: Frailty is characterized by vulnerability to stressors due to an accumulation of multiple functional deficits. Frailty is increasingly recognized as a risk factor for accelerated functional decline, increasing dependency, and risk of mortality. The objective of this study was to examine the association of frailty, at the time of critical care admission, with days alive at home and health care costs post-discharge. Methods: This retrospective cohort study used linked administrative data (2010-2016) in Ontario, Canada. We identified all patients admitted at the intensive care unit (ICU), aged 19 years and above, assessed using the Resident Assessment Instrument for Home Care (RAI-HC), within 6 months prior to index hospitalization including an ICU stay. Patients were stratified as robust, pre-frail, or frail based on a validated Frailty Index. The primary outcome was days alive at home in the year after admission. Secondary outcomes included mortality, health care–associated costs, ICU interventions, long-term care admissions, and hospital readmissions. Results: Frail patients spent significantly fewer days at home within 1 year of index hospitalization (mean 159 days vs 223 days in robust cohort, P < .001). Mortality was higher among frail patients at 1 year (59.6% in the frail cohort vs 45.9% in robust patients; odds ratio for death 1.59 [1.49-1.69]). Frail patients also had higher rates of long-term care admission within 1 year (30.1% vs 10.6% in robust patients). Total health care–associated costs per person alive were $30 450 higher the year after admission in the frail cohort. Conclusions: Frailty prior to ICU admission among patients who were eligible for RAI-HC assessment was associated with higher mortality and fewer days spent at home following admission. Frail patients had markedly higher rates of long-term care admission and increased costs per life saved following critical illness. These findings add to the discussion of risk–benefit trade-offs for ICU admission.
Influence of varying nitrogen on creep deformation and damage behaviour of type 316L in the framework of continuum damage mechanics approach
Authors: Christopher J , Praveen C , Ganesan V , Reddy GV Prasad , Albert Shaju K 
Published: July 2020

In the present study, Kachanov–Rabotnov continuum damage model has been employed to describe the steady state and tertiary creep deformation and damage behaviour of 316L austenitic stainless steel with different nitrogen contents of 0.07, 0.11 and 0.22 wt%, at 923 K. For all the nitrogen contents, the model appropriately predicts the creep strain–time data, creep rupture strain and rupture life. The model parameters such as characteristic strain and damage rates systematically decrease with the increase in nitrogen content. The derived iso-damage contours superimposed on creep strain–time data indicate that the evolution kinetics of strain, as well as damage, are unique at each applied stress level. For nitrogen added type 316L SS, the critical damage value ( ωcr) at which creep failure takes place is found to be less than 1 and is in the range of 0.35–0.60. It is observed that the dominance of damage rate ([Formula: see text]) over the strain rate ([Formula: see text]) increases with increasing nitrogen content from 0.07 to 0.22% N for the steel. A direct correlation has been established between the creep rupture ductility and the ratio of strain rate to damage rate, i.e. [Formula: see text]/[Formula: see text] using the Kachanov–Rabotnov model for different nitrogen contents and stress levels.
Highly efficient clinical trial designs for reliable screening of under-performing treatments: Application to the COVID-19 Pandemic
Authors: Piantadosi Steven 
Published: July 2020

Background: The COVID-19 pandemic presents challenges for clinical trials including urgency, disrupted infrastructure, numerous therapeutic candidates, and the need for highly efficient trial and development designs. This paper presents design components and rationale for constructing highly efficient trials to screen potential COVID-19 treatments. Methods: Key trial design elements useful in this circumstance include futility hypotheses, treatment pooling, reciprocal controls, ranking and selection, and platform administration. Assuming most of the many candidates for COVID-19 treatment are likely to be ineffective, these components can be combined to facilitate very efficient comparisons of treatments. Results: Simulations indicate such designs can reliably discard underperforming treatments using sample size to treatment ratios under 30. Conclusions: Methods to create very efficient clinical trial comparisons of treatments for COVID-19 are available. Such designs might be helpful in the pandemic and should be considered for similar needs in the future.
Protocol adherence rates in superiority and noninferiority randomized clinical trials published in high impact medical journals
Authors: Bamat Nicolas A , Ekhaguere Osayame A , Zhang Lingqiao , Flannery Dustin D , Handley Sara C , Herrick Heidi M , Ellenberg Susan S 
Published: July 2020

Background/aims: Noninferiority clinical trials are susceptible to false confirmation of noninferiority when the intention-to-treat principle is applied in the setting of incomplete trial protocol adherence. The risk increases as protocol adherence rates decrease. The objective of this study was to compare protocol adherence and hypothesis confirmation between superiority and noninferiority randomized clinical trials published in three high impact medical journals. We hypothesized that noninferiority trials have lower protocol adherence and greater hypothesis confirmation. Methods: We conducted an observational study using published clinical trial data. We searched PubMed for active control, two-arm parallel group randomized clinical trials published in JAMA: The Journal of the American Medical Association, The New England Journal of Medicine, and The Lancet between 2007 and 2017. The primary exposure was trial type, superiority versus noninferiority, as determined by the hypothesis testing framework of the primary trial outcome. The primary outcome was trial protocol adherence rate, defined as the number of randomized subjects receiving the allocated intervention as described by the trial protocol and followed to primary outcome ascertainment (numerator), over the total number of subjects randomized (denominator). Hypothesis confirmation was defined as affirmation of noninferiority or the alternative hypothesis for noninferiority and superiority trials, respectively. Results: Among 120 superiority and 120 noninferiority trials, median and interquartile protocol adherence rates were 91.5 [81.4–96.7] and 89.8 [83.6–95.2], respectively; P = 0.47. Hypothesis confirmation was observed in 107/120 (89.2%) of noninferiority and 64/120 (53.3%) of superiority trials, risk difference (95% confidence interval): 35.8 (25.3–46.3), P < 0.001. Conclusion: Protocol adherence rates are similar between superiority and noninferiority trials published in three high impact medical journals. Despite this, we observed greater hypothesis confirmation among noninferiority trials. We speculate that publication bias, lenient noninferiority margins and other sources of bias may contribute to this finding. Further study is needed to identify the reasons for this observed difference.