bluuebunny/crossref_metadata_2025 huggingface dataset:
The life history of human foraging: Cross-cultural and individual variation
Authors: Koster Jeremy , McElreath Richard , Hill Kim , Yu Douglas , Shepard Glenn , van Vliet Nathalie , Gurven Michael , Trumble Benjamin , Bird Rebecca Bliege , Bird Douglas , Codding Brian , Coad Lauren , Pacheco-Cobos Luis , Winterhalder Bruce , Lupo Karen , Schmitt Dave , Sillitoe Paul , Franzen Margaret , Alvard Michael , Venkataraman Vivek , Kraft Thomas , Endicott Kirk , Beckerman Stephen , Marks Stuart A. , Headland Thomas , Pangau-Adam Margaretha , Siren Anders , Kramer Karen , Greaves Russell , Reyes-García Victoria , Guèze Maximilien , Duda Romain , Fernández-Llamazares Álvaro , Gallois Sandrine , Napitupulu Lucentezza , Ellen Roy , Ziker John , Nielsen Martin R. , Ready Elspeth , Healey Christopher , Ross Cody
Published: June 2020

Hunters exhibit high skill across the life span, individuals vary substantially in skill, and age-related peaks vary across sites.
Coordinated regulation of cellular identity–associated H3K4me3 breadth by the COMPASS family
Authors: Sze Christie C. , Ozark Patrick A. , Cao Kaixiang , Ugarenko Michal , Das Siddhartha , Wang Lu , Marshall Stacy A. , Rendleman Emily J. , Ryan Caila A. , Zha Didi , Douillet Delphine , Chen Fei Xavier , Shilatifard Ali
Published: June 2020

The COMPASS family members Set1A, Set1B, and Mll2 differentially regulate H3K4me3 peak breadth in embryonic stem cells.
A kinase bioscavenger provides antibiotic resistance by extremely tight substrate binding
Authors: Terekhov Stanislav S. , Mokrushina Yuliana A. , Nazarov Anton S. , Zlobin Alexander , Zalevsky Arthur , Bourenkov Gleb , Golovin Andrey , Belogurov Alexey , Osterman Ilya A. , Kulikova Alexandra A. , Mitkevich Vladimir A. , Lou Hua Jane , Turk Benjamin E. , Wilmanns Matthias , Smirnov Ivan V. , Altman Sidney , Gabibov Alexander G.
Published: June 2020

The substrate-driven closure determines an outstanding efficacy of antibiotic inactivation in a new kinase subfamily.
Context for interpreting equilibrium climate sensitivity and transient climate response from the CMIP6 Earth system models
Authors: Meehl Gerald A. , Senior Catherine A. , Eyring Veronika , Flato Gregory , Lamarque Jean-Francois , Stouffer Ronald J. , Taylor Karl E. , Schlund Manuel
Published: June 2020

A historical context is provided for interpreting the equilibrium climate sensitivity (ECS) and transient climate response (TCR).
Vaccine-mediated protection against
Campylobacter
-associated enteric disease
Authors: Quintel Benjamin K. , Prongay Kamm , Lewis Anne D. , Raué Hans-Peter , Hendrickson Sara , Rhoades Nicholas S. , Messaoudi Ilhem , Gao Lina , Slifka Mark K. , Amanna Ian J.
Published: June 2020

We describe a novel vaccine that provides protection against
Campylobacter
-associated diarrhea in a natural exposure model.
Methanol conversion on borocarbonitride catalysts: Identification and quantification of active sites
Authors: Zhang Xuefei , Yan Pengqiang , Xu Junkang , Li Fan , Herold Felix , Etzold Bastian J. M. , Wang Peng , Su Dang Sheng , Lin Sen , Qi Wei , Xie Zailai
Published: June 2020

The nature of methanol conversion on borocarbonitride was revealed via active site quantification and kinetic analysis.
Iceland is an episodic source of atmospheric ice-nucleating particles relevant for mixed-phase clouds
Authors: Sanchez-Marroquin A. , Arnalds O. , Baustian-Dorsi K. J. , Browse J. , Dagsson-Waldhauserova P. , Harrison A. D. , Maters E. C. , Pringle K. J. , Vergara-Temprado J. , Burke I. T. , McQuaid J. B. , Carslaw K. S. , Murray B. J.
Published: June 2020

We show that Iceland contributes episodically to the regional atmospheric ice-nucleating particle population.
Bioinspired oral delivery of gut microbiota by self-coating with biofilms
Authors: Wang Xinyue , Cao Zhenping , Zhang Mengmeng , Meng Lu , Ming Zunzhen , Liu Jinyao
Published: June 2020

Probiotic self-coated with biofilms achieve strikingly enhanced oral availability and intestinal colonization in a porcine model.
Tumor-targeted CD28 bispecific antibodies enhance the antitumor efficacy of PD-1 immunotherapy
Authors: Waite Janelle C. , Wang Bei , Haber Lauric , Hermann Aynur , Ullman Erica , Ye Xuan , Dudgeon Drew , Slim Rabih , Ajithdoss Dharani K. , Godin Stephen J. , Ramos Ilyssa , Wu Qi , Oswald Erin , Poon Patrick , Golubov Jacquelynn , Grote Devon , Stella Jennifer , Pawashe Arpita , Finney Jennifer , Herlihy Evan , Ahmed Hassan , Kamat Vishal , Dorvilliers Amanda , Navarro Elizabeth , Xiao Jenny , Kim Julie , Yang Shao Ning , Warsaw Jacqueline , Lett Clarissa , Canova Lauren , Schulenburg Teresa , Foster Randi , Krueger Pamela , Garnova Elena , Rafique Ashique , Babb Robert , Chen Gang , Stokes Oristian Nicole , Siao Chia-Jen , Daly Christopher , Gurer Cagan , Martin Joel , Macdonald Lynn , MacDonald Douglas , Poueymirou William , Smith Eric , Lowy Israel , Thurston Gavin , Olson William , Lin John C. , Sleeman Matthew A. , Yancopoulos George D. , Murphy Andrew J. , Skokos Dimitris
Published: June 2020

Antibodies cross-linking the CD28 costimulatory pathway and a target antigen on tumors potentiate the effects of checkpoint immunotherapy.
Working on inflammatory injury in heart transplant
Authors: Rodell Christopher B.
Published: June 2020

Ex vivo perfusion for preservation of donor hearts may be improved by preventing inflammatory tissue injury, including through mechanical work.
Mild or Malign: Clinical Characteristics and Outcomes of Clostridium difficile Infection in Thailand
Authors: Imwattana Korakrit , Putsathit Papanin , Leepattarakit Teera , Kiratisin Pattarachai , Riley Thomas V.
Published: June 2020

Little is known about the clinical characteristics of
Clostridium difficile
infection (CDI) in Asia in general, and Thailand specifically, with a few studies suggesting that the disease may be milder than elsewhere. This study aimed to describe CDI in Thailand, evaluate treatment options and their outcomes, and explore possible protective factors responsible for any unique disease characteristics. From 2015 to 2018, 469 patients were included in the study. All patients had their stools tested for the
tcdB
gene by direct PCR and detection of toxigenic
C. difficile
by culture.
Induction of Rod-Shaped Structures by Herpes Simplex Virus Glycoprotein I
Authors: Zhang Wuchao , Gao Peng , Gui Xixi , Zhou Lei , Ge Xinna , Guo Xin , Wills John W. , Han Jun , Yang Hanchun
Published: June 2020

The HSV-1 gI is required for viral cell-to-cell spread within the host, but the molecular mechanisms of how gI exactly works have remained poorly understood. Here, we report a novel property of this molecule, namely, induction of rod-shaped structures, which appeared to represent a higher-order form of gI. We further mapped the critical residues and showed that the ability of gI to induce rod-shaped structures correlated well with the capability of HSV-1 to induce cell fusion in the UL24syn background, suggesting that the two events may have an intrinsic link. Our results shed light on the biological properties of HSV-1 gI and may have important implications in understanding viral pathogenesis.
Human Desmoglein-2 and Human CD46 Mediate Human Adenovirus Type 55 Infection, but Human Desmoglein-2 Plays the Major Roles
Authors: Feng Ying , Yi Changhua , Liu Xinglong , Qu Linbing , Su Wan , Shu Tao , Zheng Xuehua , Ye Xianmiao , Luo Jia , Hao Mingli , Sun Xikui , Li Liang , Liu Xiaolin , Yang Chenchen , Guan Suhua , Chen Ling , Feng Liqiang
Published: June 2020

Human adenovirus type 55 (HAdV55) has recently emerged as a highly virulent respiratory pathogen and has been linked to severe and even fatal pneumonia in immunocompetent adults. However, the cellular receptors mediating the entry of HAdV55 into host cells remain unclear, which hinders the establishment of HAdV55-infected animal models and the development of antiviral approaches. In this study, we demonstrated that human desmoglein-2 (hDSG2) plays the major roles during HAdV55 infection. Human CD46 (hCD46) could also mediate the infection of HAdV55, but the efficiency was much lower than for hDSG2. We generated two transgenic mouse lines that express either hDSG2 or hCD46, both of which enabled HAd55 infection in otherwise nontransgenic mice. hDSG2 transgenic mice enabled more efficient HAdV55 infection than hCD46 transgenic mice. Our study adds to our understanding of HAdV55 infection and provides an animal model for evaluating HAdV55 vaccines and therapeutics.
Genomic Sequence of the New Attenuated Vaccine Strain Neethling-RIBSP of the Lumpy Skin Disease Virus
Authors: Orynbayev M. B. , Nissanova R. K. , Argimbayeva T. U. , Zakarya K. D. , Myrzakhmetova B. S. , Melisbek A. M. , Barmak S. M. , Issabek A. U. , Nakhanov A. K. , Shevtsov A. , Kozhabergenov N. S. , Sultankulova K. T.
Published: June 2020

We report here the draft genome sequence of the new attenuated strain Neethling-RIBSP of the lumpy skin disease virus, obtained by sequential and alternating passages in cell culture and developing chicken embryos. Genome sequencing allowed the identification of differentiation markers of the new strain.
Diabrotica undecimpunctata virus 2
, a Novel Small RNA Virus Discovered from Southern Corn Rootworm,
Diabrotica undecimpunctata howardi
Barber (Coleoptera: Chrysomelidae)
Authors: Liu Sijun , Valencia-Jiménez Arnubio , Darlington Molly , Vélez Ana M. , Bonning Bryony C.
Published: June 2020

The genome of
Diabrotica undecimpunctata virus 2
(DuV2), a putative positive-sense, single-stranded RNA virus identified from the southern corn rootworm transcriptome, comprises 5,313 nucleotides, including a short poly(A) tail. The two open reading frames encode a nonstructural polyprotein (p156) and a putative capsid protein (p25).
Complete Genome Sequence of a Gram-Positive Bacterium,
Leifsonia
sp. Strain PS1209, a Potato Endophyte
Authors: Liu Yingyu , Ma Xing , Helmann Tyler C. , McLane Heather , Stodghill Paul , Swingle Bryan , Filiatrault Melanie J. , Perry Keith L.
Published: June 2020

We report the complete and annotated genome sequence of a Gram-positive bacterium,
Leifsonia
sp. strain PS1209, a potato endophyte that was isolated from apparently healthy tubers of potato cultivar NY166. The circular genome is 4,091,164 bp long, with a GC content of 69.08%, containing 3,926 genes.
Genome Sequence of
Arthrobacter
sp. Phage Scuttle
Authors: Harrison Melinda , Mastropaolo Matthew D. , Conboy Andrew ,   Cabrini University SEA-PHAGES Annotators
Published: June 2020

Arthrobacter
phage Scuttle was isolated by enrichment from a dry soil sample (collected in Upper Darby, Pennsylvania) on host
Arthrobacter
sp. ATCC 21022. The genome of this phage is 43,729 bp long, has a GC content of 61.1%, and has 61 annotated protein-coding genes.
Draft Genome Sequence of Clostridium cochlearium Strain AGROS13, Isolated from a Sheep Dairy Farm in New Zealand
Authors: Gupta Tanushree B. , Maclean Paul , Jauregui Ruy , Risson Alexis N. , Brightwell Gale
Published: June 2020

We report the draft genome sequence of a new
Clostridium cochlearium
strain, AGROS13, which was isolated from a sheep dairy farm environment in New Zealand. The genome is 2.7 Mbp, with a GC content of 28.2%. The genome sequence was found to be closely related to that of
Clostridium cochlearium
ATCC 17787. The new strain harbors a biosynthetic gene cluster coding for an unknown sactipeptide.
Supplemental Material: A Baltic heritage in Scotland: Basement terrane transfer during the Grenvillian orogeny
Authors: Strachan Rob , al. et
Published: June 2020

Sample descriptions, analytical procedures and results.
12-year analysis of incidence, microbiological profiles and in vitro antimicrobial susceptibility of infectious keratitis: the Nottingham Infectious Keratitis Study
Authors: Ting Darren Shu Jeng , Ho Charlotte Shan , Cairns Jessica , Elsahn Ahmad , Al-Aqaba Mouhamed , Boswell Tim , Said Dalia G , Dua Harminder Singh
Published: June 2020

Background/aims

To examine the incidence, causative microorganisms and in vitro antimicrobial susceptibility and resistance profiles of infectious keratitis (IK) in Nottingham, UK.

Methods

A retrospective study of all patients who were diagnosed with IK and underwent corneal scraping between July 2007 and October 2019 (a 12-year period) at a UK tertiary referral centre. Relevant data, including demographic factors, microbiological profiles and in vitro antibiotic susceptibility of IK, were analysed.

Results

The estimated incidence of IK was 34.7 per 100 000 people/year. Of the 1333 corneal scrapes, 502 (37.7%) were culture-positive and 572 causative microorganisms were identified. Sixty (4.5%) cases were of polymicrobial origin (caused by ≥2 different microorganisms). Gram-positive bacteria (308, 53.8%) were most commonly isolated, followed by Gram-negative bacteria (223, 39.0%), acanthamoeba (24, 4.2%) and fungi (17, 3.0%). Pseudomonas aeruginosa (135, 23.6%) was the single most common organism isolated. There was a significant increase in Moraxella spp (p<0.001) and significant decrease in Klebsiella spp (p=0.004) over time. The in vitro susceptibilities of Gram-positive and Gram-negative bacteria to cephalosporin, fluoroquinolone and aminoglycoside were 100.0% and 81.3%, 91.9% and 98.1%, and 95.2% and 98.3%, respectively. An increase in resistance against penicillin was observed in Gram-positive (from 3.5% to 12.7%; p=0.005) and Gram-negative bacteria (from 52.6% to 65.4%; p=0.22).

Conclusion

IK represents a relatively common and persistent burden in the UK and the reported incidence is likely underestimated. Current broad-spectrum antimicrobial treatment provides a good coverage for IK, although challenged by some level of antimicrobial resistance and polymicrobial infection.
Reduced vessel density in deep capillary plexus correlates with retinal layer
thickness in choroideremia
Authors: Arrigo Alessandro , Romano Francesco , Parodi Maurizio Battaglia , Charbel Issa Peter , Birtel Johannes , Bandello Francesco , Maclaren Robert E
Published: June 2020

Background

To assess retinal layer thickness in choroideremia (CHM) and to reveal its
correlation with optical coherence tomography (OCT) angiography (OCTA)
findings.

Methods

The study was designed as an observational, cross-sectional clinical
series of patients with CHM, which included 14 CHM eyes and 14 age-matched
controls. Multimodal imaging included OCT and OCTA. The vessel density (VD) of
superficial capillary (SCP), deep capillary (DCP) and choriocapillaris (CC)
plexuses was analysed by OCTA. The apparently preserved retinal islet and
atrophic regions were investigated separately. Main outcome measures were as
follows: best-corrected visual acuity (BCVA), total retinal layers, ganglion
cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer
plexiform layer (OPL), outer nuclear layer (ONL), ellipsoid zone–retinal
pigment epithelium (EZ-RPE) layer, choroidal thickness and VDs of SCP, DCP and
of CC.

Results

Mean BCVA was 0.0±0.0 LogMAR in both groups. GCL, ONL, EZ-RPE and choroid
were significantly thinned in CHM, particularly in the atrophic region. OPL was
unaffected in the apparently preserved islet, whereas INL and IPL were
similarly thinned in the atrophic and apparently preserved retina. DCP appeared
severely affected in both regions, while CC was only altered in the atrophic
retina. Significant correlations were found between OCT and OCTA
parameters.

Conclusions

Our study showed severe alterations in both outer and inner retinal layers
of patients with CHM. The extended retinal involvement might be the consequence
of neuronal and vascular trophic factor reduction produced by the primarily
altered RPE and/or secondary Müller glial cell reaction.
Hepatic venous pressure gradient-guided laparoscopic splenectomy and pericardial devascularisation versus endoscopic therapy for secondary prophylaxis for variceal rebleeding in portal hypertension (CHESS1803): study protocol of a multicenter randomised controlled trial in China
Authors: Shao Ruoyang , Li Zhiwei , Wang Jitao , Qi Ruizhao , Liu Qingbo , Zhang Weijie , Mao Xiaorong , Song Xiaojing , Li Lei , Liu Yanna , Zhao Xin , Liu Chuan , Li Xun , Zuo Changzeng , Wang Weidong , Qi Xiaolong
Published: June 2020

Introduction

Gastro-oesophageal variceal bleeding is one of the most common and severe complications with high mortality in cirrhotic patients who developed portal hypertension. Hepatic venous pressure gradient (HVPG) is a globally recommended golden standard for the portal pressure assessment and an HVPG ≥16 mm Hg indicates a higher risk of death and rebleeding. This study aims to compare the effectiveness and safety of splenectomy and pericardial devascularisation (laparoscopic therapy) plus propranolol and endoscopic therapy plus propranolol for variceal rebleeding in cirrhotic patients with HVPG between 16 and 20 mm Hg.

Methods and analysis

This is a multicenter, randomised, controlled clinical trial. Participants will be 1:1 assigned randomly into either laparoscopic or endoscopic groups. Forty participants whose transjugular HVPG lies between 16 and 20 mm Hg with a history of gastro-oesophageal variceal bleeding will be recruited from three sites in China. Participants will receive either endoscopic therapy plus propranolol or laparoscopic therapy plus propranolol. The primary outcome measure will be the occurrence of gastro-oesophageal variceal rebleeding. Secondary outcome measures will include overall survival, occurrence of hepatocellular carcinoma, the occurrence of venous thrombosis, the occurrence of adverse events, quality of life and tolerability of treatment. Outcome measures will be evaluated at baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks and 60 weeks. Multivariate COX regression model will be introduced for analyses of occurrence data and Kaplan-Meier analysis with the log-rank test for intergroup comparison.

Ethics and dissemination

Ethical approval was obtained from all three participating sites. Primary and secondary outcome data will be submitted for publication in peer-reviewed journals and widely disseminated.

Trial registration number

NCT03783065; Pre-results.

Trial status

Recruitment for this study started in December 2018 while the first participant was randomised in January 2019. Recruitment is estimated to stop in October 2019.
Impact of massive blood transfusion during adult extracorporeal membrane oxygenation support on long-term outcomes: a nationwide cohort study in Taiwan
Authors: Chen Fang-Ting , Chen Shao-Wei , Wu Victor Chien-Chia , Hung Kuo-Chun , Chang Shang-Hung , Ting Pei-Chi , Chou An-Hsun
Published: June 2020

Objectives

Bleeding is a common problem during adult extracorporeal membranes oxygenation (ECMO) support, requiring blood transfusion for correction of volume depletion and coagulopathy. The goal of this study is to investigate the long-term outcomes for adults under support of ECMO with massive blood transfusion (MBT).

Design

Retrospective nationwide cohort study.

Setting

Data were provided from Taiwan National Health Insurance Research Database (NHIRD).

Participants and interventions

Totally 2757 adult patients were identified to receive MBT (red blood cell ≥10 units) during ECMO support from 2000 to 2013 via Taiwan NHIRD.

Main outcome measures

The outcomes included in-hospital major complications/mortality, all-cause mortality, cardiovascular death, newly onset end-stage renal disease and respiratory failure during the follow-up period.

Results

Patients with MBT had higher in-hospital mortality (65.6% vs 52.1%; OR 1.74; 95% CI 1.53 to 1.98) and all-cause mortality during the follow-up (47.0% vs 35.8%; HR 1.46; 95% CI 1.25 to 1.71) than those without MBT. Not only higher incidences of post ECMO sepsis, respiratory failure and acute kidney injury, but also longer duration of ECMO support, ventilator use and intensive care unit stay were demonstrated in the MBT group. Moreover, a subdistribution hazard model presented higher cumulative of respiratory failure (19.8% vs 16.2%; subdistribution HR 1.36; 95% CI 1.07 to 1.73) for the MBT cohort. Positive dose–dependent relationship was found between the amount of transfused red blood cell product and in-hospital mortality. In the MBT subgroup analysis for the impact of transfused ratio (fresh frozen plasma/packed red blood cell) on in-hospital mortality, ratio ≥1.0 had higher mortality.

Conclusions

Patients with MBT during ECMO support had worse long-term outcomes than non-MBT population. The transfused amount of red blood cell had positive dose–dependent effect on in-hospital mortality.
Effect of knee arthroplasty on sports participation and activity levels: a systematic review and meta-analysis
Authors: Konings Marco J , De Vroey Henri , Weygers Ive , Claeys Kurt
Published: June 2020

Objective

Desires and expectations of patients in regard to resume participation in sport activities after knee arthroplasty strongly increased in recent years. Therefore, this review systematically reviewed the available scientific literature on the effect of knee arthroplasty on sports participation and activity levels.

Design

Systematic review and meta-analysis.

Data sources

PubMed, Embase, SPORTDiscus and reference lists were searched in February 2019.

Studies eligibility criteria

Inclusion of knee osteoarthritis patients who underwent total knee arthroplasty (TKA) and/or unicondylar knee arthroplasty. Studies had to include at least one preoperative and one postoperative measure (≥1 year post surgery) of an outcome variable of interest (ie, activity level: University of California, Los Angeles and/or Lower Extremity Activity Scale; sport participation: type of sport activity survey).

Results

Nineteen studies were included, consisting data from 4074 patients. Knee arthroplasty has in general a positive effect on activity level and sport participation. Most patients who have stopped participating in sport activities in the year prior to surgery, however, do not seem to reinitiate their sport activities after surgery, in particular after a TKA. In contrast, patients who continue to participate in sport activities until surgery appear to become even more active in low-impact and medium-impact sports than before the onset of restricting symptoms.

Conclusions

Knee arthroplasty is an effective treatment in resuming sports participation and physical activity levels. However, to achieve the full benefits from knee arthroplasty, strategies and guidelines aimed to keep patients capable and motivated to participate in (low-impact or medium-impact) sport activities until close before surgery are warranted.
Cross-sectional survey of the wish to die among palliative patients in Spain: one phenomenon, different experiences
Authors: Belar Alazne , Arantzamendi Maria , Santesteban Yolanda , López-Fidalgo Jesús , Martinez Marina , Lama Marcos , Rullán Maria , Olza Inés , Breeze Ruth , Centeno Carlos
Published: June 2020

Objective

Cultural backgrounds and values have a decisive impact on the phenomenon of the wish to die (WTD), and examination of this in Mediterranean countries is in its early stages. The objectives of this study were to establish the prevalence of WTD and to characterise this phenomenon in our cultural context.

Methods

A cross-sectional study with consecutive advanced inpatients was conducted. Data about WTD (Assessing Frequency & Extent of Desire to Die(AFFED) interview) and anxiety and depression (Edmonton Symptom Assessment System-revised(ESAS-r)) were collected through two face-to-face clinical encounters. Data were analysed with descriptive statistics, χ2and analysis of variance.

Results

201 patients participated and 165 (82%) completed both interviews. Prevalence of WTD was 18% (36/201) in the first interview and 16% (26/165) in the second interview (p=0.25). After the first interview, no changes in depression (p=0.60) or anxiety (p=0.90) were detected. The AFFED shows different experiences within WTD: 11% of patients reported a sporadic experience, while 7% described a persistent experience. Thinking about hastening death (HD) appeared in 8 (22%) out of 36 patients with WTD: 5 (14%) out of 36 patients considered this hypothetically but would never take action, while 3 (8%) out of 36 patients had a more structured idea about HD. In this study, no relation was detected between HD and frequency of the appearance of WTD (p=0.12).

Conclusions

One in five patients had WTD. Our findings suggest the existence of different experiences within the same phenomenon, defined according to frequency of appearance and intention to hasten death. A linguistically grounded model is proposed, differentiating the experiences of the ‘wish’ or ‘desire’ to die, with or without HD ideation.
CD200 promotes immunosuppression in the pancreatic tumor microenvironment
Authors: Choueiry Fouad , Torok Molly , Shakya Reena , Agrawal Kriti , Deems Anna , Benner Brooke , Hinton Alice , Shaffer Jami , Blaser Bradley W , Noonan Anne M , Williams Terence M , Dillhoff Mary , Conwell Darwin L , Hart Phil A , Cruz-Monserrate Zobeida , Bai Xue-Feng , Carson III William E , Mace Thomas A
Published: June 2020

Background

A significant challenge to overcome in pancreatic ductal adenocarcinoma (PDAC) is the profound systemic immunosuppression that renders this disease non-responsive to immunotherapy. Our supporting data provide evidence that CD200, a regulator of myeloid cell activity, is expressed in the PDAC microenvironment. Additionally, myeloid-derived suppressor cells (MDSC) isolated from patients with PDAC express elevated levels of the CD200 receptor (CD200R). Thus, we hypothesize that CD200 expression in the PDAC microenvironment limits responses to immunotherapy by promoting expansion and activity of MDSC.

Methods

Immunofluorescent staining was used to determine expression of CD200 in murine and human PDAC tissue. Flow cytometry was utilized to test for CD200R expression by immune populations in patient blood samples. In vivo antibody blocking of CD200 was conducted in subcutaneous MT-5 tumor-bearing mice and in a genetically engineered PDAC model (KPC-Brca2 mice). Peripheral blood mononuclear cells (PBMC) from patients with PDAC were analyzed by single-cell RNA sequencing. MDSC expansion assays were completed using healthy donor PBMC stimulated with IL-6/GM-CSF in the presence of recombinant CD200 protein.

Results

We found expression of CD200 by human pancreatic cell lines (BxPC3, MiaPaca2, and PANC-1) as well as on primary epithelial pancreatic tumor cells and smooth muscle actin+ stromal cells. CD200R expression was found to be elevated on CD11b+CD33+HLA-DRlo/−MDSC immune populations from patients with PDAC (p=0.0106). Higher expression levels of CD200R were observed in CD15+ MDSC compared with CD14+ MDSC (p<0.001). In vivo studies demonstrated that CD200 antibody blockade limited tumor progression in MT-5 subcutaneous tumor-bearing and in KPC-Brca2 mice (p<0.05). The percentage of intratumoral MDSC was significantly reduced in anti-CD200 treated mice compared with controls. Additionally, in vivo blockade of CD200 can also significantly enhance the efficacy of PD-1 checkpoint antibodies compared with single antibody therapies (p<0.05). Single-cell RNA sequencing of PBMC from patients revealed that CD200R+ MDSC expressed genes involved in cytokine signaling and MDSC expansion. Further, in vitro cytokine-driven expansion and the suppressive activity of human MDSC was enhanced when cocultured with recombinant CD200 protein.

Conclusions

These results indicate that CD200 expression in the PDAC microenvironment may regulate MDSC expansion and that targeting CD200 may enhance activity of checkpoint immunotherapy.
Hyperprogression to camrelizumab in a patient with esophageal squamous cell carcinoma harboring EGFR kinase domain duplication
Authors: Wang Wei , Wu Meihong , Liu Minglu , Yan Zhengqing , Wang Guoqiang , Mao Dongliang , Wang Mei
Published: June 2020

Background

Previous studies have reported that the amplification of some genes, such as Murine Double Minute 2 or 4 and Epidermal Growth Factor Receptor (EGFR), may be related to hyperprogressive disease (HPD). Exploring somatic gene alterations might be an effective method to predict HPD. Herein we characterize the somatic alterations in a patient with esophageal squamous cell carcinoma (ESCC) who developed HPD to investigate the potential origins of HPD.

Case presentation

A man in his mid-40s was diagnosed with ESCC. After the failure of first-line treatment with cisplatin and docetaxel, the patient participated in a phase III randomized, open, multicenter clinical trial (CTR20170307) and subsequently received camrelizumab. After 4 weeks of immunotherapy, the tumor size increased by 79% compared with baseline imaging; the progressive pace was 2.5-fold higher than preimmunotherapy, and a new liver metastasis appeared. A rare EGFR exon 2–28 duplication was discovered in both preimmunotherapy and postimmunotherapy tumor tissues.

Conclusion

This is the first report on a patient with ESCC harboring rare EGFR kinase domain duplication in exons 2–28 and developing HPD in the process of camrelizumab treatment. This case suggested that EGFR kinase domain duplication might be associated with HPD. Administration of immune checkpoint inhibitor monotherapy in this subgroup of patients harboring EGFR kinase domain duplication should be performed with caution. These results need to be further confirmed in a larger cohort of patients.
COVID-19 in South Korea
Authors: Choi Jun Yong
Published: June 2020

A novel coronavirus (severe acute respiratory syndrome-CoV-2) that initially originated from Wuhan, China, in December 2019 has already caused a pandemic. While this novel coronavirus disease (COVID-19) frequently induces mild diseases, it has also generated severe diseases among certain populations, including older-aged individuals with underlying diseases, such as cardiovascular disease and diabetes. As of 31 March 2020, a total of 9786 confirmed cases with COVID-19 have been reported in South Korea. South Korea has the highest diagnostic rate for COVID-19, which has been the major contributor in overcoming this outbreak. We are trying to reduce the reproduction number of COVID-19 to less than one and eventually succeed in controlling this outbreak using methods such as contact tracing, quarantine, testing, isolation, social distancing and school closure. This report aimed to describe the current situation of COVID-19 in South Korea and our response to this outbreak.
COVID-19: lessons for junior doctors redeployed to critical care
Authors: Coughlan Charles , Nafde Chaitanya , Khodatars Shaida , Jeanes Aimi Lara , Habib Sadia , Donaldson Elouise , Besi Christina , Kooner Gurleen Kaur
Published: June 2020

Approximately 4% of patients with coronavirus disease 2019 (COVID-19) will require admission to an intensive care unit (ICU). Governments have cancelled elective procedures, ordered new ventilators and built new hospitals to meet this unprecedented challenge. However, intensive care ultimately relies on human resources. To enhance surge capacity, many junior doctors have been redeployed to ICU despite a relative lack of training and experience. The COVID-19 pandemic poses additional challenges to new ICU recruits, from the practicalities of using personal protective equipment to higher risks of burnout and moral injury. In this article, we describe lessons for junior doctors responsible for managing patients who are critically ill with COVID-19 based on our experiences at an urban teaching hospital.
Estimation of genetic parameters and selection response for reproductive and growth traits in Rideau-Arcott sheep
Authors: Boareki Mohammed N. , Brito Luiz F. , Cánovas Ángela , Osborne Vern , Schenkel Flávio S.
Published: June 2020

The goal of this study was to estimate genetic parameters and predict direct and correlated response to selection for lamb growth traits and ewe reproductive traits, based on single-trait selection or combining multiple traits in an optimum index that targets total litter post-weaning weight in the first lambing as the main selection goal. Heritability estimates ranged from 0.04 to 0.19. Genetic correlations between growth and reproductive traits ranged from −0.24 to 0.15. The indirect response to selection for reproductive traits in later lambings, by selecting on first lambing performance, was 11%–25% greater than direct selection. The response to indirect selection for composite reproductive traits, i.e., total weaning weight or total post-weaning weight, by selecting on individual lamb weaning weight or post-weaning weight was 1%–69% greater than direct selection, but it was accompanied by a negative response on litter size. However, combining alternate growth and reproductive traits in optimum selection index resulted in correlated response of up to 96% greater than direct selection response for reproductive traits without a negative response on litter size. Therefore, multiple trait selection using an index of component traits was more effective than direct selection for a composite trait.
Perception of consultants, feedlot owners, and packers regarding the optimal economic slaughter endpoint in feedlots: a national survey in Brazil (Part I)
Authors: de Andrade Thiago Sérgio , Albertini Tiago Zanett , Barioni Luís Gustavo , de Medeiros Sérgio Raposo , Millen Danilo Domingues , dos Santos Antônio Carlos Ramos , Goulart Rodrigo Silva , Lanna Dante Pazzanese Duarte
Published: June 2020

Little information exists regarding the optimal economic slaughter endpoint (OSE) for feedlot-finished cattle in Brazil. This study investigated the perceptions of Brazilian feeders regarding the optimal time for slaughter. A total of 52 interviews were conducted involving nutritionist-consultants (n = 23), feedlot owners (n = 21), and packer-owned feedlots (n = 8). The results showed that 65% of the interviewees used weight and fat cover, both estimated visually, to determine the moment for slaughter. Identifying the ideal time for slaughter was considered a challenge for respondents, and 85% of them recognized that their current slaughter endpoint identification method needed improvements. Regarding decision support systems, 58% of respondents reported they would purchase a computer program to help identify OSE, and 73% would be interested in incorporating a prototype of such a system into their feedlots. Carcass dressing (38%) and price (25%) were the main factors driving the feeder’s choice of meatpacker, followed by carcass premiums (10%). Meat quality was found to be an irrelevant criterion for Brazilian meatpackers in awarding both premiums (5%) and deductions (3%). Slaughter endpoint is determined subjectively by the Brazilian feeders, based on a visual evaluation of both weight and fatness.
Pore size distribution and pore functional characteristics of soils as affected by rock fragments in the hilly regions of the Sichuan Basin, China
Authors: Li Jiangwen , Han Zhen , Zhong Shouqin , Gao Pengfei , Wei Chaofu
Published: June 2020

Soil pore size distribution and pore functional characteristics are the most important for soil physical properties, water retention, and transmission. Furthermore, considerable amounts of rock fragments are present in hilly region soils. In this study, we discuss the pore size distribution and pore functional characteristics of soils as affected by rock fragments in the hilly regions of Sichuan Basin, China. The soil water characteristic curve was measured to calculate the soil total porosity and the ratio of equivalent pores in each diameter class. The results suggest that the soil total porosity decreases with increasing rock fragments size. The proportion of transmission pores increased gradually with increasing rock fragment content, whereas the fractions of storage pores and residual-bonding pores decrease gradually. Furthermore, the ratio of effective soil porosity to total porosity is higher than that of ineffective porosity to total porosity with increasing rock fragment content. In summary, increasing the rock fragment content can notably increase the proportion of soil transmission pores, thereby increasing soil aeration and water permeability. However, a high rock fragment content is not conducive to maintaining the water needed for normal plant growth.
Tilted universe with big rip singularity in Lyra geometry
Authors: Dagwal V. J. , Pawar D. D. , Solanke Y. S. , Shaikh H. R.
Published: June 2020

We have examined tilted cosmological models by using conformally flat space-time with wet dark fluid in Lyra geometry. In order to solve the field equations we have considered a power law. In this paper we have discussed tilted universe with time-dependent displacement field vector, heat conduction vectors and also discussed big rip singularity. Some physical and geometrical properties are also investigated. We have also extended our work to investigate the consistency of the derived model with observational parameter from the point of astrophysical phenomenon such as look-back time-redshift, proper distance, luminosity distance, angular-diameter distance and distance modulus.
Effects of the external string cloud on the Van der Waals-like behavior and efficiency of AdS-Schwarzschild black holes in massive gravity
Authors: Ghanaatian M. , Sadeghi Mehdi , Ranjbari Hadi , Forozani Gh.
Published: June 2020

In this paper, we study AdS-Schwarzschild black holes in four and five dimensions in dRGT minimally coupled to a cloud of strings. It is observed that the entropy of the string cloud and massive terms does not affect the black hole entropy. The observations about four dimensions indicate that the massive term in the presence of external string cloud cannot exhibit Van der Waals-like behavior for AdS-Schwarzschild black holes and, therefore there is only the Hawking–Page phase transition. In contrast, in five dimensions, the graviton mass modifies this behavior through the third massive term, so that a critical behavior and second-order phase transition is deduced. Also, the Joule–Thomson effect is not observed. The black hole stability conditions are also studied in four and five dimensions and a critical value for the string cloud parameter is presented. In five dimensions a degeneracy between states for extremal black holes is investigated. After studying black holes as thermodynamic systems, we consider such systems as heat engines, and finally the efficiency of them is calculated.
Research on micro-cavity structure processing technology based on porous silicon
Authors: Liu Zhi-Yuan , Shang Ying-Qi , Yu Hai-Chao , Qi Hong , Zhang Yan , Chen Jing , Wu Ya-Lin
Published: June 2020

Aiming at the problem of heterogeneity of sealed cavity in silicon microstructure processing technology, the technology of preparing micro-cavity by using porous silicon sacrificial layer is proposed. The effect of current density on the preparation of porous silicon and the effect of porous silicon with different porosity on the formation of micro-cavity in the preparation process of porous silicon were studied. Different process parameters were selected for experiments and the prepared micro-cavities were tested and analyzed. According to the test results, the suitable electrochemical corrosion process parameters were selected to prepare porous silicon, and the micro-cavity was realized by changing the process parameters, which greatly increased the application fields of micro-sensors and micro-actuators.
A descriptive Main Gap Theorem
Authors: Mangraviti Francesco , Motto Ros Luca
Published: June 2020

Answering one of the main questions of [S.-D. Friedman, T. Hyttinen and V. Kulikov, Generalized descriptive set theory and classification theory, Mem. Amer. Math. Soc. 230(1081) (2014) 80, Chap. 7], we show that there is a tight connection between the depth of a classifiable shallow theory [Formula: see text] and the Borel rank of the isomorphism relation [Formula: see text] on its models of size [Formula: see text], for [Formula: see text] any cardinal satisfying [Formula: see text]. This is achieved by establishing a link between said rank and the [Formula: see text]-Scott height of the [Formula: see text]-sized models of [Formula: see text], and yields to the following descriptive set-theoretical analog of Shelah’s Main Gap Theorem: Given a countable complete first-order theory [Formula: see text], either [Formula: see text] is Borel with a countable Borel rank (i.e. very simple, given that the length of the relevant Borel hierarchy is [Formula: see text]), or it is not Borel at all. The dividing line between the two situations is the same as in Shelah’s theorem, namely that of classifiable shallow theories. We also provide a Borel reducibility version of the above theorem, discuss some limitations to the possible (Borel) complexities of [Formula: see text], and provide a characterization of categoricity of [Formula: see text] in terms of the descriptive set-theoretical complexity of [Formula: see text].
A Two-Sub-Step Generalized Central Difference Method for General Dynamics
Authors: Ji Yi , Xing Yufeng
Published: June 2020

This paper proposes an implicit and unconditionally stable two-sub-step composite time integration method with controllable numerical dissipation for general dynamics called the two-sub-step generalized central difference (TGCD) method. The proposed method is established by performing the generalized central difference scheme in two sub-steps as the nondissipative and dissipative parts to ensure amplitude accuracy and controllable damping, respectively. It is accurate to the second order, with the amount of numerical dissipation controlled exactly by the spectral radius [Formula: see text]. In addition, the related parameters of the proposed method are determined by optimizing the amplitude and phase accuracy of the free vibration of a single degree-of-freedom system. Several representative linear and nonlinear numerical examples are analyzed to demonstrate the advantages of the proposed method in terms of accuracy, stability and efficiency, especially its stability in solving nonlinear problems.
Sustainable Location Selection of Data Centers: Developing a Multi-Criteria Set-Covering Decision-Making Methodology
Authors: Kheybari Siamak , Davoodi Monfared Mansoor , Farazmand Hadis , Rezaei Jafar
Published: June 2020

In this paper, a multi-criteria set-covering methodology is proposed to select suitable locations for a set of data centers. First, a framework of criteria, with social, economic and environmental dimensions, is presented. The framework is used to calculate the suitability of potential data center locations in Iran. To that end, a sample of specialists in Iran was asked to take part in an online questionnaire, based on best–worst method (BWM), to determine the weight of the criteria included in the proposed framework, after which a number of potential locations are evaluated on the basis of the criteria. The proposed model is evaluated under a number of settings. Using the proposed multi-criteria set-covering model, not only the utility of candidate places is evaluated by sustainability criteria but also all service applicants are covered by at least one data center with a specific coverage radius.
Splines and fractional differential operators
Authors: Massopust Peter
Published: June 2020

Several classes of classical cardinal B-splines can be obtained as solutions of operator equations of the form [Formula: see text] where [Formula: see text] is a linear differential operator of integral order. In this paper, we consider classes of generalized B-splines consisting of cardinal polynomial B-splines of complex and hypercomplex orders and cardinal exponential B-splines of complex order and derive the fractional linear differential operators that are naturally associated with them. For this purpose, we also present the spaces of distributions onto which these fractional differential operators act.
Inhomogeneous deformation in hyperspace
Authors: Ryabov Valeriy
Published: June 2020

Geometrical approach to continuum mechanics allowing an atomistic treatment is developed. It suggests a body as a surface immersed into ambient space. Four kinds of surfaces inherent to basic deformations determine classical dynamics of the atoms alongside their spatial coordinates. For uniaxial stretch, this surface is isomorphic to the cylinder. For a simple shear, it is the twisted cylinder, for a bending — a cone, and for a torsion — a helicoid. Scalar parameters of the metric of these surfaces that are stretch ratios, shear, cone, and torsion angles used instead of the strain tensor constitute extra coordinates of the particles in hypersurface. Correspondingly, vector-valued tensions are used instead of stress. In the case of pure deformation, the normal and extra coordinates of atoms obey the classical equation of motion admitting periodic boundary conditions. It is shown how the employing of artificial orders of freedom leads to a minimum of elastic energy. In boundary problems, the system of governing equations unambiguously reproduce the stress–strain–displacement relations with the help of using the tension boundary theorem instead of the Cauchy traction principle. The derived direct method of elastostatic makes the system of governing equations closed and the compatibility condition unnecessary. Commonest examples of bending problem normally following from the Airy stress function illustrate the new concept.
HT–LP crustal syntectonic anatexis as a source of the Permian magmatism in the Eastern Southern Alps: evidence from xenoliths in the Euganean trachytes (NE Italy)
Authors: Sassi Raffaele , Mazzoli Claudio , Merle Renaud , Brombin Valentina , Chiaradia Massimo , Dunkley Daniel J. , Marzoli Andrea
Published: June 2020

Oligocene trachytes from the Euganean Hills include various regionally metamorphosed gneissic and granulitic xenoliths. These xenoliths provide the unique opportunity to investigate South Alpine intermediate to deep crustal levels that are not at present exposed in the Eastern Alps. The estimated
P
–
T
conditions are in the range of 780–850°C and 0.45–0.55 GPa for a migmatitic gneiss xenolith. Sensitive high-resolution ion microprobe (SHRIMP II) U–Pb analyses on zircon from this xenolith provide concordant ages around 259.7 ± 3.5 Ma, consistent with a proton-induced X-ray emission (PIXE) U–Th–Pb age on monazite of 262 ± 12 Ma. The Sr–Nd–Pb isotopic compositions, and major and trace element data show distinct origins for the different types of xenoliths. Mafic granulite xenoliths have an isotopic signature close to mantle-derived rocks and to Permian gabbroic rocks from the Western Southern Alps. Metapelite xenoliths have high Sr and low Nd initial ratios like those of acid crustal rocks and could possibly represent the source of the crustal component that is dominant in the acid Permian supervolcanoes. The migmatitic xenolith provides the first documented evidence for a Permian thermal event associated with crustal thinning in the Eastern Southern Alps. Here the South Alpine basement escaped most of the Alpine crustal shortening and still preserves most of the original Permian extension under thick Mesozoic cover.

Supplementary material:
Microprobe analyses of mineralogical phases and Ti-in-biotite geothermometric calculations are available at
https://doi.org/10.6084/m9.figshare.c.5032337
A bang-bang control model predicts the triphasic muscles activity during hand reaching
Authors: Leib Raz , Russo Marta , d’Avella Andrea , Nisky Ilana
Published: June 2020

While ballistic hand reaching movements are characterized by smooth position and velocity signals, the activity of the muscles exhibits bursts and silent periods. Here, we propose that a model based on bang-bang control provides the link between the abrupt changes in the muscle activity and the smooth reaching trajectory. Using bang-bang control instead of continuous control may simplify the design of prostheses and other physical human-robot interaction systems.