bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin-1β-induced pancreatitis promotes pancreatic ductal adenocarcinoma via B lymphocyte–mediated immune suppression
Authors: Takahashi Ryota , Macchini Marina , Sunagawa Masaki , Jiang Zhengyu , Tanaka Takayuki , Valenti Giovanni , Renz Bernhard W , White Ruth A , Hayakawa Yoku , Westphalen C Benedikt , Tailor Yagnesh , Iuga Alina C , Gonda Tamas A , Genkinger Jeanine , Olive Kenneth P , Wang Timothy C 
Published: May 2020

ObjectiveLong-standing chronic pancreatitis is an established risk factor for pancreatic ductal adenocarcinoma (PDAC). Interleukin-1β (IL-1β) has been associated in PDAC with shorter survival. We employed murine models to investigate the mechanisms by which IL-1β and chronic pancreatitis might contribute to PDAC progression.DesignWe crossed LSL-Kras+/G12D;Pdx1-Cre (KC) mice with transgenic mice overexpressing IL-1β to generate KC-IL1β mice, and followed them longitudinally. We used pancreatic 3D in vitro culture to assess acinar-to-ductal metaplasia formation. Immune cells were analysed by flow cytometry and immunohistochemical staining. B lymphocytes were adoptively transferred or depleted in Kras-mutant mice. B-cell infiltration was analysed in human PDAC samples.ResultsKC-IL1β mice developed PDAC with liver metastases. IL-1β treatment increased Kras+/G12Dpancreatic spheroid formation. CXCL13 expression and B lymphocyte infiltration were increased in KC-IL1β pancreata. Adoptive transfer of B lymphocytes from KC-IL1β mice promoted tumour formation, while depletion of B cells prevented tumour progression in KC-IL1β mice. B cells isolated from KC-IL1β mice had much higher expression of PD-L1, more regulatory B cells, impaired CD8+T cell activity and promoted tumorigenesis. IL-35 was increased in the KC-IL1β pancreata, and depletion of IL-35 decreased the number of PD-L1+B cells. Finally, in human PDAC samples, patients with PDAC with higher B-cell infiltration within tumours showed significantly shorter survival.ConclusionWe show here that IL-1β promotes tumorigenesis in part by inducing an expansion of immune-suppressive B cells. These findings point to the growing significance of B suppressor cells in pancreatic tumorigenesis.
Impact of procedural capacity on transcatheter aortic valve replacement wait times and outcomes: a study of regional variation in Ontario, Canada
Authors: Henning Kayley A , Ravindran Mithunan , Qiu Feng , Fam Neil P , Seth Tej N , Austin Peter C , Wijeysundera Harindra C 
Published: May 2020

BackgroundThere has been rapid growth in the demand for transcatheter aortic valve replacement (TAVR), which has the potential to overwhelm current capacity. This imbalance between demand and capacity may lead to prolonged wait times, and subsequent adverse outcomes while patients are on the waitlist. We sought to understand the relationship between regional differences in capacity, TAVR wait times and morbidity/mortality on the waitlist.Methods and resultsWe modelled the effect of TAVR capacity, defined as the number of TAVR procedures per million residents/region, on the hazard of having a TAVR in Ontario from April 2012 to March 2017. Our primary outcome was the time from referral to a TAVR procedure or other off-list reasons on the waitlist/end of the observation period as measured in days. Clinical outcomes of interest were all-cause mortality, all-cause hospitalisations or heart failure-related hospitalisations while on the waitlist for TAVR. There was an almost fourfold difference in TAVR capacity across the 14 regions in Ontario, ranging from 31.5 to 119.5 TAVR procedures per million residents. The relationship between TAVR capacity and wait times was complex and non-linear. In general, increased capacity was associated with shorter wait times (p<0.001), reduced mortality (HR 0.94; p=0.08) and all-cause hospitalisations (p=0.009).ConclusionsThe results of the present study have important policy implications, suggesting that there is a need to improve TAVR capacity, as well as develop wait-time strategies to triage patients, in order to decrease wait times and mitigate the hazard of adverse patient outcomes while on the waitlist.
Resonant contributions to three-body $$B\rightarrow KKK$$ decays in perturbative QCD approach
Authors: Zou Zhi-Tian , Li Ying , Li Qi-Xin , Liu Xin 
Published: May 2020

AbstractIn this work, we study the (S, P and D)-wave $$K^+K^-$$K+K- contributions to $$B\rightarrow KKK$$B→KKK decays in the perturbative QCD approach at leading order. Within the two-meson wave functions describing the nonperturbative dynamics in the kaon-pair for different waves, we calculate the branching fractions and the direct CP asymmetries of these decay modes in the corresponding resonance regions. Most of our numerical results are well consistent with the current measurements. We note that the narrow-width approximation is invalid in the quasi-two-body decays $$B\rightarrow Kf_0(980)\rightarrow KKK$$B→Kf0(980)→KKK. For other decays, under the narrow-width approximation we can extract the branching fractions of the corresponding two-body decays involving the intermediate resonant states, and the related branching fractions agree with the current experimental data well. Furthermore, we also predict the branching fractions of the corresponding quasi-two-body decays $$B\rightarrow K\pi ^+\pi ^-$$B→Kπ+π-, which are expected to be tested in the ongoing LHCb and Belle-II experiments.
Dipolar dark matter and CMB B-mode polarization
Authors: Mahmoudi S. , Haghighat M. , Vamegh S. Al. Modares , Mohammadi R. 
Published: May 2020

AbstractWe consider dark matter particles as singlet fermionic particles carrying magnetic dipole moment to explore its contribution on the polarization of the cosmic microwave background (CMB) photons. We show that Dirac fermionic dark matter particles have no contribution on the CMB polarization. However, in the case of Majorana dark matter, this type of interaction leads to the B-mode polarization in the presence of primordial scalar perturbations which is in contrast with the standard scenario for the CMB polarization. We numerically calculate the B-mode power spectra and plot $$C_l^{BB}$$ClBB for different dark matter masses and the r-parameter. We show that dark matter particles with masses less than 100 MeV have a valuable contribution on $$C_l^{BB}$$ClBB. Meanwhile, dark matter particles with mass $$\text {m}_{\text {DM}}\le 50\, \text {MeV}$$mDM≤50MeV for $$r=0.07$$r=0.07 ( $$\text {m}_{\text {DM}}\le 80\, \text {MeV}$$mDM≤80MeV for $$r=0.09$$r=0.09) can be excluded experimentally. Furthermore, our results put a bound on the magnetic dipole moment about $$\text {M}\le 10^{-16} e\,\, \text {cm}$$M≤10-16ecm in agreement with the other reported constraints.
A new hydrocarbon exploration play: Upper Cretaceous–Paleocene sand injection complexes in the Austral-Magallanes Basin
Authors: Serié Christophe , Pemberton Erin 
Published: May 2020

Abstract
Recent exploration activity in the Austral-Magallanes Basin revealed the presence of sand injection complexes of Upper Cretaceous–Paleocene age. The discovery of these large-scale sandstone intrusions documents the first onshore example of sand injection complexes as hydrocarbon exploration targets and confirms a more widespread phenomenon than previously known. Integration of regional understanding, three-dimensional seismic reflection data, exploration wells, and whole core have allowed the interpretation of large sand injectites associated with a deep-water depositional system in the Austral-Magallanes Basin. These injectites are characterized seismically by circular to elongate amplitude anomalies with cross-cutting and discordant stratigraphic relationships. Additionally, detailed sedimentological analysis from exploration wells and core confirm the presence of facies consistent with injected sand commonly associated with deep-water depositional systems. The presence of giant sand injection complexes in the Austral-Magallanes Basin records a previously undocumented period of pore-fluid overpressure that led to large-scale hydraulic fracturing of the overburden and subsequent fluidization of sand derived from a deep-water depositional system. The discovery of intrusive traps such as sand injection complexes defines a new play with significant exploration potential; however, additional evaluation is required to understand the nature and degree of primary sandbody geometrical modification and the subsequent impact on reservoir distribution, trap geometry, migration pathways and seals.
A Custom Genotyping Array Reveals Population-Level Heterogeneity for the Genetic Risks of Prostate Cancer and Other Cancers in Africa
Authors: Harlemon Maxine , Ajayi Olabode , Kachambwa Paidamoyo , Kim Michelle S. , Simonti Corinne N. , Quiver Melanie H. , Petersen Desiree C. , Mittal Anuradha , Fernandez Pedro W. , Hsing Ann W. , Baichoo Shakuntala , Agalliu Ilir , Jalloh Mohamed , Gueye Serigne M. , Snyper Nana Yaa F. , Adusei Ben , Mensah James E. , Abrahams Afua O.D. , Adebiyi Akindele O. , Orunmuyi Akin T. , Aisuodionoe-Shadrach Oseremen I. , Nwegbu Maxwell M. , Joffe Maureen , Chen Wenlong C. , Irusen Hayley , Neugut Alfred I. , Quintana Yuri , Seutloali Moleboheng , Fadipe Mayowa B. , Warren Christopher , Woehrmann Marcos H. , Zhang Peng , Ongaco Chrissie M. , Mawhinney Michelle , McBride Jo , Andrews Caroline V. , Adams Marcia , Pugh Elizabeth , Rebbeck Timothy R. , Petersen Lindsay N. , Lachance Joseph 
Published: May 2020

AbstractAlthough prostate cancer is the leading cause of cancer mortality for African men, the vast majority of known disease associations have been detected in European study cohorts. Furthermore, most genome-wide association studies have used genotyping arrays that are hindered by SNP ascertainment bias. To overcome these disparities in genomic medicine, the Men of African Descent and Carcinoma of the Prostate (MADCaP) Network has developed a genotyping array that is optimized for African populations. The MADCaP Array contains more than 1.5 million markers and an imputation backbone that successfully tags over 94% of common genetic variants in African populations. This array also has a high density of markers in genomic regions associated with cancer susceptibility, including 8q24. We assessed the effectiveness of the MADCaP Array by genotyping 399 prostate cancer cases and 403 controls from seven urban study sites in sub-Saharan Africa. Samples from Ghana and Nigeria clustered together, whereas samples from Senegal and South Africa yielded distinct ancestry clusters. Using the MADCaP array, we identified cancer-associated loci that have large allele frequency differences across African populations. Polygenic risk scores for prostate cancer were higher in Nigeria than in Senegal. In summary, individual and population-level differences in prostate cancer risk were revealed using a novel genotyping array.Significance:This study presents an Africa-specific genotyping array, which enables investigators to identify novel disease associations and to fine-map genetic loci that are associated with prostate and other cancers.
Differentiation Syndrome with Ivosidenib and Enasidenib Treatment in Patients with Relapsed or Refractory IDH-Mutated AML: A U.S. Food and Drug Administration Systematic Analysis
Authors: Norsworthy Kelly J. , Mulkey Flora , Scott Emma C. , Ward Ashley F. , Przepiorka Donna , Charlab Rosane , Dorff Sarah E. , Deisseroth Albert , Kazandjian Dickran , Sridhara Rajeshwari , Beaver Julia A. , Farrell Ann T. , de Claro R. Angelo , Pazdur Richard 
Published: May 2020

Abstract

Purpose:
Differentiation syndrome (DS) is a serious adverse reaction of isocitrate dehydrogenase (IDH) inhibitors ivosidenib and enasidenib in patients with (IDH)1- and IDH2-mutated acute myeloid leukemia (AML), respectively.

Experimental Design:
During FDA review of marketing applications for ivosidenib and enasidenib, data from pivotal trials were queried to identify cases of DS in patients with relapsed or refractory (R/R) AML. One hundred seventy-nine patients with R/R AML received ivosidenib and 214 received enasidenib. Adverse events, labs, and vital signs in the first 90 days of treatment were screened per diagnostic criteria, and narratives were reviewed to adjudicate DS cases.

Results:
We identified 72 of 179 (40%) potential cases for ivosidenib and 86 of 214 (40%) for enasidenib; 34 of 179 (19%) and 41 of 214 (19%) were adjudicated as DS. Leukocytosis was present in 79% and 61% of cases, respectively. Median (range) time to onset was 20 (1–78) and 19 (1–86) days. Grade ≥ 3 adverse reactions occurred in 68% and 66%; 6% and 5% were fatal. Univariate analyses suggested baseline bone marrow blasts ≥ 48% and peripheral blood blasts ≥ 25% and 15% for ivosidenib and enasidenib, respectively, were associated with increased risk of DS. Complete remission (CR) + CR with partial hematologic recovery rates were lower in patients with versus without DS [ivosidenib 18% (95% confidence interval, 7%–35%) vs. 36% (28%–45%); enasidenib 18% (7%–33%) vs. 25% (18%–32%)].

Conclusions:
DS is a common and potentially fatal adverse reaction of IDH inhibitors, and use of standardized diagnostic criteria may aid in earlier diagnosis and treatment.
See related commentary by Zeidner, p. 4174
Impact of PD-1 Blockade on Severity of COVID-19 in Patients with Lung Cancers
Authors: Luo Jia , Rizvi Hira , Egger Jacklynn V. , Preeshagul Isabel R. , Wolchok Jedd D. , Hellmann Matthew D. 
Published: May 2020

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has led to dramatic changes in oncology practice. It is currently unknown whether programmed death 1 (PD-1) blockade therapy affects severity of illness from COVID-19 in patients with cancer. To address this uncertainty, we examined consecutive patients with lung cancers who were diagnosed with COVID-19 and examined severity on the basis of no or prior receipt of PD-1 blockade. Overall, the severity of COVID-19 in patients with lung cancer was high, including need for hospitalization in more than half of patients and death in nearly a quarter. Prior PD-1 blockade was, as expected, associated with smoking status. After adjustment for smoking status, PD-1 blockade exposure was not associated with increased risk of severity of COVID-19. PD-1 blockade does not appear to affect the severity of COVID-19 in patients with lung cancers.

Significance:
A key question in oncology practice amidst the COVID-19 pandemic is whether PD-1 blockade therapy affects COVID-19 severity. Our analysis of patients with lung cancers supports the safety of PD-1 blockade treatment to achieve optimal cancer outcomes.
This article is highlighted in the In This Issue feature, p. 1079
The Tumor-Suppressive Human Circular RNA CircITCH Sponges miR-330-5p to Ameliorate Doxorubicin-Induced Cardiotoxicity Through Upregulating SIRT6, Survivin, and SERCA2a
Authors: Han Dong , Wang Yongjun , Wang Yabin , Dai Xinchun , Zhou Tingwen , Chen Jiangwei , Tao Bo , Zhang Jibin , Cao Feng 
Published: May 2020

Rationale:
Doxorubicin is one of the most potent antitumor agents available; however, its clinical use is restricted because it poses a risk of severe cardiotoxicity. Previous work has established that CircITCH (circular RNA ITCH [E3 ubiquitin-protein ligase]) is a broad-spectrum tumor-suppressive circular RNA and that its host gene, ITCH (E3 ubiquitin protein ligase), is involved in doxorubicin-induced cardiotoxicity (DOXIC). Whether CircITCH plays a role in DOXIC remains unknown.

Objective:
We aimed to dissect the role of CircITCH in DOXIC and further decipher its potential mechanisms.

Methods and Results:

Circular RNA sequencing was performed to screen the potentially involved circRNAs in DOXI pathogenesis. Quantitative polymerase chain reaction and RNA in situ hybridization revealed that CircITCH was downregulated in doxorubicin-treated human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as well as in the autopsy specimens from cancer patients who suffered from doxorubicin-induced cardiomyopathy. Cell death/viability assays, detection of cardiomyocyte necrosis markers, microelectrode array, and cardiomyocyte functional assays revealed that CircITCH ameliorated doxorubicin-induced cardiomyocyte injury and dysfunction. Detection of cellular/mitochondrial oxidative stress and DNA damage markers verified that CircITCH alleviated cellular/mitochondrial oxidative stress and DNA damage induced by doxorubicin. RNA pull-down assays, Ago2 immunoprecipitation and double fluorescent in situ hybridization identified miR-330-5p as a direct target of CircITCH. Moreover, CircITCH was found to function by acting as an endogenous sponge that sequestered miR-330-5p. Bioinformatic analysis, luciferase reporter assays, and quantitative polymerase chain reaction showed that SIRT6 (sirtuin 6), BIRC5 (baculoviral IAP repeat containing 5, Survivin), and ATP2A2 (ATPase sarcoplasmic/endoplasmic reticulum Ca
2+
transporting 2, SERCA2a [SR Ca
2+
-ATPase 2]) were direct targets of miR-330-5p and that they were regulated by the CircITCH/miR-330-5p axis in DOXIC. Further experiments demonstrated that CircITCH-mediated alleviation of DOXIC was dependent on the interactions between miR-330-5p and the 3′-UTRs of SIRT6, BIRC5, and ATP2A2 mRNA. Finally, AAV9 (adeno-associated virus serotype 9) vector-based overexpression of the well-conserved CircITCH partly prevented DOXIC in mice.

Conclusions:
CircITCH represents a novel therapeutic target for DOXIC because it acts as a natural sponge of miR-330-5p, thereby upregulating SIRT6, Survivin and SERCA2a to alleviate doxorubicin-induced cardiomyocyte injury and dysfunction.
Physical Activity and Incident Heart Failure in High‐Risk Subgroups: The ARIC Study
Authors: Florido Roberta , Kwak Lucia , Lazo Mariana , Michos Erin D. , Nambi Vijay , Blumenthal Roger S. , Gerstenblith Gary , Palta Priya , Russell Stuart D. , Ballantyne Christie M. , Selvin Elizabeth , Folsom Aaron R. , Coresh Josef , Ndumele Chiadi E. 
Published: May 2020

Background

Greater physical activity (
PA
) is associated with lower heart failure (
HF
) risk. However, it is unclear whether this inverse association exists across all subgroups at high risk for
HF
, particularly among those with preexisting atherosclerotic cardiovascular disease.

Methods and Results

We followed 13 810
ARIC
(Atherosclerosis Risk in Communities) study participants (mean age 55 years, 54% women, 26% black) without
HF
at baseline (visit 1; 1987–1989).
PA
was assessed using a modified Baecke questionnaire and categorized according to American Heart Association guidelines: recommended, intermediate, or poor. We constructed Cox models to estimate associations between
PA
categories and incident
HF
within each high‐risk subgroup at baseline, with tests for interaction. We performed additional analyses modeling incident coronary heart disease as a time‐varying covariate. Over a median of 26 years of follow‐up, there were 2994
HF
events. Compared with poor
PA
, recommended
PA
was associated with lower
HF
risk among participants with hypertension, obesity, diabetes mellitus, and metabolic syndrome (all
P
<0.01), but not among those with prevalent atherosclerotic cardiovascular disease (coronary heart disease, stroke, or peripheral arterial disease) (hazard ratio, 0.91; 95%
CI
, 0.74–1.13 [
P
interaction=0.02]). Recommended
PA
was associated with lower risk of incident coronary heart disease (hazard ratio, 0.79; 95%
CI
, 0.72–0.86), but not with lower
HF
risk in those with interim coronary heart disease events (hazard ratio, 0.90; 95%
CI
, 0.78–1.04 [
P
interaction=0.04]).

Conclusions

PA
was associated with decreased
HF
risk in patients with hypertension, obesity, diabetes mellitus, and metabolic syndrome. Despite a myriad of benefits in patients with atherosclerotic cardiovascular disease,
PA
may have weaker associations with
HF
prevention after ischemic disease is established.
Adherence to Anticoagulant Guideline for Atrial Fibrillation Improves Outcomes in Asian Population
Authors: Krittayaphong Rungroj , Winijkul Arjbordin , Kunjara-Na-Ayudhya Rapeephon , Apiyasawat Sirin , Siriwattana Khanchai , Kanjanarutjawiwat Wiwat , Dutsadeevettakul Somchai , Lip Gregory Y. H. ,   for the COOL-AF Investigators
Published: May 2020

Background and Purpose—
Guideline adherent oral anticoagulant (OAC) management of patients with nonvalvular atrial fibrillation has been associated with improved outcomes, but limited data are available from Asia. We aimed to investigate outcomes in patients who received guideline compliant management compared with those who were OAC undertreated or overtreated, in a large nationwide multicenter cohort of patients with nonvalvular atrial fibrillation in Thailand.

Methods—
Patients with nonvalvular atrial fibrillation were prospectively enrolled from 27 hospitals—all of which are data contributors to the COOL-AF Registry (Cohort of Antithrombotic Use and Optimal INR Level in Patients With Non-Valvular Atrial Fibrillation in Thailand). Patients were categorized as follows: (1) guideline adherence group when OAC was given in high-risk or intermediate-risk, but not in low-risk patients; (2) undertreatment group when OAC was not given in the high-risk or intermediate-risk groups; and (3) overtreatment group when OAC was given in the low-risk group or when OAC was given in combination with antiplatelets without indication.

Results—
A total of 3327 patients who had follow-up clinical outcome data were included. The mean age of patients was 67.4 years and 58.1% were male. The numbers of patients in the guideline adherence group, undertreatment group, and overtreatment group were 2267 (68.1%), 624 (18.8%), and 436 (13.1%) patients, respectively. The overall rate of ischemic stroke, major bleeding, all bleeding, and death was 3.0%, 4.4%, 15.1%, and 7.8%, respectively. Undertreated patients had a higher risk of ischemic stroke and death compared with guideline adherent patients, and overtreated patients had a higher risk of bleeding and death compared with OAC guideline-managed patients.

Conclusions—
Adherence to OAC management guidelines is associated with improved clinical outcomes in Asian nonvalvular atrial fibrillation patients. Undertreatment or overtreatment was found to be associated with increased risk of adverse outcomes compared with guideline-adherent management.
Elective Tracheostomy During Mechanical Ventilation in Patients Affected by COVID‐19: Preliminary Case Series From Lombardy, Italy
Authors: Turri‐Zanoni Mario , Battaglia Paolo , Czaczkes Camilla , Pelosi Paolo , Castelnuovo Paolo , Cabrini Luca 
Published: May 2020

The COVID‐19 outbreak poses continued struggles due to the unprecedented number of patients admitted to intensive care units and the overwhelming need for mechanical ventilation. We report a preliminary case series of 32 patients with COVID‐19 who underwent elective tracheostomies after a mean intubation period of 15 days (range, 9‐21 days). The procedure was performed with percutaneous (10 cases) and open (22 cases) surgical techniques. Neither procedure‐related complications nor viral transmission to health care workers was observed. Our preliminary experience supports the safety of tracheostomy, provided that appropriate protocols are strictly followed. The postoperative care is still debated, and, prudentially, our protocol includes tracheal tube change not before 2 weeks after tracheostomy, with cuff deflation and decannulation deferred until confirmation of negative SARS‐CoV‐2 test results. This is the first case series to report on such a rapidly evolving issue and might represent a source of information for clinicians worldwide who will soon be facing the same challenges.