bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transitions to smokeless tobacco use among adult cigarette smokers in the Population Assessment of Tobacco and Health (PATH) Study, Waves 3–5 (2015–2019)
Authors: Jackson Rebecca A , Ren Chunfeng , Coleman Blair , Day Hannah R , Chang Cindy M , Kofie Justina , Rivers Derick , Kanel Moana , Ambrose Bridget K 
Published: December 2021

ObjectiveExamine patterns of dual use of cigarettes and smokeless tobacco and complete switching over time among adult current cigarette smokers using data from the Population Assessment of Tobacco and Health Study Wave 3 (2015–2016), Wave 4 (2016–2018) and Wave 5 (2018–2019).MethodsWe examined four tobacco use states among 6834 exclusive smokers and 372 dual users at Wave 3 with two waves of follow-up data: exclusive cigarette use, exclusive smokeless tobacco use, dual use and use of neither product.ResultsAmong exclusive smokers at Wave 3, only 1.6% (95% CI: 1.3% to 2.1%) transitioned to dual use at Wave 4, and 0.1% (95% CI: 0.07% to 0.2%) switched to exclusive smokeless tobacco use. Among exclusive smokers who switched to dual use, 53.1% (95% CI: 40.9% to 64.9%) returned to exclusive cigarette smoking, 34.3% (95% CI: 23.8% to 46.6%) maintained dual use and 12.6% (95% CI: 7.0% to 21.7%) did not smoke cigarettes after an additional wave of follow-up. Dual users at Wave 3 were likely to maintain their dual use status at Wave 4, 51.2% (95% CI: 46.1% to 56.3%) and Wave 5, 47.9% (95% CI: 40.1% to 55.8%).ConclusionsVery few cigarette smokers transition to smokeless tobacco use, and among those who do, dual use is more common than exclusive smokeless tobacco use. Further, the majority of exclusive cigarette smokers who transition to dual use at Wave 4 continue smoking cigarettes at Wave 5, either as dual users or as exclusive smokers.
Large hadron collider constraints on some simple $$Z^\prime $$ models for $$b\rightarrow s \mu ^+\mu ^-$$ anomalies
Authors: Allanach B. C. , Butterworth J. M. , Corbett Tyler 
Published: December 2021

AbstractWe examine current Large Hadron Collider constraints on some simple $$Z^\prime $$

Z
′

models that significantly improve on Standard Model fits to $$b\rightarrow s \mu ^+\mu ^-$$

b
→
s

μ
+

μ
-

transition data. The models that we consider are the ‘third family baryon number minus second family lepton number’ ($${B_3-L_2}$$

B
3

-

L
2

) model and the ‘third family hypercharge’ model and variants. The constraints are applied on parameter regions of each model that fit the $$b\rightarrow s \mu ^+\mu ^-$$

b
→
s

μ
+

μ
-

transition data and come from high-mass Drell–Yan di-muons and measurements of Standard Model processes. This latter set of observables place particularly strong bounds upon the parameter space of the $${B_3-L_2}$$

B
3

-

L
2

model when the mass of the $$Z^\prime $$

Z
′

boson is less than 300 GeV.
Absorption by stringy black holes
Authors: Xavier Sérgio V. M. C. B. , Benone Carolina L. , Crispino Luís C. B. 
Published: December 2021

AbstractWe investigate the absorption of planar massless scalar waves by a charged rotating stringy black hole, namely a Kerr–Sen black hole. We compute numerically the absorption cross section and compare our results with those of the Kerr–Newman black hole, a classical general relativity solution. In order to better compare both charged black holes, we define the ratio of the black hole charge to the extreme charge as Q. We conclude that Kerr–Sen and Kerr–Newman black holes have a similar absorption cross section, with the difference increasing for higher values of Q.
The elements of style
Authors: Yaffe Philip 
Published: December 2021

Each "Communication Corner" essay is self-contained; however, they build on each other. For best results, before reading this essay and doing the exercise, go to the first essay "How an Ugly Duckling Became a Swan," then read each succeeding essay.
Over the decades, hundreds if not thousands of books have been published on the keys to good writing. However, barely a handful have reached the status of "must reading." Here is one of them.
Prevalence and Trajectory of COVID-19-Associated Hypercoagulability Using Serial Thromboelastography in a South African Population
Authors: van Blydenstein Sarah Alexandra , Menezes Colin Nigel , Miller Nicole , Johnson Naomi , Pillay Bavinash , Jacobson Barry F. , Omar Shahed 
Published: December 2021

Introduction. The coagulation abnormalities resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been attributed to inflammation and subsequent cytokine storm. Thromboelastography (TEG) is a point-of-care test used to assess clot formation and degradation in whole blood and is an indicator of the overall real-time coagulopathic state of the patient. Methods. A single-centre, prospective, observational cohort study was conducted in South Africa, analysing the coagulation patterns of 41 patients with hypoxia related to SARS-CoV-2 using serial thromboelastography (TEG) on admission, after 48 hours, and at resolution of hypoxia/day 10. Results: Two-thirds (n = 26) were women. The median age was 61 (IQR 50–67), and the majority (88%) were Black patients. Almost half (22) of the patients were critically ill and ventilated, with median SOFA and SAPS2 scores of 3 and 22 (IQR2-4 and 18–30), respectively. The prevalence of hypercoagulability was 0.54 (95% CI 0.46–0.62), whilst 29/41 (0.71, CI 0.64–0.78)) met the definition of hypofibrinolysis. Differences between the hypercoagulable (HC) and non-hypercoagulable groups remained apparent at 48 hours after anticoagulation. At this time point, the K time was significantly lower (

p

˂ 0,01), and the α-angle (

p

˂ 0,01) and maximum amplitude (MA) (

p

˂ 0,01) were significantly higher in the HC cohort. At resolution of hypoxia, or day 10, only MA was significantly higher in the hypercoagulable group compared to the non-hypercoagulable group (p = 0.01). The initial impairment in fibrinolysis (Ly30), α angle, and MA were significantly associated with mortality, with p values of 0.006, 0.031, and 0.04, respectively. Conclusions. In this South African population, hypercoagulability was a highly prevalent phenomenon in COVID-19 disease. It was typified by hypofibrinolysis and a persistently elevated MA, despite anticoagulation therapy.
Diagnostic Value of Prenatal Ultrasound Parameters and Esophageal Signs in Pouch and Lower Thoracic Segment in Fetuses with Esophageal Atresia
Authors: Feng Wenjun 
Published: December 2021

In order to investigate the diagnostic value of prenatal ultrasound parameters and signs of pouch and lower thoracic esophagus in the fetus with esophageal atresia (EA), the prenatal ultrasound data of 35 EA fetuses (observation group) confirmed by autopsy after induced labor or postnatal surgery and imaging examination in our hospital from May 2019 to May 2021 were retrospectively analyzed and compared with 35 normal postnatal fetuses (control group). General information and prenatal ultrasound parameters of the two groups, including head circumference (HC), abdominal circumference (AC), double parietal diameter (BPD), fetal body weight (EFW), and signs (small or unmanifested gastric vesicles, amniotic fluid, neck or upper chest pouch, lower chest esophagus not visible), were analyzed using logistic regression. The logistic multifactor regression model for EA diagnosis was established, and the diagnostic value for EA was analyzed. As a result, the HC, AC, and EFW of the observation group were lower than those of the control group, the gastric bubbles were small or not displayed, the amniotic fluid was more, and the signs of neck or upper chest pouch and lower chest esophagus were not visible in the observation group (

P
<
0.05

). Logistic regression analysis showed that decreased ultrasound parameters HC, AC, EFW, small or no gastric bubble, amniotic fluid, neck or upper chest pouch, and no visible signs of lower chest esophagus were all risk factors for EA (

P
<
0.05

). And in the prenatal ultrasound diagnostic model of EA was established, logistic

P

=
−
19.851
+
HC
×
0.384
+
AC
×
0.682
+
EFW
×
0.695
+
small

or

no

gastric

vesicle
×
3.747
+
amniotic

fluid
×
3.607
+
cervical

or

upper

chest

sac
×
4.104
+
invisible

lower

thoracic

esophagus
×
4.623

.When logistic

P

>
0.468

, AUC was 0.891,

χ
2

was 7.764, diagnostic sensitivity was 91.24%, and specificity was 79.22%. To draw a conclusion, prenatal ultrasound parameters and signs are of great value in the diagnosis of EA. Independent influencing factors of EA include small or no HC, AC, EFW and gastric vesicles, polyhydramnios, neck or upper chest pouch, and invisible lower thoracic esophagus. Logistic multifactor regression model has a high coincidence rate for the prenatal diagnosis of EA, providing a basis for clinical decision-making.
Immunomodulation of T- and NK-cell Responses by a Bispecific Antibody Targeting CD28 Homolog and PD-L1
Authors: Ramaswamy Madhu , Kim Taeil , Jones Des C. , Ghadially Hormas , Mahmoud Tamer I. , Garcia Andrew , Browne Gareth , Zenonos Zenon , Puplampu-Dove Yvonne , Riggs Jeffrey M. , Bhat Geetha K. , Herbst Ronald , Schofield Darren J. , Carlesso Gianluca 
Published: December 2021

AbstractCheckpoint blockade therapies targeting PD-1/PD-L1 and CTLA-4 are clinically successful but also evoke adverse events due to systemic T-cell activation. We engineered a bispecific, mAb targeting CD28 homolog (CD28H), a newly identified B7 family receptor that is constitutively expressed on T and natural killer (NK) cells, with a PD-L1 antibody to potentiate tumor-specific immune responses. The bispecific antibody led to T-cell costimulation, induced NK-cell cytotoxicity of PD-L1–expressing tumor cells, and activated tissue-resident memory CD8+ T cells. Mechanistically, the CD28H agonistic arm of the bispecific antibody reduced PD-L1/PD-1–induced SHP2 phosphorylation while simultaneously augmenting T-cell receptor signaling by activating the MAPK and AKT pathways. This bispecific approach could be used to target multiple immune cells, including CD8+ T cells, tissue-resident memory T cells, and NK cells, in a tumor-specific manner that may lead to induction of durable, therapeutic antitumor responses.
Spatial Organization and Prognostic Significance of NK and NKT-like Cells via Multimarker Analysis of the Colorectal Cancer Microenvironment
Authors: Väyrynen Juha P. , Haruki Koichiro , Lau Mai Chan , Väyrynen Sara A. , Ugai Tomotaka , Akimoto Naohiko , Zhong Rong , Zhao Melissa , Dias Costa Andressa , Borowsky Jennifer , Bell Phoenix , Takashima Yasutoshi , Fujiyoshi Kenji , Arima Kota , Kishikawa Junko , Shi Shan-shan , Twombly Tyler S. , Song Mingyang , Wu Kana , Chan Andrew T. , Zhang Xuehong , Fuchs Charles S. , Meyerhardt Jeffrey A. , Giannakis Marios , Ogino Shuji , Nowak Jonathan A. 
Published: December 2021

Abstract

Although tumor-infiltrating T cells hold a beneficial prognostic role in colorectal cancer, other lymphocytic populations are less characterized. We developed a multiplexed immunofluorescence assay coupled with digital image analysis and machine learning to identify natural killer (NK) cells (NCAM1+CD3−), natural killer T-like (NKT-like) cells (NCAM1+CD3+), and T cells (NCAM1−CD3+) within the PTPRC+ (CD45+) cell population and to measure their granzyme B (GZMB; cytotoxicity marker) and FCGR3A (CD16a; NK-cell maturity marker) expression. We evaluated immune cell densities and spatial configuration in 907 incident colorectal carcinoma cases within two prospective cohort studies. We found that T cells were approximately 100 times more abundant than NK and NKT-like cells. Overall, NK cells showed high GZMB expression and were located closer to tumor cells than T and NKT-like cells. In T and NKT-like cells, GZMB expression was enriched in cells in closer proximity to tumor cells. Higher densities of both T and NKT-like cells associated with longer cancer-specific survival, independent of potential confounders (Ptrend &lt; 0.0007). Higher stromal GZMB+ and FCGR3A+ NK-cell densities associated with longer cancer-specific survival (Ptrend &lt; 0.003). For T and NKT-like cells, greater proximity to tumor cells associated with longer cancer-specific survival (Ptrend &lt; 0.0001). These findings indicate that cytotoxic NCAM1+CD3−GZMB+ NK cells and NCAM1+CD3+ NKT-like cells are relatively rare lymphocytic populations within the colorectal cancer microenvironment and show distinct spatial configuration and associations with patient outcome. The results highlight the utility of a quantitative multimarker assay for in situ, single-cell immune biomarker evaluation and underscore the importance of spatial context for tumor microenvironment characterization.
Association Between Age and Outcomes of Catheter Ablation Versus Medical Therapy for Atrial Fibrillation: Results From the CABANA Trial
Authors: Bahnson Tristram D. , Giczewska Anna , Mark Daniel B. , Russo Andrea M. , Monahan Kristi H. , Al-Khalidi Hussein R. , Silverstein Adam P. , Poole Jeanne E. , Lee Kerry L. , Packer Douglas L. ,   for the CABANA Investigators
Published: December 2021

Background:
Observational data suggest that catheter ablation may be safe and effective to treat younger and older patients with atrial fibrillation. No large, randomized trial has examined this issue. This report describes outcomes according to age at entry in the CABANA trial (Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation).

Methods:
Patients with atrial fibrillation ≥65 years of age, or <65 with ≥1 risk factor for stroke, were randomly assigned to catheter ablation versus drug therapy. The primary outcome was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Secondary outcomes included all-cause mortality, the composite of mortality or cardiovascular hospitalization, and recurrence of atrial fibrillation. Treatment effect estimates were adjusted for baseline covariables using proportional hazards regression models.

Results:

Of 2204 patients randomly assigned in CABANA, 766 (34.8%) were <65 years of age, 1130 (51.3%) were 65 to 74 years of age, and 308 (14.0%) were ≥75 years of age. Catheter ablation was associated with a 43% reduction in the primary outcome for patients <65 years of age (adjusted hazard ratio [aHR], 0.57 [95% CI, 0.30–1.09]), a 21% reduction for 65 to 74 years of age (aHR, 0.79 [95% CI, 0.54–1.16]), and an indeterminate effect for age ≥75 years of age (aHR, 1.39 [95% CI, 0.75–2.58]). Four-year event rates for ablation versus drug therapy across age groups, respectively, were 3.2% versus 7.8%, 7.8% versus 9.6%, and 14.8% versus 9.0%. For every 10-year increase in age, the primary outcome aHR increased (ie, less favorable to ablation) an average of 27% (interaction
P
value=0.215). A similar pattern was seen with all-cause mortality: for every 10-year increase in age, the aHR increased an average of 46% (interaction
P
value=0.111). Atrial fibrillation recurrence rates were lower with ablation than with drug therapy across age subgroups (aHR 0.47, 0.58, and 0.49, respectively). Treatment-related complications were infrequent for both arms (<3%) regardless of age.

Conclusions:
We found age-based variations in clinical outcomes for catheter ablation compared with drug therapy, with the largest relative and absolute benefits of catheter ablation in younger patients. No prognostic benefits for ablation were seen in the oldest patients. No differences were found by age in treatment-related complications or in the relative effectiveness of catheter ablation in preventing recurrent atrial arrhythmias.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT00911508.
Impact of a Patient’s Baseline Risk on the Relative Benefit and Harm of a Preventive Treatment Strategy: Applying Trial Results in Clinical Decision Making
Authors: de Vries Tamar I. , Stam‐Slob Manon C. , Peters Ron J. G. , van der Graaf Yolanda , Westerink Jan , Visseren Frank L. J. 
Published: December 2021

Background
For translating an overall trial result into an individual patient’s expected absolute treatment effect, differences in relative treatment effect between patients need to be taken into account. The aim of this study was to evaluate whether relative treatment effects of medication in 2 large contemporary trials are influenced by multivariable baseline risk of an individual patient.

Methods and Results

In 9361 patients from SPRINT (Systolic Blood Pressure Intervention Trial), risk of major adverse cardiovascular events was assessed using a newly derived risk model. In 18 133 patients from the RE‐LY (Randomized Evaluation of Long‐Term Anticoagulant Therapy) trial, risk of stroke or systemic embolism and major bleeding was assessed using the Global Anticoagulant Registry in the Field–Atrial Fibrillation risk model. Heterogeneity of trial treatment effect was assessed using Cox models of trial allocation, model linear predictor, and their interaction. There was no significant interaction between baseline risk and relative treatment effect from intensive blood pressure lowering in SPRINT (
P
=0.92) or from dabigatran compared with warfarin for stroke or systemic embolism in the RE‐LY trial (
P
=0.71). There was significant interaction between baseline risk and treatment effect from dabigatran versus warfarin in the RE‐LY trial (
P
<0.001) for major bleeding. Quartile‐specific hazard ratios for bleeding ranged from 0.40 (95% CI, 0.26–0.61) to 1.04 (95% CI, 0.83–1.03) for dabigatran, 110 mg, and from 0.61 (95% CI, 0.42–0.88) to 1.20 (95% CI, 0.97–1.50) for dabigatran, 150 mg, compared with warfarin.

Conclusions
Effect modification of relative treatment effect by individual baseline event risk should be assessed systematically in randomized clinical trials using multivariate risk prediction, not only in terms of treatment efficacy but also for important treatment harms, as a prespecified analysis.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01206062.
Registry for Acute Coronary Events in Nigeria (RACE‐Nigeria): Clinical Characterization, Management, and Outcome
Authors: Isezuo Simeon , Sani Mahmoud Umar , Talle Abdullahi , Johnson Adeyemi , Adeoye Abiodun‐Moshood , Ulgen Mehmet S. , Mbakwem Amam , Ogah Okechukwu , Edafe Emmanuel , Kolo Philip , Nagabea Murtala , Adebayo Rasaaq , Nwafor Eze , Daniel Folasade , Zagga Muiyawa , Umar Hayatu , Oboirien Isa , Sulaiman Balarabe A. , Abdullahi Umar , Mijinyawa Muhammad Sani , Buba Farouk , Aje Akinyemi , Okolie Henry , Shehu Muhammad Nazir , Adamu Umar , Olusegun‐Joseph Akinsanya , Familoni Ranti , Chibuzor Nwuriku , Olunuga Taiwo Olabisi , Ejim Emmanuel , Rasheed Olaide Awodun , Ojji Dike , Sanni Bushra , Ajuluchukwu Jane N. , Balogun Michael O. , Omotoso Ayodele B. , Ajit Mullasari , Falase Ayodele O. ,   RACE‐Nigeria Registry Investigators
Published: December 2021

Background
Coronary artery disease was hitherto a rarity in Africa. Acute coronary syndrome (ACS) accounts for coronary artery disease–related morbidity and mortality. Reports on ACS in Africa are few.

Methods and Results
We enrolled 1072 indigenous Nigerian people 59.2±12.4 years old (men, 66.8%) with ACS in an observational multicentered national registry (2013–2018). Outcome measures included incidence, intervention times, reperfusion rates, and 1‐year mortality. The incidence of ACS was 59.1 people per 100 000 hospitalized adults per year, and comprised ST‐segment–elevation myocardial infarction (48.7%), non–ST‐segment–elevation myocardial infarction (24.5%), and unstable angina (26.8%). ACS frequency peaked 10 years earlier in men than women. Patients were predominantly from urban settings (87.3%). Median time from onset of symptoms to first medical contact (patients with ST‐segment–elevation myocardial infarction) was 6 hours (interquartile range, 20.1 hours), and only 11.9% presented within a 12‐hour time window. Traditional risk factors of coronary artery disease were observed. The coronary angiography rate was 42.4%. Reperfusion therapies included thrombolysis (17.1%), percutaneous coronary intervention (28.6%), and coronary artery bypass graft (11.2%). Guideline‐based pharmacotherapy was adequate. Major adverse cardiac events were 30.8%, and in‐hospital mortality was 8.1%. Mortality rates at 30 days, 3 months, 6 months, and 1 year were 8.7%, 9.9%, 10.9%, and 13.3%, respectively. Predictors of mortality included resuscitated cardiac arrest (odds ratio [OR], 50.0; 95% CI, 0.010–0.081), nonreperfusion (OR, 34.5; 95% CI, 0.004–0.221), pulmonary edema (OR, 11.1; 95% CI, 0.020–0.363), left ventricular diastolic dysfunction (OR, 4.1; 95% CI, 0.091–0.570), and left ventricular systolic dysfunction (OR, 2.1; 95% CI, 1.302–3.367).

Conclusions
ACS burden is rising in Nigeria, and patients are relatively young and from an urban setting. The system of care is evolving and is characterized by lack of capacity and low patient eligibility for reperfusion. We recommend preventive strategies and health care infrastructure‐appropriate management guidelines.
Validation of Specific and Reliable Genetic Tools to Identify, Label, and Target Cardiac Pericytes in Mice
Authors: Alex Linda , Tuleta Izabela , Harikrishnan Venugopal , Frangogiannis Nikolaos G. 
Published: December 2021

Background
In the myocardium, pericytes are often confused with other interstitial cell types, such as fibroblasts. The lack of well‐characterized and specific tools for identification, lineage tracing, and conditional targeting of myocardial pericytes has hampered studies on their role in heart disease. In the current study, we characterize and validate specific and reliable strategies for labeling and targeting of cardiac pericytes.

Methods and Results

Using the neuron‐glial antigen 2 (NG2)
DsRed
reporter line, we identified a large population of NG2+ periendothelial cells in mouse atria, ventricles, and valves. To examine possible overlap of NG2+ mural cells with fibroblasts, we generated NG2
DsRed
; platelet‐derived growth factor receptor (PDGFR) α
EGFP
pericyte/fibroblast dual reporter mice. Myocardial NG2+ pericytes and PDGFRα+ fibroblasts were identified as nonoverlapping cellular populations with distinct transcriptional signatures. PDGFRα+ fibroblasts expressed high levels of fibrillar collagens, matrix metalloproteinases, tissue inhibitor of metalloproteinases, and genes encoding matricellular proteins, whereas NG2+ pericytes expressed high levels of
Pdgfrb
,
Adamts1
, and
Vtn
. To validate the specificity of pericyte Cre drivers, we crossed these lines with PDGFRα
EGFP
fibroblast reporter mice. The constitutive NG2
Cre
driver did not specifically track mural cells, labeling many cardiomyocytes. However, the inducible NG2
CreER
driver specifically traced vascular mural cells in the ventricle and in the aorta, without significant labeling of PDGFRα+ fibroblasts. In contrast, the inducible PDGFRβ
CreER
line labeled not only mural cells but also the majority of cardiac and aortic fibroblasts.

Conclusions

Fibroblasts and pericytes are topographically and transcriptomically distinct populations of cardiac interstitial cells. The inducible NG2
CreER
driver optimally targets cardiac pericytes; in contrast, the inducible PDGFRβ
CreER
line lacks specificity.