bluuebunny/crossref_metadata_2025_split huggingface dataset:
Working conditions and absence from work during pregnancy in a cohort of healthcare workers
Authors: Villar Rocio , Serra Laura , Serra Consol , Benavides Fernando G 
Published: June 2022

ObjectivesTo assess the relationship between exposure to occupational risk factors during pregnancy and absence from work using two different social benefits.MethodThree working pregnancy trajectories (WPT) were identified in a cohort of 428 pregnant workers from a healthcare institution (period 2010–2014), based on absence days and using cluster analysis. WPT1 included absences mainly covered by sickness absence benefit (32.0% of women), WPT2 included absences covered by pregnancy occupational risk (POR) benefit (28.3%) and WPT3 were pregnant workers with few absences (39.9%). Exposure to occupational risk factors was assessed by experts and association with trajectories was analysed using logistic regression. Relative risks (RR) and their 95% CIs were adjusted for age, type of contract and shift work.ResultsWPT2 was associated with exposure to physical (RR=1.86, 95%CI 1.17 to 2.97), safety (RR=2.10, 95%CI 1.61 to 2.73), ergonomic (RR=2.52, 95%CI 1.89 to 3.36) and psychosocial (RR=1.79, 95%CI 1.31 to 2.46) factors, and with exposure level. For physicians, WPT1 was associated with safety risks (RR=3.13, 95%CI 1.22 to 7.99), WPT2 with chemical and ergonomic for administrative/technical support (RR=12.20, 95%CI 1.69 to 88.09; RR=14.09, 95%CI 1.34 to 148.61, respectively), with safety and ergonomic risks for nursing aides (RR=1.84, 95%CI 1.12 to 3.02; RR=3.94, 95% CI 2.38 to 6.53, respectively), and with physical (RR=1.72, 95%CI 1.04 to 2.86), safety (RR=2.21, 95%CI 1.62 to 3.03), ergonomic (RR=2.02, 95%CI 1.44 to 2.86) and psychosocial factors (RR=1.96, 95%CI 1.32 to 2.90) for nurses.ConclusionsAbsences from work covered by POR benefit show a consistent relationship with exposure to occupational risks. Sickness absence is the most frequent benefit used by pregnant workers. Current social benefits are apparently used adequately for protecting women from occupational exposures. Future studies are needed to clarify this further.
Growth and shedding of harbor seal (Phoca vitulina) whiskers
Authors: Karpovich Shawna A. , Skinner John P. , Miller Carlene N. , Polasek Lori K. , Pendleton Grey W. 
Published: June 2022

Accurate and precise estimates of the timing of whisker growth and shedding are necessary to interpret biochemical information stored in whiskers. This fine-scale examination of harbor seal ( Phoca vitulina Linnaeus, 1758) whisker growth and shedding identified an asymptotic growth pattern with initial rapid growth that decays over time that can be defined with the von Bertalanffy curve. Initial growth rates were similar among whiskers, but estimated growth coefficients ( K) and asymptotic lengths ( L∞) differed by follicle positions suggesting that differences in total whisker lengths result from dissimilarly shaped growth curves. In other words, longer whisker length is attained by delaying the growth rate decay. There was substantial intra- and interseal variation in shedding dates; whisker shedding began at the caudal margin of the whisker bed and progressed toward the nose. Shedding of marked whiskers from the three study seals took from 78 to 133 days; however, selecting whiskers only from the most caudal follicle of the bottom three rows constrained the period of whisker shedding to 7–43 days. These differences in growth and shedding of harbor seal whiskers emphasize the importance of considering follicle position to select whiskers that are the most similar for analyses of information stored in whiskers.
Postdiagnostic Inflammatory, Hyperinsulinemic, and Insulin-Resistant Diets and Lifestyles and the Risk of Prostate Cancer Progression and Mortality
Authors: Langlais Crystal S. , Graff Rebecca E. , Van Blarigan Erin L. , Kenfield Stacey A. , Neuhaus John , Tabung Fred K. , Cowan Janet E. , Broering Jeanette M. , Carroll Peter , Chan June M. 
Published: June 2022

Abstract

Background:
Inflammatory and insulin pathways have been linked to prostate cancer; postdiagnostic behaviors activating these pathways may lead to poor outcomes. The empirical dietary inflammatory pattern (EDIP), empirical dietary index for hyperinsulinemia (EDIH), and empirical dietary index for insulin resistance (EDIR), and associated lifestyle indices (ELIH, ELIR) predict biomarkers of inflammation (EDIP: IL6, TNFaR2, CRP) and insulin secretion (EDIH/ELIH: c-peptide; EDIR/ELIR: TAG:HDL) from whole foods and behaviors.

Methods:
Associations of these indices with time to prostate cancer progression (primary, n = 2,056) and prostate cancer–specific mortality (PCSM; secondary, n = 2,447) were estimated among men diagnosed with nonmetastatic prostate cancer in the Cancer of the Prostate Strategic Urologic Research Endeavor cohort diet and lifestyle sub-study. Because the true (versus clinically documented) date of progression is unobserved, we used parametric (Weibull) survival models to accommodate interval-censoringand estimated adjusted HR and 95% confidence intervals (CI) for prostate cancer progression per 1-SD increase in index. Cox proportional hazards models were used to estimate PCSM associations.

Results:
During a median [interquartile range (IQR)] 6.4 years (IQR, 1.3–12.7), 192 progression and 73 PCSM events were observed. Inflammatory (EDIP: HR, 1.27; CI, 1.17–1.37), hyperinsulinemic (EDIH: HR, 1.24; CI, 1.05–1.46. ELIH: HR, 1.34; CI, 1.17–1.54), and insulin-resistant (EDIR: HR, 1.22; CI, 1.00–1.48. ELIR: HR, 1.36; CI, 1.12–1.64) indices were positively associated with risk of prostate cancer progression. There was no evidence of associations between the indices and PCSM.

Conclusions:
Both inflammatory and insulinemic dietary and lifestyle patterns are associated with risk of prostate cancer progression.

Impact:
For men with prostate cancer, consuming dietary patterns that limit chronic systemic inflammation and insulin hypersecretion may improve survivorship, especially when coupled with active lifestyle and healthy body weight.
See related commentary by Kucuk, p. 1673
Chemical, Molecular, and Single-nucleus Analysis Reveal Chondroitin Sulfate Proteoglycan Aberrancy in Fibrolamellar Carcinoma
Authors: Francisco Adam B. , Li Jine , Farghli Alaa R. , Kanke Matt , Shui Bo , Munn Paul R. , Grenier Jennifer K. , Soloway Paul D. , Wang Zhangjie , Reid Lola M. , Liu Jian , Sethupathy Praveen 
Published: June 2022

Fibrolamellar carcinoma (FLC) is an aggressive liver cancer with no effective therapeutic options. The extracellular environment of FLC tumors is poorly characterized and may contribute to cancer growth and/or metastasis. To bridge this knowledge gap, we assessed pathways relevant to proteoglycans, a major component of the extracellular matrix. We first analyzed gene expression data from FLC and nonmalignant liver tissue (n = 27) to identify changes in glycosaminoglycan (GAG) biosynthesis pathways and found that genes associated with production of chondroitin sulfate, but not other GAGs, are significantly increased by 8-fold. We then implemented a novel LC/MS-MS based method to quantify the abundance of different types of GAGs in patient tumors (n = 16) and found that chondroitin sulfate is significantly more abundant in FLC tumors by 6-fold. Upon further analysis of GAG-associated proteins, we found that versican (VCAN) expression is significantly upregulated at the mRNA and protein levels, the latter of which was validated by IHC. Finally, we performed single-cell assay for transposase-accessible chromatin sequencing on FLC tumors (n = 3), which revealed for the first time the different cell types in FLC tumors and also showed that VCAN is likely produced not only from FLC tumor epithelial cells but also activated stellate cells. Our results reveal a pathologic aberrancy in chondroitin (but not heparan) sulfate proteoglycans in FLC and highlight a potential role for activated stellate cells.Significance:This study leverages a multi-disciplinary approach, including state-of-the-art chemical analyses and cutting-edge single-cell genomic technologies, to identify for the first time a marked chondroitin sulfate aberrancy in FLC that could open novel therapeutic avenues in the future.
Loss of Vascular Endothelial Glutaminase Inhibits Tumor Growth and Metastasis, and Increases Sensitivity to Chemotherapy
Authors: Ngwa Verra M. , Edwards Deanna N. , Hwang Yoonha , Karno Breelyn , Wang Xiaoyong , Yan Chi , Richmond Ann , Brantley-Sieders Dana M. , Chen Jin 
Published: June 2022

Glutamine is the most abundant nonessential amino acid in blood stream; yet its concentration in tumor interstitium is markedly lower than that in the serum, reflecting the huge demand of various cell types in tumor microenvironment for glutamine. While many studies have investigated glutamine metabolism in tumor epithelium and infiltrating immune cells, the role of glutamine metabolism in tumor blood vessels remains unknown. Here, we report that inducible genetic deletion of glutaminase (GLS) specifically in host endothelium, GLSECKO, impairs tumor growth and metastatic dissemination in vivo. Loss of GLS decreased tumor microvascular density, increased perivascular support cell coverage, improved perfusion, and reduced hypoxia in mammary tumors. Importantly, chemotherapeutic drug delivery and therapeutic efficacy were improved in tumor-bearing GLSECKO hosts or in combination with GLS inhibitor, CB-839. Mechanistically, loss of GLS in tumor endothelium resulted in decreased leptin levels, and exogenous recombinant leptin rescued tumor growth defects in GLSECKO mice. Together, these data demonstrate that inhibition of endothelial glutamine metabolism normalizes tumor vessels, reducing tumor growth and metastatic spread, improving perfusion, reducing hypoxia, and enhancing chemotherapeutic delivery. Thus, targeting glutamine metabolism in host vasculature may improve clinical outcome in patients with solid tumors.Significance:This study demonstrates a crucial role for glutamine metabolism in tumor endothelium, which may be exploited therapeutically to induce vascular normalization and improve drug delivery in solid tumors.
Multifaceted Intervention to Improve P2Y12 Inhibitor Adherence After Percutaneous Coronary Intervention: A Stepped Wedge Trial
Authors: Ho P. Michael , O’Donnell Colin I. , McCreight Marina , Bavry Anthony A. , Bosworth Hayden B. , Girotra Saket , Grossman P. Michael , Helfrich Christian , Latif Faisal , Lu David , Matheny Michael , Mavromatis Kreton , Ortiz Jose , Parashar Amitabh , Ratliff Devona M. , Grunwald Gary K. , Gillette Michael , Jneid Hani 
Published: June 2022

Background
P2Y12 inhibitor medications are critical following percutaneous coronary intervention (PCI); however, adherence remains suboptimal. Our objective was to assess the effectiveness of a multifaceted intervention to improve P2Y12 inhibitor adherence following PCI.

Methods and Results
This was a modified stepped wedge trial of 52 eligible hospitals, of which 15 were randomly selected and agreed to participate (29 hospitals declined, and 8 eligible hospitals were not contacted). At each intervention hospital, patient recruitment occurred for 6 months and enrolled patients were followed up for 1 year after PCI. Three control groups were used: patients at intervention hospitals undergoing PCI (1) before the intervention period (preintervention); (2) after the intervention period (postintervention); or (3) at the 8 hospitals not contacted (concurrent controls). The intervention consisted of 4 components: (1) P2Y12 inhibitor delivered to patients’ bedside after PCI; (2) education on importance of P2Y12 inhibitors; (3) automated reminder telephone calls to refill medication; and (4) outreach to patients if they delayed refilling P2Y12 inhibitor. The primary outcomes were as follows: (1) proportion of patients with delays filling P2Y12 inhibitor at hospital discharge and (2) proportion of patients who were adherent in the year after PCI using pharmacy refill data. Primary analysis compared intervention with preintervention control patients. There were 1377 (intent‐to‐treat) potentially eligible patients, of whom 803 (per protocol) were approached at intervention sites versus 5910 preintervention, 2807 postintervention, and 4736 concurrent control patients. In the intent‐to‐treat analysis, intervention patients were less likely to delay filling P2Y12 at hospital discharge (−3.4%; 98.3% CI, −1.2% to −5.6%) and more likely to be adherent to P2Y12 (4.1%; 98.3% CI, 1.0%–7.1%) at 1 year, but had more clinical events (3.2%; 98.3% CI, 2.3%–4.1%) driven by repeated PCI compared with preintervention patients. In post hoc analysis looking at myocardial infarction, stroke, and death, intervention patients had lower event rates compared with preintervention patients (−1.7%; 98.3% CI, −2.3% to –1.1%).

Conclusions
A 4‐component intervention targeting P2Y12 inhibitor adherence was difficult to implement. The intervention produced mixed results. It improved P2Y12 adherence, but there was also an increase in repeat PCI.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01609842.
Misdiagnosis of Thoracic Aortic Emergencies Occurs Frequently Among Transfers to Aortic Referral Centers: An Analysis of Over 3700 Patients
Authors: Arnaoutakis George J. , Ogami Takuya , Aranda‐Michel Edgar , Dai Yancheng , Holmes Reed , Beaver Thomas M. , Serna‐Gallegos Derek , Martin Tomas D. , Navid Forozan , Yousef Sarah , Sultan Ibrahim 
Published: June 2022

Background
Acute aortic syndromes may be prone to misdiagnosis by nonreferral aortic centers with less diagnostic experience. We evaluated regional variability in these misdiagnosis trends among patients transferred to different regional quaternary care centers with presumed acute aortic syndromes.

Methods and Results
Two institutional aortic center databases were retrospectively reviewed for emergency transfers in patients diagnosed with acute aortic dissection, intramural hematoma, penetrating aortic ulcer, thoracic aortic aneurysm, or aortic pseudoaneurysm between 2008 and 2020. Transferring diagnoses versus actual diagnoses were reviewed using physician notes and radiology reports. Misdiagnoses were confirmed by a board‐certified cardiothoracic surgeon. A total of 3772 inpatient transfers were identified, of which 1762 patients were classified as emergency transfers. The mean age was 64 years (58% male). Patients were transferred from 203 medical centers by ground (51%) or air (49%). Differences in transfer diagnosis and actual diagnosis were identified in 188 (10.7%) patients. Of those, incorrect classification of Type A versus B dissections was identified among 23%, and 30% of patients with a referring diagnosis of an acute aortic dissection did not have one. In addition, 14% transferred for contained/impending rupture did not have signs of rupture. All misdiagnoses were secondary to misinterpretation of imaging, with motion artifacts (n=32, 17%) and postsurgical changes (n=44, 23%) being common sources of diagnostic error.

Conclusions
Misdiagnosis of acute aortic syndromes commonly occurred in patients transferred to 2 separate large aortic referral centers. Although diagnostic accuracy may be improving, there are opportunities for improved physician awareness through standardized web‐based imaging education.
Left Frontal White Matter Links to Rhythm Processing Relevant to Speech Production in Apraxia of Speech
Authors: Bruffaerts Rose , Schaeverbeke Jolien , Radwan Ahmed , Grube Manon , Gabel Silvy , De Weer An-Sofie , Dries Eva , Van Bouwel Karen , Griffiths Timothy D. , Sunaert Stefan , Vandenberghe Rik 
Published: June 2022

Abstract
Recent mechanistic models argue for a key role of rhythm processing in both speech production and speech perception. Patients with the non-fluent variant (NFV) of primary progressive aphasia (PPA) with apraxia of speech (AOS) represent a specific study population in which this link can be examined. Previously, we observed impaired rhythm processing in NFV with AOS. We hypothesized that a shared neurocomputational mechanism structures auditory input (sound and speech) and output (speech production) in time, a “temporal scaffolding” mechanism. Since considerable white matter damage is observed in NFV, we test here whether white matter changes are related to impaired rhythm processing. Forty-seven participants performed a psychoacoustic test battery: 12 patients with NFV and AOS, 11 patients with the semantic variant of PPA, and 24 cognitively intact age- and education-matched controls. Deformation-based morphometry was used to test whether white matter volume correlated to rhythmic abilities. In 34 participants, we also obtained tract-based metrics of the left Aslant tract, which is typically damaged in patients with NFV. Nine out of 12 patients with NFV displayed impaired rhythmic processing. Left frontal white matter atrophy adjacent to the supplementary motor area (SMA) correlated with poorer rhythmic abilities. The structural integrity of the left Aslant tract also correlated with rhythmic abilities. A colocalized and perhaps shared white matter substrate adjacent to the SMA is associated with impaired rhythmic processing and motor speech impairment. Our results support the existence of a temporal scaffolding mechanism structuring perceptual input and speech output.
Development of a carotid artery thrombolysis stroke model in mice
Authors: Maclean Jessica A. A. , Tomkins Amelia J. , Sturgeon Sharelle A. , Hofma Benjamin R. , Alwis Imala , Samson Andre L. , Schoenwaelder Simone M. , Jackson Shaun P. 
Published: June 2022

Abstract
Recanalization with restored cerebral perfusion is the primary goal of thrombolytic therapy in acute ischemic stroke. The identification of adjunctive therapies that can be safely used to enhance thrombolysis in stroke remains an elusive goal. We report here the development of a mouse in situ carotid artery thrombolysis (iCAT) stroke model involving graded cerebral ischemia to induce unihemispheric infarction after thrombotic occlusion of the common carotid artery (CCA). Electrolytic-induced thrombotic occlusion of the left CCA enabled real-time assessment of recanalization and rethrombosis events after thrombolysis with recombinant tissue-type plasminogen activator (rtPA). Concurrent transient stenosis of the right CCA induced unihemispheric hypoperfusion and infarction in the left middle cerebral artery territory. Real-time assessment of thrombolysis revealed recanalization rates &lt;30% in rtPA-treated animals with high rates of rethrombosis. Addition of the direct thrombin inhibitor argatroban increased recanalization rates to 50% and reduced rethrombosis. Paradoxically, this was associated with increased cerebral ischemia and stroke-related mortality (25%-42%). Serial analysis of carotid and cerebral blood flow showed that coadministration of argatroban with rtPA resulted in a marked increase in carotid artery embolization, leading to distal obstruction of the middle cerebral artery. Real-time imaging of carotid thrombi revealed that adjunctive anticoagulation destabilized platelet-rich thrombi at the vessel wall, leading to dislodgement of large platelet emboli. These studies confirm the benefits of anticoagulants in enhancing thrombolysis and large artery recanalization; however, at high levels of anticoagulation (∼3-fold prolongation of activated partial thromboplastin time), this effect is offset by increased incidence of carotid artery embolization and distal middle cerebral artery occlusion. The iCAT stroke model should provide important new insight into the effects of adjunctive antithrombotic agents on real-time thrombus dynamics during thrombolysis and their correlation with stroke outcomes.
Defective VWF secretion due to expression ofMYH9-RD E1841K mutant in endothelial cells disrupts hemostasis
Authors: Cao Yang , Sun Yanjie , Deng Yanan , Wei Guoqin , Liu Junling , Jin Shengyu , Dong Chao , Kang Xuya , Huo Yingqing , Zhang Jingjing , Luo Jincai 
Published: June 2022

AbstractMutations in MYH9, the gene encoding the heavy chain of nonmuscle myosin IIa (NMII-A), cause MYH9-related disease (MYH9-RD), which is an autosomal-dominant thrombocytopenia with bleeding tendency. Previously, we showed that NMII-A in endothelial cells (ECs) is critical for hemostasis via regulating von Willebrand factor (VWF) release from Weibel-Palade bodies (WPBs). The aim of this study was to determine the role of the expression of MYH9 mutants in ECs in the pathogenesis of the MYH9-RD bleeding symptom. First, we expressed the 5 most common NMII-A mutants in ECs and found that E1841K mutant-expressing ECs secreted less VWF than the controls in response to a cyclic adenosine monophosphate (cAMP) signaling agonist. Then, we generated 2 knockin mouse lines, 1 with Myh9 E1841K in ECs and the other in megakaryocytes. Endothelium-specific E1841K mice exhibited impaired cAMP-induced VWF release and a prolonged bleeding time with normal platelets, whereas megakaryocyte-specific E1841K mice exhibited macrothrombocytopenia and a prolonged bleeding time with normal VWF release. Finally, we presented mechanistic findings that E1841K mutation not only interferes with S1943 phosphorylation and impairs the peripheral distribution of Rab27a-positive WPBs in Ecs under quiescent condition but also interferes with S1916 phosphorylation by disrupting the interaction with zyxin and CKIIα and reduces actin framework formation around WPBs and subsequent VWF secretion under the stimulation by a cAMP agonist. Altogether, our results suggest that impaired cAMP-induced endothelial VWF secretion by E1841K mutant expression may contribute to the MYH9-RD bleeding phenotype.
A case–control study of agricultural and behavioral factors associated with leptospirosis in Vietnam
Authors: Dung Luu Phuong , Hai Pham Thanh , Hoa Luong Minh , Mai Tran Ngoc Phuong , Hanh Nguyen Thi My , Than Phan Dang , Tran Van Dinh , Quyet Nguyen Tu , Hai Hoang , Ngoc Do Bich , Thu Nguyen Thị , Mai Le Thi Phuong 
Published: June 2022

AbstractIntroductionLeptospirosis is a neglected disease in Vietnam. Until now, there has been limited knowledge about risk factors of this disease in Vietnam. The study was carried out to identify agricultural and behavioral factors associated with the transmission of leptospirosis in Vietnam.MethodsThis matched retrospective hospital-community-based case–control study was conducted from 1 October 2018 to 31 October 2019. We recruited cases from 11 selected government hospitals in three provinces of Vietnam, while controls were selected from the same communes of cases and matched by age (± 2 years) and sex. Microscopic agglutination test (MAT) and enzyme-linked immunosorbent assay (ELISA) were applied to determine confirmed cases, while only MAT was used to identify controls with a single high MAT titer < 1:100.Results504 participants (252 cases and 252 controls) were identified. Cultivating (OR 2.83, CI 1.38–5.79), animal farming (OR 8.26, CI 2.24–30.52), pig owners (OR 10.48, CI 5.05–21.73), cat owners (OR 2.62, CI 1.49–4.61) and drinking unboiled water (OR 1.72, CI 1.14 –2.59, p = 0.010) were significantly associated with human leptospirosis in Vietnam. Hand washing after farming/ gardening (OR 0.57, CI 0.38–0.86, p = 0.007) and bathing after farming, gardening, contact with cattle and poultry (OR 0.33, CI 0.19–0.58, p = 0.000) were determined as protective factors for this disease.ConclusionsIn short, the case–control study has revealed the risks in agricultural and animal practices and protective behavioral factors related to human leptospirosis in Vietnam. The findings suggested promotion of communication and health education programs targeting health behaviors in daily life and agricultural practices. Using personal protective equipment such as gowns, gloves, and boots during agricultural practices, especially cultivating and animal farming, is most recommended.