bluuebunny/crossref_metadata_2025 huggingface dataset:
Superficial Temporal Artery Extended Interposition Graft to Anterior Cerebral Artery Bypass for the Treatment of a Large Fusiform Distal Anterior Cerebral Artery Aneurysm: 2-Dimensional Operative Video
Authors: Sudhir Bhanu Jayanand , Murali Sanjay Honavalli , Jamaluddin Mohamed Amjad , Venkat Easwer Hariharan
Published: July 2021

Fusiform aneurysms of the distal anterior cerebral artery (DACA) are infrequent. Clip reconstruction and sequential progressive clipping have been described in the management of giant thrombosed DACA aneurysms.
1,2
Customized revascularization with bypass, side-to-side anastomosis, and trapping of the aneurysmal segment have also been performed for treating DACA aneurysms.
3-12
We present a 2-dimensional operative video of superficial temporal artery (STA) to distal anterior cerebral artery bypass, followed by trapping of the aneurysm-bearing segment. A 57-yr-old lady presented with a large ruptured subcallosal fusiform DACA aneurysm (WFNS grade 1, Fisher grade 1). Angiography revealed a 1.3 × 0.9 cm fusiform aneurysm in the DACA.

 Informed consent was secured from the patient and her family for the surgery and permission was obtained for the publication of the patient's image/surgical video. The frontal and parietal branches of the STA were dissected. The parietal branch was explanted and used as a free interposition graft between the frontal branch (end-to-end anastomosis) and calloso-marginal artery (end-to-side anastomosis). After confirming blood flow through the bypass using Doppler, the aneurysm was trapped and excised.

 The patient had an uneventful recovery. Her postoperative computed tomography (CT) head revealed no evidence of neurological insult. The patency of the bypass conduit and the complete removal of the aneurysm were confirmed using a digital subtraction angiogram. Histopathological examination revealed an eccentric atheromatous plaque with a lipid core. There was no evidence of intraplaque hemorrhage. This extended STA graft utilizing the frontal and parietal branches of the STA, and its implantation into the distal ACA, offers a novel bypass strategy for tackling fusiform aneurysms of the DACA. Anastomosis to the calloso-marginal artery ensured perfusion of the ACA territory through the pericallosal artery during temporary occlusion.
Crowding-in or Crowding-out? How Subsidies Signal the Path to Financial Independence of Social Enterprises
Authors: Reichert Patrick , Hudon Marek , Szafarz Ariane , Christensen Robert K
Published: July 2021

In today’s multisector configurations, there is little clarity about whether and how public and private subsidies influence social enterprises’ pursuit of financial stability. We address the strategic role of donors in the social-business life cycle whereby social enterprise start-ups rely on subsidies, while mature social enterprises strive for independence from donors. To address the “missing middle,” we develop a typology of subsidy instruments and an intermediary signaling model to clarify how subsidies shape the evolution of outcomes for social enterprises. We argue that source variation matters for certain instruments like corporate intangibles and governmentally subsidized credit guarantees, which trigger crowding-in effects and attract commercial partners, while preventing perverse crowding-out effects, such as soft budget constraints. To illustrate this commercialization story, we draw upon a microfinance case study, demonstrating how public and private donors can induce crowding-in and crowding-out effects. In short, our subsidy typology helps unpack the signals that public and private subsidies send to commercial funders of social enterprises and how they shape the path to future financial independence.
On “Trade Induced Technical Change: The Impact of Chinese Imports on Innovation, IT, and Productivity”
Authors: Campbell Douglas L , Mau Karsten
Published: July 2021

Bloom et al. (2016) find that Chinese import competition induced a rise in patenting, IT adoption, and total factor productivity (TFP) by up to 30% of the total increase in Europe in the late 1990s and early 2000s. We uncover several coding errors in an important robustness check of their patent results. When corrected, we find no statistically significant relationship between Chinese competition and patents. Other specifications in the original paper use a problematic $ \log(1+\rm patents) $ transformation. This normalization induces bias given low average patent counts for firms in China-competing sectors and rapidly declining patents across the sample.
Social factors and chronic pain: the modifying effect of sex in the Stockholm Public Health Cohort Study
Authors: Prego-Domínguez Jesús , Skillgate Eva , Orsini Nicola , Takkouche Bahi
Published: July 2021

Objectives

To assess the relationship between social factors (socio-economic status, household load and job strain) and chronic pain occurrence, and the role of gender in this relationship.

Methods

We used data corresponding to 8 years of follow-up of the Stockholm Public Health Cohort Study (2006–2014) to compute Adjusted Incidence Rate Ratios (IRRs) and additive interaction measures of chronic pain episodes, social factors, and sex in 16 687 subjects.

Results

For men, increased rates of chronic pain occurrence were observed for skilled workers (IRR = 1.27, 95% CI: 0.99, 1.61) and lower non-manual employees (IRR = 1.37, 95% CI: 1.05, 1.78), compared with unskilled workers; subjects with high household load (IRR = 1.39; 95% CI: 1.03, 1.88), compared with those with a null score; and subjects with active jobs (IRR = 1.27, 95% CI: 1.06, 1.51), compared with those with low-strain jobs. For women, we observed decreased rates of chronic pain occurrence in lower (IRR = 0.82, 95% CI: 0.68, 0.99), intermediate (IRR = 0.74, 95% CI: 0.63, 0.88) and higher non-manual employees (IRR = 0.65, 95% CI: 0.54, 0.79), compared with unskilled workers. Compared with subjects with a null score, women with low household load showed a lower rate of chronic pain occurrence (IRR = 0.85; 95% CI: 0.72, 1.00). Compared with subjects with low-strain jobs, those with passive jobs (IRR = 1.21; 95% CI: 1.02, 1.44) and high-strain jobs (IRR = 1.46; 95% CI: 1.02, 2.09) showed higher rates of chronic pain occurrence.

Conclusion

In general, our analysis yielded different, if not opposite, results when data were stratified by sex. Sex may then represent an effect modifier of the relationship between social factors and chronic pain.
Do Archive Catalogues Make History?: Exploring Interactions between Historians and Archives
Authors: Dunley Richard , Pugh Jo
Published: July 2021

Archival research is foundational to the writing of most works of academic history and is a central part of the professional identity of historians. Despite this, we know very little about what historians do in archives, and how it shapes the process of writing history. This article uses quantitative data from The National Archives of the UK to analyse one part of this puzzle, namely how historians choose what to look at in an archive. It explores the nature of archive catalogues, and their relationship to the collections they describe. It goes on to assess how catalogues shape what historians choose to view when they visit an archive, and concludes by looking more widely at historians’ information seeking practices. Through this analysis the article will argue that external factors have a far greater impact on archival research, and through it the writing of history, than is traditionally acknowledged, and as such historians need to pay considerably more attention to the ways in which their access to archives is shaped by these factors.
‘Look into Their Hearts’ 7-Year-Old Boy with Sickle Cell Disease, Fever, Left Sixth and Seventh Cranial Nerve Palsy and Left Hemiplegia
Authors: Jabateh Sekou M , Mohsenibod Hadi
Published: July 2021

A 7-year-old Liberian boy presented with fever, severe headache, neck pain and ‘not being able to walk’. In the emergency room, his sickle cell screen was positive, and his haemoglobin level was 7 g/dl. Initially, he was admitted to the ward with a diagnosis of sickle cell painful crisis and was treated with ceftrixone iv, and oral morphine and paracetamol. In a more complete physical examination, he had left peripheral seventh nerve palsy, left sixth nerve palsy and ipsilateral hemiplegia, also neck rigidity. In a bedside ultrasound scan, he had a large, mobile vegetation on the aortic leaflet of the mitral valve. The final diagnosis was acute infective endocarditis with multiple embolic strokes in a child with sickle cell disease. Headache and neck rigidity was most likely due to SAH or meningitis.
Long-term Survival after Combined Epidural–General Anesthesia or General Anesthesia Alone: Follow-up of a Randomized Trial
Authors: Du Ya-Ting , Li Ya-Wei , Zhao Bin-Jiang , Guo Xiang-Yang , Feng Yi , Zuo Ming-Zhang , Fu Cong , Zhou Wei-Jie , Li Huai-Jin , Liu Ya-Fei , Cheng Tong , Mu Dong-Liang , Zeng Yuan , Liu Peng-Fei , Li Yan , An Hai-Yan , Zhu Sai-Nan , Li Xue-Ying , Li Hui-Juan , Wu Yang-Feng , Wang Dong-Xin , Sessler Daniel I. ,   for the Peking University Clinical Research Program Study Group
Published: July 2021

Background

Experimental and observational research suggests that combined epidural–general anesthesia may improve long-term survival after cancer surgery by reducing anesthetic and opioid consumption and by blunting surgery-related inflammation. This study therefore tested the primary hypothesis that combined epidural–general anesthesia improves long-term survival in elderly patients.

Methods

This article presents a long-term follow-up of patients enrolled in a previous trial conducted at five hospitals. Patients aged 60 to 90 yr and scheduled for major noncardiac thoracic and abdominal surgeries were randomly assigned to either combined epidural–general anesthesia with postoperative epidural analgesia or general anesthesia alone with postoperative intravenous analgesia. The primary outcome was overall postoperative survival. Secondary outcomes included cancer-specific, recurrence-free, and event-free survival.

Results

Among 1,802 patients who were enrolled and randomized in the underlying trial, 1,712 were included in the long-term analysis; 92% had surgery for cancer. The median follow-up duration was 66 months (interquartile range, 61 to 80). Among patients assigned to combined epidural–general anesthesia, 355 of 853 (42%) died compared with 326 of 859 (38%) deaths in patients assigned to general anesthesia alone: adjusted hazard ratio, 1.07; 95% CI, 0.92 to 1.24; P = 0.408. Cancer-specific survival was similar with combined epidural–general anesthesia (327 of 853 [38%]) and general anesthesia alone (292 of 859 [34%]): adjusted hazard ratio, 1.09; 95% CI, 0.93 to 1.28; P = 0.290. Recurrence-free survival was 401 of 853 [47%] for patients who had combined epidural–general anesthesia versus 389 of 859 [45%] with general anesthesia alone: adjusted hazard ratio, 0.97; 95% CI, 0.84 to 1.12; P = 0.692. Event-free survival was 466 of 853 [55%] in patients who had combined epidural–general anesthesia versus 450 of 859 [52%] for general anesthesia alone: adjusted hazard ratio, 0.99; 95% CI, 0.86 to 1.12; P = 0.815.

Conclusions

In elderly patients having major thoracic and abdominal surgery, combined epidural–general anesthesia with epidural analgesia did not improve overall or cancer-specific long-term mortality. Nor did epidural analgesia improve recurrence-free survival. Either approach can therefore reasonably be selected based on patient and clinician preference.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Developing the building blocks to elucidate the impact of the urban exposome on cardiometabolic-pulmonary disease
Authors: Vlaanderen Jelle , de Hoogh Kees , Hoek Gerard , Peters Annette , Probst-Hensch Nicole , Scalbert Augustin , Melén Erik , Tonne Cathryn , de Wit G. Ardine , Chadeau-Hyam Marc , Katsouyanni Klea , Esko Tõnu , Jongsma Karin R. , Vermeulen Roel
Published: July 2021

By 2030, more than 80% of Europe’s population will live in an urban environment. The urban exposome, consisting of factors such as where we live and work, where and what we eat, our social network, and what chemical and physical hazards we are exposed to, provides important targets to improve population health. The EXPANSE (EXposome Powered tools for healthy living in urbAN SEttings) project will study the impact of the urban exposome on the major contributors to Europe’s burden of disease: Cardio-Metabolic and Pulmonary Disease. EXPANSE will address one of the most pertinent questions for urban planners, policy makers, and European citizens: “How to maximize one’s health in a modern urban environment?” EXPANSE will take the next step in exposome research by (1) bringing together exposome and health data of more than 55 million adult Europeans and OMICS information for more than 2 million Europeans; (2) perform personalized exposome assessment for 5,000 individuals in five urban regions; (3) applying ultra-high-resolution mass-spectrometry to screen for chemicals in 10,000 blood samples; (4) evaluating the evolution of the exposome and health through the life course; and (5) evaluating the impact of changes in the urban exposome on the burden of cardiometabolic and pulmonary disease. EXPANSE will translate its insights and innovations into research and dissemination tools that will be openly accessible via the EXPANSE toolbox. By applying innovative ethics-by-design throughout the project, the social and ethical acceptability of these tools will be safeguarded. EXPANSE is part of the European Human Exposome Network.
Angiographic Evidence of Response to Trametinib Therapy for a Spinal Cord Arteriovenous Malformation
Authors: Cooke Daniel L. , Frieden Ilona J. , Shimano Kristin A.
Published: July 2021

Several studies have implicated RAS and the RAS-related gene family (eg, BRAF, KRAS, and MAPK) in sporadic arteriovenous malformations (AVMs) with evidence that targeted biologic agents (eg, trametinib) may be beneficial for certain patients. Despite similar genetic mutations in brain and spine AVMs, however, no evidence of molecular intervention has proven effective in impacting such cases. We describe a single patient undergoing MEK-inhibitor therapy for a KRAS-positive thoracic wall AVM with an additional spinal intramedullary AVM. Angiography demonstrated significant reduction in the flow to and size of the patient’s intramedullary AVM. Based on this result, formal trials for inoperable and/or therapeutically challenging central nervous system AVMs might be considered.
Outcomes of a Pediatric Ultrasound-Guided Short Peripheral Catheter Training Program and Hands-On Poultry Simulation Course
Authors: Russell Christina , Mullaney Kathleen , Campbell Tracy , Sabado Jeremiah , Haut Catherine
Published: July 2021

Ultrasound guidance is an effective technique for obtaining short peripheral catheter (SPC) access but requires training and practice for proficiency. The aim of this quality improvement initiative was to develop and assess a formal training program to increase the confidence and competency of intravenous (IV) therapy nurses in the placement of ultrasound-guided SPCs. IV therapy nurses completed a didactic and hands-on training course where they practiced ultrasound-guided SPC placement techniques on a poultry phantom during simulation, followed by performing ultrasound-guided SPC insertion on patients proctored by an interventional radiology physician. Data collection included preintervention and postintervention confidence self-assessment, frequency tracker, Difficult Intravenous Access (DIVA) scale scores, and total number of ultrasound-guided SPCs placed by the nurses. Ultrasound-guided SPC placement increased significantly after the training program. The IV therapy nurses placed 29 ultrasound-guided SPCs in 2017, 391 ultrasound-guided SPCs in 2018, and 711 ultrasound-guided SPCs in 2019. Mean DIVA scores rose from 4.54 in May 2018 to 5.17 in July 2018, indicating success in placing SPCs in more difficult patients. Implementation of an ultrasound-guided SPC placement program using poultry phantom simulation is a recommended nursing resource for increasing competency in ultrasound-guided SPC placement in pediatric patients.
Placement of a Peripherally Inserted Central Catheter in a Prone Patient With COVID-19
Authors: Kelly Linda , Dreher Denise , Kim Georgia , Hughes Timothy , Sabouri A. Sassan
Published: July 2021

The emergence of the coronavirus disease 2019 (COVID-19) virus has increased in patients with acute respiratory distress syndrome (ARDS). The use of prone positioning during COVID-19–associated ARDS has led to improved oxygenation and decreased mortality. Extended hours of proning may delay or prevent traditional approaches to central vascular access, such as jugular, subclavian, or femoral cannulation. A peripherally inserted central catheter (PICC) is a viable option for prone patients. This article presents a PICC placement in a 56-year-old man with COVID-19 ARDS who required 20- to 24-hour prone positioning during his care in the intensive care unit. Insertion of a PICC while the patient is prone expedites lifesaving medications and infusions without waiting for the patient to be stable enough to be turned to the supine position.
Advance Care Planning Among Chinese Americans Through a Web-Based Culturally Tailored Education Program
Authors: Ye Ping , Champion Jane Dimmitt , Fry Liam
Published: July 2021

At any time, a medical crisis could result in an individual too sick to make one's own health care decisions. Advance care planning (ACP) is an important step to ensure that each person receives the medical care desired. Despite its significant importance and proven benefits, the completion rate for advance directive is approximately one-third among the general population in the United States and lower among Chinese Americans. This study explored Chinese Americans' knowledge and attitudes about ACP following completion of a web-based culturally tailored health education program. Ninety-six individuals completed the study between October 1 and December 31, 2020. Prestudy-poststudy outcomes measured included the Advance Directive Knowledge Survey and Advance Directive Attitude Scale administered before and after completion of the education program. Each measure has 9 questions and 16 questions, respectively. Participants' Advance Directive Knowledge Survey scores (pre: mean, 6.04 [SD, 2.28]; post: mean, 8.75 [SD, 0.53]; P < .01) and Advance Directive Attitude Scale scores (pre: mean, 47.31 [SD, 5.69]; post: mean, 53.59 [SD, 4.37]; P < .01) increased significantly following program completion. Findings indicated feasibility for integration of web-based technology and culturally tailored approaches to promote ACP knowledge and attitudes among Chinese Americans.
Improving Vascular Access Dressing Integrity in the Acute Care Setting
Authors: DeVries Michelle , Sarbenoff Jill , Scott Nancy , Wickert Margaret , Hayes Lisa Marie
Published: July 2021

PURPOSE:

The purpose of this quality improvement project was to evaluate transparent vascular access dressings and the use of a liquid gum mastic adhesive on improving dressing integrity over peripheral intravenous (PIV) insertion sites without increasing medical adhesive-related skin injuries (MARSIs) such as tears.

PARTICIPANTS AND SETTING:

A multidisciplinary team consisting of specialists in infection prevention, vascular access, nursing professional development, materials management, and WOC nurses met to review current audit data and available products to trial on 2 intermediate care units in our 2 hospitals in Indiana with a combined average daily unit census of 35 patients.

APPROACH:

Four dressing protocols—including our existing dressing with education, and an updated dressing with education, and the updated and new dressing, both with education and the addition of a gum mastic adhesive agent—were sequentially implemented by nurses on the units, each over a 2-week period. The goal was for 80% of the dressings to remain with all 4 corners fully intact without reinforcement at day 7, or sooner if PIV was discontinued before day 7. Data were reported as frequencies for intact dressings and skin complications.

OUTCOMES:

Education combined with the original dressing and the updated dressing did not achieve the goal of 80% fully intact dressings in the samples evaluated. The addition of the adhesive agent to the updated and new dressings with education exceeded the 80% goal. In addition, there were zero exposed PIV insertion sites and no documented MARSI in any of the 4 protocols.

IMPLICATIONS FOR PRACTICE:

We continued to collect postproject data of 30,049 vascular access sites including central line catheters and observed the same effectiveness of incorporating a gum mastic adhesive on dressing integrity. This practice change has now become standard of care in our institution.
Clypifer cribrifer gen. nov., sp. nov. (Clypiferidae fam. nov., Pterocystida, Centroplasthelida), with notes on evolution of centrohelid siliceous coverings
Authors: Shishkin Yegor , Drachko Daria , Zlatogursky Vasily V.
Published: July 2021

A new family, genus and species of centrohelid heliozoans, Clypifer cribrifer gen. nov., sp. nov. (Clypiferidae fam. nov.), from the Gulf of Aqaba (Israel) was studied with light and electron microscopy and SSU rRNA gene sequencing. Clypifer cribrifer has only one type of scales, partially running up the sides of the axopodia. Plate scales [0.8–2.3 (av. 1.5)×0.6–1.8 (av. 1.2) μm] are flat, elliptical or circular, fenestrated with holes of irregular shape and have a marginal rim and a very short axial rib. The cell diameter is 3.9–9.6 (av. 6.0) μm. Molecular phylogenetic analysis robustly places C. cribrifer in the C4 clade for which the new family Clypiferidae is proposed here. This position is confirmed with the short sequences in the panacanthocystid increased regions. The morphology of the new genus has similarities to the genus Raphidocystis. The probability that another Clypifer species was described under a different name in the centrohelid literature is discussed. Clypiferidae represent the second lineage of Pterocystida, which are characterized by the presence of only tangentially oriented plate scales of one type. Possible ways of evolution of the centrohelid siliceous coverings are also discussed.
One Year of SARS-CoV-2: How Much Has the Virus Changed?
Authors: Vilar Santiago , Isom Daniel G.
Published: July 2021

SARS-CoV-2 coronavirus has caused a world-wide crisis with profound effects on both healthcare and the economy. In order to combat the COVID-19 pandemic, research groups have shared viral genome sequence data through the GISAID initiative. We collected and computationally profiled ∼223,000 full SARS-CoV-2 proteome sequences from GISAID over one year for emergent nonsynonymous mutations. Our analysis shows that SARS-CoV-2 proteins are mutating at substantially different rates, with most viral proteins exhibiting little mutational variability. As anticipated, our calculations capture previously reported mutations occurred in the first period of the pandemic, such as D614G (Spike), P323L (NSP12), and R203K/G204R (Nucleocapsid), but also identify recent mutations like A222V and L18F (Spike) and A220V (Nucleocapsid). Our comprehensive temporal and geographical analyses show two periods with different mutations in the SARS-CoV-2 proteome: December 2019 to June 2020 and July to November 2020. Some mutation rates differ also by geography; the main mutations in the second period occurred in Europe. Furthermore, our structure-based molecular analysis provides an exhaustive assessment of mutations in the context of 3D protein structure. Emerging sequence-to-structure data is beginning to reveal the site-specific mutational tolerance of SARS-CoV2 proteins as the virus continues to spread around the globe.
Soft robotic steerable micro-catheter for the endovascular treatment of cerebral disorders
Authors: Gopesh Tilvawala , Wen Jessica H. , Santiago-Dieppa David , Yan Bernard , Pannell J. Scott , Khalessi Alexander , Norbash Alexander , Friend James
Published: July 2021

Catheters used for endovascular navigation in interventional procedures lack dexterity at the distal tip. Neurointerventionists, in particular, encounter challenges in up to 25% of aneurysm cases largely due to the inability to steer and navigate the tip of the micro-catheters through tortuous vasculature to access aneurysms. We overcome this problem with sub-millimeter diameter, hydraulically-actuated hyperelastic polymer devices at the distal tip of micro- catheters to enable active steerability. Controlled by hand, the devices offer complete 3D orientation of the tip. Using pressures up to 400 kPa (4 atm) we demonstrate guidewire-free navigation, access, and coil deploymentin vivo, offering safety, ease of use, and design flexibility absent in other approaches to endovascular intervention. We demonstrate the ability of our device to navigate through vessels and to deliver embolization coils to the cerebral vessels in a live porcine model. This indicates the potential for microhydraulic soft robotics to solve difficult access and treatment problems in endovascular intervention.
A cross-sectional study of the association between frequency of telecommuting and unhealthy dietary habits among Japanese workers during the COVID-19 pandemic
Authors: Kubo Yoshiko , Ishimaru Tomohiro , Hino Ayako , Nagata Masako , Ikegami Kazunori , Tateishi Seiichiro , Tsuji Mayumi , Matsuda Shinya , Fujino Yoshihisa
Published: July 2021

2.

Abstract and keywords

Objective

Due to the COVID-19 pandemic, telecommuting has become a new way of working that has not only changed individuals’ work, but also their health and lifestyle. We examined the relationship between telecommuting frequency and unhealthy dietary habits among Japanese workers.

Methods

A total of 33,302 workers completed an Internet survey about telecommuting and dietary habits. Data from 13,468 office workers who telecommuted were analyzed. Telecommuting frequency during the COVID-19 pandemic was extracted from a questionnaire. The odds ratios (ORs) of four types of dietary habits, namely, skipping breakfast, solitary eating, lower meal frequency, and meal substitution associated with telecommuting frequency were estimated using multilevel logistic regression nested in the prefecture of residence to control for differences in residential area.

Results

The multivariate OR of skipping breakfast was 1.15 (95% CI: 1.03–1.29, p=0.013) for participants who telecommuted in excess of four days per week compared to those who rarely telecommuted. Similarly, the OR of solitary eating, lower meal frequency and meal substitution were 1.44 (95%CI: 1.28–1.63, p<0.001), 2.39 (95%CI: 1.66–3.44, p<0.001), and 1.26 (95%CI: 1.04–1.51, p=0.015) for those who telecommuted in excess of four days per week compared to those who rarely telecommuted. There was a statistically significant increase in the dose-response trend in ORs of solitary eating (p for trend <0.001), lower meal frequency (p for trend <0.001), and meal substitution (p for trend =0.001) with increasing telecommuting frequency.

Conclusion

Telecommuters may develop unhealthy dietary habits, indicating the need for strategies to help telecommuters manage their nutrition and diet.
Molecular pathways in post-colonoscopy versus detected colorectal cancers: results from a nested case-control study
Authors: Bogie Roel M.M. , le Clercq Chantal M.C. , Voorham Quirinus J.M. , Cordes Martijn , Sie Daoud , Rausch Christian , van den Broek Evert , de Vries Sara D.J. , van Grieken Nicole C.T. , Riedl Robert G. , Sastrowijoto Prapto , Speel Ernst-Jan , Vos Rein , Winkens Bjorn , van Engeland Manon , Ylstra Bauke , Meijer Gerrit A. , Masclee Ad A.M. , Carvalho Beatriz
Published: July 2021

Background

Post-colonoscopy colorectal cancers (PCCRCs) pose a challenge in clinical practice. PCCRCs occur due to a combination of procedural and biological causes. Specific features of lesions may contribute for this. In a nested case-control study, we compared clinical and molecular features of PCCRCs and detected CRCs (DCRCs).

Methods

PCCRCs were defined according to the WEO 2018 classification, as cancers occurring after a complete index colonoscopy, which excluded CRC. CRCs in patients without colonoscopy or with colonoscopy >10 years before were defined as DCRCs. Whole genome chromosomal copy number changes and mutation status of genes commonly affected in CRC (including APC, KRAS, BRAF, FBXW7, PIK3CA, NRAS, SMAD4 and TP53) were examined by low-coverage WGS and targeted sequencing, respectively. MSI and CIMP status were also determined.

Results

In total, 122 PCCRCs and 98 DCRCs with high quality DNA were examined. PCCRCs were more often located proximally in the colon (p<0.001), non-polypoid appearing (p=0.004), early stage (p=0.009), and poorly differentiated (p=0.006). PCCRCs showed similar patterns of DNA copy number changes typical of CRC, although significantly less 18q loss (FDR <0.2), compared to DCRCs. No significant differences in mutations were detected between PCCRCs and DCRCs. PCCRCs were more commonly CIMP-high (p=0.014) and MSI (p=0.029). After correction for tumour location, the only molecular difference between PCCRCs and DCRCs that remained significant was less frequent loss of 18q chromosome in PCCRCs (p=0.005).

Conclusion

Although PCCRCs show molecular characteristics that are common to the canonical CIN, MSI and hypermethylation pathways, molecular features associated with the sessile serrated lesions (SSLs) and non-polypoid colorectal neoplasms (CRNs) are more commonly seen in PCCRCs than in DCRCs. This and the clinical features observed in PCCRCs support the hypothesis that sessile serrated lesions and non-polypoid CRNs are contributors to the development of these cancers. In order to further reduce the occurrence of PCCRCs, the focus should be directed at improving the detection, determination and endoscopic removal of these non-polypoid CRN and SSLs.

Clinical Trial Registration

NTR3093 in the Dutch trial register (www.trialregister.nl)
Dimeric IgA is a specific biomarker of recent SARS-CoV-2 infection
Authors: Drummer Heidi E , Van Huy , Klock Ethan , Zheng Shuning , Wei Zihui , Boo Irene , Center Rob J , Li Fan , Bhat Purnima , Ffrench Rosemary , Lau Jillian SY , McMahon James , Laeyendecker Oliver , Fernandez Reinaldo E. , Manabe Yukari C. , Klein Sabra L. , Quinn Thomas C. , Anderson David A.
Published: July 2021

Current tests for SARS-CoV-2 antibodies (IgG, IgM, IgA) cannot differentiate recent and past infections. We describe a point of care, lateral flow assay for SARS-CoV-2 dIgA based on the highly selective binding of dIgA to a chimeric form of secretory component (CSC), that distinguishes dIgA from monomeric IgA. Detection of specific dIgA uses a complex of biotinylated SARS-CoV-2 receptor binding domain and streptavidin-colloidal gold. SARS-CoV-2-specific dIgA was measured both in 112 cross-sectional samples and a longitudinal panel of 362 plasma samples from 45 patients with PCR-confirmed SARS-CoV-2 infection, and 193 discrete pre-COVID-19 or PCR-negative patient samples. The assay demonstrated 100% sensitivity from 11 days post-symptom onset, and a specificity of 98.2%. With an estimated half-life of 6.3 days, dIgA provides a unique biomarker for the detection of recent SARS-CoV-2 infections with potential to enhance diagnosis and management of COVID-19 at point-of-care.
Natural and after colon washing fecal samples: the two sides of the coin for investigating the human gut microbiome
Authors: Piancone Elisabetta , Fosso Bruno , De Robertis Mariangela , Notario Elisabetta , Oranger Annarita , Manzari Caterina , Marzano Marinella , Bruno Silvia , D’Erchia Anna Maria , Maio Dominga , Minelli Martina , Vergallo Ilaria , Minelli Mauro , Pesole Graziano
Published: July 2021

To date there are several studies focusing on the importance of gut microbiome for human health, however the selection of a universal sampling matrix representative of the microbial biodiversity associated to the gastrointestinal (GI) tract, still represents a challenge. Here we present a study in which, through a deep metabarcoding analysis of the 16S rRNA gene, we compared two sampling matrices, feces (F) and colonic lavage liquid (LL), in order to evaluate their accuracy to represent the complexity of the human gut microbiome. A training set of 37 volunteers was attained and paired F and LL samples were collected from each subject. A preliminary absolute quantification of total 16S rDNA, performed by droplet digital PCR (ddPCR), confirmed that sequencing and taxonomic analysis were performed on same total bacterial abundance obtained from the two sampling methods. The taxonomic analysis of paired samples revealed that, although specific taxa were predominantly or exclusively observed in LL samples, as well as other taxa were detectable only or were predominant in stool, the microbiomes of the paired samples F and LL in the same subject hold overlapping taxonomic composition. Moreover, LL samples revealed a higher biodiversity than stool at all taxonomic ranks, as demonstrated by the Shannon Index and the Inverse Simpson’s Index. We also found greater inter-individual variability than intra-individual variability in both sample matrices. Finally, functional differences were unveiled in the gut microbiome detected in the F and LL samples. A significant overrepresentation of 22 and 13 metabolic pathways, mainly occurring in Firmicutes and Proteobacteria, was observed in gut microbiota detected in feces and LL samples, respectively. This suggests that LL samples may allow for the detection of microbes adhering to the intestinal mucosal surface as members of the resident flora that are not easily detectable in stool, most likely representative of a diet-influenced transient microbiota. This first comparative study on feces and LL samples for the study of the human gut microbiome demonstrates that the use of both types of sample matrices may represent a possible choice to obtain a more complete view of the human gut microbiota in response to different biological and clinical questions.
B1-type cyclins control microtubule organization during cell division in Arabidopsis
Authors: Motta Mariana R. , Zhao Xin’Ai , Pastuglia Martine , Belcram Katia , Roodbarkelari Farshad , Komaki Maki , Harashima Hirofumi , Komaki Shinichiro , Bulankova Petra , Heese Maren , Riha Karel , Bouchez David , Schnittger Arp
Published: July 2021

Flowering plants contain a large number of cyclin families, each containing multiple members, most of which have not been characterized to date. Here, we analyzed the role of the B1 subclass of mitotic cyclins in cell cycle control during Arabidopsis development. While we reveal CYCB1;5 to be a pseudogene, the remaining four members were found to be expressed in dividing cells. Mutant analyses showed a complex pattern of overlapping, development-specific requirements of B1-type cyclins with CYCB1;2 playing a central role. The double mutant cycb1;1 cycb1;2 is severely compromised in growth, yet viable beyond the seedling stage, hence representing a unique opportunity to study the function of B1-type cyclin activity at the organismic level. Immunolocalization of microtubules in cycb1;1 cycb1;2 and treating mutants with the microtubule drug oryzalin revealed a key role of B1-type cyclins in orchestrating mitotic microtubule networks. Subsequently, we identified the GAMMA-TUBULIN COMPLEX PROTEIN 3-INTERACING PROTEIN 1 (GIP1/MOZART) as an in vitro substrate of B1-type cyclin complexes and further genetic analyses support an important role in the regulation of GIP1 by CYCB1s.
Conversion of cancer-associated fibroblasts from pro- to antitumor improves the sensitivity of pancreatic cancer to chemotherapeutics
Authors: Iida Tadashi , Mizutani Yasuyuki , Esaki Nobutoshi , Ponik Suzanne M. , Burkel Brian M , Weng Liang , Kuwata Keiko , Masamune Atsushi , Ishihara Seiichiro , Haga Hisashi , Kataoka Kunio , Mii Shinji , Shiraki Yukihiro , Ishikawa Takuya , Ohno Eizaburo , Kawashima Hiroki , Hirooka Yoshiki , Fujishiro Mitsuhiro , Takahashi Masahide , Enomoto Atsushi
Published: July 2021

Previous therapeutic attempts to deplete cancer-associated fibroblasts (CAFs) or inhibit their proliferation in pancreatic ductal adenocarcinoma (PDAC) were not successful in mice or patients. Thus, CAFs may be tumor suppressive or heterogeneous, with distinct cancer-restraining and -promoting CAFs (rCAFs and pCAFs, respectively). Here, we show that induced expression of the glycosylphosphatidylinositol-anchored protein Meflin, a rCAF-specific marker, in CAFs by genetic and pharmacological approaches improved the chemosensitivity of mouse PDAC. A chemical library screen identified Am80, a synthetic, non-natural retinoid, as a reagent that effectively induced Meflin expression in CAFs. Am80 administration improved the sensitivity of PDAC to chemotherapeutics, accompanied by increases in tumor vessel area and intratumoral drug delivery. Mechanistically, Meflin was involved in the suppression of tissue stiffening by interacting with lysyl oxidase to inhibit its collagen crosslinking activity. These data suggested that modulation of CAF heterogeneity may represent a strategy for PDAC treatment.
Time-dependent toxicity of tire particles on soil nematodes
Authors: Kim Shin Woong , Leifheit Eva F. , Maaß Stefanie , Rillig Matthias C.
Published: July 2021

Tire-wear particles (TWPs) are being released into the environment by wearing down during car driving, and are considered an important microplastic pollution source. The chemical additive leaching from these polymer-based materials and its potential effects are likely temporally dynamic, since larger amounts of potentially toxic compounds can gradually increase with contact time of plastic particles with surrounding media. In the present study, we conducted soil toxicity tests using the soil nematode Caenorhabditis elegans with different soil pre-incubation (30 and 75 days) and exposure (short-term exposure, 2 days; lifetime exposure, 10 days) times. Soil pre-incubation increased toxicity of TWPs, and the effective concentrations after the pre-incubation were much lower than environmentally relevant concentrations. The lifetime of C. elegans was reduced faster in the TWP treatment groups, and the effective concentration for lifetime exposure tests were 100- to 1,000-fold lower than those of short-term exposure tests. Water-extractable metal concentrations (Cr, Cu, Ni, Pb, and Zn) in the TWP-soils showed no correlation with nominal TWP concentrations or pre-incubation times, and the incorporated metals in the TWPs may be not the main reason of toxicity in this study. Our results show that toxic effects of TWPs can be time-dependent, both in terms of the microplastic particles themselves and their interactions in the soil matrix, but also because of susceptibility of target organisms depending on developmental stage. It is vital that future work consider these aspects, since otherwise effects of microplastics and TWPs could be underestimated.

Graphical Abstract
Interacting effects of cold snaps, rain, and agriculture on the fledging success of a declining aerial insectivore
Authors: Garrett Daniel R. , Pelletier Fanie , Garant Dany , Bélisle Marc
Published: July 2021

Climate change predicts the increased frequency, duration, and intensity of inclement weather periods, such as unseasonably low temperatures (i.e., cold snaps) and prolonged precipitation. Many migratory species have advanced the phenology of important life history stages, and as a result will likely be exposed to these periods of inclement spring weather more often, thus risking reduced fitness and population growth. For declining avian species, including aerial insectivores, anthropogenic landscape changes such as agricultural intensification are another driver of population declines. These landscape changes may affect the foraging ability of food provisioning parents, and reduce the survival of nestlings exposed to inclement weather, through for example pesticide exposure impairing thermoregulation and punctual anorexia. Breeding in agro-intensive landscapes may thus exacerbate the negative effects of inclement weather under climate change. We observed that a significant reduction in the availability of insect prey occurred when daily maximum temperatures fell below 18.3°C, and thereby defined any day where the maximum temperature fell below this value as a day witnessing a cold snap. We then combined daily information on the occurrence of cold snaps and measures of precipitation to assess their impact on the fledging success of Tree Swallows (Tachycineta bicolor) occupying a nest box system placed across a gradient of agricultural intensification. Estimated fledging success of this declining aerial insectivore was 36.2% lower for broods experiencing four cold snap days during the 12 days post hatching period versus broods experiencing none, and this relationship was worsened when facing more precipitation. We further found that the overall negative effects of a brood experiencing periods of inclement weather was exacerbated in more agro-intensive landscapes. Our results indicate that two of the primary hypothesized drivers of many avian population declines may interact to further increase the rate of declines in certain landscape contexts.
Inbreeding and learning affect fitness and colonization of new host plants, a behavioral innovation in the spider miteTetranychus urticae
Authors: Nieberding Caroline M. , Kaisin Aubin , Visser Bertanne
Published: July 2021

Habitat fragmentation increases the isolation of natural populations resulting in reduced genetic variability and increased species extinction risk. Behavioral innovation through learning, i.e., the expression of a new learned behavior in a novel context, can help animals colonize new suitable and increasingly fragmented habitats. It has remained unclear, however, how reduced genetic variability affects learning for colonizing more or less suitable habitats. Here, we show that inbreeding in a subsocial invertebrate, the spider miteTetranychus urticae, reduces novel host plant colonization and reproductive fitness. When provided with the possibility to learn from previous experience with a host plant species, outbred mites showed aversive learning ability, but inbred mites did not adapt their behavior. We further found a putative general cost of learning in both inbred and outbred mites. Our results reveal that inbreeding affects the learning component of behavioral innovation for host plant colonization.
Protracted speciation under the state-dependent speciation and extinction approach
Authors: Hua Xia , Herdha Tyara , Burden Conrad
Published: July 2021

How long does speciation take? What are the speciation processes that generated a species group? The answers to these important questions in evolutionary biology lie in the genetic difference not only among species, but also among lineages within each species. With the advance of genome sequencing in non-model organisms and the statistical tools to improve accuracy in inferring evolutionary histories among recently diverged lineages, we now have the lineage-level trees to answer these questions. However, we do not yet have an analytical tool for inferring speciation processes from these trees. What is needed is a model of speciation processes that generates both the trees and species identities of extant lineages. The model should allow calculation of the probability that certain lineages belong to certain species and have an evolutionary history consistent with the tree. Here we propose such a model and test the model performance on both simulated data and real data. We show that maximum likelihood estimates of the model are highly accurate and give estimates from real data that generate patterns consistent with observations. We discuss how to extend the model to account for different rates and types of speciation processes across lineages in a species group. By linking evolutionary processes on lineage level to species level, the model provides a new phylogenetic approach to study not just when speciation happened, but how speciation happened.
Probing molecular specificity with deep sequencing and biophysically interpretable machine learning
Authors: Tomas Rube H. , Rastogi Chaitanya , Feng Siqian , Kribelbauer Judith F. , Li Allyson , Becerra Basheer , Melo Lucas A. N. , Do Bach Viet , Li Xiaoting , Adam Hammaad H. , Shah Neel H. , Mann Richard S. , Bussemaker Harmen J.
Published: July 2021

Quantifying sequence-specific protein-ligand interactions is critical for understanding and exploiting numerous cellular processes, including gene regulation and signal transduction. Next-generation sequencing (NGS) based assays are increasingly being used to profile these interactions with high-throughput. However, these assays do not provide the biophysical parameters that have long been used to uncover the quantitative rules underlying sequence recognition. We developed a highly flexible machine learning framework, called ProBound, to define sequence recognition in terms of biophysical parameters based on NGS data. ProBound quantifies transcription factor (TF) behavior with models that accurately predict binding affinity over a range exceeding that of previous resources, captures the impact of DNA modifications and conformational flexibility of multi-TF complexes, and infers specificity directly from in vivo data such as ChIP-seq without peak calling. When coupled with a new assay called Kd-seq, it determines the absolute affinity of protein-ligand interactions. It can also profile the kinetics of kinase-substrate interactions. By constructing a biophysically robust foundation for profiling sequence recognition, ProBound opens up new avenues for decoding biological networks and rationally engineering protein-ligand interactions.
Identification of transcription termination defects at DNA hypomethylated transcription termination sites in DNA methyltransferase 3a-deficient vertebrates
Authors: Shirai Masaki , Nara Takuya , Takahashi Haruko , Takayama Kazuya , Chen Yuan , Hirose Yudai , Fujii Masashi , Awazu Akinori , Shimoda Nobuyoshi , Kikuchi Yutaka
Published: July 2021

CpG methylation in genomic DNA is well known as a repressive epigenetic marker in eukaryotic transcription, and DNA methylation of the promoter regions is correlated with silencing of gene expression. In contrast to the promoter regions, the function of DNA methylation during transcription termination remains to be elucidated. A recent study has revealed that mouse DNA methyltransferase 3a (Dnmt3a) mainly functions inde novomethylation in the promoter and gene body regions (including transcription termination sites (TTSs)) during development. To investigate the relationship between DNA methylation overlapping the TTSs and transcription termination, we employed two strategies: informatic analysis using already deposited datasets ofDnmt3a-/-mouse cells and the zebrafish model system. Bioinformatic analysis using methylome and transcriptome data showed that hypomethylated differentially methylated regions overlapping the TTSs were associated with increased read counts and chimeric transcripts downstream of TTSs inDnmt3a-/-Agouti-related protein neurons, but not inDnmt3a-/-embryonic stem cells and mouse embryonic fibroblasts. We experimentally detected increased read-through and chimeric transcripts downstream of hypomethylated TTSs in zebrafish maternal-zygoticdnmt3aa-/-mutant. This study is the first to identify transcription termination defects in DNA hypomethylated TTSs inDnmt3a-/-vertebrates.