bluuebunny/crossref_metadata_2025 huggingface dataset:
Presepsin for pre-operative prediction of major adverse cardiovascular events in coronary heart disease patients undergoing noncardiac surgery
Authors: Handke Jessica , Scholz Anna S. , Dehne Sarah , Krisam Johannes , Gillmann Hans-Jörg , Janssen Henrike , Arens Christoph , Espeter Florian , Uhle Florian , Motsch Johann , Weigand Markus A. , Larmann Jan
Published: June 2020

BACKGROUND

Accurate pre-operative evaluation of cardiovascular risk is vital to identify patients at risk for major adverse cardiovascular and cerebrovascular events (MACCE) after noncardiac surgery. Elevated presepsin (sCD14-ST) is associated with peri-operative MACCE in coronary artery disease (CAD) patients after noncardiac surgery.

OBJECTIVES

Validating the prognostic utility of presepsin for MACCE after noncardiac surgery.

DESIGN

Prospective patient enrolment and blood sampling, followed by post hoc evaluation of pre-operative presepsin for prediction of MACCE.

SETTING

Single university centre.

PATIENTS

A total of 222 CAD patients undergoing elective, inpatient noncardiac surgery.

INTERVENTION

Pre-operative presepsin measurement.

MAIN OUTCOME MEASURES

MACCE (cardiovascular death, myocardial infarction, myocardial ischaemia and stroke) at 30 days postsurgery.

RESULTS

MACCE was diagnosed in 23 (10%) patients. MACCE patients presented with increased pre-operative presepsin (median [IQR]; 212 [163 to 358] vs. 156 [102 to 273] pgml−1, P = 0.023). Presepsin exceeding the previously derived threshold of 184 pg ml−1 was associated with increased 30-day MACCE rate. After adjustment for confounders, presepsin more than 184 pg ml−1 [OR = 2.8 (95% confidence interval 1.1 to 7.3), P = 0.03] remained an independent predictor of peri-operative MACCE. Predictive accuracy of presepsin was moderate [area under the curve (AUC) = 0.65 (0.54 to 0.75), P = 0.023]. While the basic risk model of revised cardiac risk index, high-sensitive cardiac troponin T and N-terminal fragment of pro-brain natriuretic peptide resulted in an AUC = 0.62 (0.48 to 0.75), P = 0.072, addition of presepsin to the model led to an AUC = 0.67 (0.56 to 0.78), P = 0.009 and (ΔAUC = 0.05, P = 0.438). Additive risk predictive value of presepsin was demonstrated by integrated discrimination improvement analysis (integrated discrimination improvement = 0.023, P = 0.022). Net reclassification improvement revealed that the additional strength of presepsin was attributed to the reclassification of no-MACCE patients into a lower risk group.

CONCLUSION

Increased pre-operative presepsin independently predicted 30-day MACCE in CAD patients undergoing major noncardiac surgery. Complementing cardiovascular risk prediction by inflammatory biomarkers, such as presepsin, offers potential to improve peri-operative care. However, as prediction accuracy of presepsin was only moderate, further validation studies are needed.

TRIAL REGISTRATION

Clinicaltrials.gov: NCT03105427.
Artificial intelligence and automation of systematic reviews in women's health
Authors: Amezcua-Prieto Carmen , Fernández-Luna Juan M. , Huete-Guadix Juan F. , Bueno-Cavanillas Aurora , Khan Khalid Saed
Published: June 2020

Purpose of review

Evidence-based women's healthcare is underpinned by systematic reviews and guidelines. Generating an evidence synthesis to support guidance for clinical practice is a time-consuming and labour-intensive activity that delays transfer of research into practice. Artificial intelligence has the potential to rapidly collate, combine, and update high-quality medical evidence with accuracy and precision, and without bias.

Recent findings

This article describes the main fields of artificial intelligence with examples of its application to systematic reviews. These include the capabilities of processing natural language texts, retrieving information, reasoning, and learning. The complementarity and interconnection of the various artificial intelligence techniques can be harnessed to solve difficult problems in automation of reviews. Computer science can advance evidence-based medicine through development, testing, and refinement of artificial intelligence tools to deploy automation, creating ‘living’ evidence syntheses.

Groundbreaking, high-quality, and impactful artificial intelligence will accelerate the transfer of individual research studies seamlessly into evidence syntheses for contemporaneously improving the quality of healthcare.
Ambulatory blood pressure variability and risk of cardiovascular events, all-cause mortality, and progression of kidney disease
Authors: Jhee Jong Hyun , Seo Jiwon , Lee Chan Joo , Park Jung Tak , Han Seung Hyeok , Kang Shin-Wook , Park Sungha , Yoo Tae-Hyun
Published: June 2020

Background:

Association between blood pressure (BP) variability and cardiovascular outcome remains unclear in patients with chronic kidney disease (CKD). We evaluated this association between ambulatory BP variability and cardiovascular events, mortality, and kidney disease progression in patients with CKD.

Methods:

From the Cardiovascular and Metabolic Disease Etiology Research Center-HIgh Risk study (2013–2018), a total of 470 patients with CKD were analyzed. Ambulatory BP variability was assessed using average real variability (ARV). Primary outcome was composite of nonfatal myocardial infarction, nonfatal stroke, and all-cause mortality. The secondary outcome was rapid kidney function decline [estimated glomerular filtration rate (eGFR), >3 ml/min per 1.73m2 per year].

Results:

During a median follow-up of 51.8 (40.5–56.2) months, the incidences of all-cause death and composite outcomes were higher in the high SBP-ARV group than in the low SBP-ARV group. The Kaplan–Meier analysis showed that a high SBP-ARV, but not a high DBP-ARV and heart rate-ARV, was associated with higher composite outcome risks. In multivariable Cox analysis, a high SBP-ARV correlated with increased composite outcome risks (hazard ratio, 4.53; 95% confidence interval, 1.41–14.58). When subgroup analysis was performed (low vs. high 24-h SBP), this association was only significant in the high 24-h SBP group. The risk stratification for composite outcomes by adding SBP-ARV into the basic model and 24-h SBP, improved by 1.3%. Furthermore, the mean eGFR decline rate was faster, and the rapid eGFR decline risk was 1.68-fold higher in the high SBP-ARV group.

Conclusion:

Greater ambulatory SBP variabilities were associated with increased risks for nonfatal cardiovascular diseases, all-cause mortality, and rapid kidney function decline in patients with CKD.
A Simple New Technique to Peel Epiretinal Membrane Without Removing Silicone Oil
Authors: Lo Kang-Jung , Lee Fenq-Lih , Lin Tai-Chi
Published: June 2020

Purpose:

To introduce a new surgical technique that can keep constant intraocular pressure of the eyeball during peeling epiretinal membrane under silicone oil status.

Methods:

A viscoelastic agent was injected into the air pump of the constellation system via the metal tip. This procedure offers a buffer zone to keep constant pressure within the eyeball without disturbing the surgical field by an air bubble.

Results:

Three cases were performed efficiently (15 ± 5 minutes) under this technique with improvement in anatomical feature and visual function after the surgery.

Conclusion:

Using this simple yet important technique can provide us the constant intraocular pressure without hypotony and avoid the traditional complicated procedures.
Polymorphism rs2762939 of CYP24A1 enzyme and coronary artery disease: angiographic results from a large prospective cohort of patients
Authors: Verdoia Monica , Ceccon Claudia , Nardin Matteo , Negro Federica , Marcolongo Marco , De Luca Giuseppe
Published: June 2020

Recent attention has been focused on the regulation of vitamin D metabolism as modulating the cardiovascular benefits of vitamin D. The aim of the current study was to evaluate the functional impact of the genetic polymorphism rs2762939 of CYP24A1, the hydroxylase-enzyme modulating the inactivation of vitamin D, on the prevalence and extent of coronary artery disease (CAD).A consecutive cohort of patients undergoing coronary angiography in a single centre was included. Significant CAD was defined as at least one stenosis more than 50%, severe CAD as left main and/or three-vessel disease. Among 1204 patients, 673 (55.8%) carried the C allele. Baseline features showed a lower use of beta-blockers among the C-carriers (P = 0.01) and higher levels of C-reactive protein (P = 0.05). The prevalence of CAD and severe CAD was not conditioned by CYP24A1 genetic status [78.7%-GG vs. 81.2%-C-carriers; P = 0.31; adjusted odds ratio (95% confidence interval ) = 0.71(0.20–2.56), P = 0.60 and 29.1%-GG vs. 29.5%-C carriers P = 0.95; adjusted odds ratio (95% confidence interval) = 0.87 (0.73–1.04), P = 0.13, respectively]. Coronary calcifications were significantly higher among GG homozygotes (P = 0.005). This study showed that the polymorphisms rs2762939 of CYP24A1 is not associated with the prevalence and extent of CAD. However, the C-allele carriage significantly lowers the rate of coronary calcifications.
The interplay between gastrointestinal and cardiovascular diseases: a narrative review focusing on the clinical perspective
Authors: Sbeit Wisam , Kadah Anas , Mahamid Mahmud , Mari Amir , Khoury Tawfik
Published: June 2020

Both cardiovascular and gastrointestinal disorders represent considerable health burden on community clinics and hospitals with overwhelming economic cost. An overlap in the occurrence of these disorders is encountered in daily practice. Both affect each other in bidirectional manner through several mechanisms including altered hemodynamics, systemic inflammation, bacterial overgrowth and interactions and adverse effects of medications. In addition, to the known overlap in the symptoms occurrence of upper gastrointestinal tract diseases and cardiovascular diseases (CVDs). Awareness of this interplay and its clinical manifestations optimizes patient management, and could prevent catastrophic consequences and even save lives. In this review, we highlighted the clinical aspects of this bidirectional association between gastrointestinal and CVDs aiming to shed light on this topic and improve patients’ care.
Long-term effect of hyperoxemia during chronic obstructive pulmonary disease exacerbation managed by emergency medical service and emergency department: a prospective, exploratory study
Authors: Lim Beng Leong , Cheah Si Oon , Goh Hsin Kai , Lee Francis Chun Yue , Ng Yih Ying , Asinas-Tan Marxengel , Ong Marcus Eng Hock
Published: June 2020

Objective

Long-term effects of hyperoxemia during acute exacerbation of chronic obstructive pulmonary disease (AECOPD) remained unknown. We aimed to explore these effects of hyperoxemia during AECOPD.

Methods

This was an exploratory follow-up study of a cohort with AECOPD managed by Emergency Medical Service and two emergency departments (EDs). Patients were classified as hyperoxemic (PaO2 > 65 mmHg) or nonhyperoxemic (PaO2 ≤ 65 mmHg). Patients discharged from ED/inpatient care were followed up prospectively for 1 year. The primary outcome was 1-year all-cause mortality in hyperoxemic vs. nonhyperoxemic groups. Secondary outcomes were 3-month all-cause mortality and median number of repeat AECOPD hospitalizations within 1 year. We generated Kaplan–Meier curves and compared them using log-rank test. The primary outcome was also analyzed using Cox proportional-hazards model. We reported crude and adjusted hazard ratios, their 95% confidence intervals (CIs) and P values. We adjusted for two a priori predictors of delayed mortality; age ≥ 70 years and repeat AECOPD hospitalizations.

Results

A total of 231 patients were analyzed. One-year mortality rates in hyperoxemic vs. nonhyperoxemic groups were 26/137 (19.0%) and 12/94 (12.8%), respectively (P = 0.693). Although Kaplan–Meier curves showed divergent courses favoring nonhyperoxemic group, log-rank test was not statistically significant (P = 0.203). The crude and adjusted hazard ratios (reference: nonhyperoxemic group) were 1.55 (95% CIs, 0.78–3.08; P = 0.207) and 1.57 (95% CIs, 0.79–3.13; P = 0.196), respectively. Secondary outcomes did not differ.

Conclusions

Our study reported no effect on 1-year all-cause mortality associated with hyperoxemia during AECOPD. Further studies are needed to prove/disprove our findings.
Comparison of modified Response Evaluation Criteria in Solid Tumors, European Organization for Research and Treatment of Cancer criteria, and PET Response Criteria in Solid Tumors for evaluation of tumor response to chemotherapy and prognosis prediction in patients with unresectable malignant pleural mesothelioma
Authors: Kitajima Kazuhiro , Maruyama Mitsunari , Minami Toshiyuki , Yokoi Takashi , Kuribayashi Kozo , Kijima Takashi , Hashimoto Masaki , Hasegawa Seiki , Yamakado Koichiro
Published: June 2020

Objective

To compare modified RECIST (mRECIST), EORTC criteria, and PERCIST for response evaluation and prognosis prediction in advanced malignant pleural mesothelioma (MPM) patients treated with chemotherapy.

Methods

Patients with MPM and not curative surgery candidates (n = 75) underwent standard chemotherapy with cisplatin and pemetrexed. CT and [18F]fluorodeoxyglucose PET/CT scans were performed at baseline and after three chemotherapy cycles. Chemotherapeutic response was evaluated according to mRECIST, EORTC, and PERCIST, then concordance among those was assessed using Cohen’s κ coefficient. PFS and OS were examined using log-rank and Cox methods.

Results

With EORTC, 27 patients had PMD, 23 SMD, 17 PMR, and eight CMR, while with PERCIST those were 28, 22, 11, and 14, respectively. Using mRECIST, 28 had PD, 29 SD, 18 PR, and 0 CR. Although there was high concordance between EORTC and PERCIST (82.7% of patients; κ = 0.83), that between mRECIST and EORTC (38.7%; κ = 0.27) and mRECIST and PERCIST (36.0%; κ = 0.26) was low. According to both EORTC and PERCIST, patients with no progression (CMR/PMR/SMD) showed significantly longer PFS and OS than PMD patients (EORTC: P = 0.0024 and P = 0.039, respectively, PERCIST: P = 0.0012 and P = 0.024, respectively), while according to mRECIST, those who achieved no progression (PR/SD) showed significantly longer PFS than PD patients (P = 0.011), but not significantly longer OS (P = 0.11).

Conclusion

EORTC and PERCIST are more accurate than mRECIST for evaluation of tumor response to chemotherapy and predicting prognosis in unresectable MPM patients.
Factor VII Deficiency in Patients Receiving Chronic Packed Cell Transfusions
Authors: Abu-Quider Abed , Asleh Mahdi , Fruchtman Yariv , Ben-Harosh Miriam , Beck Guy , Abuhasira Ran , Kapelushnik Joseph
Published: June 2020

Acquired factor VII deficiency is a rare coagulopathy that has not been reported in transfusion-dependent patients so far. In this study, we reviewed files of 26 transfusion-dependent patients for coagulation profiles, factor V levels, factor VII levels, possible environmental factors influencing factor VII levels, and bleeding history. In 26 of 29 patients (89.6%), we found mild factor VII deficiency (<60%) with levels ranging between 35% and 56%. Bleeding history was unremarkable. We concluded that transfusion-dependent patients may have mild factor VII deficiency with no bleeding tendency under physiologic conditions.
Primary Paraspinal and Spinal Epidural Non-Hodgkin Lymphoma in Childhood
Authors: Kurucu Nilgün , Akyüz Canan , Varan Ali , Akçören Zuhal , Aydin Burça , Yalçin Bilgehan , Kutluk Tezer
Published: June 2020

Primary paraspinal/spinal epidural lymphoma (PPSEL) is rare in childhood. Here, we retrospectively evaluated patients with PPSEL treated in our department. We also reviewed the cases reported in the literature. Fifteen of 1354 non-Hodgkin lymphoma cases diagnosed over a 38-year period were PPSEPL. There were 11 male individuals and 4 female individuals with a median age of 13 years. Most common symptoms were pain and limb weakness. Physical examination revealed spinal cord compression in 80% of patients. The most common tumor location was the lumbar region. Histopathologic subtypes were lymphoblastic lymphoma in 6 and Burkitt lymphom in 5 patients. Subtotal or near-total excision of the tumor with laminectomy was performed in 6 patients. Thirteen and 9 patients received chemotherapy and radiotherapy, respectively. Neurologic recovery was observed in 70% of patients. Seven patients were alive without disease at a median of 88 months. Overall and event-free survival rates were 61.7% and 50.1%, respectively. We reviewed clinical features, treatment, and outcome of 69 PPSEL cases reported in the literature. Neurologic recovery and long-term survival was achieved in 66.7% of them. Heterogeneity in diagnostic methods and treatment have made it difficult to establish the prognostic indicators for neurologic outcome and survival. Multicenter prospective studies with more cases are necessary to determine the prognostic factors.
Trametinib-associated Hyponatremia in a Child With Low-grade Glioma is Not Seen Following Treatment With Alternative MEK Inhibitor
Authors: Lazow Margot A. , Lawson Sarah A. , Salloum Ralph , Hummel Trent R. , Pillay Smiley Natasha , DeWire-Schottmiller Mariko D. , Fouladi Maryam , de Blank Peter
Published: June 2020

Molecularly targeted therapy with MEK inhibitors has been increasingly incorporated into the treatment of pediatric low-grade gliomas, but this promising therapy is associated with distinctive and specific toxicities. Understanding life-threatening MEK inhibitor toxicities and their management is critical to MEK inhibitor safety, especially among young children. This report describes severe hyponatremia associated with trametinib in an infant with progressive low-grade glioma without underlying endocrine dysfunction, which recurred despite significant dose reduction. Therapy with an alternative MEK inhibitor, binimetinib, provided excellent tumor response without hyponatremia, suggesting that some toxicities may be avoided by changing MEK inhibitor agents within the same class.
Building and Sustaining Optimized Diagnostic Networks to Scale-up HIV Viral Load and Early Infant Diagnosis
Authors: Alemnji George , Peter Trevor , Vojnov Lara , Alexander Heather , Zeh Clement , Cohn Jennifer , Watts Diane Heather , de Lussigny Smiljka
Published: June 2020

Background:

Progress toward meeting the UNAIDS 2014 HIV treatment (90-90-90) targets has been slow in some countries because of gaps in access to HIV diagnostic tests. Emerging point-of-care (POC) molecular diagnostic technologies for HIV viral load (VL) and early infant diagnosis (EID) may help reduce diagnostic gaps. However, these technologies need to be implemented in a complementary and strategic manner with laboratory-based instruments to ensure optimization.

Method:

Between May 2019 and February 2020, a systemic literature search was conducted in PubMed, the Cochrane Library, MEDLINE, conference abstracts, and other sources such as Unitaid, UNAIDS, WHO, and UNICEF websites to determine factors that would affect VL and EID scale-up. Data relevant to the search themes were reviewed for accuracy and were included.

Results:

Collaborations among countries, implementing partners, and donors have identified a set of framework for the effective use of both POC-based and laboratory-based technologies in large-scale VL and EID testing programs. These frameworks include (1) updated testing policies on the operational utility of POC and laboratory-based technologies, (2) expanded integrated testing using multidisease diagnostic platforms, (3) laboratory network mapping, (4) use of more efficient procurement and supply chain approaches such as all-inclusive pricing and reagent rental, and (5) addressing systemic issues such as test turnaround time, sample referral, data management, and quality systems.

Conclusions:

Achieving and sustaining optimal VL and EID scale-up within tiered diagnostic networks would require better coordination among the ministries of health of countries, donors, implementing partners, diagnostic manufacturers, and strong national laboratory and clinical technical working groups.
Acceptability of Routine Point-of-Care Early Infant Diagnosis in Eight African Countries: Findings From a Qualitative Assessment of Clinical and Laboratory Personnel
Authors: Bianchi Flavia , Clemens Sara , Arif Zainab , Sacks Emma , Cohn Jennifer ,   on behalf of the EGPAF POC EID Study Team
Published: June 2020

Background:

The Elizabeth Glaser Pediatric AIDS Foundation introduced point-of-care (POC) testing for early infant diagnosis (EID) of HIV in 8 African countries. Understanding experiences and opinions of users can help facilitate introduction and sustainability.

Setting:

Cameroon, Côte d'Ivoire, Eswatini, Kenya, Lesotho, Mozambique, Rwanda, and Zimbabwe.

Methods:

Structured interviews with health care workers (HCWs) providing EID services and semistructured interviews with national and regional laboratory managers or EID program managers were conducted before and after the implementation of POC EID. Survey responses were analyzed and compared; open-ended responses were analyzed by theme.

Results:

In total, 234 and 175 interviews with HCWs and 28 and 14 interviews with laboratory or program managers were conducted before and after the introduction of POC EID, respectively. In preintervention interviews, challenges identified with laboratory-based EID testing included distance from patients' residence to the health facility, time-consuming sample transportation to central laboratories, stockout of testing kits, and long wait times for results. Postintervention data revealed that HCWs found POC EID easy to use and were very satisfied with the fast turnaround time and ability to initiate treatment for HIV-infected infants sooner. Laboratory managers were also supportive of scaling-up POC testing although cautious of the need for reliable infrastructure to operate platforms. The recommendation was that POC EID be integrated within the national diagnostic testing network.

Conclusions:

Support for POC EID from key stakeholders is essential for sustainability. Overall, participants supported the rollout of POC testing for EID, noting challenges and opportunities for scaling-up POC EID and recommending integration into the overall EID system.
Impact of Routine Point-of-Care Versus Laboratory Testing for Early Infant Diagnosis of HIV: Results From a Multicountry Stepped-Wedge Cluster-Randomized Controlled Trial
Authors: Sacks Emma , Cohn Jennifer , Ochuka Bernard , Mafaune Haurovi , Chadambuka Addmore , Odhiambo Collins , Masaba Rose , Githuka George , Mahomva Agnes , Mushavi Angela , Lemaire Jean-Francois , Bianchi Flavia , Machekano Rhoderick
Published: June 2020

Background:

Although the World Health Organization recommends HIV-exposed infants receive a 6-week diagnostic test, few receive results by 12 weeks. Point-of-care (POC) early infant diagnosis (EID) may improve timely diagnosis and treatment. This study assesses the impact of routine POC versus laboratory-based EID on return of results by 12 weeks of age.

Methods:

This was a cluster-randomized stepped-wedge trial in Kenya and Zimbabwe. In each country, 18 health facilities were randomly selected for inclusion and randomized to timing of POC implementation.

Findings:

Nine thousand five hundred thirty-nine infants received tests: 5115 laboratory-based and 4424 POC. In Kenya and Zimbabwe, respectively, caregivers were 1.29 times [95% confidence interval (CI): 1.27 to 1.30, P < 0.001] and 4.56 times (95% CI: 4.50 to 4.60, P < 0.001) more likely to receive EID results by 12 weeks of age with POC versus laboratory-based EID. POC significantly reduced the time between sample collection and return of results to caregiver by an average of 23.03 days (95% CI: 4.85 to 21.21, P < 0.001) in Kenya and 62.37 days (95% CI: 58.94 to 65.80, P < 0.001) in Zimbabwe. For HIV-infected infants, POC significantly increased the percentage initiated on treatment, from 43.2% to 79.6% in Zimbabwe, and resulted in a nonsignificant increase in Kenya from 91.7% to 100%. The introduction of POC EID also significantly reduced the time to antiretroviral therapy initiation by an average of 17.01 days (95% CI: 9.38 to 24.64, P < 0.001) in Kenya and 56.00 days (95% CI: 25.13 to 153.76, P < 0.001) in Zimbabwe.

Conclusions:

POC confers significant advantage on the proportion of caregivers receiving timely EID results, and improves time to results receipt and treatment initiation for infected infants. Where laboratory-based EID systems are unable to deliver results to caregivers rapidly, POC should be implemented as part of an integrated testing system.
Brief Report: HIV Incidence Among Older Adults in a Rural South African Setting: 2010–2015
Authors: Gómez-Olivé F. Xavier , Houle Brian , Rosenberg Molly , Kabudula Chodziwadziwa , Mojola Sanyu , Rohr Julia K. , Clark Samuel , Angotti Nicole , Schatz Enid , Kahn Kathleen , Bärnighausen Till , Menken Jane
Published: June 2020

Introduction:

In South Africa, evidence shows high HIV prevalence in older populations, with sexual behavior consistent with high HIV acquisition and transmission risk. However, there is a dearth of evidence on older people's HIV incidence.

Methods:

We used a 2010–2011 cohort of HIV-negative adults in rural South Africa who were 40 years or older at retest in 2015–2016 to estimate HIV incidence over a 5-year period. We used Poisson regression to measure the association of HIV seroconversion with demographic and behavioral covariates. We used inverse probability sampling weights to adjust for nonresponse in 2015, based on a logistic regression with predictors of sex and age group at August 2010.

Results:

HIV prevalence increased from 21% at baseline to 23% in the follow-up survey. From a cohort of 1360 individuals, 33 seroconverted from HIV negative at baseline, giving an overall HIV incidence rate of 0.39 per 100 person-years [95% confidence interval (CI): 0.28 to 0.57]. The rate for women was 0.44 (95% CI: 0.30 to 0.67), double than that for men, 0.21 (95% CI: 0.10 to 0.51). Incidence rate ratios (IRRs) again show women's risk of seroconverting double than that of men (IRR = 2.04, P value = 0.098). In past age 60, the IRR of seroconversion was significantly lower than that for those in their 40s (60–69, IRR = 0.09, P value = 0.002; 70–79, IRR = 0.14, P value = 0.010).

Conclusions:

The risk of acquiring HIV is not zero for people older than 50 years, especially women. Our findings highlight the importance of acknowledging that older people are at high risk of HIV infection and that HIV prevention and treatment campaigns must take them into consideration.
Phagocytosis–Inflammation Crosstalk in Sepsis: New Avenues for Therapeutic Intervention
Authors: Hortová-Kohoutková Marcela , Tidu Federico , De Zuani Marco , Šrámek Vladimír , Helán Martin , Frič Jan
Published: June 2020

Phagocytosis is a complex process by which cells within most organ systems remove pathogens and cell debris. Phagocytosis is usually followed by inflammatory pathway activation, which promotes pathogen elimination and inhibits pathogen growth. Delayed pathogen elimination is the first step in sepsis development and a key factor in sepsis resolution. Phagocytosis thus has an important role during sepsis and likely contributes to all of its clinical stages. However, only a few studies have specifically explored and characterized phagocytic activity during sepsis. Here, we describe the phagocytic processes that occur as part of the immune response preceding sepsis onset and identify the elements of phagocytosis that might constitute a predictive marker of sepsis outcomes. First, we detail the key features of phagocytosis, including the main receptors and signaling hallmarks associated with different phagocytic processes. We then discuss how the initial events of phagosome formation and cytoskeletal remodeling might be associated with known sepsis features, such as a cytokine-driven hyperinflammatory response and immunosuppression. Finally, we highlight the unresolved mechanisms of sepsis development and progression and the need for cross-disciplinary approaches to link the clinical complexity of the disease with basic cellular and molecular mechanisms.
The endangered Spitsbergen bowhead whales' secrets revealed after hundreds of years in hiding
Authors: Kovacs Kit M. , Lydersen Christian , Vacquiè-Garcia Jade , Shpak Olga , Glazov Dmitry , Heide-Jørgensen Mads Peter
Published: June 2020

Spitsbergen's bowhead whales (
Balaena mysticetus
) were hunted to near extinction in the world's first commercial whaling enterprise; this population clearly remains threatened, but nothing is known about its distribution, making assessment unfeasible. In this study, we document range, movement patterns and habitat preferences of this population, based on tagging done from an icebreaker-based helicopter. Despite their reduced abundance, Spitsbergen's bowhead whales occupy much of their historical range, stretching across the northern Barents Region from East Greenland eastward to Franz Josef Land. Unlike larger bowhead populations to the west, they do not migrate in a classical sense, but rather disperse from wintering grounds in the northernmost parts of their range during spring, returning northward again in autumn, a pattern opposite in terms of directionality compared to other Arctic bowhead whale populations. The extreme affiliation of this population with cold, ice-filled waters is a concern given ongoing climate warming and concomitant rapid sea ice habitat loss.
The unexpected narrowness of eccentric debris rings: a sign of eccentricity during the protoplanetary disc phase
Authors: Kennedy Grant M.
Published: June 2020

This paper shows that the eccentric debris rings seen around the stars Fomalhaut and HD 202628 are narrower than expected in the standard eccentric planet perturbation scenario (sometimes referred to as ‘pericentre glow’). The standard scenario posits an initially circular and narrow belt of planetesimals at semi-major axis
a
, whose eccentricity is increased to
e

f

after the gas disc has dispersed by secular perturbations from an eccentric planet, resulting in a belt of width 2
ae

f

. In a minor modification of this scenario, narrower belts can arise if the planetesimals are initially eccentric, which could result from earlier planet perturbations during the gas-rich protoplanetary disc phase. However, a primordial eccentricity could alternatively be caused by instabilities that increase the disc eccentricity, without the need for any planets. Whether these scenarios produce detectable eccentric rings within protoplanetary discs is unclear, but they nevertheless predict that narrow eccentric planetesimal rings should exist before the gas in protoplanetary discs is dispersed. PDS 70 is noted as a system hosting an asymmetric protoplanetary disc that may be a progenitor of eccentric debris ring systems.
Shallow neural networks for fluid flow reconstruction with limited sensors
Authors: Erichson N. Benjamin , Mathelin Lionel , Yao Zhewei , Brunton Steven L. , Mahoney Michael W. , Kutz J. Nathan
Published: June 2020

In many applications, it is important to reconstruct a fluid flow field, or some other high-dimensional state, from limited measurements and limited data. In this work, we propose a shallow neural network-based learning methodology for such fluid flow reconstruction. Our approach learns an end-to-end mapping between the sensor measurements and the high-dimensional fluid flow field, without any heavy preprocessing on the raw data. No prior knowledge is assumed to be available, and the estimation method is purely data-driven. We demonstrate the performance on three examples in fluid mechanics and oceanography, showing that this modern data-driven approach outperforms traditional modal approximation techniques which are commonly used for flow reconstruction. Not only does the proposed method show superior performance characteristics, it can also produce a comparable level of performance to traditional methods in the area, using significantly fewer sensors. Thus, the mathematical architecture is ideal for emerging global monitoring technologies where measurement data are often limited.
DECONbench: a benchmarking platform dedicated to deconvolution methods for tumor heterogeneity quantification
Authors: Decamps Clémentine , Arnaud Alexis , Petitprez Florent , Ayadi Mira , Baurès Aurélia , Armenoult Lucile ,   HADACA consortium, Nicolle Rémy , Tomasini Richard , de Reyniès Aurélien , Cros Jérôme , Blum Yuna , Richard Magali
Published: June 2020

Motivation

Quantification of tumor heterogeneity is essential to better understand cancer progressionand to adapt therapeutic treatments to patient specificities.

Results

We present DECONbench, a web-based application to benchmark computational methods dedicated to quantify of cell-type heterogeneity in cancer. DECONbench includes benchmark datasets, computational methods and performance evaluation. It allows submission of new methods.

Availability and implementation

DECONbench is hosted on the open source codalab competition platform. It is freely available at:https://competitions.codalab.org/competitions/23660.

Supplementary information

Additional information is available online and on our website:https://cancer-heterogeneity.github.io/deconbench.html.
A molecular phylogeny of forktail damselflies (genusIschnura) reveals a dynamic macroevolutionary history of female colour polymorphisms
Authors: Blow Rachel , Willink Beatriz , Svensson Erik I.
Published: June 2020

Colour polymorphisms are popular study systems among biologists interested in evolutionary dynamics, genomics, sexual selection and sexual conflict. In many damselfly groups, such as in the globally distributed genusIschnura(forktails), sex-limited female colour polymorphisms occur in multiple species. Female-polymorphic species contain two or three female morphs, one of which phenotypically matches the male (androchrome or male mimic) and the other(s) which are phenotypically distinct from the male (heterochrome). These female colour polymorphisms are thought to be maintained by frequency-dependent sexual conflict, but their macroevolutionary histories are unknown, due to the lack of a robust molecular phylogeny. Here, we present the first time-calibrated phylogeny ofIschnura, using a multispecies coalescent approach (StarBEAST2) and incorporating both molecular and fossil data for 41 extant species (55% of the genus). We estimate the age ofIschnurato be between 13.8 and 23.4 millions of years, i.e. Miocene. We infer the ancestral state of this genus as female monomorphism with heterochrome females, with multiple gains and losses of female polymorphisms, evidence of trans-species female polymorphisms and a significant positive relationship between female polymorphism incidence and current geographic range size. Our study provides a robust phylogenetic framework for future research on the dynamic macroevolutionary history of this clade with its extraordinary diversity of sex-limited female polymorphisms.
Striatal dopamine synthesis capacity reflects smartphone social activity
Authors: Westbrook Andrew , Ghosh Arko , van den Bosch Ruben , Cools Roshan
Published: June 2020

Striatal dopamine has been implicated in social behavior across humans, rodents, and non-human primates in artificial laboratory settings with highly-practiced tasks and fixed reward contingencies. Whether striatal dopamine drives naturalistic, spontaneous social behavior remains unclear. Here, we leverage day-to-day logs of unconstrained smartphone behavior and establish a novel link between smartphone social activity and individual differences in striatal dopamine synthesis capacity using [18F]-DOPA PET in (N=22) healthy adult humans. We find a strong relationship such that a higher proportion of social app interactions correlates with lower dopamine synthesis capacity in the bi-lateral putamen. Permutation tests and penalized regressions provide evidence that this link between dopamine synthesis capacity and social versus non-social smartphone taps is specific. These observations provide a key empirical grounding for current speculations about dopamine’s role in digital social behavior.
Syntax-sensitive regions of Broca’s area and the posterior temporal lobe are differentially recruited by production and perception
Authors: Matchin William , Wood Emily
Published: June 2020

Neuroimaging studies of syntactic processing typically result in similar activation profiles in Broca’s area and the posterior temporal lobe (PTL). However, substantial functional dissociations between these regions have been demonstrated with respect to lesion-symptom mapping in aphasia. To account for this, Matchin & Hickok (2020) proposed that both regions play a role in syntactic processing, broadly construed, but attribute distinct functions to these regions with respect to production and comprehension. Here we report an fMRI study designed to test this hypothesis by contrasting the subvocal articulation and comprehension of structured jabberwocky phrases (syntactic), sequences of real words (lexical), and sequences of pseudowords (phonological). We defined two sets of language-selective regions of interest (ROIs) in individual subjects for Broca’s area and the PTL using the contrasts [syntactic > lexical] and [syntactic > phonological]. We found robust significant interactions of comprehension and production between these two regions at the syntactic level, for both sets of language-selective ROIs. This suggests a core difference in the function of these regions: language-selective subregions of Broca’s area play a role in syntax driven by the demands of production, whereas language-selective subregions of the PTL play a role in syntax driven by the demands of comprehension.
SARS-CoV-2 Whole Genome Amplification and Sequencing for Effective Population-Based Surveillance and Control of Viral Transmission
Authors: Harilal Divinlal , Ramaswamy Sathishkumar , Loney Tom , Suwaidi Hanan Al , Khansaheb Hamda , Alkhaja Abdulmajeed , Varghese Rupa , Deesi Zulfa , Nowotny Norbert , Alsheikh-Ali Alawi , Tayoun Ahmad Abou
Published: June 2020

Background

With the gradual reopening of economies and resumption of social life, robust surveillance mechanisms should be implemented to control the ongoing COVID-19 pandemic. Unlike RT-qPCR, SARS-CoV-2WholeGenomeSequencing (cWGS) has the added advantage of identifying cryptic origins of the virus, and the extent of community-based transmissions versus new viral introductions, which can in turn influence public health policy decisions. However, practical and cost considerations of cWGS should be addressed before it can be widely implemented.

Methods

We performed shotgun transcriptome sequencing using RNA extracted from nasopharyngeal swabs of patients with COVID-19, and compared it to targeted SARS-CoV-2 full genome amplification and sequencing with respect to virus detection, scalability, and cost-effectiveness. To track virus origin, we used open-source multiple sequence alignment and phylogenetic tools to compare the assembled SARS-CoV-2 genomes to publicly available sequences.

Results

We show a significant improvement in whole genome sequencing data quality and viral detection using amplicon-based target enrichment of SARS-CoV-2. With enrichment, more than 99% of the sequencing reads mapped to the viral genome compared to an average of 0.63% without enrichment. Consequently, a dramatic increase in genome coverage was obtained using significantly less sequencing data, enabling higher scalability and significant cost reductions. We also demonstrate how SARS-CoV-2 genome sequences can be used to determine their possible origin through phylogenetic analysis including other viral strains.

Conclusions

SARS-CoV-2 whole genome sequencing is a practical, cost-effective, and powerful approach for population-based surveillance and control of viral transmission in the next phase of the COVID-19 pandemic.
Effect of tocilizumab in hospitalized patients with severe pneumonia COVID-19: a cohort study
Authors: Rossi Benjamin , Nguyen Lee S. , Zimmermann Philippe , Boucenna Faiza , Dubret Louis , Baucher Louise , Guillot Helene , Bouldouyre Marie-Anne , Allenbach Yves , Salem Joe-Elie , Barsoum Paul , Oufella Arezki , Gros Helene
Published: June 2020

Background

Tocilizumab, a drug targeting interleukin-6 administrated in the right timeframe may be beneficial in coronavirus-disease-2019 (COVID-19). We aimed to assess its benefit, drawing from observations in compassionately treated patients.

Methods

In a retrospective case-control study, treatment effect (tocilizumab 400mg, single-dose) was assessed using three statistical methods: propensity-score matching, Cox multivariable survival and inverse probability score weighting (IPSW) analyses. Were included all patients hospitalized with COVID-19, who presented severity criteria with SpO2≤96% despite O2-support ≥6L/min for more than 6 hours. Were excluded patients in critical care medicine department and those under invasive mechanical ventilation. Primary outcome was a composite of mortality and ventilation, with a maximum follow-up of 28 days.

Results

246 patients were included (106 treated by tocilizumab). They were 67.6 ±15.3 years-old, with 95 (38.5%) women. Delay between first symptoms and inclusion was 8.4 ±4.5 days. Overall, 105 (42.7%) patients presented the primary outcome, with 71 (28.9%) deaths during the 28-days follow-up. Propensity-score-matched 84 pairs of comparable patients. In the matched cohort (n = 168), tocilizumab was associated with fewer primary outcomes (hazard ratio (HR) = 0.49 (95% confidence interval (95CI) = 0.3–0.81), p-value = 0.005). These results were similar in the overall cohort (n = 246), with Cox multivariable analysis yielding a protective association between tocilizumab and primary outcome (adjusted HR = 0.26 (95CI = 0.135–0.51, p = 0.0001), confirmed by IPSW analysis (p<0.0001). Analyses on mortality with 28-days follow-up yielded similar results.

Conclusion

In this retrospective study, tocilizumab single-dose was associated with improved survival without mechanical ventilation in patients with severe COVID-19.
Subcompartmentalization and pseudo-division of model protocells
Authors: Spustova Karolina , Köksal Elif Senem , Ainla Alar , Gözen Irep
Published: June 2020

Membrane enclosed intracellular compartments have been exclusively associated with the eukaryotes, represented by the highly compartmentalized last eukaryotic common ancestor. Recent evidence showing the presence of membranous compartments with specific functions in archaea and bacteria makes it conceivable that the last universal common ancestor and its hypothetical precursor, the protocell, could have exhibited compartmentalization. To our knowledge, there are no experimental studies yet that have tested this hypothesis. We report on an autonomous subcompartmentalization mechanism for protocells which results in the transformation of initial subcompartments to daughter protocells. The process is solely determined by the fundamental materials properties and interfacial events, and do not require biological machinery or chemical energy supply. In the light of our findings, we propose that similar events could have taken place under early Earth conditions, leading to the development of compartmentalized cells and potentially, primitive division.
Multiple, independent, common variants overlapping known and putative gut enhancers at RET, SEMA3 and NRG1 underlie Hirschsprung disease risk in European ancestry subjects
Authors: Kapoor Ashish , Nandakumar Priyanka , Auer Dallas R. , Sosa Maria X. , Ross Holly , Bollinger Juli , Yan Jia , Berrios Courtney ,   The Hirschsprung Disease Research Collaborative (HDRC), Chakravarti Aravinda
Published: June 2020

Purpose

Hirschsprung disease (HSCR) is a developmental disorder of the enteric nervous system (ENS) characterized by congenital aganglionosis, and where individual cases harbor coding risk variants in ENS genes. Low-penetrance, common, noncoding variants at RET, SEMA3 and NRG1 loci have been associated in HSCR as well, implicating variable gene expression mediated by cis-regulatory element (CRE) variants as the causal mechanism. However, the extent and combinatorial effects of all putative CRE variants within and across these loci on HSCR is unknown.

Methods

Using 583 HSCR subjects, one of the largest samples of European ancestry studied, and genotyping 56 tag variants we evaluated association of all common variants overlapping putative gut CREs and fine-mapped variants at RET, SEMA3 and NRG1.

Results

We demonstrate that 28 and 8 tag variants, several of which are independent, overlapping putative-enhancers at the RET and SEMA3 loci, respectively, and, 2 fine-mapped tag variants at NRG1 locus, are associated with HSCR. We demonstrate that risk increases with increasing risk allele dosage from multiple variants within and across these loci and varies >25- fold.

Conclusion

Gene regulatory networks in HSCR-relevant cell types quantify the total burden of risk alleles through sensing reduced gene expression of multiple genes on disease.
Nucleus translocation of tRNA synthetase mediates late integrated stress response
Authors: Wei Na , Cui Haissi , Shi Yi , Fu Guangsen , Rauniyar Navin , Yates John R. , Yang Xiang-Lei
Published: June 2020

Various stress conditions are signaled through phosphorylation of translation initiation factor eIF2α to inhibit global translation while selectively activating transcription factor ATF4 to aid cell survival and recovery. However, this integrated stress response is acute and cannot resolve lasting stress. Here we report that TyrRS, a member of the aminoacyl-tRNA synthetase family capable of responding to diverse stress factors through cytosol-nucleus translocation and activating stress-response genes, also inhibits global translation, however at a later stage than eIF2α/ATF4 and mTOR responses. Excluding TyrRS from the nucleus over-activates protein synthesis and increases apoptosis in cells under prolonged oxidative stress. Nuclear TyrRS transcriptionally represses translation genes by recruiting TRIM28 and/or NuRD complex. We propose TyrRS, possibly along with other family members, can sense a variety of stress signals through intrinsic properties of this enzyme and its strategically located nuclear localization signal and integrate them by nucleus-translocation to effect protective responses against prolonged stress.
NCOA3identified as a new candidate to explain autosomal dominant progressive hearing loss
Authors: da Silva Rodrigo Salazar , Dantas Vitor Lima Goes , Alves Leandro Ucela , Batissoco Ana Carla , Oiticica Jeanne , Lawrence Elizabeth A , Kawafi Abdelwahab , Yang Yushi , Nicastro Fernanda Stávale , Novaes Beatriz Caiuby , Hammond Chrissy , Kague Erika , Netto Regina Célia Mingroni
Published: June 2020

Hearing loss is a frequent sensory impairment in humans and genetic factors account for an elevated fraction of the cases. We have investigated a large family of five generations, with 15 reported individuals presenting non-syndromic, sensorineural, bilateral and progressive hearing loss, segregating as an autosomal dominant condition. Linkage analysis, using SNP-array and selected microsatellites, identified a region of 13cM in chromosome 20 as the best candidate to harbour the causative mutation. After exome sequencing and filtering of variants, only one predicted deleterious variant in theNCOA3gene (NM_181659, c.2810C>G; p.Ser937Cys) fit in with our linkage data. RT-PCR, immunostaining andin situhybridization showed expression ofncoa3in the inner ear of mice and zebrafish. We generated a stable homozygous zebrafish mutant line using the CRISPR/Cas9 system.ncoa3−/−did not display any major morphological abnormalities in the ear, however, anterior macular hair cells showed altered orientation. Surprisingly, chondrocytes forming the ear cartilage showed abnormal behaviour inncoa3−/−, detaching from their location, invading the ear canal and blocking the cristae. Adult mutants displayed accumulation of denser material wrapping the otoliths ofncoa3−/−and increased bone mineral density. Altered zebrafish swimming behaviour corroborates a potential role ofncoa3in hearing loss. In conclusion, we identified a potential candidate gene to explain hereditary hearing loss, and our functional analyses suggest subtle and abnormal skeletal behaviour as mechanisms involved in the pathogenesis of progressive sensory function impairment.