bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analyzing the Safety and Efficacy of Flow-Diverting Stents in Pediatric Aneurysms: A Systematic Review
Authors: Scoville Jonathan , Joyce Evan , Baker Cordell , Dewey Jesse , Grandhi Ramesh , Taussky Philipp 
Published: March 2021

Abstract
Ruptured intracranial aneurysms cause 50% of spontaneous subarachnoid hemorrhages in children, resulting in up to 65% mortality when left untreated. Although flow-diverting stents are especially suited to treat the fusiform and giant aneurysms more commonly found in children, the US Food and Drug Administration (FDA) has only approved their use in patients ≥22 years of age. Our objective was to assess the safety of flow-diverting stents in the treatment of pediatric patients with aneurysms through a systematic literature review using the PRISMA criteria. We used PubMed, Embase, and Web of Science to identify all published cases of pediatric aneurysms treated or retreated using flow-diverting stents from 2007 through 2019. Two independent researchers developed a consensus regarding the inclusion of all articles. Patient data were extracted from the identified articles and used to calculate the incidence rate of complications. From 1396 journal articles identified, 24 articles contained data on 37 pediatric patients that met the inclusion criteria. Of these 37 patients, 8 (21.6%) had a complication by last follow-up (death: 2; residual aneurysm: 2; parent artery occlusion: 4). This resulted in an incidence rate of 0.018 complications per patient at-risk month (95% CI 0.008-0.035). These data suggest that the use of flow-diverting stents for treatment of aneurysms in children may be safe and that FDA approval for this use should be evaluated. Although this analysis is comprised of case reports and case series, it represents the best attempt thus far to quantify the risk of using flow-diverting stents in children.
Wanted, tracked down and identified: Mesozoic non-biting midges of the subfamily Chironominae (Chironomidae, Diptera)
Authors: Giłka Wojciech , Zakrzewska Marta , Lukashevich Elena D , Vorontsov Dmitry D , Soszyńska-Maj Agnieszka , Skibińska Kornelia , Cranston Peter S 
Published: March 2021

AbstractHere we provide evidence for the presence of non-biting midges of the subfamily Chironominae in the Mesozoic, based on descriptions of exceptionally rare amber inclusions. The subfamily has already been reported, but based on a single and unspecified record from Late Cretaceous Taimyr amber (~84 Mya). That record is here revised and confirmed. Moreover, a new find in Burmese amber locates the temporal boundary of the subfamily back to the mid-Cretaceous (probably ~100 Mya). We describe two new genera assigned to the tribe Pseudochironomini: Mesoacentron gen. nov. with the species Mesoacentron kaluginae sp. nov. (Taimyr amber) and Palaeocentron gen. nov. with the species Palaeocentron krzeminskii sp. nov. (Burmese amber), the oldest known representative of the subfamily. The systematic position of the new taxa is discussed, and a key to the identification of adult males of extinct and extant Pseudochironomini genera is presented. Insights in the phylogeny and diversification tempo of the Chironominae and Pseudochironomini in the past are also provided.
Adapting to a New Normal After Severe Acute Brain Injury: An Observational Cohort Using a Sequential Explanatory Design
Authors: Rutz Voumard Rachel , Kiker Whitney A. , Dugger Kaley M. , Engelberg Ruth A. , Borasio Gian Domenico , Curtis J. Randall , Jox Ralf J. , Creutzfeldt Claire J 
Published: March 2021

OBJECTIVES:
Treatment decisions following severe acute brain injury need to consider patients’ goals-of-care and long-term outcomes. Using family members as respondents, we aimed to assess patients’ goals-of-care in the ICU and explore the impact of adaptation on survivors who did not reach the level of recovery initially considered acceptable.

DESIGN:
Prospective, observational, mixed-methods cohort study.

SETTING:
Comprehensive stroke and level 1 trauma center in Pacific Northwest United States.

PARTICIPANTS:
Family members of patients with severe acute brain injury in an ICU for greater than 2 days and Glasgow Coma Scale score less than 12.

MEASUREMENTS AND MAIN RESULTS:
At enrollment, we asked what level of physical and cognitive recovery the patient would find acceptable. At 6 months, we assessed level of recovery through family surveys and chart review. Families of patients whose outcome was below that considered acceptable were invited for semistructured interviews, examined with content analysis.

RESULTS:
For 184 patients, most family members set patients’ minimally acceptable cognitive recovery at “able to think and communicate” or better (82%) and physical recovery at independence or better (66%). Among 170 patients with known 6-month outcome, 40% had died in hospital. Of 102 survivors, 33% were able to think and communicate, 13% were independent, and 10% died after discharge. Among survivors whose family member had set minimally acceptable cognitive function at “able to think and communicate,” 64% survived below that level; for those with minimally acceptable physical function at independence, 80% survived below that. Qualitative analysis revealed two key themes: families struggled to adapt to a new, yet uncertain, normal and asked for support and guidance with ongoing treatment decisions.

CONCLUSIONS AND RELEVANCE:
Six months after severe acute brain injury, most patients survived to a state their families initially thought would not be acceptable. Survivors and their families need more support and guidance as they adapt to a new normal and struggle with persistent uncertainty.
Active role of the central amygdala in widespread mechanical sensitization in rats with facial inflammatory pain
Authors: Sugimoto Mariko , Takahashi Yukari , Sugimura Yae K. , Tokunaga Ryota , Yajima Manami , Kato Fusao 
Published: March 2021

Abstract
Widespread or ectopic sensitization is a hallmark symptom of chronic pain, characterized by aberrantly enhanced pain sensitivity in multiple body regions remote from the site of original injury or inflammation. The central mechanism underlying widespread sensitization remains unidentified. The central nucleus of the amygdala (also called the central amygdala, CeA) is well situated for this role because it receives nociceptive information from diverse body sites and modulates pain sensitivity in various body regions. In this study, we examined the role of the CeA in a novel model of ectopic sensitization of rats. Injection of formalin into the left upper lip resulted in latent bilateral sensitization in the hind paw lasting >13 days in male Wistar rats. Chemogenetic inhibition of gamma–aminobutyric acid-ergic neurons or blockade of calcitonin gene-related peptide receptors in the right CeA, but not in the left, significantly attenuated this sensitization. Furthermore, chemogenetic excitation of gamma-aminobutyric acid-ergic neurons in the right CeA induced de novo bilateral hind paw sensitization in the rats without inflammation. These results indicate that the CeA neuronal activity determines hind paw tactile sensitivity in rats with remote inflammatory pain. They also suggest that the hind paw sensitization used in a large number of preclinical studies might not be simply a sign of the pain at the site of injury but rather a representation of the augmented CeA activity resulting from inflammation/pain in any part of the body or from activities of other brain regions, which has an active role of promoting defensive/protective behaviors to avoid further bodily damage.
Migraine chronification is associated with beta-band connectivity within the pain-related cortical regions: a magnetoencephalographic study
Authors: Hsiao Fu-Jung , Chen Wei-Ta , Liu Hung-Yu , Wang Yen-Feng , Chen Shih-Pin , Lai Kuan-Lin , Hope Pan Li-Ling , Coppola Gianluca , Wang Shuu-Jiun 
Published: March 2021

AbstractPain disorders are associated with aberrant oscillations in the pain-related cortical regions; however, few studies have investigated the relationship between the functional cortical network and migraine chronification through direct neural signals. Magnetoencephalography was used to record the resting-state brain activity of healthy controls as well as patients with episodic migraine (EM) and chronic migraine (CM). The source-based oscillatory dynamics of the pain-related cortical regions, which comprises 10 node regions (the bilateral primary [SI] and secondary somatosensory cortices, insula, medial frontal cortex, and anterior cingulate cortex [ACC]), were calculated to determine the intrinsic connectivity and node strength at 1 to 40 Hz. The total node strength within the pain-related cortical regions was smaller in the beta band in patients with migraine (70 EM and 80 CM) than in controls (n = 65). In the beta band, the node strength and functional connectivity values of patients with CM and patients with EM differed from those of controls in specific cortical areas, notably the left SI (EM < control) and bilateral ACC (CM < control); moreover, the node strength was lower in patients with CM than in those with EM. In all patients with migraine, negative correlations were observed between headache frequency and node strength in the bilateral ACC. In conclusion, migraine is characterized by reduced beta oscillatory connectivity within the pain-related cortical regions. Reduced beta connectivity in the ACC is linked to migraine chronification. Longitudinal studies should verify whether this oscillation change is a brain signature and a potential neuromodulation target for migraine.
An implantable restorative-neurostimulator for refractory mechanical chronic low back pain: a randomized sham-controlled clinical trial
Authors: Gilligan Christopher , Volschenk Willem , Russo Marc , Green Matthew , Gilmore Christopher , Mehta Vivek , Deckers Kristiaan , De Smedt Kris , Latif Usman , Georgius Peter , Gentile Jonathan , Mitchell Bruce , Langhorst Meredith , Huygen Frank , Baranidharan Ganesan , Patel Vikas , Mironer Eugene , Ross Edgar , Carayannopoulos Alexios , Hayek Salim , Gulve Ashish , Van Buyten Jean-Pierre , Tohmeh Antoine , Fischgrund Jeffrey , Lad Shivanand , Ahadian Farshad , Deer Timothy , Klemme William , Rauck Richard , Rathmell James , Levy Robert , Heemels Jan Pieter , Eldabe Sam ,   for the ReActiv8-B investigators
Published: March 2021

Abstract
Chronic low back pain can be caused by impaired control and degeneration of the multifidus muscles and consequent functional instability of the lumbar spine. Available treatment options have limited effectiveness and prognosis is unfavorable. We conducted an international randomized, double-blind, sham-controlled trial at 26 multidisciplinary centers to determine safety and efficacy of an implantable, restorative neurostimulator designed to restore multifidus neuromuscular control and facilitate relief of symptoms (clinicaltrials.gov identifier: NCT02577354). Two hundred four eligible participants with refractory mechanical (musculoskeletal) chronic LBP and a positive prone instability test indicating impaired multifidus control were implanted and randomized to therapeutic (N = 102) or low-level sham (N = 102) stimulation of the medial branch of the dorsal ramus nerve (multifidus nerve supply) for 30 minutes twice daily. The primary endpoint was the comparison of responder proportions (≥30% relief on the LBP visual analogue scale without analgesics increase) at 120 days. After the primary endpoint assessment, participants in the sham-control group switched to therapeutic stimulation and the combined cohort was assessed through 1 year for long-term outcomes and adverse events. The primary endpoint was inconclusive in terms of treatment superiority (57.1% vs 46.6%; difference: 10.4%; 95% confidence interval, −3.3% to 24.1%, P = 0.138). Prespecified secondary outcomes and analyses were consistent with a modest but clinically meaningful treatment benefit at 120 days. Improvements from baseline, which continued to accrue in all outcome measures after conclusion of the double-blind phase, were clinically important at 1 year. The incidence of serious procedure- or device-related adverse events (3.9%) compared favorably with other neuromodulation therapies for chronic pain.
Assisted reproductive technology outcomes in women with a chronic viral disease
Authors: Bourdon Mathilde , Garnier Alicia , Maignien Chloé , Marcellin Louis , Dulioust Emmanuel , Sogni Philippe , Launay Odile , Cheriet Khaled Pocate , Patrat Catherine , Chapron Charles , Santulli Pietro 
Published: March 2021

Objective:
The aim of this study was to evaluate the cumulative live birth rate in women undergoing in-vitro fertilization/intracytoplasmic-sperm-injection (IVF/ICSI) according to the type of chronic viral infection [HIV, hepatitis-B virus (HBV) and hepatitis-C virus (HCV)].

Design:
A cohort study.

Setting:
A tertiary-care university hospital.

Participants:
Women with a chronic viral illness HIV, HBV or HCV- were followed until four IVF/ICSI cycles had been completed, until delivery or until discontinuation of the treatment before the completion of four cycles.

Main outcome measures:
The primary outcome was the cumulative live birth rate after up to four IVF/ICSI cycles.

Results:
A total of 235 women were allocated to the HIV-infected group (n = 101), the HBV-infected group (n = 114) and the HCV-infected group (n = 20). The cumulative live birth rate after four cycles was significantly lower in the HIV-infected women than in those with HBV [39.1%, 95% confidence interval (95% CI): 17.7–60.9 versus 52.8%, 95% CI: 41.6–65.5, respectively; P = 0.004]. Regarding the obstetrical outcomes, the mean birth weight was lower in the HIV-infected women than in those with HBV or HCV. Multivariate analysis indicated that the age, the anti-Müllerian hormone and the number of cycles performed were significantly associated with the chances of a live birth.

Conclusion:
HIV-infected women had lower cumulative live birth rate than women with chronic hepatitis, and this was due to less favourable ovarian reserve parameters. These findings underscore the need to better inform practitioners and patients regarding fertility issues and the importance of early fertility assessment. However, larger studies are necessary to gain more in-depth knowledge of the direct impact of HIV on live birth rates.
Exploring predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine: a multivariable analysis
Authors: Cutrell Amy G. , Schapiro Jonathan M. , Perno Carlo F. , Kuritzkes Daniel R. , Quercia Romina , Patel Parul , Polli Joseph W. , Dorey David , Wang Yongwei , Wu Sterling , Van Eygen Veerle , Crauwels Herta , Ford Susan L. , Baker Mark , Talarico Christine L. , Clair Marty St , Jeffrey Jerry , White C. Thomas , Vanveggel Simon , Vandermeulen Kati , Margolis David A. , Aboud Michael , Spreen William R. , van Lunzen Jan 
Published: March 2021

Objective:
Efficacy and safety of long-acting cabotegravir (CAB) and rilpivirine (RPV) dosed intramuscularly every 4 or 8 weeks has been demonstrated in three Phase 3 trials. Here, factors associated with virologic failure at Week 48 were evaluated post hoc.

Design and methods:
Data from 1039 adults naive to long-acting CAB+RPV were pooled in a multivariable analysis to examine the influence of baseline viral and participant factors, dosing regimen and drug concentrations on confirmed virologic failure (CVF) occurrence using a logistic regression model. In a separate model, baseline factors statistically associated with CVF were further evaluated to understand CVF risk when present alone or in combination.

Results:
Overall, 1.25% (n = 13/1039) of participants experienced CVF. Proviral RPV resistance-associated mutations (RAMs), HIV-1 subtype A6/A1, higher BMI (associated with Week 8 CAB trough concentration) and lower Week 8 RPV trough concentrations were significantly associated (P < 0.05) with increased odds of CVF (all except RPV trough are knowable at baseline). Few participants (0.4%) with zero or one baseline factor had CVF. Only a combination of at least two baseline factors (observed in 3.4%; n = 35/1039) was associated with increased CVF risk (25.7%, n = 9/35).

Conclusion:
CVF is an infrequent multifactorial event, with a rate of approximately 1% in the long-acting CAB+RPV arms across Phase 3 studies (FLAIR, ATLAS and ATLAS-2M) through Week 48. Presence of at least two of proviral RPV RAMs, HIV-1 subtype A6/A1 and/or BMI at least 30 kg/m2 was associated with increased CVF risk. These findings support the use of long-acting CAB+RPV in routine clinical practice.
Ecological correlates of gene family size in a pine-feeding sawfly genome and across Hymenoptera
Authors: Vertacnik Kim L. , Herrig Danielle K. , Godfrey R. Keating , Hill Tom , Geib Scott M. , Unckless Robert L. , Nelson David R. , Linnen Catherine R. 
Published: March 2021

AbstractA central goal in evolutionary biology is to determine the predictability of adaptive genetic changes. Despite many documented cases of convergent evolution at individual loci, little is known about the repeatability of gene family expansions and contractions. To address this void, we examined gene family evolution in the redheaded pine sawflyNeodiprion lecontei, a non-eusocial hymenopteran and exemplar of a pine-specialized lineage evolved from angiosperm-feeding ancestors. After assembling and annotating a draft genome, we manually annotated multiple gene families with chemosensory, detoxification, or immunity functions and characterized their genomic distributions and evolutionary history. Our results suggest that expansions of bitter gustatory receptor (GR), clan 3 cytochrome P450 (CYP3), and antimicrobial peptide (AMP) subfamilies may have contributed to pine adaptation. By contrast, there was no evidence of recent gene family contraction via pseudogenization. Next, we compared the number of genes in these same families across insect taxa that vary in diet, dietary specialization, and social behavior. In Hymenoptera, herbivory was associated with small GR and olfactory receptor (OR) families, eusociality was associated with large OR and small AMP families, and—unlike investigations in more closely related taxa—ecological specialization was not related to gene family size. Overall, our results suggest that gene families that mediate ecological interactions may expand and contract predictably in response to particular selection pressures, however, the ecological drivers and temporal pace of gene gain and loss likely varies considerably across gene families.
Hospitalisation rates differed by city district and ethnicity during the first wave of COVID-19 in Amsterdam, the Netherlands
Authors: Coyer Liza , Wynberg Elke , Buster Marcel , Wijffels Camiel , Prins Maria , Schreijer Anja , van Duijnhoven Yvonne T.H.P , van Dam Alje , van der Lubben Mariken , Leenstra Tjalling 
Published: March 2021

ABSTRACTBackgroundIt is important to gain insight into the burden of COVID-19 at city district level to develop targeted prevention strategies. We examined COVID-19 related hospitalisations by city district and migration background in the municipality of Amsterdam, the Netherlands.MethodsWe used surveillance data on all PCR-confirmed SARS-CoV-2 hospitalisations in Amsterdam until 31 May 2020, matched to municipal registration data on migration background. We calculated directly standardised (age, sex) rates (DSR) of hospitalisations, as a proxy of COVID-19 burden, per 100,000 population by city district and migration background. We calculated standardised rate differences (RD) and rate ratios (RR) to compare hospitalisations between city districts of varying socio-economic and health status and between migration backgrounds. We evaluated the effects of city district and migration background on hospitalisation after adjusting for age and sex using Poisson regression.ResultsBetween 29 February and 31 May 2020, 2326 cases (median age 57 years [IQR=37-74]) were notified in Amsterdam, of which 596 (25.6%) hospitalisations and 287 (12.3%) deaths. 526/596 (88.2%) hospitalisations could be matched to the registration database. DSR were higher in individuals living in peripheral (South-East/New-West/North) city districts with lower economic and health status, compared to central districts (Centre/West/South/East) (RD=36.87,95%CI=25.79-47.96;RR=1.82,95%CI=1.65-1.99), and among individuals with a non-Western migration background compared to ethnic-Dutch individuals (RD=57.05,95%CI=43.34-70.75; RR=2.36,95%CI=2.17-2.54). City district and migration background were independently associated with hospitalisation.ConclusionCity districts with lower economic and health status and those with a non-Western migration background had the highest burden of COVID-19 during the first wave of COVID-19 in Amsterdam.
A proteome-wide genetic investigation identifies several SARS-CoV-2-exploited host targets of clinical relevance
Authors: Karim Mohd A , Shilts Jarrod , Schwartzentruber Jeremy , Hayhurst James , Buniello Annalisa , Mohammed Elmutaz Shaikho Elhaj , Zheng Jie , Holmes Michael V , Ochoa David , Carmona Miguel , Maranville Joseph , Gaunt Tom R. , Emilsson Valur , Gudnason Vilmundur , McDonagh Ellen M. , Wright Gavin J. , Ghoussaini Maya , Dunham Ian 
Published: March 2021

AbstractThe virus SARS-CoV-2 can exploit biological vulnerabilities in susceptible hosts that predispose to development of severe COVID-19. Previous reports have identified several host proteins related to the interferon response (e.g. OAS1), interleukin-6 signalling (IL-6R), and the coagulation cascade (linked via ABO) that were associated with risk of COVID-19. In the present study, we performed proteome-wide genetic colocalisation tests leveraging publicly available protein and COVID-19 datasets, to identify additional proteins that may contribute to COVID-19 risk. Our analytic approach identified several known targets (e.g. ABO, OAS1), but also nominated new proteins such as soluble FAS (colocalisation probability > 0.9, p = 1 × 10−4), implicating FAS-mediated apoptosis as a potential target for COVID-19 risk. We also undertook polygenic (pan) and cis-Mendelian randomisation analyses that showed consistent associations of genetically predicted ABO protein with several COVID-19 phenotypes. The ABO signal was associated with plasma concentrations of several proteins, with the strongest association observed with CD209 in several proteomic datasets. We demonstrated experimentally that CD209 directly interacts with the spike protein of SARS-CoV-2, suggesting a mechanism that could explain the ABO association with COVID-19. Our work provides a prioritised list of host targets potentially exploited by SARS-CoV-2 and is a precursor for further research on CD209 and FAS as therapeutically tractable targets for COVID-19.