bluuebunny/crossref_metadata_2025 huggingface dataset:
PCARE requires coiled coil, RP62 kinase-binding and EVH1 domain-binding motifs for ciliary expansion
Authors: Afanasyeva Tess A V , Schnellbach Yan-Ting , Gibson Toby J , Roepman Ronald , Collin Rob W J
Published: March 2022

Retinitis pigmentosa (RP) is a genetically heterogeneous form of inherited retinal disease that leads to progressive visual impairment. One genetic subtype of RP, RP54, has been linked to mutations in PCARE (photoreceptor cilium actin regulator). We have recently shown that PCARE recruits WASF3 to the tip of a primary cilium, and thereby activates an Arp2/3 complex which results in the remodeling of actin filaments that drives the expansion of the ciliary tip membrane. On the basis of these findings, and the lack of proper photoreceptor development in mice lacking Pcare, we postulated that PCARE plays an important role in photoreceptor outer segment disk formation. In this study, we aimed to decipher the relationship between predicted structural and function amino acid motifs within PCARE and its function. Our results show that PCARE contains a predicted helical coiled coil domain together with evolutionary conserved binding sites for photoreceptor kinase MAK (type RP62), as well as EVH1 domain-binding linear motifs. Upon deletion of the helical domain, PCARE failed to localize to the cilia. Furthermore, upon deletion of the EVH1 domain-binding motifs separately or together, co-expression of mutant protein with WASF3 resulted in smaller ciliary tip membrane expansions. Finally, inactivation of the lipid modification on the cysteine residue at amino acid position 3 also caused a moderate decrease in the sizes of ciliary tip expansions. Taken together, our data illustrate the importance of amino acid motifs and domains within PCARE in fulfilling its physiological function.
Effects of Ocean Warming on the Underexplored Members of the Coral Microbiome
Authors: Maire Justin , Buerger Patrick , Chan Wing Yan , Deore Pranali , Dungan Ashley M , Nitschke Matthew R , van Oppen Madeleine J H
Published: March 2022

The climate crisis is one of the most significant threats to marine ecosystems. It is leading to severe increases in sea surface temperatures and in the frequency and magnitude of marine heatwaves. These changing conditions are directly impacting coral reef ecosystems, which are among the most biodiverse ecosystems on Earth. Coral-associated symbionts are particularly affected because summer heatwaves cause coral bleaching—the loss of endosymbiotic microalgae (Symbiodiniaceae) from coral tissues, leading to coral starvation and death. Coral-associated Symbiodiniaceae and bacteria have been extensively studied in the context of climate change, especially in terms of community diversity and dynamics. However, data on other microorganisms and their response to climate change are scarce. Here, we review current knowledge on how increasing temperatures affect understudied coral-associated microorganisms such as archaea, fungi, viruses, and protists other than Symbiodiniaceae, as well as microbe-microbe interactions. We show that the coral-microbe symbiosis equilibrium is at risk under current and predicted future climate change and argue that coral reef conservation initiatives should include microbe-focused approaches.
Managing the Dual Faces of International–Civil Militarized Conflict (I-CMC): The Interstate Dimension
Authors: Diehl Paul F , Owsiak Andrew P , Goertz Gary
Published: March 2022

This study examines how different conflict-management attempts over a broad time period affect the dynamics of one dimension of international–civil militarized conflict (I-CMC): the hostility–peace levels of relationships between states involved in those conflicts as well as the frequency and severity of their interactions. Using new data compilations on these conflicts and the management efforts embedded in them, we assess how effective each of the approaches and various contextual influences are in moderating state–state hostilities as well as the relative effectiveness (e.g., mediation versus military intervention). Our empirical analysis confirms that conflict-management efforts generally, and with respect to different management types, do not alter the overall hostile–peaceful relationships between states involved in I-CMCs. The empirical results on micro effects of conflict management produced clearer impacts from conflict-management approaches and contextual factors. In terms of mitigating conflict frequency, negotiation, military intervention, and peace operations had some negative effects on the time density of future militarized disputes. All approaches (the above three and mediation) were able to delay the onset of new disputes. Various contextual factors enhanced or mitigated the effects of conflict-management approaches.
Integrase resistance emergence with dolutegravir/lamivudine with prior HIV-1 suppression
Authors: Revollo Boris , Viñuela Laura , de la Mora Lorena , García Federico , Noguera-Julián Marc , Parera Mariona , Paredes Roger , Llibre Josep M.
Published: March 2022

Objectives

Integrase resistance has not been reported with co-formulated dolutegravir/lamivudine in clinical trials or real-life cohorts. We aim to report, to the best of our knowledge, the first case of selection of the key integrase mutation R263K in a subject treated with this regimen started as a switch strategy with undetectable plasma HIV-1 viraemia.

Methods

Clinical case report.

Results

A patient with long-term suppressed HIV-1 viraemia (<50 copies/mL) with no known risk factors for virological failure and never exposed previously to an integrase inhibitor developed virological failure (consecutive plasma HIV-1 RNA 149 and 272 copies/mL) with 322 CD4 cells/mm3 despite good treatment adherence. He was receiving the anticonvulsant clobazam, considered to have a potential weak interaction with dolutegravir, unlikely to require a dose adjustment. Plasma HIV-1 genotypic deep sequencing (Vela System) revealed the emergence of R263K (79.6%) and S230N (99.4%) mutations in the integrase region (intermediate resistance to dolutegravir, score = 30 Stanford HIVDB 9.0). The reverse transcriptase and protease regions could not be amplified due to low viral loads. PBMC DNA deep sequencing performed some months later revealed mutations M184I (14.29%) and M230I (6.25%) in the reverse transcriptase and G163R (9.77%) and S230N (98.8%) in the integrase. R263K was only found at extremely low levels (0.07%).

Conclusions

This case illustrates that integrase resistance can emerge in patients treated with co-formulated dolutegravir/lamivudine and raises awareness of the need to carefully consider and monitor drug–drug interactions, even when regarded as having a low potential, in subjects treated with dolutegravir/lamivudine.
Incorporation of a histone mutant with H3K56 site substitution perturbs the replication machinery in mouse embryonic stem cells
Authors: Kang Xuan , Yang Xiaomei , Guo Xiaobo , Li Yabin , Yang Chenxin , Wei Huimin , Chang Jianfeng
Published: March 2022

Sense mutations in several conserved modifiable sites of histone H3 have been found to be strongly correlated with multiple tissue-specific clinical cancers. These clinical site mutants acquire a distinctively new epigenetic role and mediate cancer evolution. In this study, we mimicked histone H3 at the 56th lysine (H3K56) mutant incorporation in mouse embryonic stem cells (mESCs) by lentivirus-mediated ectopic expression and analyzed the effects on replication and epigenetic regulation. The data show that two types of H3K56 mutants, namely H3 lysine 56-to-methionine (H3K56M) and H3 lysine 56-to-alanine (H3K56A), promote replication by recruiting more minichromosome maintenance complex component 3 and checkpoint kinase 1 onto chromatin compared with wild-type histone H3 and other site substitution mutants. Under this condition, the frequency of genomic copy number gain in H3K56M and H3K56A cells globally increases, especially in the Mycl1 region, a known molecular marker frequently occurring in multiple malignant cancers. Additionally, we found the disruption of H3K56 acetylation distribution in the copy-gain regions, which indicates a probable epigenetic mechanism of H3K56M and H3K56A. We then identified that H3K56M and H3K56A can trigger a potential adaptation to transcription; genes involved in the mitogen-activated protein kinase pathway are partially upregulated, whereas genes associated with intrinsic apoptotic function show obvious downregulation. The final outcome of ectopic H3K56M and H3K56A incorporation in mESCs is an enhanced ability to form carcinomas. This work indicates that H3K56 site conservation and proper modification play important roles in harmonizing the function of the replication machinery in mESCs.
Single-molecule observation of self-propagating amyloid fibrils
Authors: Watanabe-Nakayama Takahiro , Ono Kenjiro
Published: March 2022

The assembly of misfolded proteins into amyloid fibrils is associated with amyloidosis, including neurodegenerative diseases such as Alzheimer’s, Parkinson’s and prion diseases. The self-propagation of amyloid fibrils is widely observed in the aggregation pathways of numerous amyloidogenic proteins. This propensity with plasticity in primary nucleation allows amyloid fibril polymorphism, which is correlated with the pathology/phenotypes of patients. Because the interference with the nucleation and replication processes of amyloid fibrils can alter the amyloid structure and the outcome of the disease, these processes can be a target for developing clinical drugs. Single-molecule observations of amyloid fibril replication can be an experimental system to provide the kinetic parameters for simulation studies and confirm the effect of clinical drugs. Here, we review the single-molecule observation of the amyloid fibril replication process using fluorescence microscopy and time-lapse atomic force microscopy, including high-speed atomic force microscopy. We discussed the amyloid fibril replication process and combined single-molecule observation results with molecular dynamics simulations.
Measuring PROMIS® Social Relationships in Early Childhood
Authors: Blackwell Courtney K , Lai Jin-Shei , Kallen Michael , Bevans Katherine B , Davis Matthew M , Wakschlag Lauren S , Cella David
Published: March 2022

Objective

Apply the Patient-Reported Outcome Measurement Information System (PROMIS®) mixed-methods approach to develop and validate new parent-report measures of young children’s (1–5 years) family and peer relationships that conceptually align to those for 5–17 year olds.

Methods

Expert input, parent interviews, and reviews of theoretical and empirical literature were used to develop draft item pools, which were administered in two waves of panel surveys (N = 1,750). Psychometric evaluation was conducted using item response theory-based methods. Scores were normed to the general U.S. population. Initial validation analyses were conducted using Pearson’s correlations and analysis of variance to examine known-group differences between children with various health conditions.

Results

Experts and parents confirmed the content validity of existing PROMIS family and peer relationships domain frameworks and suggested adding child–caregiver interactions and empathic behaviors, respectively. Bi-factor model analysis supported sufficient unidimensionality where family and peer relationships were modeled as distinct subdomains of a broader concept, Social Relationships. The new measure was robust in discriminating young children with poor social relationships. Correlational and known-group analyses revealed positive associations with general health and well-being and negative associations with emotional and physical distress.

Conclusions

The PROMIS Early Childhood Parent-Report Social Relationships item bank enables clinicians and researchers a brief, efficient, and precise way to evaluate early relational health. Subdomain short forms also offer the ability to assess specific components (i.e., child–caregiver, family, and peer) for more targeted interventions and analyses.
Case report of mesenteric solitary fibrous tumour and review of the literature: ‘once in a blue moon’
Authors: Nicotera Antonella , Canova Gualtiero , Bono Dario , Gattoni Luca , Zago Marcello , Bonomo Luca Domenico
Published: March 2022

Solitary fibrous tumour (SFT) is a rare mesenchymal tumour, usually originating from the serous surfaces, typically of the pleura and pericardium. However, it can also have localizations in soft tissues and visceral organs. We report the case of a 79-year-old woman affected by mesenteric SFT, localized in the sigmoid colon. We performed open excision of the abovementioned mass en-bloc with the sigmoid colon and left adnexal tissues. Pathological examination of surgical specimen revealed a diagnosis of SFT CD34+, high-risk of metastases. Mesenteric SFTs are even rarer forms of SFT and may be asymptomatic or cause intestinal occlusion. There is no consensus on the management of this tumour. Radical surgical excision is the only curative treatment, while adjuvant therapies are indicated in case of advanced disease. Due to the high metastatic risk of malignant forms, a long follow-up is mandatory in these cases.
All-purpose, all-sky photometric redshifts for the Legacy Imaging Surveys Data Release 8
Authors: Duncan Kenneth J
Published: March 2022

In this paper, we present photometric redshift (photo-z) estimates for the Dark Energy Spectroscopic Instrument (DESI) Legacy Imaging Surveys, currently the most sensitive optical survey covering the majority of the extragalactic sky. Our photo-z methodology is based on a machine-learning approach, using sparse Gaussian processes augmented with Gaussian mixture models (GMMs) that allow regions of parameter space to be identified and trained separately in a purely data-driven way. The same GMMs are also used to calculate cost-sensitive learning weights that mitigate biases in the spectroscopic training sample. By design, this approach aims to produce reliable and unbiased predictions for all parts of the parameter space present in wide area surveys. Compared to previous literature estimates using the same underlying photometry, our photo-zs are significantly less biased and more accurate at z > 1, with negligible loss in precision or reliability for resolved galaxies at z < 1. Our photo-z estimates offer accurate predictions for rare high-value populations within the parent sample, including optically selected quasars at the highest redshifts (z > 6), as well as X-ray or radio continuum selected populations across a broad range of flux (densities) and redshift. Deriving photo-z estimates for the full Legacy Imaging Surveys Data Release 8, the catalogues provided in this work offer photo-z estimates predicted to be of high quality for ≳9 × 108 galaxies over ${\sim}19\, 400\, \text{deg}^{2}$ and spanning 0 < z ≲ 7, offering one of the most extensive samples of redshift estimates ever produced.
AlgoSCR: an algorithm for solar contamination removal from radio interferometric data
Authors: Phan Anh , Das Santanu , Stebbins Albert , Timbie Peter , Ansari Reza , Zuo Shifan , Li Jixia , Oxholm Trevor , Wu Fengquan , Chen Xuelei , Sun Shijie , Wang Yougang , Zhang Jiao
Published: March 2022

Hydrogen intensity mapping is a new field in astronomy that promises to make three-dimensional maps of the matter distribution of the Universe using the redshifted $21\, \textrm {cm}$ line of neutral hydrogen gas (HI). Several ongoing and upcoming radio interferometers, such as Tianlai, CHIME, HERA, HIRAX, etc., are using this technique. These instruments are designed to map large swaths of the sky by drift scanning over periods of many months. One of the challenges of the observations is that the daytime data are contaminated by strong radio signals from the Sun. In the case of Tianlai, this results in almost half of the measured data being unusable. We try to address this issue by developing an algorithm for solar contamination removal (AlgoSCR) from the radio data. The algorithm is based on an eigenvalue analysis of the visibility matrix and hence is applicable only to interferometers. We apply AlgoSCR to simulated visibilities, as well as real daytime data from the Tianlai dish array. The algorithm can reduce strong solar contamination by about 95 per cent without seriously affecting other weaker sky signals and thus makes the data usable for certain applications.
Dust mass loss during the recent outburst of comet C/2014 UN271 Bernardinelli–Bernstein
Authors: Wesołowski Marcin
Published: March 2022

The paper presents the results of numerical simulations of the mass ejected during the outburst of comet C/2014 UN271 Bernardinelli–Bernstein in large heliocentric distances. Determining the value of the mass ejected is one of the key factors determining the amplitude of the cometary outburst. It was assumed in the considerations that the scattering of the incident sunlight takes place on dust aggregates and dust agglomerates. In both of these cases, the key parameter in the context of determining the value of the mass ejected is the fraction of the nucleus surface that was active during quiet sublimation and the outburst. It was determined that the value of the mass ejected that caused the outburst fluctuated in the range from 107 to 108 kg. Moreover, the outburst itself, by exposing a fragment of the nucleus, rejuvenates the surface, at least on the local scale. The calculations performed refer to the outburst of comet C/2014 UN271 Bernardinelli–Bernstein on September 9, 2021.
Smart Matching Platforms and Heterogeneous Beliefs in Centralized School Choice
Authors: Arteaga Felipe , Kapor Adam J , Neilson Christopher A , Zimmerman Seth D
Published: March 2022

Many school districts with centralized school choice adopt strategy-proof assignment mechanisms to relieve applicants from needing to strategize based on beliefs about their own admissions chances. This article shows that beliefs about admissions chances shape choice outcomes even when the assignment mechanism is strategy-proof by influencing how applicants search for schools and that “smart matching platforms” that provide live feedback on admissions chances help applicants search more effectively. Motivated by a model in which applicants engage in costly search for schools and overoptimism can lead to undersearch, we use data from a large-scale survey of choice participants in Chile to show that learning about schools is hard, beliefs about admissions chances guide the decision to stop searching, and applicants systematically underestimate nonplacement risk. We use RCT and RD research designs to evaluate scaled live feedback policies in the Chilean and New Haven choice systems. Twenty-two percent of applicants submitting applications where risks of nonplacement are high respond to warnings by adding schools to their lists, reducing nonplacement risk by 58% and increasing test score value added at the schools where they enroll by 0.10 standard deviations. Reducing the burden of school choice requires not just strategy-proofness inside the centralized system but also choice supports for the strategic decisions that inevitably remain outside of it.
Cardiopulmonary Resuscitation May Not Stop Glutamate Release in the Cerebral Cortex
Authors: Fushimi Miki , Takeda Yoshimasa , Mizoue Ryoichi , Sato Sachiko , Kawase Hirokazu , Takasugi Yuji , Murai Satoshi , Morimatsu Hiroshi
Published: March 2022

Background:

Cardiopulmonary resuscitation (CPR) may not be sufficient to halt the progression of brain damage. Using extracellular glutamate concentration as a marker for neuronal damage, we quantitatively evaluated the degree of brain damage during resuscitation without return of spontaneous circulation.

Materials and Methods:

Extracellular cerebral glutamate concentration was measured with a microdialysis probe every 2 minutes for 40 minutes after electrical stimulation-induced cardiac arrest without return of spontaneous circulation in Sprague-Dawley rats. The rats were divided into 3 groups (7 per group) according to the treatment received during the 40 minutes observation period: mechanical ventilation without chest compression (group V); mechanical ventilation and chest compression (group VC) and; ventilation, chest compression and brain hypothermia (group VCH). Chest compression (20 min) and hypothermia (40 min) were initiated 6 minutes after the onset of cardiac arrest.

Results:

Glutamate concentration increased in all groups after cardiac arrest. Although after the onset of chest compression, glutamate concentration showed a significant difference at 2 min and reached the maximum at 6 min (VC group; 284±48 μmol/L vs. V group 398±126 μmol/L, P=0.003), there was no difference toward the end of chest compression (513±61 μmol/L vs. 588±103 μmol/L, P=0.051). In the VCH group, the initial increase in glutamate concentration was suddenly suppressed 2 minutes after the onset of brain hypothermia.

Conclusions:

CPR alone reduced the progression of brain damage for a limited period but CPR in combination with brain cooling strongly suppressed increases in glutamate levels.
Duration of Postpartum Magnesium Sulphate for the Prevention of Eclampsia
Authors: Okonkwo Maureen , Nash Christopher M.
Published: March 2022

OBJECTIVE:

To estimate the optimal duration of postpartum magnesium sulphate to prevent eclampsia.

DATA SOURCES:

MEDLINE, EMBASE, CINAHL, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov databases were searched from inception until January 2020 and limited to English-language human randomized controlled trials. Search strategy included the key works “eclampsia,” “magnesium sulphate,” and “postpartum.”

METHODS OF STUDY SELECTION:

Title, abstract, and full-text review was performed using Covidence data-management software. Of the 3,629 articles screened, 10 studies were included in the final review. Studies were included if they compared two different time points of magnesium sulphate postpartum in women with either preeclampsia or eclampsia.

TABULATION, INTEGRATION AND RESULTS:

Two authors reviewed studies independently. RevMan software was used to calculate risk difference (RD) for categorical outcomes and mean difference for continuous outcomes. Shorter duration of magnesium sulphate (12 hours or less) was not associated with increased risk of eclampsia compared with 24-hour postpartum regimens (RD −0.01, 95% CI −0.02 to 0.01, I2 70%). Studies randomizing women with preeclampsia did not show increased risk of eclampsia with shorter regimens (RD 0, 95% CI −0.01 to 0.01, I2 0%), nor did trials randomizing those with eclampsia (RD −0.04, 95% CI −0.14 to 0.07, I2 87%). Secondary outcomes, including flushing, duration of Foley catheter insertion, time to ambulation, and duration of hospital stay, were all reduced with shorter-duration magnesium sulphate.

CONCLUSION:

This systematic review and meta-analysis suggests that a shorter duration of postpartum magnesium sulphate does not increase the risk for eclamptic seizure; however, data remain underpowered to render firm conclusions.

SYSTEMATIC REVIEW REGISTRATION:

PROSPERO, CRD42020182432.
Digital Therapeutic Device for Urinary Incontinence
Authors: Weinstein Milena M. , Dunivan Gena , Guaderrama Noelani M. , Richter Holly E.
Published: March 2022

OBJECTIVE:

To evaluate whether pelvic floor muscle training using a motion-based digital intravaginal device is more effective than home pelvic floor muscle training for treatment of stress or stress-predominant mixed urinary incontinence (UI).

METHODS:

In a remote, virtually executed 8-week prospective randomized controlled superiority trial, women with stress or stress-predominant mixed UI were randomized to pelvic floor muscle training using a motion-based digital therapeutic device or a home training program using written and narrated instructions. Primary outcomes were change in UDI-6 (Urogenital Distress Inventory, Short Form) score and stress urinary incontinence (SUI) episodes on a 3-day bladder diary. A sample size of 139 per group (n=278) was planned to meet the power analysis requirements for the UDI-6 score (n=278) and the bladder diary (n=78). Prespecified secondary outcomes included quality-of-life surveys and adherence reporting.

RESULTS:

From September 2020 to March 2021, 5,353 participants were screened, and 363 were randomized: 182 in the intervention and 181 in the control group. There were no baseline clinicodemographic differences between groups. The mean change in UDI-6 score was significantly greater for the intervention group compared with the control group (18.8 vs 14.7, P=.01). The median (interquartile range) number of SUI episodes on the 3-day bladder diary was significantly reduced from 5 (3–8) and 5 (3–8) episodes to 1 (0–3) and 2 (1–4) (P=.005) in the intervention group compared with control group, respectively. A significantly greater number of participants in the intervention group than in the control group reported they were “much improved” or “very much improved” on the PGI-I (Patient Global Impression of Improvement) (63/143 [44.1% vs 45/156 [28.8%], odds ratio 1.94, 95% CI 1.21–3.15). There were no device-related severe adverse events.

CONCLUSION:

In this all-remote, virtually conducted trial, pelvic floor muscle training guided by a motion-based digital therapeutic device resulted in significantly improved UI symptoms and reduction of UI episodes compared with a home training program.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT04508153.

FUNDING SOURCE:

Renovia Inc.
Radiographic Characteristics of Cervical Deformity (CD) Using a Discriminant Analysis
Authors: Lafage Renaud , Virk Sohrab , Elysee Jonathan , Passias Peter , Ames Christopher , Hart Robert , Shaffrey Christopher , Mundis Gregory , Protopsaltis Themistocles , Gupta Munish , Klineberg Eric , Burton Douglas , Schwab Frank , Lafage Virginie ,   ISSG
Published: March 2022

Study Design:

This was a retrospective review of a prospectively collected database.

Objective:

The aim of this study was to delineate radiographic parameters that distinguish severe cervical spine deformity (CSD).

Summary of Background Data:

Our objective was to define parameters that distinguish severe CSD using a consensus approach combined with discriminant analysis as no system currently exists in the literature.

Methods:

Twelve CSD surgeons reviewed preoperative x-rays from a CSD database. A consensus was reached for categorizing patients into a severe cervical deformity (sCD), non–severe cervical deformity (non-sCD), or an indeterminate cohort. Radiographic parameters were found including classic cervical and spinopelvic parameters in neutral/flexion/extension alignment. To perform our discriminant analysis, we selected for parameters that had a significant difference between the sCD and non-sCD groups using the Student t test. A discriminant function analysis was used to determine which variables discriminate between the sCD versus non-sCD. A stepwise analysis was performed to build a model of parameters to delineate sCD.

Results:

A total of 146 patients with cervical deformity were reviewed (60.5±10.5 y; body mass index: 29.8 kg/m2; 61.3% female). There were 83 (56.8%) classified as sCD and 51 (34.9%) as non-sCD. The comparison analysis led to 16 radiographic parameters that were different between cohorts, and 5 parameters discriminated sCD and non-sCD. These parameters were cervical sagittal vertical axis, T1 slope, maximum focal kyphosis in extension, C2 slope in extension, and number of kyphotic levels in extension. The canonical coefficient of correlation was 0.689, demonstrating a strong association between our model and cervical deformity classification. The accuracy of classification was 87.0%, and cross-validation was 85.2% successful.

Conclusions:

More than one third of a series of CSD patients were not considered to have a sCD. Analysis of an initial 17 parameters showed that a subset of 5 parameters can discriminate between sCD versus non-sCD with 85% accuracy. Our study demonstrates that flexion/extension images are critical for defining severe CD.
Iatrogenic retroperitoneal hematoma as an access-site complication of neurointervention
Authors: Tai Wei-An , Wu Chia-Hung , Ling Kan , Chen Shu-Ting , Lin Te-Ming , Hwang Hsuen-En , Luo Chao-Bao , Guo Wan-Yuo , Chang Feng-Chi
Published: March 2022

Background:

To evaluate the clinical and imaging presentation, management, and outcome of iatrogenic retroperitoneal hematomas (IRPHs) during a series of neurointerventional procedures (NIPs).

Methods:

Six IRPH patients with complications, including five renal subcapsular hematomas (RSH) and one retroperitoneal hemorrhage, were observed among 2290 NIPs performed at our hospital from 2000 through 2020. The medical records, neurointerventional techniques, imaging data, and management of these six IRPH patients were retrospectively reviewed. All six patients received preprocedural dual antiplatelet medication and intraprocedural heparinization.

Results:

All patients underwent right femoral access. The guidewires were not handled under full course fluoroscopy monitoring. The most common symptom of IRPH was periprocedural flank/abdominal pain (6/6, 100%), including five on the left side (83.3%). Hypotension or shock was observed in three patients (50%). Two patients (33%) were diagnosed intraoperatively by sonogram and received on-site treatment, whereas the other four were diagnosed by postprocedural abdominal computed tomography. Active extravasation from a renal artery was diagnosed by angiogram in the five patients with RSH and was successfully treated with embolization. Multiple bleeders in the branches of the renal artery were noted in three RSH patients (60%). The patient with retroperitoneal hematoma was treated conservatively.

Conclusion:

Unexplained periprocedural or postprocedural abdominal/flank pain, especially contralateral to the femoral access side of the NIPs, should raise the possibility of IRPH. To prevent IRPH, the authors suggest using full visual fluoroscopic monitoring for guidewire navigation during femoral catheterization of NIPs.
Complex Suicide: A Case Series
Authors: Singh Sonwani Nagendra , Ateriya Navneet , Kumar Verma Satish , Kumar Aggarwal Narinder
Published: March 2022

Suicide is a common manner of death typically carried out via a specific mechanism. When a suicidal act is committed using more than one method, it is called a complex suicide. A complex suicide can be divided into planned and unplanned. We present three cases of complex suicide in which multiple methods were used and a previous history of self-harm was present. This case series highlights the significance of a detailed medicolegal death investigation, including interviews with relatives and other witnesses, and a thorough forensic autopsy/toxicological analysis to ascertain the cause and manner of death.
Proteome reveals antiviral host response and NETosis during acute COVID-19 in high-risk patients
Authors: Bauer Alina , Pachl Elisabeth , Hellmuth Johannes C. , Kneidinger Nikolaus , Frankenberger Marion , Stubbe Hans C. , Ryffel Bernhard , Petrera Agnese , Hauck Stefanie M. , Behr Jürgen , Kaiser Rainer , Scherer Clemens , Deng Li , Teupser Daniel , Ahmidi Narges , Muenchhoff Maximilian , Schubert Benjamin , Hilgendorff Anne
Published: March 2022

SARS-CoV-2 remains an acute threat to human health, endangering hospital capacities worldwide. Many studies have aimed at informing pathophysiologic understanding and identification of disease indicators for risk assessment, monitoring, and therapeutic guidance. While findings start to emerge in the general population, observations in high-risk patients with complex pre-existing conditions are limited.

To this end, we biomedically characterized quantitative proteomics in a hospitalized cohort of COVID-19 patients with mild to severe symptoms suffering from different (co)-morbidities in comparison to both healthy individuals and patients with non-COVID related inflammation. Deep clinical phenotyping enabled the identification of individual disease trajectories in COVID-19 patients. By the use of this specific disease phase assignment, proteome analysis revealed a severity dependent general type-2 centered host response side-by-side with a disease specific antiviral immune reaction in early disease. The identification of phenomena such as neutrophil extracellular trap (NET) formation and a pro-coagulatory response together with the regulation of proteins related to SARS-CoV-2-specific symptoms by unbiased proteome screening both confirms results from targeted approaches and provides novel information for biomarker and therapy development.

Graphical Abstract

Sars-CoV-2 remains a challenging threat to our health care system with many pathophysiological mechanisms not fully understood, especially in high-risk patients. Therefore, we characterized a cohort of hospitalized COVID-19 patients with multiple comorbidities by quantitative plasma proteomics and deep clinical phenotyping. The individual patient’s disease progression was determined and the subsequently assigned proteome profiles compared with a healthy and a chronically inflamed control cohort. The identified disease phase and severity specific protein profiles revealed an antiviral immune response together with coagulation activation indicating the formation of NETosis side-by-side with tissue remodeling related to the inflammatory signature.
Human cytomegalovirus strain diversity and dynamics reveal the donor lung as a major contributor after transplantation
Authors: Külekci Büsra , Schwarz Stefan , Brait Nadja , Perkmann-Nagele Nicole , Jaksch Peter , Hoetzenecker Konrad , Puchhammer-Stöckl Elisabeth , Goerzer Irene
Published: March 2022

Mixed human cytomegalovirus (HCMV) strain infections are frequent in lung transplant recipients (LTRs). To date, the influence of the donor (D) and recipient (R) HCMV-serostatus on intra-host HCMV strain composition and replication dynamics after transplantation is only poorly understood.

Here, we investigated ten pre-transplant lungs from HCMV-seropositive donors, and 163 sequential HCMV-DNA positive plasma and bronchoalveolar lavage samples from 50 LTRs with multiviremic episodes post-transplantation. The study cohort included D+R+ (38%), D+R− (36%), and D−R+ (26%) patients. All samples were subjected to quantitative genotyping by short amplicon deep sequencing, and 24 thereof were additionally PacBio long-read sequenced for genotype linkages.

We find that D+R+ patients show a significantly elevated intra-host strain diversity compared to D+R− and D−R+ patients (P=0.0089). Both D+ patient groups display significantly higher replication dynamics than D− patients (P=0.0061). Five out of ten pre-transplant donor lungs were HCMV-DNA positive, whereof in three multiple HCMV strains were detected, indicating that multi-strain transmission via lung transplantation is likely. Using long reads, we show that intra-host haplotypes can share distinctly linked genotypes, which limits overall intra-host diversity in mixed infections. Together, our findings demonstrate donor-derived strains as a main source for increased HCMV strain diversity and dynamics post-transplantation, while a relatively limited number of intra-host strains may facilitate rapid adaptation to changing environments in the host. These results foster targeted strategies to mitigate the potential transmission of the donor strain reservoir with the allograft.
SARS-CoV-2 Omicron Variant Infection of Individuals with High Titer Neutralizing Antibodies Post-3rd mRNA Vaccine Dose
Authors: Roeder Alexa J. , Koehler Megan A. , Svarovsky Sergei , Jasbi Paniz , Seit-Nebi Alim , Gonzalez-Moa Maria J. , Vanderhoof John , McKechnie Davis , Edwards Baylee A. , Lake Douglas F.
Published: March 2022

Background

Vaccination with COVID-19 mRNA vaccines prevent hospitalization and severe disease caused by wildtype SARS-CoV-2 and several variants, and likely prevented infection when serum neutralizing antibody (NAb) titers were >1:160. Preventing infection limits viral replication resulting in mutation, which can lead to the emergence of additional variants.

Methods

During a longitudinal study to evaluate durability of a three-dose mRNA vaccine regimen (2 primary doses and a booster) using a rapid test that semi-quantitatively measures NAbs, the Omicron variant emerged and quickly spread globally. We evaluated NAb levels measured prior to symptomatic breakthrough infection, in groups infected prior to and after the emergence of Omicron.

Results

During the SARS-CoV-2 Delta variant wave, 93% of breakthrough infections in our study occurred when serum NAb titers were <1:80. In contrast, after the emergence of Omicron, study participants with high NAb titers that had received booster vaccine doses became symptomatically infected. NAb titers prior to infection were ≥1:640 in 64% of the Omicron-infected population, ≥1:320 (14%), and ≥1:160 (21%).

Discussion

These results indicate that high titers of NAbs elicited by currently available mRNA vaccines do not protect against infection with the Omicron variant, and that mild to moderate symptomatic infections did occur in a vaccinated and boosted population, although did not require hospitalization.
Spike mutations of the SARS-CoV-2 Omicron: more likely to occur in the epitopes
Authors: Li Hu , Chen Zhiwei , Liu Xiaoqing , Hu Peng
Published: March 2022

Almost two years since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in 2019, and it is still pandemic over the world. SARS-COV-2 continuing to mutate and evolve, which further exacerbated the spread of the epidemic. Omicron variant, as an emerging mutation recently in South Africa, spreaded fastly to other countries worldwide. However, the gene charicterstic of Omicron and the effect on epitopes are still unclear. In this study, we retrieved 800 SARS-CoV-2 full-length sequences from GISAID database on 14 December 2021 (Alpha 110, Beta 101, Gamma 108, Delta 110, Omicron 107, Lambda 98, Mu 101, GH/490R 65). Overall, 1320 amino acid (AA) sites were mutated in these 800 SARS-CoV-2 sequences. Covariant network analysis showed that the covariant network of Omicron variant was significantly different from other variants. Further, 218 of the 1320 AA sites were occurred in the S gene, including 78 high-frequency mutations (>90%). Notably, we identified 25 unique AA mutations in Omicron, which may affect the transmission and pathogenicity of SARS-CoV-2. Finally, we analyzed the effect of Omicron on epitope peptide. As expected, 64.1% mutations (25/39) of Omicron variants were in epitopes, which was significantly higher than in other variants. These mutations may cause a poor response to vaccines to Omicron variants. In conclusion, Omicron variants, as an emerging mutation, should be alerted for us due that it may lead to poor vaccine response, and more data is needed to evaluate the virulence and vaccines responses to this variants.
Open label phase I/II clinical trial and predicted efficacy of SARS-CoV-2 RBD protein vaccines SOBERANA 02 and SOBERANA Plus in children
Authors: Puga-Gómez Rinaldo , Ricardo-Delgado Yariset , Rojas-Iriarte Chaumey , Céspedes-Henriquez Leyanis , Piedra-Bello Misleidys , Vega-Mendoza Dania , Pestana Pérez Noelvia , Paredes-Moreno Beatriz , Rodríguez-González Meiby , Valenzuela-Silva Carmen , Sánchez-Ramírez Belinda , Rodríguez-Noda Laura , Pérez-Nicado Rocmira , González-Mugica Raul , Hernández-García Tays , Fundora-Barrios Talía , Echevarría Martha Dubet , Enriquez-Puertas Juliet María , Infante Hernández Yenicet , Palenzuela-Díaz Ariel , Gato-Orozco Evelyn , Chappi-Estévez Yanet , Francisco-Pérez Julio Cesar , Martinez Miladi Suarez , Castillo-Quintana Ismavy C. , Fernandez-Castillo Sonsire , Climent-Ruiz Yanet , Santana-Mederos Darielys , García-Vega Yanelda , Toledo-Romani María Eugenia , Doroud Delaram , Biglari Alireza , Valdés-Balbín Yury , García-Rivera Dagmar , Vérez-Bencomo Vicente ,   SOBERANA Research Group
Published: March 2022

Objectives

To evaluate heterologous vaccination scheme in children 3-18 y/o combining two SARS-CoV-2 r-RBD protein vaccines.

Methods

A phase I/II open-label, adaptive and multicenter trial evaluated the safety and immunogenicity of two doses of SOBERANA02 and a heterologous third dose of SOBERANA Plus in 350 children 3-18 y/o in Havana Cuba. Primary outcomes were safety (in phase I) and safety/immunogenicity (in phase II) measured by anti-RBD IgG ELISA, molecular and live-virus neutralization titers and specific T-cells response. A comparison with adult‘s immunogenicity and prediction of efficacy were done based on immunological results

Results

Local pain was the unique adverse event with frequency >10%, none was serious or severe. Two doses of SOBERANA 02 elicited humoral immune response similar to natural infection; the third dose increased significantly the response in all children, similar to that achieved in vaccinated young adults and higher than in convalescents children. The neutralizing titer was evaluated in a participant‘s subset: GMT was 173.8 (CI 95% 131.7; 229.5) vs. alpha, 142 (CI 95% 101.3; 198.9) vs. delta and 24.8 (CI 95% 16.8; 36.6) vs. beta. An efficacy > 90% was estimated.

Conclusion

The heterologous scheme was safe and immunogenic in children 3-18 y/o. Trial registry: https://rpcec.sld.cu/trials/RPCEC00000374
COVID-19 Hospitalisation in Portugal, the first year: Results from hospital discharge data
Authors: Pereira João F. , Caetano Constantino , Antunes Liliana , Patrício Paula , Luísa Morgado Maria , Nunes Baltazar
Published: March 2022

Using Portuguese diagnosis-related groups (DRGs) data we analysed the dynamics of the COVID-19 hospitalisation in Portugal, with the ultimate goal of estimating parameters to be used in COVID-19 mathematical modelling.

After processing the data, corresponding to the period between March 2020 and the end of March 2021, an exploratory analysis was conducted, in which the length of stay (LoS) in hospital care, the time until death (TuD), the number of admissions and mortality count were estimated and described with respect to the age and gender of the patients, but also by region of admission and evolution over time.

The median and mean of LoS was estimated to be 8 and 12.5 days (IQR:4-15) for non-ICU patients and for ICU patients as 18 and 24.3 days (IQR:11-30). The percentage of patients that, during their hospitalisation, required ICU care was determined to be 10.9%. In-hospital mortality of non-ICU patients (22.6%) and of ICU patients (32.8%) were also calculated. In a visual exploratory analysis we observed that they changed with time, age group, gender and region.

Various univariable probability distributions were fitted to the LoS and TuD data, using maximum likelihood estimation (MLE) but also maximum goodness-of-fit estimation (MGE) to obtain the distribution parameters.

AMS Subject Classification

62-07,62E07,62F10,62P10
Features of an aseasonal 2021 RSV epidemic in the UK and Ireland: analysis of the first 10,000 patients
Authors: Roland D , Williams TC , Lyttle MD , Marlow R , Hardelid PC , Sinha I , Swann OV , Maxwell-Hodkinson A , Cunningham S
Published: March 2022

BronchStart is a prospective cohort study of infants with clinical bronchiolitis attending Emergency Departments in the United Kingdom and Ireland. We found the 2021 summer lower respiratory tract infection peak, although temporally disrupted and with an attenuated disease burden, predominantly affected younger age groups as in previous years.
Immunogenicity and reactogenicity against the SARS-CoV-2 variants following heterologous primary series involving CoronaVac and ChAdOx1 and BNT162b2 plus heterologous BNT162b2 booster vaccination: An open-label randomized study in healthy Thai adults
Authors: Niyomnaitham Suvimol , Toh Zheng Quan , Wongprompitak Patimaporn , Jansarikit Laddawan , Srisutthisamphan Kanjana , Sapsutthipas Sompong , Jantraphakorn Yuparat , Mingngamsup Natthakarn , Licciardi Paul V , Chokephaibulkit Kulkanya
Published: March 2022

We evaluated the immunogenicity and reactogenicity of heterologous COVID-19 primary series vaccination schedules. Participants were randomized to one of seven groups that received two-dose homologous BNT162b2 or heterologous combinations of CoronaVac, ChAdOx1 and BNT162b2, with 4 weeks interval. Of 210 participants, median age was 38 (19-60) years, 51% were female. The groups that received BNT162b2 as second dose induced the highest virus-specific IgG response against the ancestral strain [BNT162b2: geometric mean concentration (GMC) 2133-2249, 95%CI 1558 to 3055; ChAdOx1: 851-1201, 95%CI 649 to 1522; CoronaVac: 137-225, 95%CI 103-286 BAU/mL], neutralising antibodies (NAb) against Beta and Delta, and interferon gamma response. All groups induced low to negligible NAb against Omicron. A BNT162b2 booster (3rd dose) following heterologous CoronaVac and ChAdOx1 regimens induced >140-fold increase in NAb titres against Omicron. Our findings indicate that heterologous regimens using BNT162b2 as the second dose may be considered an alternative schedule to maximize immune response.
Evaluation of the role of home rapid antigen testing to determine isolation period after infection with SARS-CoV-2
Authors: Cosimi Lisa A. , Kelly Christina , Esposito Samantha , Seitz Scott , Sher-Jan Cole , Turcinovic Jacquelyn , Friedman Kelley , Nashed Michael , Souweine Jesse , Fitzgerald Nicholas , Gabriel Stacey , Connor John H. , Hung Deborah
Published: March 2022

Importance

Recent CDC COVID-19 isolation guidance for non-immunocompromised individuals with asymptomatic or mild infection allows ending isolation after 5 days if asymptomatic or afebrile with improving symptoms. The role of rapid antigen testing in further characterizing the risk of viral transmission to others is unclear.

Objective

Understand rates of rapid antigen test (RAT) positivity after day 5 from a positive COVID-19 test and the relationship of this result to symptoms and viral culture.

Design

In this single center, observational cohort study, ambulatory individuals newly testing SARS-CoV-2 positive completed daily symptom logs, and RAT self-testing starting day 6 until negative. Anterior nasal and oral swabs were collected on a subset for viral culture.

Main Outcomes and Measures

Day 6 SARS-CoV-2 RAT result, symptoms and viral culture.

Results

40 individuals enrolled between January 5 and February 11, 2022 with a mean age of 32 years (range 22 to 57). 23 (58%) were women and 17 (42%) men. All were vaccinated. 33 (83%) were symptomatic. Ten (25%) tested RAT negative on day 6. 61 of 90 (68%) RATs performed on asymptomatic individuals after day 5 were positive. Day 6 viral cultures were positive in 6 (35%) of 17 individuals. A negative RAT or being asymptomatic on day 6 were 100% and 78% predictive respectively for negative culture, while improving symptoms was 69% predictive. A positive RAT was 50% predictive of positive culture.

Conclusion and Relevance

RATs are suboptimal in predicting viral culture results on day 6. Use of routine RATs to guide end of COVID-19 isolation could result in significant numbers of culture negative, potentially non-infectious individuals undergoing prolonged isolation. However, a negative RAT was highly predictive of being culture negative. Complete absence of symptoms was inferior to a negative RAT in predicting a negative culture result, but performed better than improving symptoms. If a positive viral culture is a proxy for infectiousness, these data may help further refine a safer strategy for ending isolation.