bluuebunny/crossref_metadata_2025 huggingface dataset:
What If They Were White? The Differential Arrest Consequences of Victim Characteristics for Black and White Co-offenders
Authors: Lantz Brendan , Wenger Marin R , Craig Chloe J
Published: July 2021

A substantial body of research focuses on racial disparity in the criminal justice system, with mixed results due to difficulty in disentangling differential offending from racial bias. Additionally, some research has demonstrated that victim characteristics can exacerbate racial disparity in outcomes for offenders, but little research has focused on the arrest stage. We use a quasi-experimental approach that examines incidents involving co-offending pairs to isolate the influence of offender race on arrest, beyond any characteristics of the incident itself, and we test for moderating effects of victim race and sex on racial disparities in arrest. Our findings reveal that, on average, when two offenders of different races commit the same offense together against the same victim, Black offenders are significantly more likely to be arrested than their White co-offending partners, especially for assault offenses. More importantly, this effect—for both assaults and homicides—is particularly strong when the victim is a White woman. Because these differences are between two offenders who commit the same offense together, we argue that the most plausible explanation for the differences is the presence of racial bias or discrimination.
Bioefficacy of bendiocarb WP80 in vector-borne and zoonotic diseases areas in borderline of Iran and Pakistan
Authors: Abai Mohammad Reza , Vatandoost Hassan , Dorzadeh Hossein , Shayeghi Mansoreh , Hanafi-bojd Ahmad Ali , Raeisi Ahmad
Published: July 2021

Malaria and leishmaniasis are the public health problems in southern Iran. The main activity of vector control is indoor residual spraying using pyrethroids, using different insecticides as larviciding and impregnated bednets. The aim of study was to evaluate the biological assays of bendiocarb wettable powder (WP) at different surfaces of wall. The residual effect of bendiocarb WP80 at 400 milligram/meter square (mg/m2) was evaluated on various local surfaces of rooms such as mud and plaster as well as thatch roofs and wooden. World Health Organization standard cones using contact bioassays were carried out using laboratory reared sugar-fed, 48–72 h old females of Anopheles stephensi. Contact bioassays were carried out on sprayed surfaces for 150 days. Contact bioassay on surfaces treated with bendiocarb WP80 at different surfaces was estimated about 2 months. Fumigant tests of bendiocarb WP80 at 400 mg/m2 revealed 50–93.83% mortality with 1 month persistency. The results showed that carbamate insecticide could be used as rotation with pyrethroids for malaria vector control. Monitoring and evaluation of environmental toxicology of pesticides is important for decision making for choosing appropriate pesticides for disease vector control.
Does the socket design affect symmetry and spatiotemporal gait parameters? A case series of two transfemoral amputees
Authors: Yazdani Meria , Hajiaghaei Behnam , Saeedi Hassan , Kamali Mohammad , Yousefi Mohammad
Published: July 2021

Background:

Socket design is thought to improve gait performance and symmetry as the other components of the prosthesis do. This study focused on the comparison of two different sockets in transfemoral amputee patients to evaluate the influence of the socket designs on gait symmetry and various spatiotemporal gait parameters.

Methods:

Two transfemoral amputees participated in this case series study. They were asked to walk with the quadrilateral and the new modified sockets along a 10-meter walkway. The marker-based motion capture system recorded the spatiotemporal gait data during all walking trials. Kinematic data were compared between the two test conditions using the Wilcoxon signed-rank test and Symmetry Index.

Results:

The new socket increased velocity and cadence and reduced step width in both amputees, compared with the quadrilateral sockets. However, a good symmetry was observed in step length, stride length, step time, and stride time within two limbs by both sockets (SI ≤10).

Conclusions:

The design of sockets in this study had no observed effect on gait symmetry; however, the new socket increased velocity and cadence and reduced width step in both patients compared with the quadrilateral socket.

Level of Evidence:

Level IV.
Corrective Fifth Metacarpal Neck Osteotomy and Intramedullary Screw Fixation Technique: Technique and Case Report
Authors: Rosifini Alves Rezende Luis G. , Shimaoka Filipe J. , Mandarano-Filho Luiz G. , Mazzer Nilton
Published: July 2021

Malunion of metacarpal fractures can result in severe functional and esthetic impairment to the patient, thus requiring surgical correction. Traditionally, the fixation methods most commonly used for these fractures are the Kirschner wires or the plates and screws. However, one of the options for the fixation of metacarpal fractures is intramedullary fixation with a headless screw. This minimally invasive method can also be used for corrective metacarpal osteotomies. It has the advantages of being a minimally invasive technique and allowing the early range of motion. This minimally invasive method can also be used to stabilize the corrective metacarpal osteotomies for malunion. This case report presents a minimally invasive technique for corrective dorsal metacarpal osteotomy and fixation with a headless intramedullary screw. This alternative fixation method has the advantage of low damage to soft tissues and good functional outcomes.
Targeting SUMOylation in cancer
Authors: Du Li , Liu Wei , Rosen Steven T.
Published: July 2021

Purpose of review

In the article, we focus on the role of SUMOylation in tumorigenesis and cancer-related processes, including Epithelial–mesenchymal transition (EMT), metastasis, resistance to cancer therapies, and antitumor immunity. Clinical perspective on small ubiquitin-like modifier (SUMO) inhibitors will be discussed.

Recent findings

SUMOylation regulates multiple important biologic functions including gene transcription, DNA damage repair, cell cycle, and innate immunity. The SUMO pathway enzymes are usually elevated in various cancers and linked with cancer progression and poor clinical outcomes for patients. Recent studies have revealed the role of SUMOylation in EMT and metastasis through regulating E-Cadherin and Snail expression. Multiple studies demonstrate SUMOylation is involved with chemoresistance and hormone treatment resistance. Oncogene Myc and SUMOylation machinery regulation has been revealed in pancreatic cancer. SUMOylation is involved in regulating antitumor immune response through dendritic cells and T cells. A breakthrough has been made in targeting SUMOylation in cancer as first-in-class SUMO E1 inhibitor TAK-981 enters clinical trials.

SUMOylation plays an important role in tumor EMT, metastasis, therapy resistance, and antitumor immune response. Pharmaceutical inhibition of SUMOylation has become promising clinical therapy to improve the outcome of the existing chemo and immune therapies.
Alexithymia Is Associated With Internalizing Disorders in a Clinical Adolescent Outpatient Sample
Authors: Çoban Özge Gizli , Önder Arif
Published: July 2021

The aim of this study was to investigate alexithymic traits in an adolescent clinical sample with internalizing and externalizing disorders. The study group consisted of 125 adolescents aged between 12 and 17 years who applied at our outpatient unit and diagnosed with an internalizing or externalizing disorder. The healthy control group consisted of 53 adolescents with no psychiatric disorder. All subjects fulfilled the Alexithymia Questionnaire for Children (AQC). Total AQC scores were higher in the study group than in the control group. When we divided the study group into two groups as internalizing and externalizing disorders, total AQC scores, AQC–difficulty identifying feelings, and AQC–difficulty describing feelings were significantly higher in the internalizing disorder group than in the externalizing disorder group. AQC–externally oriented thinking scores were significantly higher in the externalizing disorder group than in the internalizing disorder group. In future research, it would be useful to further increase understanding of alexithymia and its association with psychiatric disorders in adolescence.
Preparing Nurse Leaders for Value-Based Care
Authors: May Nancy , Start Rachel , Ferket Kathleen , Allard Billie Lynn , Randazzo Geraldine
Published: July 2021

Organizations across the country are redesigning care delivery to improve quality and outcomes, enhance the patient experience, reduce costs, and, ultimately, produce better population health. Leaders from the American Organization for Nursing Leadership engaged key stakeholders to discuss the role nursing can play and the toolkit that will be introduced this year to guide nurse leaders in striving for value.
Effect of Shared Governance on Nurse-Sensitive Indicator and Satisfaction Outcomes by Magnet® Recognition Status
Authors: Speroni Karen Gabel , Wisner Kirsten , Ober Melanie , Haines Fiona , Walters Cynthia , Budhathoki Chakra
Published: July 2021

OBJECTIVE

Researchers examined associations between Index for Professional Nursing Governance (IPNG) types and outcomes.

BACKGROUND

Effects of professional nursing governance on nurse-related outcomes by Magnet® status are not well studied.

METHODS

Associations were evaluated between average IPNG scores from 2170 RNs, and nurse-sensitive indicators (NSIs) as well as patient and RN satisfaction outcomes (N = 205 study units; 20 hospitals), following Magnet requirements.

RESULTS

Magnet hospitals had significantly better IPNG shared governance scores than non-Magnet hospitals (Magnet, 106.7; non-Magnet, 101.3). For Magnet hospitals, units scoring as shared governance outperformed traditional governance for 9 of 19 outcomes (47.4%) (NSI, 2; patient satisfaction, 3; RN satisfaction, 4). Self-governance outperformed shared governance for 8 of 15 outcomes (53.3%) (NSI, 2; patient satisfaction, 6; RN satisfaction, 0). For non-Magnet hospitals, shared governance significantly outperformed traditional governance for 1 of 15 outcomes (6.7%) (patient satisfaction).

CONCLUSIONS

Having shared or self-governance is a strategy that can be considered by nurse leaders to improve select nurse-related outcomes.
Donor–Recipient BSA Matching Is Prognostically Significant in Solitary and En Bloc Kidney Transplantation From Pediatric Circulatory Death Donors
Authors: Little Christopher J. , Dick Andre A.S. , Perkins James D. , Reyes Jorge D.
Published: July 2021

Background.

As the rate of early postoperative complications decline after transplant with pediatric donation after circulatory death (DCD) kidneys, attention has shifted to the long-term consequences of donor–recipient (D-R) size disparity given the pernicious systemic effects of inadequate functional nephron mass.

Methods.

We conducted a retrospective cohort study using Organ Procurement and Transplantation Network data for all adult (aged ≥18 y) recipients of pediatric (aged 0–17 y) DCD kidneys in the United States from January 1, 2004 to March 10, 2020.

Results.

DCD pediatric allografts transplanted between D-R pairs with a body surface area (BSA) ratio of 0.10–0.70 carried an increased risk of all-cause graft failure (relative risk [RR], 1.36; 95% confidence interval [CI], 1.10–1.69) and patient death (RR, 1.32; 95% CI, 1.01–1.73) when compared with pairings with a ratio of >0.91. Conversely, similar graft and patient survivals were demonstrated among the >0.70–0.91 and >0.91 cohorts. Furthermore, we found no difference in death-censored graft survival between all groups. Survival analysis revealed improved 10-y patient survival in recipients of en bloc allografts (P = 0.02) compared with recipients of single kidneys with D-R BSA ratios of 0.10–0.70. A similar survival advantage was demonstrated in recipients of solitary allografts with D-R BSA ratios >0.70 compared with the 0.10–0.70 cohort (P = 0.02).

Conclusions.

Inferior patient survival is likely associated with systemic sequelae of insufficient renal functional capacity in size-disparate DCD kidney recipients, which can be overcome by appropriate BSA matching or en bloc transplantation. We therefore suggest that in DCD kidney transplantation, D-R BSA ratios of 0.10–0.70 serve as criteria for en bloc allocation or alternative recipient selection to optimize the D-R BSA ratio to >0.70.
Electroclinical Presentations of Fixation-off Sensitivity in Adults With Symptomatic Epilepsy
Authors: Das Pektezel Leyla , Tezer F. Irsel , Saygi Serap
Published: July 2021

Purpose:

Fixation-off sensitivity (FOS) is a discharge pattern on EEG that occurs owing to the loss of central vision or fixation. Knowledge regarding the relationship between FOS and symptomatic epilepsy is limited. Therefore, we aimed to evaluate the electroclinical features of FOS in adult patients with symptomatic epilepsy.

Methods:

Outpatient video-EEG records of the Hacettepe University Faculty of Medicine were reviewed from 2009 to 2019. Patients aged >18 years with symptomatic epilepsy with a FOS pattern were included. Demographic, clinical, EEG, and neuroimaging data were retrospectively evaluated from an electronic database and patient files.

Results:

Eight patients (50% female) were included in this study; seven (87%) had refractory epilepsy. Prominent risk factors were family history of epilepsy in five patients and prenatal/natal insult in four patients. Notable MRI signs included cortical developmental malformation, posterior gliosis, and frontoparietal porencephalic cyst. The FOS pattern was generalized with posterior emphasis in two patients and lateralized or localized in six patients: frontocentroparietal (n = 1) and temporoparietooccipital (n = 5). Fixation-off sensitivity discharges were found to be increased by hyperventilation and decreased by drowsiness and sleep in 50% of patients. Fixation-off sensitivity disappeared in one patient with good seizure control.

Conclusions:

In this study, the disappearance of FOS in an epileptic patient with a structural lesion and detection of FOS activity related to a frontoparietal porencephalic cyst were remarkable. Family history of epilepsy was also substantially high. Our results indicate that the underlying mechanism of FOS is much more complicated than previously thought.
Oscillatory EEG-TMS Reactivity in Parkinson Disease
Authors: Formaggio Emanuela , Tonellato Michele , Antonini Angelo , Castiglia Leonora , Gallo Laura , Manganotti Paolo , Masiero Stefano , Del Felice Alessandra
Published: July 2021

Purpose:

A dysfunction of beta oscillatory activity is the neurophysiological hallmark of Parkinson disease (PD). How cortical activity reacts to external perturbations may provide insight into pathophysiological mechanisms. This study aims at identifying modifications in EEG rhythms after transcranial magnetic stimulation (TMS) in PD. We hypothesize that single-pulse TMS can modulate brain intrinsic oscillatory properties (e.g., beta excess).

Methods:

EEG data were coregistered during single-pulse TMS (100 stimuli over the primary motor cortex [M1, hotspot for Abductor Pollicis Brevis], random intertrial interval from 8 to 13 seconds). We used a time-frequency analysis based on wavelet method to characterize modification of oscillatory rhythms (delta [1–4 Hz], theta [4–7 Hz], alpha [8–12 Hz], and beta [13–30 Hz] in 15 participants with PD compared with 10 healthy controls.

Results:

An increase in beta power over the sensorimotor areas was recorded at rest in the PD group (P < 0.05). Brain oscillations in PD transiently reset after TMS: beta power over M1 becomes comparable to that recorded in aged-matched healthy subjects in the 2 seconds following TMS.

Conclusions:

Transcranial magnetic stimulation over the dominant motor cortex transiently normalizes cortical oscillations. More user-friendly noninvasive brain stimulation needs to be trialed, based on this proof of concept, to provide practical, portable techniques to treat motor symptoms in PD.
Idification and structural characterisation of a catecholate-type siderophore produced by Stenotrophomonas maltophilia K279a
Authors: Hisatomi Atsushi , Shiwa Yuh , Fujita Nobuyuki , Koshino Hiroyuki , Tanaka Naoto
Published: July 2021

Siderophores are produced by several bacteria that utilise iron in various environments. Elucidating the structure of a specific siderophore may have valuable applications in drug development.

Stenotrophomonas maltophilia

, a Gram-negative bacterium that inhabits a wide range of environments and can cause pneumonia, produces siderophores. However, the structure was unknown, and therefore, in this study, we aimed to elucidate it. We purified siderophores from cultures of

S. maltophilia

K279a using preparative reversed-phase HPLC. The structure was analysed through LC-MS and 1H and 13C NMR. The results demonstrated that

S. maltophilia

K279a produces 2,3-dihydroxybenzoylserine (DHBS), a monomer unit of enterobactin. We suggested the uptake of Iron(III) by the DHBS complex. DHBS production by

S. maltophilia

K279a could be attributed to an incomplete enterobactin pathway. Drugs targeting DHBS synthesis could prevent

S. maltophilia

infection.
T cell receptor sequencing specifies psoriasis as a systemic and atopic dermatitis as a skin-focused, allergen-driven disease
Authors: Roesner Lennart M. , Farag Ahmed K. , Pospich Rebecca , Traidl Stephan , Werfel Thomas
Published: July 2021

Background

Atopic dermatitis (AD) and psoriasis represent two of the most common inflammatory skin diseases in developed countries. A hallmark of both diseases is T cell infiltration into the skin. However, it is still not clarified to what extent these infiltrating T cells are antigen-specific skin-homing T cells or unspecific heterogeneous bystander cells.

Methods

To elucidate this, T cells from lesional skin and from blood of 9 AD and 10 psoriasis patients were compared by receptor (TCR) sequencing. Therefore, peripheral blood mononuclear cells (PBMC) were cell-sorted according to expression of the cutaneous leukocyte antigen (CLA) into skin-homing (CLA+) and non-skin-homing (CLA-) subfractions. Aeroallergen-specific T cell lines were grown from AD patients’ PBMC in parallel.

Results

Intra-individual comparison of TCRB CDR3 regions revealed that clonally expanded T cells in skin lesions of both AD and psoriasis patients corresponded to skin-homing circulating T cells. However, in psoriasis patients, these T cell clones were also detectable to a larger extent among CLA-circulating T cells. Up to 28% of infiltrating cells in AD skin were identified as allergen-specific by overlapping TCR sequences.

Conclusions

Our data shows that in line with the systemic nature of psoriasis, T cell clones that infiltrate psoriatic skin lesions do not exclusively possess skin-homing ability and are therefore most probably specific to antigens that are not exclusively expressed or located in the skin. T cells driving AD skin inflammation appear to home nearly exclusively to the skin and are, to a certain extent, specific to aeroallergens.
Identification of loci genetically associated with antibodies to specific sets of citrullinated peptides in rheumatoid arthritis patients
Authors: Shchetynsky K , Brynedal B , Ramsköld D , Israelsson L , Hansson M , Mathsson-Alm L , Rönnelid J ,   Rheumatoid Arthritis Consortium International (RACI), Viatte S , Holmdahl R , Catrina A , Alfredsson L , Malmström V , Klareskog L , Gomez-Cabrero D , Padyukov L
Published: July 2021

Objectives

Production of anti-citrullinated peptide/protein antibodies (ACPA) is characteristic for rheumatoid arthritis (RA) and may inform about biological pathways involved in disease development in specific subgroups. Since multiple loci in genome wide association screens have been implicated in RA risk, we investigated the association between genetic variations and the development of multiple types of ACPA in three big cohorts of RA patients from Sweden, USA and UK (EIRA, NARAC and WTCCC) with overall 6,127 individuals with RA.

Methods

We combined genotyping data from Illumina Immunochip with serological data for 16 ACPA specificities from a custom-made multiplex microarray (Thermo Fisher Scientific, ImmunoDiagnostic division). A logistic regression-based association test in each cohort was followed by meta-analysis.

Results

We report several loci, harbouring three or more variants associated with ACPA, reaching study-wide significance (FDR<0.1) – PTPN22, LINC02341_TNFSF11, THADA and TMEM174. Most of these loci are not known to be associated with RA. Stratification by “shared epitope” (SE) alleles indicated an association between the PTPN22 locus and levels of antibodies binding to the vimentin peptide, Cit-Vim60-75, in SE positive cases, but not in SE negative cases.

Conclusion

Our data identifies several new loci which associate with subsets of RA characterized by presence of specific ACPA and indicate unknown disease heterogeneity.

Key messages

What is already known about this subject?

ACPA define two subgroups within RA, and has been an important biomarker included in diagnostic criteria

Commonly used ACPA test, anti-CCP, accumulate signals from autoantibodies to several peptides and does not discriminate between multiple autoantibody specificities.

What does this study add?

Our study demonstrates that different sets of ACPAs in RA have distinct genetic associations. Associated variants from our study localize in known regulatory regions and have transcriptomic effects beyond the associated locus

We find that PTPN22 locus can drive positivity for multiple APCAs, while other found loci associate with specific autoantibody positivities

How might this impact on clinical practice?

Our study will extend personalized approach in handling of rheumatoid arthritis with focus on serologically defined subgroups of the disease.
Study protocol: Assessing the association between corporate political influence and implementation of policies to tackle commercial determinants of non-communicable diseases: a cross-sectional analysis of 172 countries
Authors: Allen Luke N , Wigley Simon , Holmer Hampus
Published: July 2021

Objectives

To assess the association between corporate political influence and implementation of WHO-recommended policies to constrain sales, marketing and consumption of tobacco, alcohol, and unhealthy foods.

Design

Cross-sectional analysis using national datasets from 2015, 2017, and 2020.

Setting

Global analysis of data from 172 of the 194 WHO Member States

Main outcome measures

We will use random effects multivariate regression to test the association between implementation status of 12 WHO-recommended tobacco, alcohol, and diet policies and corporate political influence, a metric that combines disclosure of campaign donations, public campaign finance, corporate campaign donations, legislature corrupt activities, disclosure by politicians, and executive oversight. We will control for GDP per capita, population aged >65 years, urbanization, level of democracy, continent, ethno-linguistic fractionalization, legal origin, Small Island Developing States, and Muslim population (to capture alcohol policy differences). We will include year dummies to address the possibility of a spurious relationship between the outcome variable and the independent variables of interests. For example, there may be an upward global trend in policy implementation that coincides with an upward global trend in in the regulation of lobbying and campaign finance.

Ethics and dissemination

As this study uses publicly available data, ethics approval is not required. The authors have no conflicts of interest to declare. Findings will be submitted to a peer-reviewed journal for publication in the academic literature. All data, code, and syntax will be made publicly available on GitHub.
Enhancing Research Data Infrastructure to Address the Opioid Epidemic: The Opioid Overdose Network (02-Net)
Authors: Lenert Leslie A , Zhu Vivienne , Jennings Lindsey , McCauley Jenna L , Obeid Jihad S , Ward Ralph , Hassanpour Saeed , Marsch Lisa A , Hogarth Michael , Shipman Perry , Harris Daniel R , Talbert Jeffery C
Published: July 2021

Objective

Opioid Overdose Network is an effort to generalize and adapt an existing research data network, the Accrual to Clinical Trials (ACT) Network, to support design of trials for survivors of opioid overdoses presenting to emergency departments (ED). Four institutions (Medical University of South Carolina (MUSC), Dartmouth Medical School (DMS), University of Kentucky (UK), and University of California San Diego (UCSD)) worked to adapt ACT network. This paper reports their progress.

Materials and Methods

The approach taken to enhancing ACT network focused on four activities: cloning and extending the ACT infrastructure, developing an e-phenotype and corresponding registry, developing portable natural language processing (NLP) tools to enhance data capture, and developing automated documentation templates to enhance extended data capture.

Results

All four institutions were able to replicate their i2b2 and Shared Health Research Information Network (SHRINE) infrastructure. A five category e-phenotype model based on ICD-10 coding was developed from prior published work. Ongoing work is refining this via machine learning and artificial intelligence methods. Portable NLP tools, focused at the sentence level, were also developed to identify uncoded opioid overdose related concepts in provider notes.

Optimal performance was seen in NLP tools that combined rule-based with deep learning methods (F score, 0.94). A template for ED overdose documentation was developed to improve primary data capture. Interactive prompts to physicians inside ED progress notes were effective in promoting use of the template. The template had good system usability and net promoter scores (0.72 and 0.75, respectively, n=13). Work to design ED trials based on the network’s data is underway.

Discussion and Conclusions

Overall, initial results suggest that tailoring of existing multipurpose research networks to specific tasks is feasible; however, substantial efforts are required for coordination of the subnetwork and development of new tools for extension of available data.
Comparison of Pandemic Intervention Policies in Several Building Types Using Heterogeneous Population Model
Authors: Lazebnik Teddy , Alexi Ariel
Published: July 2021

In a world where pandemics are a matter of time and increasing urbanization of the world’s population, governments should be prepared with pandemic intervention policies (IPs) to minimize the crisis direct and indirect adverse effects while keeping normal life as much as possible. Successful pandemic IPs have to take into consideration the heterogeneous behavior of individuals in different types of buildings and social contexts. In this study, we propose a spatio-temporal, heterogeneous population model and in silico simulation to evaluate pandemic IPs in four types of buildings - home, office, school, and mall. We show that indeed each building type has a unique pandemic spread and therefore a different optimal IP. Moreover, we show that temporal-based IPs (such as mask wearing) have a similar influence on the pandemic spread in all four building types while spatial-based IPs (such as social distance) highly differ.
Platelet size as a predictor for severity and mortality in COVID-19 patients: a systematic review and meta-analysis
Authors: Daniels Sarah , Wei Hua , Denning David W.
Published: July 2021

Background

Parameters reflecting platelet size can be sensitive indicators that circulating platelets are activated and COVID-19 patients are at increased risk of thrombosis. This systematic review aims to assess the association of mean platelet volume (MPV), platelet distribution width (PDW) and platelet-large cell ratio (P-LCR) with disease severity and mortality in COVID-19 patients.

Methods

English and Chinese databases were searched electronically to identify studies reporting data on MPV, PDW or P-LCR in COVID-19 patients. Included articles underwent a quality rating. A meta-analysis was performed using the standard mean difference and interpreted as the common language effect size (CLES).

Results

Twenty-two studies (11,906 patients) were included in the meta-analysis. Of these, 14 were rated poor and eight were fair. The MPV and P-LCR was significantly higher at hospital admission in severe patients compared to non-severe patients. The MPV, PDW and P-LCR were significantly higher at hospital admission in non-survivors compared to survivors. There was a marked increase in the probability of a severe COVID-19 patient presenting with higher P-LCR at hospital admission than a non-severe patient (CLES: 68.7% [95% CI: 59.8%, 76.5%]), when compared with MPV and PDW ((CLES: 59.2% [95% CI: 53.1%, 65.1%]) and (CLES: 55.9% [95% CI: 50.6%, 62.2%]), respectively).

Conclusion

Severe COVID-19 disease is associated with the increased production of larger, younger platelets. When comparing MPV, PDW and P-LCR, P-LCR is the most important biomarker for evaluating platelet activity. P-LCR testing at hospital admission could identify COVID-19 patients with increased risk for thrombotic events, allowing preventative treatment.

Summary Table

What is known on this topic

The incidence of thrombotic complications is high in COVID-19 patients with severe disease.

Parameters reflecting platelet size can be sensitive indicators that circulating platelets are activated and that COVID-19 patients are at increased risk of thrombosis.

What does this paper add

When compared to MPV and PDW, P-LCR is the most important biomarker for evaluating platelet activity in COVID-19 patients at hospital admission and could be used to identify patients with increased risk for thrombotic events.

Current evidence is predominantly derived from retrospective design. Prospective studies are warranted to accurately determine cut-off values that may be used in the clinical setting.
The CT Scan Lung Severity Score and Vaccination Status in COVID-19 patients in India: Perspective of an Independent Radiology Practice
Authors: Lakhia Revat T. , Trivedi Jaimin R.
Published: July 2021

Background

The COVID-19 patients often undergo a high-resolution CT scan to determine extent of their lung involvement. The aim of this study was to determine lung involvement in confirmed/suspected COVID-19 patients (encountered at an independent radiology practice) and its correlation to vaccination status amidst the second COVID-19 wave in India.

Methods

We retrospectively queried our data since April 2021 to identify adult patients (>17 years) who had confirmed (positive RT-PCR or antigen test) or suspected COVID-19 (classic symptoms but negative RT-PCR) and received a high-resolution CT scan to determine the extent of their lung involvement using the CT severity (CT-SS) score. Patients were classified in 3 groups based on their vaccination status to determine its correlation with the CT-SS score: fully vaccinated, partially vaccinated, and unvaccinated. Basic descriptive statistics, univariate tests and multivariate linear regression analysis were used.

Results

We identified 229 patients (median age 45 years, 60% male) of which 205 (89%) had confirmed COVID-19 (positive RT-PCR) and 24 had suspected disease (negative RT-PCT but classic symptoms). Of the 229 patients 29 (13%) had complete vaccination, 38 (17%) had partial vaccination and 162 (70%) had no vaccination. The CT score of the completely vaccinated patients was significantly lower compared to partially or unvaccinated patients (median 0 v. 3.5 v. 10, respectively p<.01). A multivariate linear regression model showed that partial or fully vaccinated patients had lower CT severity score compared to unvaccinated patients (adjusted R squared = 0.47).

Conclusion

We present here the real-world findings from an independent radiology practice (a unique and common practice model), in India amid the second COVID-19 wave showing significantly lower CT severity score in fully or partially vaccinated patients compared to unvaccinated patients. Complete vaccination in patients could be critical in preventing severe lung disease.
Prevalence of anti-platelet factor4/polyanionic antibodies after COVID-19 vaccination with ChAdOx1 nCoV-19 and CoronaVac in Thais
Authors: Noikongdee Phichchapha , Police Pornnapa , Phojanasenee Tichayapa , Chantrathammachart Pichika , Niparuck Pimjai , Puavilai Teeraya , Phuphuakrat Angsana , Angchaisuksiri Pantep , Boonyawat Kochawan
Published: July 2021

Introduction

Vaccine-induced thrombotic thrombocytopenia (VITT) has been reported after vaccination with the adenoviral vector COVID-19 vaccine ChAdOx1 nCoV-19 in European countries. To date, no case of VITT has been reported in Thais after COVID-19 vaccination. We determined the frequency of anti-PF4/polyanionic antibodies in the Thai population receiving the COVID-19 vaccines.

Methods

We conducted a cross-sectional study to evaluate the prevalence of anti-PF4/polyanionic antibodies in health care workers who received COVID-19 vaccination with ChAdOx1 nCoV-19 or CoronaVac within 7-35 days. A control population who had not been vaccinated was also included. Anti-PF4/polyanionic antibodies were detected using enzyme-link immunosorbent assay (ELISA). Functional assay with platelet aggregation was performed for all positive anti-PF4/polyanionic antibody ELISA tests.

Results

A total of 646 participants were included in the study. 221 received ChAdOx1 nCoV-19, 232 received CoronaVac, and 193 participants were in the control group. The prevalence of anti-PF4 antibodies was 2.3% (95% confidence interval [CI] 0.7 to 5.2), 1.7% (95% CI, 0.5 to 4.4) in the ChAdOx1 nCoV-19 and CoronaVac groups, respectively. There was no positive test in the control group. None of the PF4/polyanionic positive sera induced platelet aggregation.

Conclusion

We found a low prevalence of anti-PF4 antibodies in Thais after vaccination with ChAdOx1 nCoV-19 and CoronaVac. Low titer positive PF4/polyanionic ELISA results should be interpreted with caution when screening asymptomatic individuals after vaccination against COVID-19.

Highlights

High titer PF4/polyanion antibodies are associated with vaccine-induced immune thrombotic thrombocytopenia (VITT).

Low titer PF4/polyanion antibodies occur after vaccination with ChAdOx1 nCoV-19 and CoronaVac in some vaccinees.

These PF4/polyanion antibodies do not activate platelets and lack of association with VITT.

Low-titer positive PF4/polyanionic ELISA results should be interpreted with caution when screening asymptomatic individuals after vaccination against COVID-19.
Body size mediates latitudinal population differences in response to Bd infection in two amphibian species
Authors: Meurling Sara , Cortazar-Chinarro Maria , Siljestam Mattias , Åhlen David , Ågren Erik , Höglund Jacob , Laurila Anssi
Published: July 2021

Populations of the same species may differ in their sensitivity to pathogens but the factors behind this variation are poorly understood. Moreover, infections may cause sub-lethal fitness effects even in species resistant or tolerant to disease. The chytrid fungus Batrachochytrium dendrobatidis (Bd), is a generalist pathogen which has caused amphibian population declines worldwide. In many species, Bd infection causes the disease chytridiomycosis, often leading to high mortality. We investigated how geographical origin affects tolerance to Bd by exposing newly metamorphosed individuals of two North European amphibians (moor frog Rana arvalis, common toad Bufo bufo) from two latitudinal regions to two different BdGPL strains. Bd exposure strongly lowered survival in B. bufo, and in both species survival was lower in the northern region, this difference being much stronger in B. bufo. Northern individuals were smaller in both species, and the survival difference between the regions was size-mediated with smaller individuals being more sensitive to Bd. In both species, Bd exposure led to sub-lethal effects in terms of reduced growth suggesting that even individuals surviving the infection may have reduced fitness mediated by smaller body size. Bd strain affected size-dependent mortality differently in the two regions. We discuss the possible mechanisms how body size and geographical origin can contribute to the present results.
Impact of acute visual experience on development of LGN receptive fields in the ferret
Authors: Stacy Andrea K. , Schneider Nathan A. , Gilman Noah K. , Van Hooser Stephen D.
Published: July 2021

Selectivity for direction of motion is a key feature of primary visual cortical neurons. Visual experience is required for direction selectivity in carnivore and primate visual cortex, but the circuit mechanisms of its formation remain incompletely understood. Here we examined how developing lateral geniculate nucleus (LGN) neurons may contribute to cortical direction selectivity. Using in vivo electrophysiology techniques, we examined LGN receptive field properties of visually naïve female ferrets before and after exposure to 6 hours of motion stimuli in order to assess the effect of acute visual experience on LGN cell development. We found that acute experience with motion stimuli did not significantly affect the weak orientation or direction selectivity of LGN neurons. In addition, we found that neither latency nor sustainedness or transience of LGN neurons significantly changed with acute experience. These results suggest that the direction selectivity that emerges in cortex after acute experience is computed in cortex and cannot be explained by changes in LGN cells.

Significance Statement

The development of typical neural circuitry requires experience-independent and experience-dependent factors. In the visual cortex of carnivores and primates, selectivity for motion arises as a result of experience, but we do not understand whether the major brain area that sits between the retina and the visual cortex – the lateral geniculate nucleus of the thalamus – also participates. Here we found that lateral geniculate neurons do not exhibit changes as a result of several hours of visual experience with moving stimuli, at a time when visual cortical neurons undergo a rapid change. We conclude that lateral geniculate neurons do not participate in this plasticity, and that changes in cortex are likely responsible for the development of direction selectivity in carnivores and primates.
Multiple stage hydra effect in a stage–structured prey–predator model
Authors: Costa Michel Iskin da S. , Anjos Lucas dos , Esteves Pedro V.
Published: July 2021

In this work, we show by means of numerical bifurcation that two alternative stable states exhibit a hydra effect in a continuous–time stage–structured predator–prey model. We denote this behavior as a stage multiple hydra effect. This concomitant effect can have significant implications in population dynamics as well as in population management.
NDC1 is necessary for the stable assembly of the nuclear pore scaffold to establish nuclear transport in early C. elegans embryos
Authors: Mauro Michael Sean , Celma Gunta , Zimyanin Vitaly , Gibson Kimberley H. , Redemann Stefanie , Bahmanyar Shirin
Published: July 2021

Nuclear pore complexes (NPCs) are large protein assemblies that facilitate transport of macromolecules across the nuclear envelope (NE) [1, 2]. How thousands of NPCs rapidly assemble after open mitosis to form a functional NE is not known. Recruitment of the Nup107-160 outer ring scaffold to chromatin initiates NPC assembly. The Nup53/93 complex bridges the outer ring to the central channel to form a functional pore [3–6]. Nup53 interacts with the conserved transmembrane nucleoporin Ndc1; however, how Ndc1 contributes to post-mitotic NPC assembly is unclear [7–9]. Here, we use C. elegans embryos to show that the timely formation of a functional NE after mitosis depends on Ndc1. Endogenously tagged Ndc1 is recruited early to the reforming NE and is highly mobile in the nuclear rim. 3D analysis of post-mitotic NE formation revealed a decreased NPC density in NEs of ndc1 deleted embryos – continuous nuclear membranes contained few holes where assembling NPCs are normally located. Nup160 is highly mobile in NEs depleted of Ndc1 and outer ring scaffold components are less enriched at the rim. When both ndc1 and nup53 are absent, nuclear assembly fails. Together, these data show that Ndc1 dynamically associates with the NE and promotes stable association of the outer ring scaffold in the NE to facilitate NPC assembly after open mitosis. Furthermore, Ndc1 and Nup53 function in parallel to drive nuclear assembly. We propose that Ndc1 is a dynamic membrane adaptor that helps recruit and promote the self-assembly of the nuclear pore scaffold to drive post-mitotic NPC assembly.
Modelling, characterization of data-dependent and process-dependent errors in DNA data storage
Authors: Wang Yixin , Noor-A-Rahim Md , Gunawan Erry , Guan Yong Liang , Poh Chueh Loo
Published: July 2021

Motivation

Using DNA as the medium to store information has recently been recognized as a promising solution for long-term data storage. While several system prototypes have been demonstrated, the error characteristics in DNA data storage are discussed with limited content. Due to the data and process variations from experiment to experiment, the error variation and its effect on data recovery remain to be uncovered. To close the gap, we systematically investigate the storage channel, i.e., error characteristics in the storage process.

Results

We first propose a new concept named sequence corruption to unify the error characteristics into the sequence level, easing the channel analysis. Then we derived the formulations of the data imperfection at the decoder including both sequence loss and sequence corruption, revealing the decoding demand and monitoring the data recovery. Furthermore, we extensively explored several data-dependent unevenness observed in the base error patterns and studied a few potential factors and their impacts on the data imperfection at the decoder both theoretically and experimentally. The results presented here introduce a more comprehensive channel model and offer a new angle towards the data recovery issue in DNA data storage by further elucidating the error characteristics of the storage process.

Contact

poh.chuehloo@nus.edu.sg
Using a Quadruplet Codon to Expand the Genetic Code of an Animal
Authors: Xi Zhiyan , Davis Lloyd , Baxter Kieran , Tynan Ailish , Goutou Angeliki , Greiss Sebastian
Published: July 2021

Genetic code expansion in multicellular organisms is currently limited to the use of repurposed amber stop codons. Here we introduce a system for the use of quadruplet codons to direct incorporation of non-canonical amino acids in vivo in an animal, the nematode worm Caenorhabditis elegans. We develop hybrid pyrrolysyl tRNA variants to incorporate non-canonical amino acids in response to the quadruplet codon UAGA. We demonstrate the efficiency of the quadruplet decoding system by incorporating photocaged amino acids into two proteins widely used as genetic tools. We use photocaged lysine to express photocaged Cre recombinase for the optical control of gene expression and photocaged cysteine to express photo-activatable caspase for light inducible cell ablation. Our approach will facilitate the routine adoption of quadruplet decoding for genetic code expansion in eukaryotic cells and multicellular organisms.
Phenotypic plasticity and genetic control in colorectal cancer evolution
Authors: Househam Jacob , Heide Timon , Cresswell George D , Lynn Claire , Spiteri Inmaculada , Mossner Max , Kimberley Chris , Gabbutt Calum , Lakatos Eszter , Fernandez-Mateos Javier , Chen Bingjie , Zapata Luis , James Chela , Berner Alison , Schmidt Melissa , Baker Ann-Marie , Nichol Daniel , Costa Helena , Mitchinson Miriam , Jansen Marnix , Caravagna Giulio , Shibata Darryl , Bridgewater John , Rodriguez-Justo Manuel , Magnani Luca , Sottoriva Andrea , Graham Trevor A
Published: July 2021

Cancer evolution is driven by natural selection acting upon phenotypic trait variation. However, the extent to which phenotypic variation within a tumour is a consequence of intra-tumour genetic heterogeneity remains undetermined. Here we show that colorectal cancer cells frequently have highly plastic phenotypic traitsin vivoin patient tumours. We measured the degree to which trait variation reflects genetic ancestry by quantifying the phylogenetic signal of gene expression across 297 samples with multi-region paired whole genome and transcriptome sequencing collected from 27 primary colorectal cancers. Within-tumour phylogenetic signal for genes and pathways was detected only infrequently, suggesting that the majority of intra-tumour variation in gene expression programmes was not strongly heritable. Expression quantitative trait loci analyses (eQTL) identified a small number of putative mechanisms of genetic control of gene expression due to thecis-acting coding, non-coding and structural genetic alteration, but most gene expression variation was not explained by our genetic analysis. Leveraging matched chromatin-accessibility sequencing data, enhancer mutations withcisregulatory effects on gene expression were associated with a change in chromatin accessibility, indicating that non-coding variation can have phenotypic consequence through modulation of the 3D architecture of the genome. This study maps the evolution of transcriptional variation during cancer evolution, highlighting that intra-tumour phenotypic plasticity is pervasive in colorectal malignancies, and may play key roles in further tumour evolution, from metastasis to therapy resistance.
Gene regulation is commonly selected for high plasticity and low noise
Authors: Vlková Markéta , Silander Olin K.
Published: July 2021

Bacteria often respond to dynamically changing environments by regulating gene expression. Despite this regulation being critically important for growth and survival, little is known about how selection shapes gene regulation in natural populations. To better understand the role natural selection plays in shaping bacterial gene regulation, here we compare differences in the regulatory behaviour of naturally segregating promoter variants from Escherichia coli (which have been subject to natural selection) to randomly mutated promoter variants (which have never been exposed to natural selection). We quantify gene expression phenotypes (expression level, plasticity, and noise) for hundreds of promoter variants across multiple environments, and show that segregating promoter variants are enriched for mutations with minimal effects on expression level. In many promoters, we infer that there is strong selection to maintain high levels of plasticity, and direct selection to decrease or increase cell-to-cell variability in expression. Finally, taking an integrated view, we show that across all phenotypes combined, segregating promoter variants are far more phenotypically similar than would be expected given their genetic divergence. This is the consequence of both stabilizing and directional selection acting on individual phenotypes to minimize differences among segregating variants. Taken together, these results expand our knowledge of how gene regulation is affected by natural selection and highlight the power of comparing naturally segregating polymorphisms to de novo random mutations to quantify the action of selection.