bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Proteomic Changes in Lung after Radiation: Toward Identifying Initiating Events of Delayed Effects of Acute Radiation Exposure in Non-human Primate after Partial Body Irradiation with Minimal Bone Marrow Sparing
Authors: Huang Weiliang , Yu Jianshi , Liu Tian , Defnet Amy E. , Zalesak-Kravec Stephanie , Farese Ann M. , MacVittie Thomas J. , Kane Maureen A.
Published: September 2021

Radiation-induced lung injury is a delayed effect of acute radiation exposure resulting in pulmonary pneumonitis and fibrosis. Molecular mechanisms that lead to radiation-induced lung injury remain incompletely understood. Using a non-human primate model of partial body irradiation with minimal bone marrow sparing, lung was analyzed from animals irradiated with 12 Gy at timepoints every 4 d up to 21 d after irradiation and compared to non-irradiated (sham) controls. Tryptic digests of lung tissues were analyzed by liquid chromatography-tandem mass spectrometry followed by pathway analysis. Out of the 3,101 unique proteins that were identified, we found that 252 proteins showed significant and consistent responses across at least three time points post-irradiation, of which 215 proteins showed strong up-regulation while 37 proteins showed down-regulation. Canonical pathways affected by irradiation, changes in proteins that serve as upstream regulators, and proteins involved in key processes including inflammation, fibrosis, and retinoic acid signaling were identified. The proteomic profiling of lung conducted here represents an untargeted systems biology approach to identify acute molecular events in the non-human primate lung that could potentially be initiating events for radiation-induced lung injury.
Chronic Relapsing Inflammatory Optic Neuropathy (CRION)
Authors: Mukharesh Loulwah , Douglas Vivian Paraskevi , Chwalisz Bart K.
Published: September 2021

Purpose of review

This review highlights the epidemiology, clinical and radiologic characteristics of chronic relapsing inflammatory optic neuropathy (CRION) and treatment modalities.

Recent findings

CRION is an inflammatory optic neuropathy that is characterized by a chronic and relapsing course, that is characterized by pain associated with subacute vision loss. It is favorably responsive but highly dependent on corticosteroids with frequent relapses in the setting of steroid tapering. Additional diagnostic biomarkers and further studies are required to better diagnose and treat this rare but potentially debilitating condition.
Update on mucinous cystic neoplasm of the pancreas: a narrative review
Authors: Xie Wen , Liang Huaiyu , Guo Yan , Xiao Shu-Yuan
Published: September 2021

Mucinous cystic neoplasm (MCN) of the pancreas is an exocrine cystic tumor with a potential of harboring malignancy. The latest World Health Organization classification of tumors of digestive system designates malignant MCN as MCN with associated invasive carcinoma (MCN-AIC). Since its separation from other pancreatic cystic tumors in 1978, much progress has been made in our understanding of MCN in epidemiology, clinical and pathological features, biological behavior, as well as prognostic characteristics. This review aims to summarize the current knowledge of MCN and MCN-AIC.
Significant difference between coagulation parameters and clinicopathological characteristics in breast cancer
Authors: Lei Zhengwu , Guo Dan
Published: September 2021

The purpose of this research is to investigate the correlation between coagulation parameters and survival on patients with breast cancer. A total of 244 patients with breast cancer and 84 patients with metastatic advanced breast cancer admitted to the Second Affiliated Hospital of Chongqing Medical University from January 2017 to February 2019 were selected as the research objects. Their age, tumor size, status of estrogen receptor and progesterone receptor status, status of Her-2 receptor and lymph node were evaluated. Additional 99 cases of benign breast tumors were selected as the control group. All patients were newly diagnosed. PTA, PT ratio, PT, APTT, APTT ratio, TT, TT ratio, PT-INR, FIB, and FDP were detected on all patients. There were significant differences in APTT, APTT ratio, FIB, TT, TT ratio, and FDP between breast cancer and benign tumor control group (P < 0.05). The changes of FIB were correlated with age (P = 0.007), PR status (P = 0.017), and Her-2 status (P = 0.008). The older the age, the higher the FIB level. The FIB level of Er negative state is higher than that of positive state, and the FIB level of PR negative state is also higher than that of positive state. Survival analysis showed that PR negative status, the elevated level of APTT, APTT ratio, TT increased, and TT ratio were the indicators affecting 3-year DFS of patients (P < 0.05). Multivariate COX regression analysis showed that APTT and TT were independent prognostic factors affecting 3 years DFS (P < 0.05). Blood hypercoagulable state in patients with breast cancer, abnormal coagulation system plays an important role in the progress of breast cancer.
Public health concerns and increased risk of severe COVID-19 disease through androgen use
Authors: Crisp Philippe , Sims Jamie
Published: September 2021

Purpose of review

Given governmental policy responses to the COVID-19 pandemic include various foci on establishing preventive measures to increase the health and constitution of populations (i.e. through renewed efforts to tackle obesity), the use of androgens in a recreational manner requires attention because of existing medical evidence related to their role in immunosuppression.

Recent findings

Whilst a broad body of work exists that outlines the mechanisms that underpin COVID-19 and public health responses, as well as the use of androgens in both recreational and medicinal contexts, the recent nature of the disease has left an area requiring greater investigation and clarification. There is emerging literature that highlights the potential complications that existing androgens use may bring to those infected with COVID-19, as well as the start of empirical evidence detailing this.

In this article, we outline the latest viewpoints and literature related to how the use of androgens may contribute to less robust immunoresponses.
Pediatric allergic fungal rhinosinusitis: optimizing outcomes
Authors: Suzuki Masanobu , Connell James , Psaltis Alkis James
Published: September 2021

Purpose of review

Allergic fungal rhinosinusitis (AFRS) is a debilitating condition for children. Despite there being several reviews on this topic in the adult population, there is a paucity of reviews of AFRS in the pediatric literature. This article reviews the recent evidence of pediatric AFRS with the aim to optimize outcomes of pediatric patients with this condition.

Recent findings

AFRS is clinically characterized by nasal polyposis, a type I hypersensitivity to fungal epitopes, very thick eosinophilic mucin, and peripheral eosinophilia. Pediatric AFRS has similar clinical characteristics to that in adults but is thought to have a more aggressive nature, with higher serum immunoglobulin E and more frequently bone erosion and malformation of facial bones. Diagnosis of pediatric AFRS is made by using the Bent and Kuhn's criteria developed for adult AFRS. The mainstay of treatment is surgery followed by postoperative corticosteroids. Adjunctive therapies, including topical/oral antifungal agents, allergen immunotherapy and biologics may improve outcomes in pediatric AFRS, but to date the current evidence is limited.

To optimize the outcome of pediatric AFRS, adequate and early diagnosis and treatment are essential. Appropriate and comprehensive endoscopic sinus surgery to open the sinuses, remove the fungal burden of disease and improve access of the sinuses to postoperative topical corticosteroid remains the standard of care.
NordiQC Assessments of Synaptophysin Immunoassays
Authors: Vyberg Mogens , Nielsen Søren , Bzorek Michael , Røge Rasmus
Published: September 2021

This paper is number 8 in a series developed through a partnership between ISIMM and NordiQC with the purpose of reporting research assessing the performance characteristics of immunoassays in an external proficiency testing program.
An Analysis of the Impact of Timing and Technique on Outcomes after Surgery for Distal Radius Fractures: The Wrist and Radius Injury Surgical Trial Collaborative Study
Authors: Hooper Rachel C. , Zhou Nina , Wang Lu , Shauver Melissa J. , Chung Kevin C.
Published: September 2021

Background:

Surgical treatment of closed distal radius fractures varies based on treatment, surgeon schedule, and patient preferences. The authors examined how timing and technique impact surgeon-perceived procedural difficulty and quality of reduction, outcomes, and complications.

Methods:

This was a retrospective study of participants in the randomized, multicenter Wrist and Radius Injury Surgical Trial with isolated unstable distal radius fractures. Participants were randomized to treatment with a volar locking plate system, closed reduction and percutaneous pinning, or external fixation. The authors analyzed surgeon-perceived procedural difficulty and reduction quality based on time to operation.

Results:

Of 184 participants, 88 underwent surgery less than 7 days after fracture (mean, 4.6 days) and 96 underwent surgery at more than 7 days after fracture (mean, 12.3 days). Surgery performed at more than 7 days was rated more difficult versus surgery at less than 7 days [4.6 versus 3.8 of 10 (1 = easiest); p = 0.05]. When the volar locking plate technique was performed, there was no difference in surgeon-perceived difficulty or reduction quality between the groups; however, surgeons performing closed reduction and percutaneous pinning more than 7 days after injury reported greater procedure difficulty (4.1 versus 2.9; p = 0.05) and poorer reduction quality compared to less than 7 days (7.2 versus 8.1; p = 0.03). Participants who underwent surgery at less than 7 days scored 8 and 7 points greater on the Michigan Hand Outcomes Questionnaire Satisfaction (p = 0.05) and Activities of Daily Living (p = 0.03) domains, respectively.

Conclusions:

Surgery performed less than 7 days after fracture leads to better surgeon-perceived reduction quality and less procedural difficulty. If surgery cannot be performed before 7 days, the authors recommend patients undergo treatment with the volar locking plate system, given the comparable level of surgeon-perceived procedural difficulty and reduction quality when surgery was performed less than 7 days after injury.

CLINICAL QUERSTION/LEVEL OF EVIDENCE:

Therapeutic, III.
A Comparative Assessment of Nasal Appearance following Nasoalveolar Molding and Primary Surgical Repair for Treatment of Unilateral Cleft Lip and Palate
Authors: Kurnik Nicole M. , Calis Mert , Sobol Danielle L. , Kapadia Hitesh , Mercan Ezgi , Tse Raymond W.
Published: September 2021

Background:

Although many cleft teams have adopted nasoalveolar molding to improve nasal form, few comparative studies have assessed the postoperative benefits of this treatment. Given that reported outcomes have been contradictory and that treatment involves considerable burden to families, the purpose of this study was to assess objective and subjective changes from nasoalveolar molding at approximately 5 years of age.

Methods:

All patients with complete unilateral cleft lip and palate who underwent primary cheiloplasty performed by a single surgeon over a 7-year period were reviewed. Patient results were grouped into nasoalveolar molding or no–nasoalveolar molding. Cleft severity and aesthetic outcomes were assessed by panels of raters who independently ranked subject images at presentation, immediately preoperative (after molding), and at 5-year follow-up. Objective symmetry was measured using standard anthropometric analysis on three-dimensional images.

Results:

Among 41 patients included, 16 successfully completed nasoalveolar molding. Both groups were similar at presentation; however, the nasoalveolar molding group had improved appearance following molding (p < 0.05). After surgery, at 5 years of age, the nasoalveolar molding group had better rank scores for overall appearance (p < 0.05), cleft nostril height, and cleft medial lip height (p < 0.05). Regression analysis revealed that nasoalveolar molding treatment was the most significant predictor of overall nasal appearance at 5 years, but that treatment team experience and initial severity were also significant predictors (p < 0.05). Qualitative audit following analysis identified favorable and unfavorable features of nasoalveolar molding.

Conclusion:

In children with complete unilateral cleft lip and palate, nasoalveolar molding was associated with better overall nasal aesthetics and improved cleft nostril height and cleft medial lip height at approximately 5 years of age.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Novel strategies for prevention and treatment of antimicrobial resistance in sexually-transmitted infections
Authors: Williams Eloise , Fairley Christopher K. , Williamson Deborah
Published: September 2021

Purpose of review

Antimicrobial resistance in sexually acquired infection (STI) pathogens is an important global public health threat. There is an urgent need for novel STI treatment and prevention strategies to tackle the rising incidence of STIs in high-income settings and the static progress in low- and middle-income settings over the past decade. The purpose of this review was to describe the research outlining the emergence of resistance in common STI pathogens and new strategies for their treatment and prevention.

Recent findings

Rates of STIs have dramatically increased over the past decade. Further, antimicrobial resistance to first-line agents among key STI pathogens continues to emerge globally. Recent findings demonstrate promising results regarding the efficacy of novel antimicrobial treatment strategies for these pathogens, including several new, repurposed and unique combinations of antimicrobials. In addition, a number of new biomedical prevention strategies, such as antibacterial mouthwash and doxycycline chemoprophylaxis, are being investigated as novel prevention strategies for bacterial STIs.

Significant progress has been made in the development of novel antimicrobials for the treatment of antimicrobial-resistant sexually acquired pathogens. However, due to the rapid development of resistance to antimicrobials demonstrated by these pathogens in the past, further research and development of effective prevention strategies should be prioritized.
Skeletal Stability of Two-Jaw Surgery Without Bone Grafting in Patients With Cleft Lip and Palate
Authors: Jang Hun , Park Jin-Young , Choi Na-Rae , Hwang Dae-Seok
Published: September 2021

Purpose:

The purpose of this study was to evaluate the postoperative skeletal stability of orthognathic surgery performed without a bone graft in cleft lip and palate patients.

Patients and Methods:

Nineteen cleft lip and palate patients that underwent orthognathic surgery from July 2008 to August 2019 at the Department of Oral and Maxillofacial Surgery of Pusan National University Dental Hospital were selected. None of these patients underwent bone grafting during orthognathic surgery. Lateral cephalograms were taken 1 month before surgery (T0), immediately after surgery (T1), and 6 months after surgery (T2). Lateral cephalograms were analyzed using the V-Ceph program. The analysis was performed using SPSS for Windows version 26.0. The analysis was conducted by repeated-measures analysis of variance.

Results:

A total of 19 patients were included in this retrospective study (9 males/10 females of overall mean age 22 ± 4.89 years). Mean maxillary depth values at the 3-time points were 85.37° ± 2.62° (T0), 90.13° ± 2.77° (T1), and 89.29° ± 2.91° (T2). Mean McNamara–N Perpend values were −5.52 ± 3.19 mm (T0), 0.09 ± 3.10 mm (T1), and −0.83 ± 3.14 mm (T2). Mean sella nasion point A (SNA) values were 75.42° ± 2.98° (T0), 79.19° ± 2.94° (T1), and 78.45° ± 2.84° (T2). Mean relapse rates were maxillary depth 20.15%, McNamara–N Perpend 17.95%, and SNA 18.74%. Mean horizontal advancement was 5.61 ± 2.32 mm based on McNamara vertical to A point, mean horizontal relapse was -0.92 ± 0.56 mm, and the mean horizontal relapse rate was 17.95%.

Conclusions:

Favorable skeletal stability can be obtained without bone graft when the amount of maxillary advancement is less than 6 mm in cleft patients.
Three-Dimensional Motion Capture of a Smile in Repaired Unilateral Cleft Lip: What's Our Vector, Victor?
Authors: Seaward James R. , Ainuz Bar Y. , Zhao Connie , Hallac Rami R.
Published: September 2021

Introduction:

Following surgical repair, patients with unilateral cleft lip (UCL) exhibit dynamic asymmetry during facial expressions compared to healthy individuals. Previous studies using Euclidean distances to describe this asymmetry fail to take the direction of the movement into account. The aim of this study is to compare differences in participants with UCL and controls using analysis of motion vectors during facial expressions.

Methods:

In this cross-sectional study, twenty-six pediatric participants were recruited: 13 participants with repaired left UCL and 13 participants with no craniofacial diagnosis. Participants were recorded performing a maximal smile by a 4D stereophotogrammetric system. Phases of the smile were divided into closed lip and open lip smiles. Ten regions of interest were analyzed: subnasal area, upper lip, lower lip, oral commissure, and ala on both sides. The motion vectors were calculated and vector magnitude and direction for each region was compared.

Results:

Between cleft and control groups, the differences in vector direction were greater than the magnitude differences. Significant differences in vector direction were identified at both oral commissures in the closed lip smile; and at the oral commissure, subnasal, upper lip, and lower lip regions during open lip smile.

Conclusions:

Vector analysis demonstrated significant movement asymmetry during facial animation in participants following UCL repair, not previously identified when analyzing magnitude of skin displacement.
A Multicenter Retrospective Study Comparing Surgical Outcomes Between the Overlap Method and Functional Method for Esophagojejunostomy in Laparoscopic Total Gastrectomy: Analysis Using Propensity Score Matching
Authors: Ebihara Yuma , Kurashima Yo , Tanaka Kimitaka , Nakanishi Yoshitsugu , Asano Toshimichi , Noji Takehiro , Nakamura Toru , Murakami Soichi , Tsuchikawa Takahiro , Okamura Keisuke , Murakami Yoshihiro , Murakawa Katsuhiko , Nakamura Fumitaka , Morita Takayuki , Okushiba Shunichi , Shichinohe Toshiaki , Hirano Satoshi
Published: September 2021

Background:

This study aimed to compare the postoperative outcomes after laparoscopic total gastrectomy (LTG) with esophagojejunostomy (EJS) performed using the overlap method or the functional method in a multicenter retrospective study with propensity score matching.

Methods:

We retrospectively enrolled all patients who underwent curative LTG for gastric cancer at 6 institutions between January 2004 and December 2018. Patients were categorized into the overlap group (OG) or functional group (FG) based on the type of anastomosis used in EJS. Patients in the groups were matched using the following propensity score covariates: age, sex, body mass index, American Society of Anesthesiologists physical status, extent of lymph node dissection, and Japanese Classification of Gastric Carcinoma stage. The surgical results and postoperative outcomes were compared.

Results:

We identified 69 propensity score-matched pairs among 440 patients who underwent LTG. There was no significant between-group difference in the median operative time, intraoperative blood, or number of lymph nodes resected. In terms of postoperative outcomes, the rates of all complications [Clavien-Dindo (CD) classification ≥II; OG 13.0 vs. FG 24.6%, respectively; P=0.082], complications more severe than CD grade III (OG 8.7 vs. FG 18.8%, respectively; P=0.084), and the occurrence of EJS leakage and stenosis more severe than CD grade III (OG 7.3% vs. FG 2.9%, P=0.245; OG 1.5 vs. FG 8.7%, P=0.115, respectively) were comparable. The median follow-up period was 830 days (range, 18 to 3376 d), and there were no differences in overall survival between the 2 groups.

Conclusions:

There was no difference in surgical outcomes and overall survival based on the type of anastomosis used for EJS after LTG. Therefore, selection of anastomosis in EJS should be based on each surgeon’s preference and experience.
High SARS-CoV-2 viral load is associated with a worse clinical outcome of COVID-19 disease
Authors: Soria María Eugenia , Cortón Marta , Martínez-González Brenda , Lobo-Vega Rebeca , Vázquez-Sirvent Lucía , López-Rodríguez Rosario , Almoguera Berta , Mahillo Ignacio , Mínguez Pablo , Herrero Antonio , Taracido Juan Carlos , Macías-Valcayo Alicia , Esteban Jaime , Fernandez-Roblas Ricardo , Gadea Ignacio , Ruíz-Hornillos Javier , Ayuso Carmen , Perales Celia
Published: September 2021

COVID-19 severity and progression are determined by several host and virological factors that may influence the final outcome of SARS-CoV-2-infected patients. The objective of this work was to determine a possible association between viral load, obtained from nasopharyngeal swabs, and the severity of the infection in a cohort of 448 SARS-CoV-2-infected patients from a hospital in Madrid during the first outbreak of the pandemic in Spain. To perform this, we clinically classified patients as mild, moderate and severe COVID-19 according to a number of clinical parameters such as hospitalization requirement, need of oxygen therapy, admission to intensive care units and/or death. Also, Ct values were determined using SARS-CoV-2-specific oligonucleotides directed to ORF1ab. Here we report a statistically significant association between viral load and disease severity, a high viral load being associated with worse clinical prognosis, independently of several previously identified risk factors such as age, sex, hypertension, cardiovascular disease, diabetes, obesity and lung disease (asthma and chronic obstructive pulmonary disease). The data presented here reinforce viral load as a potential biomarker for predicting disease severity in SARS-CoV-2-infected patients. It is also an important parameter in viral evolution since it relates to the numbers and types of variant genomes present in a viral population, a potential determinant of disease progression.
Phylogenomic and comparative genomic analyses of species of the family Pseudomonadaceae: Proposals for the genera Halopseudomonas gen. nov. and Atopomonas gen. nov., merger of the genus Oblitimonas with the genus Thiopseudomonas, and transfer of some misclassified species of the genus Pseudomonas into other genera
Authors: Rudra Bashudev , Gupta Radhey S.
Published: September 2021

The evolutionary relationships among species of the family

Pseudomonadaceae

were examined based on 255 available genomes representing >85 % of the species from this family. In a phylogenetic tree based on concatenated sequences of 118 core proteins, most species of the genus

Pseudomonas

grouped within one large cluster which also included members of the genera

Azotobacter

and

Azomonas

. Within this large cluster 18–30 clades/subclades of species of the genus

Pseudomonas

consisting of between 1 and 36 species, were observed. However, a number of species of the genus

Pseudomonas

branched outside of this main cluster and were interspersed among other genera of the family

Pseudomonadaceae

. This included a strongly supported clade (Pertucinogena clade) consisting of 19 mainly halotolerant species. The distinctness of this clade from all other members of the family

Pseudomonadaceae

is strongly supported by 24 conserved signature indels (CSIs) in diverse proteins that are exclusively found in all members of this clade. Nine uncharacterized members of the genus

Pseudomonas

also shared these CSIs and they branched within the Pertucinogena clade, indicating their affiliation to this clade. On the basis of the strong evidence supporting the distinctness of the Pertucinogena clade, we are proposing transfer of species from this clade into a novel genus Halopseudomonas gen. nov.

Pseudomonas caeni

also branches outside of the main cluster and groups reliably with

Oblitimonas alkaliphila

and

Thiopseudomonas denitrificans

. Six identified CSIs are uniquely shared by these three species and we are proposing their integration into the emended genus

Thiopseudomonas

, which has priority over the name

Oblitimonas

. We are also proposing transfer of the deep-branching

Pseudomonas hussainii

, for which 22 exclusive CSIs have been identified, into the genus Atopomonas gen. nov. Lastly, we present strong evidence that the species

Pseudomonas cissicola

and

Pseudomonas geniculata

are misclassified into the genus

Pseudomonas

and that they are specifically related to the genera

Xanthomonas

and

Stenotrophomonas

, respectively. In addition, we are also reclassifying ‘Pseudomonas acidophila’ as Paraburkholderia acidicola sp. nov. (Type strain: G-6302=ATCC 31363=BCRC 13035).
Spatiotemporal analyses illuminate the competitive advantage of a SARS-CoV-2 variant of concern over a variant of interest
Authors: Russell Alexis , O’Connor Collin , Lasek-Nesselquist Erica , Plitnick Jonathan , Kelly John P. , Lamson Daryl M. , George Kirsten St.
Published: September 2021

The emergence of novel SARS-CoV-2 variants in late 2020 and early 2021 raised alarm worldwide and prompted reassessment of the management, surveillance, and projected future of COVID-19. Mutations that confer competitive advantages by increasing transmissibility or immune evasion have been associated with the localized dominance of single variants. Thus, elucidating the evolutionary and epidemiological dynamics among novel variants is essential for understanding the trajectory of the COVID-19 pandemic. Here we show the interplay between B.1.1.7 (Alpha) and B.1.526 (Iota) in New York (NY) from December 2020 to April 2021 through phylogeographic analyses, space-time scan statistics, and cartographic visualization. Our results indicate that B.1.526 likely evolved in the Bronx in late 2020, providing opportunity for an initial foothold in the heavily interconnected New York City (NYC) region, as evidenced by numerous exportations to surrounding locations. In contrast, B.1.1.7 became dominant in regions of upstate NY where B.1.526 had limited presence, suggesting that B.1.1.7 was able to spread more efficiently in the absence of B.1.526. Clusters discovered from the spatial-time scan analysis supported the role of competition between B.1.526 and B.1.1.7 in NYC in March 2021 and the outsized presence of B.1.1.7 in upstate NY in April 2021. Although B.1.526 likely delayed the rise of B.1.1.7 in NYC, B.1.1.7 became the dominant variant in the Metro region by the end of the study period. These results reveal the advantages endemicity may grant to a variant (founder effect), despite the higher fitness of an introduced lineage. Our research highlights the dynamics of inter-variant competition at a time when B.1.617.2 (Delta) is overtaking B.1.1.7 as the dominant lineage worldwide. We believe our combined spatiotemporal methodologies can disentangle the complexities of shifting SARS-CoV-2 variant landscapes at a time when the evolution of variants with additional fitness advantages is impending.
Environmental factors and mobility predict COVID-19 seasonality
Authors: Hoogeveen Martijn J. , Kroes Aloys C.M. , Hoogeveen Ellen K.
Published: September 2021

Background

We recently showed that seasonal patterns of COVID-19 incidence and Influenza-Like Illnesses incidence are highly similar, in a country in the temperate climate zone, such as the Netherlands (latitude: 52°N). We hypothesize that in The Netherlands the same environmental factors and mobility trends that are associated with the seasonality of flu-like illnesses are predictors of COVID-19 seasonality as well.

Methods

We used meteorological, pollen/hay fever and mobility data from the Netherlands with its 17.4 million inhabitants. For the reproduction number of COVID-19 (Rt), we used data from the Dutch State Institute for Public Health. This Rt metric is a daily estimate that is based on positive COVID-19 tests in the Netherlands in hospitals and municipalities. For all datasets we selected the overlapping period of COVID-19 and the first allergy season: from February 17, 2020 till September 21, 2020 (total number of measurements: n = 218), the end of pollen season. Backward stepwise multiple linear regression was used to develop an environmental prediction model of the Rt of COVID-19. Next, we studied whether adding mobility trends to an environmental model improved the predictive power.

Results

By means of stepwise backward multiple linear regression four highly significant (p value < 0.01) predictive factors are selected in our combined model: temperature, solar radiation, hay fever incidence, and mobility to indoor recreation locations. Our combined model explains 87.5% of the variance of Rt of COVID-19 and has a good and highly significant fit: F(4, 213) = 374.2, p-value < 0.00001. The combined model had a better overall predictive performance compared to a solely environmental model, which still explains 77.3% of the variance of Rt, and a good and highly significant fit: F(4, 213) = 181.3, p < 0.00001.

Conclusions

We conclude that the combined mobility and environmental model can adequately predict the seasonality of COVID-19 in a country with a temperate climate like the Netherlands. In this model higher solar radiation, higher temperature and hay fever are related to lower COVID-19 reproduction, and mobility to indoor recreation locations with increased COVID-19 spread.

Highlights

The seasonality of COVID-19 can be well-explained by environmental factors and mobility.

A combined model explains 87.5% of the variance of the reproduction number of COVID-19

Inhibitors of the reproduction number of COVID-19 are higher solar radiation, and seasonal allergens/allergies.

Mobility, especially to indoor recreation locations, increases the reproduction number of COVID-19.

Temperature has no direct effect on the reproduction number of COVID-19, but affects mobility and seasonal allergens.

Adding mobility trends to an environmental model improves the predictive value regarding the reproduction number of COVID-19.
Impaired Lymphocyte Responses in Pediatric Sepsis Vary by Pathogen Type
Authors: Lindell Robert B. , Zhang Donglan , Bush Jenny , Wallace Douglas C. , Rabinowitz Joshua D. , Lu Wenyun , Wherry E. John , Weiss Scott L. , Henrickson Sarah E.
Published: September 2021

Background

Sepsis is the leading cause of death in hospitalized children worldwide. Despite its hypothesized immune-mediated mechanism, targeted immunotherapy for sepsis is not available for clinical use.

Objective

To determine the association between cytometric, proteomic, bioenergetic, and metabolomic abnormalities and pathogen type in pediatric sepsis.

Methods

Serial PBMC samples were obtained from 14 sepsis patients (34 samples) and 7 control patients for this pilot study. Flow cytometry was used to define immunophenotype, including T cell subset frequency and activation state, and assess intracellular cytokine production. Global immune dysfunction was assessed by TNF-production capacity and monocyte HLA-DR expression. Mitochondrial function was assessed by bulk respirometry. Plasma cytokine levels were determined via Luminex assay. Metabolites were measured by liquid chromatography-mass spectrometry. Results were compared by timepoint and pathogen type.

Results

Sepsis patients were older and had higher illness severity compared to controls; demographics were otherwise similar. Compared to controls, sepsis patients demonstrated global immune dysfunction, loss of peripheral of non-naïve CD4+ T cells, and reduced PBMC mitochondrial function. Metabolomic findings in sepsis patients were most pronounced at sepsis onset and included elevated uridine and 2-dehydrogluconate and depleted citrulline. Loss of peripheral non-naïve CD4+ T cells was associated with immune dysfunction and reduced cytokine production despite increased T cell activation. CD4+ T cell differentiation and corresponding pro- and anti-inflammatory cytokines varied by pathogen.

Conclusion

Pediatric sepsis patients exhibit a complex, dynamic physiologic state characterized by immunometabolic dysregulation which varies by pathogen type.
Characterisation of the blood RNA host response underpinning severity in COVID-19 patients
Authors: Jackson Heather , Calle Irene Rivero , Broderick Claire , Habgood-Coote Dominic , d’Souza Giselle , Nichols Samuel , Gómez-Rial Jose , Rivero-Velasco Carmen , Rodríguez-Núñez Nuria , Barbeito-Castiñeiras Gema , Pérez-Freixo Hugo , Acosta Manuel Barreiro-de , Cunnington Aubrey J. , Herberg Jethro A. , Wright Victoria J. , Gómez-Carballa Alberto , Salas Antonio , Levin Mike , Martinon-Torres Federico , Kaforou Myrsini ,   PERFORM consortium and GEN-COVID study group
Published: September 2021

Infection with SARS-CoV-2 has highly variable clinical manifestations, ranging from asymptomatic infection through to life-threatening disease. Host whole blood transcriptomics can offer unique insights into the biological processes underpinning infection and disease, as well as severity. We performed whole blood RNA Sequencing of individuals with varying degrees of COVID-19 severity. We used differential expression analysis and pathway enrichment analysis to explore how the blood transcriptome differs between individuals with mild, moderate, and severe COVID-19, performing pairwise comparisons between groups. Increasing COVID-19 severity was characterised by an abundance of inflammatory immune response genes and pathways, including many related to neutrophils and macrophages, in addition to an upregulation of immunoglobulin genes. Our insights into COVID-19 severity reveal the role of immune dysregulation in the progression to severe disease and highlight the need for further research exploring the interplay between SARS-CoV-2 and the inflammatory immune response.
Blood biochemical parameters as predictors of disease severity and mortality in COVID-19 patients- an updated systematic review and meta-analysis
Authors: Majid Afsha , Mishra Pinki , Parveen Rizwana , Bajpai Ram , Khan Mohd. Ashif , Agarwal Nidhi Bharal
Published: September 2021

Background

The outbreak of coronavirus disease 2019 (COVID-19) has been rapidly spreading across the globe and poses a great risk to human health. Patients with abnormalities in laboratory parameters are more susceptible to COVID-19. Therefore, we explored the association of blood biochemical parameters with severity and mortality of COVID-19 amongst 3695 patients across seventeen studies.

Methods

We searched PubMed, Cochrane library and LitCOVID database until February 28, 2021. Seventeen studies were included in the meta-analysis with 3695 COVID-19 patients.

Results

The pooled analysis showed that compared to non-severe group, severe group was characterised by significantly elevated alanine aminotransferase (ALT) (standardised mean difference [SMD]: 0.65, 95% confidence interval [CI]: 0.23 to 1.06; p<0.001, erythrocyte sedimentation rate (ESR) (SMD: 0.55, 95%CI: 0.02 to 1.07 p=0.004) and lymphopenia (SMD: -1.22, 95% CI: -2.15 to -0.30; p<0.01), decreased serum albumin (SMD: -1.60, 95% CI: -2.96 to -0.22 ; p<0.001), creatinine (SMD: 0.54, 95% CI: 0.17 to 0.90; p<0.001), lactate dehydrogenase (LDH)(SMD: -1.54, 95% CI: - 2.27 to -0.80; p=0.002) and haemoglobin (SMD:-0.89, 95% CI: ; p<0.001). Additionally, in the non-survivor group, elevated lactate dehydrogenase (LDH) (SMD: 1.54 95% CI: -2.27 to 0.80; p=0.002), decreased serum albumin (SMD: 1.08, 95% CI: 0.75 to 1.42; p<0.001) were reported. There was no comorbidity which was found to be significant in the severe group.

Conclusion

Serum albumin, ALT, ESR, lymphopenia, haemoglobin, and leucocytosis can reflect the severity of COVID-19, while the LDH, leucocytosis and albumin can be considered as risk factor to higher mortality.

Our manuscript discusses the various blood biochemical markers as potential predictors of disease severity and mortality in COVID-19 patients. The timely detection of these parameters can help in providing appropriate course of treatment and reducing the mortality rate in the patients. We have found an association between the blood biochemical markers and disease severity and mortality in COVID-19 patients. Serum albumin, alanine aminotransferase (ALT), Erythrocyte Sedimentation Rate (ESR), lymphopenia, hemoglobin, and leukocytosis can reflect the severity of the disease, while the LDH, leukocytosis and albumin can be considered as risk factor to higher mortality.
Association of inflammatory markers with severity of disease and mortality in COVID-19 patients: a systematic review and meta-analysis
Authors: Khan Sara , Mishra Pinki , Parveen Rizwana , Bajpai Ram , Khan Mohd Ashif , Agarwal Nidhi Bharal
Published: September 2021

Purpose

Literature suggests association of inflammatory markers with the severity and mortality related to COVID-19, but there are varying conclusions available. We aimed to provide an overview of the association of inflammatory markers with the severity and mortality of COVID-19 patients.

Methods

We searched Medline (via PubMed), Cochrane, Clinicaltrials.gov databases until Sept 1, 2020.

Results

A total of 21 studies comprising 4023 patients with COVID-19 were included in our analysis. Levels of IL-6 (WMD=18.17 95%CI 3.38 to 32.96, p=0.016), IL-8 (WMD=12.09 95%CI 4.41 to 19.77, p=0.002), MCP-1 (WMD=146.66 95%CI 88.16 to 205.16, p<0.001), CRP (WMD=31.09 95%CI 10.08 to 52.10, p=0.004), PCT (WMD= -31.23 95%CI -37.70 to -24.76, p<0.001), IL-2R (WMD=861.93 95%CI 275.45 to 1448.41, p=0.004), ferritin (WMD= 1083.34 95%CI 431.99 to 1734.70, p=0.001) were found significantly higher in the severe group compared with the non-severe group of COVID-19 patients. Moreover, non-survivors had a higher levels of IL-2R (WMD= -666.06 95%CI -782.54 to -549.59, p<0.001), IL-8 (WMD= -26.63 95%CI -33.031 to -20.236, p<0.001), IL-10 (WMD= -7.60 95%CI -8.93 to -6.26, p<0.001), TNF-α (WMD= -4.60 95%CI -5.71 to -3.48, p<0.001), IL-1β (WMD=22.66 95%CI 8.13 to 37.19, p=0.002), CRP (WMD= -96.40 95%CI -117.84 to -74.97, p<0.001), and ferritin (WMD= -937.60 95%CI -1084.15 to -791.065, p<0.001) when compared to the non-survivor group.

Conclusion

This meta-analysis highlights the association of inflammatory markers with the severity and mortality of COVID-19 patients. Measurement of these inflammatory markers may assist clinicians to monitor and evaluate the severity and prognosis of COVID-19 thereby reducing the mortality rate.
Risk of heart disease following breast cancer: results from a population-based cohort study
Authors: Yang Haomin , Bhoo-Pathy Nirmala , Brand Judith S. , Hedayati Elham , Grassmann Felix , Zeng Erwei , Bergh Jonas , Bian Weiwei , Ludvigsson Jonas F. , Hall Per , Czene Kamila
Published: September 2021

BACKGROUND

There is a rising concern about treatment-associated cardiotoxicities in breast cancer patients.

OBJECTIVES

This study aimed to determine the time- and treatment-specific incidence of arrhythmia, heart failure and ischemic heart disease in women diagnosed with breast cancer.

METHODS

A register-based matched cohort study was conducted including 8338 breast cancer patients diagnosed from 2001-2008 in the Stockholm-Gotland region and followed-up until 2017. Overall and time dependent risks of arrhythmia, ischemic heart disease and heart failure in breast cancer patients were assessed using flexible parametric models as compared to matched controls from general population. Treatment-specific effects were estimated in breast cancer patients using Cox model.

RESULTS

During a median follow-up of 10.8 years, the hazard ratios for arrhythmia, heart failure and ischemic heart disease, were 1.27 (95% CI = 1.18-1.37), 1.38 (95% CI = 1.23-1.55), and 0.93 (95% CI = 0.84-1.03), respectively. Time-dependent analyses revealed long-term increased risks of arrhythmia, and heart failure in breast cancer patients compared to matched controls. The risk of ischemic heart disease was only elevated in the first year after cancer diagnosis. Trastuzumab and anthracyclines were associated with increased risk of heart failure. Aromatase inhibitors, but not tamoxifen, were associated with risk of ischemic heart disease. No increased risk of heart disease was identified following loco-regional radiotherapy.

CONCLUSIONS

Administration of systemic adjuvant therapies appear to be associated with increased risks of heart disease. The risk estimates observed in this study may serve as reference to aid adjuvant therapy decision-making and patient counseling in oncology practices.
A novel method for an unbiased estimate of cross-ancestry genetic correlation using individual-level data
Authors: Momin Md. Moksedul , Shin Jisu , Lee Soohyun , Truong Buu , Benyamin Beben , Lee S. Hong
Published: September 2021

Cross-ancestry genetic correlation is an important parameter to understand the genetic relationship between two ancestry groups for a complex trait. However, existing methods cannot properly account for ancestry-specific genetic architecture, which is diverse across ancestries, producing biased estimates of cross-ancestry genetic correlation. Here, we present a method to construct a genomic relationship matrix (GRM) that can correctly account for the relationship between ancestry-specific allele frequencies and ancestry-specific causal effects. Through comprehensive simulations, we show that the proposed method outperforms existing methods in the estimations of SNP-based heritability and cross-ancestry genetic correlation. The proposed method is further applied to six anthropometric traits from the UK Biobank data across 5 ancestry groups. One of our findings is that for obesity, the estimated genetic correlation between African and European ancestry cohorts is significantly different from unity, suggesting that obesity is genetically heterogenous between these two ancestry groups.
The supramolecular organization of SARS-CoV and SARS-CoV-2 virions revealed by coarse-grained models of intact virus envelopes
Authors: Wang Beibei , Zhong Changqing , Tieleman D. Peter
Published: September 2021

The coronavirus disease 19 (COVID-19) pandemic is causing a global health crisis and has already caused a devastating societal and economic burden. The pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a high sequence and architecture identity with SARS-CoV, but far more people have been infected by SARS-CoV-2. Here, combining structural data from cryo-EM and structure prediction, we constructed bottom-up Martini coarse-grained models of intact SARS-CoV and SARS-CoV-2 envelopes. Microsecond molecular dynamics simulations were performed, allowing us to explore their dynamics and supramolecular organization. Both SARS-CoV and SARS-CoV-2 envelopes present a spherical morphology with structural proteins forming multiple string-like islands in the membrane and clusters between heads of spike proteins. Critical differences between the SARS-CoV and SARS-CoV-2 envelopes are the interaction pattern between spike proteins and the flexibility of spike proteins. Our models provide structural and dynamic insights in the SARS virus envelopes, and could be used for further investigation, such as drug design, and fusion and fission processes.
A shared brain system forming confidence judgment across cognitive domains
Authors: Rouault Marion , Lebreton Maël , Pessiglione Mathias
Published: September 2021

Confidence is typically defined as a subjective judgment about whether a decision is right. Decisions are based on sources of information that come from various cognitive domains and are processed in different brain systems. An unsettled question is whether the brain computes confidence in a similar manner whatever the domain or in a manner that would be idiosyncratic to each domain. To address this issue, human participants of both sexes performed two tasks probing confidence in decisions made about the same material (history and geography statements), but based on different cognitive processes: semantic memory for deciding whether the statement was true or false, and duration perception for deciding whether the statement display was long or short. At the behavioral level, we found that the same factors (difficulty, accuracy, response time and confidence in the preceding decision) predicted confidence judgments in both tasks. At the neural level, we observed using fMRI that confidence judgments in both tasks were associated to activity in the same brain regions: positively in the ventromedial prefrontal cortex and negatively in a prefronto-parietal network. Together, these findings suggest the existence of a shared brain system that generates confidence judgments in a similar manner across cognitive domains.
Myelin Imaging Using Dual-echo 3D Ultra-short Echo Time MRI with Rosette k-Space Pattern
Authors: Shen Xin , Özen Ali Caglar , Sunjar Antonia , Ilbey Serhat , Shi Riyi , Chiew Mark , Emir Uzay
Published: September 2021

Purpose

This study aimed to develop a new 3D dual-echo rosette k-space trajectory, specifically for ultra-short echo time (UTE) magnetic resonance imaging (MRI) applications. The direct imaging of the myelin bilayer, which has ultra-short transverse relaxation time (uT2), was acquired to test the performance of the proposed UTE sequence.

Theory and Methods

The rosette trajectory was developed based on rotations of a ‘petal-like’ pattern in the kx-kyplane, with oscillated extensions in kz-direction for 3D coverage. Five healthy volunteers were recruited and underwent ten dual-echo 3D rosette UTE scans with various echo times (TEs). Dual-exponential complex model fitting was performed on the magnitude data to separate uT2signals, with the output of uT2fraction, uT2value, and long T2value.

Results

The reconstructed images’ signal contrast between whiate matter (WM) and grey matter (GM) increased with longer TEs. The WM regions had higher uT2fraction values than GM (10.9%±1.9% vs. 5.7%±2.4%). The uT2value was approximately 0.15 milliseconds in WM.

Conclusion

The higher uT2fraction value in WM compared to GM demonstrated the ability of the proposed sequence to capture rapidly decaying signals.