bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Recurrence Detection of Glioma Using 18F-Fluorocholine PET/CT
Authors: García Vicente Ana María , Amo-Salas Mariano , Sandoval Valencia Hernán , Lozano Setien Elena , Soriano Castrejón Ángel María
Published: July 2022

Objective

The aim of this study was to analyze the usefulness of 18F-fluorocholine PET/CT in the early diagnosis of tumor recurrence, increasing the diagnosis confidence of MRI.

Methods

Patients with a previous gross total resection of glioma and the first suspicious or doubtful for recurrence MRI were prospectively included and subjected to 18F-fluorocholine PET/CT. An independent and combined assessment of 18F-fluorocholine PET/CT and multimodal MRI was performed classifying the studies as positive or negative for tumor recurrence. Final diagnosis (recurrence or not) was obtained by histological confirmation or clinical and imaging follow-up. The relation of SUVmax and tumor-to-background ratio with progression, the diagnostic performance of imaging techniques, and their concordance (κ Cohen) were analyzed.

Results

Twenty-four studies on 21 patients were assessed. Recurrence was diagnosed in 20 cases. PET/CT was positive in 23 cases (3 false positive), whereas MRI was positive in 15 cases (1 false positive). MRI was false negative in 6 cases. There was no false negative on 18F-fluorocholine PET/CT. Accuracy of PET/CT versus MRI was 87.5% and 70.8%, respectively. The combined evaluation of both techniques did not show any advantage with respect to PET/CT results alone. The concordance between both imaging techniques was low (κ = 0.135; P = 0.375). SUVmax and tumor-to-background ratio were related to recurrence (areas under the curve of 0.844 [P = 0.033] and 0.869 [P = 0.022], respectively).

Conclusions

18F-fluorocholine PET/CT was helpful for increasing the diagnostic confidence in the cases of MRI doubtful for recurrence in order to avoid a delayed diagnosis.
Looking Beyond Physical Disability: Cognitive Impairment in Persons With Multiple Sclerosis
Authors: Lott Shelley , Koszalinski Rebecca , Hurt Maria , Harris Robin
Published: July 2022

Purpose

Cognitive impairment (CI) is an underestimated part of disability in persons with multiple sclerosis (PwMS). The purpose of this evidence-based project was to influence clinicians treating PwMS by education of the current guidelines on cognition and multiple sclerosis and to screen CI with a valid neuropsychological tool.

Methods

Staff were educated on the 2018 National Multiple Sclerosis Society guidelines about CI in PwMS. The Processing Speed Test (PST) measured CI.

Results

Of 50 eligible patients in a 3-month period, 21 (42%) PwMS were cognitively screened. Of the 21 enrolled patients, nine (42.9%) patients were cognitively impaired. Employed patients’ PST scores tended to be higher than unemployed patients. As age increased, PST raw scores decreased.

Conclusions

In this project, less than half of eligible patients received cognitive screening after an extensive education program. Thus, education alone was not sufficient to change behavior. Other strategies to influence change may be more effective.
Gastrointestinal Bleeding in COVID-19 Patients
Authors: Negro Alessandra , Villa Giulia , Rolandi Stefano , Lucchini Alberto , Bambi Stefano
Published: July 2022

The incidence of COVID-19 gastrointestinal manifestations has been reported to range from 3% to 61%. There are limited data on the incidence rates and risk factors associated with gastrointestinal bleeding (GIB) in patients with COVID-19. A rapid review has been designed to investigate whether there is a relationship between COVID-19 and GIB in adult patients. PubMed, CINAHL, EMBASE, Cochrane Library, and Scopus databases have been analyzed. A total of 129 studies were found; 29 full texts were analyzed, and of these, 20 were found to be relevant to the topic.

The key findings of the included studies present an overall GIB rate in COVID-19 patients ranging from 1.1% to 13%. The bleeding involves mucosal damage of the duodenum, stomach, colon, and rectum. The management of gastrointestinal bleeding could be conservative. The use of fecal diversion systems for the management of diarrhea in COVID-19 patients should be minimized and closely evaluated for the risk of rectal mucosal damages and erosions. It is recommended to provide an accurate nutritional assessment; an early setting up of enteral nutrition, if not contraindicated, can help protect the gut mucosa of patients and restore normal intestinal flora. Larger cohort studies are needed to increase the information about this topic.
Long-term Transplant Function After Thrombolytic Treatment Ex Vivo of Donated Kidneys Retrieved 4 to 5 H After Circulatory Death
Authors: Olausson Michael , Antony Deepti , Johansson Martin , Travnikova Galina , Nayakawde Nikhil B. , Banerjee Debashish , Mackay Søfteland John , Ognissanti Damiano , Andresen Bergström Moa , Hammarsten Ola , Premaratne Goditha U.
Published: July 2022

Background.

Using a novel thrombolytic technique, we present long-term transplant function, measured by creatinine and iohexol clearance, after utilizing kidneys from porcine donors with uncontrolled donation after circulatory deaths, with 4.5–5 h of warm ischemia.

Methods.

Pigs in the study group were subjected to simulated circulatory death. After 2 h, ice slush was inserted into the abdomen and 4.5 h after death, the kidneys were retrieved. Lys-plasminogen, antithrombin-III, and alteplase were injected through the renal arteries on the back table. Subsequent ex vivo perfusion was continued for 3 h at 15°C, followed by 3 h with red blood cells at 32°C, and then transplanted into pigs as an autologous graft as only renal support. Living-donor recipient pigs that did not receive ex vivo perfusion, and unilateral nephrectomized pigs served as the controls.

Results.

Pigs in the study group (n = 13), surviving 10 d or more were included, of which 7 survived for 3 mo. Four animals in the living-donor group (n = 6) and all 5 nephrectomized animals survived for 3 mo. Creatinine levels in the plasma and urine, neutrophil gelatinase-associated lipocalin levels, Kidney Injury Marker-1 expression, and iohexol clearance at 3 mo did not differ significantly between the study and living-donor groups. Histology and transmission electron microscopy after 3 mo showed negligible fibrosis and no other damage.

Conclusions.

The present method salvages kidneys from extended unontrolled donation after circulatory death using thrombolytic treatment while preserving histology and enabling transplantation after ex vivo reconditioning, with clinically acceptable late function after 3 mo, as measured by creatinine and iohexol clearance.
Nocardioides nematodiphilus sp. nov., isolated from rhizosphere of Arabidopsis thaliana
Authors: Zhang Xue-Mei , Mo Wan-Ting , Wei Yu-Qian , Li Xin , Ma Gui-Mei , Yang Yu-Sen , Wang Xue-Jian , Liu Jian-Jin , Liu Zi-Yi , Zhou Xing-Kui , Zhang Ti-Kun
Published: July 2022

An actinobacterial strain, designated R-N-C8T, was isolated from the rhizosphere soil of Arabidopsis thaliana collected in Yunnan Province, south-west China. Based on the results of 16S rRNA gene sequence analysis, strain R-N-C8T had highest similarity to

Nocardioides terrae

CGMCC 1.7056T (96.5%),

Nocardioides opuntiae

KCTC 19804T (96.3%) and

Nocardioides currus

IB-3T (96.1%), and lower than 96.0 % similarity to other members of the genus

Nocardioides

. Phylogenetic trees based on 16S rRNA gene sequences indicated that strain R-N-C8T formed an isolated branch with

N. terrae

CGMCC 1.7056T and

N. opuntiae

KCTC 19804T. The polar lipids contained phosphatidylglycerol, diphosphatidylglycerol, one unidentified phosphoglycolipid and four unidentified phospholipids in the cellular membrane. The major fatty acids were identified as iso-C16 : 0, anteiso-C17 : 0, iso-C17 : 0, summed feature 9 (iso-C17 : 1 ω9c and/or C16 : 0 10-methyl) and iso-C15 : 0. The predominant respiratory quinone was MK-8(H4) and ll-diaminopimelic acid was the diagnostic diamino acid in the cell-wall peptidoglycan. The genomic DNA G+C content was 70.9 mol%. The orthologous average nucleotide identiy values between

N. terrae

CGMCC 1.7056T,

N. currus

IB-3T and strain R-N-C8T were 77.1 and 75.1 %, respectively. DNA–DNA hybridization values between

N. terrae

CGMCC 1.7056T,

N. currus

IB-3T and strain R-N-C8T were 20.7 and 19.9 % respectively. Data from phenotypic and genotypic analyses supported that strain R-N-C8T represents a new species of

Nocardioides

, for which the name Nocardioides nematodiphilus sp. nov. is proposed. The type strain is R-N-C8T (=CGMCC 1.18723T= KCTC 49528T).
The Effects of RNA.DNA-DNA Triple Helices on Nucleosome Structures and Dynamics
Authors: Kohestani Havva , Wereszczynski Jeff
Published: July 2022

Non-coding RNAs (ncRNAs) are an emerging epigenetic factor and have been recognized as playing a key role in many gene expression pathways. Structurally, binding of ncRNAs to isolated DNA is strongly dependent on sequence complementary, and results in the formation of an RNA.DNA-DNA (RDD) triple helix. However, in vivo DNA is not isolated, but is packed in chromatin fibers, the fundamental unit of which is the nucleosome. Biochemical experiments have shown that ncRNA binding to nucleosomal DNA is elevated at DNA entry and exit sites and is dependent on the presence of the H3 N-terminal tails. However, the structural and dynamical bases for these mechanisms remains unknown. Here, we have examined the mechanisms and effects of RDD formation in the context of the nucleosome using a series of all-atom molecular dynamics simulations. Results highlight the importance of DNA sequence on complex stability, elucidate the effects of the H3 tails on RDD structures, show how RDD formation impacts the structure and dynamics of the H3 tails, and show how RNA alters the local and global DNA double helical structure. Together, our results suggest ncRNAs can modify nucleosome, and potentially higher-order chromatin, structures and dynamics as a means of exerting epigenetic control.

SIGNIFICANCE

Non-coding RNAs (ncRNAs) play an essential role in gene regulation by binding to DNA and forming RNA.DNA-DNA (RDD) triple helices. In the cell, this occurs in the context where DNA is not a free double helix but is instead condensed into chromatin fibers. At the fundamental level, this compaction involves wrapping approximately 147 DNA basepairs around eight histone proteins to form the nucleosome. Here, we have used molecular dynamics simulations to understand the interplay between the structure and dynamics of RDD triple helices with the nucleosome. Results highlight the importance of RNA sequence on RDD stability regardless of its environment and suggest potential mechanisms for cross-talk between epigenetic factors and the effects of ncRNA binding on local and higher-order chromatin structures.
Class switch towards non-inflammatory IgG isotypes after repeated SARS-CoV-2 mRNA vaccination
Authors: Irrgang Pascal , Gerling Juliane , Kocher Katharina , Lapuente Dennis , Steininger Philipp , Wytopil Monika , Schäfer Simon , Habenicht Katharina , Zhong Jahn , Ssebyatika George , Krey Thomas , Falcone Valeria , Schülein Christine , Peter Antonia Sophia , Nganou-Makamdop Krystelle , Hengel Hartmut , Held Jürgen , Bogdan Christian , Überla Klaus , Schober Kilian , Winkler Thomas H. , Tenbusch Matthias
Published: July 2022

Repeated mRNA vaccinations are an efficient tool to combat the SARS-CoV-2 pandemic. High levels of neutralizing SARS-CoV-2-antibodies are an important component of vaccine-induced immunity. Shortly after the first or second mRNA vaccine dose, the IgG response mainly consists of the pro-inflammatory isotypes IgG1 and IgG3 and is driven by T helper (Th) 1 cells. Here, we report that several months after the second vaccination, SARS-CoV-2-specific antibodies were increasingly composed of non-inflammatory IgG2 and particularly IgG4, which were further boosted by a third mRNA vaccination and/or SARS-CoV-2 variant breakthrough infections. While IgG antibodies were affinity matured and of high neutralization capacity, the switch in constant domains caused changes in fragment crystallizable (Fc)-receptor mediated effector functions, including a decreased capacity to facilitate phagocytosis. IgG4 induction was neither induced by Th2 cells nor observed after homologous or heterologous SARS-CoV-2 vaccination with adenoviral vectors. In addition, IgG2- and IgG4-producing memory B cells were phenotypically indistinguishable from IgG1- or IgG3-producing cells. Since Fc-mediated effector functions are critical for antiviral immunity, the described class switch towards non-inflammatory IgG isotypes, which otherwise rarely occurs after vaccination or viral infection, may have consequences for the choice and timing of vaccination regimens using mRNA vaccines.
Automated Interictal Epileptiform Discharge Detection From Scalp EEG Using Scalable Time-series Classification Approaches
Authors: Nhu D. , Janmohamed M. , Shakhatreh L. , Gonen O. , Perucca P. , Gilligan A. , Kwan P. , O’Brien T. , Tan C. W. , Kuhlmann L.
Published: July 2022

Deep learning for automated interictal epileptiform discharge (IED) detection has been topical with many published papers in recent years. All existing work viewed EEG signals as time-series and developed specific models for IED classification; however, general time-series classification (TSC) methods were not considered. Moreover, none of these methods were evaluated on any public datasets, making direct comparisons challenging. This paper explored two state-of-the-art convolutional-based TSC algorithms, InceptionTime and Minirocket, on IED detection. We fine-tuned and cross-evaluated them on two private and public (Temple University Events - TUEV) datasets and provided ready metrics for benchmarking future work. We observed that the optimal parameters correlated with the clinical duration of an IED and achieved the best AUC, AUPRC and F1 scores of 0.98, 0.80 and 0.77 on the private datasets, respectively. The AUC, AUPRC and F1 on TUEV were 0.99, 0.99 and 0.97, respectively. While algorithms trained on the private sets maintained the performance when tested on the TUEV data, those trained on TUEV could not generalise well to the private data. These results emerge from differences in the class distributions across datasets and indicate a need for public datasets with a better diversity of IED waveforms, background activities and artifacts to facilitate standardisation and benchmarking of algorithms.
Expression of specific HLA class II alleles is associated with an increased risk for active tuberculosis and a distinct gene expression profile
Authors: Chihab Leila Y. , Kuan Rebecca , Phillips Elizabeth J. , Mallal Simon A. , Rozot Virginie , Davis Mark M. , Scriba Thomas J. , Sette Alessandro , Peters Bjoern , Lindestam Arlehamn Cecilia S. ,   the SATVI Study Group
Published: July 2022

Several HLA allelic variants have been associated with protection from or susceptibility to infectious and autoimmune diseases. Here, we examined whether specific HLA alleles would be associated with different Mycobacterium tuberculosis (Mtb) infection outcomes. The HLA alleles present at the -A, -B, -C, -DPA1, -DPB1, -DQA1, -DQB1, -DRB1, and -DRB3/4/5 loci were determined in a cohort of 636 individuals with known Mtb infection outcomes from South Africa and the US. Among these individuals, 233 were QuantiFERON (QFT) negative, and 433 were QFT positive, indicating Mtb exposure. Of these, 99 QFT positive participants either had active tuberculosis (TB) upon enrollment or were diagnosed in the past. We found that DQA1*03:01, DPB1*04:02, and DRB4*01:01 were significantly more frequent in individuals with active TB (susceptibility alleles), as judged by Odds Ratios and associated p-values, while DPB1*105:01 was associated with protection from active TB. Peripheral blood mononuclear cells (PMBCs) from a subset of individuals were stimulated with Mtb antigens, revealing individuals who express any of the three susceptibility alleles were associated with lower magnitude of responses. Furthermore, we defined a gene signature associated with individuals expressing the susceptibility alleles that was characterized by lower expression of APC-related genes. In summary, we have identified specific HLA alleles associated with susceptibility to active TB and found that the expression of these alleles was associated with a decreased Mtb-specific T cell response and a specific gene expression signature. These results will help understand individual risk factors in progressing to active TB.
Seroprevalence of anti-SARS-CoV-2 specific antibodies in vaccinated and vaccine naïve adult Nigerians
Authors: Onifade Abdulfattah Adekunle , Fowotade Adeola , Rahamon Sheu Kadiri , Edem Victory Fabian , Yaqub Surajudeen Adebayo , Akande Olatunji Kadri , Arinola Olatunbosun Ganiyu
Published: July 2022

Background

Reports on the evaluation of immune responses to different COVID-19 vaccines are limited. Similarly, effects of age and gender have not been well explored as variables that could impact on the vaccine-induced antibody response. Therefore, seroprevalence of anti-SARS-CoV-2 specific antibodies in vaccinated and vaccine naïve adult Nigerians was determined in this study.

Methodology

A total of 141 adults were enrolled into this study. Presence or absence of SARS-CoV-2 infection was confirmed by real-time reverse-transcriptase polymerase-chain reaction (RT-PCR) assay on nasopharyngeal and oropharyngeal swab specimens. Anti-SARS-CoV-2 Specific IgG and IgM antibodies were qualitatively detected using a Rapid Diagnostic Test kit.

Results

Pre-vaccination, 77% of the study participants had never had PCR-confirmed COVID-19 test yet 66.7% of them were seropositive for SARS-CoV-2 antibodies. Of 111 COVID-19 vaccinated participants, 69.2% and 73.8% of them had SARS-CoV-2 specific IgG post-first and second doses of COVID-19 vaccine respectively. However, 23.1% and 21.4% of the participants who have had first and second doses respectively had no detectable anti-SARS-CoV-2 antibodies. The proportion of participants with SARS-CoV-2 specific IgG was insignificantly higher in those between the ages of 18 – 40 years and 41 – 59 years compared with individuals aged ≥60 years. No significant association was observed between gender and seropositivity for SARS-CoV-2 antibodies.

Conclusion

There is high SARS-CoV-2 antibody seroprevalence among Nigerian adults who never had PCR-confirmed COVID-19. Also, there is the need for anti-SARS-CoV-2 antibodies screening post vaccination as this could be essential in achieving herd immunity. Age and gender do not seem to have significant association with seropositivity.
Estimating the prevalence of LAMA2 congenital muscular dystrophy using population genetic databases
Authors: Lake Nicole J. , Phua Joel , Liu Wei , Moors Tristen , Axon Steven , Lek Monkol
Published: July 2022

BACKGROUND

Recessive pathogenic variants in LAMA2 resulting in complete or partial loss of laminin α2 protein cause congenital muscular dystrophy (LAMA2 CMD). The prevalence of LAMA2 CMD has been estimated by epidemiological studies to lie between 1.36 - 20 cases per million. However, prevalence estimates from epidemiological studies are vulnerable to inaccuracies owing to challenges with studying rare diseases. Population genetic databases offer an alternative method for estimating prevalence.

OBJECTIVE

We aim to use population allele frequency data for reported and predicted pathogenic variants to estimate the birth prevalence of LAMA2 CMD.

METHODS

A list of reported pathogenic LAMA2 variants was compiled from public databases, and supplemented with predicted loss of function (LoF) variants in genome aggregation database (gnomAD). gnomAD allele frequencies for 273 reported pathogenic and predicted LoF LAMA2 variants were used to calculate disease prevalence using a Bayesian methodology.

RESULTS

The world-wide birth prevalence of LAMA2 CMD was estimated to be 8.3 per million (95% confidence interval (CI) 6.27 – 10.5 per million). The prevalence estimates for each population in gnomAD varied, ranging from 1.79 per million in East Asians (95% CI 0.63 – 3.36) to 10.1 per million in Europeans (95% CI 6.74 – 13.9). These estimates were generally consistent with those from epidemiological studies, where available.

CONCLUSIONS

We provide robust world-wide and population-specific birth prevalence estimates for LAMA2 CMD, including for non-European populations in which LAMA2 CMD prevalence hadn’t been studied. This work will inform the design and prioritization of clinical trials for promising LAMA2 CMD treatments.
SARS-CoV-2 Omicron BA.5: Evolving tropism and evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern
Authors: Aggarwal Anupriya , Akerman Anouschka , Milogiannakis Vanessa , Silva Mariana Ruiz , Walker Gregory , Kidinger Andrea , Angelovich Thomas , Waring Emily , Amatayakul-Chantler Supavadee , Roth Nathan , Coppola Germano , Yeang Malinna , Jean Tyra , Foster Charles , Hoppe Alexandra Carey , Ling Munier C. Mee , Darley David , Churchill Melissa , Starck Damian , Christ Daniel , Matthews Gail , Rawlinson William , Kelleher Anthony D. , Turville Stuart
Published: July 2022

Genetically distinct viral variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been recorded since January 2020. Over this time global vaccine programs have been introduced, contributing to lower COVID-19 hospitalisation and mortality rates, particularly in developed countries. In late 2021, the Omicron BA.1 variant emerged, with substantially different genetic differences and clinical effects from other variants of concern (VOC). This variant demonstrated higher numbers of polymorphisms in the gene encoding the Spike (S) protein, and it has displaced the previously dominant Delta variant. Shortly after dominating global spread in early 2022, BA.1 was supplanted by the genetically distinct Omicron lineage BA.2. A sub-lineage of BA.2, designated BA.5 has now started to dominate globally, with the potential to supplant BA.2. To address the relative threat of BA.5, we determined infectivity to particle ratios in primary nasopharyngeal samples and expanded low passage isolates in a well characterised, genetically engineered ACE2/TMPRSS2 cell line. We then assessed the impact of BA.5 infection on humoral neutralisation in vitro, in vaccinated and convalescent cohorts, using concentrated human IgG pooled from thousands of plasma donors, and licensed monoclonal antibody therapies. The infectivity of virus in primary swabs and expanded isolates revealed that whilst BA.1 and BA.2 are attenuated through ACE2/TMPRSS2, BA.5 infectivity is equivalent to that of an early 2020 circulating clade and has greater sensitivity to the TMPRSS2 inhibitor Nafamostat. As with BA.1, we observed BA.5 to significantly reduce neutralisation titres across all donors. Concentrated pooled human IgG from convalescent and vaccinated donors had greater breadth of neutralisation, although the potency was still reduced 7-fold with BA.5. Of all therapeutic antibodies tested, we observed a 14.3-fold reduction using Evusheld and 16.8-fold reduction using Sotrovimab when neutralising a Clade A versus BA.5 isolate. These results have implications for ongoing tracking and management of Omicron waves globally.
Assessing the impact of SARS-CoV-2 lineages and mutations on patient survival
Authors: Loucera Carlos , Perez-Florido Javier , Casimiro-Soriguer Carlos S. , Ortuño Francisco M. , Carmona Rosario , Bostelmann Gerrit , Martínez-González L. Javier , Muñoyerro-Muñiz Dolores , Villegas Román , Rodriguez-Baño Jesus , Romero-Gomez Manuel , Lorusso Nicola , Garcia-León Javier , Navarro-Marí Jose M. , Camacho-Martinez Pedro , Merino-Diaz Laura , de Salazar Adolfo , Viñuela Laura ,   The Andalusian COVID-19 sequencing initiative, Lepe Jose A , Garcia Federico , Dopazo Joaquin
Published: July 2022

After more than two years of COVID-19 pandemic, SARS-CoV-2 still remains a global public health problem. Successive waves of infection have produced new SARS-CoV-2 variants with new mutations whose impact on COVID-19 severity and patient survival is uncertain. A total of 764 SARS-CoV-2 genomes sequenced from COVID-19 patients, hospitalized from 19th February 2020 to 30st April 2021, along with their clinical data, were used for survival analysis. A significant association of B.1.1.7, the alpha lineage, with patient mortality (Log Hazard ratio LHR=0.51, C.I.=[0.14,0.88]) was found upon adjustment by all the covariates known to affect COVID-19 prognosis. Moreover, survival analysis of mutations in the SARS-CoV-2 genome rendered 27 of them significantly associated with higher mortality of patients. Most of these mutations were located in the S, ORF8 and N proteins. This study illustrates how a combination of genomic and clinical data provide solid evidence on the impact of viral lineage on patient survival.
PET/CT and SPECT/CT imaging of 90Y hepatic radioembolization at therapeutic and diagnostic activity levels: anthropomorphic phantom study
Authors: Budzyńska A , Kubik A , Kacperski K , Szubstarska P , Kuć M , Piasecki P , Konior M , Gryziński M , Dziuk M , Iller E
Published: July 2022

Purpose

Prior to 90Y radioembolization procedure a pretherapy simulation using 99mTc-MAA is performed. Alternatively, a small dosage of 90Y microspheres could be used. We aimed to assess the accuracy of lung shunt fraction (LSF) estimation in both high activity 90Y posttreatment and pretreatment scans with isotope activity of ∼100 MBq, using different imaging techniques. Additionally, we assessed the feasibility of visualising hot and cold hepatic tumours in PET/CT and Bremsstrahlung SPECT/CT images.

Materials and Methods

Anthropomorphic phantom including liver (with two spherical tumours) and lung inserts was filled with 90Y chloride to simulate an LSF of 9.8%. The total initial activity in the liver was 1451 MBq, including 19.4 MBq in the hot sphere. Nine measurement sessions including PET/CT, SPECT/CT, and planar images were acquired at activities in the whole phantom ranging from 1618 MBq down to 43 MBq.

The visibility of the tumours was appraised based on independent observers’ scores. Quantitatively, contrast-to-noise ratio (CNR) was calculated for both spheres in all images.

Results

LSF estimation: For high activity in the phantom, PET reconstructions slightly underestimated the LSF; absolute difference was <1.5pp (percent point). For activity <100 MBq, the LSF was overestimated. Both SPECT and planar scintigraphy overestimated the LSF for all activities.

Foci visibility: For SPECT/CT the cold tumour proved too small to be discernible (CNR <0.5) regardless of the 90Y activity in the liver, while hot sphere was visible for activity >200 MBq (CNR>4). For PET/CT, the cold tumour was only visible with the highest 90Y activity (CNR>4), whereas the hot one was seen for activity >100 MBq (CNR>5).

Conclusions

PET/CT may accurately estimate the LSF in a 90Y posttreatment procedure. However, at low activities of about 100 MBq it seems to provide unreliable estimations. PET imaging provided better visualisation of both hot and cold tumours.
Monkeypox caused less worry than COVID-19 among the general population during the first month of the WHO Monkeypox alert
Authors: Temsah Mohamad-Hani , Aljamaan Fadi , Alenezi Shuliweeh , Alhasan Khalid , Saddik Basema , Al-Barag Ahmad , Alhaboob Ali , Bahabri Nezar , Alshahrani Fatimah , Alrabiaah Abdulkarim , Alaraj Ali , Bahkali Feras , Alkriadees Khaled , Jamal Amr , Halwani Rabih , AlZamil Fahad , Al-Subaie Sarah , Barry Mazin , Memish Ziad A , Al-Tawfiq Jaffar A.
Published: July 2022

Background

Monkeypox re-emerged in May 2022 as another global health threat. This study assessed the public’s perception, worries, and vaccine acceptance for Monkeypox and COVID-19 during the first month of WHO announcement.

Methods

A national cross-sectional survey was conducted between May 27 and June 5, 2022, in Saudi Arabia. Data were collected on sociodemographic characteristics, previous infection with COVID-19, worry levels regarding Monkeypox compared to COVID-19, awareness, and perceptions of Monkeypox, and vaccine acceptance.

Results

Among the 1546 participants, most respondents (62%) were more worried about COVID-19 than Monkeypox. Respondents aged 45 years and above and those with a university degree or higher had lower odds of agreement with Monkeypox vaccination (OR .871, p-value .006, OR .719, p-value <0.001), respectively. Respondents with moderate to a high level of self and family commitment to infection control precautionary measures and those who expressed self and family worry of Monkeypox infection had significantly higher odds of vaccination agreement (OR 1.089 p-value=0.047, OR1.395 p-value=0.003) respectively. On the other hand, respondents who previously developed COVID-19 were significantly more worried about the Monkeypox disease (1.30 times more, p-value=0.020).

Conclusion

Worry levels amongst the public are higher from COVID-19 than Monkeypox. Perception of Monkeypox as a dangerous and virulent disease, worry from contracting the disease, and high commitment to infection precautionary measures were predictors of agreement with Monkeypox vaccination. While advanced age and high education level are predictors of low agreement with vaccination.
COVID-19 in non-hospitalised adults caused by either SARS-CoV-2 sub-variants Omicron BA.1, BA.2, BA.5 or Delta associates with similar illness duration, symptom severity and viral kinetics, irrespective of vaccination history
Authors: Townsley Hermaleigh , Gahir Joshua , Russell Timothy W , Carr Edward J , Dyke Matala , Adams Lorin , Miah Murad , Clayton Bobbi , Smith Callie , Miranda Mauro , Mears Harriet V , Bailey Chris , Black James RM , Fowler Ashley S , Crawford Margaret , Wilkinson Katalin , Hutchinson Matthew , Harvey Ruth , O’Reilly Nicola , Kelly Gavin , Goldstone Robert , Beale Rupert , Papineni Padmasayee , Corrah Tumena , Gilson Richard , Caidan Simon , Nicod Jerome , Gamblin Steve , Kassiotis George , Libri Vincenzo , Williams Bryan , Gandhi Sonia , Kucharski Adam J , Swanton Charles , Bauer David LV , Wall Emma C
Published: July 2022

Background

SARS-CoV-2 variant Omicron rapidly evolved over 2022, causing three waves of infection due to sub-variants BA.1, BA.2 and BA.4/5. We sought to characterise symptoms and viral loads over the course of COVID-19 infection with these sub-variants in otherwise-healthy, vaccinated, non-hospitalised adults, and compared data to infections with the preceding Delta variant of concern (VOC).

Methods

In a prospective, observational cohort study, healthy vaccinated UK adults who reported a positive PCR or lateral flow test, self-swabbed on alternate days until day 10. We compared symptoms and viral load trajectories between infections caused by VOCs Delta and Omicron (sub-variants BA.1, BA.2 and BA.4/5), and tested for relationships between vaccine dose, symptoms and PCR Ct value as a proxy for viral load.

Results

555 infection episodes were reported among 483 participants. Across VOCs, symptom burden and duration were similar, however symptom profiles differed among infections caused by Delta compared to Omicron sub-variants; symptoms of all Omicron sub-variants BA.1, BA.2 and BA.4/5 were very similar. Anosmia was reported in 7-13% of participants with Omicron sub-variants, compared to 25/60 (42%) with Delta infection (P= 1.31e-08 or 1.03e-05 or 5.63e-05; χ2test d2+Delta vs. Omicron BA.1 or vs. BA.2, or BA.5, respectively), fever was more common with Omicron BA.5 (30/55, 55%) than Delta (20/60, 33%) (p 0.03). Amongst infections with all Omicron sub-variants, symptoms of coryza, fatigue, cough and myalgia predominated. Viral load trajectories and peaks did not differ between Delta, and Omicron, irrespective of symptom severity (including asymptomatic participants), VOC or vaccination status. Ct values were negatively associated with time since vaccination in participants infected with BA.1; however, this trend was not observed in BA.2/BA.4/5 infections.

Conclusion

Our study emphasises both the changing symptom profile of COVID-19 infections in the Omicron era, and ongoing transmission risk of Omicron sub-variants in vaccinated adults.

Trial registration

NCT04750356
Modeling the impact of the Omicron infection wave in Germany
Authors: Maier Benjamin F. , Burdinski Angelique , Wiedermann Marc , Rose Annika H. , der Heiden Matthias an , Wichmann Ole , Harder Thomas , Schlosser Frank , Brockmann Dirk
Published: July 2022

BACKGROUND

In November 2021, the first case of SARS-CoV-2 “variant of concern” (VOC) B.1.1.529 (“Omicron”) was reported in Germany, alongside global reports of reduced vaccine efficacy against infections with this variant. The potential threat posed by the rapid spread of this variant in Germany remained, at the time, elusive.

METHODS

We developed a variant-dependent population-averaged susceptible-exposed-infected-recovered (SEIR) infectious disease model. The model was calibrated on the observed fixation dynamics of the Omicron variant in December 2021, and allowed us to estimate potential courses of upcoming infection waves in Germany, focusing on the corresponding burden on intensive care units (ICUs) and the efficacy of contact reduction strategies.

RESULTS

A maximum median incidence of approximately 300 000 (50% PI in 1000: [181,454], 95% PI in 1000: [55,804]) reported cases per day was expected with the median peak occurring in the mid of February 2022, reaching a cumulative Omicron case count of 16.5 million (50% PI in mio: [11.4, 21.3], 95% PI in mio: [4.1, 27.9]) until Apr 1, 2022. These figures were in line with the actual Omicron waves that were subsequently observed in Germany with respective peaks occurring in mid February (peak: 191k daily new cases) and mid March (peak: 230k daily new cases), cumulatively infecting 14.8 million individuals during the study period. The model peak incidence was observed to be highly sensitive to variations in the assumed generation time and decreased with shorter generation time. Low contact reductions were expected to lead to containment. Early, strict, and short contact reductions could have led to a strong “rebound” effect with high incidences after the end of the respective non-pharmaceutical interventions. Higher vaccine uptake would have led to a lower outbreak size. To ensure that ICU occupancy remained below maximum capacity, a relative risk of requiring ICU care of 10%–20% was necessary (after infection with Omicron vs. infection with Delta).

CONCLUSIONS

We expected a large cumulative number of infections with the VOC Omicron in Germany with ICU occupancy likely remaining below capacity nevertheless, even without additional non-pharmaceutical interventions. Our estimates were in line with the retrospectively observed waves. The results presented here informed legislation in Germany. The methodology developed in this study might be used to estimate the impact of future waves of COVID-19 or other infectious diseases.
Cohort-mean measured macromolecules lead to more robust linear-combination modeling than parameterized and subject-specific ones
Authors: Zöllner Helge J. , Davies-Jenkins Christopher W. , Murali-Manohar Saipavitra , Gong Tao , Hui Steve C. N. , Song Yulu , Chen Weibo , Wang Guangbin , Edden Richard A. E. , Oeltzschner Georg
Published: July 2022

Expert consensus recommends linear-combination modeling (LCM) of 1H MR spectra with sequence-specific simulated metabolite basis function and experimentally derived macromolecular (MM) basis functions. Measured MM basis functions have been derived from metabolite-nulled spectra averaged across a small cohort. The use of subject-specific instead of cohort-averaged measured MM basis functions has not been studied. Furthermore, measured MM basis functions are not widely available to non-expert users, who commonly rely on parameterized MM signals internally simulated by LCM software. To investigate the impact of the choice of MM modeling, this study, therefore, compares metabolite level estimates between different MM modeling strategies (cohort-mean measured; subject-specific measured; parameterized) in a lifespan cohort and characterizes its impact on metabolite-age associations.

100 conventional (TE = 30 ms) and metabolite-nulled (TI = 650 ms) PRESS datasets, acquired from the medial parietal lobe in a lifespan cohort (20-70 years of age), were analyzed in Osprey. Short-TE spectra were modeled in Osprey using six different strategies to consider the macromolecular baseline. Fully tissue- and relaxation-corrected metabolite levels were compared between MM strategies. Model performance was evaluated by model residuals, the Akaike information criterion (AIC), and the impact on metabolite-age associations.

The choice of MM strategy had a significant impact on the mean metabolite level estimates and no major impact on variance. Correlation analysis revealed moderate-to-strong agreement between different MM strategies (r > 0.6). The lowest relative model residuals and AIC values were found for the cohort-mean measured MM. Metabolite-age associations were consistently found for two major singlet signals (tCr, tCho) for all MM strategies, however, findings for highly J-coupled metabolites it was depended on the MM strategy. A variance partition analysis indicated that up to 44% of the total variance was related to the choice of MM strategy. Additionally, the variance partition analysis reproduced the metabolite-age association for tCr and tCho found in the simpler correlation analysis.

In summary, the inclusion of a single high-SNR MM basis function (cohort-mean) leads to more robust metabolite estimation (lower model residuals and AIC values) compared to MM strategies with more degrees of freedom (Gaussian parametrization) or subject-specific MM information. Integration of multiple LCM analyses into a single statistical model potentially improves the robustness in the detection of underlying effects (e.g. metabolite vs age), reduces algorithm-based bias, and estimates algorithm-related variance.
Ethanol Exposure Perturbs Sea Urchin Development and Disrupts Developmental Timing
Authors: Rodríguez-Sastre Nahomie , Shapiro Nicholas , Hawkins Dakota Y. , Lion Alexandra T. , Peyreau Monique , Correa Andrea E. , Dionne Kristin , Bradham Cynthia A.
Published: July 2022

Ethanol is a known vertebrate teratogen that causes craniofacial defects as a component of fetal alcohol syndrome (FAS). Our results show that sea urchin embryos treated with ethanol similarly show broad skeletal patterning defects, potentially analogous to the defects associated with FAS. The sea urchin larval skeleton is a simple patterning system that involves only two cell types: the primary mesenchymal cells (PMCs) that secrete the calcium carbonate skeleton and the ectodermal cells that provide migratory, positional, and differentiation cues for the PMCs. Perturbations in RA biosynthesis and Hh signaling pathways are thought to be causal for the FAS phenotype in vertebrates. Surprisingly, our results indicate that these pathways are not functionally relevant for the teratogenic effects of ethanol in developing sea urchins. We found that developmental morphology as well as the expression of ectodermal and PMC genes was delayed by ethanol exposure. Temporal transcriptome analysis revealed significant impacts of ethanol on signaling and metabolic gene expression, and a disruption in the timing of GRN gene expression that includes both delayed and precocious gene expression throughout the specification network. We conclude that the skeletal patterning perturbations in ethanol-treated embryos likely arise from a loss of temporal synchrony within and between the instructive and responsive tissues.
Virus exposure and neurodegenerative disease risk across national biobanks
Authors: Levine Kristin , Leonard Hampton L. , Blauwendraat Cornelis , Iwaki Hirotaka , Johnson Nicholas , Bandres-Ciga Sara , Koroshetz Walter , Ferrucci Luigi , Faghri Faraz , Singleton Andrew B. , Nalls Mike A.
Published: July 2022

BACKGROUND

With recent findings connecting Epstein-Barr virus to increased risk of multiple sclerosis and growing concerns regarding the potential neurological impact of the coronavirus pandemic, we surveyed biobank scale real-world data to identify potential links between viral exposures and neurodegenerative disease risks.

METHODS

To assess the potential increased risk of neurodegenerative diseases due to viral exposures, we mined time series data from FinnGen as a discovery dataset and cross-sectional data from the UK Biobank as a replication dataset for 73 pairs of common viral exposures and neurodegenerative disease outcomes. We investigated the impact of time span between viral exposure and disease risk using time series data from FinnGen at 1, 5, and 15 year intervals between exposure and disease onset. This analysis helped us to avoid the potential confounding of concurrent diagnosis due to hospitalization with viral infection. Further, to address the possible bias of reverse causality we examined risk for severe viral infections after NDD diagnosis.

RESULTS

We identified 45 viral exposures significantly associated with increased risk of post-exposure neurodegenerative disease onset after multiple test correction in the discovery phase using longitudinal data. 22 of these associations were replicated in cross sectional data from the UK Biobank. The largest effect association we saw replicated was between viral encephalitis exposure and Alzheimer’s disease, with discovery hazard estimates of ∼30 and a replication odds ratio of ∼22. We also replicated the association between Epstein-Barr virus exposure and multiple sclerosis 5-15 years before diagnosis of multiple sclerosis. In total, 17 virus/neurodegeneration pairs were significant with 5-15 years between viral exposure and NDD diagnosis. In an investigation of potential confounding and reverse causality, we generally see larger hazard ratios associated with viruses preceding NDD diagnosis than viruses post NDD diagnosis.

CONCLUSIONS

Viral exposures contribute to later in life risk of neurodegenerative disease with increased risk of neurodegeneration still significant at up to 15 years between some events in this report.
MultiCPA: Multimodal Compositional Perturbation Autoencoder
Authors: Inecik Kemal , Uhlmann Andreas , Lotfollahi Mohammad , Theis Fabian
Published: July 2022

Single-cell multimodal profiling provides a high-resolution view of cellular information. Recently, multimodal profiling approaches have been coupled with CRISPR technologies to perform pooled screens of single or combinatorial perturbations. This opens the possibility of exploring the massive space of combinatorial perturbations and their regulatory effects computationally from the extrapolation of a few experimentally feasible combinations. Here, we proposeMultiCPA, an end-to-end generative architecture to predict multimodal perturbation response at single cell level. Two mixing strategies to integrate multiple modalities are introduced and compared with existing methods. MultiCPA was also shown to accurately predict unseen combinatorial perturbation responses for multiple modalities. The code to reproduce the results is available onGitHub,theislab/multicpa.
Multiomics analyses reveal the central role of nucleolus and nucleoid machinery during heat stress acclimation in Pinus radiata
Authors: Escandón Mónica , Valledor Luis , Lamelas Laura , Álvarez Jóse M , Cañal María Jesús , Meijón Mónica
Published: July 2022

Climate warming is causing quick changes in mean annual temperature and more severe drought period. These are major contributors of forest dieback, which is becoming more frequent and widespread, particularly in warm and drought-prone regions. Despite being a hot topic in non-woody plant sciences, the information about how heatwaves impact in tree molecular biology is still scarce. In this work we investigated how the transcriptome of Pinus radiata changes during initial stress response and stress acclimation. To this end, and considering this species is non sequenced, we generated a deep dataset employing Illumina technology. This approach allowed us to reconstruct 77335 contigs which were annotated following gene ontology, and to define 12164 and 13590 transcripts as down- and upregulated, respectively, across the three sampled experimental points. Enrichment analysis allowed to distinguish 9 down-regulated pathways, the most of them related to the reduction of apoplast, and water transport. While 22 were upregulated, which followed two different trends those pathways that peaks at short-term (acute response) from those which accumulated long-term (acclimation response) being most of them related to heat shock response, redox machinery and RNA processing. Additionally, the combination of transcriptome data with other available omics layers, allowed an exceptional understanding of the mechanisms behind heat stress response, involving complex interrelated processes from molecular to physiological level. Nucleolus and nucleoid activities seem to be a central core in acclimating process, producing specific RNA isoforms and other essential elements for anterograde-retrograde stress signaling as NAC proteins, Helicase RVB, RZ1 RNA chaperone, or ribosomal RPS4. These mechanisms are connected by elements already known in heat stress-response (redox, heat shock proteins or ABA-related). But also, novel candidates, as photosynthetic pigments, shikimate, or proline centric proteases activities, have been identified effectively networking biochemical responses to its potential regulatory element. This work provides a first deep overview about what molecular mechanisms underlying heat stress response and acclimation in pines, supporting the development of new breeding strategies to face the challenges that the climate change will impose to forests.
Testing Human Anxiety Associations of Genes Previously Implicated by Mouse Anxiety Models
Authors: Brasher Maizy S. , Mize Travis J. , Thomas Aimee L. , Hoeffer Charles A. , Ehringer Marissa A. , Evans Luke M.
Published: July 2022

Anxiety disorders are common and can be debilitating, with effective treatments remaining hampered by an incomplete understanding of the underlying genetic etiology. Improvements have been made in understanding the genetic influences on mouse behavioral models of anxiety, yet it is unclear the extent to which genes identified in these experimental systems contribute to genetic variation in human anxiety phenotypes. Leveraging new and existing large-scale human genome-wide association studies, we tested whether sets of genes previously identified in mouse anxiety-like behavior studies contribute to a range of human anxiety disorders. When tested as individual genes, thirteen mouse-identified genes were associated with human anxiety phenotypes, suggesting an overlap of individual genes contributing to both mouse models of anxiety-like behaviors and human anxiety traits. When genes were tested as sets, we did identify fourteen significant associations between mouse gene sets and human anxiety, but the majority of gene sets showed no significant association with human anxiety phenotypes. These few significant associations indicate a need to identify and develop more translatable mouse models by identifying sets of genes that ‘match’ between model systems and specific human phenotypes of interest. We suggest that continuing to develop improved behavioral paradigms and finer-scale experimental data, for instance from individual neuronal subtypes or cell-type-specific expression data, is likely to improve our understanding of the genetic etiology and underlying functional changes in anxiety disorders.