bluuebunny/crossref_metadata_2025 huggingface dataset:
A Systematic Review and Meta-Analysis of Low-Residue Diet Versus Clear Liquid Diet
Authors: Wu Rui , Ji Wen-ya , Yang Cheng , Zhan Qiang
Published: July 2021

The goal of this systematic review was to compare the clear liquid diet and the low-residue diet to determine which is better for bowel preparation before colonoscopy. A literature search for randomized controlled trials on the effects of employing the clear liquid diet and low-residue diets before colonoscopy was conducted in major online English databases (PubMed, Web of Science, and Ovid EMBASE). After the systematic review of all 16 studies, the outcomes including quality of bowel preparation, tolerance, willingness to repeat, and adverse effects were analyzed through meta-analysis. The statistical analysis was performed by using RevMan 5.3 software. No statistically significant difference was observed between the low-residue diet and clear liquid diet groups (odds ratio [95% confidence interval] = 1.19 [0.79, 1.81]; p = .41). There was no statistically significant difference between the Boston Bowel Preparation Scale (standard mean difference [95% confidence interval] =−0.04 [−0.21, −0.14]; p = .68) Ottawa Bowel Preparation Scale (standard mean difference [95% confidence interval] =−0.04 [−0.19, 0.11]; p = .59) scores of the two groups. The quality indicators for colonoscopy of the two groups were not statistically significant. However, patient tolerance to the low-residue diet was higher (odds ratio [95% confidence interval] = 1.86 [1.47, 2.36]; p < .01). More patients in the low-residue diet group were willing to repeat the low-residue diet for bowel preparation (odds ratio [95% confidence interval] = 2.34 [1.72, 3.17]; p < .01). More patients in the clear liquid diet group experienced hunger, nausea, and vomiting. People who employed the low-residue diet before colonoscopy had the same quality of bowel preparation as those with clear liquid diet. Meanwhile, the tolerance of people with low-residue diet was better than people with clear liquid diet, and these people were more willing to repeat the colonoscopy with less adverse events.
FUNDC1 Regulates Autophagy by Inhibiting ROS-NLRP3 Signaling to Avoid Apoptosis in the Lung in a Lipopolysaccharide-Induced Mouse Model
Authors: Pan Pan , Chen Jie , Liu Xudong , Fan Junping , Zhang Dong , Zhao Weiguo , Xie Lixin , Su Longxiang
Published: July 2021

The incidence and mortality of acute respiratory distress syndrome (ARDS) are high, but the relevant mechanism for this disorder remains unclear. Autophagy plays an important role in the development of ARDS. The mitochondrial outer membrane protein FUNDC1 is involved in hypoxia-mediated mitochondrial autophagy, which may contribute to ARDS development. This study explored whether FUNDC1 regulates autophagy by inhibiting ROS-NLRP3 signaling to avoid apoptosis in the lung in a lipopolysaccharide-induced mouse model. In this study, FUNDC1 knockout mice were constructed, and a lipopolysaccharide-induced mouse model was generated. HE staining of pathological sections from the lung, wet/dry lung measurements, myeloperoxidase concentration/neutrophil counts in BALF and survival time of mice were examined to determine the effect of modeling. The release of cytokines (TNF-α, IL-1β, IL-6, and IL-10) in response to LPS in the BALF and plasma was assessed using ELISA. The effects of oxidative stress (malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase) in lung tissue in response to LPS were detected by biochemical analysis. Oxidative stress damage was validated by iNOS staining, and apoptosis was assessed by TUNEL staining after LPS. Finally, the expression of autophagy-associated proteins and inflammasome-associated proteins in lung tissue after LPS intervention was analyzed by western blot. We found that wild-type control, FUNDC1 knockout control, lipopolysaccharide-induced wild-type, and FUNDC1 knockout mouse models were used to investigate whether FUNDC1-mediated autophagy is involved in lung injury and its possible molecular mechanisms. Compared with the normal control group, lung tissue FUNDC1 and LC3 II increased and p62/SQSTM1 decreased after LPS intervention, and increased ROS levels led to a decrease in corresponding antioxidant enzymes along with an increased inflammatory response and apoptosis. Levels of autophagy in lipopolysaccharide-induced mice deficient in FUNDC1 were significantly decreased, but the expression of ROS and inflammatory factors in lung tissue was more severe than in lipopolysaccharide-induced wild-type mice, and the survival rate was significantly decreased. Western blot analysis showed that autophagy was significantly inhibited in the FUNDC1 KO+LPS group, and there was a significant increase in NLRP3, caspase-1, IL-1β, and ASC compared with the lipopolysaccharide-induced wild-type group. In summary, lipopolysaccharide-induced wild-type mice exhibit ROS-dependent activation of autophagy, and knocking out FUNDC1 promotes inflammasome activation and exacerbates lung injury.
Outcomes in Endoscopic and Operative Transgastric Pancreatic Debridement
Authors: Maatman Thomas K. , McGuire Sean P. , Flick Katelyn F. , Madison Mackenzie K. , Al-Haddad Mohammad A. , Bick Benjamin L. , Ceppa Eugene P. , DeWitt John M. , Easler Jeffrey J. , Fogel Evan L. , Gromski Mark A. , House Michael G. , Lehman Glen A. , Nakeeb Attila , Schmidt C. Max , Sherman Stuart , Watkins James L. , Zyromski Nicholas J.
Published: July 2021

Objectives:

Select patients with anatomically favorable walled off pancreatic necrosis may be treated by endoscopic (Endo-TGD) or operative (OR-TGD) transgastric debridement (TGD). We compared our experience with these 2 approaches.

Summary Background Data:

Select necrotizing pancreatitis (NP) patients are suitable for TGD which may be accomplished endoscopically or surgically. Limited experience exists contrasting these techniques exists.

Methods:

Patients undergoing Endo-TGD and OR-TGD at a single, high-volume pancreatic center between 2008 and 2019 were identified from a prospective database. Patient characteristics, procedural details, and outcomes of these 2 groups were compared.

Results:

Among 498 NP patients undergoing necrosis intervention, 160 (32%) had TGD: 59 Endo-TGD and 101 OR-TGD. The groups were statistically similar in age, comorbidity, pancreatitis etiology, necrosis anatomy, pancreatitis severity, and timing of TGD from pancreatitis insult. OR-TGD required 1.1 ± 0.5 and Endo-TGD 3.0 ± 2.0 debridements/patient. Fewer hospital readmissions and repeat necrosis interventions, and shorter total inpatient length of stay were observed in OR-TGD patients. New-onset organ failure [Endo-TGD (13%); OR-TGD (13%); P = 1.0] was similar between groups. Hospital length of stay after TGD was significantly longer in patients undergoing Endo-TGD (13.8 ± 20.8 days) compared to OR-TGD (9.4 ± 6.1 days; P = 0.047). Mortality was 7% in Endo-TGD and 1% in OR-TGD (P = 0.04).

Conclusions:

Operative and endoscopic transgastric debridement achieve necrosis resolution with different temporal and procedural profiles. Clear multidisciplinary communication is essential to determine appropriate approach to individual necrotizing pancreatitis patients.
Variation in pediatric cervical spine imaging across trauma centers—A cause for concern?
Authors: Massoumi Roxanne , Wertz Joseph , Duong Tuyen , Tseng Chi-Hon , Jen Howard Chung-Hao
Published: July 2021

BACKGROUND

Traumatic pediatric cervical spine injury can be challenging to diagnose, and the clinical algorithms meant to aid physicians differ from adult trauma protocols. Despite the existence of standardized guidelines, imaging decisions may vary according to physician education, subjective assessment, and experience with pediatric trauma patients. Our study investigates the rates of pediatric posttraumatic cervical spine imaging across trauma centers, hypothesizing that more specialized centers will have lower rates of advanced cervical spine imaging.

METHODS

The 2015 to 2016 Trauma Quality Improvement Program database was reviewed for patients younger than 18 years- to assess rates of cervical spine imaging on presentation across different trauma centers. Propensity stratification logistic regression was performed controlling for patient- and center-specific variables. p Values less than 0.05 were considered significant.

RESULTS

Of 110,769 pediatric trauma patients, 35.2% were female, and the average age was 9.6 years. Overall, 3.6% had cervical spine computed tomography (CT) and less than 1% had cervical spine MRI or X-ray. Compared with all others, Level I trauma centers were significantly less likely to use cervical spine CT for the initial evaluation of younger (≤14 years) but not older trauma patients (adjusted odds ratio [AOR], 0.89; 95% confidence interval [CI], 0.80–0.99; AOR, 0.97; 95% CI, 0.87–1.09); Level I centers had higher odds of cervical spine MRI use, but only for patients 14 years or younger (AOR, 1.63; 95% CI, 1.09–2.44). Pediatric-designated trauma centers had significantly lower odds of cervical spine CT (≤14 years: AOR, 0.70; 95% CI, 0.63–0.78; >14 years: AOR, 0.67; 95% CI, 0.67–0.75) and higher odds of cervical spine X-ray (≤14 years: AOR, 4.75; 95% CI, 3.55–6.36; >14 years: AOR, 4.50; 95% CI, 2.72–7.45) for all ages, but higher odds of cervical spine MRI for younger patients only (≤14 years: AOR, 2.10; 95% CI, 1.38–3.21).

CONCLUSION

Level I and pediatric designations were associated with lower rates of cervical spine CT. Pediatric centers were also more likely to use cervical spine X-ray. This variability of imaging use further supports the need to disseminate and educate providers on pediatric-specific cervical spine evaluation guidelines.

LEVEL OF EVIDENCE

Prognostic and epidemiological, level III.
Vagus nerve stimulation modulates arachidonic acid production in the mesenteric lymph following intestinal ischemia-reperfusion injury
Authors: Nakatsutsumi Keita , Morishita Koji , Yagi Masayuki , Doki Sanae , Watanabe Arisa , Ikegami Nahoko , Kobayashi Testuyuki , Kojima Mitsuaki , Senda Atsushi , Yamamoto Kouhei , Aiboshi Junichi , Coimbra Raul , Otomo Yasuhiro
Published: July 2021

BACKGROUND

Inflammatory lipid mediators in mesenteric lymph (ML), including arachidonic acid (AA), are considered to play an important role in the pathogenesis of multiple-organ dysfunction after hemorrhagic shock. A previous study suggested that vagus nerve stimulation (VNS) could relieve shock-induced gut injury and abrogate ML toxicity, resulting in the prevention of multiple-organ dysfunction. However, the detailed mechanism of VNS in lymph toxicity remains unclear. The study aimed to investigate the relationship between VNS and inflammatory lipid mediators in ML.

METHODS

Male Sprague-Dawley rats underwent laparotomy and superior mesenteric artery obstruction (SMAO) for 60 minutes to induce intestinal ischemia followed by reperfusion and observation. The ML duct was cannulated, and ML samples were obtained both before and after SMAO. The distal ileum was removed at the end of the observation period. In one group of animals, VNS was performed from 10 minutes before 10 minutes after SMAO (5 V, 0.5 Hz). Liquid chromatography–electrospray ionization–tandem mass spectrometry analysis of AA was performed for each ML sample. The biological activity of ML was examined using a monocyte nuclear factor κ-light-chain-enhancer of activated B cells activation assay. Western blotting of phospholipase A2 group IIA (PLA2-IIA) was also performed for ML and ileum samples.

RESULTS

Vagus nerve stimulation relieved the SMAO-induced histological gut injury. The concentration of AA and level of nuclear factor κ-light-chain-enhancer of activated B cells activation in ML increased significantly after SMAO, whereas VNS prevented these responses. Western blotting showed PLA2-IIA expression in the ML and ileum after SMAO; however, the appearance of PLA2-IIA band was remarkably decreased in the samples from VNS-treated animals.

CONCLUSION

The results suggested that VNS could relieve gut injury induced by SMAO and decrease the production of AA in ML by altering PLA2-IIA expression in the gut and ML.
Severe Demyelinating Polyneuropathy and Cranial Neuropathy During Avelumab Treatment of Metastatic Merkel Cell Carcinoma
Authors: Bilić Hrvoje , Sitaš Barbara , Hančević Mirea , Habek Mario , Simetić Luka , Bilić Ervina
Published: July 2021

Introduction

Avelumab is a programmed death ligand 1–blocking monoclonal antibody used for the treatment of Merkel cell carcinoma (MCC), urothelial carcinoma, and other solid tumors. It acts as an immune checkpoint inhibitor and prolongs survival of MCC patients. Immune-mediated neurological adverse effects are rare and usually respond well to specific therapy.

Methods and Results

A case of a 70-year-old man with metastatic MCC is described in this study. The patient developed diplopia after the fourth dose of avelumab, which was then discontinued. Seven months later, therapy was reinitiated and followed by a new adverse neurological event: severe demyelinating polyneuropathy combined with ophthalmoplegia refractory to a plethora of immune suppressive/modulatory treatment regimes.

Discussion

This report of severe demyelinating polyneuropathy and cranial neuropathy associated with an anti–programmed death ligand 1 drug refractory to immune suppressive/modulatory treatments sheds a new light to evolving spectrum of immune checkpoint inhibitor immune-related neurological adverse events.
Paracentral Acute Middle Maculopathy Associated With Anterior Ischemic Optic Neuropathy and Cilioretinal Artery Occlusion in Giant Cell Arteritis
Authors: Kasimov Michelle , Popovic Marko M. , Micieli Jonathan A.
Published: July 2021

Paracentral acute middle maculopathy (PAMM) is a relatively new optical coherence tomography finding, defined by hyperreflectivity in the inner nuclear layer. In this article, we present a case of a 73-year-old woman who presented with transient vision loss followed by the sudden onset of complete vision loss to counting fingers at 1 foot for one day in the left eye. Dilated examination showed a right cotton wool spot, left pallid optic disc edema, and retinal edema in the distribution of the cilioretinal artery. OCT demonstrated hyperreflective band at the level of the inner nuclear layer, compatible with PAMM. Clinical and laboratory findings were consistent with GCA, for which she was prescribed high-dose oral prednisone, with confirmation of GCA on a subsequent temporal artery biopsy. PAMM may be seen in the context of GCA, and OCT of the macula serves as an important adjunct to define the retinal manifestations of this condition.
Mycobacterium tuberculosis complex lineage 5 exhibits high levels of within-lineage genomic diversity and differing gene content compared to the type strain H37Rv
Authors: Sanoussi C. N'Dira , Coscolla Mireia , Ofori-Anyinam Boatema , Otchere Isaac Darko , Antonio Martin , Niemann Stefan , Parkhill Julian , Harris Simon , Yeboah-Manu Dorothy , Gagneux Sebastien , Rigouts Leen , Affolabi Dissou , de Jong Bouke C. , Meehan Conor J.
Published: July 2021

Pathogens of the

Mycobacterium tuberculosis

complex (MTBC) are considered to be monomorphic, with little gene content variation between strains. Nevertheless, several genotypic and phenotypic factors separate strains of the different MTBC lineages (L), especially L5 and L6 (traditionally termed

Mycobacterium africanum

) strains, from each other. However, this genome variability and gene content, especially of L5 strains, has not been fully explored and may be important for pathobiology and current approaches for genomic analysis of MTBC strains, including transmission studies. By comparing the genomes of 355 L5 clinical strains (including 3 complete genomes and 352 Illumina whole-genome sequenced isolates) to each other and to H37Rv, we identified multiple genes that were differentially present or absent between H37Rv and L5 strains. Additionally, considerable gene content variability was found across L5 strains, including a split in the L5.3 sub-lineage into L5.3.1 and L5.3.2. These gene content differences had a small knock-on effect on transmission cluster estimation, with clustering rates influenced by the selected reference genome, and with potential overestimation of recent transmission when using H37Rv as the reference genome. We conclude that full capture of the gene diversity, especially high-resolution outbreak analysis, requires a variation of the single H37Rv-centric reference genome mapping approach currently used in most whole-genome sequencing data analysis pipelines. Moreover, the high within-lineage gene content variability suggests that the pan-genome of

M. tuberculosis

is at least several kilobases larger than previously thought, implying that a concatenated or reference-free genome assembly (de novo) approach may be needed for particular questions.
DiSCo: a sequence-based type-specific predictor of Dsr-dependent dissimilatory sulphur metabolism in microbial data
Authors: Neukirchen Sinje , Sousa Filipa L.
Published: July 2021

Current methods in comparative genomic analyses for metabolic potential prediction of proteins involved in, or associated with the Dsr (dissimilatory sulphite reductase)-dependent dissimilatory sulphur metabolism are both time-intensive and computationally challenging, especially when considering metagenomic data. We developed DiSCo, a Dsr-dependent dissimilatory sulphur metabolism classification tool, which automatically identifies and classifies the protein type from sequence data. It takes user-supplied protein sequences and lists the identified proteins and their classification in terms of protein family and predicted type. It can also extract the sequence data from user-input to serve as basis for additional downstream analyses. DiSCo provides the metabolic functional prediction of proteins involved in Dsr-dependent dissimilatory sulphur metabolism with high levels of accuracy in a fast manner. We ran DiSCo against a dataset composed of over 190 thousand (meta)genomic records and efficiently mapped Dsr-dependent dissimilatory sulphur proteins in 1798 lineages across both prokaryotic domains. This allowed the identification of new micro-organisms belonging to Thaumarchaeota and Spirochaetes lineages with the metabolic potential to use the Dsr-pathway for energy conservation. DiSCo is implemented in Perl 5 and freely available under the GNU GPLv3 at https://github.com/Genome-Evolution-and-Ecology-Group-GEEG/DiSCo.
Rhodococcus comparative genomics reveals a phylogenomic-dependent non-ribosomal peptide synthetase distribution: insights into biosynthetic gene cluster connection to an orphan metabolite
Authors: Undabarrena Agustina , Valencia Ricardo , Cumsille Andrés , Zamora-Leiva Leonardo , Castro-Nallar Eduardo , Barona-Gomez Francisco , Cámara Beatriz
Published: July 2021

Natural products (NPs) are synthesized by biosynthetic gene clusters (BGCs), whose genes are involved in producing one or a family of chemically related metabolites. Advances in comparative genomics have been favourable for exploiting huge amounts of data and discovering previously unknown BGCs. Nonetheless, studying distribution patterns of novel BGCs and elucidating the biosynthesis of orphan metabolites remains a challenge. To fill this knowledge gap, our study developed a pipeline for high-quality comparative genomics for the actinomycete genus

Rhodococcus

, which is metabolically versatile, yet understudied in terms of NPs, leading to a total of 110 genomes, 1891 BGCs and 717 non-ribosomal peptide synthetases (NRPSs). Phylogenomic inferences showed four major clades retrieved from strains of several ecological habitats. BiG-SCAPE sequence similarity BGC networking revealed 44 unidentified gene cluster families (GCFs) for NRPS, which presented a phylogenomic-dependent evolution pattern, supporting the hypothesis of vertical gene transfer. As a proof of concept, we analysed in-depth one of our marine strains,

Rhodococcus

sp. H-CA8f, which revealed a unique BGC distribution within its phylogenomic clade, involved in producing a chloramphenicol-related compound. While this BGC is part of the most abundant and widely distributed NRPS GCF, corason analysis unveiled major differences regarding its genetic context, co-occurrence patterns and modularity. This BGC is composed of three sections, two well-conserved right/left arms flanking a very variable middle section, composed of nrps genes. The presence of two non-canonical domains in H-CA8f’s BGC may contribute to adding chemical diversity to this family of NPs. Liquid chromatography-high resolution MS and dereplication efforts retrieved a set of related orphan metabolites, the corynecins, which to our knowledge are reported here for the first time in

Rhodococcus

. Overall, our data provide insights to connect BGC uniqueness with orphan metabolites, by revealing key comparative genomic features supported by models of BGC distribution along phylogeny.
Preferential preservation of visuospatial memory over verbal memory in the Old Order Amish
Authors: Prough Michael B. , Caywood Laura J. , Clouse Jason E. , Herington Sharlene D. , Slifer Susan H. , Dorfsman Daniel A. , Adams Larry D. , Laux Reneé A. , Song Yeunjoo E. , Lynn Audrey , Fuzzell M. Denise , Fuzzell Sarada L. , Hochstetler Sherri D. , Miskimen Kristy , Main Leighanne R. , Osterman Michael D. , Ogrocki Paula , Lerner Alan J. , Ramos Jairo , Vance Jeffery M. , Cuccaro Michael L. , Haines Jonathan L. , Scott William K. , Pericak-Vance Margaret A.
Published: July 2021

Background

While studying cognition in the Old Order Amish (OOA), we have observed strong performance on the constructional praxis delayed recall (CPDR) as compared to other cognitive tests, independent of overall cognitive status. This may indicate a preferential preservation of visuospatial memory in this population. Here, we investigate this by comparing the CPDR to the word list delayed recall (WLDR) within the OOA, as well as by comparing these results to a non-Amish cohort.

Method

420 OOA individuals in Indiana/Ohio age 66-95 who had complete data for the CPDR and WLDR were included. From the non-Amish CERAD cohort, 401 individuals age 60-96 with the same tests were included. For both cohorts, education-adjusted Z-scores were calculated for the CPDR and WLDR. The difference between the CPDR Z-score and the WLDR Z-score was calculated as a measure of the preservation of visuospatial memory over verbal memory. T-tests were first used to compare the tests within both cohorts and then stratified by case/control status. Linear regression was then used to investigate the effects of age, sex, cognitive status, and cohort on the Z-scores and difference between Z-scores. Additional t-tests and regressions were then performed to further investigate the effect of sex and its interaction with cohort.

Result

We found a significantly better performance on CPDR over WLDR in every cognitive status group in the OOA, but not in all groups of the CERAD cohort. After controlling for age, sex, and cognitive status, this preferential preservation remains significantly higher in the Amish, with being in the Amish cohort increasing the difference between Z-scores by an average of 0.615 units when compared to being in the CERAD cohort. When adjusting for age, sex, cognitive status, and cohort, the interaction between cohort and sex is significant, with the Amish males exhibiting a greater difference between Z-scores compared to other groups, with a significant interaction value of 0.676.

Discussion

Overall, these findings suggest that the OOA preferentially preserve visuospatial memory over verbal memory, regardless of cognitive status. This effect is particularly strong in OOA males. In summary, this study gives additional evidence that the Amish exhibit unique patterns of memory loss and aging, with a preferential preservation of visuospatial memory over verbal memory. Additional studies are needed to further explain this phenomenon.
Following the science? Views from scientists on government advisory boards during the COVID-19 pandemic: a qualitative interview study in five European countries
Authors: Colman Elien , Wanat Marta , Goosens Herman , Tonkin-Crine Sarah , Anthierens Sibyl
Published: July 2021

Objectives: To explore the views and experiences of scientists working on government advisory boards during the COVID-19 pandemic, with the aim to learn lessons for future pandemic management and preparedness.
Design: Explorative qualitative interview study.
Participants: Twenty one scientists with an official government advisory role during the COVID-19 pandemic in Belgium, the Netherlands, UK, Sweden or Germany.
Methods: Online video or telephone semi-structured interviews took place between December 2020 and April 2021. They were audio recorded and transcribed, and analyzed using a combination of inductive and deductive thematic analysis techniques.
Results: Scientists found working on the advisory boards during the COVID-19 pandemic to be a rewarding experience. However, they identified numerous challenges including learning to work in an interdisciplinary way, ensuring that evidence is understood and taken on board by governments, and dealing with media and public reactions. Scientists found themselves taking on new roles, the boundaries of which were not clearly defined. Consequently, they received substantial media attention and were often perceived and treated as a public figure.
Conclusions: Scientists working on advisory boards in European countries faced similar challenges, highlighting key lessons to be learnt. Future pandemic preparedness efforts should focus on building interdisciplinary collaboration within advisory boards; ensuring transparency in how boards operate; defining and protecting boundaries of the scientific advisor role; and supporting scientists to inform the public in the fight against disinformation, whilst dealing with potential hostile reactions.
AI-DRIVEN QUANTIFICATION OF GROUND GLASS OPACITIES IN LUNGS OF COVID-19 PATIENTS USING 3D COMPUTED TOMOGRAPHY IMAGING
Authors: Saha Monjoy , Amin Sagar B. , Sharma Ashish , Kumar T. K. Satish , Kalia Rajiv K.
Published: July 2021

Objectives

Ground-glass opacity (GGO) — a hazy, gray appearing density on computed tomography (CT) of lungs — is one of the hallmark features of SARS-CoV-2 in COVID-19 patients. This AI-driven study is focused on segmentation, morphology, and distribution patterns of GGOs.

Method

We use an AI-driven unsupervised machine learning approach called PointNet++ to detect and quantify GGOs in CT scans of COVID-19 patients and to assess the severity of the disease. We have conducted our study on the “MosMedData”, which contains CT lung scans of 1110 patients with or without COVID-19 infections. We quantify the morphologies of GGOs using Minkowski tensors and compute the abnormality score of individual regions of segmented lung and GGOs.

Results

PointNet++ detects GGOs with the highest evaluation accuracy (98%), average class accuracy (95%), and intersection over union (92%) using only a fraction of 3D data. On average, the shapes of GGOs in the COVID-19 datasets deviate from sphericity by 15% and anisotropies in GGOs are dominated by dipole and hexapole components. These anisotropies may help to quantitatively delineate GGOs of COVID-19 from other lung diseases.

Conclusion

The PointNet++ and the Minkowski tensor based morphological approach together with abnormality analysis will provide radiologists and clinicians with a valuable set of tools when interpreting CT lung scans of COVID-19 patients. Implementation would be particularly useful in countries severely devastated by COVID-19 such as India, where the number of cases has outstripped available resources creating delays or even breakdowns in patient care. This AI-driven approach synthesizes both the unique GGO distribution pattern and severity of the disease to allow for more efficient diagnosis, triaging and conservation of limited resources.

Key Points

Our approach to GGO analysis has four distinguishing features:

We combine an unsupervised computer vision approach with convex hull and convex points algorithms to segment and preserve the actual structure of the lung.

To the best of our knowledge, we are the first group to use PointNet++ architecture for 3D visualization, segmentation, classification, and pattern analysis of GGOs.

We make abnormality predictions using a deep network and Cox proportional hazards model using lung CT images of COVID-19 patients.

We quantify the shapes and sizes of GGOs using Minkowski tensors to understand the morphological variations of GGOs within the COVID-19 cohort.
The role of the uncinate fasciculus in the risk-architecture of bipolar disorders: A meta-analysis
Authors: Xu Ellie , Nguyen Lynn , Hu Rebecca , Stavish Caitlin M. , Leibenluft Ellen , Linke Julia O.
Published: July 2021

Background

Bipolar disorder (BD) is a severe mental disorder, characterized by prominent mood swings and emotion regulation (ER) deficits. The uncinate fasciculus (UF), a white matter tract connecting the amygdala and the ventral prefrontal cortex, has been implicated in ER. Aberrancies in UF microstructure may be an endophenotype associated with increased risk for BD. However, findings in individuals with BD and at familial risk for BD (AR) have yielded inconsistent findings. This meta-analysis takes a region-of-interest approach to consolidate the available evidence and elucidate the role of the UF in the risk-architecture of BD.

Methods

Using web-based search engines, we identified diffusion tensor imaging studies focusing on the left and right UF and conducted meta-analyses comparing fractional anisotropy (FA) and radial diffusivity (RD) between BD or AR to healthy volunteers (HV).

Results

We included 32 studies (nBD=1186, nHV=2001; nAR=289, nHV=314). Compared to HV, individuals with BD showed lower FA in the right (p<.0001) and left UF (p=.010), and higher RD in the right UF (p=.009). We found no significant differences between AR and HV. In the right but not the left UF, AR individuals showed higher FA than BD (p=.043).

Conclusion

Comparable UF microstructure between AR and HV and higher FA in the right UF in AR compared to BD suggest that aberrancies in UF microstructure is not an endophenotype for BD. Longitudinal studies are needed to determine when UF abnormalities emerge in the context of BD.
BNT162b2 vaccine-induced humoral and cellular responses against SARS-CoV-2 variants in Systemic Lupus Erythematosus
Authors: Moyon Quentin , Sterlin Delphine , Miyara Makoto , Anna François , Mathian Alexis , Lhote Raphael , Ghillani-Dalbin Pascale , Breillat Paul , Mudumba Sasi , de Alba Sophia , Cohen-Aubart Fleur , Haroche Julien , Pha Micheline , Du Boutin Thi Huong , Chaieb Hedi , Pedro Flores , Charneau Pierre , Gorochov Guy , Amoura Zahir
Published: July 2021

Objectives

Our aims were to evaluate Systemic Lupus Erythematosus (SLE) disease activity and SARS-CoV-2 specific immune responses after BNT162b2 vaccination.

Methods

In this prospective study, disease activity and clinical assessments were recorded from the first dose of vaccine, until day 15 after the second dose in 126 SLE patients. SARS-CoV-2 antibody responses were measured against wild-type spike antigen while serum-neutralizing activity was assessed against the SARS-CoV-2 historical strain and variants of concerns (VOCs). Vaccine-specific T-cell responses were quantified by Interferon (IFN)-γ release assay after the second dose.

Results

BNT162b2 was well tolerated and no statistically significant variations of BILAG and SLEDAI scores were observed throughout the study in SLE patients with active and inactive disease at baseline. Mycophenolate Mofetil (MMF) and Methotrexate (MTX) treatments were associated with drastically reduced BNT162b2 antibody-response (β=-78; p=0.007, β=-122; p<0.001, respectively). Anti-spike antibody response was positively associated with baseline total IgG serum levels, naïve B cell frequencies (β=2; p=0.018, β=2.5; p=0.003) and SARS-CoV-2-specific T cell response (r=0.462; p=0.003). In responders, serum neutralization activity decreased against VOCs bearing the E484K mutation but remained detectable in a majority of patients.

Conclusion

MMF, MTX and poor baseline humoral immune status, particularly: low naïve B cell frequencies, are independently associated with impaired BNT162b2 mRNA antibody response, delineating SLE patients who might need adapted vaccine regimens and follow-up.

KEY MESSAGES

What is already known about this subject?

BNT162b2 efficacy and safety has been described in studies mixing different RMDs

What does this study add?

No serious adverse effects, nor SLE flares have been documented after BNT162b2 in SLE patients.

Not only MMF and MTX, but also a poor humoral immune status at baseline impair vaccine antibody response

Albeit decreased, serum neutralizing activity against VOCs is conferred to vaccine-responders.

How might this impact on clinical practice or future developments?

These parameters could be helpful for physicians to delineate which patients should have antibody measurement after full BNT162b2 vaccination and should be proposed a third injection of BNT162b2 vaccine.
“What do you mean I can’t have a doctor? This is Canada!” – A Qualitative Study of the Myriad Consequences for Unattached Patients Awaiting Primary Care Attachment
Authors: Marshall Emily Gard , Wuite Sara , Lawson Beverley , Andrew Melissa K. , Edwards Lynn , MacKenzie Adrian , Woodrow Ana Correa , Peddle Sarah
Published: July 2021

Background

Patient access to primary healthcare (PHC) is the foundation of a strong healthcare system and healthy populations. Attachment to a regular PHC provider, a key to healthcare access, has seen a decline in some jurisdictions. This study explored the consequences of unattachment from a patient perspective, an under-studied phenomenon to date.

Methods

A realist-informed qualitative study was conducted with unattached patients in Nova Scotia, Canada. Semi-structured interviews with nine participants were conducted and transcribed for analysis. The framework method was used to carry out analysis, which was guided by Donabedian’s model of assessing healthcare access and quality.

Results

Five key findings were noted in this study: 1) Participants experienced a range of consequences from not having a regular PHC provider. Participants used creative strategies to 2) attempt to gain attachment to a regular PHC provider, and, to 3) address their health needs in the absence of a regular PHC provider. 4) Participants experienced negative feelings about themselves and the healthcare system, and 5) stress related to the consequences and added work of being unattached and lost care.

Conclusions

Unattached patients experienced a burden of care related to lost care and managing their own health and related information, due to the download of medical record management and system navigation to them. These findings may underestimate the consequences for further at-risk populations who would not have been included in our recruitment. This may result in poorer health outcomes, which could be mitigated by interventions at the structural level, such as enhanced centralized waitlists to promote attachment. Such waitlists may benefit from a triage approach to appropriately attach patients based on need.
The Impact of Sampling Type, Frequency and Scale of Collection System on SARS-CoV-2 Quantification Fidelity
Authors: George Andrea D. , Kaya Devrim , Layton Blythe A. , Bailey Kestrel , Kelly Christine , Williamson Kenneth J. , Radniecki Tyler S.
Published: July 2021

With the rapid onset of the COVID-19 pandemic, wastewater-based epidemiology (WBE) sampling methodologies for SARS-CoV-2 were often implemented quickly and may not have taken the unique drainage catchment characteristics into account. One question of debate is the relevance of grab versus composite samples when surveying for SARS-CoV-2 at various catchment scales. This study assessed the impact of grab versus composite sampling on the detection and quantification of SARS-CoV-2 in catchment basins with flow rates ranging from high-flow (wastewater treatment plant influent), to medium-flow (neighborhood-scale micro-sewershed), to low-flow (city block-scale micro-sewershed) and down to ultra-low flow (building scale). At the high-flow site, grab samples were reasonably comparable to 24-h composite samples with the same non-detect rate (0%) and SARS-CoV-2 concentrations that differed by 32% on the Log10 scale. However, as the flow rates decreased, the percentage of false-negative grab samples increased up to 44% and the SARS-CoV-2 concentrations of grab samples varied by up to 1-2 orders of magnitude compared to their respective composite sample concentrations. At the ultra-low-flow site, increased sampling frequencies down to every 5 min led to composite samples with higher fidelity to the SARS-CoV-2 load. Thus, composite sampling is superior to grab sampling, especially as flow decreases.

Synopsis

The need for composite sampling to generate reliable SARS-CoV-2 wastewater based epidemiology results increases as the collection basin scale decreases.

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Twins in Guinea-Bissau have a ‘thin-fat’ body composition compared to singletons
Authors: Wagh Rucha , Bjerregaard-Andersen Morten , Bandyopadhyay Souvik , Yajnik Pranav , Prasad Rashmi B , Otiv Suhas , Byberg Stine , Hennild Ditte Egegaard , Gomes Gabriel Marciano , Christensen Kaare , Sodemann Morten , Jensen Dorte Møller , Yajnik Chittaranjan
Published: July 2021

‘Thrifty phenotype’ hypothesis proposed that fetal undernutrition increases risk of diabetes in later life. Undernourished low birthweight Indian babies are paradoxically more adipose compared to well-nourished European babies, and are at higher risk of diabetes in later life. Twin pregnancies are an example ofin uterogrowth restrictive environment due to shared maternal nutrition. There are few studies of body composition in twins. We performed secondary analysis of anthropometric body composition of twins and singletons in Guinea-Bissau, an economically deprived African country.

Anthropometric data was available on 7–34 year-old twins (n=209, 97 males) and singletons (n=182, 86 males) in the Guinea-Bissau Twin Registry at the Bandim Health Project. Twins had lower birth weight (2420 vs 3100 g, p<0.001); and at follow-up, lower height (HAZ mean Z-score difference, -0.21, p=0.055), weight (WAZ -0.73, p=0.024) and BMI (BAZ -0.22, p=0.079) compared to singletons but higher adiposity (skinfolds: +0.33 SD, p=0.001). Twins also had higher fasting (+0.38 SD, p<0.001) and 2-hr OGTT glucose concentrations (+0.29 SD, p<0.05). Linear mixed-effect model accounting for intrapair correlations and interactions confirmed that twins were thinner but fatter across the age range. Data on maternal morbidity and prematurity were not available in this cohort.

African populations are known to have a muscular (less adipose) body composition. Demonstration of a thin-fat phenotype in twins in a low socioeconomic African country supports the thesis that it could be a manifestation of early life undernutrition and not exclusive to Indians. This phenotype could increase risk of diabetes and related conditions.
The potential for mobile demersal fishing to reduce carbon storage and sequestration in seabed sediments
Authors: Epstein Graham , Hawkins Julie P. , Norris Catrin R. , Roberts Callum M.
Published: July 2021

Subtidal marine sediments are one of the planet’s primary carbon stores and strongly influence the oceanic sink for atmospheric CO2. By far the most pervasive human activity occurring on the seabed is bottom trawling and dredging for fish and shellfish. A global first-order estimate suggested mobile demersal fishing activities may cause 160-400 Mt of organic carbon (OC) to be remineralised annually from seabed sediment carbon stores. There are, however, many uncertainties in this calculation. Here, we discuss the potential drivers of change in seabed OC stores due to mobile demersal fishing activities and conduct a systematic review, synthesising studies where this interaction has been directly investigated. Mobile demersal fishing would be expected to reduce OC in seabed stores, albeit with site-specific variability. Reductions would occur due to lower production of flora and fauna, the loss of fine flocculent material, increased sediment resuspension, mixing and transport, and increased oxygen exposure. This would be offset to some extent by reduced faunal bioturbation and respiration, increased off-shelf transport and increases in primary production from the resuspension of nutrients. Studies which directly investigated the impact of demersal fishing on OC stocks had mixed results. A finding of no significant effect was reported in 51% of 59 experimental contrasts; 41% reported lower OC due to fishing activities, with 8% reporting higher OC. In relation to remineralisation rates within the seabed, 14 experimental contrasts reported that demersal fishing activities decreased remineralisation, with four reporting higher remineralisation rates. The direction of effects was related to sediment type, impact duration, study design and local hydrography. More evidence is urgently needed to accurately quantify the impact of anthropogenic physical disturbance on seabed carbon in different environmental settings, and incorporate full evidence-based carbon considerations into global seabed management.
MPA_Pathway_Tool: User-friendly, automatic assignment of microbial community data on metabolic pathways
Authors: Walke Daniel , Schallert Kay , Ramesh Prasanna , Benndorf Dirk , Lange Emanuel , Reichl Udo , Heyer Robert
Published: July 2021

Motivation

Taxonomic and functional characterization of microbial communities from diverse environments such as the human gut or biogas plants by multi-omics methods plays an ever more important role. Researchers assign all identified genes, transcripts, or proteins to biological pathways to better understand the function of single species and microbial communities. However, due to the versatility of microbial metabolism and a still increasing number of new biological pathways, linkage to standard pathway maps such as the KEGG (Kyoto Encyclopedia of Genes and Genomes) central carbon metabolism is often problematic.

Results

We successfully implemented and validated a new user-friendly, stand-alone web application, the MPA_Pathway_Tool. It consists of two parts, called ‘Pathway-Creator’ and ‘Pathway-Calculator’. The ‘Pathway-Creator’ enables an easy setup of user-defined pathways with specific taxonomic constraints. The ‘Pathway-Calculator’ automatically maps microbial community data from multiple measurements on selected pathways and visualizes the results.

Availability and Implementation

The MPA_Pathway_Tool is implemented in Java and ReactJS. It is freely available onhttp://mpa-pathwaymapper.ovgu.de/. Further documentation and the complete source code are available on GitHub (https://github.com/danielwalke/MPA_Pathway_Tool).

Contact

daniel.walke@ovgu.de, mailto:heyer@mpi-magdeburg.mpg.deheyer@mpi-magdeburg.mpg.de

Supplementary Information

Additional files and images are available atMDPIonline.

Highlights

user-friendly generation of pathways, re-using of existent metabolic pathways, automated mapping of data
Identifying Protein Complexes in Protein-protein Interaction Data using Graph Convolution Network
Authors: Zaki Nazar , Singh Harsh
Published: July 2021

Protein complexes are groups of two or more polypeptide chains that join together to build noncovalent networks of protein interactions. A number of means of computing the ways in which protein complexes and their members can be identified from these interaction networks have been created. While most of the existing methods identify protein complexes from the protein-protein interaction networks (PPIs) at a fairly decent level, the applicability of advanced graph network methods has not yet been adequately investigated. In this paper, we proposed various graph convolutional networks (GCNs) methods to improve the detection of the protein functional complexes. We first formulated the protein complex detection problem as a node classification problem. Second, the Neural Overlapping Community Detection (NOCD) model was applied to cluster the nodes (proteins) using a complex affiliation matrix. A representation learning approach, which combines the multi-class GCN feature extractor (to obtain the features of the nodes) and the mean shift clustering algorithm (to perform clustering), is also presented. We have also improved the efficiency of the multi-class GCN network to reduce space and time complexities by converting the dense-dense matrix operations into dense-spares or sparse-sparse matrix operations. This proposed solution significantly improves the scalability of the existing GCN network. Finally, we apply clustering aggregation to find the best protein complexes. A grid search was performed on various detected complexes obtained by applying three well-known protein detection methods namely ClusterONE, CMC, and PEWCC with the help of the Meta-Clustering Algorithm (MCLA) and Hybrid Bipartite Graph Formulation (HBGF) algorithm. The proposed GCN-based methods were tested on various publicly available datasets and provided significantly better performance than the previous state-of-the-art methods. The code and data used in this study are available fromhttps://github.com/Analystharsh/GCN_complex_detection
Gene co-expression reveals the modularity and integration of C4and CAM inPortulaca
Authors: Gilman Ian S. , Moreno-Villena Jose J. , Lewis Zachary R. , Goolsby Eric W. , Edwards Erika J.
Published: July 2021

C4photosynthesis and Crassulacean acid metabolism (CAM) have been considered as largely independent adaptations in spite of sharing key biochemical modules.Portulacais a geographically widespread clade of over 100 annual and perennial angiosperm species that primarily use C4, but facultatively exhibit CAM when drought stressed, a photosynthetic system known as C4+CAM. It has been hypothesized that C4+CAM is rare because of pleiotropic constraints, but these have not been deeply explored. We generated a chromosome-level genome assembly ofP. amilisand sampled mRNA fromP. amilisandP. oleraceaduring CAM induction. Gene co-expression network analyses identified C4and CAM gene modules shared and unique to bothPortulacaspecies. A conserved CAM module linked phosphoenolpyruvate carboxylase (PEPC) to starch turnover during the day-night transition and was enriched in circadian clock regulatory motifs in theP. amilisgenome. Preservation of this co-expression module regardless of water status suggests thatPortulacaconstitutively operate a weak CAM cycle that is transcriptionally and post-transcriptionally upregulated during drought. C4and CAM mostly used mutually exclusive genes for primary carbon fixation and it is likely that nocturnal CAM malate stores are shuttled into diurnal C4decarboxylation pathways, but we find evidence that metabolite cycling may occur at low levels. C4likely evolved inPortulacathrough co-option of redundant genes and integration of the diurnal portion of CAM. Thus, the ancestral CAM system did not strongly constrain C4evolution because photosynthetic gene networks are not co-regulated for both daytime and nighttime functions.