bluuebunny/crossref_metadata_2025 huggingface dataset:
Combining natural language processing and metabarcoding to reveal pathogen-environment associations
Authors: Molik David C. , Tomlinson DeAndre , Davitt Shane , Morgan Eric L. , Sisk Matthew , Roche Benjamin , Meyers Natalie , Pfrender Michael E.
Published: April 2021

Cryptococcus neoformans is responsible for life-threatening infections that primarily affect immunocompromised individuals and has an estimated worldwide burden of 220,000 new cases each year—with 180,000 resulting deaths—mostly in sub-Saharan Africa. Surprisingly, little is known about the ecological niches occupied by C. neoformans in nature. To expand our understanding of the distribution and ecological associations of this pathogen we implement a Natural Language Processing approach to better describe the niche of C. neoformans. We use a Latent Dirichlet Allocation model to de novo topic model sets of metagenetic research articles written about varied subjects which either explicitly mention, inadvertently find, or fail to find C. neoformans. These articles are all linked to NCBI Sequence Read Archive datasets of 18S ribosomal RNA and/or Internal Transcribed Spacer gene-regions. The number of topics was determined based on the model coherence score, and articles were assigned to the created topics via a Machine Learning approach with a Random Forest algorithm. Our analysis provides support for a previously suggested linkage between C. neoformans and soils associated with decomposing wood. Our approach, using a search of single-locus metagenetic data, gathering papers connected to the datasets, de novo determination of topics, the number of topics, and assignment of articles to the topics, illustrates how such an analysis pipeline can harness large-scale datasets that are published/available but not necessarily fully analyzed, or whose metadata is not harmonized with other studies. Our approach can be applied to a variety of systems to assert potential evidence of environmental associations.
An update on the occurrence of Paracoccidioides species in the Midwest region, Brazil: Molecular epidemiology, clinical aspects and serological profile of patients from Mato Grosso do Sul State
Authors: Mattos Karine , Cocio Tiago Alexandre , Chaves Edilânia Gomes Araújo , Borges Clayton Luiz , Venturini James , de Carvalho Lídia Raquel , Mendes Rinaldo Poncio , Paniago Anamaria Mello Miranda , Weber Simone Schneider
Published: April 2021

Background

Paracoccidioidomycosis (PCM) is a systemic and endemic fungal infection in Latin American, mainly in Brazil. The majority of PCM cases occur in large areas in Brazil, comprising the South, Southeast and Midwest regions, with the latter demonstrating a higher incidence of the species Paracoccidioides lutzii.

Methodology and main findings

This study presents clinical, molecular and serological data of thirteen new PCM cases during 2016 to 2019 from the state of Mato Grosso do Sul, located in the Midwest region, Brazil. From these thirteen cases, sixteen clinical isolates were obtained and their genomic DNAs were subjected to genotyping by tub1 -PCR-RFLP. Results showed Paracoccidioides brasiliensis sensu stricto (S1) (11/16; 68.8%), Paracoccidioides restrepiensis (PS3) (4/16; 25.0%) and P. lutzii (1/16; 6.2%) as Paracoccidiodes species. Therefore, in order to understand whether the type of phylogenetic species that are circulating in the state influence the reactivity profile of serological tests, we performed double agar gel immunodiffusion (DID), using exoantigens from genotyped strains found in this series of PCM cases. Overall, our DID tests have been false negative in about 30% of confirmed PCM cases. All patients were male, most with current or previous rural activity, with ages ranging from 17 to 59 years, with 11 patients (84.6%) over 40 years of age. No clinical or epidemiological differences were found between Paracoccidioides species. However, it is important to note that the only case of P. lutzii died as an outcome.

Conclusions

This study suggests P. brasiliensis sensu stricto (S1) as the predominant species, showing its wide geographic distribution in Brazil. Furthermore, our findings revealed, for the first time, the occurrence of P. restrepiensis (PS3) in the state of Mato Grosso do Sul, Brazil. Despite our setbacks, it would be interesting to provide the complete sequencing of these clinical isolates to complement the molecular information presented.
Aedes aegypti dyspepsia encodes a novel member of the SLC16 family of transporters and is critical for reproductive fitness
Authors: Tsujimoto Hitoshi , Anderson Michelle A. E. , Eggleston Heather , Myles Kevin M. , Adelman Zach N.
Published: April 2021

As a key vector for major arthropod-borne viruses (arboviruses) such as dengue, Zika and chikungunya, control of Aedes aegypti represents a major challenge in public health. Bloodmeal acquisition is necessary for the reproduction of vector mosquitoes and pathogen transmission. Blood contains potentially toxic amounts of iron while it provides nutrients for mosquito offspring; disruption of iron homeostasis in the mosquito may therefore lead to novel control strategies. We previously described a potential iron exporter in Ae. aegypti after a targeted functional screen of ZIP (zinc-regulated transporter/Iron-regulated transporter-like) and ZnT (zinc transporter) family genes. In this study, we performed an RNAseq-based screen in an Ae. aegypti cell line cultured under iron-deficient and iron-excess conditions. A subset of differentially expressed genes were analyzed via a cytosolic iron-sensitive dual-luciferase reporter assay with several gene candidates potentially involved in iron transport. In vivo gene silencing resulted in significant reduction of fecundity (egg number) and fertility (hatch rate) for one gene, termed dyspepsia. Silencing of dyspepsia reduced the induction of ferritin expression in the midgut and also resulted in delayed/impaired excretion and digestion. Further characterization of this gene, including a more direct confirmation of its substrate (iron or otherwise), could inform vector control strategies as well as to contribute to the field of metal biology.
Interaction of amphiphilic lipoarabinomannan with host carrier lipoproteins in tuberculosis patients: Implications for blood-based diagnostics
Authors: Jakhar Shailja , Sakamuri Ramamurthy , Vu Dung , Dighe Priya , Stromberg Loreen R. , Lilley Laura , Hengartner Nicolas , Swanson Basil I. , Moreau Emmanuel , Dorman Susan E. , Mukundan Harshini
Published: April 2021

Lipoarabinomannan (LAM), an amphiphilic lipoglycan of the Mycobacterium tuberculosis cell wall, is a diagnostic target for tuberculosis. Previous work from our laboratory and others suggests that LAM is associated with host serum lipoproteins, which may in turn have implications for diagnostic assays. Our team has developed two serum assays for amphiphile detection: lipoprotein capture and membrane insertion. The lipoprotein capture assay relies on capture of the host lipoproteins, exploiting the biological association of host lipoprotein with microbial amphiphilic biomarkers to “concentrate” LAM. In contrast, the membrane insertion assay is independent of the association between pathogen amphiphiles and host lipoprotein association, and directly captures LAM based on its thermodynamic propensity for association with a supported lipid membrane, which forms the functional surface of an optical biosensor. In this manuscript, we explored the use of these assays for the detection of LAM in sera from adults whose tuberculosis status had been well-characterized using conventional microbiological tests, and endemic controls. Using the lipoprotein capture assay, LAM signal/noise ratios were >1.0 in 29/35 (83%) individuals with culture-confirmed active tuberculosis, 8/13 (62%) individuals with tuberculosis symptoms, but no positive culture for M. tuberculosis, and 0/6 (0%) symptom-free endemic controls. To evaluate serum LAM levels without bias associated with potential differences in circulating host lipoprotein concentrations between individuals, we subsequently processed available samples to liberate LAM from associated host lipoprotein assemblies followed by direct detection of the pathogen biomarker using the membrane insertion approach. Using the membrane insertion assay, signal/noise for detection of serum LAM was greater than that observed using the lipoprotein capture method for culture-confirmed TB patients (6/6), yet remained negative for controls (2/2). Taken together, these results suggest that detection of serum LAM is a promising TB diagnostic approach, but that further work is required to optimize assay performance and to decipher the implications of LAM/host lipoprotein associations for diagnostic assay performance and TB pathogenesis.
Reward signalling in brainstem nuclei under fluctuating blood glucose
Authors: Morville Tobias , Madsen Kristoffer H. , Siebner Hartwig R. , Hulme Oliver J.
Published: April 2021

Phasic dopamine release from mid-brain dopaminergic neurons is thought to signal errors of reward prediction (RPE). If reward maximisation is to maintain homeostasis, then the value of primary rewards should be coupled to the homeostatic errors they remediate. This leads to the prediction that RPE signals should be configured as a function of homeostatic state and thus diminish with the attenuation of homeostatic error. To test this hypothesis, we collected a large volume of functional MRI data from five human volunteers on four separate days. After fasting for 12 hours, subjects consumed preloads that differed in glucose concentration. Participants then underwent a Pavlovian cue-conditioning paradigm in which the colour of a fixation-cross was stochastically associated with the delivery of water or glucose via a gustometer. This design afforded computation of RPE separately for better- and worse-than expected outcomes during ascending and descending trajectories of serum glucose fluctuations. In the parabrachial nuclei, regional activity coding positive RPEs scaled positively with serum glucose for both ascending and descending glucose levels. The ventral tegmental area and substantia nigra became more sensitive to negative RPEs when glucose levels were ascending. Together, the results suggest that RPE signals in key brainstem structures are modulated by homeostatic trajectories of naturally occurring glycaemic flux, revealing a tight interplay between homeostatic state and the neural encoding of primary reward in the human brain.
Network analysis of narrative discourse and attention-deficit hyperactivity symptoms in adults
Authors: Coelho Rafael Martins , Drummond Cláudia , Mota Natália Bezerra , Erthal Pilar , Bernardes Gabriel , Lima Gabriel , Molina Raquel , Sudo Felipe Kenji , Tannock Rosemary , Mattos Paulo
Published: April 2021

Previous research investigating language in attention-deficit hyperactivity disorder (ADHD) has demonstrated several deficits in many aspects. However, no previous study employed quantitative methodology providing objective measures that could be compared among different studies with diverse samples. To fill this gap, we used network analysis to investigate how ADHD symptomatology impacts narrative discourse, a complex linguistic task considered to be an ecological measure of language. Fifty-eight adults (34 females and 24 males) with a mean age of 26 years old and a mean of 17 years of educational level were administered the Adult Self-Rating Scale for ADHD symptomatology. They also completed the State-Trait Anxiety Inventory, the Beck Depression Inventory and the Urgency, Premeditation, Perseverance, Sensation Seeking Behavior Scale. Intelligence quotient was calculated. Individuals were asked to tell a story based on a wordless picture book. Speech was recorded and transcribed as an input to SpeechGraphs software. Parameters were total number of words (TNW), number of loops of one node (L1), repeated edges (RE), largest strongly connected component (LSC) and average shortest path (ASP). Verbosity was controlled. Statistical analysis was corrected for multiples comparisons and partial correlations were performed for confounding variables. After controlling for anxiety, depression, IQ, and impulsiveness ADHD symptomatology was positively correlated with L1 and negatively correlated with LSC. TNW was positively correlated with ADHD symptoms. In a subdomain analysis, both inattention and hyperactivity-impulsivity were negatively correlated with LSC. Only hyperactivity-impulsivity positively correlated with TNW and L1. Results indicated a correlation between ADHD symptoms and lower connectedness in narrative discourse (as indicated by higher L1 and lower LSC), as well as higher total number of words (TNW). Our results suggest that the higher the number of ADHD symptoms, the less connectivity among words, and a higher number of words in narrative discourse.
Genotyping-by-Sequencing of the regional Pacific abalone (Haliotis discus) genomes reveals population structures and patterns of gene flow
Authors: Nam Bo-Hye , Kim Hyaekang , Seol Donghyeok , Kim Heebal , Noh Eun Soo , Kim Eun Mi , Noh Jae Koo , Kim Young-Ok , Park Jung Youn , Kwak Woori
Published: April 2021

Continuous monitoring of the present genetic status is essential to preserve the genetic resource of wild populations. In this study, we sequenced regional Pacific abalone Haliotis discus samples from three different locations around the Korean peninsula to assess population structure, utilizing Genotyping-by-Sequencing (GBS) method. Using PstI enzyme for genome reduction, we demonstrated the resultant library represented the whole genome region with even spacing, and as a result 16,603 single nucleotide variants (SNVs) were produced. Genetic diversity and population structure were investigated using several methods, and a strong genetic heterogeneity was observed in the Korean abalone populations. Additionally, by comparison of the variant sets among population groups, we were able to discover 26 Korean abalone population-specific SNVs, potentially associated with phenotype differences. This is the first study demonstrating the feasibility of GBS for population genetic study on H. discus. Our results will provide valuable data for the genetic conservation and management of wild abalone populations in Korea and help future GBS studies on the marine mollusks.
Identifying treatment options for BRAFV600 wild-type metastatic melanoma: A SU2C/MRA genomics-enabled clinical trial
Authors: LoRusso Patricia M. , Sekulic Aleksandar , Sosman Jeffrey A. , Liang Winnie S. , Carpten John , Craig David W. , Solit David B. , Bryce Alan H. , Kiefer Jeffrey A. , Aldrich Jessica , Nasser Sara , Halperin Rebecca , Byron Sara A. , Pilat Mary Jo , Boerner Scott A. , Durecki Diane , Hendricks William P. D. , Enriquez Daniel , Izatt Tyler , Keats Jonathan , Legendre Christophe , Markovic Svetomir N. , Weise Amy , Naveed Fatima , Schmidt Jessica , Basu Gargi D. , Sekar Shobana , Adkins Jonathan , Tassone Erica , Sivaprakasam Karthigayini , Zismann Victoria , Calvert Valerie S. , Petricoin Emanuel F. , Fecher Leslie Anne , Lao Christopher , Eder J. Paul , Vogelzang Nicholas J. , Perlmutter Jane , Gorman Mark , Manica Barbara , Fox Lisa , Schork Nicholas , Zelterman Daniel , DeVeaux Michelle , Joseph Richard W. , Cowey C. Lance , Trent Jeffrey M.
Published: April 2021

Although combination BRAF and MEK inhibitors are highly effective for the 40–50% of cutaneous metastatic melanomas harboring BRAFV600 mutations, targeted agents have been ineffective for BRAFV600wild-type (wt) metastatic melanomas. The SU2C Genomics-Enabled Medicine for Melanoma Trial utilized a Simon two-stage optimal design to assess whether comprehensive genomic profiling improves selection of molecular-based therapies for BRAFV600wt metastatic melanoma patients who had progressed on standard-of-care therapy, which may include immunotherapy. Of the response-evaluable patients, binimetinib was selected for 20 patients randomized to the genomics-enabled arm, and nine were treated on the alternate treatment arm. Response rates for 27 patients treated with targeted recommendations included one (4%) partial response, 18 (67%) with stable disease, and eight (30%) with progressive disease. Post-trial genomic and protein pathway activation mapping identified additional drug classes that may be considered for future studies. Our results highlight the complexity and heterogeneity of metastatic melanomas, as well as how the lack of response in this trial may be associated with limitations including monotherapy drug selection and the dearth of available single and combination molecularly-driven therapies to treat BRAFV600wt metastatic melanomas.
Spatial distribution of the summer subsurface chlorophyll maximum in the North South China Sea
Authors: Chen Ying , Zhao Hui
Published: April 2021

Based on the biological, nutrients and hydrological data in August 2018, the vertical chlorophyll a (Chl-a) concentration profiles and the relationship among surface Chl-a(Chl-a(0)) concentration, maximum Chl-a(Chl-a(m)) concentration and depth-integrated Chl-a(Chl-a(int)) concentration were studied in the Northern South China Sea (NSCS). The results indicate that there are 4 different patterns in the vertical Chl-aprofiles in the NSCS: (i) Chl-aincreases with depth from the surface (e.g. station 1); (ii) there exists subsurface chlorophyll maximum (SCM), with low Chl-aon the surface and at the bottom layers respectively (e.g. station 5); (iii) there is no SCM, only with high Chl-aon the surface and in the bottom (e.g. station 14); (iv) the 4thpattern is similar to (ii), with the higher Chl-a(0)(e.g. station 28). The SCM is observed at 95% stations in the NSCS and is not detected only at a few stations near the Pearl River (PR) estuary. These patterns are mainly regulated by alternative limitation of nutrients and light from the surface to the bottom of euphotic layer. For the pattern 1 (e.g. station 1), light is not a limited factor, and Chl-aand nutrients increase with depth. The pattern 2 (e.g. station 5) exists with the limitation of surface nutrients in offshore region. The nutrients increases with depth and the nutrients limitation turns to light limitation gradually from surface to bottom. And the SCM appears in the layer which need of the light and nutrients is roughly equivalent. Compared with that the offshore SCM, the nutrients for the pattern 3 (e.g. station 14) are rich on the surface with nutrients concentration and light irradiance. Therefore, it is seawater intrusion from the bottom that brings the higher nutrients concentration. The reason for the high Chl-a(0)on the pattern 4 (e.g. station 28) is terrestrial matter from the nearshore. High correlation (R2= 0.5206, p<0.01) between the depth of SCM (Depth(m)) and Chl-a(0)indicates that the SCM depth is regulated by light masking effect of surface phytoplankton, generally with shallow nutriclines and fast light attenuation for high Chl-a(0)and vice versa low Chl-a(0)brings deeper nutriclines and light attenuate slowly with less shading effect. Further research results shows that Chl-a(int)and Chl-a(m)have a good correlation(R2= 0.6397, p<0.01). However, the correlation between Chl-a(int)and Chl-a(0)is relative weak (R2= 0.3202, p<0.01). That could be attributed to the availability of nutrients playing an important role in growth of phytoplankton, with high nutrients at upper euphotic layers for the stations with high Chl-a(0).
Biochemical and phylogenetic characterization of the wastewater tolerant Chlamydomonas biconvexa Embrapa|LBA40 strain cultivated in palm oil mill effluent
Authors: Pascoal Patrícia Verdugo , Ribeiro Dágon Manoel , Cereijo Carolina Ribeiro , Santana Hugo , Nascimento Rodrigo Carvalho , Steindorf Andrei Stecca , Calsing Lorena C. G. , Formighieri Eduardo Fernandes , Brasil Bruno S. A. F.
Published: April 2021

The increasing demand for water, food and energy poses challenges for the world´s sustainability. Tropical palm oil is currently the major source of vegetable oil worldwide with a production that exceeds 55 million tons per year, while generating over 200 million tons of palm oil mill effluent (POME). It could potentially be used as a substrate for production of microalgal biomass though. In this study, the microalgal strain Chlamydomonas biconvexa Embrapa|LBA40, originally isolated from a sugarcane vinasse stabilization pond, was selected among 17 strains tested for growth in POME retrieved from anaerobic ponds of a palm oil industrial plant located within the Amazon rainforest region. During cultivation in POME, C. biconvexa Embrapa|LBA40 biomass productivity reached 190.60 mgDW • L-1 • d-1 using 15L airlift flat plate photobioreactors. Carbohydrates comprised the major fraction of algal biomass (31.96%), while the lipidic fraction reached up to 11.3% of dry mass. Reductions of 99% in ammonium and nitrite, as well as 98% reduction in phosphate present in POME were detected after 5 days of algal cultivation. This suggests that the aerobic pond stage, usually used in palm oil industrial plants to reduce POME inorganic load, could be substituted by high rate photobioreactors, significantly reducing the time and area requirements for wastewater treatment. In addition, the complete mitochondrial genome of C. biconvexa Embrapa|LBA40 strain was sequenced, revealing a compact mitogenome, with 15.98 kb in size, a total of 14 genes, of which 9 are protein coding genes. Phylogenetic analysis confirmed the strain taxonomic status within the Chlamydomonas genus, opening up opportunities for future genetic modification and molecular breeding programs in these species.
Increased prevalence of obstructive sleep apnea in women diagnosed with endometrial or breast cancer
Authors: Madut Ayey , Fuchsova Veronika , Man Hong , Askar Shabeel , Trivedi Ritu , Elder Elisabeth , Clarke Christine L. , Wain Gerard , Brand Alison , DeFazio Anna , Amis Terence , Kairaitis Kristina
Published: April 2021

Background

Epidemiological studies demonstrate associations between obstructive sleep apnea (OSA) and cancer incidence and mortality. The aim of this study was to measure OSA in women with breast (BC) or endometrial cancer (EC) and associations with clinico-pathological tumor variables.

Methods and findings

In a cross sectional study, women with BC (12 months) or EC (3 months) post-diagnosis were recruited from cancer clinics. We collected demographic, anthropometric data, cancer stage, grade, histopathology and history of cancer treatment and all subjects had in-laboratory polysomnography. Sleepiness was assessed with the Epworth Sleepiness Scale (ESS). We compared anthropometric and polysomnographic data between cancer groups (unpaired t-tests), and assessed relationships between cancer characteristics and OSA variables (Fishers exact test). There were no significant differences between average age (BC:59.6±8.7 years(n = 50); EC:60.3±7.7 years(n = 37)), or ESS score (BC:6.4±4.4; EC 6.8±4.7; mean±SD; all p>0.2), however, BMI was higher in EC (BC: 29.7±7.9kgm-2; EC: 34.2±8.0 kgm-2; p<0.05). BC had longer sleep latency (BC:31.8±32minutes; EC:19.3±17.9 minutes), less Stage 3 sleep (BC:20.0±5.2%; EC:23.6±8.2%) and more REM sleep (BC:21.1±6.9%; EC: 16.6±5.7%), all p<0.05. EC had lower average awake and asleep oxygen saturation levels (BC: 95.6±1.3%; EC: 94.6±1.9% [awake]: BC: 94.8±2.1%; EC: 93.3±2.4% [asleep]; both p<0.05). Apnea-Hypopnea Index (AHI) (BC: 21.2(7.3–36.9) events/hr; EC: 15.7 (10–33.5) events/hour (median (interquartile range)) was not different p = 0.7), however, 58% and 57% of women with BC and EC respectively, had an AHI>15 events/hour. In this small sample size group, no significant associations (all p>0.1) were detected between OSA metrics and clinico-pathological tumor variables.

Conclusion

In postmenopausal women with breast or endometrial cancer there is high prevalence of OSA, with no association with specific tumor characteristics detected. Recognition of the high prevalence of OSA in women with cancer is important to recognise as it may impact on surgical risk and quality of life.
Prevalence and predictors of obesity-related cancers among racial/ethnic groups with metabolic syndrome
Authors: Monestime Shanada , Beech Bettina , Kermah Dulcie , Norris Keith
Published: April 2021

Background

Obesity-related cancer (ORC) is associated with higher amounts of body fat, which could increase the risk of developing cardiovascular disease (CVD). A significant factor associated with CVD is metabolic syndrome (MetS), and MetS prevalence differs by race/ethnicity. The purpose of this study was to compare the prevalence and predictors of ORCs by race/ethnicity among adults (>18) with MetS.

Methods

This was a retrospective, cross-sectional study using data from the 1999–2014 National Health and Nutrition Examination Survey (NHANES). A chi-square test was performed to determine differences in ORC prevalence between non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic participants with MetS. A multivariate logistic regression was used to evaluate predictors (race, sex, income, insurance, education, marital status, and smoking status) of ORC among adults with MetS.

Results

Of the 1,554 adults, the prevalence of ORC was 30.6% among NHWs, 51.3% in NHBs, and 54.1% in Hispanics (p = <0.001). Females were 6.27 times more likely to have an ORC compared to males (95% CI = 4.95–14.11). Compared to NHWs, NHBs were 2.1 times more likely to have an ORC (95% CI = 1.40–3.38); and Hispanics were 2.5 times more likely (95% CI = 1.39–4.77). For every 1-year unit increase in age, the odds of ORC increased by 3% (95% CI = 1.00–1.05).

Conclusions

Among NHANES participants with MetS, the prevalence of ORCs was significantly higher in NHBs and Hispanics, females, and older adults with MetS. Future studies, by race/ethnicity, are warranted on mortality risk of persons with MetS and ORC.
Association of ABO blood groups with presentation and outcomes of confirmed SARS CoV-2 infection: A prospective study in the largest COVID-19 dedicated hospital in Bangladesh
Authors: Mahmud Reaz , Rassel Mohammad Aftab , Monayem Farhana Binte , Sayeed S. K. Jakaria Been , Islam Md Shahidul , Islam Mohammed Monirul , Yusuf Mohammad Abdullah , Rahman Sabrina , Islam K. M. Nazmul , Mahmud Imran , Hossain Mohammad Zaid , Chowdhury Ahmed Hossain , Kabir A. K. M. Humayon , Ahmed Kazi Gias Uddin , Rahman Md. Mujibur
Published: April 2021

Background

Globally, studies have shown conflicting results regarding the association of blood groups with SARS CoV-2 infection.

Objective

To observe the association between ABO blood groups and the presentation and outcomes of confirmed COVID-19 cases.

Design, setting, and participants

This was a prospective cohort study of patients with mild-to-moderately severe COVID-19 infections who presented in the COVID-19 unit of Dhaka Medical College Hospital and were enrolled between 01 June and 25 August, 2020. Patients were followed up for at least 30 days after disease onset. We grouped participants with A-positive and A-negative blood groups into group I and participants with other blood groups into group II.

Results

The cohort included 438 patients; 52 patients were lost to follow-up, five died, and 381 completed the study. The prevalence of blood group A [144 (32.9%)] was significantly higher among COVID-19 patients than in the general population (p < 0.001). The presenting age [mean (SD)] of group I [42.1 (14.5)] was higher than that of group II [38.8 (12.4), p = 0.014]. Sex (p = 0.23) and co-morbidity (hypertension, p = 0.34; diabetes, p = 0.13) did not differ between the patients in groups I and II. No differences were observed regarding important presenting symptoms, including fever (p = 0.72), cough (p = 0.69), and respiratory distress (p = 0.09). There was no significant difference in the median duration of symptoms in the two group (12 days), and conversion to the next level of severity was observed in 26 (20.6%) and 36 patients (13.8%) in group I and II, respectively. However, persistent positivity of RT-PCR at 14 days of initial positivity was more frequent among the patients in group I [24 (19%)] than among those in group II [29 (11.1%)].

Conclusions

The prevalence of blood group A was higher among COVID-19 patients. Although ABO blood groups were not associated with the presentation or recovery period of COVID-19, patients with blood group A had delayed seroconversion.
Outcomes in asymptomatic, severe aortic stenosis
Authors: Kvaslerud Anette Borger , Santic Kenan , Hussain Amjad Iqbal , Auensen Andreas , Fiane Arnt , Skulstad Helge , Aaberge Lars , Gullestad Lars , Broch Kaspar
Published: April 2021

Background and aim of the study

Patients with asymptomatic, severe aortic stenosis are presumed to have a benign prognosis. In this retrospective cohort study, we examined the natural history of contemporary patients advised against aortic valve replacement due to a perceived lack of symptoms.

Materials and methods

We reviewed the medical records of every patient given the ICD-10-code for aortic stenosis (I35.0) at Oslo University Hospital, Rikshospitalet, between Dec 1st, 2002 and Dec 31st, 2016. Patients who were evaluated by the heart team due to severe aortic stenosis were categorized by treatment strategy. We recorded baseline data, adverse events and survival for the patients characterized as asymptomatic and for 100 age and gender matched patients scheduled for aortic valve replacement.

Results

Of 2341 patients who were evaluated for aortic valve replacement due to severe aortic stenosis, 114 patients received conservative treatment due to a lack of symptoms. Asymptomatic patients had higher mortality than patients who had aortic valve replacement, log-rank p<0.001 (mean follow-up time: 4.0 (SD: 2.5) years). Survival at 1, 2 and 3 years for the asymptomatic patients was 88%, 75% and 63%, compared with 92%, 83% and 78% in the matched patients scheduled for aortic valve replacement. 28 (25%) of the asymptomatic patients had aortic valve replacement during follow-up. Age, previous history of coronary artery disease and N-terminal pro B-type natriuretic peptide (NT-proBNP) were predictors of mortality and coronary artery disease and NT-proBNP were predictors of 3-year morbidity in asymptomatic patients.

Conclusions

In this retrospective study, asymptomatic patients with severe aortic stenosis who were advised against surgery had significantly higher mortality than patients who had aortic valve replacement.
Safety and efficacy of allylamines in the treatment of cutaneous and mucocutaneous leishmaniasis: A systematic review
Authors: Bezemer Jacob M. , van der Ende Jacob , Limpens Jacqueline , de Vries Henry J. C. , Schallig Henk D. F. H.
Published: April 2021

Cutaneous and mucocutaneous leishmaniasis affect a million people yearly, leading to skin lesions and potentially disfiguring mucosal disease. Current treatments can have severe side effects. Allylamine drugs, like terbinafine, are safe, including during pregnancy. This review assesses efficacy and safety of allylamines for the treatment of cutaneous and mucocutaneous leishmaniasis. It followed the PRISMA statement for reporting and was preregistered in PROSPERO(CRD4201809068). MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Global Health Library, Web of Science, Google Scholar, and clinical trial registers were searched from their creation to May 24th, 2020. All original human, animal, andin vitrostudies concerning allylamines and cutaneous or mucocutaneous leishmaniasis were eligible for inclusion. Comparators—if any—included both placebo or alternative cutaneous or mucocutaneous leishmaniasis treatments. Complete cure, growth inhibition, or adverse events served as outcomes. The search identified 312 publications, of which 22 were included in this systematic review. There were one uncontrolled and two randomised controlled trials. The only well-designed randomised controlled trial that compared the treatment efficacy of oral terbinafine versus intramuscular meglumine antimoniate in 80Leismania tropicainfected patients showed a non-significant lower cure rate for terbinafine vs meglumine antimoniate (38% vs 53%). A meta-analysis could not be performed due to the small number of studies, their heterogeneity, and low quality. This systematic review shows that there is no evidence of efficacy of allylamine monotherapy against cutaneous and mucocutaneous leishmaniasis. Further trials of allylamines should be carefully considered as the outcomes of an adequately designed trial were disappointing andin vitrostudies indicate minimal effective concentrations that are not achieved in the skin during standard doses. However, thein vitrosynergistic effects of allylamines combined with triazole drugs warrant further exploration.
Fibrotic expression profile analysis reveals repurposed drugs with potential anti-fibrotic mode of action
Authors: Karatzas Evangelos , Kakouri Andrea C. , Kolios George , Delis Alex , Spyrou George M.
Published: April 2021

Fibrotic diseases cover a spectrum of systemic and organ-specific maladies that affect a large portion of the population, currently without cure. The shared characteristic these diseases feature is their uncontrollable fibrogenesis deemed responsible for the accumulated damage in the susceptible tissues.Idiopathic Pulmonary Fibrosis, an interstitial lung disease, is one of the most common and studied fibrotic diseases and still remains an active research target. In this study we highlight unique and common (i) genes, (ii) biological pathways and (iii) candidate repurposed drugs among 9 fibrotic diseases. We identify 7 biological pathways involved in all 9 fibrotic diseases as well as pathways unique to some of these diseases. Based on our Drug Repurposing results, we suggest captopril and ibuprofen that both appear to slow the progression of fibrotic diseases according to existing bibliography. We also recommend nafcillin and memantine, which haven’t been studied against fibrosis yet, for further wet-lab experimentation. We also observe a group of cardiomyopathy-related pathways that are exclusively highlighted forOral Submucous Fibrosis. We suggest digoxin to be tested againstOral Submucous Fibrosis, since we observe cardiomyopathy-related pathways implicated inOral Submucous Fibrosisand there is bibliographic evidence that digoxin may potentially clear myocardial fibrosis. Finally, we establish thatIdiopathic Pulmonary Fibrosisshares several involved genes, biological pathways and candidate inhibiting-drugs withDupuytren’s Disease,IgG4-related Disease,Systemic SclerosisandCystic Fibrosis. We propose that treatments for these fibrotic diseases should be jointly pursued.
Characterizing the cytotoxic effects and several antimicrobial phytocompounds of Argemone mexicana
Authors: Orozco-Nunnelly Danielle Annette , Pruet Jeffery , Rios-Ibarra Clara Patricia , Bocangel Gamarra Estefany Lucia , Lefeber Theodore , Najdeska Teodora
Published: April 2021

Commonly called the Mexican prickly poppy, Argemone mexicana is a stress-resistant member of the Papaveraceae family of plants that has been used in traditional medicine for centuries by indigenous communities in Mexico and Western parts of the United States. This plant has been exploited to treat a wide variety of ailments, with reported antimicrobial and antioxidant properties, as well as cytotoxic effects against some human cancer cell lines. Due to its various therapeutic uses and its abundance of secondary metabolites, A. mexicana has great potential as a drug discovery candidate. Herein, the germination conditions of A. mexicana are described and the cytotoxic activities of different parts (seeds, leaves, inner vs. outer roots) of the plant from methanol or hexane extracts are preliminarily characterized against cells of seven unique organisms. When comparing 1 mg of each sample normalized to background solvent alone, A. mexicana methanol outer root and leaf extracts possessed the strongest antimicrobial activity, with greatest effects against the Gram-positive bacteria tested, and less activity against the Gram-negative bacteria and fungi tested. Additionally, using the MTT colorimetric assay, the outer root methanol and seed hexane extracts displayed pronounced inhibitory effects against human colon cancer cells. Quantification of c-MYC (oncogene) and APC (tumor suppressor) mRNA levels help elucidate how the A. mexicana root methanol extract may be affecting colon cancer cells. After ultra-performance liquid chromatography coupled with mass spectrometry and subsequent nuclear magnetic resonance analysis of the root and leaf methanol fractions, two main antibacterial compounds, chelerythrine and berberine, have been identified. The roots were found to possess both phytocompounds, while the leaf lacked chelerythrine. These data highlight the importance of plants as an invaluable pharmaceutical resource at a time when antimicrobial and anticancer drug discovery has plateaued.
Spatial heterogeneity of Pelagia noctiluca ephyrae linked to water masses in the Western Mediterranean
Authors: Pastor-Prieto Marina , Bahamon Nixon , Sabatés Ana , Canepa Antonio , Gili Josep-Maria , Carreton Marta , Company Joan B.
Published: April 2021

Pelagia noctiluca is the most common jellyfish in the Western Mediterranean Sea, living in oceanic waters with a holoplanktonic lifecycle. Frequent outbreaks have been well documented in coastal areas, yet little is known about their offshore distribution. In this study we address the relationship between oceanographic structures and the distribution of P. noctiluca ephyrae along the central continental slope of the Western Mediterranean, covering a wide latitudinal gradient, during July-August 2016. The region is characterized by a rich and complex mesoscale surface circulation driven by the inflow of Atlantic Water into the Western Mediterranean through the Strait of Gibraltar. The results revealed a high variability in the ephyrae spatial paterns related with different water masses and the resulting mesoscale hydrographic features. Their horizontal distribution showed a clear latitudinal gradient with high abundances in the south, associated with recent Atlantic Water, and low abundances or absence in the north, in coincidence with the old Atlantic Water transported by the Northern Current. Ephyrae showed diel vertical migrations of short-extent in the first 50 m, with a wide distribution above the thermocline and the Deep Chlorophyll Maximum during daytime, being more concentrated towards the surface at night. The results suggest the population connectivity of P. noctiluca between the Atlantic and the Mediterranean. In that case, the abundance variability of the species in the Mediterranean could be modulated by its entrance associated with the inflow of Atlantic Water through the Strait of Gibraltar.
The influence of the native lung on early outcomes and survival after single lung transplantation
Authors: Gonzalez Francisco Javier , Alvarez Enriqueta , Moreno Paula , Poveda David , Ruiz Eloisa , Fernandez Alba Maria , Salvatierra Angel , Alvarez Antonio
Published: April 2021

Objective

To determine whether problems arising in the native lung may influence the short-term outcomes and survival after single lung transplantation (SLT), and therefore should be taken into consideration when selecting the transplant procedure.

Patients and methods

Retrospective review of 258 lung transplants performed between June 2012 and June 2019. Among them, 161 SLT were selected for the analysis. Complications in the native lung were recorded and distributed into two groups: early and late complications (within 30 days or after 30 days post-transplant). Donor and recipient preoperative factors, 30-day mortality and survival were analysed and compared between groups by univariable and multivariable analyses, and adjusting for transplant indication.

Results

There were 161 patients (126M/35F; 57±7 years) transplanted for emphysema (COPD) (n = 72), pulmonary fibrosis (IPF) (n = 77), or other indications (n = 12). Forty-nine patients (30%) presented complications in the native lung. Thirty-day mortality did not differ between patients with or without early complications (6% vs. 12% respectively; p = 0.56). Twelve patients died due to a native lung complication (7.4% of patients; 24% of all deaths). Survival (1,3,5 years) without vs. with late complications: COPD (89%, 86%, 80% vs. 86%, 71%, 51%; p = 0.04); IPF (83%, 77%, 72% vs. 93%, 68%, 58%; p = 0.65). Among 30-day survivors: COPD (94%, 91%, 84% vs. 86%, 71%, 51%; p = 0.01); IPF (93%, 86%, 81% vs. 93%, 68%, 58%; p = 0.19). Native lung complications were associated to longer ICU stay (10±17 vs. 33±96 days; p<0.001), longer postoperative intubation (41±85 vs. 99±318 hours; p = 0.006), and longer hospital stay (30±24 vs. 45±34 days; p = 0.03). The presence of late native lung problems predicted survival in COPD patients (OR: 2.55; p = 0.07).

Conclusion

The native lung is a source of morbidity in the short-term and mortality in the long-term after lung transplantation. This should be taken into consideration when choosing the transplant procedure, especially in COPD patients.
Experiences, impacts and mental health functioning during a COVID-19 outbreak and lockdown: Data from a diverse New York City sample of college students
Authors: López-Castro Teresa , Brandt Laura , Anthonipillai Nishanthi J. , Espinosa Adriana , Melara Robert
Published: April 2021

In March 2020, New York City (NYC) experienced an outbreak of coronavirus disease 2019 (COVID-19) which resulted in a 78-day mass confinement of all residents other than essential workers. The aims of the current study were to (1) document the breadth of COVID-19 experiences and their impacts on college students of a minority-serving academic institution in NYC; (2) explore associations between patterns of COVID-19 experiences and psychosocial functioning during the prolonged lockdown, and (3) explore sex and racial/ethnic differences in COVID-19-related experiences and mental health correlates. A total of 909 ethnically and racially diverse students completed an online survey in May 2020. Findings highlight significant impediments to multiple areas of students’ daily life during this period (i.e., home life, work life, social environment, and emotional and physical health) and a vast majority reported heightened symptoms of depression and generalized anxiety. These life disruptions were significantly related to poorer mental health. Moreover, those who reported the loss of a close friend or loved one from COVID-19 (17%) experienced significantly more psychological distress than counterparts with other types of infection-related histories. Nonetheless, the majority (96%) reported at least one positive experience since the pandemic began. Our findings add to a growing understanding of COVID-19 impacts on psychological health and contribute the important perspective of the North American epicenter of the pandemic during the time frame of this investigation. We discuss how the results may inform best practices to support students’ well-being and serve as a benchmark for future studies of US student populations facing COVID-19 and its aftermath.
Elicitation of potent serum neutralizing antibody responses in rabbits by immunization with an HIV-1 clade C trimeric Env derived from an Indian elite neutralizer
Authors: Kumar Rajesh , Deshpande Suprit , Sewall Leigh M. , Ozorowski Gabriel , Cottrell Christopher A. , Lee Wen-Hsin , Holden Lauren G. , Richey Sara T. , Chandrawacar Antra Singh , Dhiman Kanika , Ashish  , Kumar Vivek , Ahmed Shubbir , Hingankar Nitin , Kumar Naresh , Murugavel Kailapuri G. , Srikrishnan Aylur K. , Sok Devin , Ward Andrew B. , Bhattacharya Jayanta
Published: April 2021

Evaluating the structure-function relationship of viral envelope (Env) evolution and the development of broadly cross-neutralizing antibodies (bnAbs) in natural infection can inform rational immunogen design. In the present study, we examined the magnitude and specificity of autologous neutralizing antibodies induced in rabbits by a novel HIV-1 clade C Env protein (1PGE-THIVC) vis-à-vis those developed in an elite neutralizer from whom the env sequence was obtained that was used to prepare the soluble Env protein. The novel 1PGE-THIVC Env trimer displayed a native like pre-fusion closed conformation in solution as determined by small angle X-ray scattering (SAXS) and negative stain electron microscopy (EM). This closed spike conformation of 1PGE-THIVC Env trimers was correlated with weak or undetectable binding of non-neutralizing monoclonal antibodies (mAbs) compared to neutralizing mAbs. Furthermore, 1PGE-THIVC SOSIP induced potent neutralizing antibodies in rabbits to autologous virus variants. The autologous neutralizing antibody specificity induced in rabbits by 1PGE-THIVC was mapped to the C3/V4 region (T362/P401) of viral Env. This observation agreed with electron microscopy polyclonal epitope mapping (EMPEM) of the Env trimer complexed with IgG Fab prepared from the immunized rabbit sera. Our study demonstrated neutralization of sequence matched and unmatched autologous viruses by serum antibodies induced in rabbits by 1PGE-THIVC and also highlighted a comparable specificity for the 1PGE-THIVC SOSIP trimer with that seen with polyclonal antibodies elicited in the elite neutralizer by negative-stain electron microscopy polyclonal epitope (ns-EMPEM) mapping.
Integration in oncogenes plays only a minor role in determining the in vivo distribution of HIV integration sites before or during suppressive antiretroviral therapy
Authors: Coffin John M. , Bale Michael J. , Wells Daria , Guo Shuang , Luke Brian , Zerbato Jennifer M. , Sobolewski Michele D. , Sia Twan , Shao Wei , Wu Xiaolin , Maldarelli Frank , Kearney Mary F. , Mellors John W. , Hughes Stephen H.
Published: April 2021

HIV persists during antiretroviral therapy (ART) as integrated proviruses in cells descended from a small fraction of the CD4+ T cells infected prior to the initiation of ART. To better understand what controls HIV persistence and the distribution of integration sites (IS), we compared about 15,000 and 54,000 IS from individuals pre-ART and on ART, respectively, with approximately 395,000 IS from PBMC infected in vitro. The distribution of IS in vivo is quite similar to the distribution in PBMC, but modified by selection against proviruses in expressed genes, by selection for proviruses integrated into one of 7 specific genes, and by clonal expansion. Clones in which a provirus integrated in an oncogene contributed to cell survival comprised only a small fraction of the clones persisting in on ART. Mechanisms that do not involve the provirus, or its location in the host genome, are more important in determining which clones expand and persist.
Temporal dynamics of SARS-CoV-2 mutation accumulation within and across infected hosts
Authors: Valesano Andrew L. , Rumfelt Kalee E. , Dimcheff Derek E. , Blair Christopher N. , Fitzsimmons William J. , Petrie Joshua G. , Martin Emily T. , Lauring Adam S.
Published: April 2021

Analysis of SARS-CoV-2 genetic diversity within infected hosts can provide insight into the generation and spread of new viral variants and may enable high resolution inference of transmission chains. However, little is known about temporal aspects of SARS-CoV-2 intrahost diversity and the extent to which shared diversity reflects convergent evolution as opposed to transmission linkage. Here we use high depth of coverage sequencing to identify within-host genetic variants in 325 specimens from hospitalized COVID-19 patients and infected employees at a single medical center. We validated our variant calling by sequencing defined RNA mixtures and identified viral load as a critical factor in variant identification. By leveraging clinical metadata, we found that intrahost diversity is low and does not vary by time from symptom onset. This suggests that variants will only rarely rise to appreciable frequency prior to transmission. Although there was generally little shared variation across the sequenced cohort, we identified intrahost variants shared across individuals who were unlikely to be related by transmission. These variants did not precede a rise in frequency in global consensus genomes, suggesting that intrahost variants may have limited utility for predicting future lineages. These results provide important context for sequence-based inference in SARS-CoV-2 evolution and epidemiology.