bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic SARS-CoV-2 S Gene Sequencing in Wastewater Samples Enables Early Lineage Detection and Uncovers Rare Mutations in Portugal
Authors: Reis Ana C. , Pinto Daniela , Monteiro Sílvia , Santos Ricardo , Martins João Vieira , Sousa Alexandra , Páscoa Rute , Lourinho Rita , Cunha Mónica V. 
Published: October 2023

ABSTRACTAs the COVID-19 pandemic reached its peak, many countries implemented genomic surveillance systems to track the evolution and transmission of SARS-CoV-2. Transition from the pandemic to the endemic phase prioritized alternative testing strategies to maintain effective epidemic surveillance at the population level, with less intensive sequencing efforts. One such promising approach was Wastewater-Based Surveillance (WBS), which offers non-invasive, cost-effective means for analysing virus trends at the sewershed level. From 2020 onwards, wastewater has been recognized as an instrumental source of information for public health, with national and international authorities exploring options to implement national wastewater surveillance systems and increasingly relying on WBS as early warning of potential pathogen outbreaks. In Portugal, several pioneer projects joined the academia, water utilities and Public Administration around WBS.To validate WBS as an effective genomic surveillance strategy, it is crucial to collect long term performance data. In this work, we present one year of systematic SARS-CoV-2 wastewater surveillance in Portugal, representing 35% of the mainland population. We employed two complementary methods for lineage determination - allelic discrimination by RT-PCR and S gene sequencing. This combination allowed us to monitor variant evolution in near-real-time and identify low-frequency mutations.Over the course of this year-long study, spanning from May 2022 to April 2023, we successfully tracked the dominant Omicron sub-lineages, their progression and evolution, which aligned with concurrent clinical surveillance data. Our results underscore the effectiveness of WBS as a tracking system for virus variants, with the ability to unveil mutations undetected via massive sequencing of clinical samples from Portugal, demonstrating the ability of WBS to uncover new mutations and detect rare genetic variants.Our findings emphasize that knowledge of the genetic diversity of SARS-CoV-2 at the population level can be extended far beyond via the combination of routine clinical genomic surveillance with wastewater sequencing and genotyping.
Early screening of colorectal cancer using feature engineering with artificial intelligence-enhanced analysis of nanoscale chromatin modifications
Authors: Chang Andrew , Prabhala Sravya , Daneshkhah Ali , Lin Jianan , Subramanian Hariharan , Roy Hemant Kumar , Backman Vadim 
Published: October 2023

AbstractColonoscopy is accurate but inefficient for colorectal cancer (CRC) prevention due to the low (~7-8%) prevalence of target lesions, advanced adenomas. We leveraged rectal mucosa to identify patients who harbor CRC field carcinogenesis by evaluating chromatin 3D architecture. Supranucleosomal disordered chromatin chains (~5-20 nm, ~1 kbp) fold into chromatin packing domains (~100-200 nm, ~100–1,000 kbp). In turn, the fractal-like conformation of DNA within chromatin domains and the folding of the genome into packing domains has been shown to influence multiple facets of gene transcription, including the transcriptional plasticity of cancer cells. We deployed an optical spectroscopic nanosensing technique, chromatin-sensitive partial wave spectroscopic microscopy (csPWS), to evaluate the packing density scaling D of the chromatin chain conformation within packing domains from rectal mucosa in 256 patients with varying degrees of progression to colorectal cancer. We found average packing scaling D of chromatin domains was elevated in tumor cells, histologically normal-appearing cells 4 cm proximal to the tumor, and histologically normal-appearing rectal mucosa compared to cells from control patients (p<0.001). Nuclear D had a robust correlation with the model of 5-year risk of CRC with r2=0.94. Furthermore, rectal D was evaluated as a screening biomarker for patients with advanced adenomas presenting an AUC of 0.85 and 85% sensitivity and specificity. Artificial Intelligence (AI)-enhanced csPWS improved diagnostic performance with AUC=0.90. Considering the low sensitivity of existing CRC tests, including liquid biopsies, to early-stage cancers our work highlights the potential of chromatin biomarkers of field carcinogenesis in detecting early, significant precancerous colon lesions.
Nucleoprotein reassortment enhanced transmissibility of H3 1990.4.a clade influenza A virus in swine
Authors: Thomas Megan N. , Ciacci Zanella Giovana , Cowan Brianna , Caceres C. Joaquin , Rajao Daniela S. , Perez Daniel R. , Gauger Phillip C. , Vincent Baker Amy L. , Anderson Tavis K. 
Published: October 2023

AbstractThe increased detection of H3 C-IVA (1990.4.a) clade influenza A viruses (IAV) in U.S. swine in 2019 was associated with a reassortment event to acquire an H1N1pdm09 lineage nucleoprotein (pdmNP) gene, replacing a TRIG lineage NP (trigNP). We hypothesized that acquiring the pdmNP conferred a selective advantage over prior circulating H3 viruses with a trigNP. To investigate the role of the NP reassortment in transmission, we identified two contemporary 1990.4.a representative strains (NC/19 and MN/18) with different evolutionary origins of the NP gene. A reverse genetics system was used to generate wild-type (wt) strains and to swap the pdm and TRIG lineage NP genes, generating four viruses: wtNC/19-pdmNP, NC/19-trigNP, wtMN/18-trigNP, MN/18-pdmNP. Pathogenicity and transmission of the four viruses were compared in pigs. All four viruses infected 10 primary pigs and transmitted to 5 indirect contact pigs per group. Pigs infected via contact with MN/18-pdmNP shed virus two days earlier than pigs infected with wtMN/18-trigNP. The inverse did not occur for wtNC/19-pdmNP and NC/19-trigNP. These data suggest that reassortment to acquire a pdmNP gene improved transmission efficiency in the 1990.4.a, but this is likely a multigenic trait. Replacing a trigNP gene alone may not diminish the transmission of a wild-type virus sampled from the swine population. This study demonstrates how reassortment and subsequent evolutionary change of internal genes can result in more transmissible viruses that impact the detection frequency of specific HA clades. Thus, rapidly identifying novel reassortants paired with dominant HA/NA may improve prediction of strains to include in vaccines.ImportanceInfluenza A viruses (IAV) are composed of eight non-continuous gene segments that can reassort during coinfection of a host, creating new combinations. Some gene combinations may convey a selective advantage and be paired together preferentially. A reassortment event was detected in swine in the United States that involved the exchange of two lineages of nucleoprotein (NP) genes (trigNP to pdmNP) that became a predominant genotype detected in surveillance. Using a transmission study, we demonstrated that exchanging the trigNP for a pdmNP caused the virus to shed from the nose at higher levels and transmit to other pigs more rapidly. Replacing a pdmNP with a trigNP did not hinder transmission, suggesting that transmission efficiency depends on interactions between multiple genes. This demonstrates how reassortment alters IAV transmission and that reassortment events can provide an explanation for why genetically related viruses with different internal gene combinations experience rapid fluxes in detection frequency.
Uncultivated DPANN archaea are ubiquitous inhabitants of global oxygen deficient zones with diverse metabolic potential
Authors: Zhang Irene H. , Borer Benedict , Zhao Rui , Wilbert Steven , Newman Dianne K. , Babbin Andrew R. 
Published: October 2023

AbstractArchaea belonging to the DPANN superphylum have been found within an expanding number of environments and perform a variety of biogeochemical roles, including contributing to carbon, sulfur, and nitrogen cycling. Generally characterized by ultrasmall cell sizes and reduced genomes, DPANN archaea may form mutualistic, commensal, or parasitic interactions with various archaeal and bacterial hosts, influencing the ecology and functioning of microbial communities. While DPANN archaea reportedly comprise 15–26% of the archaeal community within marine oxygen deficient zone (ODZ) water columns, little is known about their metabolic capabilities in these ecosystems. We report 33 novel metagenome-assembled genomes belonging to DPANN phyla Nanoarchaeota, Pacearchaeota, Woesarchaeota, Undinarchaeota, Iainarchaeota, and SpSt-1190 from pelagic ODZs in the Eastern Tropical North Pacific and Arabian Sea. We find these archaea to be permanent, stable residents of all 3 major ODZs only within anoxic depths, comprising up to 1% of the total microbial community and up to 25–50% of archaea. ODZ DPANN appear capable of diverse metabolic functions, including fermentation, organic carbon scavenging, and the cycling of sulfur, hydrogen, and methane. Within a majority of ODZ DPANN, we identify a gene homologous to nitrous oxide reductase. Modeling analyses indicate the feasibility of a nitrous oxide reduction metabolism for host-attached symbionts, and the small genome sizes and reduced metabolic capabilities of most DPANN MAGs suggest host-associated lifestyles within ODZs.ImportanceArchaea from the DPANN superphylum have diverse metabolic capabilities and participate in multiple biogeochemical cycles. While metagenomics and enrichments have revealed that many DPANN are characterized by ultrasmall genomes, few biosynthetic genes, and episymbiotic lifestyles, much remains unknown about their biology. We report 33 new DPANN metagenome-assembled genomes originating from the 3 global marine oxygen deficient zones (ODZs), the first from these regions. We survey DPANN abundance and distribution within the ODZ water column, investigate their biosynthetic capabilities, and report potential roles in the cycling of organic carbon, methane, and nitrogen. We test the hypothesis that nitrous oxide reductases found within several ODZ DPANN genomes may enable ultrasmall episymbionts to serve as nitrous oxide consumers when attached to a host nitrous oxide producer. Our results indicate DPANN archaea as ubiquitous residents within the anoxic core of ODZs with the potential to produce or consume key compounds.
Identifying cellular RNA-binding proteins during infection uncovers a role for MKRN2 in influenza mRNA trafficking
Authors: Bonazza Stefano , Coutts Hannah , Sukumar Swathi , Turkington Hannah , Courtney David G 
Published: October 2023

AbstractUtilisation of RNA-binding proteins (RBPs) is an important aspect of post-transcriptional regulation of viral RNA. Viruses such as influenza A viruses (IAV) interact with RBPs to regulate processes including splicing, nuclear export and trafficking, while also encoding RBPs within their genomes, such as NP and NS1. But with almost 1000 RBPs encoded within the human genome it is still unclear what role, if any, many of these proteins play during viral replication. Using the RNA interactome capture (RIC) technique, we isolated RBPs from IAV infected cells to unravel the RBPome of mRNAs from IAV infected human cells. This led to the identification of one particular RBP, MKRN2, that associates with and positively regulates IAV mRNA. Through further validation, we determined that MKRN2 is involved in the nuclear-cytoplasmic trafficking of IAV mRNA likely through an association with the RNA export mediator GLE1. In the absence of MKRN2, IAV mRNAs accumulate in the nucleus of infected cells, which we suspect leads to their degradation by the nuclear RNA exosome complex. MKRN2, therefore, appears to be required for the efficient nuclear export of IAV mRNAs in human cells.
Vascular abnormalities in heart and brain are associated with cardiovascular and neurological symptoms in a novel mouse model for Williams syndrome
Authors: el Azzouzi Hamid , Bosman Laurens W.J. , Kros Lieke , van Vliet Nicole , Ridwan Yanto , Dijkhuizen Stéphanie , Sabel-Goedknegt Erika , Generowicz Bastian S. , Novello Manuele , Kretschmann Emma , Snoeren Morrisen , Broere Danique , Caliandro Rocco , Koekkoek Sebastiaan K.E. , Kruizinga Pieter , van Dis Vera , Zhou Haibo , Yang Hui , Zhou Changyang , van der Pluijm Ingrid , Essers Jeroen , De Zeeuw Chris I. 
Published: October 2023

AbstractWilliams syndrome is a developmental disorder caused by a microdeletion entailing loss of a single copy of 25-27 genes on chromosome 7q11.23. Patients with Williams syndrome suffer from cardiovascular and neuropsychological symptoms. So far, the structural abnormalities of the cardiovascular system in Williams syndrome have been attributed to the loss of a copy of the elastin (ELN) gene. In contrast, the neuropsychological consequences of Williams syndrome, including motor deficits, hypersociability and cognitive impairments, have been mainly attributed to altered expression of transcription factors like LIMK1, GTF2I and GTF2IRD1, while the potential secondary impact of altered cerebrovascular function has been largely ignored. To study the relation between the mutation underlying Williams syndrome and vascularization of not only the heart but also that of the brain, we generated a mouse model with a relatively long microdeletion, including theNcf1gene to reduce the confounding impact of hypertension. The affected mice had an elongated and tortuous aorta, but unlike inElnhaploinsufficient mice, there were no signs of structural cardiac hypertrophy. Our Williams syndrome mice had similar structural abnormalities in their coronary and brain vessels, showing disorganized extracellular matrices of the vessel walls. Moreover, our mouse model faithfully replicated both cardiovascular and neurological symptoms of Williams syndrome, highlighting that accurate non-invasive evaluation of complex vascular abnormalities is feasible. Altogether, we present evidence for vascular malformations that are similar in heart and brain, suggesting that cardiovascular and neurological symptoms can both by impacted by changes in the vascular structure in patients with Williams syndrome.
The LexA-RecA* structure reveals a lock-and-key mechanism for SOS activation
Authors: Cory Michael B. , Li Allen , Hurley Christina M. , Carman Peter J. , Pumroy Ruth A. , Hostetler Zachary M. , Venkatesh Yarra , Gupta Kushol , James Petersson E. , Kohli Rahul M. 
Published: October 2023

ABSTRACTThe bacterial SOS response plays a key role in adaptation to DNA damage, including that caused by antibiotics. SOS induction begins when activated RecA*, an oligomeric nucleoprotein filament formed on single-stranded DNA, binds to and stimulates autoproteolysis of the repressor LexA. Here, we present the structure of the complete SOS signal complex, constituting full-length LexA bound to RecA*. We uncover an extensive interface unexpectedly including the LexA DNA-binding domain, providing a new molecular rationale for ordered SOS response gene induction. Furthermore, we find that the interface involves three RecA monomers, with a single residue in the central monomer acting as a molecular key, inserting into an allosteric binding pocket to induce LexA cleavage. Given the pro-mutagenic nature of SOS activation, our structural and mechanistic insights provide a foundation for developing new therapeutics to slow the evolution of antibiotic resistance.
Peptide-mimetic treatment ofPseudomonas aeruginosain a mouse model of respiratory infection
Authors: Moule Madeleine G. , Benjamin Aaron B. , Buger Melanie L. , Herlan Claudine , Lebedev Maxim , Lin Jennifer S. , Koster Kent J. , Wavare Neha , Adams Leslie G. , Bräse Stefan , Barron Annelise E. , Cirillo Jeffrey D. 
Published: October 2023

AbstractThe rise of drug resistance has become a global crisis, with >1 million deaths due to resistant bacterial infections each year.Pseudomonas aeruginosa,in particular, remains a serious problem with limited solutions due to complex resistance mechanisms that now lead to more than 32,000 multidrug-resistant (MDR) infections and over 2,000 deaths annually. While the emergence of resistant bacteria has become concerningly common, identification of useful new drug classes has been limited over the past 40+ years. We found that a potential novel therapeutic, the peptide-mimetic TM5, is effective at killingP. aeruginosaand displays sufficiently low toxicity for mammalian cells to allow for use in treatment of infections. Interestingly, TM5 killsP. aeruginosamore rapidly than traditional antibiotics, within 30-60 minutesin vitro, and is effective against a range of clinical isolates.In vivo, TM5 significantly reduced bacterial load in the lungs within 24 hours compared to untreated mice and demonstrated few adverse effects. Taken together, these observations suggest that TM5 shows promise as an alternative therapy for MDRP. aeruginosarespiratory infections.
Maternal immunization with distinct influenza vaccine platforms elicits unique antibody profiles that impact the protection of offspring
Authors: Vazquez-Pagan Ana , Roubidoux Ericka Kirkpatrick , Cherry Sean , Livingston Brandi , Bub Theresa , Lazure Lauren , Sharp Bridgett , Confer Thomas , Brigleb Pamela H. , Honce Rebekah , Whitt Kendall T. , Johnson Melissa , Meliopoulos Victoria , Schultz-Cherry Stacey 
Published: October 2023

AbstractPregnant women and infants are considered high-risk groups for increased influenza disease severity. While influenza virus vaccines are recommended during pregnancy, infants cannot be vaccinated until at least six months of age. Passive transfer of maternal antibodies (matAbs) becomes vital for the infant’s protection. Here, we employed an ultrasound-based timed-pregnancy murine model and examined matAb responses to distinct influenza vaccine platforms and influenza A virus (IAV) infection in dams and their offspring. We demonstrate vaccinating dams with a live-attenuated influenza virus (LAIV) vaccine or recombinant hemagglutinin (rHA) proteins administered with adjuvant resulted in enhanced and long-lasting immunity and protection from influenza in offspring. In contrast, a trivalent split-inactivated vaccine (TIV) afforded limited protection in our model. By cross-fostering pups, we show the timing of antibody transfer from vaccinated dams to their offspring (prenatal versus postnatal) can shape the antibody profile depending on the vaccine platform. Our studies provide information on how distinct influenza vaccines lead to immunogenicity and efficacy during pregnancy, impact the protection of their offspring, and detail roles for IgG1 and IgG2c in the development of vaccine administration during pregnancy that stimulate and measure expression of both antibody subclasses.
Inequality and redistribution: evidence from Scandinavian and Mediterranean countries
Authors: Claveria Oscar , Sorić Petar 
Published: October 2023

Purpose
The purpose of this paper is to investigate the adjustment of government redistributive policies in Scandinavian and Mediterranean countries following changes in income inequality over the period 1980–2021.

Design/methodology/approach
The authors first modelled the time-varying dynamics between income inequality and redistribution and then used a non-linear framework to test for the existence of asymmetries and cointegration in their long-run relationship. The authors used two complementary measures of inequality – the share of total income accruing to top percentile income holders and the ratio of the share of total income accruing to top decile income holders divided by that accumulated by the bottom 50% – and computed redistribution as the difference between the two inequality indicators before and after taxes and transfers.

Findings
The authors found that the sign of the relationship between income inequality and redistribution is mostly positive and time-varying. Overall, the authors also found evidence that the impact of increases in inequality on redistributive measures is higher than that of decreases. Finally, the authors obtained a significant long-run relationship between both variables in all countries except Denmark and Spain. These results hold for both Scandinavian and Mediterranean countries.

Originality/value
To the best of the authors’ knowledge, this is the first paper to account for the potential existence of non-linearities and to examine the asymmetries in the adjustment of redistributive policies to increases in income inequality using alternative income inequality metrics.
Forensic mental health intellectual and developmental disability service: an analysis of referral patterns and comparison with community mental health intellectual disability (MHID) services in Ireland
Authors: Wahab Afwan Abdul , Har Calvin , Casey Sarah , Ramsay Hugh , McCormack Brendan , Mulryan Niamh , Ambikapathy Anita , Kearns Anthony 
Published: October 2023

Purpose
The purpose of this study is to analyse the characteristics of all the referrals to the forensic MHIDD service over the past five years and to compare these characteristics to the cohort of service users attending the three general MHID services based in Dublin which are Service 1, Service 2 and Service 3.

Design/methodology/approach
This is a cross-sectional study of adults attending the three generic MHID services and the national forensic MHIDD service. The medical files of service users attending the MHID services were reviewed, and data such as age, gender, level of intellectual disability and psychiatric diagnoses were extracted and compiled into a database. The forensic MHIDD service has since its inception maintained a database of all referrals received and reviewed. The characteristics data needed were extracted from the forensic MHIDD database. All these data were then analysed using the Statistical Package for Social Sciences (SPSS).

Findings
The majority of the three MHID service users were in the moderate to profound range of intellectual disability, while the majority of the cases assessed by forensic MHIDD had normal IQ, borderline IQ and mild intellectual disability with 66.1%. The prevalence of neurodevelopmental disorder, schizophrenia and emotionally unstable personality disorder in the forensic MHIDD is comparable to the three MHID services. The prevalence of depression, bipolar affective disorder (BPAD), anxiety disorder and obsessive-compulsive disorder (OCD) is higher in the three MHID services than in the forensic MHIDD service.

Originality/value
The FHMIDD received referrals at a greater level of overall ability, with two-thirds of the service users having mild intellectual disability to normal IQ. The prevalence of neurodevelopmental disorder such as ASD and schizophrenia is comparable between the forensic MHIDD and the three MHID services. There is a higher prevalence of depression, BPAD, anxiety disorder and OCD in the three MHID services as compared to the forensic MHIDD service.