bluuebunny/crossref_metadata_2025_split huggingface dataset:
Type I interferon signaling induces a delayed antiproliferative response in respiratory epithelial cells during SARS-CoV-2 infection
Authors: Bragazzi Cunha Juliana , Leix Kyle , Sherman Emily J. , Mirabelli Carmen , Frum Tristan , Zhang Charles J. , Kennedy Andrew A. , Lauring Adam S. , Tai Andrew W. , Sexton Jonathan Z. , Spence Jason R. , Wobus Christiane E. , Emmer Brian T. 
Published: November 2023

ABSTRACT

Disease progression during SARS-CoV-2 infection is tightly linked to the fate of lung epithelial cells, with severe cases of COVID-19 characterized by direct injury of the alveolar epithelium and an impairment in its regeneration from progenitor cells. The molecular pathways that govern respiratory epithelial cell death and proliferation during SARS-CoV-2 infection, however, remain unclear. We now report a high-throughput CRISPR screen for host genetic modifiers of the survival and proliferation of SARS-CoV-2-infected Calu-3 respiratory epithelial cells. The top four genes identified in our screen encode components of the same type I interferon (IFN-I) signaling complex
—IFNAR1
,
IFNAR2
,
JAK1
, and
TYK2
. The fifth gene,
ACE2
, was an expected control encoding the SARS-CoV-2 viral receptor. Surprisingly, despite the antiviral properties of IFN-I signaling, its disruption in our screen was associated with an increase in Calu-3 cell fitness. We validated this effect and found that IFN-I signaling did not sensitize SARS-CoV-2-infected cultures to cell death but rather inhibited the proliferation of surviving cells after the early peak of viral replication and cytopathic effect. We also found that IFN-I signaling alone, in the absence of viral infection, was sufficient to induce this delayed antiproliferative response in both Calu-3 cells and iPSC-derived type 2 alveolar epithelial cells. Together, these findings highlight a cell autonomous antiproliferative response by respiratory epithelial cells to persistent IFN-I signaling during SARS-CoV-2 infection. This response may contribute to the deficient alveolar regeneration that has been associated with COVID-19 lung injury and represents a promising area for host-targeted therapeutic development.

IMPORTANCE
The proliferation of respiratory epithelial cells is crucial to host recovery from acute lung injury caused by SARS-CoV-2 and other viral pathogens, but the molecular pathways that govern this process are poorly understood. We performed a high-throughput CRISPR screen that surprisingly revealed a detrimental effect of specific host response, type I interferon (IFN-I) signaling, on the fitness of SARS-CoV-2-infected Calu-3 cells. While IFN-I signaling has been previously associated with several potential downstream responses, we found this effect to be primarily mediated by an inhibition of Calu-3 cellular proliferation after the early peak of SARS-CoV-2-induced cell death. Our findings provide a plausible mechanism for how sustained IFN-I signaling during SARS-CoV-2 infection might worsen lung pathology by blocking the regeneration of the alveolar epithelium from progenitor cells.
Ancient Roman bacterium against current issues: strain Aquil_B6,
Paenisporosarcina quisquiliarum,
or
Psychrobacillus psychrodurans
?
Authors: Colautti Andrea , Comi Giuseppe , Peterlunger Enrico , Iacumin Lucilla 
Published: November 2023

ABSTRACT

Thanks to the development of whole-genome sequencing technologies, nowadays researchers have access to rapid, effective, and precise resources for the genetic analysis of prokaryotes. The use of metrics that consider the entire DNA sequence, such as average nucleotide identity and digital DNA-DNA hybridization calculation, in fact, allows better results when compared to single-target gene analysis. However, it is increasingly important to employ reference databases containing correct information with high-quality sequences. The aim of this work is to taxonomically identify an unknown bacterial strain isolated from an ancient Roman amphora. However, it was necessary to resequence the genomes of the reference strains
Paenisporosarcina quisquiliarum
SK 55 and
Psychrobacillus psychrodurans
DSM 11713 to obtain correct and more reliable sequences than those available. It was, therefore, possible to uniquely identify the strain Aquil_B6 as
Psy. psychrodurans
. Also, to obtain further genetic information, given the low number of sequences available for this species, the genome of strain DSM 30747 was sequenced. Further characterization was made to identify the presence of possible genetic characteristic features such as CRISPR-Cas, prophages, resistance factors, and bacteriocins of this species, making a comparison between the available genomes of
Paenisporosarcina quisquiliarum
SK 55 and
Psychrobacillus psychrodurans
strains DSM 11713, DSM 30747, and Aquil_B6, to evaluate the impact of time on the evolution of the considered species.

IMPORTANCE

Since 1988, through the United States government’s founding, the National Center for Biotechnology Information (NCBI) has provided an invaluable service to scientific advancement. The universality and total freedom of use if on the one hand allow the use of this database on a global level by all researchers for their valuable work, on the other hand, it has the disadvantage of making it difficult to check the correctness of all the materials present. It is, therefore, of fundamental importance for the correctness and ethics of research to improve the databases at our disposal, identifying and amending the critical issues. This work aims to provide the scientific community with a new sequence for the type strain
Paenisporosarcina quisquiliarum
SK 55 and broaden the knowledge of the
Psychrobacillus psychrodurans
species, in particular, considering the ancient strain Aquil_B6 found in an ancient Roman amphora.
Post-salt carbonates control salt-tectonic minibasin formation
Authors: Pichel Leonardo M. , Huismans Ritske S. , Gawthorpe Robert , Faleide Jan Inge 
Published: November 2023

Abstract
Salt tectonics on passive margins are driven by sediment loading and gliding with minimal influence from basement-involved tectonics and is associated with variable and complex salt structures, such as minibasins and diapirs. A major enigma in salt tectonics is the origin of load-driven diapir-flanked minibasins, synclinal depocenters formed by localized subsidence of synkinematic sediments into salt. How can less-dense clastic sediments sink into the denser salt, promoting diapirism at their flanks? We use two-dimensional numerical modeling of lithospheric extension including syn- and post-rift sedimentation to understand the evolution of salt-tectonic minibasins along rifted passive margins. Our results show that these minibasins are driven by deposition of dense early post-salt carbonates and then amplified during progradation of less-dense and compacting clastics. In contrast, basin-scale salt flow driven by clastic progradation alone, without deposition of early post-salt carbonates, does not produce minibasins as observed on salt-bearing passive margins.
Strongly peraluminous granites provide independent evidence for an increase in biomass burial across the Precambrian–Phanerozoic boundary
Authors: Mikhail Sami , Stüeken Eva E. , Boocock Toby J. , Athey Megan , Mappin Nick , Boyce Adrian J. , Liebmann Janne , Spencer Christopher J. , Bucholz Claire E. 
Published: November 2023

Abstract
Strongly peraluminous granites (SPGs) are generated by the partial melting of sedimentary rocks and can thus provide a novel archive to reveal secular trends in Earth’s environmental history that integrate siliciclastic sedimentary lithologies. The nitrogen (N) content of Archean, Proterozoic, and Phanerozoic SPGs reveals a systematic increase across the Precambrian–Phanerozoic boundary. This rise is supported by a coeval increase in the phosphorus (P) contents of SPGs. Collectively, these data are most parsimoniously explained by an absolute increase in biomass burial in the late Proterozoic or early Phanerozoic by a factor of ~5 and as much as 8. The Precambrian–Phanerozoic transition was a time of progressive oxygenation of surface environments paired with major biological innovations, including the rise of eukaryotic algae to ecological dominance. Because oxygenation suppresses biomass preservation in sediments, the increase in net biomass burial preserved in SPGs reveals an expansion of the biosphere and an increase in primary production across this interval.
Community perceptions matter: a mixed-methods study using local knowledge to define features of success for a community intervention to improve quality of care for children under-5 in Jigawa, Nigeria
Authors: Iuliano Agnese , Shittu Funmilayo , Colbourn Timothy , Salako Julius , Bakare Damola , Bakare Ayobami Adebayo A , King Carina , Graham Hamish , McCollum Eric D , Falade Adegoke G , Uchendu Obioma , Haruna Ibrahim , Valentine Paula , Burgess Rochelle 
Published: November 2023

ObjectivesIn this study, we used the information generated by community members during an intervention design process to understand the features needed for a successful community participatory intervention to improve child health.DesignWe conducted a concurrent mixed-methods study (November 2019–March 2020) to inform the design and evaluation of a community–facility linkage participatory intervention.SettingKiyawa Local Government Area (Jigawa State, Nigeria)—population of 230 000 (n=425 villages).ParticipantsQualitative data included 12 community conversations with caregivers of children under-5 (men, older and younger women; n=9 per group), 3 focus group discussions (n=10) with ward development committee members and interviews with facility heads (n=3). Quantitative data comprised household surveys (n=3464) with compound heads (n=1803) and women (n=1661).ResultsWe analysed qualitative data with thematic network analysis and the surveys with linear regression—results were triangulated in the interpretation phase. Participants identified the following areas of focus: community health education; facility infrastructure, equipment and staff improvements; raising funds to make these changes. Community involvement, cooperation and empowerment were recognised as a strategy to improve child health, and the presence of intermediate bodies (development committees) was deemed important to improve communication and solve problems between community and facility members. The survey showed functional community relations’ dynamics, with high levels of internal cohesion (78%), efficacy in solving problems together (79%) and fairness of the local leaders (82%).ConclusionsCombining the results from this study and critical theories on successful participation identified community-informed features for a contextually tailored community–facility link intervention. The need to promote a more inclusive approach to future child health interventions was highlighted. In addition to health education campaigns, the relationship between community and healthcare providers needs strengthening, and development committees were identified as an essential feature for successfully linking communities and facilities for child health.Trial registration numberISRCTN39213655.
Development of peanut, sesame and tree nut allergy in Polish children at high risk of food allergy: a protocol for a cross-sectional study
Authors: Ryczaj Klaudia , Szczukocka-Zych Agnieszka , Wawszczak Maria , Gawryjołek Julia , Krogulska Aneta , Krawiec Marta , Horvath Andrea , Szajewska Hania , Santos Alexandra , Bahnson Henry T , Kulus Marek 
Published: November 2023

IntroductionPeanut allergies cause serious health problems worldwide. A strong finding has shown that the early introduction of peanuts into the diet of infants at high risk of food allergy reduces the prevalence of peanut allergy. Allergies to peanuts, sesame and tree nuts have been shown to coexist in 60% of cases and vary according to geographical location and dietary habits. Insights into the prevalence of nut and seed allergies in societies with varying consumption levels are essential for developing population-specific weaning guidelines. Understanding the age at which peanut allergy develops is paramount for successful early introduction strategies.Methods and analysisWe will perform a cross-sectional study at two tertiary allergy centres in Warsaw and Bydgoszcz. Two hundred forty children aged 4–36 months with eczema or egg allergy will undergo an extensive assessment of their peanut, sesame and tree nut allergy status through skin testing, specific IgE measurements and oral food challenges. The primary outcome is the prevalence of peanut, sesame and tree nut allergies in Polish children at high risk of food allergy. Additionally, the timing of the development of peanut, sesame and tree nut allergies in the first 3 years of life in a high-risk population will be assessed.Ethics and disseminationThe Ethics Committee of the Medical University of Warsaw, Poland approved this protocol (KB/86/2021). The results of this study will be submitted to a peer-reviewed journal no later than 1 year after data collection. The abstract will be presented at relevant national and international conferences.Although the authors may be able to commit to journal submission no later than 1 year after data collection, publication dates remain beyond their control.Trial registration numberNCT05662800.
Dynamic changes in methadone utilisation for opioid use disorder treatment: a retrospective observational study during the COVID-19 pandemic
Authors: Kennalley Amy L , Fanelli Jessica L , Furst John A , Mynarski Nicholas J , Jarvis Margaret A , Nichols Stephanie D , McCall Kenneth L , Piper Brian J 
Published: November 2023

ObjectivesOpioid use disorder (OUD) is a major public health concern in the USA, resulting in high rates of overdose and other negative outcomes. Methadone, an OUD treatment, has been shown to be effective in reducing the risk of overdose and improving overall health and quality of life. This study analysed the distribution of methadone for the treatment of OUD across the USA over the past decade and through the COVID-19 pandemic.DesignRetrospective observational study using secondary data analysis of the Drug Enforcement Administration and Medicaid Databases.SettingUSA.ParticipantsPatients who were dispensed methadone at US opioid treatment programmes (OTPs).Primary and secondary outcome measuresThe primary outcomes were the overall pattern in methadone distribution and the number of OTPs in the USA per year. The secondary outcome was Medicaid prescriptions for methadone.ResultsMethadone distribution for OUD has expanded significantly over the past decade, with an average state increase of +96.96% from 2010 to 2020. There was a significant increase in overall distribution of methadone to OTP from 2010 to 2020 (+61.00%, p<0.001) and from 2015 to 2020 (+26.22%, p<0.001). However, the distribution to OTPs did not significantly change from 2019 to 2021 (−5.15%, p=0.491). There was considerable state-level variation in methadone prescribing to Medicaid patients with four states having no prescriptions.ConclusionsThere have been dynamic changes in methadone distribution for OUD. Furthermore, pronounced variation in methadone distribution among states was observed, with some states having no OTPs or Medicaid coverage. New policies are urgently needed to increase access to methadone treatment, address the opioid epidemic in the USA and reduce overdose deaths.
Relationship between diabetic knowledge, attitudes and practices among patients with diabetes in China: a structural equation model
Authors: Zhu Wenjun , Liang Di , Petersen Jindong Ding , Zhang Weijun , Huang Jiayan , Dong Yin 
Published: November 2023

ObjectivesWhether the routine delivery of diabetes-related knowledge can change patients’ attitudes and hence influence their self-management activities remains unknown in primary healthcare settings in China. Thus, this study aims to explore the complex transformation process between knowledge, attitude and practice (KAP) among patients with diabetes in a city in China.DesignA cross-sectional study.SettingYuhuan City, Zhejiang Province, China.ParticipantsA total of 803 patients with diabetes were invited to attend a questionnaire survey and 782 patients with type 2 diabetes completed the survey. The average age of participants was 58.47 years old, 48.21% of whom only attended primary school or below.Primary and secondary outcome measuresA questionnaire based on existing scales and expert consultation was applied to assess patients’ socio-demographic information (SI), disease progression risk and diabetes-related KAP. A structural equation model was built to analyse the relationships between patients’ characteristics and KAP.ResultsNo significant association was found between patients’ knowledge and attitude (β=0.01, p=0.43). Better knowledge and attitude were both found to be associated with better diet and physical activities (β=0.58, p<0.001; β=0.46, p=0.01). However, patients with a more positive attitude toward diabetic care showed worse foot care practice (β=−0.13, p=0.02), while better knowledge was associated with better foot care practice (β=0.29, p<0.001). In addition, patients with higher SI (β=0.88, p<0.001) and/or disease progression risk (β=0.42, p<0.001) tended to present higher levels of disease knowledge.ConclusionsWhile successful KAP transformation has been achieved in practice for diet and physical activities, there is a need to improve foot care practice. Health education should also prioritise the prevention, detection and care of diabetic foot. Also, appropriate methods should be adopted to deliver health education to vulnerable patients, such as the elderly, those living in rural areas, those with minimal education, the unemployed and low-income patients.
Whole slide imaging of tumour microenvironment in classical Hodgkin’s lymphoma: development of a clinical prediction model based on programmed death-ligand 1 and tumorous Reed-Sternberg cells
Authors: Santisteban Espejo Antonio , Bernal-Florindo Irene , Montero-Pavon Pedro , Perez-Requena Jose , Atienza-Cuevas Lidia , Villalba-Fernandez Ana , Garcia-Rojo Marcial 
Published: November 2023

AimsThe prognostic impact of programmed death-ligand 1 (PD-L1) cells in classic Hodgkin lymphoma (cHL) tumour microenvironment remains undefined.MethodsModel development via Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines were followed. PD-L1+ and CD30+ tumoral Reed-Sternberg cells were quantified through whole slide imaging and digital image analysis in 155 digital histopathological slides of cHL. Univariate and multivariate survival analyses were performed. The analyses were reproduced for patients with advanced stages (IIB, III and IV) using the Advanced-stage cHL International Prognostic Index.ResultsThe PD-L1/CD30 ratio was statistically significantly associated with survival outcomes. Patients with a PD-L1/CD30 ratio above 47.1 presented a shorter overall survival (mean OS: 53.7 months; 95% CI: 28.7 to 78.7) in comparison with patients below this threshold (mean OS: 105.4 months; 95% CI: 89.6 to 121.3) (p=0.04). When adjusted for covariates, the PD-L1/CD30 ratio retained prognostic impact, both for the OS (HR: 1.005; 95% CI: 1.002 to 1.008; p=0.000) and the progression-free survival (HR: 3.442; 95% CI: 1.045 to 11.340; p=0.04) in a clinical and histopathological multivariate model including the male sex (HR: 3.551; 95% CI: 0.986 to 12.786; p=0.05), a percentage of tumoral cells ≥10.1% (HR: 1.044; 95% CI: 1.003 to 1.087; p=0.03) and high risk International Prognostic Score (≥3 points) (HR: 6.453; 95% CI: 1.970 to 21.134; p=0.002).ConclusionsThe PD-L1/CD30 ratio identifies a group of cHL patients with an increased risk of treatment failure. Its clinical application can be performed as it constitutes an easy to implement pathological information in the diagnostic work-up of patients with cHL.
Register-based observational study of associations between inflammatory remission, formal treatment targets and the use of disease-modifying antirheumatic drugs among patients with early rheumatoid arthritis
Authors: Lindqvist Joakim , Askling Johan , Lampa Jon 
Published: November 2023

ObjectiveTo assess associations between inflammatory remission, formal treatment targets and the likelihood of starting a new disease-modifying antirheumatic drug (DMARD), among patients with early rheumatoid arthritis (RA).MethodsPatients newly diagnosed with RA were identified in the Swedish Rheumatology Quality Register (n=11 784). Disease Activity Score 28 (DAS28) and DMARD-treatment were assessed at RA diagnosis and 3, 6, 12 and 24 months thereafter. Inflammatory remission was defined as: swollen joints (0–28)=0 and C reactive protein <10 mg/L and normal erythrocyte sedimentation rate. The primary treatment target was DAS28 remission (<2.6). The proportion of patients in inflammatory remission who failed to reach DAS28 targets was assessed at each follow-up visit, and their likelihood of starting a new DMARD was compared with patients in inflammatory remission who reached the treatment target. rate ratios (RR) and 95% CIs were estimated with modified Poisson regression.ResultsOverall, 34%, 39%, 44% and 47% were in inflammatory remission at 3, 6, 12 and 24 months. Among these, 20%, 22%, 20% and 19%, respectively, failed to reach DAS28 remission. Patients who failed to reach DAS28 remission despite being in inflammatory remission were more likely to start a new DMARD treatment (RR (95% CI) at 6 months=1.59 (1.29 to 1.96), 12 months=1.52 (1.23 to 1.87)) and 24 months=1.47 (1.20 to 1.80).ConclusionFailing to reach formal treatment targets, despite being in inflammatory remission, is common among patients with early RA, and is associated with an increased likelihood of starting a new DMARD-treatment.
New animal model of chronic gout reproduces pathological features of the disease in humans
Authors: Wang Jiwei , Hao Peiqi , Sun Xianrun , Ward Richard , Tang Tao , Chen Xi , Liu Yihong , Luo Guancong , Yang Yang , Xiang Cheng , An Su , Xu Tian-Rui 
Published: November 2023

ObjectivesGout, as the most prevalent form of inflammatory arthritis, necessitates the use of animal models to investigate the molecular mechanisms involved in its development. Therefore, our objective was to develop a novel chronic mouse model of gout that more closely mimics the progression of gout in humans.MethodsA novel chronic mouse model of gout was established by a simple method, which does not require high technical proficiency, predominantly involves daily intraperitoneal injections of potassium oxonate for approximately 4 months, combined with a high fat-diet and injections of acetic acid into the hind paws to facilitate the formation of monosodium urate (MSU). Arthritis scores and paw oedema were assessed, behavioural tests were conducted, and histopathological and imaging evaluations of the arthritic paw joints were performed.ResultsAfter 4 months of induction, mice in the model group exhibited noticeable increases in arthritis severity, joint and cartilage damage, as well as bone erosion. Gomori’s methenamine silver stain revealed the presence of MSU crystal deposition or tophi in the paw joints or ankle joints of up to 37.9% of the model mice (11 out of 29 mice). Moreover, treatment with benzbromarone effectively prevented the further development of gout or tophi formation in model mice.ConclusionsOur model more accurately replicates the pathological features of gouty arthritis compared with gout induced by MSU crystal injections. Therefore, it is particularly suitable for further investigations into the pathogenesis of gout and also serves as a valuable platform for screening potential antigout agents.