bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vibrational Spectroscopy Identifies Myocardial Chemical Modifications in Heart Failure with Preserved Ejection Fraction
Authors: Pioppi Leonardo , Parvan Reza , Samrend Alan , da Silva Gustavo Justo , Paolantoni Marco , Sassi Paola , Cataliotti Alessandro 
Published: March 2023

AbstractBackgroundVibrational spectroscopy can be a valuable tool to monitor the markers of cardiovascular diseases. In the present work, we explored the vibrational spectroscopy characteristics of the cardiac tissue in an experimental model of heart failure with preserved ejection fraction (HFpEF).MethodsWe used the Fourier-transform infrared (FTIR) and Raman micro-spectroscopic techniques to provide complementary and objective tools for the histological assessment of heart tissues from an animal model of HFpEF. A new sampling technique was adopted (tissue print on a CaF2 disk) to characterize the extracellular matrix.ResultsSeveral spectroscopic markers (lipids, carbohydrates, and glutamate bands) were recognized in the cardiac ventricles as due to the comorbidities associated with the pathology, such as obesity and diabetes. Besides, abnormal collagen cross-linking and a decrease in tryptophan content were observed and related to the stiffening of ventricles and to the inflammatory state which is a favorable condition for HFpEF.ConclusionsBy the analyses of tissues and tissue prints, FTIR and Raman techniques were shown to be highly sensitive and selective in detecting changes in the chemistry of the heart in experimental HFpEF and its related comorbidities.
NE contribution to rebooting unconsciousness caused by midazolam
Authors: Gu LeYuan , Shao WeiHui , Liu Lu , Xu Qing , Wang YuLing , Gu JiaXuan , Yang Yue , Zhang ZhuoYue , Wu YaXuan , Shen Yue , Yu Qian , Lian XiTing , Ma Haixiang , Zhang YuanLi , Zhang HongHai 
Published: March 2023

AbstractThe advent of midazolam holds profound implications for modern clinical practice. The hypnotic and sedative effects of midazolam afford it broad clinical applicability. However, the specific mechanisms underlying the modulation of altered consciousness by midazolam remain elusive. Herein, using pharmacology, optogenetics, chemogenetics, fiber photometry, and gene knockdown, we revealed the role of locus coeruleus (LC)-ventrolateral preoptic nucleus (VLPO) noradrenergic neural circuit in regulating midazolam-induced altered consciousness. This effect was mediated by α1 adrenergic receptors. Moreover, gamma-aminobutyric acid receptor type A (GABAA-R) represents a mechanistically crucial binding site in the LC for midazolam. Our findings will provide novel insights into the neural circuit mechanisms underlying the recovery of consciousness after midazolam administration and will help guide the timing of clinical dosing and propose effective intervention targets for timely recovery from midazolam-induced loss of consciousness.
DISTINCT ROLES OF VIRAL US3 AND UL13 PROTEIN KINASES IN HERPES VIRUS SIMPLEX TYPE 1 (HSV-1) NUCLEAR EGRESS
Authors: Bahnamiri Masoudeh Masoud , Roller Richard J. 
Published: March 2023

ABSTRACTHerpesviruses transport nucleocapsids from the nucleus to the cytoplasm by capsid envelopment into the inner nuclear membrane and de-envelopment from the outer nuclear membrane, a process that is coordinated by nuclear egress complex (NEC) proteins, pUL34, and pUL31. Both pUL31 and pUL34 are phosphorylated by the virus-encoded protein kinase, pUS3, and phosphorylation of pUL31 regulates NEC localization at the nuclear rim. pUS3 also controls apoptosis and many other viral and cellular functions in addition to nuclear egress, and the regulation of these various activities in infected cells is not well understood. It has been previously proposed that pUS3 activity is selectively regulated by another viral protein kinase, pUL13 such that its activity in nuclear egress is pUL13-dependent, but apoptosis regulation is not, suggesting that pUL13 might regulate pUS3 activity on specific substrates. We compared HSV-1 UL13 kinase-dead and US3 kinase-dead mutant infections and found that pUL13 kinase activity does not regulate the substrate choice of pUS3 in any defined classes of pUS3 substrates and that pUL13 kinase activity is not important for promoting de-envelopment during nuclear egress. We also find that mutation of all pUL13 phosphorylation motifs in pUS3, individually or in aggregate, does not affect the localization of the NEC, suggesting that pUL13 regulates NEC localization independent of pUS3. Finally, we show that pUL13 co-localizes with pUL31 inside the nucleus in large aggregates, further suggesting a direct effect of pUL13 on the NEC and suggesting a novel mechanism for both UL31 and UL13 in the DNA damage response pathway.IMPORTANCEHerpes simplex virus infections are regulated by two virus-encoded protein kinases, pUS3 and pUL13, which each regulate multiple processes in the infected cell, including capsid transport from the nucleus to the cytoplasm. Regulation of the activity of these kinases on their various substrates is poorly understood, but importantly, kinases are attractive targets for the generation of inhibitors. It has been previously suggested that pUS3 activity on specific substrates is differentially regulated by pUL13 and, specifically, that pUL13 regulates capsid egress from the nucleus by phosphorylation of pUS3. In this study, we determined that pUL13 and pUS3 have different effects on nuclear egress and that pUL13 may interact directly with the nuclear egress apparatus with implications both for virus assembly and egress and, possibly, the host cell DNA- damage response.
Implication ofFOXD2dysfunction in syndromic congenital anomalies of the kidney and urinary tract (CAKUT)
Authors: Riedhammer Korbinian M. , Nguyen Thanh-Minh T. , Koşukcu Can , Calzada-Wack Julia , Li Yong , Saygılı Seha , Wimmers Vera , Kim Gwang-Jin , Chrysanthou Marialena , Bakey Zeineb , Kraiger Markus , Sanz-Moreno Adrián , Amarie Oana V , Rathkolb Birgit , Klein-Rodewald Tanja , Garrett Lillian , Hölter Sabine M. , Seisenberger Claudia , Haug Stefan , Marschall Susan , Wurst Wolfgang , Fuchs Helmut , Gailus-Durner Valerie , Wuttke Matthias , Hrabe de Angelis Martin , Ćomić Jasmina , Akgün Doğan Özlem , Özlük Yasemin , Taşdemir Mehmet , Ağbaş Ayşe , Canpolat Nur , Çalışkan Salim , Weber Ruthild , Bergmann Carsten , Jeanpierre Cecile , Saunier Sophie , Lim Tze Y. , Hildebrandt Friedhelm , Alhaddad Bader , Wu Kaman , Antony Dinu , Matschkal Julia , Schaaf Christian , Renders Lutz , Schmaderer Christoph , Meitinger Thomas , Heemann Uwe , Köttgen Anna , Arnold Sebastian , Ozaltin Fatih , Schmidts Miriam , Hoefele Julia 
Published: March 2023

AbstractBackgroundCongenital anomalies of the kidney and urinary tract (CAKUT) are the predominant cause for chronic kidney disease below 30 years of age. Many monogenic forms have been discovered mainly due to comprehensive genetic testing like exome sequencing (ES). However, disease-causing variants in known disease-associated genes still only explain a proportion of cases. Aim of this study was to unravel the underlying molecular mechanism of syndromic CAKUT in two multiplex families with presumed autosomal recessive inheritance.Methods and ResultsES in the index individuals revealed two different rare homozygous variants inFOXD2,a transcription factor not previously implicated in CAKUT in humans: a frameshift in family 1 and a missense variant in family 2 with family segregation patterns consistent with autosomal-recessive inheritance. CRISPR/Cas9-derivedFoxd2knock-out (KO) mice presented with bilateral dilated renal pelvis accompanied by renal papilla atrophy while extrarenal features included mandibular, ophthalmologic, and behavioral anomalies, recapitulating the phenotype of humans withFOXD2dysfunction. To study the pathomechanism ofFOXD2-dysfunction-mediated developmental renal defects, in a complementary approach, we generated CRISPR/Cas9-mediated KO ofFoxd2in ureteric-bud-induced mouse metanephric mesenchyme cells. Transcriptomic analyses revealed enrichment of numerous differentially expressed genes important in renal/urogenital development, includingPax2andWnt4as well as gene expression changes indicating a cell identity shift towards a stromal cell identity. Histology ofFoxd2KO mouse kidneys confirmed increased fibrosis. Further, GWAS data (genome-wide association studies) suggests thatFOXD2could play a role for maintenance of podocyte integrity during adulthood.ConclusionsIn summary, our data implicate thatFOXD2dysfunction is a very rare cause of autosomal recessive syndromic CAKUT and suggest disturbances of the PAX2-WNT4 cell signaling axis contribute to this phenotype.
Endemic-epidemic modelling of school closure to prevent spread of COVID-19 in Switzerland
Authors: Dunbar M. Bekker-Nielsen , Hofmann F. , Meyer S. , Held L. 
Published: March 2023

SummaryThe coronavirus disease 2019 (COVID-19) pandemic disrupted daily life and changes to routines were made in accordance with public health regulations. In 2020, nonpharmaceutical interventions were put in place to reduce exposure to and spread of the disease. The goal of this work was to quantify the effect of school closure during the first year of COVID-19 pandemic in Switzerland. This allowed us to determine the usefulness of school closures as a pandemic countermeasure for emerging coronaviruses in the absence of pharmaceutical interventions. The use of multivariate endemic-epidemic modelling enabled us to analyse disease spread between age groups which we believe is a necessary inclusion in any model seeking to achieve our goal. Sophisticated time-varying contact matrices encapsulating four different contact settings were included in our complex statistical modelling approach to reflect the amount of school closure in place on a given day. Using the model, we projected case counts under various transmission scenarios (driven by implemented social distancing policies). We compared these counterfactual scenarios against the true levels of social distancing policies implemented, where schools closed in the spring and reopened in the autumn. We found that if schools had been kept open, the vast majority of additional cases would be expected among primary school-aged children with a small fraction of cases percolating into other age groups following the contact matrix structure. Under this scenario where schools were kept open, the cases were highly concentrated among the youngest age group. In the scenario where schools had remained closed, most reduction would also be expected in the lowest age group with less effects seen in other groups.
Employment outcomes of people with Long Covid symptoms: community-based cohort study
Authors: Ayoubkhani Daniel , Zaccardi Francesco , Pouwels Koen B. , Walker A. Sarah , Houston Donald , Alwan Nisreen A. , Martin Josh , Khunti Kamlesh , Nafilyan Vahé 
Published: March 2023

AbstractBackgroundEvidence on the long-term employment consequences of SARS-CoV-2 infection is lacking. We used data from a large, community-based sample in the UK to estimate associations between Long Covid and subsequent employment outcomes.MethodsThis was an observational, longitudinal study using a pre-post design. We included survey participants from 3 February 2021 to 30 September 2022 when they were aged 16 to 64 years and not in full-time education. Using conditional logit modelling, we explored the time-varying relationship between Long Covid status ≥12 weeks after a first test-confirmed SARS-CoV-2 infection (reference: pre-infection) and labour market inactivity (neither working nor looking for work) or workplace absence lasting ≥4 weeks.ResultsOf 206,299 included participants (mean age 45 years, 54% female, 92% white), 15% were ever inactive in the labour market and 10% were ever long-term absent during follow-up. Compared with pre-infection, inactivity was higher in participants reporting Long Covid 30 to <40 weeks (adjusted odds ratio (aOR): 1.45; 95% CI: 1.17 to 1.81) or 40 to <52 weeks (1.34; 1.05 to 1.72) post-infection. Combining with official statistics on Long Covid prevalence, our estimates translate to 27,000 (95% CI: 6,000 to 47,000) working-age adults in the UK being inactive because of Long Covid in July 2022.ConclusionsLong Covid is likely to have contributed to reduced levels of participation in the UK labour market, though it is unlikely to be the sole driver. Further research is required to quantify the contribution of other factors, such as indirect health effects of the pandemic.
The trend of hypertension-related chronic kidney disease from 1990 to 2019 and its predictions over 25 years: An analysis of the Global Burden of Disease Study 2019
Authors: Ren Yi , Zhang Honggang 
Published: March 2023

AbstractBackgroundHigh blood pressure is a key pathogenetic factor that contributes to the deterioration of kidney function. However, the incidence trend of hypertension-related chronic kidney disease (CKD) has rarely been studied; therefore, we aimed to analyze the global, regional, and national patterns, temporal trends as well as burden of hypertension-related CKD.MethodsWe extracted data on hypertension-related CKD from the Global Burden of Disease (GBD) study database, including the incidence, prevalence, disability-adjusted life years (DALYs), and mortality numbers and rates (per 100,000 population) and further described according to year, location, sex, age, and socio-demographic index (SDI). The estimated annual percentage changes (EAPCs) were calculated to assess the variation in incidence, DALYs, and mortality. We used an age-period-cohort (APC) model framework to analyze the underlying trends in prevalence by age, period, and birth cohort. Nordpred APC analysis was performed to predict the future morbidity and mortality of hypertension-related CKD.ResultsIn 2019, a total of over 1.57 million new hypertension-related CKD cases were reported worldwide, a 161.97% increase from 1990. Compared to 1990, the ASIR increased in all 21 regions in 2019. In all countries and territories except Iceland, the EAPC in ASIR and the lower boundary of its 95% confidence interval (CI) were higher than 0. ASIR, ASPR, ASDR, and ASMR were not identical among countries with different SDI regions in 2019; additionally, ASIR and ASMR were significantly different among sexes in all SDI regions in 2019. The predicted incidence and mortality counts globally continue to increase to 2044, and there is an upward trend in ASIR for both men and women.ConclusionsHypertension-related CKD cannot be ignored either as a subcategory of CKD or as a complication of hypertension. Between 1990 and 2019, the ASIR of hypertension-related CKD demonstrated an ascending trend, and according to our projections, it would remain on the rise for the next 25 years. With remarkable global population growth, aging, and an increasing number of patients with hypertension, the burden of disease caused by hypertension-related CKD continues to increase.
Prospective Assessment of Bone Marrow Involvement with Positron Emission Tomography vs Bone Marrow Biopsy in Patients with Lymphoma
Authors: Singla Suhas , Batra Sandeep , Dougall Pankaj , Dayal Nitin , Naithani Rahul 
Published: March 2023

AbstractBackgroundBone marrow involvement (BM involvement) in lymphoma is a known adverse prognostic factor. Bone marrow biopsy (BMB) is the gold standard for detection of bone marrow involvement but is invasive modality. Positron Emission Tomography with Computed Tomography (PET-CT) scan has the ability to assess bone marrow involvement. We aimed to assess the concordance of PET-CT for BM involvement with BMB.Methods75 consecutive newly diagnosed cases of lymphoma were enrolled and were assessed for BM involvement with PET-CT and BMB.ResultsOf 75 patients, eighteen patients (24%) had BM involvement, with 19% (n=14) detected with BMB, and 13 (17%) with FDG 18 PET CT. There was a concordance rate of 88% amongst PET-CT and BMB. It was 92% in Hodgkin’s lymphoma (HL), 71.4% in non-Hodgkin’s lymphoma (NHL), and 91% and 70% in high-grade (HG) and low-grade (LG) NHL, respectively. Sensitivity, specificity, PPV, NPV, and accuracy of PET-CT for study population were 69.23%, 93.44%, 69.23%, 93.44%, and 89.19 % respectively. In patients with NHL sensitivity, specificity, NPV, PPV, and accuracy of PET-CT were 54.55%, 94.23%, 66.67%, 90.74%, and 87.30%, respectively; whereas in HL group these were 100%, 88.89%, 75%, 100%, and 91.67%, respectively.ConclusionsPET-CT has got a high concordance with bone marrow biopsy in detecting bone marrow involvement with high specificity, NPV and accuracy. A high sensitivity, specificity, NPV and accuracy for detecting bone marrow involvement in patients with HL, aggressive B cell NHL, and T cell NHL was observed but the same parameters were not at par in patient with indolent (low-grade) NHL.
RNase L activating 2′–5′ oligoadenylates bind ABCF1, -3 and Decr-1
Authors: Govande Apurva A. , Babnis Aleksandra W. , Urban Christian , Habjan Matthias , Hartmann Rune , Kranzusch Philip J. , Pichlmair Andreas 
Published: March 2023

AbstractA notable signaling mechanism employed by mammalian innate immune signaling pathways uses nucleotide based second messengers such as 2′–3′-cGAMP and 2′–5′-oligoadenylates (2′–5′ OA), which bind and activate STING and RNase L, respectively. Interestingly, the involvement of nucleotide second messengers to activate antiviral responses is evolutionary conserved, evidenced by the identification of an antiviral cGAMP-dependent pathway inDrosophila. Using a mass spectrometry approach, we identified several members of the ABCF family in human, mouse, andDrosophilacell lysates as 2′–5′ OA binding proteins, suggesting an evolutionary conserved function. Biochemical characterization of these interactions demonstrates high-affinity binding of 2′–5′ OA to ABCF1, which depended on phosphorylated 2′–5′ OA and an intact Walker A/B motif of the ABC cassette of ABCF1. As further support for species-specific interactions with 2′–5′ OA, we additionally identified that the metabolism enzyme Decr1 from mouse, but not human orDrosophilacells forms a high-affinity complex with 2′–5′ OA. A 1.4 Å co-crystal structure of the mouse Decr1–2′–5′ OA complex explains high-affinity recognition of 2′–5′ OA and the mechanism of species-specificity. Despite clear evidence of physical interactions, we could not identify profound antiviral functions of ABCF1, ABCF3 or Decr1 or 2′–5′ OA-dependent regulation of cellular translation rates as suggested by the engagement of ABCF proteins. Thus, although the biological consequences of the here identified interactions need to be identified, our data suggests that 2′–5′ OA can serve as signaling hub to distribute a signal to different recipient proteins.
Comparative genomics ofMycoplasma feriruminatoris, a fast-growing pathogen of wildCaprinae
Authors: Baby Vincent , Ambroset Chloé , Gaurivaud Patrice , Falquet Laurent , Boury Christophe , Guichoux Erwan , Jores Joerg , Lartigue Carole , Tardy Florence , Sirand-Pugnet Pascal 
Published: March 2023

AbstractMycoplasma feriruminatorisis a fast-growingMycoplasmaspecies isolated from wildCaprinaeand first described in 2013.M. feriruminatorisisolates have been associated with arthritis, keratoconjunctivitis, pneumonia and septicemia, but were also recovered from apparently healthy animals. To better understand what defines this species, we performed a genomic survey on 14 strains collected from free-ranging or zoo-housed animals between 1987 and 2017. The average chromosome size of theM. feriruminatorisstrains was 1,040 ± 0,024 kbp, with 24% G+C and 852 ± 31 CDS. The core genome and pan-genome of theM. feriruminatorisspecies contained 628 and 1,312 protein families, respectively. TheM. feriruminatorisstrains displayed a relatively closed pan-genome, with many features and putative virulence factors shared with species from theM. mycoidescluster, including the MIB-MIP Ig cleavage system, a repertoire of DUF285 surface proteins and a complete biosynthetic pathway for galactan.M. feriruminatorisgenomes were found to be mostly syntenic, although repertoires of mobile genetic elements, including Mycoplasma Integrative and Conjugative Elements, insertion sequences, and a single plasmid varied. Phylogenetic- and gene content analyzes confirmed thatM. feriruminatoriswas closer to theM. mycoidescluster than to the ruminant speciesM. yeatsiiandM. putrefaciens. Ancestral genome reconstruction showed that the emergence of theM. feriruminatorisspecies was associated with the gain of 17 gene families, some of which encode defense enzymes and surface proteins, and the loss of 25 others, some of which are involved in sugar transport and metabolism. This comparative study suggests that theM. mycoidescluster could be extended to includeM. feriruminatoris. We also find evidence that the specific organization and structure of the DnaA boxes around theoriCofM. feriruminatorismay contribute to drive the remarkable fast growth of this minimal bacterium.
Partial genome characterization of a novel potentially zoonotic parapoxvirus in a horse, Finland
Authors: Virtanen Jenni , Hautaniemi Maria , Dutra Lara , Plyusnin Ilya , Hautala Katja , Smura Teemu , Vapalahti Olli , Sironen Tarja , Kant Ravi , Kinnunen Paula M. 
Published: March 2023

AbstractWe report a sequencing protocol and 121 kb poxvirus sequence from a clinical sample of a horse with dermatitis. Based on phylogenetic analyses, the virus is a novel parapoxvirus. We show association with recent epidemic, and previous data suggest zoonotic potential. Further characterization and development of diagnostic protocols are necessary.