bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene family expansion and functional diversification of chitinase and chitin synthase genes in Atlantic salmon (Salmo salar)
Authors: Holen Matilde Mengkrog , Vaaje-Kolstad Gustav , Kent Matthew Peter , Sandve Simen Rød 
Published: March 2023

Abstract
Chitin is one of the most abundant polysaccharides in nature, forming important structures in insects, crustaceans, and fungal cell walls. Vertebrates on the other hand are generally considered “nonchitinous” organisms, despite having highly conserved chitin metabolism-associated genes. Recent work has revealed that the largest group of vertebrates, the teleosts, have the potential to both synthesize and degrade endogenous chitin. Yet, little is known about the genes and proteins responsible for these dynamic processes. Here, we used comparative genomics, transcriptomics, and chromatin accessibility data to characterize the repertoire, evolution, and regulation of genes involved in chitin metabolism in teleosts, with a particular focus on Atlantic salmon. Reconstruction of gene family phylogenies provides evidence for an expansion of teleost and salmonid chitinase and chitin synthase genes after multiple whole-genome duplications. Analyses of multi-tissue gene expression data demonstrated a strong bias of gastrointestinal tract expression for chitin metabolism genes, but with different spatial and temporal tissue specificities. Finally, we integrated transcriptomes from a developmental time series of the gastrointestinal tract with chromatin accessibility data to identify putative transcription factors responsible for regulating chitin metabolism gene expression (CDX1 and CDX2) as well as tissue-specific divergence in the regulation of gene duplicates (FOXJ2). The findings presented here support the hypothesis that chitin metabolism genes in teleosts play a role in developing and maintaining a chitin-based barrier in the teleost gut and provide a basis for further investigations into the molecular basis of this barrier.
Recurrent mutation in the ancestry of a rare variant
Authors: Wakeley John , Fan Wai-Tong (Louis) , Koch Evan , Sunyaev Shamil 
Published: March 2023

Abstract
Recurrent mutation produces multiple copies of the same allele which may be co-segregating in a population. Yet, most analyses of allele-frequency or site-frequency spectra assume that all observed copies of an allele trace back to a single mutation. We develop a sampling theory for the number of latent mutations in the ancestry of a rare variant, specifically a variant observed in relatively small count in a large sample. Our results follow from the statistical independence of low-count mutations, which we show to hold for the standard neutral coalescent or diffusion model of population genetics as well as for more general coalescent trees. For populations of constant size, these counts are distributed like the number of alleles in the Ewens sampling formula. We develop a Poisson sampling model for populations of varying size and illustrate it using new results for site-frequency spectra in an exponentially growing population. We apply our model to a large data set of human SNPs and use it to explain dramatic differences in site-frequency spectra across the range of mutation rates in the human genome.
Mosaic Chromosomal Alterations and Human Longevity
Authors: Leshchyk Anastasia , Xiang Qingyan , Andersen Stacy L , Gurinovich Anastasia , Song Zeyuan , Lee Joseph H , Christensen Kaare , Yashin Anatoliy , Wojczynski Mary , Schwander Karen , Perls Thomas T , Monti Stefano , Sebastiani Paola 
Published: March 2023

Abstract
Mosaic chromosomal alterations (mCAs) are structural alterations associated with aging, cancer, cardiovascular disease, infectious diseases, and mortality. The distribution of mCAs in centenarians and individuals with familial longevity is poorly understood. We used MOsaic CHromosomal Alteration (MoChA) to discover mCAs in 2050 centenarians, offspring, and 248 controls from the New England Centenarian Study (NECS) and in 3 642 subjects with familial longevity and 920 spousal controls from the Long-Life Family Study (LLFS). We analyzed study-specific associations of somatic mCAs with age, familial longevity, the incidence of age-related diseases, and mortality and aggregated the results by meta-analysis. We show that the accumulation of mCAs &gt; 100 KB increased to 102 years and plateaued at older ages. Centenarians and offspring accumulated fewer autosomal mCAs compared with controls (relative risk 0.637, p = .0147). Subjects with the APOE E4 allele had a 35.3% higher risk of accumulating autosomal mCAs (p = .002). Males were at higher risk for mCAs compared to females (male relative risk 1.36, p = 5.15e−05). mCAs were associated with increased hazard for cancer (hazard ratio 1.2) and dementia (hazard ratio 1.259) at a 10% false discovery rate. We observed a borderline significant association between mCAs and risk for mortality (hazard ratio 1.07, p = .0605). Our results show that the prevalence of individuals with mCAs does not continue to increase at ages &gt;102 years and factors promoting familial longevity appear to confer protections from mCAs. These results suggest that limited mCA accumulation could be an important mechanism for extreme human longevity that needs to be investigated.
The HSPB1-p62/SQSTM1 functional complex regulates the unconventional secretion and transcellular spreading of the HD-associated mutant huntingtin protein
Authors: Bonavita R , Scerra G , Di Martino R , Nuzzo S , Polishchuk E , Di Gennaro M , Williams S V , Caporaso M G , Caiazza C , Polishchuk R , D’Agostino M , Fleming A , Renna M 
Published: March 2023

AbstractConformational diseases, such as Alzheimer, Parkinson and Huntington diseases, are part of a common class of neurological disorders characterized by the aggregation and progressive accumulation of proteins bearing aberrant conformations. Huntington disease (HD) has autosomal dominant inheritance and is caused by mutations leading to an abnormal expansion in the polyglutamine (polyQ) tract of the huntingtin (HTT) protein, leading to the formation of HTT inclusion bodies in neurons of affected patients. Interestingly, recent experimental evidence is challenging the conventional view by which the disease pathogenesis is solely a consequence of the intracellular accumulation of mutant protein aggregates. These studies reveal that transcellular transfer of mutated huntingtin protein is able to seed oligomers involving even the wild-type (WT) forms of the protein. To date, there is still no successful strategy to treat HD. Here, we describe a novel functional role for the HSPB1-p62/SQSTM1 complex, which acts as a cargo loading platform, allowing the unconventional secretion of mutant HTT by extracellular vesicles. HSPB1 interacts preferentially with polyQ-expanded HTT compared with the WT protein and affects its aggregation. Furthermore, HSPB1 levels correlate with the rate of mutant HTT secretion, which is controlled by the activity of the PI3K/AKT/mTOR signalling pathway. Finally, we show that these HTT-containing vesicular structures are biologically active and able to be internalized by recipient cells, therefore providing an additional mechanism to explain the prion-like spreading properties of mutant HTT. These findings might also have implications for the turn-over of other disease-associated, aggregation-prone proteins.
Novel Findings of Early Cardiac Dysfunction in Patients With Childhood-Onset Inflammatory Bowel Disease Using Layer-Specific Strain Analysis
Authors: Akiya Azusa , Takahashi Ken , Akimoto Satoshi , Hosono Yu , Ifuku Mayumi , Iso Takeshi , Yazaki Kana , Shigemitsu Sachie , Jimbo Keisuke , Kudo Takahiro , Ohtsuka Yoshikazu , Shimizu Toshiaki 
Published: March 2023

Abstract

Background
Patients with inflammatory bowel disease (IBD) are at a higher risk of developing cardiovascular diseases than healthy individuals, owing to persistent chronic inflammation and treatment effects. This study aimed to assess left ventricular function in patients with childhood-onset IBD using layer-specific strain analysis and to identify early indicators of cardiac dysfunction in them.

Methods
A total of 47 patients with childhood-onset ulcerative colitis (UC), 20 patients with Crohn’s disease (CD), and 75 age- and sex-matched healthy control subjects were included in this study. Conventional echocardiographic measurements of layer-specific (ie, endocardium, midmyocardium, and epicardium) global longitudinal strain and global circumferential strain (GCS) were evaluated in these participants.

Results
Layer-specific strain analysis showed that global longitudinal strain was lower in all layers for the UC (P &lt; .001) and CD (P &lt; .001) groups, regardless of the age at onset, but that GCS was only lower in the midmyocardial (P = .032) and epicardial (P = .018) layers in the CD group than in the control group. Although the mean left ventricular wall thickness was not significantly different among the groups, it was significantly correlated with the GCS of the endocardial layer in the CD group (ρ= -0.615; P = .004), suggesting that thickening of the left ventricular wall occurred as a compensatory mechanism to maintain the endocardial strain in the CD group layer.

Conclusions
Children and young adults with childhood-onset IBD displayed decreased midmyocardial deformation. Layer-specific strain could also be useful to identify indicators of cardiac dysfunction in patients with IBD.
Effects of 2 and 3 Vaccinations With the Bivalent Human Papillomavirus (HPV) Vaccine on the Prevalence and Load of HPV in Clearing and Persistent Infections in Young Women
Authors: van Eer Kahren , Middeldorp Marit , Dzebisasjvili Tsira , Lamkaraf Najima , de Melker Hester E , Steenbergen Renske D M , King Audrey J 
Published: March 2023

Abstract

Background
Human papillomavirus (HPV) viral load (VL) is associated with persistence, which increases cervical cancer risk. The bivalent vaccine protects against oncogenic HPV-16/18 and cross-protects against several nonvaccine types. We examined the effect of 2-dose (2D) and 3-dose (3D) vaccination on HPV prevalence and VL in clearing infections and persistent infections, 6 years and 12 years postvaccination, respectively.

Methods
Vaginal swabs collected from the “HPV Amongst Vaccinated and Non-vaccinated Adolescents” study (HAVANA, 3D-eligible) and HAVANA-2 (2D-eligble) participants were genotyped for HPV with the SPF10-DEIA-LiPA25 system. HPV VL was measured with type-specific quantitative polymerase chain reaction (qPCR).

Results
HPV-16, -18, -31, -33, and -45 clearing and/or persistent infection prevalence and HPV-16, -18, and -31 VLs in clearing infections were significantly reduced in 3D-vaccinated women compared to unvaccinated women. Except for HPV-11 and -59 clearing infections, no significant VL differences were observed among vaccinated women, ≤6 and &gt;6 years post-vaccination. Infection numbers were low in 2D-eligible women, with no HPV-16/18 in vaccinated women. No VL differences for the remaining types were found.

Conclusions
3D vaccination reduces HPV prevalence in clearing infections and persistent infections and decreases HPV VLs in clearing infections, 12 years post-vaccination for vaccine and several nonvaccine types. 2D-eligible women had low infection numbers, with no HPV-16/18 among vaccinated women.
Development of a local antibiogram for a teaching hospital in Ghana
Authors: Dodoo Cornelius C , Odoi Hayford , Mensah Adelaide , Asafo-Adjei Karikari , Ampomah Ruth , Obeng Lydia , Jato Jonathan , Hutton-Nyameaye Araba , Aku Thelma A , Somuah Samuel O , Sarkodie Emmanuel , Orman Emmanuel , Mfoafo Kwadwo A , Ben Inemesit O , Kpokiri Eneyi E , Abba Fatima , Jani Yogini H 
Published: March 2023

AbstractBackgroundAntimicrobial resistance threatens adequate healthcare provision against infectious diseases. Antibiograms, combined with patient clinical history, enable clinicians and pharmacists to select the best empirical treatments prior to culture results.ObjectivesTo develop a local antibiogram for the Ho Teaching Hospital.MethodsThis was a retrospective cross-sectional study, using data collected on bacterial isolates from January–December 2021. Samples from urine, stool, sputum, blood, and cerebrospinal fluid (CSF) were considered as well as, aspirates and swabs from wound, ears and vagina of patients. Bacteria were cultured on both enrichment and selective media including blood agar supplemented with 5% sheep blood and MacConkey agar, and identified by both the VITEK 2 system and routine biochemical tests. Data on routine culture and sensitivity tests performed on bacterial isolates from patient samples were retrieved from the hospital’s health information system. Data were then entered into and analysed using WHONET.ResultsIn all, 891 pathogenic microorganisms were isolated from 835 patients who had positive culture tests. Gram-negative isolates accounted for about 77% of the total bacterial species. Escherichia coli (246), Pseudomonas spp. (180), Klebsiella spp. (168), Citrobacter spp. (101) and Staphylococcus spp. (78) were the five most isolated pathogens. Most of the bacterial isolates showed high resistance (&gt;70%) to ampicillin, piperacillin, ceftazidime, ceftriaxone, cefotaxime, penicillin G, amoxicillin, amoxicillin/clavulanic acid, ticarcillin/clavulanic acid and trimethoprim/sulfamethoxazole.ConclusionsThe isolates from the various samples were not susceptible to most of the antibiotics used in the study. The study reveals the resistance patterns of E. coli and Klebsiella spp. to some antibiotics on the WHO ‘Watch’ and ‘Reserve’ lists. Using antibiograms as part of antimicrobial stewardship programmes would optimize antibiotic use and preserve their efficacy.
Accuracy of antibacterial indication documentation in an electronic medicines management system
Authors: Yao Wendy , Peel Trisha N , Cairns Kelly A 
Published: March 2023

AbstractIntroductionElectronic medicines management (EMM) systems are relatively new in the Australian healthcare system. This tertiary hospital network implemented an EMM in 2018, with mandatory documentation of antimicrobial indication when prescribing. Free-text (unrestricted) and pre-defined dropdown (restricted) indications are utilized according to antimicrobial restriction.ObjectivesTo determine accuracy of antibacterial indication documentation on the medication administration record (MAR) when prescribing and to evaluate factors influencing accuracy of documentation.MethodsA random sample of 400 inpatient admissions of ≥24 h, between March and September 2019, with the first antibacterial prescription per encounter reviewed retrospectively. Demographic and prescription details were extracted. Indication accuracy was assessed by comparing MAR documentation with the medical notes (gold standard). Statistical analysis compared factors associated with accuracy of indication using chi-squared and Fisher’s exact tests.ResultsAntibacterials were prescribed in 9708 admissions. Of the 400 patients included (60% male; median age 60 years, IQR 40–73), 225 prescriptions were unrestricted and 175 were restricted. Patients were managed by emergency (118), surgical (178) and medical (104) teams. Overall accuracy of antibacterial indication documentation on the MAR was 86%. A higher accuracy rate was found for the unrestricted proportion compared with the restricted proportion (94.2% versus 75.2%; P &lt; 0.0001). Surgical teams had higher accuracy compared with medical and emergency teams (94.4% versus 78.8% versus 79.7%; P &lt; 0.0001).DiscussionAntibacterial indication documentation on the MAR when prescribing demonstrated a high rate of accuracy. Multiple factors influenced this accuracy, which requires further study to determine the impact on accuracy, with a view to improve future EMM builds.
Mitigating antimicrobial resistance (AMR) using implementation research: a development funder’s approach
Authors: Khurana Mark P , Essack Sabiha , Zoubiane Ghada , Sreenivasan Nandini , Cordoba Gloria Cristina , Westwood Erica , Dalsgaard Anders , Mdegela Robinson H , Mpundu Mirfin , Scotini Rodrigo , Matondo Augustine B , Mzula Alexanda , Chanishvili Nina , Gogebashvili Dimitri , Beruashvili Maia , Tsereteli Marika , Sooronbaev Talant , Kjærgaard Jesper , Bloch Joakim , Isaeva Elvira , Mainda Geoffrey , Muuka Geoffrey , Mudenda Ntombi B , Goma Fusya Y , Chu Duc-Huy , Chanda Duncan , Chirwa Uchizi , Yamba Kaunda , Kapolowe Kenneth , Fwoloshi Sombo , Mwenge Lawrence , Skov Robert 
Published: March 2023

AbstractDespite the escalating burden of antimicrobial resistance (AMR), the global response has not sufficiently matched the scale and scope of the issue, especially in low- and middle-income countries (LMICs). While many countries have adopted national action plans to combat AMR, their implementation has lagged due to resource constraints, dysfunctional multisectoral coordination mechanisms and, importantly, an under-recognized lack of technical capacity to adapt evidence-based AMR mitigation interventions to local contexts. AMR interventions should be tailored, context-specific, cost-effective and sustainable. The implementation and subsequent scale-up of these interventions require multidisciplinary intervention-implementation research (IIR). IIR involves both quantitative and qualitative approaches, occurs across a three-phase continuum (proof of concept, proof of implementation and informing scale-up), and across four context domains (inner setting, outer setting, stakeholders and the implementation process). We describe the theoretical underpinnings of implementation research (IR), its various components, and how to construct different IR strategies to facilitate sustainable uptake of AMR interventions. Additionally, we provide real-world examples of AMR strategies and interventions to demonstrate these principles in practice. IR provides a practical framework to implement evidence-based and sustainable AMR mitigation interventions.
Influence of fiber-rich coproducts on nutrient and energy digestibility and utilization in sows
Authors: Wisbech Sigrid J , Jørgensen Henry , Nielsen Tina S , Bach Knudsen Knud E 
Published: March 2023

Abstract
Coproducts from the food and agricultural industries can potentially be used to replace concentrated high-value grain crops in diets for sows. The coproducts are typically high in fiber and with diverse composition. Energy digestibility and utilization are generally high in sows fed fiber-rich feedstuff, but nitrogen digestion and utilization may be compromised. The purpose of this study was to quantify the apparent total tract digestibility (ATTD) of nutrients and utilization of energy and nitrogen in empty nonlactating sows fed with six different fiber-rich coproducts (FRCP). Brewers spent grain (BSG), pea hull (PH), potato pulp (PP), pectin residue (PR), sugar beet pulp (SBP), and seed residue (SR) were mixed into a basal diet (BD) with as high an inclusion level as possible, or the BD was fed solely to eight empty sows in a Youden square incomplete cross-over design. The collection period consisted of a total collection period of 5 d, of which 2 d were in a respiration chamber. The sows had a gross energy (GE) intake between 28.5 and 42.3 MJ/d; greatest for the PH fed sows and lowest for the PP fed sows. The ATTD of dry matter, organic matter, GE, and N did not differ among the BD and the PH and SBP fed sows, while the ATTDs of all nutrients and energy were intermediate for PR and BSG lowest in SR fed sows (P &lt; 0.01). The differences were caused by variation in digestible and metabolizable energy content of the FRCP ingredients, which was lowest for SR, intermediate for PR followed by BSG and greatest for SBP, PP, and PH (P &lt; 0.001). Total heat production (HP) did not differ among treatments but the nonactivity related HP was highest in SR fed sows and lowest in PH and SBP fed sows (P &lt; 0.05). Retention of energy was greatest following the PH and BD (7.42 and 2.19 MJ/d, respectively), intermediate for PP, SBP, and BSG fed sows (−0.22 to −0.69 MJ/d) and lowest for the PR and SR fed sows (−4.26 and −6.17 MJ/d, respectively; P &lt; 0.001). From a sow feeding perspective, SBP and PH have the potential to partly replace high-value grain crops due to high ATTD of all nutrients and because sows can efficiently utilize energy and protein. In contrast, SR and PR show low ATTD of nutrients and energy, thereby compromising the nutritive value. PP and BSG also have the potential to be included in sow diets, but caution should be taken because of compromised N utilization and thereby increased environmental impact.
Effects of dietary crude protein level and sodium butyrate protected by medium-chain fatty acid salts on performance and gut health in weaned piglets
Authors: Sadurní M , Barroeta A C , Sol C , Puyalto M , Castillejos L 
Published: March 2023

Abstract
To reduce the use of antibiotics, research into nutritional strategies designed to improve the gut health of weaned pigs are underway. This study sought to examine the effects of reducing dietary crude protein (CP) and/or supplementing the feed with sodium butyrate protected by the sodium salts of medium-chain fatty acids on the growth performance and gut health of weaned piglets. Ninety-six weaned piglets (Landrace x Large White, 21 days of age) were allotted to four experimental treatments for 14 days. The experimental design was factorial with 2 CP levels and 2 feed-additive doses (0 vs 1 kg/t). Results showed that reducing CP from 22.2 to 18.8% diet had no effect on piglet growth performance parameters during the first post-weaning week (P &gt; 0.05), but did compromise growth in the second week (P = 0.011), impacting on overall growth performance results (P = 0.019). Nonetheless, dietary CP level reduction led to reduce crypt depth (P = 0.036). In addition, Lactobacillus counts that were increased in the ileum (P = 0.032) and reduced in the colon (P = 0.032). Furthermore, apparent ileal digestibility of organic matter (P = 0.026) and fecal consistency (P &lt; 0.05) were improved throughout the experiment. Moreover, in piglets fed diets containing 22.2% CP, the use of the feed-additive tended to improve the gain-to-feed ratio (P = 0.091) compared to those fed supplemented diets containing 18.8% CP. In addition, feed supplementation increased ileal numbers of goblet cells (P = 0.036), as well as apparent ileal digestibility of dry matter (P = 0.057) and organic matter (P = 0.003). Supplementation also had beneficial effects on the microbiota of the colon, increasing Lactobacillus counts (P = 0.006) and diminishing Enterobacteriaceae counts (P = 0.003), as well as affecting microbial metabolite profiles in that acetic acid concentrations tended to be increased (P = 0.088) and valeric acid concentrations were reduced (P = 0.002). These findings support the use of both strategies can improve the gut health of weaned piglets and prompt further research into the possible benefits of combining these two nutritional strategies on gut health and growth performance.