bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparison of optophysiological biomarkers of photoreceptor stress and phototoxicity in BALB/cJ, B6(Cg)-Tyrc-2J/J, and C57Bl/6J mouse strains
Authors: Bell Brent A. , Kaul Charles , Dunaief Joshua L. , Hollyfield Joe G. , Bonilha Vera L. 
Published: March 2023

IntroductionOphthalmic imaging instruments, including the confocal scanning laser ophthalmoscope and spectral-domain optical coherence tomography system, originally intended for revealing ocular microstructures in the human eye, have been deployed by vision researchers to evaluate the eyes of numerous small and large animal species for more than two decades. In this study, we have used these two instruments to obtain imaging data sequentially from the retinas of three prominent, widely used experimental mouse models to document changes induced by two contrasting vivarium lighting conditions. Mice studied include albino BALB/cJ and B6(Cg)-Tyrc-2J/J and pigmented C57Bl/6J.MethodsMice were reared under dim light conditions until ~8 weeks of age where they underwent baseline imaging. Following, mice were returned to the dim vivarium or relocated to the top rack cage position in a standard vivarium. Mice were then followed for several months by ocular imaging to catalog the retinal dynamics as a function of long-term dim vs. elevated, standard vivarium lighting exposure levels.ResultsUpon exposure to elevated light levels, B6(Cg)-Tyrc-2J/J underwent similar changes as BALB/cJ in regard to photoreceptor outer segment shortening, photoreceptor layer proximal aspect hyperreflective changes, and the development of retinal infoldings and autofluorescent sub-retinal inflammatory monocyte infiltrate. Noteworthy, however, is that infoldings and infiltrate occurred at a slower rate of progression in B6(Cg)-Tyrc-2J/J vs. BALB/cJ. The photoreceptor outer nuclear layer thickness of BALB/cJ degenerated steadily following elevated light onset. In contrast, B6(Cg)-Tyrc-2J/J degeneration was unremarkable for many weeks before experiencing a noticeable change in the rate of degeneration that was concomitant with a plateau and decreasing trend in number of retinal infoldings and monocyte infiltrate. Pathological changes in C57Bl/6J mice were unremarkable for all imaging biomarkers assessed with exception to autofluorescent sub-retinal inflammatory monocyte infiltrate, which showed significant accumulation in dim vs. elevated light exposed mice following ~1 year of observation. These data were evaluated using Spearman’s correlation and Predictive Power Score matrices to determine the best imaging optophysiological biomarkers for indicating vivarium light stress and light-induced photoreceptor degeneration.DiscussionThis study suggests that changes in proximal aspect hyperreflectivity, outer segment shortening, retinal infoldings and autofluorescent sub-retinal inflammatory monocyte infiltrate are excellent indicators of light stress and light-induced degeneration in albino B6(Cg)-Tyrc-2J/J and BALB/cJ mouse strains.
Population pharmacokinetics of vancomycin in very low birth weight neonates
Authors: Alsultan Abdullah , Al Munjem Manea Fares , Atiq Khulood Mohammed , Aljehani Zekra Kamel , Al Muqati Hessa , Almohaizeie Abdullah , Ballal Dalia Ahmed , Refaei Tahani Makki , Al Jeraisy Majed , Assiri Abdulmohsen , Abouelkheir Manal 
Published: March 2023

IntroductionVancomycin dosing in very low birth weight (VLBW) neonates is challenging. Compared with the general neonatal population, VLBW neonates are less likely to achieve the vancomycin therapeutic targets. Current dosing recommendations are based on studies of the general neonatal population, as only a very limited number of studies have evaluated vancomycin pharmacokinetics in VLBW neonates. The main aim of this study was to develop a vancomycin population pharmacokinetic model to optimize vancomycin dosing in VLBW neonates.MethodsThis multicenter study was conducted at six major hospitals in Saudi Arabia. The study included VLBW neonates who received vancomycin and had at least one vancomycin serum trough concentration measurement at a steady state. We developed a pharmacokinetic model and performed Monte Carlo simulations to develop an optimized dosing regimen for VLBW infants. We evaluated two different targets: AUC0–24 of 400–600 or 400–800 µg. h/mL. We also estimated the probability of trough concentrations &gt;15 and 20 µg/mL.ResultsIn total, we included 236 neonates, 162 in the training dataset, and 74 in the validation dataset. A one-compartment model was used, and the distribution volume was significantly associated only with weight, whereas clearance was significantly associated with weight, postmenstrual age (PMA), and serum creatinine (Scr).DiscussionWe developed dosing regimens for VLBW neonates, considering the probability of achieving vancomycin therapeutic targets, as well as different toxicity thresholds. The dosing regimens were classified according to PMA and Scr. These dosing regimens can be used to optimize the initial dose of vancomycin in VLBW neonates.
Case report: Three novel variants on SLC25A13 in four infants with neonatal intrahepatic cholestasis caused by citrin deficiency
Authors: Wang Kena , Zou Biao , Chen Fan , Zhang Jianling , Huang Zhihua , Shu Sainan 
Published: March 2023

BackgroundNeonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a common clinical phenotype of citrin deficiency in infants. Its phenotype is atypical, so genetic testing is quite necessary for the diagnosis.Case presentationWe report 4 patients with jaundice and low body weight. Furthermore, the biochemical examination of all showed abnormal liver function and metabolic changes. DNA samples of the patients were extracted and subjected to genetic screening. All candidate pathogenic variants were validated by Sanger sequencing, and CNVs were ascertained by qPCR. The genetic screening revealed 6 variants in 4 patients, and all patients carried compound heterozygous variants of SLC25A13. Importantly, 3 variants were newly discovered: a nonsense mutation in exon17 (c.1803C &gt; G), a frameshift mutation in exon 11(c.1141delG) and a deletion of the whole exon11. Thus, four NICCD patients were clearly caused by variants of SLC25A13. Biochemical indicators of all patients gradually returned to normal after dietary adjustment.ConclusionsOur study clarified the genetic etiology of the four infants, expanded the variant spectrum of SLC25A13, and provided a basis for genetic counseling of the family. Early diagnosis and intervention should be given to patients with NICCD.
Subclinical cardiac abnormalities in children with biliary atresia correlate with outcomes after liver transplantation
Authors: Li Tingting , Wei Xinzhe , Hao Xiaoye , Ye Xuying , Li Chao , Li Qi , Li Zhuqing , Gao Wei , Lu Chengzhi 
Published: March 2023

ObjectiveThere are subclinical cardiac abnormalities (SCA) in children with biliary atresia (BA). However, data on the consequences of these cardiac changes after liver transplantation (LT) remain controversial in the pediatric field. We aimed to determine the relationship between outcomes and the subclinical cardiac abnormalities in pediatric patients with BA based on two-dimensional echocardiography (2DE) parameters.MethodsA total of 205 children with BA were enrolled in this study. The relationship between 2DE parameters and outcomes, including death and serious adverse events (SAE) after LT, was analyzed by regression analysis. Using receiver operator characteristic (ROC) curves to determine the optimal cut-off values of 2DE parameters for outcomes. Differences in the AUCs were compared using DeLong's test. The Kaplan -Meier method with log-rank testing was used to evaluate survival outcomes between groups.ResultsLeft ventricular mass index (LVMI) and relative wall thickness (RWT) were found to be independently associated with SAE (OR: 1.112, 95% CI: 1.061 − 1.165, P &lt; 0.001 and OR: 1.193, 95% CI: 1.078 − 1.320, P = 0.001, respectively). The cutoff value of LVMI for predicting the SAE was 68 g/m2.7 (AUC = 0.833, 95% CI 0.727-0.940, P &lt; 0.001), and the cutoff value of RWT for predicting the SAE was 0.41 (AUC = 0.732, 95% CI 0.641-0.823, P &lt; 0.001). The presence of subclinical cardiac abnormalities (LVMI &gt; 68 g/m2.7, and/or RWT &gt; 0.41) was associated with lower patient survival (1-year, 90.5% vs 100.0%; 3-year, 89.7% vs 100.0, log-rank P = 0.001). and higher incidence of SAE events.ConclusionsSubclinical cardiac abnormalities were correlated with post-LT mortality and morbidity in children with BA. LVMI can predict the occurrence of death and serious adverse events after liver transplantation.
Associations of parental reproductive age and elevated blood pressure in offspring: An observational study
Authors: Deng Rui , Lou Ke , Zhou Siliang , Li Xingxiu , Dong Bin , Ma Jun , Hu Jie 
Published: March 2023

BackgroundIncreased parental reproductive age has been a social trend around the world, and elevated blood pressure in children leads to an approximately two-fold increased risk of hypertension in adulthood. Aim of this study is to assess the associations of parental reproductive age with the risk of elevated blood pressure in offspring, and to explore the influence of offspring lifestyle on the associations.MethodsData was obtained from a national school program conducted in 7 Chinese provinces, and the final sample was 39,190 students aged 7–18 years. Anthropometric measurements and questionnaires were designed to collect data of children blood pressure and information respectively.ResultsIn this study, 26.7% of children were defined as elevated blood pressure. A U-shaped pattern was observed in the relationship between maternal age and risk of elevated blood pressure, while risk of elevated blood pressure decreased continuously with paternal age increased. After adjustment, offspring of paternal age ≤27 &amp; maternal age ≤26 years and those of paternal age &gt;30 &amp; maternal age &gt;32 years were related to great risk of elevated blood pressure (OR = 1.18, 95% CI: 1.08–1.29, P &lt; 0.001; OR = 1.18, 95% CI: 1.01–1.38, P &lt; 0.05). When stratified by lifestyle status, significant associations between maternal/paternal age and risk of elevated blood pressure were only observed in those with worse lifestyle behaviors, but not in offspring with healthier lifestyle.ConclusionOur findings demonstrate that risk of elevated blood pressure in children is independently related to parental reproductive age, and children maintaining a healthy lifestyle may mitigate the adverse effect.
Serum vascular endothelial growth factor is a potential biomarker for acute mountain sickness
Authors: Nourkami-Tutdibi Nasenien , Küllmer Jennifer , Dietrich Sven , Monz Dominik , Zemlin Michael , Tutdibi Erol 
Published: March 2023

Background: Acute mountain sickness (AMS) is the most common disease caused by hypobaric hypoxia (HH) in high-altitude (HA) associated with high mortality when progressing to high-altitude pulmonary edema (HAPE) and/or high-altitude cerebral edema (HACE). There is evidence for a role of pro- and anti-inflammatory cytokines in development of AMS, but biological pathways and molecular mechanisms underlying AMS remain elusive. We aimed to measure changes in blood cytokine levels and their possible association with the development of AMS.Method: 15 healthy mountaineers were included into this prospective clinical trial. All participants underwent baseline normoxic testing with venous EDTA blood sampling at the Bangor University in United Kingdom (69 m). The participants started from Beni at an altitude of 869 m and trekked same routes in four groups the Dhaulagiri circuit in the Nepali Himalaya. Trekking a 14-day route, the mountaineers reached the final HA of 5,050 m at the Hidden Valley Base Camp (HVBC). Venous EDTA blood sampling was performed after active ascent to HA the following morning after arrival at 5,050 m (HVBC). A panel of 21 cytokines, chemokines and growth factors were assessed using Luminex system (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-1ra, sIL-2Rα, IFN-γ, TNF-α, MCP-1, MIP-1α, MIP-1β, IP-10, G-CSF, GM-CSF, EGF, FGF-2, VEGF, and TGF-β1).Results: There was a significant main effect for the gradual ascent from sea-level (SL) to HA on nearly all cytokines. Serum levels for TNF-α, sIL-2Rα, G-CSF, VEGF, EGF, TGF-β1, IL-8, MCP-1, MIP-1β, and IP-10 were significantly increased at HA compared to SL, whereas levels for IFN-γ and MIP-1α were significantly decreased. Serum VEGF was higher in AMS susceptible versus AMS resistant subjects (p &lt; 0.027, main effect of AMS) and increased after ascent to HA in both AMS groups (p &lt; 0.011, main effect of HA). Serum VEGF increased more from SL values in the AMS susceptible group than in the AMS resistant group (p &lt; 0.049, interaction effect).Conclusion: Cytokine concentrations are significantly altered in HA. Within short interval after ascent, cytokine concentrations in HH normalize to values at SL. VEGF is significantly increased in mountaineers suffering from AMS, indicating its potential role as a biomarker for AMS.
Pioneer colonizers: Bacteria that alter the chicken intestinal morphology and development of the microbiota
Authors: Lee Margie D. , Pedroso Adriana A. , Lumpkins Brett , Cho Youngjae , Maurer John J. 
Published: March 2023

Microbes commonly administered to chickens facilitate development of a beneficial microbiome that improves gut function, feed conversion and reduces pathogen colonization. Competitive exclusion products, derived from the cecal contents of hens and shown to reduceSalmonellacolonization in chicks, possess important pioneer-colonizing bacteria needed for proper intestinal development and animal growth. We hypothesized that inoculation of these pioneer-colonizing bacteria to day of hatch chicks would enhance the development of their intestinal anatomy and microbiome. A competitive exclusion product was administered to broiler chickens, in their drinking water, at day of hatch, and its impact on intestinal morphometrics, intestinal microbiome, and production parameters, was assessed relative to a control, no treatment group. 16S rRNA gene, terminal restriction fragment length polymorphism (T-RFLP) was used to assess ileal community composition. The competitive exclusion product, administered on day of hatch, increased villus height, villus height/width ratio and goblet cell production ∼1.25-fold and expression of enterocyte sugar transporters 1.25 to 1.5-fold in chickens at 3 days of age, compared to the control group. As a next step, chicks were inoculated with a defined formulation, containingBacteroidiaandClostridiarepresenting pioneer-colonizing bacteria of the two major bacterial phyla present in the competitive exclusion product. The defined formulation, containing both groups of bacteria, were shown, dependent on age, to improve villus height (jejunum: 1.14 to 1.46-fold; ileum: 1.17-fold), goblet cell numbers (ileum 1.32 to 2.51-fold), and feed efficiency (1.18-fold, day 1) while decreasingLactobacillusileal abundance by one-third to half in birds at 16 and 42 days of age, respectively; compared to the phosphate buffered saline treatment group.Therefore, specific probiotic formulations containing pioneer colonizing species can provide benefits in intestinal development, feed efficiency and body weight gain.
RAGE is a critical factor of sex-based differences in age-induced kidney damage
Authors: Bajwa Seerat , Luebbe Alexander , Vo Ngoc Dong Nhi , Piskor Eva-Maria , Kosan Christian , Wolf Gunter , Loeffler Ivonne 
Published: March 2023

Introduction: Advanced glycation end products (AGEs) are a heterogeneous group of molecules with potential pathophysiological effects on the kidneys. Fibrosis together with the accumulation of AGEs has been investigated for its contribution to age-related decline in renal function. AGEs mediate their effects in large parts through their interactions with the receptor for AGEs (RAGE). RAGE is a transmembrane protein that belongs to the immunoglobulin superfamily and has the ability to interact with multiple pro-inflammatory/pro-oxidative ligands. The role of RAGE in aging kidneys has not been fully characterized, especially for sex-based differences.Methods: Therefore, we analyzed constitutive RAGE knockout (KO) mice in an age- and sex-dependent manner. Paraffin-embedded kidney sections were used for histological analysis and protein expression of fibrosis and damage markers. RNA expression analysis from the kidney cortex was done by qPCR for AGE receptors, kidney damage, and early inflammation/fibrosis factors. FACS analysis was used for immune cell profiling of the kidneys.Results: Histological analysis revealed enhanced infiltration of immune cells (positive for B220) in aged (&gt;70 weeks old) KO mice in both sexes. FACS analysis revealed a similar pattern of enhanced B-1a cells in aged KO mice. There was an age-based increase in pro-fibrotic and pro-inflammatory markers (IL-6, TNF, TGF-β1, and SNAIL1) in KO male mice that presumably contributed to renal fibrosis and renal damage (glomerular and tubular). In fact, in KO mice, there was an age-dependent increase in renal damage (assessed by NGAL and KIM1) that was accompanied by increased fibrosis (assessed by CTGF). This effect was more pronounced in male KO mice than in the female KO mice. In contrast to the KO animals, no significant increase in damage markers was detectable in wild-type animals at the age examined (&gt;70 weeks old). Moreover, there is an age-based increase in AGEs and scavenger receptor MSR-A2 in the kidneys.Discussion: Our data suggest that the loss of the clearance receptor RAGE in male animals further accelerates age-dependent renal damage; this could be in part due to an increase in AGEs load during aging and the absence of protective female hormones. By contrast, in females, RAGE expression seems to play only a minor role when compared to tissue pathology.
Potential inhibitory effects of compounds ZK-PI-5 and ZK-PI-9 on trehalose and chitin metabolism in Spodoptera frugiperda (J. E. Smith)
Authors: Zhong Fan , Yu Liuhe , Jiang Xinyi , Chen Yan , Wang Sitong , Chao Lei , Jiang Zhiyang , He Biner , Xu Caidi , Wang Shigui , Tang Bin , Duan Hongxia , Wu Yan 
Published: March 2023

Introduction:Spodoptera frugiperda is an omnivorous agricultural pest which is great dangerous for grain output.Methods: In order to investigate the effects of potential trehalase inhibitors, ZK-PI-5 and ZK-PI-9, on the growth and development of S. frugiperda, and to identify new avenues for S. frugiperda control, we measured the content of the trehalose, glucose, glycogen and chitin, enzyme activity, and gene expression levels in trehalose and chitin metabolism of S. frugiperda. Besides, their growth and development were also observed.Results: The results showed that ZK-PI-9 significantly reduced trehalase activity and ZK-PI-5 significantly reduced membraned-bound trehalase activity. Moreover, ZK-PI-5 inhibited the expression of SfTRE2, SfCHS2, and SfCHT, thus affecting the chitin metabolism. In addition, the mortality of S. frugiperda in pupal stage and eclosion stage increased significantly after treatment with ZK-PI-5 and ZK-PI-9, which affected their development stage and caused death phenotype (abnormal pupation and difficulty in breaking pupa).Discussion: These results have provided a theoretical basis for the application of trehalase inhibitors in the control of agricultural pests to promote future global grain yield.
Prevalence and associated factors of apathy in Chinese ALS patients
Authors: Wei Qian-Qian , Guo Yuan , Li Shirong , Yang Tianmi , Hou Yanbing , Ou Ruwei , Lin Junyu , Jiang Qirui , Shang Huifang 
Published: March 2023

ObjectivveThis study aimed to explore the prevalence and clinical correlates of apathy in amyotrophic lateral sclerosis (ALS) in a cohort of Chinese patients.MethodsA total of 1,013 ALS patients were enrolled in this study. Apathy was recorded during face-to-face interviews using Frontal Behavioral Inventory, and other patient characteristics, including depression, anxiety, and cognitive function, were collected using Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), and Chinese version of Addenbrooke’s Cognitive Examination-revised. Health-related quality of life of ALS patients and their caregivers was also evaluated, and the potential factors associated with apathy were explored using forward binary regression analysis. Survival was analyzed using the Cox proportional hazards model.ResultsThe prevalence of apathy in all patients was 28.9%. Patients in the late disease stage had a higher prevalence of apathy than those in the early disease stage. Furthermore, patients with apathy had a lower ALS Functional Rating Scale revised (ALSFRS-R) score, higher HDRS score, HARS score and higher proportion of reported problems in the anxiety/depression. Additionally, their caregivers had higher score of depression and higher Zarit-Burden Interview scores. Multivariate regression analysis revealed that apathy in ALS was associated with the onset region (p = 0.027), ALSFRS-R score (p = 0.007), depression (p = 0.001) and anxiety (p &lt; 0.001). Apathy had a significant negative effect on survival in ALS patients (p = 0.032).ConclusionApathy is relatively common (28.9%) in Chinese patients with ALS. Apathy is related to both the severity of the disease, and the presentation of non-motor symptoms in ALS, such as depression and anxiety disorders. Apathy is an independent prognostic factor for survival and requires early intervention and management.