bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using genetics to investigate the association between lanosterol and cataract
Authors: Hashimi Munisa , Amin Hasnat A. , Zagkos Loukas , Day Alexander C. , Drenos Fotios 
Published: February 2024

Background: Cataract is one of the most prevalent causes of blindness worldwide. Whilst surgery is the primary treatment for cataracts, it is not always an available option, particularly in developing countries. Non-surgical methods of treatment would increase treatment availability for more patients. Several studies have investigated how topical application of oxysterols, such as lanosterol, may break down aggregated proteins and restore lens transparency. However, the results are conflicting and inconclusive.Aim: In this study, we focus on combining genetic evidence for associations between lanosterol related genetic variation and cataract to explore whether lanosterol is a potentially suitable drug treatment option.Method: Using data from 45,449 available cataract cases from the UK Biobank, with participant ages ranging from 40–69, we conducted a genetic association study (GWAS) to assess the risk of cataract. Cataract cases were defined using diagnostic and operation codes. We focused on genetic variants in the lanosterol synthase gene region. We also compared our results with previously published genetic associations of phytosterol-to-lanosterol ratios. Finally, we performed a genetic risk score analysis to test the association between lanosterol within the cholesterol synthesis pathway and the risk of cataract.Results: No statistically significant single nucleotide polymorphisms (SNPs) associations with cataract were observed in the gene region of lanosterol synthase at a multiple testing adjusted significance threshold of p &lt; 0.05/13. The comparison between cataract risk and genetic association of 8 phytosterol-to-lanosterol GWAS results also showed no evidence to support lanosterol’s protective properties for cataract risk. No statistically significant association was found between the lanosterol within the cholesterol synthesis pathway genetic risk score and cataract outcomes (OR = 1.002 p = 0.568).Conclusion: There was no evidence observed for genetic associations between lanosterol and cataract risk. Our results do not support lanosterol’s potential role in treating cataracts. Further research may be needed to address the effect of lanosterol on specific cataract subtypes.
Identification and validation of a novel glycolysis-related ceRNA network for sepsis-induced cardiomyopathy
Authors: Cheng Lulu , Liang Jiabin , Xie Fangmei , Han Zeping , Luo Wenfeng , Chen Hanwei , He Jinhua 
Published: February 2024

PurposeSepsis-induced cardiomyopathy (SIC) is a major life-threatening condition in critically infected patients. Early diagnosis and intervention are important to improve patient prognosis. Recognizing the pivotal involvement of the glycolytic pathway in SIC, this study aims to establish a glycolysis-related ceRNA network and explore novel diagnostic avenues.Materials and methodsSIC-related datasets were carefully filtered from the GEO database. CytoHubba was used to identify differentially expressed genes (DEGs) associated with glycolysis. A predictive method was then used to construct an lncRNA-miRNA-mRNA network. Dual-luciferase reporter assays validated gene interactions, and the specificity of this ceRNA network was confirmed in peripheral blood mononuclear cells (PBMCs) from SIC patients. Logistic analysis was used to examine the correlation between the ceRNA network and SIC. Diagnostic potential was assessed using receiver operating characteristic (ROC) curves, and correlation analysis investigated any associations between gene expression and clinical indicators.ResultsIER3 was identified as glycolysis-related DEG in SIC, and a ceRNA network (SNHG17/miR-214-3p/IER3) was established by prediction. Dual luciferase reporter gene assay confirmed the presence of mutual binding between IER3, miR-214-3p and SNHG17. RT-qPCR verified the specific expression of this ceRNA network in SIC patients. Multivariate logistic analysis established the correlation between the ceRNA network and SIC. ROC analysis demonstrated its high diagnostic specificity (AUC &gt; 0.8). Correlation analysis revealed a negative association between IER3 expression and oxygenation index in SIC patients (p &lt; 0.05). Furthermore, miR-214-3p expression showed a negative correlation with NT-proBNP (p &lt; 0.05).ConclusionIn this study, we identified and validated a ceRNA network associated with glycolysis in SIC: SNHG17/miR-214-3p/IER3. This ceRNA network may play a critical role in the onset and development of SIC. This finding is important to further our understanding of the pathophysiological mechanisms underlying SIC and to explore potential diagnostic and therapeutic targets for SIC.
Improving depression-like behaviors caused by diabetes is likely to offer a new perspective for the treatment of non-healing chronic wounds
Authors: Dong Zhiqin , Wu Jijin , Cao Hanchen , Lu Jinqiang 
Published: February 2024

BackgroundThree phases are often involved in the intricate process of wound healing: inflammatory exudation, cell proliferation, and tissue remodeling. It is challenging for wounds to heal if conditions like ischemia, persistent pressure, infection, repetitive trauma, or systemic or localized illnesses arise during the healing process. Chronic wounds are persistent injuries that do not follow the normal healing process and fail to progress through the stages of healing within a reasonable timeframe, like diabetic ulcers, vascular ulcers, pressure sores, and infectious wounds. Various factors affect chronic wound healing. A large body of research has illuminated that psychological distress may often be related to wound healing in clinical settings. Our observations have indicated that the pace of wound healing in diabetic mice is generally slower than that of healthy mice, and mice induced by streptozotocin (STZ) and fed a high-fat diet generally exhibit depression-like behavior. Our experiment delves into whether there is an inherent correlation and provides new ideas for clinical treatment to promote wound healing.MethodsIn order to explore the relationship between diabetes, depression, and wound healing, we observed wound healing through HE staining, Masson's trichrome staining, and IHC staining for CD31 and detected the depressive condition through behavioral tests. Then, RT-PCR was used to detect the mRNA expression levels of α-SMA, Col1, CD31, and VEGF in wound tissue. Finally, the related brain areas were regulated through chemical genetic methods and the process of wound healing was observed.ConclusionIt has been observed that the lateral habenula (LHb) areas are associated with depression-like behavior induced by diabetes. Inhibiting LHb neuronal activity mitigates these depressive symptoms and enhances wound healing. Refractory wounds can be improved by considering patients' emotional issues from a broad standpoint, which provides fresh concepts for potential clinical treatments in the future.
Automated volumetric evaluation of intracranial compartments and cerebrospinal fluid distribution on emergency trauma head CT scans to quantify mass effect
Authors: Puzio Tomasz , Matera Katarzyna , Wiśniewski Karol , Grobelna Milena , Wanibuchi Sora , Jaskólski Dariusz J. , Bobeff Ernest J. 
Published: February 2024

BackgroundIntracranial space is divided into three compartments by the falx cerebri and tentorium cerebelli. We assessed whether cerebrospinal fluid (CSF) distribution evaluated by a specifically developed deep-learning neural network (DLNN) could assist in quantifying mass effect.MethodsHead trauma CT scans from a high-volume emergency department between 2018 and 2020 were retrospectively analyzed. Manual segmentations of intracranial compartments and CSF served as the ground truth to develop a DLNN model to automate the segmentation process. Dice Similarity Coefficient (DSC) was used to evaluate the segmentation performance. Supratentorial CSF Ratio was calculated by dividing the volume of CSF on the side with reduced CSF reserve by the volume of CSF on the opposite side.ResultsTwo hundred and seventy-four patients (mean age, 61 years ± 18.6) after traumatic brain injury (TBI) who had an emergency head CT scan were included. The average DSC for training and validation datasets were respectively: 0.782 and 0.765. Lower DSC were observed in the segmentation of CSF, respectively 0.589, 0.615, and 0.572 for the right supratentorial, left supratentorial, and infratentorial CSF regions in the training dataset, and slightly lower values in the validation dataset, respectively 0.567, 0.574, and 0.556. Twenty-two patients (8%) had midline shift exceeding 5 mm, and 24 (8.8%) presented with high/mixed density lesion exceeding &gt;25 ml. Fifty-five patients (20.1%) exhibited mass effect requiring neurosurgical treatment. They had lower supratentorial CSF volume and lower Supratentorial CSF Ratio (both p &lt; 0.001). A Supratentorial CSF Ratio below 60% had a sensitivity of 74.5% and specificity of 87.7% (AUC 0.88, 95%CI 0.82–0.94) in identifying patients that require neurosurgical treatment for mass effect. On the other hand, patients with CSF constituting 10–20% of the intracranial space, with 80–90% of CSF specifically in the supratentorial compartment, and whose Supratentorial CSF Ratio exceeded 80% had minimal risk.ConclusionCSF distribution may be presented as quantifiable ratios that help to predict surgery in patients after TBI. Automated segmentation of intracranial compartments using the DLNN model demonstrates a potential of artificial intelligence in quantifying mass effect. Further validation of the described method is necessary to confirm its efficacy in triaging patients and identifying those who require neurosurgical treatment.
The composition of phenolic compounds in Chinese olive (Canarium album L.) cultivars and their contribution to the anti-inflammatory properties of the cultivars
Authors: He Fangqing , Du Yixuan , Pan Zhuangguang , Zeng Huize , Luo Haolin , Wang Junyi , Sun Yuanming , Li Meiying 
Published: February 2024

ObjectiveThis study aimed to explore the phenolic compounds (PCs) present in three Chinese olive (Canarium album L.) cultivars and the contribution of these PCs to the anti-inflammatory activities of the cultivars.MethodsUltra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap/mass spectrometry (UPLC-Q-Exactive/MS) was used to identify and quantify the PCs present in three Chinese olive cultivars, “Na zhong,” “Tan xiang,” and “Xiang zhong”. 2,2-diphenyl-1-picrylhydrazyl (DPPH); 2,2′-azinobis (3-ethylbenzothiazoline 6-sulfonate) (ABTS); and oxygen radical absorption capacity (ORAC) assays were used to assess the antioxidant activities of the PCs. Furthermore, we analyzed the anti-inflammatory action of these PCs using lipopolysaccharide (LPS)-induced RAW264.7 cells.ResultsA total of 44 PCs were identified in the three cultivars. Of these, 17 PCs were previously unidentified in Chinese olive. Among the cultivars, the free phenolics (FPs) of “Tan xiang” showed the strongest antioxidant activity. All cultivars have shown significant inhibition of TNF-α and IL-6 production. Clustering correlation analysis showed galloyl-bis-HHDP-glucose and paeonol have significant anti-inflammatory ability in FPs. Quininic, galloylquinic acid, 4-hydroxycinnamic acid and gallic acid hexoside have shown significant inhibition of IL-6 production in BPs. Furthermore, gallic acid, catechin, syringic acid, and nobiletin exhibit negative correlation in FPs and positive correlation in BPs of cytokine production, while corilagin and methyl ellagic acid pentoside exhibited opposite correlation.ConclusionIn summary, this study contributed to the literature on PCs in Chinese olives and the potential health benefits of FPs and BPs.
Multi-center implementation of rapid whole genome sequencing provides additional evidence of its utility in the pediatric inpatient setting
Authors: Thompson Lauren , Larson Austin , Salz Lisa , Veith Regan , Tsai John-Paul , Jayakar Anuj , Chapman Rachel , Gupta Apeksha , Kingsmore Stephen F. , Dimmock David , Bedrick Alan , Galindo Maureen Kelly , Casas Kari , Mohamed Mohamed , Straight Lisa , Khan M. Akram , Salyakina Daria 
Published: February 2024

ObjectiveMulti-center implementation of rapid whole genome sequencing with assessment of the clinical utility of rapid whole genome sequencing (rWGS), including positive, negative and uncertain results, in admitted infants with a suspected genetic disease.Study designrWGS tests were ordered at eight hospitals between November 2017 and April 2020. Investigators completed a survey of demographic data, Human Phenotype Ontology (HPO) terms, test results and impacts of results on clinical care.ResultsA total of 188 patients, on general hospital floors and intensive care unit (ICU) settings, underwent rWGS testing. Racial and ethnic characteristics of the tested infants were broadly representative of births in the country at large. 35% of infants received a diagnostic result in a median of 6 days. The most common HPO terms for tested infants indicated an abnormality of the nervous system, followed by the cardiovascular system, the digestive system, the respiratory system and the head and neck. Providers indicated a major change in clinical management because of rWGS for 32% of infants tested overall and 70% of those with a diagnostic result. Also, 7% of infants with a negative rWGS result and 23% with a variant of unknown significance (VUS) had a major change in management due to testing.ConclusionsOur study demonstrates that the implementation of rWGS is feasible across diverse institutions, and provides additional evidence to support the clinical utility of rWGS in a demographically representative sample of admitted infants and includes assessment of the clinical impact of uncertain rWGS results in addition to both positive and negative results.
Human milk-derived versus bovine milk-derived fortifier use in very low birth weight infants: growth and vitamin D status
Authors: Lavassani Emmanuelle , Tauber Kate A. , Cerone Jennifer B. , Ludke Jennifer , Munshi Upender K. 
Published: February 2024

BackgroundHuman milk-derived fortifier (HMDF) coupled with human milk feeding in extremely premature infants reduces the adverse outcome risks of early exposure to bovine milk ingredients but may not provide enough nutrients for adequate catch-up growth compared with bovine milk-derived fortifier (BMDF).ObjectiveThis study aims to compare HMDF and BMDF effects on growth parameters and serum 25-hydroxy vitamin D (25OHD) levels in preterm very low birth weight (VLBW) infants during the first 8 weeks of life.MethodsWe present a retrospective chart review of inpatient VLBW infants with birth weight &lt;1,500 g and gestational age &lt;32 completed weeks who received either their mother’s milk or donor breast human milk fortified with HMDF or BMDF for the first 8 weeks. Weight, head circumference, length gain, and 25OHD level were calculated at 4 and 8 weeks of age.ResultsA total of 139 VLBW infants (91 HMDF + 48 BMDF) received fortified human milk without any supplemental premature formula from birth to 4 weeks of age, of whom 44 (37 HMDF + 7 BMDF) continued until 8 weeks of age. There was no statistically significant difference in the growth parameters between the two groups at 4 and 8 weeks of age. Serum 25OHD level in the HMDF group was significantly higher compared with that in the BMDF group at 4 weeks of age despite receiving lower vitamin D supplementation.ConclusionSimilar gain in growth parameters in HMDF and BMDF groups at 4 and 8 weeks of age was observed, suggesting that HMDF provides adequate nutrients for growth in VLBW infants. A higher 25OHD level in HMDF may suggest better absorption.
Xylem plasticity of root, stem, and branch in Cunninghamia lanceolata under drought stress: implications for whole-plant hydraulic integrity
Authors: Li Shubin , Huang Xiaoyan , Zheng Ruping , Zhang Maxiao , Zou Zhiguang , Heal Kate V. , Zhou Lili 
Published: February 2024

IntroductionA better understanding of xylem hydraulic characteristics in trees is critical to elucidate the mechanisms of forest decline and tree mortality from water deficit. As well as temperate forests and forests growing in arid regions, subtropical and tropical forests are also predicted to experience an increased frequency and intensity of climate change-induced drought in the near future.MethodsIn this study, 1-year-old Cunninghamia lanceolata seedlings (a typical subtropical species in southern China) were selected for a continuous controlled drought pot experiment of 45 days duration. The experimental treatments were non-drought (control), light drought, moderate drought and severe drought stress, which were 80%, 60%, 50%, and 40%, respectively of soil field maximum moisture capacity.ResultsThe hydraulic conductivity, specific conductivity and water potential of roots, stems, and branches of C. lanceolata all decreased with the prolonging of drought in the different drought intensities. The relative decrease in these hydraulic values were greater in roots than in stems and branches, indicating that roots are more sensitive to drought. Root tracheid diameters normally reduce to ensure security of water transport with prolonged drought, whilst the tracheid diameters of stems and branches expand initially to ensure water transport and then decrease to reduce the risk of embolism with continuing drought duration. The pit membrane diameter of roots, stems and branches generally increased to different extents during the 15–45 days drought duration, which is conducive to enhanced radial water transport ability. The tracheid density and pit density of stems generally decreased during drought stress, which decreased water transport efficiency and increased embolism occurrence. Correlation analysis indicated that anatomical plasticity greatly influenced the hydraulic properties, whilst the relationships varied among different organs. In roots, tracheid diameter decreased and tracheid density increased to enhance water transport security; stems and branches may increase tracheid diameter and pit membrane diameter to increase hydraulic conductivity ability, but may increase the occurrence of xylem embolism.DiscussionIn summary, under drought stress, the xylem anatomical characteristics of C. lanceolata organs were highly plastic to regulate water transport vertically and radially to maintain the trade-off between hydraulic conductivity efficiency and safety.
Anhedonia and depression severity measures during ketamine administration in treatment-resistant depression
Authors: Kwaśny Aleksander , Cubała Wiesław Jerzy , Włodarczyk Adam 
Published: February 2024

BackgroundAnhedonia is a core symptom of depression characterized by a diminished ability to experience pleasure. Currently available treatments for depression often fall short in adequately addressing anhedonia that often presents as a chronic and debilitating symptom. Ketamine is known to possess antianhedonic properties.MethodsThis post-hoc analysis of a naturalistic observational study of treatment-resistant depression inpatients (n=28) analyzed antianhedonic response patterns measured by Snaith-Hamilton Pleasure Scale and changes in Inventory of Depressive Symptomatology in responders (n=6) and non-responders (n=22) stratified per Montgomery-Åsberg Depression Rating Scale during short-term ketamine treatment.ResultsResults show that responders significantly improve in anhedonia over time (p=0.0084) and at the 7th infusion and follow-up (both p&lt;0.05). Non-responders reported significant reduction in anhedonia over time (p=0.0011) and at the 5th, 7th infusion and at the follow-up (all p’s&lt;0.05). Non-responders were also observed to improve significantly in self-reported depression at the 7th infusion (p=0.0219) but not at the follow-up.DiscussionThere is no complete overlap between change in depressive symptoms and anhedonia. Therefore, it might be assumed ketamine alleviates anhedonia as an individual symptom domain regardless of formal treatment outcome.
Normal variation of clinical mobility of the mandibular symphysis in cats
Authors: Minei Sergio , Auriemma Edoardo , Bonacini Serena , Kent Michael S. , Gracis Margherita 
Published: February 2024

IntroductionThe primary objective of this retrospective study was to document the normal variation of clinical mobility of the mandibular symphysis in cats and possible associations with bodyweight, age, sex, sexual status, breed and skull morphology. Secondarily, the radiographic appearance of the mandibular symphysis and possible associations with the analyzed data were evaluated.Materials and methodsTwo hundred and sixteen cats of 15 different breeds that underwent maxillofacial, oral and dental procedures from April 2015 to December 2021 were included. Clinical mobility was evaluated under general anesthesia using a 0 to 3 scale in lateromedial (LM) and dorsoventral (DV) directions. The symphysis was radiographically classified on the occlusal radiographic view of the rostral mandibles as fused or open, and with parallel or divergent margins.ResultsBodyweight ranged from 2.2 to 12.5 kg (median 4.0 kg), age from 4 months to 17 years and 4 months (median 6 years and 4 months). At the first evaluation DV symphyseal mobility was 0 in 177 cases (82%), 1 in 32 cases (14.8%) and 2 in 7 cases (3.2%), LM mobility was 0 in 61 cases (28.3%), 1 in 110 cases (50.9%) and 2 in 45 cases (20.8%). 81.1% of the radiographs were included in the statistical analysis. Three symphyses (1.6%) were classified as fused and 190 (98.4%) as open, 129 (68.8%) having divergent margins and 61 (31.6%) parallel. One hundred and forty-eight cases (76.7%) did not show the presence of odontoclastic replacement resorption on the canine teeth (TR subgroup 1), 23 (11.9%) showed stage ≤3 lesions (TR subgroup 2) and 22 (11.4%) stage 4 lesions (TR subgroup 3). Logistic regression models exploring factors that affected DV and LM mobility were statistically significant (p &lt; 0.0001; p &lt; 0.0001) with an increase in LM mobility predicting an increase in DV mobility, and vice versa. An increase in DV mobility was associated with an increase in age and in having resorptive lesions. A decrease in LM symphyseal mobility was associated with being brachycephalic.ConclusionThe great majority of cases showed some degree of LM symphyseal mobility, and 18% showed DV mobility. Symphyseal bony fusion is rare but possible.
Patient weight has diverse effects on the prescribing of different antibiotics to dogs
Authors: Becker Stuart D. , Hughes David M. 
Published: February 2024

IntroductionVarious factors including body weight-associated treatment cost may influence the probability of dispensing antibiotics to dogs in first-opinion practice, but their effect on specific drug choice remains unclear.MethodsMultiple membership regression modeling was used to investigate the probability of dispensing 12 different antibiotics to dogs of different weights in the context of various disease presentations, using anonymized data obtained from electronic health records of 18 clinics between 2020 and 2022. Data from 14,259 dogs were analyzed.ResultsTreatment choice varied significantly with animal weight. Higher body weight was associated with an increased likelihood of dispensing lower cost antimicrobials such as amoxicillin and trimethoprim sulfonamide, while use of higher cost antimicrobials such as cefovecin was strongly biased to smaller animals. However, these effects were limited when restricted treatment options were available for the target condition.ConclusionThis work demonstrates that anticipated financial costs may result in different treatment choices for canine patients depending on their body weight. Further work is needed to understand the impact of financial pressures on veterinarians’ treatment choices, and the implications for the optimization of antimicrobial stewardship in first opinion practice.